diff --git a/.DS_Store b/.DS_Store index e8a8d11..285b77c 100644 Binary files a/.DS_Store and b/.DS_Store differ diff --git a/.gitignore b/.gitignore index 72745e9..0ad7b14 100644 --- a/.gitignore +++ b/.gitignore @@ -6,4 +6,5 @@ packrat/lib*/ PubMed pathologyarticles packrat/src/ -data/ \ No newline at end of file +data/ +Neurosurgery-Articles diff --git a/BibliographicStudies.Rmd b/BibliographicStudies.Rmd index 1b4b1c4..e6ec1df 100644 --- a/BibliographicStudies.Rmd +++ b/BibliographicStudies.Rmd @@ -48,10 +48,14 @@ This document will be continiously updated and the last update was on `r Sys.Dat # Analysis +--- + ## Country Based Comparison To see the analysis comparing number of pathology articles from Turkey, German and Japan see this analysis: [Country Based Comparison](https://sbalci.github.io/pubmed/CountryBasedComparison.html) +--- + ## Articles per Journals per Country In this analysis we aimed to compare number articles per journals per country. We tried to identify if articles from a country is published in certain journals: [Articles Per Journals Per Country](https://sbalci.github.io/pubmed/ArticlesPerJournalsPerCountry.html) @@ -62,6 +66,31 @@ In this analysis we aimed to identify the common research topics Turkish patholo [MeSH Terms Pathology Articles From Turkey](https://sbalci.github.io/pubmed/MeSH_Terms_Pathology_Articles_From_Turkey.html) +--- + + + +--- + + + +--- + + + +--- + + + +--- + + + +--- + + + + --- # Sources Used For Analysis diff --git a/BibliographicStudies.nb.html b/BibliographicStudies.nb.html index 7f84dc8..35ebb95 100644 --- a/BibliographicStudies.nb.html +++ b/BibliographicStudies.nb.html @@ -11,7 +11,7 @@ - + Bibliographic Studies @@ -2661,6 +2661,9 @@ .tabbed-pane { padding-top: 12px; } +.html-widget { + margin-bottom: 20px; +} button.code-folding-btn:focus { outline: none; } @@ -2829,7 +2832,7 @@

Bibliographic Studies

Reproducible Bibliometric Analysis of Pathology Articles Using PubMed, E-direct, WoS, Google Scholar

Serdar Balcı, MD, Pathologist

-

2018-06-27

+

2018-10-16

@@ -2844,14 +2847,16 @@

1 Introduction


If you want to see the code used in the analysis please click the code button on the right upper corner or throughout the page.

I would like to hear your feedback: https://goo.gl/forms/YjGZ5DHgtPlR1RnB3

-

This document will be continiously updated and the last update was on 2018-06-27.

+

This document will be continiously updated and the last update was on 2018-10-16.


2 Analysis

+

2.1 Country Based Comparison

To see the analysis comparing number of pathology articles from Turkey, German and Japan see this analysis: Country Based Comparison

+

2.2 Articles per Journals per Country

@@ -2861,6 +2866,18 @@

2.2 Articles per Journals per Cou

2.3 Most Common MeSH Terms and Keywords used in Pathology Articles from Turkey

In this analysis we aimed to identify the common research topics Turkish pathologists are interested. We extracted most common MeSH terms and keywords from PubMed articles using EDirect: MeSH Terms Pathology Articles From Turkey


+ +
+ +
+ +
+ +
+ +
+ +
@@ -2871,12 +2888,12 @@

3 Sources Used For Analysis

4 Feedback

Serdar Balcı, MD, Pathologist would like to hear your feedback: https://goo.gl/forms/YjGZ5DHgtPlR1RnB3

-

This document will be continiously updated and the last update was on 2018-06-27.

+

This document will be continiously updated and the last update was on 2018-10-16.


-
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diff --git a/Making proper trend graphs.htm b/Making proper trend graphs.htm new file mode 100644 index 0000000..a408446 --- /dev/null +++ b/Making proper trend graphs.htm @@ -0,0 +1,443 @@ + + + + + + + + + + + + + + + + +Making proper trend graphs + + + + + + + + + + + + + + + + + +

Making proper trend graphs

+

Najko Jahn

+

2018-04-20

+ + + +

Trend graphs in literature reviews show the development of concepts in scholarly communication. Some trend graphs, however, don’t acknowledge that the number of scholarly publications is growing each year, but simply display the absolute number of hits they have found for a given concept. Noam Ross called these misleading graphs evergreen review graphs because of their enduring popularity in review papers. Examples can be found on Twitter under the Hashtag #evergreenreviewgraph.

+

This vignette guides you how to make proper trend graphs when reviewing Europe PMC literature. In these graphs, the number of hits found is divided by the total number of records indexed in Europe PMC for a given search query.

+
+

Preparing proper review graphs with epmc_hits_trend()

+

We use epmc_hits_trend() function, which was firstly introduced in Maëlle Salmon’s blog post about “How not to make an evergreen review graph”1. The function takes a query in the Europe PMC search syntax2 and the period of years over which to perform the search as arguments, and returns a data-frame with year, total number of hits (all_hits) and number of hits for the query (query_hits).

+
library(europepmc)
+europepmc::epmc_hits_trend(query = "aspirin", period = 2010:2016)
+#> # A tibble: 7 x 3
+#>    year all_hits query_hits
+#>   <int>    <dbl>      <dbl>
+#> 1  2010   849169       6727
+#> 2  2011   901436       7304
+#> 3  2012   943688       8319
+#> 4  2013  1001227       9290
+#> 5  2014  1054856      10038
+#> 6  2015  1119091      10909
+#> 7  2016  1101704      10443
+

By default, synonym search is disabled and only Medline/PubMed index is searched.

+
+
+

Use Cases

+
+

Use Case: Growth of Open Access Literature

+

There is a growing interest in knowing the proportion of open access to scholarly literature. Europe PMC allows searching for open access content with the OPEN_ACCESS:Y parameter. At the moment, Europe PMC contains 1,915,802 open access full-texts. Let’s see how they are relatively distributed over the period 1995 - 2016.

+
tt_oa <- europepmc::epmc_hits_trend("OPEN_ACCESS:Y", period = 1995:2016, synonym = FALSE)
+tt_oa
+#> # A tibble: 22 x 3
+#>     year all_hits query_hits
+#>    <int>    <dbl>      <dbl>
+#>  1  1995   448613       2827
+#>  2  1996   458180       3082
+#>  3  1997   455775       3143
+#>  4  1998   473280       3327
+#>  5  1999   492902       3347
+#>  6  2000   531355       3743
+#>  7  2001   544446       4549
+#>  8  2002   560848       5303
+#>  9  2003   587570       6103
+#> 10  2004   627164       8097
+#> # ... with 12 more rows
+# we use ggplot2 for plotting the graph
+library(ggplot2)
+ggplot(tt_oa, aes(year, query_hits / all_hits)) + 
+  geom_point() + 
+  geom_line() +
+  xlab("Year published") + 
+  ylab("Proportion of OA full-texts in Europe PMC")
+

+

Be careful with the interpretation of the slower growth in the last years because there are several ways how open access content is added to Europe PMC including the digitalization of back issues.3

+
+
+

Use Case: Cited open source software in scholarly publications

+

Another nice use case for trend graphs is to study how code and software repositories are cited in scientific literature. In recent years, it has become a good practice not only to re-use openly available software, but also to cite them. The FORCE11 Software Citation Working Group states:

+
+

In general, we believe that software should be cited on the same basis as any other research product such as a paper or book; that is, authors should cite the appropriate set of software products just as they cite the appropriate set of papers. (doi:10.7717/peerj-cs.86)

+
+

So let’s see whether we can find evidence for this evolving practice by creating a proper review graph. As a start, we examine these four general purpose hosting services for version-controlled code:

+ +

and, of course, CRAN, the R archive network.

+
+

How to query Europe PMC?

+

We only want to search reference lists. Because Europe PMC does not index references for its complete collection, we use has_reflist:y to restrict our search to those publications with reference lists. These literature sections can be searched with the REF: parameter.

+

Let’s prepare the queries for links to the above mentioned code hosting services:

+
dvcs <- c("code.google.com", "github.com", 
+          "sourceforge.net", "bitbucket.org", "cran.r-project.org")
+# make queries including reference section
+dvcs_query <- paste0('REF:"', dvcs, '"')
+

and get publications for which Europe PMC gives access to reference lists for normalizing the review graph.

+
library(dplyr)
+my_df <- purrr::map_df(dvcs_query, function(x) {
+  # get number of publications with indexed reference lists
+  refs_hits <- 
+    europepmc::epmc_hits_trend("has_reflist:y", period = 2009:2016, synonym = FALSE)$query_hits
+  # get hit count querying for code repositories 
+  europepmc::epmc_hits_trend(x, period = 2009:2016, synonym = FALSE) %>% 
+    dplyr::mutate(query_id = x) %>%
+    dplyr::mutate(refs_hits = refs_hits) %>%
+    dplyr::select(year, all_hits, refs_hits, query_hits, query_id)
+}) 
+my_df
+#> # A tibble: 40 x 5
+#>     year all_hits refs_hits query_hits query_id                 
+#>    <int>    <dbl>     <dbl>      <dbl> <chr>                    
+#>  1  2009   792034    536035      13.0  "REF:\"code.google.com\""
+#>  2  2010   849169    519841      40.0  "REF:\"code.google.com\""
+#>  3  2011   901436    580391      66.0  "REF:\"code.google.com\""
+#>  4  2012   943688    610446      91.0  "REF:\"code.google.com\""
+#>  5  2013  1001227    740280     136    "REF:\"code.google.com\""
+#>  6  2014  1054856    777127     141    "REF:\"code.google.com\""
+#>  7  2015  1119091    770816     119    "REF:\"code.google.com\""
+#>  8  2016  1101704    729815      63.0  "REF:\"code.google.com\""
+#>  9  2009   792034    536035       4.00 "REF:\"github.com\""     
+#> 10  2010   849169    519841      10.0  "REF:\"github.com\""     
+#> # ... with 30 more rows
+
+### total
+hits_summary <- my_df %>% 
+  group_by(query_id) %>% 
+  summarise(all = sum(query_hits)) %>% 
+  arrange(desc(all))
+hits_summary
+#> # A tibble: 5 x 2
+#>   query_id                       all
+#>   <chr>                        <dbl>
+#> 1 "REF:\"cran.r-project.org\""  8201
+#> 2 "REF:\"sourceforge.net\""     2210
+#> 3 "REF:\"github.com\""          1627
+#> 4 "REF:\"code.google.com\""      669
+#> 5 "REF:\"bitbucket.org\""        101
+

The proportion of papers where Europe PMC was able to make the cited literature available was 68 for the period 2009-2016. There also seems to be a time-lag between indexing reference lists because the absolute number of publication was decreasing over the years. This is presumably because Europe PMC also includes delayed open access content, i.e. content which is not added immediately with the original publication.4

+

Now, let’s make a proper review graph normalizing our query results with the number of publications with indexed references.

+
library(ggplot2)
+ggplot(my_df, aes(factor(year), query_hits / refs_hits, group = query_id, 
+                  color = query_id)) +
+  geom_line(size = 1, alpha = 0.8) +
+  geom_point(size = 2) +
+  scale_color_brewer(name = "Query", palette = "Set1")+
+  xlab("Year published") +
+  ylab("Proportion of articles in Europe PMC")
+

+
+
+

Discussion and Conclusion

+

Although this figure illustrates the relative popularity of citing code hosted by CRAN and GitHub in recent years, there are some limits that needs to be discussed. As said before, Europe PMC does not extract reference lists from every indexed publication. It furthermore remains open whether and to what extent software is cited outside the reference section, i.e. as footnote or in the acknowledgements.

+

Another problem of our query approach is that we did not consider that DOIs can also be used to cite software, a best-practice implemented by Zenodo and GitHub or the The Journal of Open Source Software.

+

Lastly, it actually remains unclear, which and what kind of software is cited how often. We could also not control if authors just cited the homepages and not a particular source code repository. One paper can also cite more than one code repository, which is also not represented in the trend graph.

+

To conclude, a proper trend graph on the extent of software citation can only be the start for a more sophisticated approach that mines links to software repositories from scientific literature and fetches metadata about these code repositories from the hosting facilities.

+
+
+
+
+

Conclusion

+

This vignette presented first steps on how to make trend graphs with europepmc. As our use-cases suggest, please carefully consider how you queried Europe PMC in the interpretation of your graph. Although trend graphs are a nice way to illustrate the development of certain concepts in scientific literature or recent trends in scholarly communication, they must be put in context in order to become meaningful.

+
+
+

Acknowledgements

+

Big thanks to Maëlle Salmon for getting me started to write this vignette.

+
+
+
+
    +
  1. http://www.masalmon.eu/2017/05/14/evergreenreviewgraph/

  2. +
  3. Europe PMC Search Syntax: https://europepmc.org/Help#mostofsearch

  4. +
  5. See section “Content Growth” in: McEntyre JR, Ananiadou S, Andrews S, et al. UKPMC: a full text article resource for the life sciences. Nucleic Acids Research. 2011;39(Database):D58–D65. https://doi.org/10.1093/nar/gkq1063.

  6. +
  7. Ebd.

  8. +
+
+ + + + + + + + diff --git a/PubMedPackages.Rmd b/PubMedPackages.Rmd new file mode 100644 index 0000000..95e4cba --- /dev/null +++ b/PubMedPackages.Rmd @@ -0,0 +1,374 @@ +--- +title: "PubMed Packages" +output: + html_notebook: + highlight: tango + number_sections: yes + theme: spacelab + toc: yes +--- + +# easyPubMed + +```{r} +library(easyPubMed) +library(XML) +``` + + +## easyPubMed: Search and Retrieve Scientific Publication Records from PubMed + + +https://cran.r-project.org/web/packages/easyPubMed/index.html + +https://cran.r-project.org/web/packages/easyPubMed/easyPubMed.pdf + +https://cran.r-project.org/web/packages/easyPubMed/vignettes/easyPM_vignette_html.html + +https://cran.r-project.org/web/packages/easyPubMed/vignettes/easyPM_vignette_pdf.pdf + +```{r} +my_query <- "Damiano Fantini[AU]" +my_entrez_id <- get_pubmed_ids(my_query) +my_abstracts_txt <- fetch_pubmed_data(my_entrez_id, format = "abstract") +my_abstracts_txt[1:10] +``` + + + +```{r} +my_abstracts_xml <- fetch_pubmed_data(my_entrez_id) +class(my_abstracts_xml) +``` + + +```{r} +# +# apply "saveXML" to each //ArticleTitle tag via XML::xpathApply() +my_titles <- unlist(xpathApply(my_abstracts_xml, "//ArticleTitle", saveXML)) +# +# use gsub to remove the tag, also trim long titles +my_titles <- gsub("(^.{5,10}Title>)|(<\\/.*$)", "", my_titles) +my_titles[nchar(my_titles)>75] <- paste(substr(my_titles[nchar(my_titles)>75], 1, 70), + "...", sep = "") +print(my_titles) +``` + + + + +```{r} +new_query <- "(APE1[TI] OR OGG1[TI]) AND (2012[PDAT]:2016[PDAT])" +out.A <- batch_pubmed_download(pubmed_query_string = new_query, + format = "xml", + batch_size = 150, + dest_file_prefix = "easyPM_example") +``` + + + +```{r} +out.A # this variable stores the name of the output files +``` + +```{r} +my_PM_list <- articles_to_list(my_abstracts_xml) +class(my_PM_list[[4]]) +``` + + +```{r} +cat(substr(my_PM_list[[4]], 1, 984)) +``` + + +```{r} +curr_PM_record <- my_PM_list[[4]] +custom_grep(curr_PM_record, tag = "DateCompleted") +``` + + +```{r} +custom_grep(curr_PM_record, tag = "LastName", format = "char") +``` + + +```{r} +my.df <- article_to_df(curr_PM_record, max_chars = 18) +# +# Fields extracted from the PubMed record +colnames(my.df) +``` + + +```{r} +# +# Trim long strings and then Display some content: each row corresponds to one author +my.df$title <- substr(my.df$title, 1, 15) +my.df$address <- substr(my.df$address, 1, 19) +my.df$jabbrv <- substr(my.df$jabbrv, 1, 10) +my.df[,c("pmid", "title", "jabbrv", "firstname", "address")] +``` + + +```{r} +my.df2 <- article_to_df(curr_PM_record, autofill = TRUE) +my.df2$title <- substr(my.df2$title, 1, 15) +my.df2$jabbrv <- substr(my.df2$jabbrv, 1, 10) +my.df2$address <- substr(my.df2$address, 1, 19) +my.df2[,c("pmid", "title", "jabbrv", "firstname", "address")] +``` + + +```{r} +new_PM_query <- "(APEX1[TI] OR OGG1[TI]) AND (2010[PDAT]:2013[PDAT])" +out.B <- batch_pubmed_download(pubmed_query_string = new_PM_query, dest_file_prefix = "apex1_sample") +``` + +```{r} +# Retrieve the full name of the XML file downloaded in the previous step +new_PM_file <- out.B[1] +new_PM_df <- table_articles_byAuth(pubmed_data = new_PM_file, included_authors = "first", max_chars = 0) +# Alternatively, the output of a fetch_pubmed_data() could have been used +# +# Printing a sample of the resulting data frame +new_PM_df$address <- substr(new_PM_df$address, 1, 28) +new_PM_df$jabbrv <- substr(new_PM_df$jabbrv, 1, 9) +print(new_PM_df[1:10, c("pmid", "year", "jabbrv", "lastname", "address")]) +``` + + + +## Querying PubMed via the easyPubMed package in R + +http://www.biotechworld.it/bioinf/2016/01/05/querying-pubmed-via-the-easypubmed-package-in-r/ + + +## easyPubMed for business: scraping PubMed data in R for a targeting campaign + +http://www.biotechworld.it/bioinf/2016/01/21/scraping-pubmed-data-via-easypubmed-xml-and-regex-in-r-for-a-targeting-campaign/ + + +# europepmc + +europepmc: R Interface to the Europe PubMed Central RESTful Web Service + +https://cran.r-project.org/web/packages/europepmc/index.html + +https://cran.r-project.org/web/packages/europepmc/europepmc.pdf + +## Making proper trend graphs + +https://cran.r-project.org/web/packages/europepmc/vignettes/evergreenreviewgraphs.html + + +```{r} +library(europepmc) +``` + + +```{r} +europepmc::epmc_hits_trend(query = "aspirin", period = 2010:2016) +``` + + +```{r} +tt_oa <- europepmc::epmc_hits_trend("OPEN_ACCESS:Y", period = 1995:2017, synonym = FALSE) +tt_oa +``` + + +```{r} +library(ggplot2) +ggplot(tt_oa, aes(year, query_hits / all_hits)) + + geom_point() + + geom_line() + + xlab("Year published") + + ylab("Proportion of OA full-texts in Europe PMC") +``` + + +```{r} +dvcs <- c("code.google.com", "github.com", + "sourceforge.net", "bitbucket.org", "cran.r-project.org") +# make queries including reference section +dvcs_query <- paste0('REF:"', dvcs, '"') +``` + +```{r} +library(dplyr) +my_df <- purrr::map_df(dvcs_query, function(x) { + # get number of publications with indexed reference lists + refs_hits <- + europepmc::epmc_hits_trend("has_reflist:y", period = 2009:2016, synonym = FALSE)$query_hits + # get hit count querying for code repositories + europepmc::epmc_hits_trend(x, period = 2009:2016, synonym = FALSE) %>% + dplyr::mutate(query_id = x) %>% + dplyr::mutate(refs_hits = refs_hits) %>% + dplyr::select(year, all_hits, refs_hits, query_hits, query_id) +}) +my_df +``` + + + +```{r} +### total +hits_summary <- my_df %>% + group_by(query_id) %>% + summarise(all = sum(query_hits)) %>% + arrange(desc(all)) +hits_summary +``` + + +```{r} +library(ggplot2) +ggplot(my_df, aes(factor(year), query_hits / refs_hits, group = query_id, + color = query_id)) + + geom_line(size = 1, alpha = 0.8) + + geom_point(size = 2) + + scale_color_brewer(name = "Query", palette = "Set1")+ + xlab("Year published") + + ylab("Proportion of articles in Europe PMC") +``` + + + + + +## Introducing europepmc, an R interface to Europe PMC RESTful API + +https://cran.r-project.org/web/packages/europepmc/vignettes/introducing-europepmc.html + + +```{r} +library(europepmc) +europepmc::epmc_search('malaria') +``` + + +```{r} +europepmc::epmc_search('malaria', synonym = FALSE) +``` + + +```{r} +europepmc::epmc_search('"Human malaria parasites"') +``` + + +```{r} +europepmc::epmc_search('"Human malaria parasites"', limit = 10) +``` + + + +``` +sort = 'cited' +sort = 'date' +``` + +```{r} +my_dois <- c( + "10.1159/000479962", + "10.1002/sctm.17-0081", + "10.1161/strokeaha.117.018077", + "10.1007/s12017-017-8447-9" + ) + plyr::ldply(my_dois, function(x) { + europepmc::epmc_search(paste0("DOI:", x)) + }) +``` + +``` +output = "id_list" +output = "raw" +``` + +```{r} +europepmc::epmc_search('AUTH:"Salmon Maelle"') +``` + + +```{r} +q <- 'AUTH:"PÜHLER Alfred" OR AUTH:"Pühler Alfred Prof. Dr." OR AUTH:"Puhler A"' +europepmc::epmc_search(q, limit = 1000) +``` + + +```{r} +europepmc::epmc_search('AUTHORID:"0000-0002-7635-3473"', limit = 200, sort = "cited") +``` + + +```{r} +europepmc::epmc_search('disease:meningitis') +``` + + +```{r} +europepmc::epmc_tm(30242204) +``` + + + +```{r} +europepmc::epmc_search('(HAS_PDB:y) AND FIRST_PDATE:2016') +``` + + + +```{r} +europepmc::epmc_citations("9338777", limit = 500) +``` + + + + +```{r} +europepmc::epmc_refs("28632490", limit = 200) +``` + + + + +```{r} +europepmc::epmc_ftxt("PMC3257301") +``` + + + + + + + + + + + +# pubmed.mineR + +pubmed.mineR: Text Mining of PubMed Abstracts + + +https://cran.r-project.org/web/packages/pubmed.mineR/index.html + +https://cran.r-project.org/web/packages/pubmed.mineR/pubmed.mineR.pdf + + +# PubMedWordcloud + +PubMedWordcloud: 'Pubmed' Word Clouds + + +https://cran.r-project.org/web/packages/PubMedWordcloud/index.html + +https://cran.r-project.org/web/packages/PubMedWordcloud/PubMedWordcloud.pdf + + + + + + + diff --git a/PubMedPackages.nb.html b/PubMedPackages.nb.html new file mode 100644 index 0000000..ac106e7 --- /dev/null +++ b/PubMedPackages.nb.html @@ -0,0 +1,2458 @@ + + + + + + + + + + + + + +PubMed Packages + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + + + + + + + + + +
+ +
+ + +
+

1 easyPubMed

+ + + + + + + +
+

1.1 easyPubMed: Search and Retrieve Scientific Publication Records from PubMed

+

https://cran.r-project.org/web/packages/easyPubMed/index.html

+

https://cran.r-project.org/web/packages/easyPubMed/easyPubMed.pdf

+

https://cran.r-project.org/web/packages/easyPubMed/vignettes/easyPM_vignette_html.html

+

https://cran.r-project.org/web/packages/easyPubMed/vignettes/easyPM_vignette_pdf.pdf

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ +
+

1.3 easyPubMed for business: scraping PubMed data in R for a targeting campaign

+

http://www.biotechworld.it/bioinf/2016/01/21/scraping-pubmed-data-via-easypubmed-xml-and-regex-in-r-for-a-targeting-campaign/

+
+
+
+

2 europepmc

+

europepmc: R Interface to the Europe PubMed Central RESTful Web Service

+

https://cran.r-project.org/web/packages/europepmc/index.html

+

https://cran.r-project.org/web/packages/europepmc/europepmc.pdf

+
+

2.1 Making proper trend graphs

+

https://cran.r-project.org/web/packages/europepmc/vignettes/evergreenreviewgraphs.html

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

+Attaching package: ‘dplyr’
+
+The following objects are masked from ‘package:stats’:
+
+    filter, lag
+
+The following objects are masked from ‘package:base’:
+
+    intersect, setdiff, setequal, union
+ + + + + +
+ +
+ + + + + + + + + +
+ +
+ + + + + + + + + +

+ + + +
+
+

2.2 Introducing europepmc, an R interface to Europe PMC RESTful API

+

https://cran.r-project.org/web/packages/europepmc/vignettes/introducing-europepmc.html

+ + + + + + +
165187 records found, returning 100
+ + +
+ +
+ + + + + + + + + +
162730 records found, returning 100
+ + +
+ +
+ + + + + + + + + +
1413 records found, returning 100
+ + +
+ +
+ + + + + + + + + +
1413 records found, returning 10
+ + +
+ +
+ + + +
sort = 'cited'
+sort = 'date' 
+ + + + + + +
1 records found, returning 1
+1 records found, returning 1
+1 records found, returning 1
+1 records found, returning 1
+ + +
+ +
+ + + +
output = "id_list" 
+output = "raw"
+ + + + + + +
9 records found, returning 9
+ + +
+ +
+ + + + + + + + + +
564 records found, returning 564
+
+(-) [================>--------------------------------]  35%
+(\) [=========================>-----------------------]  53%
+(|) [==================================>--------------]  71%
+(/) [==========================================>------]  89%
+(-) [=================================================] 100%
+ + +
+ +
+ + + + + + + + + +
134 records found, returning 134
+
+(-) [=================================================] 100%
+ + +
+ +
+ + + + + + + + + +
70624 records found, returning 100
+ + +
+ +
+ + + + + + + + + +
48 records found. Returning 48
+ + +
[[1]]
+[[1]]$chemical
+ + +
+ +
+ + +

+[[1]]$disease
+ + +
+ +
+ + +

+[[1]]$gene_protein
+ + +
+ +
+ + +

+[[1]]$go_term
+ + +
+ +
+ + +

+[[1]]$organism
+ + +
+ +
+ + +

+[[1]]$efo
+ + +
+ +
+ + +

+
+attr(,"hit_count")
+[1] 48
+ + + + + + + + + +
3496 records found, returning 100
+ + +
+ +
+ + + + + + + + + +
223 records found. Returning 223
+ + +
+ +
+ + + + + + + + + +
169 records found. Returning 169
+ + +
+ +
+ + + + + + + + + +
{xml_document}
+<article article-type="research-article" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML">
+[1] <front>\n  <journal-meta>\n    <journal-id journal-id-type="nlm-ta">PLoS Pathog</journal-id>\n     ...
+[2] <body>\n  <sec id="s1">\n    <title>Introduction</title>\n    <p>Atmospheric carbon dioxide (CO<su ...
+[3] <back>\n  <ack>\n    <p>We would like to thank Dr. C. Gourlay and Dr. T. von der Haar for their fr ...
+ + + +
+
+
+

3 pubmed.mineR

+

pubmed.mineR: Text Mining of PubMed Abstracts

+

https://cran.r-project.org/web/packages/pubmed.mineR/index.html

+

https://cran.r-project.org/web/packages/pubmed.mineR/pubmed.mineR.pdf

+
+
+

4 PubMedWordcloud

+

PubMedWordcloud: ‘Pubmed’ Word Clouds

+

https://cran.r-project.org/web/packages/PubMedWordcloud/index.html

+

https://cran.r-project.org/web/packages/PubMedWordcloud/PubMedWordcloud.pdf

+ +
+ +
---
title: "PubMed Packages"
output: 
  html_notebook: 
    highlight: tango
    number_sections: yes
    theme: spacelab
    toc: yes
---

# easyPubMed

```{r}
library(easyPubMed)
library(XML)
```


## easyPubMed: Search and Retrieve Scientific Publication Records from PubMed  


https://cran.r-project.org/web/packages/easyPubMed/index.html

https://cran.r-project.org/web/packages/easyPubMed/easyPubMed.pdf

https://cran.r-project.org/web/packages/easyPubMed/vignettes/easyPM_vignette_html.html

https://cran.r-project.org/web/packages/easyPubMed/vignettes/easyPM_vignette_pdf.pdf

```{r}
my_query <- "Damiano Fantini[AU]"
my_entrez_id <- get_pubmed_ids(my_query)
my_abstracts_txt <- fetch_pubmed_data(my_entrez_id, format = "abstract")
my_abstracts_txt[1:10]
```



```{r}
my_abstracts_xml <- fetch_pubmed_data(my_entrez_id)
class(my_abstracts_xml) 
```


```{r}
#
# apply "saveXML" to each //ArticleTitle tag via XML::xpathApply()
my_titles <- unlist(xpathApply(my_abstracts_xml, "//ArticleTitle", saveXML))
#
# use gsub to remove the tag, also trim long titles
my_titles <- gsub("(^.{5,10}Title>)|(<\\/.*$)", "", my_titles)
my_titles[nchar(my_titles)>75] <- paste(substr(my_titles[nchar(my_titles)>75], 1, 70), 
                                        "...", sep = "")
print(my_titles)
```




```{r}
new_query <- "(APE1[TI] OR OGG1[TI]) AND (2012[PDAT]:2016[PDAT])"
out.A <- batch_pubmed_download(pubmed_query_string = new_query, 
                               format = "xml", 
                               batch_size = 150,
                               dest_file_prefix = "easyPM_example")
```



```{r}
out.A # this variable stores the name of the output files
```

```{r}
my_PM_list <- articles_to_list(my_abstracts_xml)
class(my_PM_list[[4]])
```


```{r}
cat(substr(my_PM_list[[4]], 1, 984))
```


```{r}
curr_PM_record <- my_PM_list[[4]]
custom_grep(curr_PM_record, tag = "DateCompleted")
```


```{r}
custom_grep(curr_PM_record, tag = "LastName", format = "char")
```


```{r}
my.df <- article_to_df(curr_PM_record, max_chars = 18)
#
# Fields extracted from the PubMed record
colnames(my.df)
```


```{r}
#
# Trim long strings and then Display some content: each row corresponds to one author
my.df$title <- substr(my.df$title, 1, 15)
my.df$address <- substr(my.df$address, 1, 19)
my.df$jabbrv <- substr(my.df$jabbrv, 1, 10)
my.df[,c("pmid", "title", "jabbrv", "firstname", "address")]
```


```{r}
my.df2 <- article_to_df(curr_PM_record, autofill = TRUE)
my.df2$title <- substr(my.df2$title, 1, 15)
my.df2$jabbrv <- substr(my.df2$jabbrv, 1, 10)
my.df2$address <- substr(my.df2$address, 1, 19)
my.df2[,c("pmid", "title", "jabbrv", "firstname", "address")]
```


```{r}
new_PM_query <- "(APEX1[TI] OR OGG1[TI]) AND (2010[PDAT]:2013[PDAT])"
out.B <- batch_pubmed_download(pubmed_query_string = new_PM_query, dest_file_prefix = "apex1_sample")
```

```{r}
# Retrieve the full name of the XML file downloaded in the previous step
new_PM_file <- out.B[1]
new_PM_df <- table_articles_byAuth(pubmed_data = new_PM_file, included_authors = "first", max_chars = 0)
# Alternatively, the output of a fetch_pubmed_data() could have been used
#
# Printing a sample of the resulting data frame
new_PM_df$address <- substr(new_PM_df$address, 1, 28)
new_PM_df$jabbrv <- substr(new_PM_df$jabbrv, 1, 9)
print(new_PM_df[1:10, c("pmid", "year", "jabbrv", "lastname", "address")])  
```



## Querying PubMed via the easyPubMed package in R  

http://www.biotechworld.it/bioinf/2016/01/05/querying-pubmed-via-the-easypubmed-package-in-r/


## easyPubMed for business: scraping PubMed data in R for a targeting campaign  

http://www.biotechworld.it/bioinf/2016/01/21/scraping-pubmed-data-via-easypubmed-xml-and-regex-in-r-for-a-targeting-campaign/


# europepmc

europepmc: R Interface to the Europe PubMed Central RESTful Web Service

https://cran.r-project.org/web/packages/europepmc/index.html

https://cran.r-project.org/web/packages/europepmc/europepmc.pdf

## Making proper trend graphs

https://cran.r-project.org/web/packages/europepmc/vignettes/evergreenreviewgraphs.html


```{r}
library(europepmc)
```


```{r}
europepmc::epmc_hits_trend(query = "aspirin", period = 2010:2016)
```


```{r}
tt_oa <- europepmc::epmc_hits_trend("OPEN_ACCESS:Y", period = 1995:2017, synonym = FALSE)
tt_oa
```


```{r}
library(ggplot2)
ggplot(tt_oa, aes(year, query_hits / all_hits)) +
  geom_point() + 
  geom_line() +
  xlab("Year published") + 
  ylab("Proportion of OA full-texts in Europe PMC")
```


```{r}
dvcs <- c("code.google.com", "github.com", 
          "sourceforge.net", "bitbucket.org", "cran.r-project.org")
# make queries including reference section
dvcs_query <- paste0('REF:"', dvcs, '"')
```

```{r}
library(dplyr)
my_df <- purrr::map_df(dvcs_query, function(x) {
  # get number of publications with indexed reference lists
  refs_hits <- 
    europepmc::epmc_hits_trend("has_reflist:y", period = 2009:2016, synonym = FALSE)$query_hits
  # get hit count querying for code repositories 
  europepmc::epmc_hits_trend(x, period = 2009:2016, synonym = FALSE) %>% 
    dplyr::mutate(query_id = x) %>%
    dplyr::mutate(refs_hits = refs_hits) %>%
    dplyr::select(year, all_hits, refs_hits, query_hits, query_id)
}) 
my_df
```



```{r}
### total
hits_summary <- my_df %>% 
  group_by(query_id) %>% 
  summarise(all = sum(query_hits)) %>% 
  arrange(desc(all))
hits_summary
```


```{r}
library(ggplot2)
ggplot(my_df, aes(factor(year), query_hits / refs_hits, group = query_id, 
                  color = query_id)) +
  geom_line(size = 1, alpha = 0.8) +
  geom_point(size = 2) +
  scale_color_brewer(name = "Query", palette = "Set1")+
  xlab("Year published") +
  ylab("Proportion of articles in Europe PMC")
```





## Introducing europepmc, an R interface to Europe PMC RESTful API

https://cran.r-project.org/web/packages/europepmc/vignettes/introducing-europepmc.html


```{r}
library(europepmc)
europepmc::epmc_search('malaria')
```


```{r}
europepmc::epmc_search('malaria', synonym = FALSE)
```


```{r}
europepmc::epmc_search('"Human malaria parasites"')
```


```{r}
europepmc::epmc_search('"Human malaria parasites"', limit = 10)
```



```
sort = 'cited'
sort = 'date' 
```

```{r}
my_dois <- c(
  "10.1159/000479962",
  "10.1002/sctm.17-0081",
  "10.1161/strokeaha.117.018077",
  "10.1007/s12017-017-8447-9"
  )
  plyr::ldply(my_dois, function(x) {
  europepmc::epmc_search(paste0("DOI:", x))
  })
```

```
output = "id_list" 
output = "raw"
```

```{r}
europepmc::epmc_search('AUTH:"Salmon Maelle"')
```


```{r}
q <- 'AUTH:"PÜHLER Alfred" OR AUTH:"Pühler Alfred Prof. Dr." OR AUTH:"Puhler A"'
europepmc::epmc_search(q, limit = 1000)
```


```{r}
europepmc::epmc_search('AUTHORID:"0000-0002-7635-3473"', limit = 200, sort = "cited")
```


```{r}
europepmc::epmc_search('disease:meningitis')
```


```{r}
europepmc::epmc_tm(30242204)
```



```{r}
europepmc::epmc_search('(HAS_PDB:y) AND FIRST_PDATE:2016')
```



```{r}
europepmc::epmc_citations("9338777", limit = 500)
```




```{r}
europepmc::epmc_refs("28632490", limit = 200)
```




```{r}
europepmc::epmc_ftxt("PMC3257301")
```











# pubmed.mineR

pubmed.mineR: Text Mining of PubMed Abstracts


https://cran.r-project.org/web/packages/pubmed.mineR/index.html

https://cran.r-project.org/web/packages/pubmed.mineR/pubmed.mineR.pdf


# PubMedWordcloud

PubMedWordcloud: 'Pubmed' Word Clouds


https://cran.r-project.org/web/packages/PubMedWordcloud/index.html

https://cran.r-project.org/web/packages/PubMedWordcloud/PubMedWordcloud.pdf








+ + + +
+ + + + + + + + diff --git a/Retrieving and Processing PubMed Records via easyPubMed (html).htm b/Retrieving and Processing PubMed Records via easyPubMed (html).htm new file mode 100644 index 0000000..b422c0f --- /dev/null +++ b/Retrieving and Processing PubMed Records via easyPubMed (html).htm @@ -0,0 +1,374 @@ + + + + + + + + + + + + + + + +Retrieving and Processing PubMed Records via easyPubMed (html) + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + + + + + + + + +

PubMed is an online repository of references and abstracts of publications in the fields of medicine and life sciences. PubMed is a free resource that is developed and maintained by the National Center for Biotechnology Information (NCBI), at the U.S. National Library of Medicine (NLM), located at the National Institutes of Health (NIH). PubMed homepage is located at the following URL: https://www.ncbi.nlm.nih.gov/pubmed/. Alternatively, PubMed can be programmatically queried via the NCBI Entrez E-utilities interface.

+

easyPubMed is an R interface to the Entrez Programming Utilities aimed at allowing an easy and smooth programmatic access to PubMed. The package is suitable for batch downloading large volumes of records (via the batch_pubmed_download() function) and also comes with a set of functions to perform basic processing of the PubMed query output. easyPubMed can request and handle PubMed records in either XML or TXT format. This vignette covers the key functions of the package and provides informative examples.

+
+

Retrieving data from PubMed

+

The first section of this tutorial covers how to use easyPubMed for querying Entrez and how to retrieve or download the desired PubMed records from the Entrez History Server.

+
+

A simple PubMed query via easyPubMed

+

Performing a standard PubMed search via easyPubMed is a two-step process: 1) the PubMed query step and 2) the data retrieval step. PubMed is queried via the get_pubmed_ids() function, that only takes one Query string as argument. The standard PubMed synthax applies, i.e. you can use the same tags-filters as in the This has two results. 1) the query results are posted on the Entrez History Server ready for retrieval and 2) the function returns a list containing all information to access and download these resuts from the server. Data can be retrieved from the History Server via the fetch_pubmed_data() function. The records can be requested in either XML or TXT format. Here following you can find a very simple example.

+
my_query <- "Damiano Fantini[AU]"
+my_entrez_id <- get_pubmed_ids(my_query)
+my_abstracts_txt <- fetch_pubmed_data(my_entrez_id, format = "abstract")
+my_abstracts_txt[1:10]
+
##  [1] ""                                                                               
+##  [2] "1. Oncotarget. 2017 Dec 16;9(4):4537-4548. doi: 10.18632/oncotarget.23344."     
+##  [3] "eCollection 2018 Jan 12."                                                       
+##  [4] ""                                                                               
+##  [5] "APOBEC-mediated mutagenesis in urothelial carcinoma is associated with improved"
+##  [6] "survival, mutations in DNA damage response genes, and immune response."         
+##  [7] ""                                                                               
+##  [8] "Glaser AP(1)(2), Fantini D(1)(2), Wang Y(1)(2), Yu Y(1)(2), Rimar KJ(1)(2),"    
+##  [9] "Podojil JR(3), Miller SD(3), Meeks JJ(1)(2)."                                   
+## [10] ""
+

Here, the PubMed records were retrieved in the Abstract format. The formats supported by Entrez and easyPubMed are the following: “asn.1”, “xml”, “medline”, “uilist”, “abstract”. The following example shows how to retrieve PubMed records in XML format. In this case, the resulting output will be a XMLInternalDocument and XMLAbstractDocument class object. To access such XML object, we recommend using the functions included in the XML package. For example, it is possible to extract the title of each Article as follows.

+
my_abstracts_xml <- fetch_pubmed_data(my_entrez_id)
+class(my_abstracts_xml) 
+
## [1] "XMLInternalDocument" "XMLAbstractDocument"
+
#
+# apply "saveXML" to each //ArticleTitle tag via XML::xpathApply()
+my_titles <- unlist(xpathApply(my_abstracts_xml, "//ArticleTitle", saveXML))
+#
+# use gsub to remove the tag, also trim long titles
+my_titles <- gsub("(^.{5,10}Title>)|(<\\/.*$)", "", my_titles)
+my_titles[nchar(my_titles)>75] <- paste(substr(my_titles[nchar(my_titles)>75], 1, 70), 
+                                        "...", sep = "")
+print(my_titles)
+
##  [1] "APOBEC-mediated mutagenesis in urothelial carcinoma is associated with..."
+##  [2] "A Carcinogen-induced mouse model recapitulates the molecular alteratio..."
+##  [3] "DDB2 Is a Novel Regulator of Wnt Signaling in Colon Cancer."              
+##  [4] "The evolving genomic landscape of urothelial carcinoma."                  
+##  [5] "Chromatin association of XRCC5/6 in the absence of DNA damage depends ..."
+##  [6] "The prion protein is critical for DNA repair and cell survival after g..."
+##  [7] "Rapid inactivation and proteasome-mediated degradation of OGG1 contrib..."
+##  [8] "Understanding different functions of mammalian AP endonuclease (APE1) ..."
+##  [9] "Critical lysine residues within the overlooked N-terminal domain of hu..."
+## [10] "APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the..."
+## [11] "APE1/Ref-1 regulates PTEN expression mediated by Egr-1."
+
+
+

Downloading and saving records as XML or TXT files

+

Instead of retrieving PubMed records as character- or XML-class objects, it is also possible to download all records of a PubMed query and save them as txt or xml files on the local computer. Downloaded records will be saved locally as one or more files with the same prefix followed by a sequential number and the txt or xml extension. If a destination folder is not specified, the current directory will be used as target directory for the download. The batch_pubmed_download() function is suitable for downloading very large volumes of PubMed records.

+
new_query <- "(APE1[TI] OR OGG1[TI]) AND (2012[PDAT]:2016[PDAT])"
+out.A <- batch_pubmed_download(pubmed_query_string = new_query, 
+                               format = "xml", 
+                               batch_size = 150,
+                               dest_file_prefix = "easyPM_example")
+
## [1] "PubMed data batch 1 / 2 downloaded..."
+## [1] "PubMed data batch 2 / 2 downloaded..."
+
out.A # this variable stores the name of the output files
+
## [1] "easyPM_example01.xml" "easyPM_example02.xml"
+
+
+
+

Manipulating PubMed records

+

The second section of this tutorial covers those easyPubMed functionalities aimed at transforming and analyzing PubMed records. While using the functions from the XML package is usually the recommended approach to deal with data stored in XML format, there are some exceptions where it may be convenient to coerce these records to Strings. easyPubMed comes with a set of dedicated functions that perform this task and manipulate the results. These functions will be covered in this section.

+
+

Extracting Affiliation data from a single PubMed record

+

TO convert XML PubMed records to strings, the articles_to_list() function is used. This function converts an an XML object containing PubMed records (identified by the \\PubmedArticle tag) into a list of individual records from or an XML file obtained as shown above. Each record in the list is a string (character-class vector of length 1) that still includes XML tags.

+
my_PM_list <- articles_to_list(my_abstracts_xml)
+class(my_PM_list[[4]])
+
## [1] "character"
+
cat(substr(my_PM_list[[4]], 1, 984))
+
## <PubmedArticle>
+##   <MedlineCitation Status="Publisher" Owner="NLM">
+##     <PMID Version="1">28169993</PMID>
+##     <DateRevised>
+##       <Year>2017</Year>
+##       <Month>06</Month>
+##       <Day>03</Day>
+##     </DateRevised>
+##     <Article PubModel="Print-Electronic">
+##       <Journal>
+##         <ISSN IssnType="Electronic">1759-4820</ISSN>
+##         <JournalIssue CitedMedium="Internet">
+##           <Volume>14</Volume>
+##           <Issue>4</Issue>
+##           <PubDate>
+##             <Year>2017</Year>
+##             <Month>Feb</Month>
+##             <Day>07</Day>
+##           </PubDate>
+##         </JournalIssue>
+##         <Title>Nature reviews. Urology</Title>
+##         <ISOAbbreviation>Nat Rev Urol</ISOAbbreviation>
+##       </Journal>
+##       <ArticleTitle>The evolving genomic landscape of urothelial carcinoma.</ArticleTitle>
+##       <Pagination>
+##         <MedlinePgn>215-229</MedlinePgn>
+##       </Pagination>
+##       <ELocationID EIdType="doi" ValidYN="Y">10.1038/nrurol.2017.11</ELocationID>
+##       <Abstract>
+##         <AbstractT
+

Affiliations or other fields of interest can be extracted from a specific record using the custom_grep() function, that combines regular expressions (regexpr, gsub) and substring extraction (substr). The fields extracted from the record will be returned as elements of a list or a character vector.

+
curr_PM_record <- my_PM_list[[4]]
+custom_grep(curr_PM_record, tag = "DateCompleted")
+
## list()
+
custom_grep(curr_PM_record, tag = "LastName", format = "char")
+
## [1] "Glaser"      "Fantini"     "Shilatifard" "Schaeffer"   "Meeks"
+

easyPubMed implements out of the box a tool for extracting data from a PubMed record: the article_to_df() function. This function accepts a string as input (typically, an element of the list outputted by an articles_to_list() call) and returns a data.frame. Each row corresponds to a different author; columns include values extracted from the following fields: c(“pmid”, “doi”, “title”, “abstract”, “year”, “month”, “day”, “jabbrv”, “journal”, “lastname”, “firstname”, “address”, “email”). One of these fields corresponds to the Article Abstract text (column n. 2). If the full text Abstract is not required, it is possible to limit the number of chars retrieved from this field by setting the max_chars argument to a small integer (>= 1).

+
my.df <- article_to_df(curr_PM_record, max_chars = 18)
+#
+# Fields extracted from the PubMed record
+colnames(my.df)
+
##  [1] "pmid"      "doi"       "title"     "abstract"  "year"     
+##  [6] "month"     "day"       "jabbrv"    "journal"   "lastname" 
+## [11] "firstname" "address"   "email"
+
#
+# Trim long strings and then Display some content: each row corresponds to one author
+my.df$title <- substr(my.df$title, 1, 15)
+my.df$address <- substr(my.df$address, 1, 19)
+my.df$jabbrv <- substr(my.df$jabbrv, 1, 10)
+my.df[,c("pmid", "title", "jabbrv", "firstname", "address")]
+
##       pmid           title     jabbrv   firstname             address
+## 1 28169993 The evolving ge Nat Rev Ur Alexander P Northwestern Univer
+## 2 28169993 The evolving ge Nat Rev Ur     Damiano Northwestern Univer
+## 3 28169993 The evolving ge Nat Rev Ur         Ali Northwestern Univer
+## 4 28169993 The evolving ge Nat Rev Ur    Edward M Northwestern Univer
+## 5 28169993 The evolving ge Nat Rev Ur    Joshua J Northwestern Univer
+

When affiliation info are identical for multiple authors, they are usually omitted as in the example above. Addresses may be imputed for all authors in the dataframe by setting the “autofill” argument to TRUE.

+
my.df2 <- article_to_df(curr_PM_record, autofill = TRUE)
+my.df2$title <- substr(my.df2$title, 1, 15)
+my.df2$jabbrv <- substr(my.df2$jabbrv, 1, 10)
+my.df2$address <- substr(my.df2$address, 1, 19)
+my.df2[,c("pmid", "title", "jabbrv", "firstname", "address")]
+
##       pmid           title     jabbrv   firstname             address
+## 1 28169993 The evolving ge Nat Rev Ur Alexander P Northwestern Univer
+## 2 28169993 The evolving ge Nat Rev Ur     Damiano Northwestern Univer
+## 3 28169993 The evolving ge Nat Rev Ur         Ali Northwestern Univer
+## 4 28169993 The evolving ge Nat Rev Ur    Edward M Northwestern Univer
+## 5 28169993 The evolving ge Nat Rev Ur    Joshua J Northwestern Univer
+
+
+

Automatic Data Extraction from XML PubMed Records

+

To retrieve author information and publication data from multiple XML records at once, it is possible to use the table_articles_byAuth() function. This function relies on the funcions discussed above and returns a dataframe including all the fields extracted in the previous example. The function accepts five arguments. * pubmed_data: an XML file or an XML object with PubMed records
+* max_chars and autofill: same as discussed in the previous example * included_authors: one of the following options c(“first”, “last”, “all”). The function can return data corresponding to the first, the last or all the authors for each PubMed record. * dest_file: if not NULL, the function attempts writing its output to the selected file. Existing files will be overwritten.

+
new_PM_query <- "(APEX1[TI] OR OGG1[TI]) AND (2010[PDAT]:2013[PDAT])"
+out.B <- batch_pubmed_download(pubmed_query_string = new_PM_query, dest_file_prefix = "apex1_sample")
+
## [1] "PubMed data batch 1 / 1 downloaded..."
+
# Retrieve the full name of the XML file downloaded in the previous step
+new_PM_file <- out.B[1]
+new_PM_df <- table_articles_byAuth(pubmed_data = new_PM_file, included_authors = "first", max_chars = 0)
+# Alternatively, the output of a fetch_pubmed_data() could have been used
+#
+# Printing a sample of the resulting data frame
+new_PM_df$address <- substr(new_PM_df$address, 1, 28)
+new_PM_df$jabbrv <- substr(new_PM_df$jabbrv, 1, 9)
+print(new_PM_df[1:10, c("pmid", "year", "jabbrv", "lastname", "address")])  
+
##        pmid year    jabbrv    lastname                      address
+## 1  24190502 2015 Arch. Tox        Bach Grup de Mutagènesi, Departam
+## 2  24186001 2014 Tumour Bi         Yan Department of Clinical Labor
+## 3  24175791 2014 Asian Pac          Li Cancer Center, Daping Hospit
+## 4  24121118 2014 Mech. Age    Lillenes Centre for Molecular Biology
+## 5  24101388 2014 J. Physio Antushevich The Kielanowski Institute of
+## 6  24075420 2014 DNA Repai          Gu State Key Laboratory of Repr
+## 7  23999824 2014 Tumour Bi        Chen Department of Hepatobiliary 
+## 8  23959014 2014 Biol. Res     Alanazi Genome Research Chair, Depar
+## 9  23909557 2014 Genet Tes        Wang Department of Oncology, Shan
+## 10 23892003 2014 Exp. Cell         Yan State Key Laboratory of Repr
+
+
+
+

References

+ +
+
+

Feedback and Citation

+

Thank you very much for using easyPubMed and/or reading this vignette. Please, feel free to contact me (author/maintainer) for feedback, questions and suggestions: my email is <damiano.fantini(at)gmail(dot)com>.

+

easyPubMed Copyright (C) 2017 Damiano Fantini. This program is free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; either version 2 of the License, or any later version. This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details.

+

If you are using easyPubMed for a scientific publication, please name the package in the Materials and Methods section of the paper. Thanks! Also, I am always open to collaborations. If you have an idea you would like to discuss or develop based on what you read in this Vignette, feel free to contact me via email. Thank you.

+
+
+

SessionInfo

+
sessionInfo()
+
## R version 3.4.3 (2017-11-30)
+## Platform: x86_64-pc-linux-gnu (64-bit)
+## Running under: Ubuntu 16.04.3 LTS
+## 
+## Matrix products: default
+## BLAS: /usr/lib/libblas/libblas.so.3.6.0
+## LAPACK: /usr/lib/lapack/liblapack.so.3.6.0
+## 
+## locale:
+##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
+##  [3] LC_TIME=en_US.UTF-8        LC_COLLATE=C              
+##  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
+##  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
+##  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
+## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
+## 
+## attached base packages:
+## [1] stats     graphics  grDevices utils     datasets  methods   base     
+## 
+## other attached packages:
+## [1] easyPubMed_2.5 XML_3.98-1.9  
+## 
+## loaded via a namespace (and not attached):
+##  [1] compiler_3.4.3  backports_1.1.2 magrittr_1.5    rprojroot_1.3-2
+##  [5] htmltools_0.3.6 tools_3.4.3     yaml_2.1.16     Rcpp_0.12.15   
+##  [9] stringi_1.1.7   rmarkdown_1.8   knitr_1.19      stringr_1.3.0  
+## [13] digest_0.6.15   evaluate_0.10.1
+
+ + + + +
+ + + + + + + + diff --git a/SEERResearchPerCountries.Rmd b/SEERResearchPerCountries.Rmd index 1435790..133e1ef 100644 --- a/SEERResearchPerCountries.Rmd +++ b/SEERResearchPerCountries.Rmd @@ -315,7 +315,6 @@ deneme4 <- deneme2 %>% ```{r} deneme4 %>% - ggplot() + aes(y = total, x = year, group = Country, color = Country) + geom_line() + @@ -331,6 +330,28 @@ ggplot() +

While helping the preparation of #PBPath Journal Watch (https://t.co/WiBsJixzlc) I thought that many SEER @NCICancerStats studies are from China. So using edirect @NCBI and #RStats I draw the attached graph. What do you think? Do Chinese do research on SEER that much? pic.twitter.com/3Op5r9ofbK

— Serdar Balcı (@serdarbalci) October 6, 2018
+```{r} +p <- deneme4 %>% +ggplot() + + aes(y = total, x = year, group = Country, color = Country) + + geom_line() + + # guides(fill=FALSE, color=FALSE) + + theme(axis.text.x = element_text(angle = 90, hjust = 1)) + + +``` + + + + + + + + + + + + diff --git a/SEERResearchPerCountries.nb.html b/SEERResearchPerCountries.nb.html index 9f470ff..6f74c02 100644 --- a/SEERResearchPerCountries.nb.html +++ b/SEERResearchPerCountries.nb.html @@ -11,7 +11,7 @@ - + Bibliographic Studies @@ -1743,7 +1743,7 @@

Bibliographic Studies

SEER Research Per Countries / Who is doing SEER Research?

Serdar Balcı, MD, Pathologist

-

2018-10-06

+

2018-10-08

@@ -2074,18 +2074,28 @@

Data retriveal from PubMed using EDirect

+ +
deneme4 <- deneme2 %>% 
+  gather(key = "Country", value = "Number", -c(1:2)) %>% 
+  group_by(Country, year) %>% 
+  summarise(total = sum(Number)) %>% 
+  filter(year != "na") %>%
+  filter(year != "2017") %>% 
+  filter(year != "2018") %>% 
+  filter(total != "0")
+ -
deneme4 %>% 
-
-ggplot() +
-  aes(y = total, x = year, group = Country, color = Country) +
-  geom_line() + 
-  # guides(fill=FALSE, color=FALSE) +
-  theme(axis.text.x = element_text(angle = 90, hjust = 1))
+
deneme4 %>% 
+
+ggplot() +
+  aes(y = total, x = year, group = Country, color = Country) +
+  geom_line() + 
+  # guides(fill=FALSE, color=FALSE) +
+  theme(axis.text.x = element_text(angle = 90, hjust = 1))

@@ -2111,6 +2121,22 @@

Data retriveal from PubMed using EDirect

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t.nodeType===Node.ELEMENT_NODE?void(l=t):u.isType("function",t)?void(c=t):void(u.isType("object",t)&&(d=t))}),h.length!==t.length||0===p.length?(c&&u.async(function(){c(!1)}),i.reject(new Error("Not enough parameters. Expected: "+r))):l?(d=u.aug({},d||{},e),t.forEach(function(t){d[t]=h.shift()}),a.asBoolean(d.dnt)&&s.setOn(),f=o.addWidget(n(d,l)),c&&f.then(c,function(){c(!1)}),f):(c&&u.async(function(){c(!1)}),i.reject(new Error("No target element specified. Expected: "+r)))}}var i=n(2),o=n(35),s=n(47),a=n(27),u=n(12);t.exports=r},function(t,e,n){var r=n(117),i=n(246),o=i(["screenName"],{},r);t.exports={createFollowButton:o}},function(t,e,n){var r=n(131),i=n(246),o=i(["collectionId"],{},r);t.exports={createGridFromCollection:o}},function(t,e,n){var r=n(161),i=n(246),o=i(["momentId"],{},r);t.exports={createMoment:o}},function(t,e,n){var r=n(175),i=n(246),o=i(["username"],{},r);t.exports={createPeriscopeOnAirButton:o}},function(t,e,n){function r(t){var e,n=a.toRealArray(arguments).slice(1);return u.isString(t)||u.isNumber(t)?h.reject("Embedded timelines with widget settings have been deprecated. See https://twittercommunity.com/t/deprecating-widget-settings/102295."):a.isObject(t)?(t=t||{},n.forEach(function(t){a.isType("object",t)&&(e=t,i(e))}),e||(e={},n.push(e)),t.lang=e.lang,t.tweetLimit=e.tweetLimit,t.showReplies=e.showReplies,e.dataSource=c(t),f.apply(this,n)):h.reject("data source must be an object.")}function i(t){t.ariaLive=t.ariaPolite}var o=n(11),s=n(25),a=n(12),u=n(27),c=n(181),d=n(194),l=n(246),f=l([],{},d),h=n(2),p={createTimeline:r};s.isTwitterURL(o.href)&&(p.createTimelinePreview=function(t,e,n){var r={previewParams:t,useLegacyDefaults:!0,isPreviewTimeline:!0};return r.dataSource=c(r),f(e,r,n)}),t.exports=p},function(t,e,n){function r(t){return function(){return i.toRealArray(arguments).slice(1).forEach(function(t){i.isType("object",t)&&(t.hideCard="none"==t.cards||"hidden"==t.cards,t.hideThread="none"==t.conversation||"hidden"==t.conversation)}),t.apply(this,arguments)}}var i=n(12),o=n(221),s=n(246),a=r(s(["tweetId"],{},o));t.exports={createTweet:a,createTweetEmbed:a,createVideo:a}},function(t,e,n){function r(t){return function(){return i.toRealArray(arguments).slice(1).forEach(function(t){i.isType("object",t)&&(t.screenName=t.screenName||t.screen_name,t.buttonHashtag=t.buttonHashtag||t.button_hashtag||t.hashtag)}),t.apply(this,arguments)}}var i=n(12),o=n(240),s=n(246),a=s(["url"],{type:"share"},o),u=s(["buttonHashtag"],{type:"hashtag"},o),c=s(["screenName"],{type:"mention"},o);t.exports={createShareButton:r(a),createHashtagButton:r(u),createMentionButton:r(c)}},function(t,e,n){function r(){var t,e;for(c=1,t=0,e=d.length;t + + + + + + +
no non-missing arguments to min; returning InfError: time data must either be integer, numeric, POSIXct, Date, difftime, orhms
+ + + + + + + @@ -2317,7 +2343,7 @@

Data retriveal from PubMed using EDirect

- + @@ -2326,7 +2352,7 @@

Data retriveal from PubMed using EDirect

-
---
title: "Bibliographic Studies"
subtitle: "SEER Research Per Countries / Who is doing SEER Research?"
author: "Serdar Balcı, MD, Pathologist"
date: '`r format(Sys.Date())`'
output: 
  html_notebook: 
    code_folding: hide
    fig_caption: yes
    highlight: kate
    theme: cerulean
    toc_float: yes
  html_document: 
    code_folding: hide
    df_print: kable
    fig_caption: yes
    highlight: kate
    keep_md: yes
    theme: cerulean
    toc_float: yes
---



```{r global_options, include=FALSE}
knitr::opts_chunk$set(fig.width = 12, fig.height = 8, fig.path = 'figure/', echo = FALSE, warning = FALSE, message = FALSE, error = FALSE, eval = TRUE, tidy = TRUE, comment = NA)
```

```{r library, include=FALSE}
library(tidyverse)
```


```{r}
state.name
```


```{r}
# install.packages("maps")
# library(maps)
# x <- map("world", plot=FALSE)
# glimpse(x)
# x$names

```

```{r}
install.packages("rworldmap")
library(rworldmap)
vignette('rworldmap')
data(countryExData)
countryExData
```












SEER China vs others

https://www.rdocumentation.org/packages/bayesTFR/versions/6.1-2/topics/country.names


https://stat.ethz.ch/R-manual/R-devel/library/datasets/html/state.html




# Who works on SEER {.tabset .tabset-fade .tabset-pills}

If you want to see the code used in the analysis please click the code button on the right upper corner or throughout the page.  
Select from the tabs below.

---

## Aim 

**Aim:**



---

## Data retriveal from PubMed using EDirect 

Articles are downloaded as `xml`.

```{r Search PubMed write all data as xml, eval=FALSE, include=FALSE}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(
    myTerm,
    "esearch -db pubmed -query \"'SEER Program'[Mesh]
\" -datetype PDAT -mindate 1800 -maxdate 3000 | efetch -format xml > data/pubmed_result_SEER_MeSH.xml \n"
)
Sys.sleep(1)
repeat {
    Sys.sleep(0.1)
    if (rstudioapi::terminalBusy(myTerm) == FALSE) {
        print("Code Executed")
        break
    }
}
```



```{r extract journal names from all data xml, message=FALSE, warning=FALSE}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(
myTerm,
"xtract -input data/pubmed_result_SEER_MeSH.xml -pattern PubmedArticle -sep ' ' -def 'na' -element MedlineCitation/PMID PubDate/Year Affiliation> data/SEER_countries.csv \n"
)
Sys.sleep(1)
repeat {
Sys.sleep(0.1)
if (rstudioapi::terminalBusy(myTerm) == FALSE) {
print("Code Executed")
break
}
}
```


```{r}
library(readr)
SEER_countries <- read_delim("data/SEER_countries.csv", 
    "\t", escape_double = FALSE, col_names = c("PMID", "year", "Affiliations"), 
    na = "NA", trim_ws = TRUE)
# View(SEER_countries)
```

```{r}
countries <- read_delim("data/countries.txt", delim = "|", col_names = c("abb", "country"))

country <- countries$country

country <- c(country, state.name)

country[80] <- "Georgia_"

```



```{r}
# SEER_countries <- cbind(SEER_countries, setNames(lapply(country, function(x) x=NA), country))

# names(SEER_countries)[254] <- "GeorgiaUSA"


```

```{r}
# grepl(pattern = "China", x = SEER_countries$Affiliations)
```


```{r}
# deneme1 <- grepl(pattern = country[44], x = SEER_countries$Affiliations)
    
# deneme2 <- sapply(country, function(x) grepl(x, SEER_countries$Affiliations))

# sum(deneme1 != deneme2[,44])

```

```{r}
# deneme2 <- as.data.frame(deneme2)

# sum(deneme2$Turkey)
```

```{r}
SEER_countries <- cbind(SEER_countries, sapply(country, function(x) grepl(x, SEER_countries$Affiliations)))
```


```{r}
dim(SEER_countries)[1]
```

At the time of the research the number of articles with 'SEER Program'[Mesh] formula is `r dim(SEER_countries)[1]`.

```{r}
# deneme <- colSums(SEER_countries[,-(1:3)])

# deneme <- as.data.frame(deneme)

# deneme <- rownames_to_column(deneme, var = "countries")

# names(deneme) <- c("countries", "number")

# deneme %>% arrange(desc(number))


```

```{r}
SEER_countries[SEER_countries == FALSE] <- 0

SEER_countries[SEER_countries == TRUE] <- 1

```



```{r}
countryTotals <- SEER_countries %>% 
  select(-c(1:3)) %>% 
  summarise_all(funs(sum)) 

countryTotals[which(countryTotals>0)]

publisherCountries <- names(countryTotals[which(countryTotals>0)])

SEER_countries <- SEER_countries %>% 
  select(c(1:3, publisherCountries))

```



```{r}
deneme <- SEER_countries %>% 
  gather(key = "Country", value = "Number", -c(1:3)) %>% 
  group_by(Country, year) %>% 
  summarise(total = sum(Number))
```


```{r}
deneme %>% 
  filter(year != "na") %>%
  filter(year != "2017") %>% 
  filter(year != "2018") %>% 
ggplot() +
  aes(y = total, x = year, group = Country, color = Country) +
  geom_line() + 
  guides(fill=FALSE, color=FALSE) +
  theme(axis.text.x = element_text(angle = 90, hjust = 1))
```


```{r}
USAnames <- names(SEER_countries) %in% state.name

Others <- setdiff(names(SEER_countries[-c(1:3)]), c(USAnames,"United States", "China"))


deneme2 <- SEER_countries %>% 
  mutate(
    sumUSA = rowSums(
      select(., one_of(USAnames), `United States`)
      )
    ) %>% 
mutate(
    sumOthers = rowSums(
      select(., one_of(Others))
      )
    ) %>% 
  select(PMID, year, China, USA = sumUSA, Others = sumOthers)

```

```{r}
deneme3 <- deneme2 %>% 
  gather(key = "Country", value = "Number", -c(1:2)) %>% 
  group_by(PMID, Country, year) %>% 
  summarise(total = sum(Number)) %>% 
  filter(year != "na") %>%
  filter(year != "2017") %>% 
  filter(year != "2018") %>% 
  filter(total != "0")
```


```{r}
# which(duplicated(deneme3$PMID))
# which(duplicated(deneme3$PMID))-1

# deneme3[which(duplicated(deneme3$PMID)),]

together <- bind_cols(
First = deneme3$Country[which(duplicated(deneme3$PMID))],
Second = deneme3$Country[which(duplicated(deneme3$PMID))-1]
)

table(together$First, together$Second) %>% addmargins()
bind_cols(

```



```{r}
deneme4 <- deneme2 %>% 
  gather(key = "Country", value = "Number", -c(1:2)) %>% 
  group_by(Country, year) %>% 
  summarise(total = sum(Number)) %>% 
  filter(year != "na") %>%
  filter(year != "2017") %>% 
  filter(year != "2018") %>% 
  filter(total != "0")
```



```{r}
deneme4 %>% 

ggplot() +
  aes(y = total, x = year, group = Country, color = Country) +
  geom_line() + 
  # guides(fill=FALSE, color=FALSE) +
  theme(axis.text.x = element_text(angle = 90, hjust = 1))
```



<iframe src="https://www.facebook.com/plugins/post.php?href=https%3A%2F%2Fwww.facebook.com%2Fserdarbalcimdpathologist%2Fposts%2F1919706581479009&width=500" width="500" height="529" style="border:none;overflow:hidden" scrolling="no" frameborder="0" allowTransparency="true" allow="encrypted-media"></iframe>


<blockquote class="twitter-tweet" data-lang="en"><p lang="en" dir="ltr">While helping the preparation of <a href="https://twitter.com/hashtag/PBPath?src=hash&amp;ref_src=twsrc%5Etfw">#PBPath</a> Journal Watch (<a href="https://t.co/WiBsJixzlc">https://t.co/WiBsJixzlc</a>)  I thought that many SEER <a href="https://twitter.com/NCICancerStats?ref_src=twsrc%5Etfw">@NCICancerStats</a> studies are from China. So using edirect <a href="https://twitter.com/NCBI?ref_src=twsrc%5Etfw">@NCBI</a> and <a href="https://twitter.com/hashtag/RStats?src=hash&amp;ref_src=twsrc%5Etfw">#RStats</a> I draw the attached graph. What do you think? Do Chinese do research on SEER that much? <a href="https://t.co/3Op5r9ofbK">pic.twitter.com/3Op5r9ofbK</a></p>&mdash; Serdar Balcı (@serdarbalci) <a href="https://twitter.com/serdarbalci/status/1048663302916788224?ref_src=twsrc%5Etfw">October 6, 2018</a></blockquote><script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>




<!-- ```{r Search PubMed write 2018 data as xml, eval=FALSE, include=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!--     myTerm, -->
<!--     "esearch -db pubmed -query \"Turkey[Affiliation]\" -datetype PDAT -mindate 2018 -maxdate 3000 | efetch -format xml > data/Turkey_2018.xml \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!--     Sys.sleep(0.1) -->
<!--     if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!--         print("Code Executed") -->
<!--         break -->
<!--     } -->
<!-- } -->
<!-- ``` -->




<!-- ```{r Search PubMed write all data as xml, eval=FALSE, include=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!--     myTerm, -->
<!--     "esearch -db pubmed -query \"Turkey[Affiliation]\" -datetype PDAT -mindate 1800 -maxdate 3000 | efetch -format xml > data/Turkey_all.xml \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!--     Sys.sleep(0.1) -->
<!--     if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!--         print("Code Executed") -->
<!--         break -->
<!--     } -->
<!-- } -->
<!-- ``` -->





<!-- ```{r Search PubMed get 2018 data on the fly, eval=FALSE, include=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!--     myTerm, -->
<!--     "esearch -db pubmed -query \"Turkey[Affiliation]\" -datetype PDAT -mindate 2018 -maxdate 3000 | efetch -format xml | xtract  -pattern PubmedArticle -element MedlineCitation/PMID PubDate/Year Journal/ISSN ISOAbbreviation> data/onthefly_Turkey_2018.csv \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!--     Sys.sleep(0.1) -->
<!--     if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!--         print("Code Executed") -->
<!--         break -->
<!--     } -->
<!-- } -->
<!-- ``` -->



<!-- ```{r Search PubMed get all data on the fly, eval=FALSE, include=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!--     myTerm, -->
<!--     "esearch -db pubmed -query \"Turkey[Affiliation]\" -datetype PDAT -mindate 1800 -maxdate 3000 | efetch -format xml | xtract  -pattern PubmedArticle -element MedlineCitation/PMID PubDate/Year Journal/ISSN ISOAbbreviation> data/onthefly_Turkey_all.csv \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!--     Sys.sleep(0.1) -->
<!--     if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!--         print("Code Executed") -->
<!--         break -->
<!--     } -->
<!-- } -->
<!-- ``` -->



<!-- Journal Names are extracted from xml. -->



<!-- ```{r extract journal names from 2018 xml, eval=FALSE, message=FALSE, warning=FALSE, include=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!-- myTerm, -->
<!-- "xtract -input data/Turkey_2018.xml -pattern PubmedArticle -element MedlineCitation/PMID PubDate/Year Journal/ISSN ISOAbbreviation > data/Turkey2018.csv \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!-- Sys.sleep(0.1) -->
<!-- if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!-- print("Code Executed") -->
<!-- break -->
<!-- } -->
<!-- } -->
<!-- ``` -->


<!-- ```{r extract journal names from all data xml, message=FALSE, warning=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!-- myTerm, -->
<!-- "xtract -input data/Turkey_all.xml -pattern PubmedArticle -sep ' ' -def 'na' -element MedlineCitation/PMID Journal/ISSN ISOAbbreviation PubDate/Year > data/TurkeyAll.csv \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!-- Sys.sleep(0.1) -->
<!-- if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!-- print("Code Executed") -->
<!-- break -->
<!-- } -->
<!-- } -->
<!-- ``` -->



<!-- ---- -->


<!-- ## Retrieval of Data of Properties of Journals -->



<!-- [nlmcatalog_result_journals_pmc.xml](https://www.ncbi.nlm.nih.gov/portal/utils/file_backend.cgi?Db=nlmcatalog&HistoryId=NCID_1_69755278_130.14.18.97_5555_1534585934_3590606783_0MetA0_S_HStore&QueryKey=2&Sort=PubDate&Filter=all&CompleteResultCount=2559&Mode=file&View=xml&p$l=Email&portalSnapshot=%2Fprojects%2Fentrez%2Fpubmed%2FPubMedGroup@1.136&BaseUrl=&PortName=live&RootTag=NLMCatalogRecordSet&DocType=NLMCatalogRecordSet%20PUBLIC%20%22-%2F%2FNLM%2F%2FDTD%20NLMCatalogRecordSet,%201st%20June%202017%2F%2FEN%22%20%22https://www.nlm.nih.gov/databases/dtd/nlmcatalogrecordset_170601.dtd%22&FileName=&ContentType=xml) -->


<!-- [nlmcatalog_result_currentlyindexed.xml](https://www.ncbi.nlm.nih.gov/portal/utils/file_backend.cgi?Db=nlmcatalog&HistoryId=NCID_1_69755278_130.14.18.97_5555_1534585934_3590606783_0MetA0_S_HStore&QueryKey=1&Sort=PubDate&Filter=all&CompleteResultCount=5242&Mode=file&View=xml&p$l=Email&portalSnapshot=%2Fprojects%2Fentrez%2Fpubmed%2FPubMedGroup@1.136&BaseUrl=&PortName=live&RootTag=NLMCatalogRecordSet&DocType=NLMCatalogRecordSet%20PUBLIC%20%22-%2F%2FNLM%2F%2FDTD%20NLMCatalogRecordSet,%201st%20June%202017%2F%2FEN%22%20%22https://www.nlm.nih.gov/databases/dtd/nlmcatalogrecordset_170601.dtd%22&FileName=&ContentType=xml) -->


<!-- [scimagojr2017.csv](https://www.scimagojr.com/journalrank.php?out=xls) -->

<!-- [scimagojr2017-wos.csv](https://www.scimagojr.com/journalrank.php?wos=true&out=xls) -->


<!-- ![](images/scidata.png) -->





<!-- --- -->






<!-- ## Analysis -->

<!-- ```{r Organize Journal Data 1, message=FALSE, warning=FALSE} -->
<!-- library(tidyverse) -->
<!-- library(readr) -->

<!-- TurkeyAll <- read_delim("data/TurkeyAll.csv",  -->
<!--     "\t", escape_double = FALSE, col_names = FALSE, -->
<!--     na = "na", trim_ws = TRUE) -->

<!-- names(TurkeyAll) <- c("PMID", "ISSN", "JournalName", "Year") -->

<!-- # dim(TurkeyAll)[1] -->

<!-- # min(TurkeyAll[,4], na.rm = TRUE) -->

<!-- # max(TurkeyAll[,4], na.rm = TRUE) -->

<!-- # glimpse(TurkeyAll) -->

<!-- ``` -->



<!-- ```{r Organize Journal Data 2} -->
<!-- uniqueJournals <- TurkeyAll %>%  -->
<!--     select(JournalName, ISSN) %>%  -->
<!--     unique() -->

<!-- # dim(uniqueJournals)[1] -->

<!-- ``` -->


<!-- ```{r Organize Journal Data 3} -->

<!-- TurkeyAll2 <- TurkeyAll %>%  -->
<!--     mutate(Journal = paste(JournalName, ISSN, sep = " ISSN ")) -->

<!-- ArticlesByYear <- TurkeyAll2 %>%  -->
<!--     group_by(Journal, Year) %>%  -->
<!--     summarise(n = n()) -->

<!-- ArticlesByYear <- ArticlesByYear %>%  -->
<!--     spread(key = Year, value = n) -->

<!-- TurkeyAll2 <- TurkeyAll2 %>%  -->
<!--     select(Journal, JournalName, ISSN) %>%  -->
<!--     unique() -->

<!-- ArticlesByYear <- left_join(ArticlesByYear, TurkeyAll2, by = "Journal")  -->

<!-- ArticlesByYear <- ArticlesByYear %>% -->
<!--     select( -->
<!--     Journal, JournalName, ISSN, everything() -->
<!--     ) -->

<!-- ``` -->


<!-- ```{r scimagojr2017} -->

<!-- ``` -->



<!-- -element MedlineTA  NLMCatalogRecord/NlmUniqueID -def 'na' -sep '\t' -block TitleAlternate/Title   -element TitleAlternate/Title    -->

<!-- "xtract -input data/nlmcatalog_result_currentlyindexed.xml -pattern NCBICatalogRecord -element ISSNLinking -def 'na' -sep ' ' -block TitleAlternate/Title -if TitleAlternate/Title@Sort -equals N -element TitleAlternate/Title  > data/nlmcatalog.csv \n" -->

<!-- -sep '\t'  -->


<!-- NLMCatalogRecord/NlmUniqueID ISSNLinking -->

<!-- ```{r nlmcatalog, message=FALSE, warning=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!-- myTerm, -->
<!-- "xtract -input data/nlmcatalog_result_currentlyindexed.xml -pattern NCBICatalogRecord -tab '|' -element NLMCatalogRecord/NlmUniqueID -block ISSNLinking -tab '|' -element ISSNLinking -block Title -if Title@Sort -equals N -def 'na' -tab '|' -element TitleAlternate/Title > data/nlmcatalog.csv \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!-- Sys.sleep(0.1) -->
<!-- if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!-- print("Code Executed") -->
<!-- break -->
<!-- } -->
<!-- } -->

<!-- ```  -->


<!-- ```{r} -->
<!-- library(readr) -->
<!-- nlmcatalog <- read_delim("data/nlmcatalog.csv",  -->
<!--                          delim = "|", -->
<!--                          escape_double = FALSE, -->
<!--                          col_names = FALSE,  -->
<!--                          trim_ws = TRUE) -->

<!-- ``` -->

<!-- ```{r} -->

<!-- library(xml2) -->
<!-- data <- read_xml("data/nlmcatalog_result_currentlyindexed.xml") -->

<!-- # Point locations -->
<!-- point <- data %>% xml_find_all("//pointer") -->
<!-- point %>% xml_attr("latitude") %>% as.numeric() -->
<!-- point %>% xml_attr("longitude") %>% as.numeric() -->

<!-- # Start time -->
<!-- data %>%  -->
<!--   xml_find_all("//start-valid-time") %>%  -->
<!--   xml_text() -->

<!-- # Temperature -->
<!-- data %>%  -->
<!--   xml_find_all("//temperature[@type='hourly']/value") %>%  -->
<!--   xml_text() %>%  -->
<!--   as.integer() -->



<!-- ``` -->


<!-- --- -->

<!-- ## Results -->

<!-- - PubMed'de **`r min(TurkeyAll[,4], na.rm = TRUE)`-`r max(TurkeyAll[,4], na.rm = TRUE)`** tarihleri arasında, *Türkiye* adresli **`r dim(TurkeyAll)[1]`** adet yayın mevcuttur. -->

<!-- - PubMed'de **`r min(TurkeyAll[,4], na.rm = TRUE)`-`r max(TurkeyAll[,4], na.rm = TRUE)`** tarihleri arasında, *Türkiye* adresli yayınlar **`r dim(uniqueJournals)[1]`** farklı dergide yayımlanmıştır. -->





<!-- --- -->

<!-- ## Discussion -->

<!-- türkiye adresli olup da pubmedde yer alan makaleler hangi dergilerde kaçar adet yayınlanmış -->


<!-- The retrieved information was compiled in a table. -->





<!-- **Methods:** -->









<!-- **Result:** -->


<!-- ```{r plot 1} -->
<!-- ggplot(data = articles_per_journal, aes(x = Journal, y = n, group = Country, -->
<!--                                      colour = Country, shape = Country, -->
<!--                                      levels = Country -->
<!-- )) + -->
<!--     geom_point() + -->
<!--     labs(x = "Journals with decreasing impact factor", y = "Number of Articles") + -->
<!--     ggtitle("Pathology Articles Per Journal") +  -->
<!--     theme(plot.title = element_text(hjust = 0.5), -->
<!--           axis.text.x=element_blank()) -->

<!-- ``` -->


<!-- **Comment:** -->




<!-- --- -->


<!-- ## Feedback -->

<!-- [Serdar Balcı, MD, Pathologist](https://github.com/sbalci) would like to hear your feedback: https://goo.gl/forms/YjGZ5DHgtPlR1RnB3 -->

<!-- This document will be continiously updated and the last update was on `r Sys.Date()`. -->

<!-- --- -->

<!-- ## Back to Main Menu -->

<!-- [Main Page for Bibliographic Analysis](https://sbalci.github.io/pubmed/BibliographicStudies.html) -->

<!-- --- -->
+
---
title: "Bibliographic Studies"
subtitle: "SEER Research Per Countries / Who is doing SEER Research?"
author: "Serdar Balcı, MD, Pathologist"
date: '`r format(Sys.Date())`'
output: 
  html_notebook: 
    code_folding: hide
    fig_caption: yes
    highlight: kate
    theme: cerulean
    toc_float: yes
  html_document: 
    code_folding: hide
    df_print: kable
    fig_caption: yes
    highlight: kate
    keep_md: yes
    theme: cerulean
    toc_float: yes
---



```{r global_options, include=FALSE}
knitr::opts_chunk$set(fig.width = 12, fig.height = 8, fig.path = 'figure/', echo = FALSE, warning = FALSE, message = FALSE, error = FALSE, eval = TRUE, tidy = TRUE, comment = NA)
```

```{r library, include=FALSE}
library(tidyverse)
```


```{r}
state.name
```


```{r}
# install.packages("maps")
# library(maps)
# x <- map("world", plot=FALSE)
# glimpse(x)
# x$names

```

```{r}
install.packages("rworldmap")
library(rworldmap)
vignette('rworldmap')
data(countryExData)
countryExData
```












SEER China vs others

https://www.rdocumentation.org/packages/bayesTFR/versions/6.1-2/topics/country.names


https://stat.ethz.ch/R-manual/R-devel/library/datasets/html/state.html




# Who works on SEER {.tabset .tabset-fade .tabset-pills}

If you want to see the code used in the analysis please click the code button on the right upper corner or throughout the page.  
Select from the tabs below.

---

## Aim 

**Aim:**



---

## Data retriveal from PubMed using EDirect 

Articles are downloaded as `xml`.

```{r Search PubMed write all data as xml, eval=FALSE, include=FALSE}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(
    myTerm,
    "esearch -db pubmed -query \"'SEER Program'[Mesh]
\" -datetype PDAT -mindate 1800 -maxdate 3000 | efetch -format xml > data/pubmed_result_SEER_MeSH.xml \n"
)
Sys.sleep(1)
repeat {
    Sys.sleep(0.1)
    if (rstudioapi::terminalBusy(myTerm) == FALSE) {
        print("Code Executed")
        break
    }
}
```



```{r extract journal names from all data xml, message=FALSE, warning=FALSE}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(
myTerm,
"xtract -input data/pubmed_result_SEER_MeSH.xml -pattern PubmedArticle -sep ' ' -def 'na' -element MedlineCitation/PMID PubDate/Year Affiliation> data/SEER_countries.csv \n"
)
Sys.sleep(1)
repeat {
Sys.sleep(0.1)
if (rstudioapi::terminalBusy(myTerm) == FALSE) {
print("Code Executed")
break
}
}
```


```{r}
library(readr)
SEER_countries <- read_delim("data/SEER_countries.csv", 
    "\t", escape_double = FALSE, col_names = c("PMID", "year", "Affiliations"), 
    na = "NA", trim_ws = TRUE)
# View(SEER_countries)
```

```{r}
countries <- read_delim("data/countries.txt", delim = "|", col_names = c("abb", "country"))

country <- countries$country

country <- c(country, state.name)

country[80] <- "Georgia_"

```



```{r}
# SEER_countries <- cbind(SEER_countries, setNames(lapply(country, function(x) x=NA), country))

# names(SEER_countries)[254] <- "GeorgiaUSA"


```

```{r}
# grepl(pattern = "China", x = SEER_countries$Affiliations)
```


```{r}
# deneme1 <- grepl(pattern = country[44], x = SEER_countries$Affiliations)
    
# deneme2 <- sapply(country, function(x) grepl(x, SEER_countries$Affiliations))

# sum(deneme1 != deneme2[,44])

```

```{r}
# deneme2 <- as.data.frame(deneme2)

# sum(deneme2$Turkey)
```

```{r}
SEER_countries <- cbind(SEER_countries, sapply(country, function(x) grepl(x, SEER_countries$Affiliations)))
```


```{r}
dim(SEER_countries)[1]
```

At the time of the research the number of articles with 'SEER Program'[Mesh] formula is `r dim(SEER_countries)[1]`.

```{r}
# deneme <- colSums(SEER_countries[,-(1:3)])

# deneme <- as.data.frame(deneme)

# deneme <- rownames_to_column(deneme, var = "countries")

# names(deneme) <- c("countries", "number")

# deneme %>% arrange(desc(number))


```

```{r}
SEER_countries[SEER_countries == FALSE] <- 0

SEER_countries[SEER_countries == TRUE] <- 1

```



```{r}
countryTotals <- SEER_countries %>% 
  select(-c(1:3)) %>% 
  summarise_all(funs(sum)) 

countryTotals[which(countryTotals>0)]

publisherCountries <- names(countryTotals[which(countryTotals>0)])

SEER_countries <- SEER_countries %>% 
  select(c(1:3, publisherCountries))

```



```{r}
deneme <- SEER_countries %>% 
  gather(key = "Country", value = "Number", -c(1:3)) %>% 
  group_by(Country, year) %>% 
  summarise(total = sum(Number))
```


```{r}
deneme %>% 
  filter(year != "na") %>%
  filter(year != "2017") %>% 
  filter(year != "2018") %>% 
ggplot() +
  aes(y = total, x = year, group = Country, color = Country) +
  geom_line() + 
  guides(fill=FALSE, color=FALSE) +
  theme(axis.text.x = element_text(angle = 90, hjust = 1))
```


```{r}
USAnames <- names(SEER_countries) %in% state.name

Others <- setdiff(names(SEER_countries[-c(1:3)]), c(USAnames,"United States", "China"))


deneme2 <- SEER_countries %>% 
  mutate(
    sumUSA = rowSums(
      select(., one_of(USAnames), `United States`)
      )
    ) %>% 
mutate(
    sumOthers = rowSums(
      select(., one_of(Others))
      )
    ) %>% 
  select(PMID, year, China, USA = sumUSA, Others = sumOthers)

```

```{r}
deneme3 <- deneme2 %>% 
  gather(key = "Country", value = "Number", -c(1:2)) %>% 
  group_by(PMID, Country, year) %>% 
  summarise(total = sum(Number)) %>% 
  filter(year != "na") %>%
  filter(year != "2017") %>% 
  filter(year != "2018") %>% 
  filter(total != "0")
```


```{r}
# which(duplicated(deneme3$PMID))
# which(duplicated(deneme3$PMID))-1

# deneme3[which(duplicated(deneme3$PMID)),]

together <- bind_cols(
First = deneme3$Country[which(duplicated(deneme3$PMID))],
Second = deneme3$Country[which(duplicated(deneme3$PMID))-1]
)

table(together$First, together$Second) %>% addmargins()
bind_cols(

```



```{r}
deneme4 <- deneme2 %>% 
  gather(key = "Country", value = "Number", -c(1:2)) %>% 
  group_by(Country, year) %>% 
  summarise(total = sum(Number)) %>% 
  filter(year != "na") %>%
  filter(year != "2017") %>% 
  filter(year != "2018") %>% 
  filter(total != "0")
```



```{r}
deneme4 %>% 
ggplot() +
  aes(y = total, x = year, group = Country, color = Country) +
  geom_line() + 
  # guides(fill=FALSE, color=FALSE) +
  theme(axis.text.x = element_text(angle = 90, hjust = 1))
```



<iframe src="https://www.facebook.com/plugins/post.php?href=https%3A%2F%2Fwww.facebook.com%2Fserdarbalcimdpathologist%2Fposts%2F1919706581479009&width=500" width="500" height="529" style="border:none;overflow:hidden" scrolling="no" frameborder="0" allowTransparency="true" allow="encrypted-media"></iframe>


<blockquote class="twitter-tweet" data-lang="en"><p lang="en" dir="ltr">While helping the preparation of <a href="https://twitter.com/hashtag/PBPath?src=hash&amp;ref_src=twsrc%5Etfw">#PBPath</a> Journal Watch (<a href="https://t.co/WiBsJixzlc">https://t.co/WiBsJixzlc</a>)  I thought that many SEER <a href="https://twitter.com/NCICancerStats?ref_src=twsrc%5Etfw">@NCICancerStats</a> studies are from China. So using edirect <a href="https://twitter.com/NCBI?ref_src=twsrc%5Etfw">@NCBI</a> and <a href="https://twitter.com/hashtag/RStats?src=hash&amp;ref_src=twsrc%5Etfw">#RStats</a> I draw the attached graph. What do you think? Do Chinese do research on SEER that much? <a href="https://t.co/3Op5r9ofbK">pic.twitter.com/3Op5r9ofbK</a></p>&mdash; Serdar Balcı (@serdarbalci) <a href="https://twitter.com/serdarbalci/status/1048663302916788224?ref_src=twsrc%5Etfw">October 6, 2018</a></blockquote><script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>


```{r}
p <- deneme4 %>% 
ggplot() +
  aes(y = total, x = year, group = Country, color = Country) +
  geom_line() + 
  # guides(fill=FALSE, color=FALSE) +
  theme(axis.text.x = element_text(angle = 90, hjust = 1))


```



```{r}


  
```












<!-- ```{r Search PubMed write 2018 data as xml, eval=FALSE, include=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!--     myTerm, -->
<!--     "esearch -db pubmed -query \"Turkey[Affiliation]\" -datetype PDAT -mindate 2018 -maxdate 3000 | efetch -format xml > data/Turkey_2018.xml \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!--     Sys.sleep(0.1) -->
<!--     if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!--         print("Code Executed") -->
<!--         break -->
<!--     } -->
<!-- } -->
<!-- ``` -->




<!-- ```{r Search PubMed write all data as xml, eval=FALSE, include=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!--     myTerm, -->
<!--     "esearch -db pubmed -query \"Turkey[Affiliation]\" -datetype PDAT -mindate 1800 -maxdate 3000 | efetch -format xml > data/Turkey_all.xml \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!--     Sys.sleep(0.1) -->
<!--     if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!--         print("Code Executed") -->
<!--         break -->
<!--     } -->
<!-- } -->
<!-- ``` -->





<!-- ```{r Search PubMed get 2018 data on the fly, eval=FALSE, include=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!--     myTerm, -->
<!--     "esearch -db pubmed -query \"Turkey[Affiliation]\" -datetype PDAT -mindate 2018 -maxdate 3000 | efetch -format xml | xtract  -pattern PubmedArticle -element MedlineCitation/PMID PubDate/Year Journal/ISSN ISOAbbreviation> data/onthefly_Turkey_2018.csv \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!--     Sys.sleep(0.1) -->
<!--     if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!--         print("Code Executed") -->
<!--         break -->
<!--     } -->
<!-- } -->
<!-- ``` -->



<!-- ```{r Search PubMed get all data on the fly, eval=FALSE, include=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!--     myTerm, -->
<!--     "esearch -db pubmed -query \"Turkey[Affiliation]\" -datetype PDAT -mindate 1800 -maxdate 3000 | efetch -format xml | xtract  -pattern PubmedArticle -element MedlineCitation/PMID PubDate/Year Journal/ISSN ISOAbbreviation> data/onthefly_Turkey_all.csv \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!--     Sys.sleep(0.1) -->
<!--     if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!--         print("Code Executed") -->
<!--         break -->
<!--     } -->
<!-- } -->
<!-- ``` -->



<!-- Journal Names are extracted from xml. -->



<!-- ```{r extract journal names from 2018 xml, eval=FALSE, message=FALSE, warning=FALSE, include=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!-- myTerm, -->
<!-- "xtract -input data/Turkey_2018.xml -pattern PubmedArticle -element MedlineCitation/PMID PubDate/Year Journal/ISSN ISOAbbreviation > data/Turkey2018.csv \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!-- Sys.sleep(0.1) -->
<!-- if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!-- print("Code Executed") -->
<!-- break -->
<!-- } -->
<!-- } -->
<!-- ``` -->


<!-- ```{r extract journal names from all data xml, message=FALSE, warning=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!-- myTerm, -->
<!-- "xtract -input data/Turkey_all.xml -pattern PubmedArticle -sep ' ' -def 'na' -element MedlineCitation/PMID Journal/ISSN ISOAbbreviation PubDate/Year > data/TurkeyAll.csv \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!-- Sys.sleep(0.1) -->
<!-- if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!-- print("Code Executed") -->
<!-- break -->
<!-- } -->
<!-- } -->
<!-- ``` -->



<!-- ---- -->


<!-- ## Retrieval of Data of Properties of Journals -->



<!-- [nlmcatalog_result_journals_pmc.xml](https://www.ncbi.nlm.nih.gov/portal/utils/file_backend.cgi?Db=nlmcatalog&HistoryId=NCID_1_69755278_130.14.18.97_5555_1534585934_3590606783_0MetA0_S_HStore&QueryKey=2&Sort=PubDate&Filter=all&CompleteResultCount=2559&Mode=file&View=xml&p$l=Email&portalSnapshot=%2Fprojects%2Fentrez%2Fpubmed%2FPubMedGroup@1.136&BaseUrl=&PortName=live&RootTag=NLMCatalogRecordSet&DocType=NLMCatalogRecordSet%20PUBLIC%20%22-%2F%2FNLM%2F%2FDTD%20NLMCatalogRecordSet,%201st%20June%202017%2F%2FEN%22%20%22https://www.nlm.nih.gov/databases/dtd/nlmcatalogrecordset_170601.dtd%22&FileName=&ContentType=xml) -->


<!-- [nlmcatalog_result_currentlyindexed.xml](https://www.ncbi.nlm.nih.gov/portal/utils/file_backend.cgi?Db=nlmcatalog&HistoryId=NCID_1_69755278_130.14.18.97_5555_1534585934_3590606783_0MetA0_S_HStore&QueryKey=1&Sort=PubDate&Filter=all&CompleteResultCount=5242&Mode=file&View=xml&p$l=Email&portalSnapshot=%2Fprojects%2Fentrez%2Fpubmed%2FPubMedGroup@1.136&BaseUrl=&PortName=live&RootTag=NLMCatalogRecordSet&DocType=NLMCatalogRecordSet%20PUBLIC%20%22-%2F%2FNLM%2F%2FDTD%20NLMCatalogRecordSet,%201st%20June%202017%2F%2FEN%22%20%22https://www.nlm.nih.gov/databases/dtd/nlmcatalogrecordset_170601.dtd%22&FileName=&ContentType=xml) -->


<!-- [scimagojr2017.csv](https://www.scimagojr.com/journalrank.php?out=xls) -->

<!-- [scimagojr2017-wos.csv](https://www.scimagojr.com/journalrank.php?wos=true&out=xls) -->


<!-- ![](images/scidata.png) -->





<!-- --- -->






<!-- ## Analysis -->

<!-- ```{r Organize Journal Data 1, message=FALSE, warning=FALSE} -->
<!-- library(tidyverse) -->
<!-- library(readr) -->

<!-- TurkeyAll <- read_delim("data/TurkeyAll.csv",  -->
<!--     "\t", escape_double = FALSE, col_names = FALSE, -->
<!--     na = "na", trim_ws = TRUE) -->

<!-- names(TurkeyAll) <- c("PMID", "ISSN", "JournalName", "Year") -->

<!-- # dim(TurkeyAll)[1] -->

<!-- # min(TurkeyAll[,4], na.rm = TRUE) -->

<!-- # max(TurkeyAll[,4], na.rm = TRUE) -->

<!-- # glimpse(TurkeyAll) -->

<!-- ``` -->



<!-- ```{r Organize Journal Data 2} -->
<!-- uniqueJournals <- TurkeyAll %>%  -->
<!--     select(JournalName, ISSN) %>%  -->
<!--     unique() -->

<!-- # dim(uniqueJournals)[1] -->

<!-- ``` -->


<!-- ```{r Organize Journal Data 3} -->

<!-- TurkeyAll2 <- TurkeyAll %>%  -->
<!--     mutate(Journal = paste(JournalName, ISSN, sep = " ISSN ")) -->

<!-- ArticlesByYear <- TurkeyAll2 %>%  -->
<!--     group_by(Journal, Year) %>%  -->
<!--     summarise(n = n()) -->

<!-- ArticlesByYear <- ArticlesByYear %>%  -->
<!--     spread(key = Year, value = n) -->

<!-- TurkeyAll2 <- TurkeyAll2 %>%  -->
<!--     select(Journal, JournalName, ISSN) %>%  -->
<!--     unique() -->

<!-- ArticlesByYear <- left_join(ArticlesByYear, TurkeyAll2, by = "Journal")  -->

<!-- ArticlesByYear <- ArticlesByYear %>% -->
<!--     select( -->
<!--     Journal, JournalName, ISSN, everything() -->
<!--     ) -->

<!-- ``` -->


<!-- ```{r scimagojr2017} -->

<!-- ``` -->



<!-- -element MedlineTA  NLMCatalogRecord/NlmUniqueID -def 'na' -sep '\t' -block TitleAlternate/Title   -element TitleAlternate/Title    -->

<!-- "xtract -input data/nlmcatalog_result_currentlyindexed.xml -pattern NCBICatalogRecord -element ISSNLinking -def 'na' -sep ' ' -block TitleAlternate/Title -if TitleAlternate/Title@Sort -equals N -element TitleAlternate/Title  > data/nlmcatalog.csv \n" -->

<!-- -sep '\t'  -->


<!-- NLMCatalogRecord/NlmUniqueID ISSNLinking -->

<!-- ```{r nlmcatalog, message=FALSE, warning=FALSE} -->
<!-- myTerm <- rstudioapi::terminalCreate(show = FALSE) -->
<!-- rstudioapi::terminalSend( -->
<!-- myTerm, -->
<!-- "xtract -input data/nlmcatalog_result_currentlyindexed.xml -pattern NCBICatalogRecord -tab '|' -element NLMCatalogRecord/NlmUniqueID -block ISSNLinking -tab '|' -element ISSNLinking -block Title -if Title@Sort -equals N -def 'na' -tab '|' -element TitleAlternate/Title > data/nlmcatalog.csv \n" -->
<!-- ) -->
<!-- Sys.sleep(1) -->
<!-- repeat { -->
<!-- Sys.sleep(0.1) -->
<!-- if (rstudioapi::terminalBusy(myTerm) == FALSE) { -->
<!-- print("Code Executed") -->
<!-- break -->
<!-- } -->
<!-- } -->

<!-- ```  -->


<!-- ```{r} -->
<!-- library(readr) -->
<!-- nlmcatalog <- read_delim("data/nlmcatalog.csv",  -->
<!--                          delim = "|", -->
<!--                          escape_double = FALSE, -->
<!--                          col_names = FALSE,  -->
<!--                          trim_ws = TRUE) -->

<!-- ``` -->

<!-- ```{r} -->

<!-- library(xml2) -->
<!-- data <- read_xml("data/nlmcatalog_result_currentlyindexed.xml") -->

<!-- # Point locations -->
<!-- point <- data %>% xml_find_all("//pointer") -->
<!-- point %>% xml_attr("latitude") %>% as.numeric() -->
<!-- point %>% xml_attr("longitude") %>% as.numeric() -->

<!-- # Start time -->
<!-- data %>%  -->
<!--   xml_find_all("//start-valid-time") %>%  -->
<!--   xml_text() -->

<!-- # Temperature -->
<!-- data %>%  -->
<!--   xml_find_all("//temperature[@type='hourly']/value") %>%  -->
<!--   xml_text() %>%  -->
<!--   as.integer() -->



<!-- ``` -->


<!-- --- -->

<!-- ## Results -->

<!-- - PubMed'de **`r min(TurkeyAll[,4], na.rm = TRUE)`-`r max(TurkeyAll[,4], na.rm = TRUE)`** tarihleri arasında, *Türkiye* adresli **`r dim(TurkeyAll)[1]`** adet yayın mevcuttur. -->

<!-- - PubMed'de **`r min(TurkeyAll[,4], na.rm = TRUE)`-`r max(TurkeyAll[,4], na.rm = TRUE)`** tarihleri arasında, *Türkiye* adresli yayınlar **`r dim(uniqueJournals)[1]`** farklı dergide yayımlanmıştır. -->





<!-- --- -->

<!-- ## Discussion -->

<!-- türkiye adresli olup da pubmedde yer alan makaleler hangi dergilerde kaçar adet yayınlanmış -->


<!-- The retrieved information was compiled in a table. -->





<!-- **Methods:** -->









<!-- **Result:** -->


<!-- ```{r plot 1} -->
<!-- ggplot(data = articles_per_journal, aes(x = Journal, y = n, group = Country, -->
<!--                                      colour = Country, shape = Country, -->
<!--                                      levels = Country -->
<!-- )) + -->
<!--     geom_point() + -->
<!--     labs(x = "Journals with decreasing impact factor", y = "Number of Articles") + -->
<!--     ggtitle("Pathology Articles Per Journal") +  -->
<!--     theme(plot.title = element_text(hjust = 0.5), -->
<!--           axis.text.x=element_blank()) -->

<!-- ``` -->


<!-- **Comment:** -->




<!-- --- -->


<!-- ## Feedback -->

<!-- [Serdar Balcı, MD, Pathologist](https://github.com/sbalci) would like to hear your feedback: https://goo.gl/forms/YjGZ5DHgtPlR1RnB3 -->

<!-- This document will be continiously updated and the last update was on `r Sys.Date()`. -->

<!-- --- -->

<!-- ## Back to Main Menu -->

<!-- [Main Page for Bibliographic Analysis](https://sbalci.github.io/pubmed/BibliographicStudies.html) -->

<!-- --- -->
diff --git a/Semantic Scholar Open Research Corpus/Open Research Corpus Public Datasets of Scholarly Research Papers.html b/Semantic Scholar Open Research Corpus/Open Research Corpus Public Datasets of Scholarly Research Papers.html new file mode 100644 index 0000000..23d2465 --- /dev/null +++ b/Semantic Scholar Open Research Corpus/Open Research Corpus Public Datasets of Scholarly Research Papers.html @@ -0,0 +1 @@ +Open Research Corpus: Public Datasets of Scholarly Research Papers
\ No newline at end of file diff --git a/Semantic Scholar Open Research Corpus/sample-S2-records.gz b/Semantic Scholar Open Research Corpus/sample-S2-records.gz new file mode 100644 index 0000000..307e2d5 Binary files /dev/null and b/Semantic Scholar Open Research Corpus/sample-S2-records.gz differ diff --git a/SemanticScholar.Rmd b/SemanticScholar.Rmd new file mode 100644 index 0000000..8c93167 --- /dev/null +++ b/SemanticScholar.Rmd @@ -0,0 +1,19 @@ +--- +title: "Semantic Scholar" +output: html_notebook +--- + +This is an [R Markdown](http://rmarkdown.rstudio.com) Notebook. When you execute code within the notebook, the results appear beneath the code. + +Try executing this chunk by clicking the *Run* button within the chunk or by placing your cursor inside it and pressing *Cmd+Shift+Enter*. + +```{r} +plot(cars) +``` + +Add a new chunk by clicking the *Insert Chunk* button on the toolbar or by pressing *Cmd+Option+I*. + +When you save the notebook, an HTML file containing the code and output will be saved alongside it (click the *Preview* button or press *Cmd+Shift+K* to preview the HTML file). + +The preview shows you a rendered HTML copy of the contents of the editor. Consequently, unlike *Knit*, *Preview* does not run any R code chunks. Instead, the output of the chunk when it was last run in the editor is displayed. + diff --git a/SemanticScholar.nb.html b/SemanticScholar.nb.html new file mode 100644 index 0000000..9b30204 --- /dev/null +++ b/SemanticScholar.nb.html @@ -0,0 +1,1757 @@ + + + + + + + + + + + + + +Semantic Scholar + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + + + + + + + + + + + +

This is an R Markdown Notebook. When you execute code within the notebook, the results appear beneath the code.

+

Try executing this chunk by clicking the Run button within the chunk or by placing your cursor inside it and pressing Cmd+Shift+Enter.

+ + + +
plot(cars)
+ + + +

Add a new chunk by clicking the Insert Chunk button on the toolbar or by pressing Cmd+Option+I.

+

When you save the notebook, an HTML file containing the code and output will be saved alongside it (click the Preview button or press Cmd+Shift+K to preview the HTML file).

+

The preview shows you a rendered HTML copy of the contents of the editor. Consequently, unlike Knit, Preview does not run any R code chunks. Instead, the output of the chunk when it was last run in the editor is displayed.

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1432-07388832014MarArchives of toxicologyArch. Toxicol.Ogg1 genetic background determines the genotoxic potential of environmentally relevant arsenic exposures.585-9610.1007/s00204-013-1151-0Inorganic arsenic (i-As) is a well-established human carcinogen to which millions of people are exposed worldwide. It is generally accepted that the genotoxic effects of i-As after an acute exposure are partially linked to the i-As-induced production of reactive oxygen species, but it is necessary to better determine whether chronic sub-toxic i-As doses are able to induce biologically significant levels of oxidative DNA damage (ODD). To fill in this gap, we have tested the genotoxic and oxidative effects of environmentally relevant arsenic exposures using mouse embryonic fibroblast MEF mutant Ogg1 cells and their wild-type counterparts. Effects were examined by using the comet assay complemented with the use of FPG enzyme. Our findings indicate that MEF Ogg1-/- cells are more sensitive to arsenite-induced acute toxicity, genotoxicity and ODD. Long-term exposure to sub-toxic doses of arsenite generates a detectable increase in ODD and genotoxic DNA damage only in MEF Ogg1-deficient cells. Altogether, the data presented here point out the relevance of ODD and Ogg1 genetic background on the genotoxic risk of i-As at environmentally plausible doses. The persistent accumulation of DNA 8-OH-dG lesions in Ogg1-/- cells during the complete course of the exposure suggests a relevant role in arsenic-associated carcinogenic risk in turn.BachJordiJGrup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Edifici Cn, Campus de Bellaterra, 08193, Cerdanyola del Vallès, Spain.Sampayo-ReyesAdrianaAMarcosRicardRHernándezAlbaAengJournal ArticleResearch Support, Non-U.S. Gov't20131105
GermanyArch Toxicol04176150340-576188847-89-68-oxo-7-hydrodeoxyguanosineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseG9481N71RODeoxyguanosineN712M78A8GArsenicIMAnimalsArsenictoxicityCell Survivaldrug effectsCells, CulturedComet AssayDNA Damagedrug effectsDNA GlycosylasesgeneticsmetabolismDeoxyguanosineanalogs & derivativesmetabolismFibroblastsdrug effectsphysiologyMiceMice, KnockoutMutagenicity Tests
2013080720131022201311660201311660201551360ppublish2419050210.1007/s00204-013-1151-0
241860012014060320170220
1423-03803532014MarTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Association of OGG1 Ser326Cys polymorphism and pancreatic cancer susceptibility: evidence from a meta-analysis.2397-40210.1007/s13277-013-1317-7The 8-oxoguanine DNA glycosylase (OGG1) gene has been considered to be associated with cancer susceptibility. The OGG1 Ser326Cys polymorphism has been reported to be associated with pancreatic cancer (PC), but the published studies have yielded inconsistent results. For better understanding of the effect of OGG1 Ser326Cys polymorphism on PC susceptibility, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database before May 2013. The association between the OGG1 Ser326Cys polymorphism and PC risk was conducted by odds ratios (ORs) and 95% confidence intervals (CIs). A total of five case-control studies with 1,690 cases and 3,650 controls were eventually collected. Overall, we found that OGG1 Ser326Cys polymorphism was not associated with PC susceptibility (Cys/Cys vs. Ser/Ser: OR = 0.95, 95% CI = 0.80-1.14; Cys/Cys vs. Ser/Ser + Ser/Cys: OR = 0.95, 95% CI = 0.78-1.14; Cys/Cys + Ser/Cys vs. Ser/Ser (OR = 1.00, 95% CI = 0.89-1.12)). In the subgroup analysis based on ethnicity, source of control, sample size, and genotyping method, no significant association was found in any genetic models. This meta-analysis suggests that the OGG1 Ser326Cys polymorphism may not associated with PC susceptibility. Considering the limited sample size and ethnicity included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results.YanYulanYDepartment of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China, xueying201120521@163.com.ChenXuXLiTaijieTLiMengMLiangHongjieHengJournal ArticleMeta-Analysis20131103
United StatesTumour Biol84099221010-4283EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMCancer Res. 2008 Jun 15;68(12):4928-3518544627Ann Oncol. 2009 Aug;20(8):1387-9619502533Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1470-918559563BMJ. 1998 Feb 7;316(7129):469; author reply 470-19492685Biometrika. 1950 Dec;37(3-4):256-6614801052J Gastroenterol. 2011 Dec;46(12):1345-5222048257JAMA. 2008 May 28;299(20):2423-3618505952Control Clin Trials. 1986 Sep;7(3):177-883802833Breast Cancer Res Treat. 2010 Aug;122(3):835-4220058067DNA Repair (Amst). 2006 Jan 5;5(1):43-5116111924Mol Carcinog. 2005 Mar;42(3):127-4115584022Carcinogenesis. 2007 Mar;28(3):657-6417028303Genome Res. 2004 Oct;14(10B):2121-715489334Int J Colorectal Dis. 2011 Dec;26(12):1525-3021695387PLoS One. 2011;6(7):e2231521811587CA Cancer J Clin. 2012 Jan-Feb;62(1):10-2922237781Ann Oncol. 2012 Feb;23(2):374-8221536662Nucleic Acids Res. 1999 Oct 15;27(20):4001-710497264Oncogene. 1998 Jun 25;16(25):3219-259681819J Epidemiol. 2012;22(6):477-8322850545J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060CA Cancer J Clin. 2008 Mar-Apr;58(2):71-9618287387Int J Mol Epidemiol Genet. 2011 Aug 30;2(3):236-4421915362BMJ. 1997 Sep 13;315(7109):629-349310563Tumour Biol. 2012 Aug;33(4):1237-4322396042Gut. 2007 Aug;56(8):1134-5217625148CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855Clin Cancer Res. 2009 Jan 15;15(2):740-619147782J Epidemiol Community Health. 1999 Sep;53(9):583-410562886PLoS One. 2012;7(4):e3597022540013Asian Pac J Cancer Prev. 2011;12(12):3427-3122471492HPB (Oxford). 2008;10(1):58-6218695761Ann Oncol. 2012 Feb;23(2):401-521515665PLoS One. 2011;6(11):e2792122125638Langenbecks Arch Surg. 2008 Jul;393(4):535-4518193270Ann Oncol. 2012 Oct;23(10):2536-4622539563Case-Control StudiesDNA GlycosylasesgeneticsGenetic Predisposition to DiseasegeneticsGenotypeHumansOdds RatioPancreatic NeoplasmsgeneticsPolymorphism, Single Nucleotidegenetics
201306192013101420131156020131156020146460ppublish2418600110.1007/s13277-013-1317-7PMC3967056
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2476-762X1492013Asian Pacific journal of cancer prevention : APJCPAsian Pac. J. Cancer Prev.Association of DNA base-excision repair XRCC1, OGG1 and APE1 gene polymorphisms with nasopharyngeal carcinoma susceptibility in a Chinese population.5145-51Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles.To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma.We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models.After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02- 3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1- 141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants ,was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004).This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1- 141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.LiQingQCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China E-mail : dongwang64@hotmail.com.WangJian-MinJMPengYuYZhangShi-HengSHRenTaoTLuoHaoHChengYiYWangDongDengJournal ArticleResearch Support, Non-U.S. Gov't
ThailandAsian Pac J Cancer Prev1011306251513-73680DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseNasopharyngeal carcinomaIMAsian Continental Ancestry GroupgeneticsCarcinomaetiologygeneticsCase-Control StudiesChinaDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGenetic Predisposition to DiseaseHumansLogistic ModelsMaleMiddle AgedMultivariate AnalysisNasopharyngeal NeoplasmsetiologygeneticsPolymorphism, Single NucleotideProtective FactorsSmokingadverse effectsX-ray Repair Cross Complementing Protein 1
20131126020131126020151160ppublish24175791
241211182014070920161128
1872-6216134102013OctMechanisms of ageing and developmentMech. Ageing Dev.Transient OGG1, APE1, PARP1 and Polβ expression in an Alzheimer's disease mouse model.467-7710.1016/j.mad.2013.09.002S0047-6374(13)00109-7Alzheimer's disease (AD) is a disease of major public health significance, whose pathogenesis is strongly linked to the presence of fibrillar aggregates of amyloid-beta (Aβ) in the aging human brain. We exploited the transgenic (Tg)-ArcSwe mouse model for human AD to explore whether oxidative stress and the capacity to repair oxidative DNA damage via base excision repair (BER) are related to Aβ pathology in AD. Tg-ArcSwe mice express variants of Aβ, accumulating senile plaques at 4-6 months of age, and develop AD-like neuropathology as adult animals. The relative mRNA levels of genes encoding BER enzymes, including 8-oxoguanine glycosylase (OGG1), AP endonuclease 1 (APE1), polymerase β (Polβ) and poly(ADP-ribose) polymerase 1 (PARP1), were quantified in various brain regions of 6 weeks, 4 months and 12 months old mice. The results show that OGG1 transcriptional expression was higher, and APE1 expression lower, in 4 months old Tg-ArcSwe than in wildtype (wt) mice. Furthermore, Polβ transcriptional expression was significantly lower in transgenic 12 months old mice than in wt. Transcriptional profiling also showed that BER repair capacity vary during the lifespan in Tg-ArcSwe and wt mice. The BER expression pattern in Tg-ArcSwe mice thus reflects responses to oxidative stress in vulnerable brain structures. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.LillenesMeryl SMSCentre for Molecular Biology and Neuroscience, Department of Microbiology, Oslo University Hospital, Norway.StøenMariMGómez-MuñozMartaMTorpReidunRGüntherClara-CecilieCCNilssonLars N GLNTønjumToneTengJournal ArticleResearch Support, Non-U.S. Gov't20131011
IrelandMech Ageing Dev03472270047-63740Nerve Tissue ProteinsEC 2.4.2.30Parp1 protein, mouseEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 2.7.7.-DNA Polymerase betaEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAlzheimer DiseaseenzymologygeneticspathologyAnimalsBrainenzymologypathologyDNA DamageDNA GlycosylasesbiosynthesisgeneticsDNA Polymerase betabiosynthesisgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisgeneticsDisease Models, AnimalGene Expression Regulation, EnzymologicHumansMiceMice, TransgenicNerve Tissue ProteinsbiosynthesisgeneticsOxidative StressgeneticsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesbiosynthesisgeneticsTranscription, GeneticgeneticsAlzheimer's diseaseAβPP mutationBase excision repair (BER)DNA repairOGG1, APE1, PARP1, PolβTransgenic (Tg-ArcSwe) mice
20130510201309232013092820131015602013101560201471060ppublish24121118S0047-6374(13)00109-710.1016/j.mad.2013.09.002
241013882014051220131008
1899-15056442013AugJournal of physiology and pharmacology : an official journal of the Polish Physiological SocietyJ. Physiol. Pharmacol.Influence of fundectomy and intraperitoneal or intragastric administration of apelin on apoptosis, mitosis, and DNA repair enzyme OGG1,2 expression in adult rats gastrointestinal tract and pancreas.423-8Apelin, endogenous ligand of G protein-coupled apelin receptor (APJ), is released into the gastrointestinal lumen, however, local effect of luminal apelin on gut epithelium has not been elucidated so far. The present study aimed to determine the effects of fundectomy, and intraperitoneal or intragastric administration of apelin on pancreatic, gastric and intestinal epithelium apoptosis, mitosis and DNA repair enzyme OGG1,2 expression in adult Wistar rats. Apelin-13 was given by intraperitoneal or gastric gavage twice a day for 10 days (100 nmol/kg b. wt./day). Fundectomized rats did not receive apelin. Control groups received saline as placebo. At the end of the experiment the rats were sacrificed and the pancreas, gastric fundus, duodenum, middle jejunum and colon tissue samples were harvested for immunofluorescence studies. Intraperitoneal and intragastric apelin-13 reduced apoptosis, mitosis and number of DNA damages in rats gastrointestinal tract (p≤0.001) as compared to control. In fundectomized rats, the apoptotic index in the pancreas and colon was decreased (p<0.001), and in the stomach and jejunum was increased (p<0.001). Mitotic index was decreased in all gastrointestinal tissues. Number of DNA damages (p≤0.001) in fundectomized rats was reduced except stomach where OGG1,2 expression was increased (p≤0.001) as compared to control. In conclusion, circulating and luminal exogenous apelin-13 caused similar effects on intestinal epithelium. Endogenous (gastric) apelin is important for renewal of intestinal epithelium in adult rats. Pharmacological doses of apelin-13 may reduce the cell turnover in the upper gastrointestinal tract epithelium and pancreas, and improve the overall gut health. AntushevichHHThe Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Jablonna, Poland. antuszewicz@op.pl.PawlinaBBKapicaMMKrawczynskaAAHermanA PAPKuwaharaAAKatoIIZabielskiRRengJournal ArticleResearch Support, Non-U.S. Gov't
PolandJ Physiol Pharmacol91145010867-59100Intercellular Signaling Peptides and Proteins0Ki-67 Antigen0apelin-13 peptideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-OGG1 protein, ratEC 3.4.22.-Caspase 3IMAnimalsApoptosisdrug effectsCaspase 3metabolismDNA Damagedrug effectsDNA GlycosylasesmetabolismDrug Administration RoutesGastrointestinal Tractdrug effectsmetabolismsurgeryIntercellular Signaling Peptides and ProteinspharmacologyIntestinal Mucosacytologydrug effectsmetabolismKi-67 AntigenmetabolismMaleMitosisdrug effectsPancreasdrug effectsmetabolismRatsRats, Wistar
2013052120130815201310960201310960201451360ppublish24101388
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1568-785612122013DecDNA repairDNA Repair (Amst.)The 8-oxoguanine DNA glycosylase 1 (ogg1) decreases the vulnerability of the developing brain to DNA damage.1094-10410.1016/j.dnarep.2013.08.018S1568-7864(13)00230-9The developing brain is particularly vulnerable to oxidative DNA damage, which may be the cause of most major congenital mental anomalies. The repair enzyme ogg1 initiates the highly conserved base-excision repair pathway. However, its function in the embryonic brain is largely unknown. This study is the first to validate the function of ogg1 during brain development using zebrafish embryos. Ogg1 was found to be highly expressed in the brain throughout early embryonic development, with particularly enrichment observed in the midbrain. The lack of ogg1 causes severe brain defects including changes in brain volume and integrity, destruction of the midbrain-hindbrain boundary, and balance and motor impairment, while overexpression of ogg1 can partially rescue these defects. Multiple cellular and molecular events were involved in the manifestation of brain defects due primarily to the lack of ogg1. These included (1) increased apoptosis; (2) decreased proliferation; and (3) aberrant axon distribution and extension from the inner surface towards the outer layers. The results of a microarray analysis showed that the expression of genes involved in cell cycle checkpoint, apoptosis, and neurogenesis were significantly changed in response to ogg1 knockdown. Cmyb was the key downstream gene that responses to DNA damage caused by ogg1 deficiency. Notably, the recruitment of ogg1 mRNA can alleviate the effects on the brain due to neural DNA damage. In summary, we introduce here that ogg1 is fundamentally required for protecting the developing brain, which may be helpful in understanding the aetiology of congenital brain deficits. Copyright © 2013 Elsevier B.V. All rights reserved.GuAihuaAState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China. Electronic address: aihuagu@njmu.edu.cn.JiGuixiangGYanLifengLZhouYongYengJournal ArticleResearch Support, Non-U.S. Gov't20130925
NetherlandsDNA Repair (Amst)1011391381568-785608-oxoguanine DNA glycosylase 1, zebrafish0Multifunctional Enzymes0Zebrafish ProteinsEC 3.2.2.-DNA GlycosylasesEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsBrainabnormalitiesembryologyphysiologyCloning, MolecularDNA DamageDNA GlycosylasesmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismEmbryo, NonmammalianGene Expression Regulation, DevelopmentalGene Knockdown TechniquesLarvametabolismMultifunctional EnzymesmetabolismOligonucleotide Array Sequence AnalysisOxidative StressPhenotypeZebrafishembryologygeneticsmetabolismZebrafish Proteinsmetabolismphysiology
201306212013081720130827201310160201310160201471660ppublish24075420S1568-7864(13)00230-910.1016/j.dnarep.2013.08.018
239998242014032620171111
1423-03803512014JanTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Association between single-nucleotide polymorphisms of OGG1 gene and pancreatic cancer risk in Chinese Han population.809-1310.1007/s13277-013-1111-6The purpose of this study was to test the association between single-nucleotide polymorphisms (SNPs) of 8-oxoguanine DNA glycosylase (OGG1) gene and susceptibility to pancreatic cancer (PC). A total of 347 PC patients and 364 healthy subjects were enrolled in this case-control study. The c.269C>A genetic variant was investigated using the created restriction site-polymerase chain reaction method. The c.627T>C genetic variant was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Our data indicated that the alleles and genotypes frequencies of these two SNPs were statistically different in PC cases and controls. As for c.269C>A, the AA genotype was statistically associated with decreased PC susceptibility compared to CC wild genotype (odds ratio (OR) = 0.44, 95% confidence interval (CI) 0.27-0.73, P = 0.001). As for c.627T>C, statistically significant decreased PC susceptibility was detected in CC genotype compared to TT wild genotype (OR = 0.57, 95% CI 0.35-0.94, P = 0.028). The allele A of c.269C>A and allele C of c.627T>C might be associated with a protection from PC (for c.269C>A, A versus (vs.) C, OR = 0.69, 95% CI 0.55-0.86, P < 0.001; for c.627T>C, C vs. T, OR = 0.72, 95% CI 0.58-0.91, P = 0.005). Results from this study indicate that the c.269C>A and c.627T>C SNPs of OGG1 gene are associated with PC susceptibility in Chinese Han ethnicity.ChenHongxuHDepartment of Hepatobiliary Surgery, Daping Hospital, The Third Military Medical University, No. 10 Changjiangzhilu Daping, Chongqing, 400042, People's Republic of China.ZhouBoBLanXiangXWeiDongDYuanTaoTChenPingPengJournal ArticleRetracted Publication20130903
United StatesTumour Biol84099221010-4283EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMTumour Biol. 2017 Apr 20;:28792236Cancer. 2011 Feb 15;117(4):744-5120922799Cancer Res. 2008 Jun 15;68(12):4928-3518544627Nucleic Acids Res. 1989 May 11;17(9):36062726503Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1470-918559563Pancreatology. 2003;3(1):1-712683400Int J Cancer. 2007 May 1;120(9):1993-817266034Mol Biol Rep. 2013 Feb;40(2):1947-5423143182Asian Pac J Cancer Prev. 2001;2(4):271-28012718618Mol Biol Rep. 2013 Jan;40(1):7-1223114911JOP. 2010 May 05;11(3):203-1220442513Cancer Causes Control. 2007 Aug;18(6):603-1217401636Yi Chuan. 2003 May;25(3):327-915639881Best Pract Res Clin Gastroenterol. 2006 Apr;20(2):197-20916549324J Epidemiol. 2012;22(6):477-8322850545Mutat Res. 2009 Mar-Jun;681(2-3):299-30719150414Gene. 2012 Aug 15;505(1):190-422583824Int J Mol Epidemiol Genet. 2011 Aug 30;2(3):236-4421915362Dig Dis. 2011;29(2):235-4221734390Clin Cancer Res. 2009 Jan 15;15(2):740-619147782Int J Cancer. 2007 Apr 15;120(8):1748-5417230526J Clin Oncol. 2006 Apr 10;24(11):1720-816520463CA Cancer J Clin. 2007 Jan-Feb;57(1):43-6617237035AdultAgedAllelesAsian Continental Ancestry GroupgeneticsCase-Control StudiesChinaDNA GlycosylasesgeneticsFemaleGene FrequencyGenetic Association StudiesGenotypeHumansMaleMiddle AgedOdds RatioPancreatic NeoplasmsgeneticsPolymorphism, Single NucleotideRisk
20130722201308122013946020139460201432960ppublish2399982410.1007/s13277-013-1111-6
239590142014100220171116
0717-62874622013Biological researchBiol. Res.DNA Repair Genes XRCC1, XRCC3, XPD, and OGG1 Polymorphisms among the Central Region Population of Saudi Arabia.161-710.4067/S0716-97602013000200007S0716-97602013000200007DNA repair is one of the central defense mechanisms against mutagenic exposures. Inherited SNPs of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. Saudi Arabia harbors enormous genetic and cultural diversity. In the present study we aimed to determine the genotype and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 386 healthy individuals residing in the central region of Saudi Arabia and compare them with HapMap and other populations. The genotype and allele frequencies of the four DNA repair gene loci in central Saudi population showed a distinctive pattern. Furthermore, comparison of polymorphisms in these genes with other populations also showed a unique pattern for the central Saudi population. To the best of our knowledge, this is the first report that deals with these DNA repair gene polymorphisms among the central Saudi population. AlanaziMohammadMGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.PathanAkbar Ali KhanAAAjajSana AbdullaSAKhanWajahatullahWShaikJilani PJPAl TassanNadaNParineNarasimha ReddyNRengJournal ArticleResearch Support, Non-U.S. Gov't
EnglandBiol Res93082710716-97600DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10X-ray repair cross complementing protein 30XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanIMAdultAgedAllelesChi-Square DistributionDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-Binding ProteinsgeneticsFemaleGene FrequencyGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotidegeneticsSaudi ArabiaX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
2012112820130415201382160201382160201410360ppublish23959014S0716-9760201300020000710.4067/S0716-97602013000200007
239095572014041820160511
1945-025717102013OctGenetic testing and molecular biomarkersGenet Test Mol BiomarkersThe OGG1 Ser326Cys polymorphism and the risk of esophageal cancer: a meta-analysis.780-510.1089/gtmb.2013.0224The oxoguanine DNA glycosylase (OGG1) Ser326Cys polymorphism has been implicated in susceptibility to esophageal cancer. Several studies investigated the association of this polymorphism with esophageal cancer in different populations. However, the results were contradictory. A meta-analysis was conducted to assess the association between the OGG1 Ser326Cys polymorphism and esophageal cancer susceptibility.Databases, including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A random-effects model was used.Twelve studies involving 2363 cases and 3621 controls were included. Overall, a significant association between the OGG1 Ser326Cys polymorphism and esophageal cancer was observed for Cys/Cys versus Cys/Ser+Ser/Ser (OR=1.40; 95% CI 1.12-1.74; p=0.003; Pheterogeneity=0.18). In the subgroup analysis by ethnicity, a significant association was found among Asians (OR=1.51; 95% CI 1.15-1.96; p=0.002; Pheterogeneity=0.22), but not among Caucasians (OR=1.21; 95% CI 0.81-1.81; p=0.35; Pheterogeneity=0.21). In the subgroup analysis by pathologic type, we found that the Cys/Cys genotype was associated with increased esophageal squamous cell carcinoma risk (OR=1.86; 95% CI 1.36-2.53; p<0.0001; Pheterogeneity=0.73).This meta-analysis suggested that the OGG1 Ser326Cys polymorphism was a risk factor of esophageal cancer.WangZhanZ1 Department of Oncology, Shanghai Changzheng Hospital, Second Military Medical University , Shanghai, China .GanLuLNieWeiWGengYanYengJournal ArticleMeta-AnalysisReview20130803
United StatesGenet Test Mol Biomarkers1014942101945-0257EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAmino Acid SubstitutionDNA GlycosylasesgeneticsEsophageal NeoplasmsenzymologygeneticsFemaleHumansMaleModels, GeneticMutation, MissensePolymorphism, GeneticPubMedRisk Factors
2013866020138660201442060ppublish2390955710.1089/gtmb.2013.0224
238920032014021320131101
1090-2422319192013Nov15Experimental cell researchExp. Cell Res.8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish.2954-6310.1016/j.yexcr.2013.07.012S0014-4827(13)00301-7Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes and nkx2.5(+) cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits.© 2013 Elsevier Inc. All rights reserved.YanLifengLState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.ZhouYongYYuShanheSJiGuixiangGWangLeiLLiuWeiWGuAihuaAengJournal ArticleResearch Support, Non-U.S. Gov't20130724
United StatesExp Cell Res03732260014-482708-oxoguanine DNA glycosylase 1, zebrafish0Multifunctional Enzymes0Transcription Factors0Zebrafish ProteinsEC 3.2.2.-DNA GlycosylasesEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsDNA DamagephysiologyDNA GlycosylasesmetabolismDNA RepairphysiologyDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismEmbryonic Stem CellsmetabolismHeartembryologyMesodermmetabolismMultifunctional EnzymesmetabolismMyocardiumcytologymetabolismPhenotypeTranscription FactorsmetabolismZebrafishembryologygeneticsmetabolismZebrafish ProteinsmetabolismCardiac progenitor cellsDNA repairHeart developmentOgg1Oxidative DNA damage
201304012013070820130710201373060201373160201421460ppublish23892003S0014-4827(13)00301-710.1016/j.yexcr.2013.07.012
238721292014032820161125
1873-6351592013SepFood and chemical toxicology : an international journal published for the British Industrial Biological Research AssociationFood Chem. Toxicol.Wogonin attenuates etoposide-induced oxidative DNA damage and apoptosis via suppression of oxidative DNA stress and modulation of OGG1 expression.724-3010.1016/j.fct.2013.07.022S0278-6915(13)00477-8Damage to DNA can lead to many different acute and chronic pathophysiological conditions, ranging from cancer to endothelial damage. The current study has been initiated to determine whether the flavonoid wogonin can attenuate etoposide-induced oxidative DNA damage and apoptosis in mouse bone marrow cells. We found that oral administration of wogonin before etoposide injection significantly attenuates etoposide-induced oxidative DNA damage and apoptosis in a dose dependent manner. Etoposide induced a significant down-regulation of mRNA expression of the OGG1 repair gene and marked biochemical alterations characteristic of oxidative DNA stress, including increased 8-OHdG, enhanced lipid peroxidation and reduction in reduced glutathione. Prior administration of wogonin ahead of etoposide challenge restored these altered parameters. Importantly, wogonin had no antagonizing effect on etoposide-induce topoisomerase-II inhibition. Conclusively, our study indicates that wogonin has a protective role in the abatement of etoposide-induced oxidative DNA damage and apoptosis in the bone marrow cells of mice via suppression of oxidative DNA stress and enhancing DNA repair through modulation of OGG1 repair gene expression. Therefore, wogonin can be a promising chemoprotective agent and might be useful to avert secondary leukemia and other drug-related cancers in cured cancer patients and medical personnel exposing to the potent carcinogen etoposide. Copyright © 2013 Elsevier Ltd. All rights reserved.AttiaSabry MSMDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. attiasm@ksu.edu.saAhmadSheikh FayazSFHarisaGamaleldin IGIMansourAhmed MAMEl SayedEl Sayed Mel SMBakheetSaleh ASAengJournal ArticleResearch Support, Non-U.S. Gov't20130717
EnglandFood Chem Toxicol82074830278-69150Anticarcinogenic Agents0Antioxidants0Flavanones0RNA, Messenger0Topoisomerase II Inhibitors6PLQ3CP4P3EtoposideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mousePOK93PO28WwogoninIMAnimalsAnticarcinogenic Agentsadministration & dosageadverse effectstherapeutic useAntioxidantsadministration & dosageadverse effectstherapeutic useApoptosisdrug effectsBone Marrow Cellsdrug effectsmetabolismpathologyDNA Damagedrug effectsDNA GlycosylasesbiosynthesisgeneticsmetabolismDose-Response Relationship, DrugEtoposideadverse effectsantagonists & inhibitorsFlavanonesadministration & dosageadverse effectstherapeutic useGene Expression Regulationdrug effectsLeukemiachemically inducedmetabolismpathologyprevention & controlMaleMiceMicronucleus TestsMutagenicity TestsOxidative Stressdrug effectsRNA, MessengermetabolismRandom AllocationTopoisomerase II Inhibitorsadverse effectschemistryApoptosisDNA damage/repairOxidative DNA stressSecondary tumors
201302202013070420130710201372360201372360201432960ppublish23872129S0278-6915(13)00477-810.1016/j.fct.2013.07.022
238680642014022520161019
2041-488942013Jul18Cell death & diseaseCell Death DisInteraction of Sirt3 with OGG1 contributes to repair of mitochondrial DNA and protects from apoptotic cell death under oxidative stress.e73110.1038/cddis.2013.254Sirtuin 3 (Sirt3), a major mitochondrial NAD(+)-dependent deacetylase, targets various mitochondrial proteins for lysine deacetylation and regulates important cellular functions such as energy metabolism, aging, and stress response. In this study, we identified the human 8-oxoguanine-DNA glycosylase 1 (OGG1), a DNA repair enzyme that excises 7,8-dihydro-8-oxoguanine (8-oxoG) from damaged genome, as a new target protein for Sirt3. We found that Sirt3 physically associated with OGG1 and deacetylated this DNA glycosylase and that deacetylation by Sirt3 prevented the degradation of the OGG1 protein and controlled its incision activity. We further showed that regulation of the acetylation and turnover of OGG1 by Sirt3 played a critical role in repairing mitochondrial DNA (mtDNA) damage, protecting mitochondrial integrity, and preventing apoptotic cell death under oxidative stress. We observed that following ionizing radiation, human tumor cells with silencing of Sirt3 expression exhibited deteriorated oxidative damage of mtDNA, as measured by the accumulation of 8-oxoG and 4977 common deletion, and showed more severe mitochondrial dysfunction and underwent greater apoptosis in comparison with the cells without silencing of Sirt3 expression. The results reported here not only reveal a new function and mechanism for Sirt3 in defending the mitochondrial genome against oxidative damage and protecting from the genotoxic stress-induced apoptotic cell death but also provide evidence supporting a new mtDNA repair pathway. ChengYYDepartment of Pharmacology, Milton S Hershey Medical Center, Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033-0850, USA. yxc24@psu.eduRenXXGowdaA S PASShanYYZhangLLYuanY-SYSPatelRRWuHHHuber-KeenerKKYangJ WJWLiuDDSprattT ETEYangJ-MJMengR01 CA135038CANCI NIH HHSUnited StatesR01CA135038CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.20130718
EnglandCell Death Dis1015240920DNA, MitochondrialEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.4.22.-CalpainEC 3.5.1.-SIRT3 protein, humanEC 3.5.1.-Sirtuin 3IMCell Metab. 2010 Dec 1;12(6):662-721109198J Cell Sci. 2010 Dec 1;123(Pt 23):4117-2721062897Mol Cell. 2010 Dec 22;40(6):893-90421172655BMC Med Genet. 2011;12:821232124Cancer Cell. 2011 Mar 8;19(3):416-2821397863Cancer. 2011 Apr 15;117(8):1670-821472714EMBO Rep. 2011 Jun;12(6):534-4121566644Biochim Biophys Acta. 2011 Aug;1816(1):80-821586315Oncogene. 2011 Jun 30;30(26):2986-9621358671EMBO Rep. 2011 Aug;12(8):840-621720390Cell Death Differ. 2012 Nov;19(11):1815-2522595756Cancer Res. 2012 May 15;72(10):2468-7222589271J Biol Chem. 2012 Apr 20;287(17):14078-8622416140Biochem Biophys Res Commun. 2013 Jan 11;430(2):798-80323201401Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4156-6110725358Trends Biochem Sci. 2000 Nov;25(11):555-6011084368J Biol Chem. 2000 Dec 1;275(48):37518-2310982789Cancer Res. 2001 Jul 15;61(14):5378-8111454679Gene. 2002 Mar 6;286(1):127-3411943468Oncogene. 2002 Aug 8;21(34):5204-1212149642Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13653-812374852J Biol Chem. 2003 May 23;278(21):19541-812644468FEBS Lett. 2004 Jul 30;571(1-3):227-3215280047Proc Natl Acad Sci U S A. 1988 Sep;85(17):6465-73413108J Biol Chem. 1992 Jan 5;267(1):166-721730583Trends Genet. 1993 Jul;9(7):246-98379000Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8016-209223306Nucleic Acids Res. 1998 Jun 15;26(12):2917-229611236Mol Cell Biol. 2006 Mar;26(5):1654-6516478987Diabetes. 2006 Apr;55(4):1022-816567524Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10230-516790548Br J Cancer. 2006 Oct 23;95(8):1056-6117003781Exp Biol Med (Maywood). 2007 May;232(5):592-60617463155Mol Cell Biol. 2007 Dec;27(24):8807-1417923681EMBO J. 2008 Jan 23;27(2):421-3218188152Am J Physiol Cell Physiol. 2008 Feb;294(2):C413-2218077603DNA Repair (Amst). 2008 Apr 2;7(4):648-5418294929Oncogene. 2008 Jun 12;27(26):3710-2018246124J Mol Biol. 2008 Oct 10;382(3):790-80118680753Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14447-5218794531Mol Cell Biol. 2008 Oct;28(20):6384-40118710944Methods Mol Biol. 2009;554:199-21219513676Nature. 2009 Jul 30;460(7255):587-9119641587Biochemistry. 2010 Jan 19;49(2):304-1120000467Cancer Cell. 2010 Jan 19;17(1):41-5220129246J Cell Sci. 2010 Mar 15;123(Pt 6):894-90220159966Cell. 2010 Nov 24;143(5):802-1221094524AcetylationApoptosisCalpainmetabolismCell Line, TumorCell ProliferationDNA DamageDNA GlycosylasesmetabolismDNA RepairDNA, MitochondrialgeneticsGene Knockdown TechniquesHEK293 CellsHumansMembrane Potential, MitochondrialOxidative StressProtein BindingProtein Interaction MappingProtein Processing, Post-TranslationalProteolysisSirtuin 3geneticsmetabolism
201303062013052020130604201372360201372360201422660epublish23868064cddis201325410.1038/cddis.2013.254PMC3730425
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1558-82382013Jul01The Journal of clinical investigationJ. Clin. Invest.Colon cancer progression is driven by APEX1-mediated upregulation of Jagged.6552110.1172/JCI65521Aberrant expression of apurinic-apyrimidinic endonuclease-1 (APEX1) has been reported in numerous human solid tumors and is positively correlated with cancer progression; however, the role of APEX1 in tumor progression is poorly defined. Here, we show that APEX1 contributes to aggressive colon cancer behavior and functions as an upstream activator in the Jagged1/Notch signaling pathway. APEX1 overexpression or knockdown in human colon cancer cell lines induced profound changes in malignant properties such as cell proliferation, anchorage-independent growth, migration, invasion, and angiogenesis in vitro and in tumor formation and metastasis in mouse xenograft models. These oncogenic effects of APEX1 were mediated by the upregulation of Jagged1, a major Notch ligand. Furthermore, APEX1 expression was associated with Jagged1 in various colon cancer cell lines and in tissues from colon cancer patients. This finding identifies APEX1 as a positive regulator of Jagged1/Notch activity and suggests that it is a potential therapeutic target in colon cancers that exhibit high levels of Jagged1/Notch signaling.KimMi-HwaMHKimHong-BeumHBYoonSang PilSPLimSung-ChulSCChaMan JinMJJeonYoung JinYJParkSang GonSGChangIn-YoubIYYouHo JinHJengJournal Article20130701
United StatesJ Clin Invest78028770021-9738Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Carcinogenesis. 2007 Nov;28(11):2382-9017566060Mol Cancer Ther. 2005 Dec;4(12):1923-3516373707Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Clin Cancer Res. 2005 Sep 1;11(17):6205-1116144922DNA Repair (Amst). 2008 Feb 1;7(2):177-8617974506Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6315-2019325125Oncotarget. 2010 Jul;1(3):210-820953350Mol Cancer Ther. 2011 Sep;10(9):1698-70821700832J Pathol. 2011 Aug;224(4):448-6021598247J Cell Biol. 2004 Oct 25;167(2):215-2115492044Cancer Res. 2006 Jun 15;66(12 ):6312-816778208Cancer Cell. 2011 Feb 15;19(2):192-20521295524Br J Cancer. 1998 Apr;77(7):1169-739569057Free Radic Res. 2008 Jan;42(1):20-918324520Cell. 2009 Apr 17;137(2):216-3319379690Cancer Res. 2004 Oct 1;64(19):6854-715466172Nature. 2005 Jun 16;435(7044):959-6315959515Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Hum Pathol. 2008 Feb;39(2):201-817949784Mol Cancer Ther. 2008 Jul;7(7):2012-2118645011J Exp Med. 2007 Nov 26;204(12 ):2935-4817984306Cancer Res. 1997 May 1;57(9):1794-79135024Nature. 2005 Jun 16;435(7044):964-815959516Mol Cell Biol. 2009 Apr;29(8):2264-7719188437Curr Mol Med. 2006 Dec;6(8):905-1817168741Nature. 2010 Apr 15;464(7291):1052-720393564Cancer Res. 2009 Aug 1;69(15):6065-7319622776Circ Res. 2009 Feb 27;104(4):466-7519150886J Natl Cancer Inst. 2007 Sep 5;99(17):1284-517728207Clin Cancer Res. 2001 Nov;7(11):3510-811705870Mol Med. 2007 Jan-Feb;13(1-2):89-9617515960Carcinogenesis. 2009 Dec;30(12):1979-8619793799Oncogene. 2008 Sep 1;27(38):5132-718758482Mol Cell. 2005 Feb 4;17(3):463-7015694346J Cell Physiol. 2009 Apr;219(1):209-1819097035Cancer Res. 2008 Jul 15;68(14 ):5716-2318632624Nat Rev Mol Cell Biol. 2006 Sep;7(9):678-8916921404Mol Cancer Ther. 2010 Jan;9(1):202-1020053782Oncogene. 2010 Feb 18;29(7):992-100219935714Biochem Pharmacol. 2010 Sep 1;80(5):690-70120361945Nature. 1998 May 28;393(6683):382-69620803Clin Cancer Res. 2000 Feb;6(2):602-910690545Clin Cancer Res. 2001 Apr;7(4):824-3011309329Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6309-1419251639Cancer Res. 2005 Sep 15;65(18):8530-716166334
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1460-2105105162013Aug21Journal of the National Cancer InstituteJ. Natl. Cancer Inst.Role of the oxidative DNA damage repair gene OGG1 in colorectal tumorigenesis.1249-5310.1093/jnci/djt183Biallelic inherited mutations in the oxidative DNA damage repair gene MUTYH predispose to colorectal adenomas and colorectal carcinoma (CRC) with high penetrance. We investigated whether rare inherited variants in other oxidative DNA damage repair genes predisposed to CRC. Single marker association analyses were assessed under an allelic model with Bonferroni correction for multiple testing. All statistical tests were two-sided. A rare inherited nonsynonymous variant in OGG1 (Gly308Glu), the functional partner of MUTYH, was over-represented in case patients with advanced CRC compared with population-based control subjects (n = 36 of 2142 case patients vs n = 15 of 2175 control subjects in the training phase, P = 1.8×10(-3); and n = 22 of 1005 case patients vs n = 8 of 1389 control subjects in the validation phase, P = 4.8×10(-4); P = 1.4×10(-5) combined; odds ratio = 2.92, 95% confidence interval = 1.80 to 4.74). Glycine at residue 308 was highly conserved through evolution, and the glutamic acid substitution was predicted as likely to interfere with function. Biallelic inherited and somatic OGG1 mutations were rarely observed in OGG1 (Gly308Glu) carriers, nor did we find any associated somatic mutator phenotype. These data suggest that OGG1 (Gly308Glu) may act as a low-penetrance allele that contributes to colorectal tumorigenesis. SmithChristopher GCGInstitute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.WestHannahHHarrisRebeccaRIdziaszczykShelleySMaughanTimothy STSKaplanRichardRRichmanSusanSQuirkePhilipPSeymourMatthewMMoskvinaValentinaVSteinkeVerenaVProppingPeterPHesFrederik JFJWijnenJuulJCheadleJeremy PJPengMC_U122861325Medical Research CouncilUnited KingdomMC_UU_12023/3Medical Research CouncilUnited KingdomCancer Research UKUnited KingdomMedical Research CouncilUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20130712
United StatesJ Natl Cancer Inst75030890027-88743KX376GY7LGlutamic AcidEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanTE7660XO1CGlycineIMJ Natl Cancer Inst. 2014 May;106(5). pii: dju086. doi: 10.1093/jnci/dju08624771875J Natl Cancer Inst. 2014 May;106(5). pii: dju087. doi: 10.1093/jnci/dju08724771876AdenomageneticsAdultAgedAged, 80 and overAllelesCarcinomageneticsCase-Control StudiesColorectal NeoplasmsgeneticsDNA DamageDNA GlycosylasesgeneticsDNA RepairgeneticsFemaleGene Expression Regulation, NeoplasticGlutamic AcidGlycineHumansMaleMiddle AgedMutationOdds RatioOxidation-ReductionPenetranceUp-Regulation
201371660201371660201311560ppublish23852950djt18310.1093/jnci/djt183
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0027-510775522013Aug15Mutation researchMutat. Res.The impact of single-nucleotide polymorphisms (SNPs) in OGG1 and XPC on the age at onset of Huntington disease.115-910.1016/j.mrgentox.2013.04.020S1383-5718(13)00185-XThe age at onset of Huntington disease (HD) shows a strong, negative correlation with the number of CAG repeats within the huntingtin (HTT) gene. However, this does not account for all the inter-individual variability seen among patients. In order to assess whether single-nucleotide polymorphisms (SNPs) in the OGG1 and XPC genes, both implicated in responses to oxidative stress, are associated with the age of onset of HD, 9 SNPs have been genotyped in 299 individuals with HD and 582 controls. After correction for multiple testing, two OGG1/XPC haplotypes were found to be associated with younger age at onset independently of the number of CAG repeats within the HTT gene. Both haplotypes contain XPC coding variants that would be expected to impact on protein function and/or variants in the 3'UTR that could result in altered protein levels via allele-specific mIR binding. One haplotype also contains the OGG1-326Cys (rs1052133) allele that has been associated with a lower 8-oxoG repair activity and is particularly sensitive to the cellular redox status. These results highlight the potential role of oxidative stress in determining the age at onset of HD. Copyright © 2013 Elsevier B.V. All rights reserved.BergerFrédériqueFInstitut Curie, Centre de Recherche, 91405 Orsay, France.VaslinLaurenceLBelinLisaLAsselainBernardBForlaniSylvieSHumbertSandrineSDurrAlexandraAHallJanetJengJournal ArticleResearch Support, Non-U.S. Gov't20130702
NetherlandsMutat Res04007630027-510703' Untranslated Regions0DNA-Binding Proteins0HTT protein, human0Huntingtin Protein0MicroRNAs0Nerve Tissue Proteins0RNA, Messenger156533-34-5XPC protein, human5614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIM3' Untranslated RegionsgeneticsAdultAge of OnsetDNA DamageDNA GlycosylasesgeneticsphysiologyDNA RepairgeneticsDNA-Binding ProteinsgeneticsphysiologyFemaleGenotypeGuanineanalogs & derivativesmetabolismHaplotypesgeneticsHumansHuntingtin ProteinHuntington DiseaseepidemiologygeneticsMaleMicroRNAsmetabolismMiddle AgedNerve Tissue ProteinsgeneticsOxidative StressgeneticsPolymorphism, Single NucleotideRNA, MessengermetabolismTrinucleotide RepeatsAge at onsetHuntington diseaseOGG1XPC
20121208201304112013041520137960201379602013101860ppublish23830927S1383-5718(13)00185-X10.1016/j.mrgentox.2013.04.020
237483602013102920161019
1945-717015482013AugEndocrinologyEndocrinologyAlteration of mitochondrial function and insulin sensitivity in primary mouse skeletal muscle cells isolated from transgenic and knockout mice: role of ogg1.2640-910.1210/en.2013-1076Recent evidence has linked mitochondrial dysfunction and DNA damage, increased oxidative stress in skeletal muscle, and insulin resistance (IR). The purpose of this study was to determine the role of the DNA repair enzyme, human 8-oxoguanine DNA glycosylase/apurinic/apyrimidinic lyase (hOGG1), on palmitate-induced mitochondrial dysfunction and IR in primary cultures of skeletal muscle derived from hind limb of ogg1(-/-) knockout mice and transgenic mice, which overexpress human (hOGG1) in mitochondria (transgenic [Tg]/MTS-hOGG1). Following exposure to palmitate, we evaluated mitochondrial DNA (mtDNA) damage, mitochondrial function, production of mitochondrial reactive oxygen species (mtROS), mitochondrial mass, JNK activation, insulin signaling pathways, and glucose uptake. Palmitate-induced mtDNA damage, mtROS, mitochondrial dysfunction, and activation of JNK were all diminished, whereas ATP levels, mitochondrial mass, insulin-stimulated phosphorylation of Akt (Ser 473), and insulin sensitivity were increased in primary myotubes isolated from Tg/MTS-hOGG1 mice compared to myotubes isolated from either knockout or wild-type mice. In addition, both basal and maximal respiratory rates during mitochondrial oxidation on pyruvate showed a variable response, with some animals displaying an increased respiration in muscle fibers isolated from the transgenic mice. Our results support the model that DNA repair enzyme OGG1 plays a pivotal role in repairing mtDNA damage, and consequently, in mtROS production and regulating downstream events leading to IR in skeletal muscle. YuzefovychLarysa VLVDepartment of Cell Biology and Neuroscience, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.SchulerA MicheleAMChenJemimahJAlvarezDiego FDFEideLarsLLedouxSusan PSPWilsonGlenn LGLRachekLyudmila ILIengR01 DK073808DKNIDDK NIH HHSUnited StatesDK073808DKNIDDK NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20130607
United StatesEndocrinology03750400013-72270DNA, Mitochondrial0Insulin0Palmitates0Reactive Oxygen Species8L70Q75FXEAdenosine TriphosphateEC 2.7.11.1Proto-Oncogene Proteins c-aktEC 2.7.11.24JNK Mitogen-Activated Protein KinasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 3.2.2.-oxoguanine glycosylase 1, humanAIMIMHum Hered. 2010;70(2):97-10120606456Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315J Biol Chem. 2000 Dec 1;275(48):37518-2310982789Am J Physiol Endocrinol Metab. 2001 Jul;281(1):E16-2411404219Cancer Res. 2001 Jul 15;61(14):5378-8111454679Clin Orthop Relat Res. 2002 Oct;(403 Suppl):S153-6212394464J Biol Chem. 2002 Nov 22;277(47):44932-712244119Cancer Res. 2003 Mar 1;63(5):902-512615700Mol Endocrinol. 2004 Aug;18(8):2024-3415143153Diabetes. 1988 Jun;37(6):667-873289989Baillieres Clin Haematol. 1989 Apr;2(2):195-2562660928J Neurochem. 1990 Jul;55(1):186-912355219Nature. 1991 Jan 31;349(6308):431-41992344Am J Physiol. 1994 Mar;266(3 Pt 1):C751-88166238Biochem J. 1996 Jan 1;313 ( Pt 1):17-298546679Nucleic Acids Res. 1997 Nov 1;25(21):4362-99336469Biochimie. 1999 Jan-Feb;81(1-2):59-6710214911Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L530-515563690Free Radic Biol Med. 2005 Mar 15;38(6):737-4515721984Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1864-916446448Free Radic Biol Med. 2006 Mar 1;40(5):754-6216520228Diabetes. 2006 Apr;55(4):1022-816567524Toxicology. 2006 Apr 17;221(2-3):179-8616494984Endocrinology. 2007 Jan;148(1):293-917023529Anal Bioanal Chem. 2007 Apr;387(8):2775-8217377779Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12587-9417640906Carcinogenesis. 2007 Aug;28(8):1629-3717389610Mech Ageing Dev. 2007 Nov-Dec;128(11-12):637-4918006041J Clin Invest. 2008 Feb;118(2):789-80018188455Am J Physiol Cell Physiol. 2008 Feb;294(2):C413-2218077603Cell Motil Cytoskeleton. 2008 Dec;65(12):945-5418792955Free Radic Biol Med. 2009 Sep 15;47(6):750-919524665Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17787-9219805130Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E1096-10520876761Am J Pathol. 2011 Apr;178(4):1715-2721435453J Clin Invest. 2009 Mar;119(3):573-8119188683Free Radic Biol Med. 2011 May 1;50(9):1107-1320969951J Lipid Res. 2011 Jun;52(6):1234-4621447485Eur J Endocrinol. 2011 Jun;164(6):899-90421436346J Neurosci. 2011 Jun 29;31(26):9746-5121715639Endocrinology. 2012 Jan;153(1):92-10022128025Gene. 2012 Aug 15;505(1):121-722652274Diabetologia. 2012 Oct;55(10):2759-6822782287PLoS One. 2012;7(12):e5169723284747PLoS One. 2013;8(1):e5405923342074Adenosine TriphosphatemetabolismAnimalsBlotting, WesternCells, CulturedDNA DamageDNA GlycosylasesgeneticsmetabolismDNA, MitochondrialgeneticsmetabolismEnzyme Activationdrug effectsHumansInsulinmetabolismpharmacologyphysiologyJNK Mitogen-Activated Protein KinasesmetabolismMiceMice, KnockoutMice, TransgenicMitochondria, MusclegeneticsmetabolismphysiologyMuscle, Skeletalcytologydrug effectsmetabolismPalmitatespharmacologyPhosphorylationdrug effectsProto-Oncogene Proteins c-aktmetabolismReactive Oxygen SpeciesmetabolismSignal Transductiondrug effects
2013611602013612602013103060ppublish23748360en.2013-107610.1210/en.2013-1076PMC3713209
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1873-4596632013OctFree radical biology & medicineFree Radic. Biol. Med.Genotype-phenotype analysis of S326C OGG1 polymorphism: a risk factor for oxidative pathologies.401-910.1016/j.freeradbiomed.2013.05.031S0891-5849(13)00241-48-Oxoguanine DNA glycosylase (OGG) activity was measured by an in vitro assay in lymphocytes of healthy volunteers genotyped for various OGG1 polymorphisms. Only homozygous carriers of the polymorphic C326 allele showed a significantly lower OGG activity compared to the homozygous S326 genotype. The purified S326C OGG1 showed a decreased ability to complete the repair synthesis step in a base excision repair reaction reconstituted in vitro. The propensity of this variant to dimerize as well as its catalytic impairment were shown to be enhanced under oxidizing conditions. Mass spectrometry revealed that the extra cysteine of the variant protein is involved in disulfide bonds compatible with significant conformational changes and/or dimerization. We propose that the S326C OGG1 catalytic impairment and its susceptibility to dimerization and disulfide bond formation in an oxidizing environment all concur to decrease repair capacity. Consequently, the C326 homozygous carriers may be at increased risk of oxidative pathologies. Copyright © 2013 Elsevier Inc. All rights reserved.SimonelliValeriaVDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, 00161 Rome, Italy.CameriniSerenaSMazzeiFilomenaFVan LoonBarbaraBAllioneAlessandraAD'ErricoMariarosariaMBaroneFlaviaFMinoprioAnnaARicceriFulvioFGuarreraSimonettaSRussoAlessiaADalhusBjørnBCrescenziMarcoMHübscherUlrichUBjøråsMagnarMMatulloGiuseppeGDogliottiEugeniaEengJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20130528
United StatesFree Radic Biol Med87091590891-5849EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultAllelesDNA DamagegeneticsDNA GlycosylasesgeneticsmetabolismDNA RepairgeneticsFemaleGenetic Association StudiesHomozygoteHumansLymphocytesmetabolismMaleMiddle AgedOxidation-ReductionOxidative StressPolymorphism, Single NucleotideRisk FactorsDNA repairDisulfide bond profileFree radicalsGenotype–phenotype analysisSingle-nucleotide polymorphisms
2013010420130507201305212013646020136460201311260ppublish23726996S0891-5849(13)00241-410.1016/j.freeradbiomed.2013.05.031
237001562013112620171116
1423-03803452013OctTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Polymorphisms of DNA repair genes XPD, XRCC1, and OGG1, and lung adenocarcinoma susceptibility in Chinese population.2843-810.1007/s13277-013-0844-6Lung adenocarcinoma (ADC) is one of the major histological types of lung cancer. Genetic polymorphism in DNA repair genes and lung ADC susceptibility is well documented. In this case-control study, the association between the polymorphic sites of DNA repair genes XPD-751, XRCC1-399, and OGG1-326, and lung ADC susceptibility in ethnic Han Chinese population has been investigated. Genomic DNA was isolated from the peripheral blood of 201 healthy controls and 82 lung ADC patients from the people of Hunan Province, China. Polymorphisms of the investigated genes were analyzed by using polymerase chain reaction-restriction fragment length polymorphism. There was no significant difference between the samples from lung ADC patients and healthy controls about the genotype frequencies of XPD-751, XRCC1-399, and OGG1-326 sites. However, multifactor dimensionality reduction analysis showed that the genetic polymorphisms of the three-loci models of DNA repair genes (XPD-751/XRCC1-399/OGG1-326) are associated with lung ADC. Thus, this study reveals that a three-order interaction among the polymorphic sites of XPD-751, XRCC1-399, and OGG1-326 is associated with lung ADC risk in the studied population, although polymorphism in individual gene was not associated.OuyangFang-danFDDepartment of Biochemistry, School of Life Sciences, Central South University, Changsha, Hunan, 410013, China.YangFu-lanFLChenHan-chunHCKhanMd AsaduzzamanMAHuangFeng-maoFMWanXin-xingXXXuAi-huaAHHuangXingXZhouMei-juanMJFangQianQZhangDian-zhengDZengJournal ArticleResearch Support, Non-U.S. Gov't20130523
United StatesTumour Biol84099221010-42830DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanAdenocarcinoma of lungIMLung Cancer. 2007 May;56(2):153-6017316890Mutat Res. 1998 May 25;400(1-2):15-249685572Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):669-7410744126Mutat Res. 2011 Jun 3;711(1-2):100-1221167187Cancer Sci. 2006 Aug;97(8):724-816800823Carcinogenesis. 2002 Apr;23(4):599-60311960912Pharmacogenetics. 2004 Feb;14(2):103-915077011BMC Cancer. 2007 Aug 16;7:16217705814Int J Surg Pathol. 2006 Jan;14(1):21-3316501831Carcinogenesis. 2009 Jan;30(1):2-1018978338Ophthalmology. 2012 May;119(5):900-622306120Mutat Res. 2001 Jan 5;461(4):273-811104903Antioxid Redox Signal. 2001 Aug;3(4):597-60911554447Mutagenesis. 2010 Nov;25(6):569-7520817763Mol Biol Rep. 2012 Oct;39(10):9535-4722729882EMBO J. 2008 Feb 20;27(4):589-60518285820Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Carcinogenesis. 2001 Aug;22(8):1185-811470747Arch Med Res. 2011 Apr;42(3):226-3421722819Mutat Res. 2004 Feb 26;546(1-2):65-7414757194Oncogene. 1998 Jun 25;16(25):3219-259681819Genomics. 2004 Jun;83(6):970-915177551Int J Cancer. 2003 Oct 20;107(1):84-812925960World J Gastroenterol. 2003 May;9(5):956-6012717837Mutat Res. 2000 Feb 16;459(1):1-1810677679Nat Genet. 1998 Oct;20(2):184-89771713CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855J Epidemiol. 2002 May;12(3):258-6512164330Zhonghua Zhong Liu Za Zhi. 2005 Dec;27(12):713-616483478Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2003 Feb;20(1):35-812579497Carcinogenesis. 2012 May;33(5):1059-6422382497Cancer Res. 2005 Feb 1;65(3):722-615705867AdenocarcinomageneticsAdultAgedCase-Control StudiesChinaDNA GlycosylasesgeneticsDNA-Binding ProteinsgeneticsFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseHumansLung NeoplasmsgeneticsMaleMiddle AgedPolymorphism, Restriction Fragment LengthRisk FactorsSequence Analysis, DNAX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
20130423201305032013524602013524602013121660ppublish2370015610.1007/s13277-013-0844-6
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1471-2407132013May22BMC cancerBMC CancerAntioxidant-mediated up-regulation of OGG1 via NRF2 induction is associated with inhibition of oxidative DNA damage in estrogen-induced breast cancer.25310.1186/1471-2407-13-253Estrogen metabolism-mediated oxidative stress is suggested to play an important role in estrogen-induced breast carcinogenesis. We have earlier demonstrated that antioxidants, vitamin C (Vit C) and butylated hydroxyanisole (BHA) inhibit 17β-estradiol (E2)-mediated oxidative stress and oxidative DNA damage, and breast carcinogenesis in female August Copenhagen Irish (ACI) rats. The objective of the present study was to characterize the mechanism by which above antioxidants prevent DNA damage during breast carcinogenesis.Female ACI rats were treated with E2; Vit C; Vit C + E2; BHA; and BHA + E2 for up to 240 days. mRNA and protein levels of a DNA repair enzyme 8-Oxoguanine DNA glycosylase (OGG1) and a transcription factor NRF2 were quantified in the mammary and mammary tumor tissues of rats after treatment with E2 and compared with that of rats treated with antioxidants either alone or in combination with E2.The expression of OGG1 was suppressed in mammary tissues and in mammary tumors of rats treated with E2. Expression of NRF2 was also significantly suppressed in E2-treated mammary tissues and in mammary tumors. Vitamin C or BHA treatment prevented E2-mediated decrease in OGG1 and NRF2 levels in the mammary tissues. Chromatin immunoprecipitation analysis confirmed that antioxidant-mediated induction of OGG1 was through increased direct binding of NRF2 to the promoter region of OGG1. Studies using silencer RNA confirmed the role of OGG1 in inhibition of oxidative DNA damage.Our studies suggest that antioxidants Vit C and BHA provide protection against oxidative DNA damage and E2-induced mammary carcinogenesis, at least in part, through NRF2-mediated induction of OGG1.SinghBhupendraBDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Room 5251, Kansas City, MO 64108, USA.ChatterjeeAnweshaARongheAmruta MAMBhatNimee KNKBhatHari KHKengCA109551CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20130522
EnglandBMC Cancer1009678001471-24070Antioxidants0Estrogens0NF-E2-Related Factor 20Nfe2l2 protein, rat88847-89-68-oxo-7-hydrodeoxyguanosineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-OGG1 protein, ratG9481N71RODeoxyguanosineIMFood Chem Toxicol. 1999 Sep-Oct;37(9-10):993-710541456Cancer Lett. 2012 Mar;316(1):62-922082530Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2779-8410688907Arch Biochem Biophys. 2000 May 1;377(1):1-810775435J Natl Cancer Inst Monogr. 2000;(27):67-7310963620Mutat Res. 2000 Oct 16;461(2):109-1811018584J Biol Chem. 2000 Dec 22;275(51):40134-4111013233Anal Cell Pathol. 2001;23(1):21-811790856Mol Carcinog. 2002 Jan;33(1):56-6511807958J Biol Chem. 2003 Mar 7;278(10):8135-4512506115Carcinogenesis. 2003 Mar;24(3):511-512663512Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3913-812655060Ann N Y Acad Sci. 2004 Apr;1011:101-1115126288Mutat Res. 2004 Sep;567(1):1-6115341901Cancer Res. 1982 Jul;42(7):2609-156805943J Steroid Biochem. 1986 Jan;24(1):353-63009986Carcinogenesis. 1994 May;15(5):997-10008200107Cancer Res. 1997 Jun 1;57(11):2151-69187114Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-59223305Carcinogenesis. 1997 Aug;18(8):1595-6019276635Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10937-429380738Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18123-815601761J Steroid Biochem Mol Biol. 2004 Dec;92(5):391-815698544Neuroscience. 2005;136(1):135-4616182450Clin Chim Acta. 2006 Mar;365(1-2):30-4916214123Carcinogenesis. 2006 Mar;27(3):491-816311245Mol Cell Biol. 2006 Oct;26(20):7430-616923968Annu Rev Pharmacol Toxicol. 2007;47:89-11616968214J Physiol Pharmacol. 2006 Nov;57 Suppl 7:33-4917228095Oncogene. 2007 May 24;26(24):3587-9017160017Physiol Genomics. 2007 Dec 19;32(1):74-8117895394Toxicol Appl Pharmacol. 2008 Oct 1;232(1):78-8518640140Mol Carcinog. 2009 Feb;48(2):91-10418618599J Biochem Mol Toxicol. 2009 May-Jun;23(3):202-1119526586Carcinogenesis. 2009 Jul;30(7):1202-819406931Carcinogenesis. 2010 Jan;31(1):90-919793802Toxicol Appl Pharmacol. 2010 Sep 1;247(2):83-9020600213PLoS One. 2011;6(9):e2512521966433Toxicol Lett. 2011 Nov 30;207(2):143-821925250Br J Cancer. 2012 Jan 17;106(2):344-722108520Carcinogenesis. 2012 Dec;33(12):2601-1023027624Carcinogenesis. 2012 Jan;33(1):156-6322072621Carcinogenesis. 2000 Mar;21(3):427-3310688862AnimalsAntioxidantspharmacologyBlotting, WesternCell Line, TumorChromatin ImmunoprecipitationDNA DamagephysiologyDNA GlycosylasesbiosynthesisDeoxyguanosineanalogs & derivativesanalysisbiosynthesisEstrogenstoxicityFemaleHumansMammary Neoplasms, Experimentalchemically inducedmetabolismpathologyNF-E2-Related Factor 2biosynthesisOxidation-Reductiondrug effectsOxidative Stressdrug effectsRNA InterferenceRatsRats, Inbred ACIReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionSignal Transductiondrug effectsUp-Regulation
20130122201305072013524602013524602013121660epublish236975961471-2407-13-25310.1186/1471-2407-13-253PMC3665669
236848972013110120180425
1873-4596632013OctFree radical biology & medicineFree Radic. Biol. Med.Alzheimer's disease-associated polymorphisms in human OGG1 alter catalytic activity and sensitize cells to DNA damage.115-2510.1016/j.freeradbiomed.2013.05.010S0891-5849(13)00220-7Brain tissues from Alzheimer's disease (AD) patients show increased levels of oxidative DNA damage and 7,8-dihydro-8-oxoguanine (8-oxoG) accumulation. In humans, the base excision repair protein 8-oxoguanine-DNA glycosylase (OGG1) is the major enzyme that recognizes and excises the mutagenic DNA base lesion 8-oxoG. Recently, two polymorphisms of OGG1, A53T and A288V, have been identified in brain tissues of AD patients, but little is known about how these polymorphisms may contribute to AD. We characterized the A53T and A288V polymorphic variants and detected a significant reduction in the catalytic activity for both proteins in vitro and in cells. Additionally, the A53T polymorphism has decreased substrate binding, whereas the A288V polymorphism has reduced AP lyase activity. Both variants have decreased binding to known OGG1 binding partners PARP-1 and XRCC1. We found that OGG1(-/-) cells expressing A53T and A288V OGG1 were significantly more sensitive to DNA damage and had significantly decreased survival. Our results provide both biochemical and cellular evidence that A53T and A288V polymorphic proteins have deficiencies in catalytic and protein-binding activities that could be related to the increase in oxidative damage to DNA found in AD brains. Published by Elsevier Inc.JacobKimberly DKDLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6825, USA.Noren HootenNicoleNTadokoroTakashiTLohaniAlthafABarnesJaniceJEvansMichele KMKengZIA AG000517-09NULLIntramural NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Intramural20130514
United StatesFree Radic Biol Med87091590891-584907,8-dihydro-8-oxoguanine0DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, human0Xrcc1 protein, mouse5Z93L87A1RGuanineEC 2.4.2.30PARP1 protein, humanEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMNucleic Acids Res. 2006;34(5):1620-3216549874Nucleic Acids Res. 2007;35(16):5545-5517704129Mutat Res. 2011 Jun 3;711(1-2):100-1221167187Science. 1993 Oct 29;262(5134):689-957901908Biochemistry. 2003 Feb 18;42(6):1564-7212578369Nucleic Acids Res. 2007;35(8):2759-6617426120Nature. 2000 Feb 24;403(6772):859-6610706276Mech Ageing Dev. 2013 Mar;134(3-4):139-5723428415Nature. 1995 Jun 29;375(6534):754-607596406Science. 2002 Jul 19;297(5580):353-612130773Cell Res. 2008 Jan;18(1):48-6318166976Anal Biochem. 2006 Oct 15;357(2):289-9816962548Nucleic Acids Res. 2004;32(2):570-814752045Ann Neurol. 1993 Oct;34(4):609-168215249Cancer Detect Prev. 2007;31(3):237-4317651912DNA Repair (Amst). 2007 Mar 1;6(3):317-2817126083Ann Neurol. 1997 May;41(5):646-539153527Mol Carcinog. 2005 Mar;42(3):127-4115584022J Biol Chem. 2011 Dec 30;286(52):44679-9022057269Free Radic Res. 2006 Dec;40(12):1295-30217090419Ann Neurol. 1994 Nov;36(5):747-517979220Nature. 2005 Mar 31;434(7033):612-815800616Ann Neurol. 1992;32 Suppl:S22-71510377J Neurochem. 1997 Nov;69(5):2064-749349552Nature. 1991 Feb 21;349(6311):704-61671712J Neurochem. 2006 Feb;96(3):825-3216405502FEBS J. 2009 Sep;276(18):5149-6219674107Fold Des. 1998;3(2):119-269565756J Neurochem. 1997 Sep;69(3):1326-99282961PLoS Genet. 2010 May;6(5):e100095120485567Free Radic Biol Med. 1997;23(1):134-479165306Neurobiol Aging. 2002 Sep-Oct;23(5):655-6412392766Mol Chem Neuropathol. 1997 May;31(1):53-649271005Biopolymers. 1987 Nov;26(11):1859-773689874Mutat Res. 2001 Jun 5;486(1):31-4011356334Nucleic Acids Res. 2001 Mar 15;29(6):1285-9211238994Nat Rev Mol Cell Biol. 2006 Jul;7(7):517-2816829982Neurotoxicology. 1986 Spring;7(1):195-2063714121Biochem Biophys Res Commun. 2008 Nov 14;376(2):336-4018774780Curr Protoc Mol Biol. 2001 May;Chapter 16:Unit16.718265134J Neurochem. 2006 Jun;97(6):1634-5816805774Nucleic Acids Res. 1989 Aug 11;17(15):64192771659Curr Alzheimer Res. 2009 Feb;6(1):36-4719199873J Biol Chem. 2003 Nov 7;278(45):44068-7412933815Nature. 1995 Aug 31;376(6543):775-87651536Biochemistry. 1998 May 26;37(21):7733-409601033J Nerv Ment Dis. 1953 Aug;118(2):97-13013109530J Neurochem. 1995 Nov;65(5):2146-567595501Nucleic Acids Res. 2001 Jan 15;29(2):430-811139613J Neurosci. 2001 May 1;21(9):3017-2311312286Science. 1995 Aug 18;269(5226):973-77638622Alzheimer DiseasegeneticsmetabolismpathologyCatalysisDNA DamagegeneticsDNA GlycosylasesgeneticsmetabolismDNA RepairgeneticsDNA-Binding ProteinsmetabolismGuanineanalogs & derivativesmetabolismHumansOxidative StressPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesmetabolismPolymorphism, GeneticProtein BindingSubstrate SpecificityX-ray Repair Cross Complementing Protein 17,8-dihydro-8-oxoguanine8-Oxoguanine8-Oxoguanine-DNA glycosylase8-oxoG8-oxoguanine-DNA glycosylaseADAlzheimer's diseaseBERBase excision repairDNA damageDNA repairFree radicalsMEFOGG1Oxidative stressPARPARP-1ROSX-ray cross-complementing protein 1XRCC1base excision repairmouse embryo fibroblastpoly(ADP-ribose) polymerase 1poly(ADP-ribosyl)ationreactive oxygen species
201209072013040920130506201352160201352160201311260ppublish23684897S0891-5849(13)00220-710.1016/j.freeradbiomed.2013.05.010PMC3767440NIHMS482197
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0219-10323562013JunMolecules and cellsMol. CellsDecreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth.489-9710.1007/s10059-013-2343-4Many solid tumor cells exhibit mitochondrial respiratory impairment; however, the mechanisms of such impairment in cancer development remain unclear. Here, we demonstrate that SNU human hepatoma cells with declined mitochondrial respiratory activity showed decreased expression of mitochondrial 8-oxoguanine DNA glycosylase/lyase (mtOGG1), a mitochondrial DNA repair enzyme; similar results were obtained with human hepatocellular carcinoma tissues. Among several OGG1-2 variants with a mitochondrial-targeting sequence (OGG1-2a, -2b, -2c, -2d, and -2e), OGG1-2a was the major mitochondrial isoform in all examined hepatoma cells. Interestingly, hepatoma cells with low mtOGG1 levels showed delayed cell growth and increased intracellular reactive oxygen species (ROS) levels. Knockdown of OGG1-2 isoforms in Chang-L cells, which have active mitochondrial respiration with high mtOGG1 levels, significantly decreased cellular respiration and cell growth, and increased intracellular ROS. Overexpression of OGG1-2a in SNU423 cells, which have low mtOGG1 levels, effectively recovered cellular respiration and cell growth activities, and decreased intracellular ROS. Taken together, our results suggest that mtOGG1 plays an important role in maintaining mitochondrial respiration, thereby contributing to cell growth of hepatoma cells.LeeYoung-KyoungYKDepartment of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721, Korea.YounHwang-GuemHGWangHee-JungHJYoonGyesoonGengJournal ArticleResearch Support, Non-U.S. Gov't20130514
Korea (South)Mol Cells96109361016-84780Protein Isoforms0Reactive Oxygen SpeciesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMInt J Cancer. 1995 Jul 28;62(3):276-827543080Arch Biochem Biophys. 2000 May 1;377(1):1-810775435Science. 1956 Feb 24;123(3191):309-1413298683Nature. 1981 Apr 9;290(5806):457-657219534Exp Dermatol. 2006 Dec;15(12):1005-1517083367N Engl J Med. 2003 Jun 26;348(26):2656-6812826641Exp Cell Res. 2012 Sep 10;318(15):1808-1922652454Mutat Res. 1999 Jul 30;434(3):161-7610486590Exp Gerontol. 2006 Jan;41(1):11-2416307857J Biol Chem. 2003 Dec 19;278(51):51577-8614512425Biochim Biophys Acta. 1995 May 24;1271(1):171-67599205Cancer Res. 2002 Nov 15;62(22):6674-8112438266Curr Opin Genet Dev. 1995 Jun;5(3):315-227549425Physiol Rev. 2008 Apr;88(2):611-3818391175DNA Repair (Amst). 2004 Apr 1;3(4):403-1115010316Mol Biol Cell. 1999 May;10(5):1637-5210233168Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10771-87971961Oncogene. 2006 Aug 7;25(34):4647-6216892079Cell Death Differ. 2013 Jan;20(1):31-4222743996Prog Exp Tumor Res. 1978;22:190-274149996Mitochondrion. 2005 Apr;5(2):89-10816050976Circ Res. 2012 Oct 12;111(9):1208-2123065344J Cell Physiol. 2006 Nov;209(2):468-8016883569Methods Cell Biol. 2001;65:119-3111381589Nucleic Acids Res. 2004;32(18):5596-60815494448Cancer Res. 2001 Mar 1;61(5):1843-511280735Aging Cell. 2008 Dec;7(6):894-90718782348Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):719-2415647368Trends Biochem Sci. 1999 Feb;24(2):68-7210098401Exp Cell Res. 2011 May 1;317(8):1108-1821356207Mol Cells. 2011 Apr;31(4):327-3521448585Lancet. 1989 Mar 25;1(8639):642-52564461Nat Rev Genet. 2001 May;2(5):342-5211331900Nat Genet. 1999 Oct;23(2):14710508508Mutat Res. 2009 Nov 2;670(1-2):99-10219646455Biochim Biophys Acta. 1999 Feb 9;1410(2):103-2310076021Front Biosci (Landmark Ed). 2010;15:437-6020036829Nat Rev Cancer. 2012 Oct;12(10):685-9823001348Prog Nucleic Acid Res Mol Biol. 2001;68:257-7111554302Oncogene. 2006 Aug 7;25(34):4663-7416892080Cancer Res Treat. 2005 Feb;37(1):1-1919956504Carcinoma, HepatocellularmetabolismpathologyCell Growth ProcessesgeneticsCell Line, TumorCell RespirationgeneticsDNA GlycosylasesgeneticsmetabolismDown-RegulationGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansLiver NeoplasmsmetabolismpathologyMitochondria, LivergeneticsmetabolismProtein IsoformsgeneticsmetabolismReactive Oxygen SpeciesmetabolismTransgenesgenetics
201212272013040820130313201351760201351760201422660ppublish2367737710.1007/s10059-013-2343-4PMC3887880
236186152013082920171116
0027-5107745-7462013 May-JunMutation researchMutat. Res.An association selected polymorphisms of XRCC1, OGG1 and MUTYH gene and the level of efficiency oxidative DNA damage repair with a risk of colorectal cancer.6-1510.1016/j.mrfmmm.2013.04.002S0027-5107(13)00043-2Oxidative damage has been implicated in the pathogenesis of colorectal cancer (CRC). The base excision repair (BER) pathway is the major DNA repair pathway for oxidative DNA damage and genetic variation associated with impaired BER might thus increase a risk of CRC. In this work, we evaluated associations between the repair efficiency of oxidative DNA lesions and single-nucleotide polymorphisms of BER genes: the 194Trp/Arg and the 399Arg/Gln XRCC1, the 326Ser/Cys OGG1 and the 324Gln/His MUTYH and CRC occurrence in a Polish population. These polymorphisms were genotyped in 182 CRC patients and 245 control subjects, using a PCR-RFLP approach. The level of oxidative damage and DNA repair capacity in lymphocytes and CRC tissue samples was evaluated by comet assay using FPG and Nth glycosidases. The 326Ser/Cys OGG1 and the 324Gln/His as well as the 324His/His MUTYH genotypes were found to be associated with an increased CRC risk, while no association was found for the XRCC1 gene polymorphisms. It was also demonstrated the reduced capacity of oxidative damage repair in CRC patients in comparison to healthy controls. Moreover, the decrease efficiency of DNA repair were correlated with the 399Gln/Gln XRCC1 and the 324His/His MUTYH genotypes occurrence in CRC patients. The results obtained in our study indicated an association of OGG1 and MUTYH genes polymorphisms involved in oxidative DNA lesions repair with the risk occurrence of colorectal cancer in Polish patients. It was also found that studied polymorphisms might affect DNA repair capacity suggesting their role in CRC pathogenesis. Finally, we conclude that BER pathway may be an important target for the diagnosis and treatment of colorectal patients.Copyright © 2013 Elsevier B.V. All rights reserved.PrzybylowskaKarolinaKDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, Poland.KabzinskiJacekJSygutAndrzejADzikiLukaszLDzikiAdamAMajsterekIreneuszIengJournal Article20130423
NetherlandsMutat Res04007630027-51070DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanBBX060AN9VHydrogen PeroxideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanIMAgedCase-Control StudiesColorectal NeoplasmsgeneticspathologyComet AssayDNA DamageDNA GlycosylasesgeneticsDNA Repairdrug effectsgeneticsDNA-Binding ProteinsgeneticsEpistasis, GeneticFemaleGene FrequencyGenetic Predisposition to DiseaseHumansHydrogen PeroxidepharmacologyMaleMiddle AgedPolandPolymorphism, Single NucleotideX-ray Repair Cross Complementing Protein 1
201204272013032520130409201342760201342760201383060ppublish23618615S0027-5107(13)00043-210.1016/j.mrfmmm.2013.04.002
234992412013071620171116
0027-510775312013Apr30Mutation researchMutat. Res.Association of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326Ser/Cys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of primary open-angle glaucoma.12-2210.1016/j.mrgentox.2012.12.019S1383-5718(13)00067-3Numerous data have shown that progressive loss of human trabecular meshwork (TM) cells may be connected with oxidative stress. This hypothesis may suggest an association of base excision repair with the risk of primary open angle glaucoma development.The aim of this study was to evaluate the role of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326SerCys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of POAG.Our research included 170 patients with POAG and 193 healthy controls. Gene polymorphisms were investigated by PCR-RFLP. The Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed.The 399Arg/Gln genotype of the XRCC1 gene was associated with an increased risk for POAG (OR 2.50; 95% CI, 1.54-4.07, P=0.0002). The 399Gln/Gln XRCC1 genotype may increase the risk for POAG progression according to clinical parameters such as cup/disk ratio (c/d) (OR 1.93; 95% CI, 1-3.73, P=0.04) and Rim area (RA factor) (OR 3.88; 95% CI, 1.01-14.82, P=0.04). Moreover, an association was found of retinal nerve-fiber layer (RNFL factor) with the 399Arg/Gln XRCC1 genotype distribution and POAG progression (OR 2.46; 95% CI, 1.06-5.68, P=0.03). In contrast, analysis of the 324Gln/His MUTYH gene polymorphism distribution in the patient group according to RA factor showed that it may reduce the progression of POAG (OR 0.14; 95% CI, 0.02-0.89, P=0.05). Our current study demonstrates an association between the 326Ser/Cys OGG1 gene polymorphism and the 326Cys allele of the OGG1 gene, and progression of POAG. In addition, the presence of the 326His allele of the MUTYH gene may increase the risk for POAG progression, according to the VF parameter (OR 2.57; 95% CI, 1.47-4.57, P=0.0001).We suggest that the 399Arg/Gln genotype and the 399Gln allele of the XRCC1 gene may be risk factors for POAG development. Moreover, we postulate that the 399 Arg/Gln XRCC1, the 326 Ser/Cys OGG1 and the 324 Gln/His MUTYH genes polymorphisms may be associated with progression of POAG.Copyright © 2013 Elsevier B.V. All rights reserved.SzaflikJacek PJPDepartment of Ophthalmology II, Medical Faculty, Medical University of Warsaw, Poland.CuchraMagdaMPrzybylowska-SygutKarolinaKDzikiLukaszLKurowskaAnna KAKGacekMiraMDrzewoskiJozefJSzaflikJerzyJMajsterekIreneuszIengJournal ArticleResearch Support, Non-U.S. Gov't20130307
NetherlandsMutat Res04007630027-51070Codon0DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanIMAgedAged, 80 and overAllelesAmino Acid SubstitutionCardiovascular DiseasesepidemiologyCodongeneticsComorbidityDNA GlycosylasesgeneticsphysiologyDNA-Binding ProteinsgeneticsphysiologyDiabetic RetinopathyepidemiologyDisease ProgressionFemaleGenetic Predisposition to DiseaseGenotypeGlaucoma, Open-AngleepidemiologygeneticsHumansMaleMiddle AgedMutation, MissensePoint MutationPolymorphism, Single NucleotideRiskSeverity of Illness IndexSmokingepidemiologyX-ray Repair Cross Complementing Protein 1
201204172012102420121205201331960201331960201371760ppublish23499241S1383-5718(13)00067-310.1016/j.mrgentox.2012.12.019
234088432013081620130214
1464-38042822013MarMutagenesisMutagenesisGenetic and expressional variations of APEX1 are associated with increased risk of head and neck cancer.213-810.1093/mutage/ges074The aetiology of head and neck cancer (HNC) has been shown to be associated with genetic and certain environmental factors that produce DNA damage. Base excision repair (BER) genes are responsible for repair of DNA damage caused by reactive oxygen species and other electrophiles and therefore are good candidate susceptibility genes for HNC. Apurinic/apyrimidinic endonuclease-1 (APEX1) proteins have important functions in the BER pathway. In this case-control study, all exons of the APEX1 gene and its exon/intron boundaries were amplified in 300 HNC cases and 300 matched healthy controls and then analysed by single-stranded conformational polymorphism. Amplified products showing altered mobility patterns were sequenced and analysed. To confirm our observations, we examined APEX1 expression at mRNA level on 50 head and neck squamous cell carcinoma (HNSCC) and 50 normal control samples by quantitative real-time polymerase chain reaction. At germ line level, three novel mutations (13T > G, Ser129Arg and Val131Gly) of APEX1 were observed. The homozygous and heterozygous genotypes of APEX1 13T > G, Ser129Arg and Val131Gly appear to be significantly involved in the development of HNC. In the case of expressional level, APEX1 mRNA expression was positively correlated with tumour size, clinical stage and positive lymph node metastasis. Statistical analysis showed a significantly higher APEX1 mRNA level in HNC tumour tissue than in control samples. Our study demonstrated that APEX1 mutations and deregulation of APEX1 are associated with increased risk of HNC in the Pakistani population.MahjabeenIshratICancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Park Road Chak shazad, Islamabad, Pakistan.BaigRuqia MehmoodRMSabirMaimoonaMKayaniMahmood AkhtarMAengJournal ArticleResearch Support, Non-U.S. Gov't
EnglandMutagenesis87078120267-83570Genetic Markers0RNA, MessengerEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdultAgedAged, 80 and overCase-Control StudiesDNA DamageDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismFemaleGene Expression Regulation, NeoplasticGene-Environment InteractionGenetic MarkersHead and Neck NeoplasmsgeneticsHeterozygoteHumansMaleMiddle AgedMutationPakistanPolymorphism, Single-Stranded ConformationalRNA, MessengergeneticsmetabolismReal-Time Polymerase Chain ReactionRisk FactorsSequence Analysis, DNA
201321560201321560201382160ppublish23408843ges07410.1093/mutage/ges074
233780242013121720130506
1477-9137126Pt 62013Mar15Journal of cell scienceJ. Cell. Sci.The presence of a truncated base excision repair pathway in human spermatozoa that is mediated by OGG1.1488-9710.1242/jcs.121657DNA repair has long been considered impossible in human spermatozoa due to the high level of DNA compaction observed in these cells. However, detailed examination of the base excision repair pathway in human spermatozoa has revealed the presence of an enzyme critical to this pathway, 8-oxoguanine DNA glycosylase 1 (OGG1). This glycosylase was associated with the sperm nucleus and mitochondria and could actively excise 8-hydroxy-2'-deoxyguanosine (8OHdG), releasing this adduct into the extracellular space. This activity was significantly reduced in the presence of cadmium (II), a recognized inhibitor of OGG1, in a time- and dose-dependent manner (P<0.001). Remarkably, spermatozoa do not possess the downstream components of the base excision repair pathway, apurinic endonuclease 1 (APE1) and X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1). The absence of these proteins was particularly significant, as APE1 is required to create a 3'-hydroxyl (3'-OH) terminus at the apurinic site created by OGG1, which would be recognized by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. As a result, TUNEL was unable to detect oxidatively induced DNA damage in spermatozoa following exposure to hydrogen peroxide. In the same cells, intracellular and extracellular 8OHdG could be clearly detected in a manner that was highly correlated with the outcome of the sperm chromatin structure assay (SCSA). However, incubation of these cells for 48 hours revealed a time-dependent increase in TUNEL positivity, suggesting the perimortem activation of a nuclease. These results emphasize the limited capacity of mature spermatozoa to mount a DNA repair response to oxidative stress, and highlight the importance of such mechanisms in the oocyte in order to protect the embryo from paternally mediated genetic damage.SmithTegan BTBPriority Research Centre in Reproductive Science, Discipline of Biological Sciences, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.DunMatthew DMDSmithNathan DNDCurryBen JBJConnaughtonHaley SHSAitkenRobert JRJengJournal ArticleResearch Support, Non-U.S. Gov't20130201
EnglandJ Cell Sci00524570021-95330DNA Adducts00BH33GNGHCadmiumBBX060AN9VHydrogen PeroxideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAnimalsCOS CellsCadmiummetabolismCell NucleusmetabolismCercopithecus aethiopsCricetinaeDNA AdductsmetabolismDNA DamageDNA GlycosylasesmetabolismDNA RepairphysiologyHumansHydrogen PeroxidemetabolismMaleMitochondriametabolismOxidative StressProtein TransportSignal TransductionSpermatozoaphysiologyDNA damageHuman spermatozoaOGG1Oxidative stress
20132560201325602013121860ppublish23378024jcs.12165710.1242/jcs.121657
233764762013042920131121
1879-316921822013Apr12Toxicology lettersToxicol. Lett.OGG1 Ser326Cys polymorphism interacts with cigarette smoking to increase oxidative DNA damage in human sperm and the risk of male infertility.144-910.1016/j.toxlet.2013.01.017S0378-4274(13)00039-88-Oxoguanine DNA glycosylase 1 (OGG1) plays an important role in repairing oxidative DNA damage induced by chemical agents, such as tobacco. This study examined the effects of OGG1 Ser326Cys polymorphism and cigarette smoking, alone or combined, on sperm oxidative DNA damage and the risk of male infertility. A total of 620 idiopathic infertile subjects and 480 fertile controls were recruited in this study. Sperm 8-hydroxydeoxyguanine (8-OHdG) was measured by immunofluorescent assay using flow cytometry and genotypes were determined by OpenArray platform with a chip-based Taq-Man genotyping technology. Our results demonstrated that both cigarette smoking and OGG1 polymorphism can affect the sperm 8-OHdG levels. Individuals with variant Cys/Cys homozygote showed higher levels of sperm 8-OHdG than wide-type homozygote carriers (Ser/Ser). Stratified analysis found that the association between OGG1 polymorphism and sperm 8-OHdG levels was only observed among smokers with pack-years ≥5 but not among those subjects with pack-years<5 (pack-years=packs smoked per day×years as a smoker). Further analysis based on the case-control study revealed that variant allele (Cys) of OGG1 was significantly associated with male infertility risk in a dominant model (OR=1.35, 95% CI: 1.01-1.82; trend P<0.001). Furthermore, we found a significant gene-environment interaction between OGG1 Ser326Cys polymorphism and cigarette smoking in relation to male infertility risk (Pinteration=0.0003). These findings provided the first evidence about potential interactive effects of OGG1 polymorphism and cigarette smoking on male infertility risk.Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.JiGuixiangGNanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042, China.YanLifengLLiuWeiWQuJianhuaJGuAihuaAengJournal ArticleResearch Support, Non-U.S. Gov't20130131
NetherlandsToxicol Lett77090270378-42745Z93L87A1RGuanine6957-76-28-oxo-7,8-dihydrodeoxyguanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultCase-Control StudiesDNA Damagedrug effectsDNA GlycosylasesgeneticsmetabolismGene-Environment InteractionGenotypeGuanineanalogs & derivativesanalysisHumansInfertility, Malechemically inducedgeneticsMaleOxidative Stressdrug effectsPolymorphism, Single NucleotideRisk FactorsSmokingadverse effectsSpermatozoadrug effectsmetabolism
2012102420130104201301232013256020132560201343060ppublish23376476S0378-4274(13)00039-810.1016/j.toxlet.2013.01.017
233685322013091620160511
1945-02571742013AprGenetic testing and molecular biomarkersGenet Test Mol BiomarkersIs there any association between the Ser326Cys polymorphism of the 8-oxoguanine glycosylase 1 (OGG1) gene and risk of colon polyp and abnormal glucose tolerance in acromegaly patients?267-7310.1089/gtmb.2012.0398Evidence arising from experimental studies indicates an association between increased levels of the growth hormone/insulin-like growth factor 1 and oxidative stress. The association of the Ser326Cys polymorphism in the 8-oxoguanine glycosylase (OGG1) gene with a colon carcinoma and diabetes mellitus has been examined. The aim of the study was to compare the genotypic distribution of OGG1 Ser326Cys between acromegaly patients and nonacromegalic subjects and to explore whether this polymorphism is associated with a colon polyp risk and abnormal glucose tolerance.We examined 98 acromegaly patients, and 99 healthy subjects who can be compared in terms of age and gender. All participants were evaluated by anthropometric and biochemical measurements. Also, a 75-g oral glucose test and colonoscopy was applied to the patients. Genomic DNA was isolated from peripheral blood leucocytes and the genotype was assessed by melting temperature analyses after using a real-time polymerase chain reaction protocol.Colon polyps were detected in 13 (30.2%) of 43 patients who underwent the colonoscopy. Except for diastolic blood pressure, clinical and biochemical characteristics were similar between the patients diagnosed with and without a colon polyp. A higher proportion of acromegaly patients had the Ser326Ser genotype when compared to the control group (p=0.007). Genotypes were similar between the patients with a normal glucose tolerance and an abnormal glucose tolerance (p=0.774). The frequency of the Cys allele was significantly higher in patients with polyps than those without a polyp (38.5% vs. 18.3%) (p=0.029).Our results suggest that the Cys allele may influence the colon polyp risk in acromegaly patients. Large-scale studies with acromegaly patients are required to show whether being a carrier of the Cys allele is associated with the risk of a colorectal polyp.ZengiAyhanADepartment of Endocrinology and Metabolism, Isparta Public Hospital, Isparta, Turkey.KaradenizMuammerMCetintasVildan BozokVBHarmanEceETetikAslıAOrmanMehmetMErogluZuhalZCetinkalpSevkiSOzgenAhmet GokhanAGSaygiliFusunFYilmazCandegerCengJournal Article20130131
United StatesGenet Test Mol Biomarkers1014942101945-0257EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAcromegalycomplicationsgeneticsAdultColonic NeoplasmsgeneticsmetabolismColonic PolypsdiagnosisgeneticsDNA GlycosylasesgeneticsFemaleGenetic Predisposition to DiseaseGenotypeGlucose IntolerancegeneticsGlucose Tolerance TestHumansMaleMiddle AgedOxidative StressPolymorphism, GeneticRisk Factors
2013226020132260201391760ppublish2336853210.1089/gtmb.2012.0398
233329712013080720161125
1568-78561232013Mar01DNA repairDNA Repair (Amst.)Rapid inactivation and proteasome-mediated degradation of OGG1 contribute to the synergistic effect of hyperthermia on genotoxic treatments.227-3710.1016/j.dnarep.2012.12.006S1568-7864(12)00309-6Inhibition of DNA repair has been proposed as a mechanism underlying heat-induced sensitization of tumour cells to some anticancer treatments. Base excision repair (BER) constitutes the main pathway for the repair of DNA lesions induced by oxidizing or alkylating agents. Here, we report that mild hyperthermia, without toxic consequences per se, affects cellular DNA glycosylase activities, thus impairing BER. Exposure of cells to mild hyperthermia leads to a rapid and selective inactivation of OGG1 (8-oxoguanine DNA glycosylase) associated with the relocalisation of the protein into a detergent-resistant cellular fraction. Following its inactivation, OGG1 is ubiquitinated and directed to proteasome-mediated degradation, through a CHIP (C-terminus of HSC70-interacting protein) E3 ligase-mediated process. Moreover, the residual OGG1 accumulates in the perinuclear region leading to further depletion from the nucleus. As a consequence, HeLa cells subjected to hyperthermia and exposed to a genotoxic treatment have a reduced capacity to repair OGG1 cognate base lesions and an enhanced cell growth defect. The partial alleviation of this response by OGG1 overexpression indicates that heat-induced glycosylase inactivation contributes to the synergistic effect of hyperthermia on genotoxic treatments. Taken together, our results suggest that OGG1 inhibition contributes to heat-induced chemosensitisation of cells and could lay the basis for new anticancer therapeutic protocols that include hyperthermia.Copyright © 2012 Elsevier B.V. All rights reserved.FantiniDamianoDCEA, Institute of Molecular and Cellular Radiobiology, 18 route du Panorama, Fontenay aux Roses, F-92265, France.MoritzEvaEAuvréFrédéricFAmourouxRachelRCampalansAnnaAEpeBerndBBravardAnneARadicellaJ PabloJPengJournal ArticleResearch Support, Non-U.S. Gov't20130115
NetherlandsDNA Repair (Amst)1011391381568-78560Photosensitizing Agents0Pyrrolidines0Quinolizines104604-66-2Ro 19-8022EC 2.3.2.27STUB1 protein, humanEC 2.3.2.27Ubiquitin-Protein LigasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.4.25.1Proteasome Endopeptidase ComplexIMCell NucleusmetabolismCell ProliferationDNA DamageDNA GlycosylasesgeneticsmetabolismDNA RepairEnzyme StabilityHeLa CellsHeat-Shock ResponseHumansPhotosensitizing AgentspharmacologyProteasome Endopeptidase ComplexProtein TransportProteolysisPyrrolidinespharmacologyQuinolizinespharmacologyUbiquitin-Protein LigasesmetabolismUbiquitination
20121008201212182012122120131226020131226020138860ppublish23332971S1568-7864(12)00309-610.1016/j.dnarep.2012.12.006
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1932-62037122012PloS onePLoS ONE8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction.e5169710.1371/journal.pone.0051697Oxidative damage to DNA is mainly repaired via base excision repair, a pathway that is catalyzed by DNA glycosylases such as 8-oxoguanine DNA glycosylase (OGG1). While OGG1 has been implicated in maintaining genomic integrity and preventing tumorigenesis, we report a novel role for OGG1 in altering cellular and whole body energy homeostasis. OGG1-deficient (Ogg1(-/-)) mice have increased adiposity and hepatic steatosis following exposure to a high-fat diet (HFD), compared to wild-type (WT) animals. Ogg1(-/-) animals also have higher plasma insulin levels and impaired glucose tolerance upon HFD feeding, relative to WT counterparts. Analysis of energy expenditure revealed that HFD-fed Ogg1(-/-) mice have a higher resting VCO(2) and consequently, an increased respiratory quotient during the resting phase, indicating a preference for carbohydrate metabolism over fat oxidation in these mice. Additionally, microarray and quantitative PCR analyses revealed that key genes of fatty acid oxidation, including carnitine palmitoyl transferase-1, and the integral transcriptional co-activator Pgc-1α were significantly downregulated in Ogg1(-/-) livers. Multiple genes involved in TCA cycle metabolism were also significantly reduced in livers of Ogg1(-/-) mice. Furthermore, hepatic glycogen stores were diminished, and fasting plasma ketones were significantly reduced in Ogg1(-/-) mice. Collectively, these data indicate that OGG1 deficiency alters cellular substrate metabolism, favoring a fat sparing phenotype, that results in increased susceptibility to obesity and related pathologies in Ogg1(-/-) mice.SampathHariniHDepartment of Molecular and Medical Genetics, Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR, USA.VartanianVladimirVRollinsM RickMRSakumiKunihikoKNakabeppuYusakuYLloydR StephenRSengR01 DK075974DKNIDDK NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20121217
United StatesPLoS One1012850811932-62030DNA, Mitochondrial0Insulin0Lipids9005-79-2GlycogenEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIY9XDZ35W2GlucoseIMFree Radic Biol Med. 2010 Aug 15;49(4):587-9620483371J Hum Genet. 2009 Dec;54(12):739-4519881468Semin Cancer Biol. 2010 Oct;20(5):320-820955798Nature. 2011 Feb 17;470(7334):359-6521307849Am J Clin Nutr. 2011 Apr;93(4):884S-9021289221Acta Biochim Biophys Sin (Shanghai). 2011 Apr;43(4):248-5721325336Am J Physiol Endocrinol Metab. 2011 Apr;300(4):E724-3421285402Free Radic Biol Med. 2011 Jul 15;51(2):417-2321569841Acta Biochim Biophys Sin (Shanghai). 2011 Aug;43(8):589-9421733854Folia Neuropathol. 2011;49(2):123-3121845541Free Radic Biol Med. 2012 Jan 15;52(2):392-40122100973Free Radic Res. 2012 Apr;46(4):460-7822300253Hum Hered. 2010;70(2):97-10120606456Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Acta Neuropathol. 2002 Jan;103(1):20-511837743Pflugers Arch. 2002 Nov;445(2):273-812457248Cancer Res. 2003 Mar 1;63(5):902-512615700Int J Cancer. 2003 Sep 20;106(5):752-712866036Cancer Lett. 2004 Jan 8;203(1):25-3314670614Oncol Rep. 2004 Aug;12(2):483-815254719J Bacteriol. 1992 Oct;174(20):6321-51328155Mutat Res. 1996 May;316(5-6):277-858649461Mol Gen Genet. 1997 Mar 26;254(2):171-89108279Curr Biol. 1997 Jun 1;7(6):397-4079197244Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7429-349207108Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-59223305Oncogene. 1998 Jun 11;16(23):3083-69662341Mol Biol Cell. 1999 May;10(5):1637-5210233168Cell. 2005 Jan 28;120(2):261-7315680331Int J Obes (Lond). 2005 Mar;29 Suppl 1:S5-915711583Acta Neuropathol. 2005 Mar;109(3):256-6215841414Gene Expr. 2005;12(4-6):315-2316358418J Biochem. 2005 Dec;138(6):763-7216428305Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1864-916446448Toxicology. 2006 Apr 17;221(2-3):179-8616494984J Biol Chem. 2006 Jul 14;281(28):19000-816670093Biol Res Nurs. 2006 Oct;8(2):157-6917003255DNA Repair (Amst). 2007 Apr 1;6(4):470-8017116430DNA Repair (Amst). 2007 Apr 1;6(4):481-817127104J Neurosci Res. 2007 Apr;85(5):919-3417279544Nucleic Acids Res. 2007;35(8):2759-6617426120Cancer Lett. 2008 Jul 18;266(1):60-7218374480Free Radic Biol Med. 2008 Sep 15;45(6):813-918598755Biochem Biophys Res Commun. 2009 Aug 14;386(1):26-919486888DNA Cell Biol. 2009 Nov;28(11):579-8819630534PLoS One. 2010;5(8):e1207020706593AdiposityAnimalsDNA GlycosylasesphysiologyDNA, MitochondrialgeneticsDiet, High-Fatadverse effectsEnergy MetabolismFatty LiveretiologymetabolismpathologyGlucosemetabolismGlucose Tolerance TestGlycogenmetabolismInsulinmetabolismLipidsanalysisMaleMiceMice, Inbred C57BLMice, KnockoutObesityetiologymetabolismpathologyOxidative Stress
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0027-51077501-22013Jan20Mutation researchMutat. Res.The role of base excision repair genes OGG1, APN1 and APN2 in benzo[a]pyrene-7,8-dione induced p53 mutagenesis.121-810.1016/j.mrgentox.2012.10.003S1383-5718(12)00296-3Lung cancer is primarily caused by exposure to tobacco smoke. Tobacco smoke contains numerous carcinogens, including polycyclic aromatic hydrocarbons (PAH). The most common PAH studied is benzo[a]pyrene (B[a]P). B[a]P is metabolically activated through multiple routes, one of which is catalyzed by aldo-keto reductase (AKR) to B[a]P-7,8-dione (BPQ). BPQ undergoes a futile redox cycle in the presence of NADPH to generate reactive oxygen species (ROS). ROS, in turn, damages DNA. Studies with a yeast p53 mutagenesis system found that the generation of ROS by PAH o-quinones may contribute to lung carcinogenesis because of similarities between the patterns (types of mutations) and spectra (location of mutations) and those seen in lung cancer. The patterns were dominated by G to T transversions, and the spectra in the experimental system have mutations at lung cancer hotspots. To address repair mechanisms that are responsible for BPQ induced damage we observed the effect of mutating two DNA repair genes OGG1 and APE1 (APN1 in yeast) and tested them in a yeast reporter system for p53 mutagenesis. There was an increase in both the mutant frequency and the number of G:C/T:A transversions in p53 treated with BPQ in ogg1 yeast but not in apn1 yeast. Knocking out APN2 increased mutagenesis in the apn1 cells. In addition, we did not find a strand bias on p53 treated with BPQ in ogg1 yeast. These studies suggest that Ogg1 is involved in repairing the oxidative damage caused by BPQ, Apn1 and Apn2 have redundant functions and that the stand bias seen in lung cancer may not be due to impaired repair of oxidative lesions.Copyright © 2012 Elsevier B.V. All rights reserved.AbedinZahidurZDepartment of Pharmacology, Centers for Excellence in Environmental Toxicology and Cancer Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6084, USA.Louis-JusteMelissaMStanglMelissaMFieldJeffreyJengR25 ES021649ESNIEHS NIH HHSUnited StatesR25 ESO016146PHS HHSUnited StatesR25 ES016146ESNIEHS NIH HHSUnited StatesP30 ES013508ESNIEHS NIH HHSUnited StatesP30 ESO013508PHS HHSUnited StatesR01 ES015662ESNIEHS NIH HHSUnited StatesR01 GM048241GMNIGMS NIH HHSUnited StatesR01PHS HHSUnited StatesR01 GM48241GMNIGMS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20121029
NetherlandsMutat Res04007630027-51070Mutagens0Saccharomyces cerevisiae Proteins3417WMA06DBenzo(a)pyreneEC 3.1.-EndodeoxyribonucleasesEC 3.1.25.-Apn1 protein, S cerevisiaeEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APN2 protein, S cerevisiaeEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 6.5.1.-DNA Repair EnzymesIMMol Cell Biol. 2010 Jul;30(13):3206-1520421413Biochimie. 1997 Oct;79(9-10):559-669466693Carcinogenesis. 2003 Jun;24(6):1031-712807753Arch Biochem Biophys. 2000 May 1;377(1):1-810775435Science. 1978 Feb 17;199(4330):778-81622566Annu Rev Biochem. 1994;63:915-487979257Science. 1996 Oct 18;274(5286):430-28832894Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915-228367443Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3963-77732013DNA Repair (Amst). 2004 Jan 5;3(1):1-1214697754Mol Cell Biol. 1991 Sep;11(9):4537-441715020Chem Res Toxicol. 2006 Nov;19(11):1441-5017112231Mutat Res. 2000 Oct 16;461(2):83-10811018583Nucleic Acids Res. 1998 Mar 1;26(5):1228-339469830Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8165-97520176J Natl Cancer Inst. 1999 Jul 21;91(14):1194-21010413421Nat Rev Mol Cell Biol. 2008 Dec;9(12):958-7019023283Mutat Res. 2001 May 10;485(4):283-30711585362Carcinogenesis. 1998 Feb;19(2):347-519498287Chem Res Toxicol. 2007 Sep;20(9):1331-4117702526Carcinogenesis. 2001 Mar;22(3):367-7411238174Nucleic Acids Res. 1998 Jan 1;26(1):200-49399836Chem Res Toxicol. 2011 Nov 21;24(11):1905-1421962213Chem Res Toxicol. 2006 Sep;19(9):1215-2016978026Yeast. 2004 Sep;21(12):991-100315449310Chem Res Toxicol. 2012 Oct 15;25(10):2117-2622768918Mol Cell. 2003 Oct;12(4):959-7014580346Curr Biol. 1997 Jun 1;7(6):397-4079197244Mutagenesis. 2007 Sep;22(5):343-5117630408Physiol Rev. 1980 Oct;60(4):1107-667001511Chem Res Toxicol. 1999 Mar;12(3):237-4610077486Mutat Res. 2009 Mar 9;662(1-2):67-7419162045Science. 1991 Jul 5;253(5015):49-531905840Mutat Res. 2000 Aug 30;460(3-4):211-2910946230Mutat Res. 2009 Feb 19;673(1):3-819100859DNA Repair (Amst). 2004 May 4;3(5):483-9415084310Antioxid Redox Signal. 2001 Aug;3(4):597-60911554447Cancer Res. 2008 Sep 1;68(17):6863-7218757397DNA Repair (Amst). 2004 Nov 2;3(11):1457-6815380101Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8397-40210890888J Neurochem. 2007 Jul;102(1):13-2417506861J Natl Cancer Inst. 2008 Dec 3;100(23):1672-9419033571Cancer Res. 1982 Dec;42(12):4875-9176814745Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4091-58633021Nucleic Acids Res. 2005;33(10):3271-8215942030Hum Mutat. 2003 Mar;21(3):229-3912619108Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10422-67479797Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12244-911035769Mutat Res. 2001 Jun 5;486(1):31-4011356334Chem Res Toxicol. 2002 Jun;15(6):832-4212067251Chem Res Toxicol. 2008 May;21(5):1039-4918489080Chem Res Toxicol. 1999 Jan;12(1):1-189894013Mol Cell Biol. 1999 Apr;19(4):2929-3510082560Chem Res Toxicol. 2012 Jan 13;25(1):113-2122053912Carcinogenesis. 1993 Mar;14(3):475-828384091Mol Gen Genet. 1997 Mar 26;254(2):171-89108279Chem Res Toxicol. 2006 May;19(5):719-2816696575Carcinogenesis. 2003 Jan;24(1):113-912538356Xenobiotica. 1995 Jul;25(7):677-887483666Proc Jpn Acad Ser B Phys Biol Sci. 2006 May;82(4):127-4125792776Mol Cell Biol. 2005 Aug;25(15):6380-9016024777Proc Natl Acad Sci U S A. 2008 May 13;105(19):6846-5118474869DNA Repair (Amst). 2002 Apr 29;1(4):261-7312509245Nucleic Acids Res. 2001 Jan 15;29(2):430-811139613Biochemistry. 1977 Mar 8;16(5):932-8843522Carcinogenesis. 1992 Dec;13(12):2241-71473230Benzo(a)pyrenetoxicityDNA DamageDNA GlycosylasesgeneticsDNA RepairgeneticsDNA Repair EnzymesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsEndodeoxyribonucleasesgeneticsGenes, p53MutagenesisMutagenschemistrytoxicitySaccharomyces cerevisiae Proteinsgenetics
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1460-2105104222012Nov21Journal of the National Cancer InstituteJ. Natl. Cancer Inst.N-methylpurine DNA glycosylase and OGG1 DNA repair activities: opposite associations with lung cancer risk.1765-910.1093/jnci/djs445Only a minority of smokers develop lung cancer, possibly due to genetic predisposition, including DNA repair deficiencies. To examine whether inter-individual variations in DNA repair activity of N-methylpurine DNA glycosylase (MPG) are associated with lung cancer, we conducted a blinded, population-based, case-control study with 100 lung cancer case patients and 100 matched control subjects and analyzed the data with conditional logistic regression. All statistical tests were two-sided. MPG enzyme activity in peripheral blood mononuclear cells from case patients was higher than in control subjects, results opposite that of 8-oxoguanine DNA glycosylase (OGG1) DNA repair enzyme activity. For lung cancer associated with one standard deviation increase in MPG activity, the adjusted odds ratio was 1.8 (95% confidence interval [CI] = 1.2 to 2.6; P = .006). A combined MPG and OGG1 activities score was more strongly associated with lung cancer risk than either activity alone, with an odds ratio of 2.3 (95% CI = 1.4 to 3.6; P < .001). These results form a basis for a future panel of risk biomarkers for lung cancer risk assessment and prevention.Leitner-DaganYaelYDepartment of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.SevilyaZivZPinchevMilaMKramerRanRElingerDaliaDRoismanLaila CLCRennertHedy SHSSchechtmanEdnaEFreedmanLaurenceLRennertGadGLivnehZviZPaz-ElizurTamarTengU01 CA111219CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20121027
United StatesJ Natl Cancer Inst75030890027-88740Biomarkers, TumorEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.2.2.21DNA-3-methyladenine glycosidase IIIMMol Cancer Ther. 2004 Aug;3(8):955-6715299078J Biol Chem. 2004 Apr 23;279(17):17723-3014761949Mutat Res. 1995 Jan;336(1):9-177528899Biochem J. 1997 Jul 1;325 ( Pt 1):1-169224623Nucleic Acids Res. 1998 Sep 1;26(17):4034-419705516Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9997-100029707589Cancer Res. 2005 Jul 15;65(14):6394-40016024643Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1585-716030087N Engl J Med. 2006 Oct 26;355(17):1763-7117065637Cancer Res. 2006 Dec 15;66(24):11683-917178863DNA Repair (Amst). 2007 Jan 4;6(1):45-6016982217DNA Repair (Amst). 2007 Jan 4;6(1):71-8117018265Cancer Sci. 2007 Apr;98(4):465-7017425590Cancer Res. 2007 Apr 15;67(8):3493-517440053Cancer Res. 2008 Apr 15;68(8):3049-5618413776Cancer Lett. 2008 Jul 18;266(1):60-7218374480Adv Exp Med Biol. 2005;570:125-7318727500Cell Mol Life Sci. 2009 Mar;66(6):981-9319153658Am J Respir Crit Care Med. 2009 May 15;179(10):860-819423719Biochemistry. 2009 Mar 10;48(9):1850-6119219989JAMA. 2009 Sep 16;302(11):1210-719755700Mol Cell. 2010 Mar 26;37(6):843-5320347426N Engl J Med. 2011 Aug 4;365(5):395-40921714641Nat Neurosci. 2011 Sep;14(9):1105-721878926DNA Repair (Amst). 2012 Jan 2;11(1):46-5222079122CA Cancer J Clin. 2012 Jan-Feb;62(1):10-2922237781Mutat Res. 2012 Apr 1;732(1-2):43-622266085FEBS Lett. 2000 Jun 30;476(1-2):73-710878254J Natl Cancer Inst. 2000 Nov 1;92(21):1764-7211058619Nature. 2001 May 17;411(6835):366-7411357144Cancer Res. 2003 Aug 1;63(15):4351-712907604Cancer Res. 2003 Aug 15;63(16):4899-90212941813J Natl Cancer Inst. 2003 Sep 3;95(17):1312-912953085J Clin Invest. 2003 Dec;112(12):1887-9414679184Eur J Epidemiol. 1988 Dec;4(4):461-93203727AdultAgedBiomarkers, TumorgeneticsmetabolismCase-Control StudiesDNA GlycosylasesgeneticsmetabolismDNA RepairFemaleHumansLeukocytes, MononuclearenzymologyLogistic ModelsLung NeoplasmsenzymologygeneticsMaleMiddle AgedOdds RatioRisk Factors
20121030602012103060201311560ppublish23104324djs44510.1093/jnci/djs445PMC3502197
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1573-497839122012DecMolecular biology reportsMol. Biol. Rep.Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis.11249-6210.1007/s11033-012-2035-8The previous published data on the association between the 8-oxo-guanine glycosylase-1 (OGG1) and apurinic/apyrimidinic-endonuclease-1 (APEX1/APE1) polymorphisms and lung cancer risk remained controversial. Several polymorphisms in the OGG1 and APEX1 gene have been described, including the commonly occurring Ser326Cys in OGG1 and Asp148Glu in APEX1. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 37 studies were identified to the meta-analysis, including 9,203 cases and 10,994 controls for OGG1 Ser326Cys (from 25 studies) and 3,491 cases and 4,708 controls for APEX1 Asp148Glu (from 12 studies). When all the eligible studies were pooled into the meta-analysis of OGG1 Ser326Cys polymorphism, significantly increased lung cancer risk was observed in recessive model (OR = 1.17, 95 % CI = 1.03-1.33) and in additive model (OR = 1.21, 95 % CI = 1.03-1.42). In the stratified analysis, significantly increased risk of lung cancer was also observed on the population-based studies (recessive model: OR = 1.26, 95 % CI = 1.08-1.46, additive model: OR = 1.42, 95 % CI = 1.06-1.73) and non-smokers (dominant model: OR = 1.20, 95 % CI = 1.02-1.42, recessive model: OR = 1.20, 95 % CI = 1.02-1.40, additive model: OR = 1.35, 95 % CI = 1.08-1.68). Additionally, when one study was deleted in the sensitive analysis, the results of OGG1 Ser326Cys were changed in Asians (recessive model: OR = 1.16, 95 % CI = 1.06-1.27, additive model: OR = 1.23, 95 % CI = 1.09-1.38). When all the eligible studies were pooled into the meta-analysis of APEX1 Asp148Glu polymorphism, there was no evidence of significant association between lung cancer risk and APEX1 Asp148Glu polymorphism in any genetic model. In the stratified analysis, significantly decreased lung adenocarcinoma risk was observed in recessive model (OR = 0.68, 95 % CI = 0.48-0.97, P (h) = 0.475, I(2) = 0.0 %). Additionally, when one study was deleted in the sensitive analysis, the results of APEX1 Asp148Glu were changed in Asians (recessive model: OR = 1.21, 95 % CI = 1.03-1.43) and smokers (dominant model: OR = 1.62, 95 % CI = 1.08-2.44, additive model: OR = 1.37, 95 % CI = 1.02-1.84). In summary, this meta-analysis indicates that OGG1 Ser326Cys show an increased lung cancer risk in Asians and non-smokers, APEX1 Asp148Glu polymorphism may be associated with decreased lung adenocarcinoma risk, and APEX1 Asp148Glu polymorphism show an increased lung cancer risk in Asians and smokers. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk.WeiWuWDepartment of Hematology, Peace Hospital of Changzhi Medical College, Changzhi, 046000, China. weiwuhxf@163.comHeXiao-FengXFQinJiang-BoJBSuJiaoJLiShao-XiaSXLiuYiYZhangYingYWangWeiWengJournal ArticleMeta-Analysis20121012
NetherlandsMol Biol Rep04032340301-4851EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnticancer Res. 2010 Oct;30(10):4141-521036733Cancer Lett. 2005 Jun 8;223(2):265-7415896461Asian Pac J Cancer Prev. 2010;11(5):1181-621198260Demography. 2003 Feb;40(1):45-6512647513Anticancer Res. 2005 Jan-Feb;25(1B):537-4215816625Biochem Genet. 2004 Dec;42(11-12):453-6015587988Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):669-7410744126J Hum Genet. 2009 Dec;54(12):739-4519881468Cancer Sci. 2006 Aug;97(8):724-816800823Asian Pac J Cancer Prev. 2011;12(4):1067-7221790253Free Radic Res. 2006 Aug;40(8):885-9117015267Biometrics. 1994 Dec;50(4):1088-1017786990J Exp Clin Cancer Res. 2009 Jan 22;28:1019161591Pharmacogenetics. 2004 Feb;14(2):103-915077011Free Radic Biol Med. 2012 Jan 1;52(1):167-7222044660Lung Cancer. 2006 Dec;54(3):267-8316982113Mutat Res. 2011 May 10;709-710:21-3121376741Cancer Epidemiol Biomarkers Prev. 2008 Jul;17(7):1739-4518628426Genet Med. 2002 Mar-Apr;4(2):45-6111882781Control Clin Trials. 1986 Sep;7(3):177-883802833Mol Biol Rep. 2011 Oct;38(7):4537-4321132382Int J Epidemiol. 2008 Feb;37(1):120-3217898028Arh Hig Rada Toksikol. 2008 Dec;59(4):241-5019064361Zhongguo Fei Ai Za Zhi. 2011 Mar;14(3):205-1021426661Cancer Lett. 2003 Mar 10;191(2):171-812618330Carcinogenesis. 2006 May;27(5):997-100716308313Med Oncol. 2011 Sep;28(3):667-7220354815Lung Cancer. 2011 Aug;73(2):138-4621195504Chemosphere. 2011 Feb;82(7):941-621183201Mutat Res. 2007 Jul 28;631(2):101-1017531525Anticancer Res. 2009 Jun;29(6):2417-2019528510Carcinogenesis. 2006 Jun;27(6):1245-5016364924Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502Am J Epidemiol. 2009 Sep 15;170(6):695-70219671832Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Carcinogenesis. 2000 Jul;21(7):1329-3410874010Int J Cancer. 2000 Dec 15;88(6):932-711093817Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Lancet. 1997 Oct 18;350(9085):11829343537Carcinogenesis. 2004 Aug;25(8):1395-40115044328J Thorac Oncol. 2011 Apr;6(4):813-721623257J Natl Cancer Inst. 2000 Nov 1;92(21):1764-7211058619Arch Med Res. 2011 Apr;42(3):226-3421722819Carcinogenesis. 2006 Mar;27(3):560-716195237Oncogene. 1998 Jun 25;16(25):3219-259681819Genomics. 2004 Jun;83(6):970-915177551Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):9886-9110944198J Clin Oncol. 2010 Nov 20;28(33):4945-5220940192Int J Cancer. 2003 Oct 20;107(1):84-812925960Cancer Epidemiol Biomarkers Prev. 2002 Aug;11(8):730-812163326J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060Cancer Res. 1996 Sep 15;56(18):4103-78797573J Prev Med Public Health. 2006 Mar;39(2):130-416615267Mutat Res. 2008 Mar 1;639(1-2):45-5418155253BMJ. 1997 Sep 13;315(7109):629-349310563Carcinogenesis. 2004 Dec;25(12):2433-4115333465FASEB J. 2009 Oct;23(10):3459-6919541747CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855J Epidemiol. 2002 May;12(3):258-6512164330Clin Cancer Res. 2001 Apr;7(4):824-3011309329Cancer Res. 2003 Aug 15;63(16):4899-90212941813J Natl Cancer Inst. 2005 Apr 20;97(8):567-7615840879Carcinogenesis. 2004 Nov;25(11):2177-8115284179Nature. 2001 May 17;411(6835):366-7411357144Amino Acid SubstitutiongeneticsCase-Control StudiesDNA GlycosylasesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGene FrequencygeneticsGenetic Association StudiesGenetic Predisposition to DiseaseHumansLung NeoplasmsenzymologygeneticspathologyPolymorphism, Single NucleotidegeneticsPublication BiasRisk FactorsSmokinggenetics
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1422-00671372012International journal of molecular sciencesInt J Mol SciMolecular cloning and 3D structure modeling of APEX1, DNA base excision repair enzyme from the Camel, Camelus dromedarius.8578-9610.3390/ijms13078578The domesticated one-humped camel, Camelus dromedarius, is one of the most important animals in the Arabian Desert. It is exposed most of its life to both intrinsic and extrinsic genotoxic factors that are known to cause gross DNA alterations in many organisms. Ionic radiation and sunlight are known producers of Reactive Oxygen Species (ROS), one of the causes for DNA lesions. The damaged DNA is repaired by many enzymes, among of them Base Excision Repair enzymes, producing the highly mutagenic apurinic/apyrimidinicsites (AP sites). Therefore, recognition of AP sites is fundamental to cell/organism survival. In the present work, the full coding sequence of a putative cAPEX1 gene was amplified for the first time from C. dromedarius by RT-PCR and cloned (NCBI accession number are HM209828 and ADJ96599 for nucleotides and amino acids, respectively). cDNA sequencing was deduced to be 1041 nucleotides, of which 954 nucleotides encode a protein of 318 amino acids, similar to the coding region of the APEX1 gene and the protein from many other species. The calculated molecular weight and isoelectric point of cAPEX1 using Bioinformatics tools was 35.5 kDa and 8.11, respectively. The relative expressions of cAPEX1 in camel kidney, spleen, lung and testis were examined using qPCR and compared with that of the liver using a 18S ribosomal subunit as endogenous control. The highest level of cAPEX1 transcript was found in the testis; 325% higher than the liver, followed by spleen (87%), kidney (20%) and lung (5%), respectively. The cAPEX1 is 94%-97% similar to their mammalian counterparts. Phylogenetic analysis revealed that cAPEX1 is grouped together with that of S. scrofa. The predicted 3D structure of cAPEX1 has similar folds and topology with the human (hAPEX1). The root-mean-square deviation (rmsd) between cAPEX1 and hAPEX1 was 0.582 and the Q-score was 0.939.AtayaFarid ShokryFSDepartment of Biochemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.FouadDaliaDMalikAjamaluddinASaeedHesham MahmoudHMengJournal ArticleResearch Support, Non-U.S. Gov't20120710
SwitzerlandInt J Mol Sci1010927911422-0067EC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMDNA Repair (Amst). 2007 Apr 1;6(4):470-8017116430Annu Rev Genet. 2004;38:445-7615568983Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Mutat Res. 2008 Aug 25;643(1-2):54-6318579163Nat Rev Cancer. 2006 Dec;6(12):947-6017128211Nucleic Acids Res. 2006;34(7):2067-7616617147Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116DNA Cell Biol. 1993 Apr;12(3):265-738466649Bioinformatics. 2006 Jan 15;22(2):195-20116301204EMBO J. 1997 Nov 3;16(21):6548-589351835Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Eur J Clin Nutr. 2011 Sep;65(9):1048-5221629270J Med Microbiol. 2012 Mar;61(Pt 3):375-8322052996J Med Food. 2009 Apr;12(2):461-519459752Free Radic Biol Med. 2005 May 1;38(9):1121-3815808410Nature. 2000 Jan 27;403(6768):451-610667800Mol Cell Biol. 1993 Sep;13(9):5370-68355688Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7271968Protein J. 2010 Jul;29(5):306-1320532968Mutat Res. 1990 Sep-Nov;237(5-6):189-2102079959Nucleic Acids Res. 2007;35(8):2522-3217403694Mutat Res. 1990 Sep-Nov;236(2-3):173-2011697933Nucleic Acids Res. 2004;32(12):3531-615247342Science. 1990 Sep 7;249(4973):1157-612118682Int J Mol Sci. 2012;13(1):879-90022312292Hepat Mon. 2011 Sep;11(9):724-3022235215Circ Res. 2001 Jun 22;88(12):1247-5311420300Eur J Cancer. 2007 Aug;43(12):1791-80117588740Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Annu Rev Genet. 1986;20:201-303545059Mol Cell. 2005 Feb 4;17(3):463-7015694346Proteomics. 2009 Feb;9(4):1058-7419180539Nucleic Acids Res. 2010 Dec;38(22):8239-5620699270EMBO J. 1992 Sep;11(9):3323-351380454Nature. 1993 Apr 22;362(6422):709-158469282J Mol Biol. 2000 May 5;298(3):447-5910772862Mutat Res. 1998 Jun;407(3):203-159653447Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Carcinogenesis. 2000 Mar;21(3):361-7010688856Nucleic Acids Res. 2009 Jul;37(12):3946-5819401441Asia Pac J Clin Nutr. 2005;14(4):432-816326652Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H804-1212730053DNA Repair (Amst). 2007 Apr 1;6(4):461-917166779Chem Res Toxicol. 1993 Nov-Dec;6(6):771-858117915Amino Acid SequenceAnimalsBase SequenceCamelusCatalytic DomainCloning, MolecularConserved SequenceDNA-(Apurinic or Apyrimidinic Site) LyasechemistrygeneticsMaleModels, MolecularMolecular Sequence DataPhylogenyProtein Structure, SecondaryStructural Homology, Protein3D structure modelingApe1/Ref-1/APEX1BERDNA repaircloningmolecular characterizationone-humped camelqPCROriginal DateCompleted: 20130704
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1464-38042762012NovMutagenesisMutagenesisSkin tumours induced by narrowband UVB have higher frequency of p53 mutations than tumours induced by broadband UVB independent of Ogg1 genotype.637-4310.1093/mutage/ges029Different wavelengths of ultraviolet (UV) light have different promoting effects on skin carcinogenesis. Narrowband UVB (NB-UVB) has a single-peak wavelength of 311 nm and is widely used for treating skin diseases. Our previous work showed that, in comparison with conventional broadband UVB (BB-UVB), long-term exposure to NB-UVB induces higher frequency of skin cancer in mice, and it suggested that this is mediated through the formation of cyclobutane pyrimidine dimers (CPDs). To explore whether the frequency of p53 mutations in skin tumours correlates with CPD-induced mutations, we compared the frequency and types of p53 mutations between NB-UVB-induced and BB-UVB-induced malignant skin tumours produced in wild-type and Ogg1 knockout mice, which are deficient in repair of oxidative 8-oxoguanine (8-oxoG), a DNA damage mediated by reactive oxygen species (ROS). The frequency of p53 mutation was significantly higher in NB-UVB-induced than in BB-UVB-induced tumours in both wild-type and Ogg1 knockout mice. Most of the p53 mutations found were G:C → A:T transitions at dipyrimidine sites in both the NB-UVB- and BB-UVB-exposed groups. However, G:C → T:A mutations caused by 8-oxoG did not increase in Ogg1 knockout mice exposed to either NB-UVB or BB-UVB. Our results strongly suggest that NB-UVB induces highly malignant tumours caused by p53 dipyrimidine mutations through the formation of CPDs.YogiantiFlandianaFDivision of Dermatology, Department of Internal Related, Graduate School of Medicine, Kobe University, Kobe, Japan.KunisadaMakotoMOnoRyusukeRSakumiKunihikoKNakabeppuYusakuYNishigoriChikakoCengJournal ArticleResearch Support, Non-U.S. Gov't20120727
EnglandMutagenesis87078120267-83570Tumor Suppressor Protein p53EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMAnimalsDNA DamageDNA GlycosylasesgeneticsmetabolismGenotypeImmunohistochemistryMiceMice, Inbred C57BLMice, KnockoutMutationSkinpathologyradiation effectsSkin NeoplasmsgeneticspathologyTumor Suppressor Protein p53geneticsmetabolismUltraviolet Rays
20127316020127316020134560ppublish22844076ges02910.1093/mutage/ges029
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1573-72921142012DecFamilial cancerFam. CancerNovel mutations of OGG1 base excision repair pathway gene in laryngeal cancer patients.587-9310.1007/s10689-012-9554-2OGG1 (The human 8-oxoguanine glycosylase 1) is the primary enzyme in BER (base excision repair) pathway, responsible for the excision of 7, 8-dihydro-8-oxoguanine (8-oxoG), a mutagenic base byproduct that occurs as a result of exposure to reactive oxygen species. OGG1 gene is highly polymorphic among humans and is mutated in cancer cells. In this case control study, all exons of OGG1 gene and its exon/intron boundaries were amplified in 210 laryngeal cancer cases and 210 matched controls and then analyzed by single stranded conformational polymorphism. Amplified products showing altered mobility patterns were sequenced and analyzed. Two silent (Gln718Gln, His699-700His) and three missense (Ala597, Thr608-610Pro and Glu707Lys) mutations were observed in exon 2. In addition to this one missense mutation (1578G > A) was also observed in 3'UTR region. We found a significant association between OGG1 mutations and laryngeal cancer and observed that His699-His700, silent mutation exhibited an enhanced risk of ~9.0 folds (OR = 9.07, 95 % CI = 4.73-17.39) and 1578G > A, missense mutation ~0.4 folds (OR = 0.37, 95 % CI = 0.15-0.90). Furthermore, a positive association of OGG1 mutations with smoking was observed in laryngeal cancer cases when compared to controls. Heavy smokers have higher incidence of OGG1 mutations when compared to light smokers in present study. Our results demonstrate that OGG1 mutations are associated with an increased risk of laryngeal cancer. OGG1 mutations were found to accumulate more of 8-OHdG in smokers, which may serve as a biomarker for early diagnosis of laryngeal cancer.MahjabeenIshratICancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan. ishrat_qau@yahoo.comMasoodNosheenNBaigRuqia MehmoodRMSabirMaimoonaMInayatUzmaUMalikFaraz ArshadFAKayaniMahmood AkhtarMAengComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't
NetherlandsFam Cancer1008982111389-96000Reactive Oxygen SpeciesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMBreast Cancer Res Treat. 2005 Jan;89(1):15-2115666192Mod Pathol. 1999 Jan;12(1):47-539950162Int J Cancer. 2001 May 20;95(3):140-311307145Biol Pharm Bull. 2004 Apr;27(4):480-515056851Cancer Res. 1996 Feb 15;56(4):683-88630995Carcinogenesis. 2007 Aug;28(8):1629-3717389610Clin Cancer Res. 2000 Apr;6(4):1394-40010778969Carcinogenesis. 1997 Sep;18(9):1763-69328173J Pharmacol Exp Ther. 2000 Oct;295(1):1-910991953Cold Spring Harb Symp Quant Biol. 2000;65:103-1112760025J Mol Biol. 2002 Mar 22;317(2):171-711902834Cancer Sci. 2004 Dec;95(12):977-8315596047Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502Carcinogenesis. 2004 Sep;25(9):1689-9415073047Cancer Res. 2000 Sep 1;60(17):4740-410987279Prog Nucleic Acid Res Mol Biol. 2001;68:305-1411554308Cancer Res. 2003 Jul 15;63(14):4287-9212874039J Epidemiol. 2003 Jan;13(1):29-3712587611Oncogene. 1998 Jun 25;16(25):3219-259681819Cell. 1996 Jul 26;86(2):321-98706136Cancer Res. 2006 Dec 15;66(24):11683-917178863Oncogene. 1998 Jun 11;16(23):3083-69662341IARC Monogr Eval Carcinog Risks Hum. 2004;83:1-143815285078Oral Oncol. 2006 Apr;42(4):350-6216324877Free Radic Res Commun. 1990;11(1-3):23-72074046J Biol Chem. 2003 Nov 28;278(48):47937-4512966098Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4156-6110725358Cancer Res. 1996 Jun 1;56(11):2546-98653695J Epidemiol. 2007 Sep;17(5):156-6017827862Curr Opin Struct Biol. 2004 Feb;14(1):43-915102448AdultCase-Control StudiesDNA GlycosylasesgeneticsFemaleHumansLaryngeal NeoplasmsgeneticspathologyMaleMiddle AgedMutationgeneticsPolymerase Chain ReactionPolymorphism, Single-Stranded ConformationalPrognosisReactive Oxygen SpeciesmetabolismSmokingadverse effects
201272660201272660201342460ppublish2282901510.1007/s10689-012-9554-2
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1872-97546152012OctNeurochemistry internationalNeurochem. Int.Ogg1 null mice exhibit age-associated loss of the nigrostriatal pathway and increased sensitivity to MPTP.721-3010.1016/j.neuint.2012.06.013S0197-0186(12)00210-0Cumulative damage to cellular macromolecules via oxidative stress is a hallmark of aging and neurodegenerative disease. Whether such damage is a cause or a subsequent effect of neurodegeneration is still unknown. This paper describes the development of an age-associated mild parkinsonian model in mice that lack the DNA repair enzyme 8-oxoguanine glycosylase 1 (Ogg1). Aged OGG1 knock-out (OGG1 KO) mice show a decreased spontaneous locomotor behavior and evidence a decrease in striatal dopamine levels, a loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN), and an increase in ubiquitin-positive inclusions in their remaining SN neurons. In addition, young OGG1 KO mice are more susceptible to the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) than their wild-type (WT) counterparts. Age-associated increases in 7,8-dihydro-2'-deoxyguanine (oxo(8)dG) have been reported in brain regions and neuronal populations affected in Parkinson's disease (PD), toxin-induced parkinsonian models, and mice harboring genetic abnormalities associated with PD. Because of these increased oxo(8)dG levels, the OGG1 KO mouse strain could shed light on molecular events leading to neuronal loss as a consequence of cumulative oxidative damage to DNA during aging and after toxicological challenge.Published by Elsevier Ltd.Cardozo-PelaezFernandoFCenter for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA. Fernando.Cardozo@umontana.eduSanchez-ContrerasMonicaMNevinAndrew B CABengP20 RR015583RRNCRR NIH HHSUnited StatesP20 RR017670RRNCRR NIH HHSUnited StatesR01 AG031184AGNIA NIH HHSUnited StatesP20RR017670RRNCRR NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20120626
EnglandNeurochem Int80069590197-0186EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMFree Radic Biol Med. 2005 Mar 15;38(6):737-4515721984Neurotoxicology. 1999 Apr-Jun;20(2-3):415-3210385901Neurology. 2005 Mar 22;64(6):1081-315781836J Neurochem. 2005 May;93(4):953-6215857398J Pineal Res. 2005 Aug;39(1):34-4215978055Gene Expr. 2005;12(4-6):315-2316358418DNA Repair (Amst). 2006 Feb 3;5(2):189-20916290067Genet Mol Res. 2005;4(4):822-3116475130Cell Death Differ. 2006 Apr;13(4):551-6316273081Neurobiol Dis. 2006 Nov;24(2):308-1716959493Front Biosci. 2007;12:1107-2317127365Mitochondrion. 2007 Feb-Apr;7(1-2):58-6217300997J Neurosci Res. 2007 Apr;85(5):919-3417279544J Neurosci. 2008 Sep 3;28(36):9047-5418768699Free Radic Biol Med. 2008 Sep 15;45(6):813-918598755J Cereb Blood Flow Metab. 2011 Feb;31(2):680-9220736962Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Mov Disord. 1999 Nov;14(6):972-8010584672Free Radic Biol Med. 2000 Mar 1;28(5):779-8510754274Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4156-6110725358Nat Neurosci. 2000 Dec;3(12):1301-611100151Brain Res. 2000 Dec 1;885(1):45-5211121528J Neurochem. 2001 Feb;76(4):998-100911181819J Neurochem. 2001 Mar;76(5):1265-7411238711Neurol Sci. 2001 Feb;22(1):83-411487213Carcinogenesis. 2001 Sep;22(9):1459-6311532868Int J Radiat Biol. 2001 Dec;77(12):1195-20511747544Free Radic Res. 2002 Feb;36(2):157-6211999383Free Radic Biol Med. 2002 Jun 1;32(11):1102-1512031895Neuron. 2002 May 16;34(4):521-3312062037Neurology. 2002 Jun 25;58(12):1809-1512084881Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8968-7312084935Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14524-912376616Neurosci Lett. 2003 Jan 16;336(2):105-812499051Clin Chim Acta. 2003 Aug;334(1-2):87-9412867278Parkinsonism Relat Disord. 2003 Aug;9 Suppl 2:S59-6412915069Neuron. 2004 Feb 19;41(4):549-6114980204J Neurosci Methods. 2004 Jun 15;136(1):69-7615126047Arch Biochem Biophys. 1986 May 1;246(2):501-143010861Life Sci. 1988;43(11):913-222901021Lancet. 1989 Jun 3;1(8649):12692566813Biochem Biophys Res Commun. 1989 Sep 29;163(3):1450-52551290Mov Disord. 1991;6(1):2-111848677Biochemistry. 1991 Jun 25;30(25):6283-92059635Ann Neurol. 1992 Dec;32(6):804-121471873Adv Neurol. 1993;60:251-88380519BMJ. 1996 Mar 16;312(7032):702-3; author reply 704-58597746BMJ. 1996 Mar 16;312(7032):703; author reply 704-58597748Neurotoxicol Teratol. 1997 Jan-Feb;19(1):17-259088007Science. 1997 Jun 27;276(5321):2045-79197268J Neurochem. 1997 Sep;69(3):1196-2039282943Nat Genet. 1998 Feb;18(2):106-89462735Acta Neuropathol. 1998 Nov;96(5):445-529829807Trends Neurosci. 1998 Dec;21(12):516-209881849Am J Pathol. 1999 May;154(5):1423-910329595Nucleic Acids Res. 2005;33(4):1230-915731343Agingdrug effectsgeneticspathologyAnimalsCorpus Striatumdrug effectsmetabolismpathologyDNA GlycosylasesdeficiencygeneticsFemaleMPTP PoisoninggeneticspathologyMaleMiceMice, 129 StrainMice, KnockoutNeural Pathwaysdrug effectsmetabolismpathologySubstantia Nigradrug effectsenzymologymetabolism
201201132012051820120618201263060201263060201373160ppublish22743193S0197-0186(12)00210-010.1016/j.neuint.2012.06.013PMC3468700NIHMS389696
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1524-457111122012Jul06Circulation researchCirc. Res.APEX1 regulation of aldosterone synthase gene transcription is disrupted by a common polymorphism in humans.212-910.1161/CIRCRESAHA.111.262931The genetic mechanisms underlying hypertension are unclear, but relative aldosterone excess, present in ≈10% of hypertensive patients, is known to be a heritable trait. This phenotype associates with a T/C single nucleotide polymorphism (SNP) at position -344 of the aldosterone synthase gene (CYP11B2). However, deletion of this SNP has no effect on gene transcription. We have identified another T/C SNP at -1651, in tight linkage disequilibrium with the -344 SNP and here investigate its functional effect on CYP11B2 transcription.We assessed the effect on transcriptional activity of the -1651 T/C SNP in vivo and in vitro and propose the mechanism by which transcriptional activity is altered.We demonstrated that the SNP at -1651 exerts significant allele-dependent effects on CYP11B2 transcription. We confirm binding of the transcriptional repressor APEX1 to -1651T, which is associated with reduced transcriptional activity in relation to the less strongly bound -1651C. We show that inhibiting APEX1 by small molecule inhibition or small interfering RNA (SiRNA) leads to increased CYP11B2 transcription. In addition, overexpression of APEX1 is associated with reduced transcriptional activity. Finally, we also show that -1651T associates with lower excretion rates of aldosterone metabolites in human subjects.We conclude that APEX1 is a novel transcriptional repressor of CYP11B2 and that differential APEX1 binding at -1651 of CYP11B2 results in altered gene expression. This mechanism may contribute to the observed relationship between CYP11B2 genotype and aldosterone phenotype in a subgroup of hypertensive patients.McManusFrancesFInstitute of Cardiovascular and Medical Sciences, University of Glasgow, UK. Frances.McManus@Glasgow.ac.ukSandsWilliamWDiverLouiseLMacKenzieScott MSMFraserRobertRDaviesEleanorEConnellJohn MJMengG0601322Medical Research CouncilUnited KingdomMedical Research CouncilUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20120531
United StatesCirc Res00471030009-73300RNA, Small InterferingEC 1.14.15.4Cytochrome P-450 CYP11B2EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdultAgedCytochrome P-450 CYP11B2antagonists & inhibitorsbiosynthesisgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsphysiologyDown-RegulationgeneticsFemaleHumansMaleMiddle AgedPolymorphism, Single NucleotidegeneticsProtein BindinggeneticsRNA, Small InterferinggeneticsmetabolismTranscription, GeneticgeneticsUp-Regulationgenetics
2012626020126260201291860ppublish22652909CIRCRESAHA.111.26293110.1161/CIRCRESAHA.111.262931
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1879-003850512012Aug15GeneGeneThe role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population.121-710.1016/j.gene.2012.05.025The aim of the present study was to investigate the role of some polymorphisms in GSTs (GSTM1, GSTT1 and GSTP1) which are very important protective mechanisms against oxidative stress and in OGG1 gene which is important in DNA repair, against the risk of type 2 diabetes mellitus (T2DM). 127 T2DM and 127 control subjects were included in the study. DNA was extracted from whole blood. Analyses of GSTM1 and GSTT1 gene polymorphisms were performed by allele specific PCR and those of GSTP1 Ile105Val and OGG1 Ser326Cys by PCR-RFLP. Our data showed that GSTM1 null genotype frequency had a 2-6 times statistically significant increase in a patient group (OR=3.841, 95% CI=2.280-6.469, p<0.001) but no significance with GSTT1 null/positive and GSTP1 Ile105Val genotypes was observed. When T2DM patients with OGG1 Ser326Cys polymorphism were compared with patients with a wild genotype, a 2-3 times statistically significant increase has been observed (OR 1.858, 95% CI=1.099-3.141, p=0.021). The combined effect of GSTM1 null and OGG1 variant genotype frequencies has shown to be statistically significant. Similarly, the risk of T2DM was statistically increased with GSTM1 null (OR=3.841, 95% CI=2.28-6.469), GSTT1 null+GSTP1 (H+M) (OR=4.118, 95% CI=1.327-12.778) and GSTM1 null+OGG1 (H+M) (OR=3.322, 95% CI=1.898-5.816) and GSTT1 null+OGG1 (H+M) (OR=2.179, 95% CI=1.083-4.386) as compared to the control group. According to our study results, it has been observed that the combined evaluation of GSTM1-GSTT1-GSTP1 and OGG1 Ser326Cys gene polymorphisms can be used as candidate genes in the etiology of T2DM, especially in the development of T2DM.Copyright © 2012 Elsevier B.V. All rights reserved.GönülNüvitNRefik Saydam National Health Public Agency, Toxicology Department, National Poison Center, Ankara, Turkey. nuvitgonul@gmail.comKadiogluElaEKocabaşNeslihan AygünNAOzkayaMesutMKarakayaAli EsatAEKarahalilBensuBengJournal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov't20120528
NetherlandsGene77067610378-1119EC 2.5.1.-glutathione S-transferase T1EC 2.5.1.18GSTP1 protein, humanEC 2.5.1.18Glutathione S-Transferase piEC 2.5.1.18Glutathione TransferaseEC 2.5.1.18glutathione S-transferase M1EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultAgedCase-Control StudiesDNA GlycosylasesgeneticsDiabetes Mellitus, Type 2epidemiologygeneticsFemaleGenotypeGlutathione S-Transferase pigeneticsGlutathione TransferasegeneticsHumansMaleMiddle AgedPolymorphism, GeneticRisk FactorsTurkeyepidemiology
2011122420120404201205102012626020126260201292660ppublish22652274S0378-1119(12)00600-210.1016/j.gene.2012.05.025
225647412012102220171116
1090-210442342012Jul13Biochemical and biophysical research communicationsBiochem. Biophys. Res. Commun.The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells.621-610.1016/j.bbrc.2012.04.125Embryonic neural stem cells (NSCs) exhibit self-renewal and multipotency as intrinsic characteristics that are key parameters for proper brain development. When cells are challenged by oxidative stress agents the resulting DNA lesions are repaired by DNA glycosylases through the base excision repair (BER) pathway as a means to maintain the fidelity of the genome, and thus, proper cellular characteristics. The functional roles for DNA glycosylases in NSCs have however remained largely unexplored. Here we demonstrate that RNA knockdown of the DNA glycosylases OGG1 and NEIL3 decreased NSC differentiation ability and resulted in decreased expression of both neuronal and astrocytic genes after mitogen withdrawal, as well as the stem cell marker Musashi-1. Furthermore, while cell survival remained unaffected, NEIL3 deficient cells displayed decreased cell proliferation rates along with an increase in HP1γ immunoreactivity, a sign of premature senescence. Our results suggest that DNA glycosylases play multiple roles in governing essential neural stem cell characteristics.Copyright © 2012 Elsevier Inc. All rights reserved.ReisAmilcarALinnaeus Center in Developmental Biology for Regenerative Medicine, Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm, Sweden.HermansonOlaOengJournal ArticleResearch Support, Non-U.S. Gov't20120430
United StatesBiochem Biophys Res Commun03725160006-291X0Biomarkers0Enzyme Inhibitors0Msi1h protein, rat0Nerve Tissue Proteins0RNA, Small Interfering0RNA-Binding Proteins5614-64-28-hydroxyguanine5Z93L87A1RGuanine614OI1Z5WIValproic AcidEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-OGG1 protein, ratIMAnimalsBiomarkersmetabolismCell NucleusmetabolismCell ProliferationCells, CulturedCellular SenescencegeneticsphysiologyDNA Glycosylasesantagonists & inhibitorsgeneticsphysiologyEnzyme InhibitorspharmacologyGene Knockdown TechniquesGuanineanalogs & derivativesmetabolismNerve Tissue ProteinsmetabolismNeural Stem CellscytologyphysiologyNeurogenesisgeneticsphysiologyRNA, Small InterferinggeneticsRNA-Binding ProteinsmetabolismRatsValproic Acidpharmacology
201204182012042120125960201259602012102360ppublish22564741S0006-291X(12)00807-810.1016/j.bbrc.2012.04.125
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1932-6203742012PloS onePLoS ONEThe association between OGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis of 27 studies.e3597010.1371/journal.pone.0035970Numerous studies have investigated association of OGG1 Ser326Cys polymorphism with lung cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 27 publications encompass 9663 cases and 11348 controls to comprehensively evaluate such associations.We searched publications from MEDLINE and EMBASE which were assessing the associations between OGG1 Ser326Cys polymorphism and lung cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We used genotype based mRNA expression data from HapMap for SNP rs1052133 in normal cell lines among 270 subjects with four different ethnicities.The results showed that individuals carrying the Cys/Cys genotype did not have significantly increased risk for lung cancer (OR = 1.15, 95% CI = 0.98-1.36) when compared with the Ser/Ser genotype; similarly, no significant association was found in recessive, dominant or heterozygous co-dominant model (Ser/Cys vs. Cys/Cys). However, markedly increased risks were found in relatively large sample size (Ser/Ser vs. Cys/Cys: OR = 1.29, 95% CI = 1.13-1.48, and recessive model: OR = 1.19, 95% CI = 1.07-1.32). As to histological types, we found the Cys/Cys was associated with adenocarcinoma risk (Ser/Ser vs. Cys/Cys: OR = 1.32, 95% CI = 1.12-1.56; Ser/Cys vs. Cys/Cys: OR = 1.19, 95% CI = 1.04-1.37, and recessive model OR = 1.23, 95% CI = 1.08-1.40). No significant difference of OGG1 mRNA expression was found among genotypes between different ethnicities.Despite some limitations, this meta-analysis established solid statistical evidence for an association between the OGG1 Cys/Cys genotype and lung cancer risk, particularly for studies with large sample size and adenocarcinoma, but this association warrants additional validation in larger and well designed studies.DuanWei-XunWXDepartment of Cardiothoracic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.HuaRui-XiRXYiWeiWShenLi-JunLJJinZhen-XiaoZXZhaoYu-HongYHYiDing-HuaDHChenWen-ShengWSYuShi-QiangSQengJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov't20120423
United StatesPLoS One1012850811932-62030RNA, MessengerEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAnticancer Res. 2010 Oct;30(10):4141-521036733Cancer Lett. 2005 Jun 8;223(2):265-7415896461Carcinogenesis. 2009 Jan;30(1):78-8719029194J Hum Genet. 2009 Dec;54(12):739-4519881468Mutat Res. 2005 Dec 11;591(1-2):60-7316081110Cancer Sci. 2006 Aug;97(8):724-816800823Pharmacogenetics. 2004 Feb;14(2):103-915077011J Natl Cancer Inst. 1999 Jul 21;91(14):1194-21010413421Cancer Detect Prev. 2007;31(3):237-4317651912Mutat Res. 2011 May 10;709-710:21-3121376741Cancer Epidemiol Biomarkers Prev. 2008 Jul;17(7):1739-4518628426Control Clin Trials. 1986 Sep;7(3):177-883802833Mutat Res. 2005 Apr 4;582(1-2):53-6015781210Arh Hig Rada Toksikol. 2008 Dec;59(4):241-5019064361Carcinogenesis. 2006 May;27(5):997-100716308313Science. 2007 Feb 9;315(5813):848-5317289997Lung Cancer. 2011 Aug;73(2):138-4621195504Lancet. 2003 Sep 13;362(9387):847-5213678970J Exp Clin Cancer Res. 2009;28:1019161591FASEB J. 2002 Dec;16(14):1895-90212468454Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502Am J Epidemiol. 2009 Sep 15;170(6):695-70219671832Prog Nucleic Acid Res Mol Biol. 2001;68:285-9711554304Bioessays. 2001 Mar;23(3):270-8111223884J Thorac Oncol. 2011 Apr;6(4):813-721623257Science. 2001 Feb 16;291(5507):1284-911181991BMC Bioinformatics. 2010;11:60021167019Arch Med Res. 2011 Apr;42(3):226-3421722819Carcinogenesis. 2006 Mar;27(3):560-716195237J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060Oncogene. 1998 Jun 11;16(23):3083-69662341J Prev Med Public Health. 2006 Mar;39(2):130-416615267Mutat Res. 2008 Mar 1;639(1-2):45-5418155253J Biol Chem. 2001 Jul 13;276(28):25639-4211371576BMJ. 1997 Sep 13;315(7109):629-349310563CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855J Natl Cancer Inst. 2005 Apr 20;97(8):567-7615840879Nature. 2003 Dec 18;426(6968):789-9614685227Carcinogenesis. 2004 Nov;25(11):2177-8115284179Oncogene. 2005 Jun 30;24(28):4496-50815856018Cancer Genet Cytogenet. 2009 Dec;195(2):143-919963114Amino Acid SubstitutionDNA GlycosylasesgeneticsmetabolismDatabases, GeneticGenetic Predisposition to DiseaseGenotypeHapMap ProjectHumansLung NeoplasmsgeneticsOdds RatioPolymorphism, Single NucleotideRNA, MessengermetabolismRisk Factors
2012011720120324201242860201242860201291160ppublish2254001310.1371/journal.pone.0035970PONE-D-12-01517PMC3335067
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1932-6203742012PloS onePLoS ONEThe DNA glycosylases Ogg1 and Nth1 do not contribute to Ig class switching in activated mouse splenic B cells.e3606110.1371/journal.pone.0036061During activation of B cells to undergo class switching, B cell metabolism is increased, and levels of reactive oxygen species (ROS) are increased. ROS can oxidize DNA bases resulting in substrates for the DNA glycosylases Ogg1 and Nth1. Ogg1 and Nth1 excise oxidized bases, and nick the resulting abasic sites, forming single-strand DNA breaks (SSBs) as intermediates during the repair process. In this study, we asked whether splenic B cells from mice deficient in these two enzymes would show altered class switching and decreased DNA breaks in comparison with wild-type mice. As the c-myc gene frequently recombines with the IgH S region in B cells induced to undergo class switching, we also analyzed the effect of deletion of these two glycosylases on DSBs in the c-myc gene. We did not detect a reduction in S region or c-myc DSBs or in class switching in splenic B cells from Ogg1- or Nth1-deficient mice or from mice deficient in both enzymes.UcherAnna JAJDepartment of Microbiology and Physiological Systems, Medical School, University of Massachusetts, Worcester, Massachusetts, United States of America.LinehanErin KEKTeeborGeorge WGWSchraderCarol ECEStavnezerJanetJengAI-R21-088578AINIAID NIH HHSUnited StatesAI-RO1-023283AINIAID NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20120420
United StatesPLoS One1012850811932-62030Immunoglobulin Heavy ChainsEC 3.1.25.1Deoxyribonuclease (Pyrimidine Dimer)EC 3.1.25.1Nth1 protein, mouseEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMProc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Mol Cell. 2011 Jan 21;41(2):232-4221255732J Immunol. 2003 Jun 1;170(11):5558-6212759433J Immunol. 2003 Sep 1;171(5):2504-912928399Nat Immunol. 2003 Oct;4(10):1023-812958596Int J Immunopharmacol. 1994 Jul;16(7):533-467928003Cell Immunol. 1999 Feb 25;192(1):41-710066345J Exp Med. 2005 Aug 15;202(4):561-816103411J Immunol. 2007 Jan 1;178(1):103-1017182545J Immunol. 2007 Nov 1;179(9):6064-7117947680DNA Repair (Amst). 2007 Dec 1;6(12):1764-7317681497J Exp Med. 2007 Nov 26;204(12):3017-2618025127Nature. 2008 Feb 14;451(7180):841-518273020Annu Rev Immunol. 2008;26:261-9218370922J Exp Med. 2008 Oct 27;205(11):2465-7218824584Cell. 2008 Dec 12;135(6):1028-3819070574DNA Repair (Amst). 2009 Jul 4;8(7):786-9419346169Mol Cell. 2009 Nov 25;36(4):631-4119941823J Immunol. 2010 Jun 1;184(11):6177-8720483782Nat Immunol. 2011 Jan;12(1):62-921113164Mol Cell Biol. 2002 Sep;22(17):6111-2112167705AnimalsB-LymphocytesenzymologyimmunologyCell ProliferationCells, CulturedDNA Breaks, Double-StrandedDNA GlycosylasesdeficiencygeneticsmetabolismDeoxyribonuclease (Pyrimidine Dimer)deficiencygeneticsGene Knockout TechniquesGenes, mycImmunoglobulin Class SwitchingImmunoglobulin Heavy ChainsgeneticsMiceMice, Inbred C57BLMice, KnockoutReal-Time Polymerase Chain ReactionRecombination, GeneticSpleencytologyTranscription, Genetic
201202292012033020124276020124276020129160ppublish2253645510.1371/journal.pone.0036061PONE-D-12-06485PMC3334981
225232322012111320120709
1096-092912812012JulToxicological sciences : an official journal of the Society of ToxicologyToxicol. Sci.Oxoguanine glycosylase 1 (OGG1) protects cells from DNA double-strand break damage following methylmercury (MeHg) exposure.272-8310.1093/toxsci/kfs138Methylmercury (MeHg) is a potent neurotoxin, teratogen, and probable carcinogen, but the underlying mechanisms of its actions remain unclear. Although MeHg causes several types of DNA damage, the toxicological consequences of this macromolecular damage are unknown. MeHg enhances oxidative stress, which can cause various oxidative DNA lesions that are primarily repaired by oxoguanine glycosylase 1 (OGG1). Herein, we compared the response of wild-type and OGG1 null (Ogg1(-/-)) murine embryonic fibroblasts to environmentally relevant, low micromolar concentrations of MeHg by measuring clonogenic efficiency, cell cycle arrest, DNA double-strand breaks (DSBs), and activation of the DNA damage response pathway.Ogg1(-/-) cells exhibited greater sensitivity to MeHg than wild-type controls, as measured by the clonogenic assay, and showed a greater propensity for MeHg-initiated apoptosis. Both wild-type and Ogg1(-/-) cells underwent cell cycle arrest when exposed to micromolar concentrations of MeHg; however, the extent of DSBs was exacerbated in Ogg1(-/-) cells compared with that in wild-type controls. Pretreatment with the antioxidative enzyme catalase reduced levels of DSBs in both wild-type and Ogg1(-/-) cells but failed to block MeHg-initiated apoptosis at micromolar concentrations. Our findings implicate reactive oxygen species mediated DNA damage in the mechanism of MeHg toxicity; and demonstrate for the first time that impaired DNA repair capacity enhances cellular sensitivity to MeHg. Accordingly, the genotoxic properties of MeHg may contribute to its neurotoxic and teratogenic effects, and an individual's response to oxidative stress and DNA damage may constitute an important determinant of risk.OndovcikStephanie LSLDepartment of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada.TamblynLauraLMcPhersonJohn PeterJPWellsPeter GPGengCanadian Institutes of Health ResearchCanadaJournal ArticleResearch Support, Non-U.S. Gov't20120420
United StatesToxicol Sci98054611096-09290Methylmercury CompoundsEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMAnimalsDNA DamageDNA GlycosylasesmetabolismFlow CytometryHumansMethylmercury CompoundstoxicityMiceMice, Knockout
2012424602012424602012111460ppublish22523232kfs13810.1093/toxsci/kfs138
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1791-75303242012AprAnticancer researchAnticancer Res.Study of AP endonuclease (APEX1/REF1), a DNA repair enzyme, in gallbladder carcinoma.1489-92This study investigated the levels of Apurinic/Apyrimidinic Endonuclease (APEX1) in gallbladder carcinoma (CaGB) tissue and co-related these levels with various clinicopathological parameters.Twenty cases of CaGB and cholelithiasis were included in the study. Western blot analysis of APEX1 protein was performed using actin as the reference point. Densitometric analysis and the integrated density value (IDV) of APEX1 protein samples were determined. The ratio of IDV of APEX1/actin was determined.The mean IDV ratio of APEX1 in CaGB was 0.63±0.33 and 0.45±0.19 in cholelithiasis. The mean IDV ratio of a variant of APEX1 (ΔAPEX1) in CaGB was 0.50±0.09, whereas it was 0.40±0.16 in cholelithiasis. Calculating the mean IDV ratio of total APEX (APEX1+ΔAPEX1) in CaGB was 1.13±0.31 whereas in cholelithiasis, 0.85±0.23. The differences were statistically significant (p<0.05).A significant correlation was found between the relative expressions of APEX1 in cancer as compared to that in cholelithiasis patients. There was significant association between APEX1 expression and perineural invasion. A variant of APEX1 correlated with tumor infiltration. Hence APEX1 may be of use as a prognostic marker in patients with CaGB.ShuklaV KVKDepartment of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. vkshuklabhu@gmail.comdasP CPCDixitRRBhartiyaS KSKBasuSSRamanM JMJengJournal Article
GreeceAnticancer Res81029880250-7005EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdultAgedDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismFemaleGallbladder NeoplasmsenzymologyHumansMaleMiddle Aged
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1464-38042742012JulMutagenesisMutagenesisRepair of oxidative DNA damage is delayed in the Ser326Cys polymorphic variant of the base excision repair protein OGG1.501-1010.1093/mutage/ges012Gene-environment interactions influence an individual's risk of disease development. A common human 8-oxoguanine DNA glycosylase 1 (OGG1) variant, Cys326-hOGG1, has been associated with increased cancer risk. Evidence suggests that this is due to reduced repair ability, particularly under oxidising conditions but the underlying mechanism is poorly understood. Oxidising conditions may arise due to internal cellular processes, such as inflammation or external chemical or radiation exposure. To investigate wild-type and variant OGG1 regulation and activity under oxidising conditions, we generated mOgg1 (-/-) null mouse embryonic fibroblasts cells stably expressing Ser326- and Cys326-hOGG1 and measured activity, gene expression, protein expression and localisation following treatment with the glutathione-depleting compound L-buthionine-S-sulfoximine (BSO). Assessment of OGG1 activity using a 7,8-dihydro-8-oxodeoxyguanine (8-oxo dG) containing molecular beacon demonstrated that the activity of both Ser326- and Cys326-hOGG1 was increased following oxidative treatment but with different kinetics. Peak activity of Ser326-hOGG1 occurred 12 h prior to that of Cys326-hOGG1. In both variants, the increased activity was not associated with any gene expression or protein increase or change in protein localisation. These findings suggest that up-regulation of OGG1 activity in response to BSO-induced oxidative stress is via post-transcriptional regulation and provide further evidence for impaired Cys326-hOGG1 repair ability under conditions of oxidative stress. This may have important implications for increased mutation frequency resulting from increased oxidative stress in individuals homozygous for the Cys326 hOGG1 allele.KershawRachael MRMSchool of Biosciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK.HodgesNikolas JNJengBiotechnology and Biological Sciences Research CouncilUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20120325
EnglandMutagenesis87078120267-83570Antimetabolites0Deoxyadenosines0RNA, Messenger0Reactive Oxygen Species452VLY9402Serine5072-26-4Buthionine Sulfoximine62471-63-02'-deoxy-7,8-dihydro-8-oxoadenosineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 3.2.2.-oxoguanine glycosylase 1, humanGAN16C9B8OGlutathioneK848JZ4886CysteineIMAnimalsAntimetabolitespharmacologyBlotting, WesternButhionine SulfoximinepharmacologyCells, CulturedCysteinechemistrygeneticsDNA DamagegeneticsDNA GlycosylasesgeneticsmetabolismphysiologyDNA RepairgeneticsDeoxyadenosinesmetabolismEmbryo, Mammaliancytologydrug effectsmetabolismFibroblastscytologydrug effectsmetabolismFlow CytometryGene-Environment InteractionGlutathionemetabolismHumansMiceMice, KnockoutMutation RateOxidative StressgeneticsPolymorphism, GeneticgeneticsRNA, MessengergeneticsReactive Oxygen SpeciesmetabolismReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionSerinechemistrygeneticsUp-Regulation
201232860201232860201211260ppublish22451681ges01210.1093/mutage/ges012
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2476-762X12102011Asian Pacific journal of cancer prevention : APJCPAsian Pac. J. Cancer Prev.OGG1 gene sequence variation in head and neck cancer patients in Pakistan.2779-83In Pakistani culture tobacco use is very high and a well known risk factor for developing head and neck cancer (HNC), tobacco smoke containing high quantities of chemical carcinogens such as aromatic amines and reactive oxygen species. OGG1 is the primary enzyme in the base excision repair (BER) pathway, responsible for the excision of 7, 8-dihydro-8-oxoguanine, a mutagenic base byproduct that occurs as a result of exposure to reactive oxygen species. Groups of 300 already diagnosed HNC patients along with normal controls were included in this study. PCR-single-strand conformation polymorphism and DNA sequencing were used to analyze the whole coding region of OGG1 gene. Sequence analysis revealed eight novel mutations (six missense and two frame shift mutations). Frequencies of missense mutations, Asp267Asn, Ser279Gly and Ile253Phe were 0.12, 0.13 and 0.06 respectively. Frequencies of other missense mutations, 1578A> T, 1582C> T and Ala399Glu (1542C> A) were 0.13, 0.13 and 0.16, whereas values for the frame shift mutations 1582insG and 1543-1544delCT were 0.13 and 0.16. In our study, incidence of these mutations was found higher in oral cancers (p<0.002) and in smokers (p<0.002) when compared with other sites of HNC and nonsmokers, respectively. Our finding suggests that these germline mutations in OGG1 gene contribute to risk of developing HNC.MahjabeenIshratICancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.BaigRuqia MehmoodRMMasoodNosheenNSabirMaimoonaMMalikFaraz ArshadFAKayaniMahmood AkhtarMAengJournal ArticleResearch Support, Non-U.S. Gov't
ThailandAsian Pac J Cancer Prev1011306251513-7368EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMBase SequenceDNA GlycosylasesgeneticsDNA RepairFemaleFrameshift MutationGenetic VariationGerm-Line Mutationdrug effectsgeneticsHead and Neck NeoplasmsgeneticsHumansMaleMutation, MissensePakistanSequence Analysis, DNASmokingadverse effectsTobacco Use Disorder
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1549-471311952012MayOphthalmologyOphthalmologyGenetic polymorphisms in DNA repair genes OGG1, APE1, XRCC1, and XPD and the risk of age-related cataract.900-610.1016/j.ophtha.2011.11.004To analyze the association of the polymorphisms in 8-oxoguanine glycosylase-1 (OGG1), X-ray repair cross-complementing-1 (XRCC1), and AP endonuclease-1 (APE1) genes in the base excision repair pathway and xeroderma pigmentosum complementation group D (XPD) in the nucleotide excision repair pathway with the risk of cataract in a Chinese population.Case-control study.Subjects with cataract (n = 415) or no cataract (n = 386) in the Age Related Eye Disease Ancillary Study.The study included 415 cataract patients and 386 controls. Genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism method. Differences in the frequencies were estimated by the chi-square test, and risk was estimated by using unconditional logistic regression after adjusting for age and gender.Association of single nucleotide polymorphisms in OGG1-Ser326Cys with the development of age-related cataract.The OGG1 Cys/Cys genotype frequency was significantly higher in cataract patients (P = 0.014; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.171-3.624). The OGG1 Ser/Ser genotype (P = 0.003; OR, 0.647; 95% CI, 0.487-0.860) seems to have a protective role against cataract, and the Cys allele (P<0.001; OR, 1.517; 95% CI, 1.204-1.911) seems to have a deleterious role in the development of cataract. The genotype frequency of the Ser/Ser of OGG1-Ser326Cys was significantly different in the cortical and mixed-type cataract group (P = 0.014; OR, 0.591; 95% CI, 0.391-0.893; and P = 0.035; OR, 0.639; 95% CI, 0.425-0.960; respectively), and the Cys/Cys genotype of OGG1-Ser326Cys was significantly different in the mixed-type cataract group (P = 0.012; OR, 2.610; 95% CI, 1.284-5.306) compared with that of healthy controls. In XRCC1-Arg399Gln, APE1-Asp148Glu, and XPD-Lys751Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls.Results suggest that the Cys/Cys genotype of the OGG1-Ser326Cys polymorphism may be associated with increased risk of age-related cataract. However, in XRCC1-Arg399Gln, APE1-Asp148Glu, and XPD-Lys751Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls.Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.ZhangYiYHarbin Medical University, Harbin, China.ZhangLanLSongZhenZSunDong LinDLLiuHan RuoHRFuSong BinSBLiuDong RuiDRLiuPingPengJournal ArticleResearch Support, Non-U.S. Gov't20120204
United StatesOphthalmology78024430161-64200Codon0DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 5.99.-ERCC2 protein, humanIMAgedAgingAsian Continental Ancestry GroupgeneticsCase-Control StudiesCataractgeneticsCodongeneticsDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGenotypeHumansMalePolymerase Chain ReactionPolymorphism, Restriction Fragment LengthPolymorphism, Single NucleotideRisk FactorsX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
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1530-68602652012MayFASEB journal : official publication of the Federation of American Societies for Experimental BiologyFASEB J.Nutrient deprivation regulates DNA damage repair in cardiomyocytes via loss of the base-excision repair enzyme OGG1.2117-2410.1096/fj.11-197525Oxidative stress contributes to the pathogenesis of many diseases, including heart failure, but the role and regulation of oxidative DNA damage in many cases have not been studied. Here, we set out to examine how oxidative DNA damage is regulated in cardiomyocytes. Compared to normal healthy controls, human hearts in end-stage cardiomyopathy (EsCM) showed a high degree of DNA damage by histological evidence of damage markers, including 8-oxoG and γH2AX (8-oxoG: 4.7±0.88 vs. 99.9±0.11%; γH2AX: 2.1±0.33 vs. 85.0±13.8%; P<0.01) This raised the possibility that defective DNA repair may be partly responsible. Indeed, nutrient deprivation led to impaired base-excision repair (BER) in cardiomyocytes in vitro, accompanied by loss of the BER enzyme OGG1, while BER activity was rescued by recombinant OGG1 (control vs. nutrient deprived vs. nutrient deprived+OGG1; 100±2.96 vs. 68.2±7.53 vs. 94.0±0.72%; ANOVA, P<0.01). Hearts from humans with EsCM and two murine models of myocardial stress also showed a loss of OGG1 protein. OGG1 loss was inhibited by the autophagy inhibitor bafilomycin and in autophagy-deficient Atg5(-/-) mouse embryonic fibroblasts. However, pharmacological activation of autophagy, itself, did not induce OGG1 loss, suggesting that autophagy is necessary but not sufficient for OGG1 turnover, and OGG1 loss requires concurrent nutrient deprivation. Finally, we found that the role of autophagy in nutrient starvation is complex, since it balanced the positive effects of ROS inhibition against the negative effect of OGG1 loss. Therefore, we have identified a central role for OGG1 in regulating DNA repair in cardiomyopathy. The manipulation of OGG1 may be used in future studies to examine the direct contribution of oxidative DNA damage to the progression of heart failure.SiggensLeeLDivision of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Centre of Clinical Investigation Building, Level 6, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.FiggNicholaNBennettMartinMFooRogerRengRG/08/009/25841British Heart FoundationUnited KingdomBritish Heart FoundationUnited KingdomG0800784Medical Research CouncilUnited Kingdom086797Wellcome TrustUnited KingdomG1000847Medical Research CouncilUnited KingdomWellcome TrustUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20120201
United StatesFASEB J88044840892-66380DNA PrimersEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMNature. 2007 Jun 21;447(7147):941-5017581577Annu Rev Nutr. 2007;27:19-4017311494PLoS One. 2010;5(1):e856420084101Circ Res. 2007 Mar 30;100(6):914-2217332429FASEB J. 2003 Jul;17(10):1195-21412832285Circulation. 2005 Feb 8;111(5):591-715668342Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2979-849501201DNA Repair (Amst). 2010 Feb 4;9(2):144-5220042377N Engl J Med. 2007 Mar 15;356(11):1140-5117360992Nature. 2007 Mar 22;446(7134):444-817334357Circ Res. 1999 Sep 3;85(5):403-1410473670J Biol Chem. 2010 Jan 1;285(1):667-7419850931Mol Cancer Res. 2010 Jan;8(1):67-7920068071J Clin Invest. 2007 Jul;117(7):1782-9317607355Mutat Res. 2007 May 1;618(1-2):65-8017291544Annu Rev Physiol. 2001;63:391-42611181961Biol Chem. 2002 Mar-Apr;383(3-4):467-7512033436J Biol Chem. 2007 Feb 23;282(8):5529-3517142834Annu Rev Physiol. 2010;72:19-4420148665Nat Med. 2007 May;13(5):619-2417450150Cardiovasc Res. 2004 Nov 1;64(2):279-8815485687Autophagy. 2009 Oct;5(7):1034-619587530Cell. 2005 Sep 23;122(6):927-3916179260EMBO J. 2008 Jan 23;27(2):421-3218188152Cell. 2011 Apr 1;145(1):54-6621458667Annu Rev Physiol. 2010;72:45-5920148666J Clin Invest. 2005 Mar;115(3):500-815765131J Cell Physiol. 2006 Oct;209(1):1-716826603Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18877-8219020090Heart Fail Rev. 2010 Jul;15(4):331-4119363700Cardiovasc Res. 2001 Aug 1;51(2):304-1211470470Genome Med. 2010 Jun 14;2(6):3720546595Circ Res. 2001 Aug 3;89(3):198-20011485969J Clin Invest. 2003 May;111(10):1497-50412750399DNA Repair (Amst). 2008 Apr 2;7(4):648-5418294929Mol Biol Cell. 2004 Mar;15(3):1101-1114699058Nature. 2009 Oct 22;461(7267):1071-819847258Antioxid Redox Signal. 2007 Sep;9(9):1303-717627470AnimalsBase SequenceDNA DamageDNA GlycosylasesmetabolismDNA PrimersDNA RepairHumansImmunohistochemistryMiceMyocardiumenzymologymetabolismEMS52834
2012246020122460201263060ppublish22302830fj.11-19752510.1096/fj.11-197525PMC3630495EMS52834
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1568-78561132012Mar01DNA repairDNA Repair (Amst.)Lack of the DNA glycosylases MYH and OGG1 in the cancer prone double mutant mouse does not increase mitochondrial DNA mutagenesis.278-8510.1016/j.dnarep.2011.12.001Reactive oxygen species (ROS) are formed as natural byproducts during aerobic metabolism and readily induce premutagenic base lesions in the DNA. The 8-oxoguanine DNA glycosylase (OGG1) and MutY homolog 1 (MYH) synergistically prevent mutagenesis and cancer formation in mice. Their localization in the mitochondria as well as in the nucleus suggests that mutations in mitochondrial DNA (mtDNA) contribute to the carcinogenesis in the myh⁻/⁻/ogg1⁻/⁻ double knockout mouse. In order to test this hypothesis, we analyzed mtDNA mutagenesis and mitochondrial function in young (1month) and adult (6months) wt and myh⁻/⁻/ogg1⁻/⁻ mice. To our surprise, the absence of OGG1 and MYH had no impact on mtDNA mutation rates in these mice, even at the onset of cancer. This indicates that mtDNA mutagenesis is not responsible for the carcinogenesis of myh⁻/⁻/ogg1⁻/⁻ mice. In line with these results, mitochondrial function was unaffected in the cancerous tissues liver and lung, whereas a significant reduction in respiration capacity was observed in brain mitochondria from the adult myh⁻/⁻/ogg1⁻/⁻ mouse. The reduced respiration capacity correlated with a specific reduction (-25%) in complex I biochemical activity in brain mitochondria. Our results demonstrate that mtDNA mutations are not associated with cancer development in myh⁻/⁻/ogg1⁻/⁻ mice, and that impairment of mitochondrial function in brain could be linked to nuclear DNA mutations in this strain. OGG1 and MYH appear to be dispensable for antimutator function in mitochondria.Copyright © 2011 Elsevier B.V. All rights reserved.HalsneRuthRDepartment of Medical Biochemistry, University of Oslo and Oslo University Hospital, Norway.EsbensenYingYWangWeiWSchefflerKatjaKSuganthanRajikalaRBjøråsMagnarMEideLarsLengJournal ArticleResearch Support, Non-U.S. Gov't20111230
NetherlandsDNA Repair (Amst)1011391381568-78560DNA, MitochondrialEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 3.2.2.-mutY adenine glycosylaseIMAnimalsCell RespirationgeneticsDNA DamagegeneticsDNA GlycosylasesdeficiencymetabolismDNA, MitochondrialgeneticsMiceMice, Inbred C57BLMice, Mutant StrainsMutagenesisgeneticsMutationgeneticsMutation RateNeoplasmsenzymologygeneticsOrgan Specificitygenetics
2011090220111104201112052012136020121360201291160ppublish22209780S1568-7864(11)00347-810.1016/j.dnarep.2011.12.001
234644762014100920171116
2476-762X13122012Asian Pacific journal of cancer prevention : APJCPAsian Pac. J. Cancer Prev.DNA repair gene polymorphisms at XRCC1, XRCC3, XPD, and OGG1 Loci in the hyderabad population of India.6469-74DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inherited SNPs of DNA repair genes may contribute to variation in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. India harbors enormous genetic and cultural diversity.In the present study we aimed to determine the genotypes and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 186 healthy individuals residing in the Hyderabad region of India and to compare them with HapMap and other populations.The genotype and allele frequency distribution at the four DNA repair gene loci among Hyderabad population of India revealed a characteristic pattern. Comparison of these gene polymorphisms with other populations revealed a distinctiveness of Hyderabad population from the Deccan region of India. To the best of our knowledge, this is the first report of such DNA repair gene polymorphisms in the Deccan Indian population.ParineNarasimha ReddyNRGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. reddyparine@gmail.comPathanAkbar Ali KhanAABobbaralaVaraprasadVAbduljaleelZainularifeenZKhanWajahatullahWAlanaziMohammedMengJournal ArticleResearch Support, Non-U.S. Gov't
ThailandAsian Pac J Cancer Prev1011306251513-73680DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10X-ray repair cross complementing protein 30XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanIMAdultAgedAsian Continental Ancestry GroupgeneticsDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-Binding ProteinsgeneticsGene FrequencygeneticsGenotypeHumansIndiaMiddle AgedPolymorphism, Single NucleotidegeneticsX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
20133860201211002014101060ppublish23464476
221937132012062920171116
1949-25532122011DecOncotargetOncotargetMechanism of activation of AMPK and upregulation of OGG1 by rapamycin in cancer cells.958-9HabibSamy LSLengEditorialResearch Support, Non-U.S. Gov't
United StatesOncotarget1015329651949-25530Antibiotics, AntineoplasticEC 2.7.1.1MTOR protein, humanEC 2.7.1.1TOR Serine-Threonine KinasesEC 2.7.11.31AMP-Activated Protein KinasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanW36ZG6FT64SirolimusIMCancer Res. 2000 Sep 1;60(17):4740-410987279J Biol Chem. 2002 Sep 20;277(38):35364-7012167664J Cell Sci. 2004 Nov 1;117(Pt 23):5479-8715509864Science. 2005 Feb 18;307(5712):1098-10115718470N Engl J Med. 2008 Jan 10;358(2):140-5118184959Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12932-719625624Nat Rev Clin Oncol. 2010 Apr;7(4):209-1920234352Eur J Cancer. 2010 Oct;46(15):2806-2020656472AMP-Activated Protein KinasesmetabolismAntibiotics, AntineoplasticpharmacologyDNA GlycosylasesmetabolismHumansNeoplasmsmetabolismSirolimuspharmacologyTOR Serine-Threonine Kinasesmetabolism
20111224602011122460201263060ppublish22193713381PMC328209910.18632/oncotarget.381
221936212012101820131121
1432-07388662012JunArchives of toxicologyArch. Toxicol.Elevated risk of hypertension induced by arsenic exposure in Taiwanese rural residents: possible effects of manganese superoxide dismutase (MnSOD) and 8-oxoguanine DNA glycosylase (OGG1) genes.869-7810.1007/s00204-011-0797-8Heavy metals, including arsenic and lead, may lead to cellular oxidative damage that is linked to hypertension. Manganese superoxide dismutase (MnSOD) is a scavenger of reactive oxygen species, and 8-oxoguanine DNA glycosylase (OGG1) is the major glycosylase that repairs DNA lesions. Interestingly, whether there is an elevated risk of hypertension with arsenic or lead exposure in individuals with genetic variations in MnSOD or OGG1 has not yet been investigated. Questionnaires were administered to 240 Taiwanese rural residents. Blood pressure and biochemical indicators were assessed in each subject. Urinary levels of arsenic and lead were measured with atomic absorption spectrometry; and MnSOD and OGG1 genotypes were identified via polymerase chain reaction. There was a dose-response relationship between urinary arsenic levels and risk of hypertension (P = 0.021, test for trend). However, there was no association between urinary lead levels and hypertension risk. Individuals with high urinary arsenic levels and the MnSOD Val-Ala/Ala-Ala genotypes had a greater risk of hypertension than those with low urinary arsenic levels and the MnSOD Val-Val genotype (odds ratio [OR] = 4.2, 95% confidence interval [CI] = 1.7-10.3). Subjects with a high urinary arsenic level and the OGG1 Cys-Cys genotype also had a greater risk of hypertension than those with a low urinary arsenic level and the OGG1 Ser-Ser/Ser-Cys genotypes (OR = 3.4, 95% CI = 1.1-10.7). Thus, both MnSOD and OGG1 genotypes may be prone to an increased risk of hypertension associated with arsenic exposure.ChenShiuan-ChihSCDepartment of Family and Community Medicine, Chung Shan Medical University Hospital, No. 110 Chien-Kuo N Rd, Sec. 1, Taichung 40242, Taiwan.ChenChun-ChiehCCKuoChung-YihCYHuangChun-HuangCHLinChin-HsiuCHLuZi-YunZYChenYi-YuYYLeeHong-ShenHSWongRuey-HongRHengComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't20111223
GermanyArch Toxicol04176150340-57612P299V784PLead5Z93L87A1RGuanine82014-86-68-oxyguanineEC 1.15.1.1Superoxide DismutaseEC 3.2.2.-DNA GlycosylasesN712M78A8GArsenicIMAdultAgedArsenictoxicityurineCross-Sectional StudiesDNA GlycosylasesgeneticsDose-Response Relationship, DrugFemaleGenetic Predisposition to DiseaseepidemiologyGenotypeGuanineanalogs & derivativesmetabolismHumansHypertensionchemically inducedepidemiologygeneticsurineLeadtoxicityurineMaleMiddle AgedOccupational Exposureadverse effectsstatistics & numerical dataOxidative StressgeneticsPolymorphism, GeneticRisk FactorsRural Populationstatistics & numerical dataSuperoxide DismutasegeneticsTaiwanepidemiology
2011092320111212201112246020111224602012101960ppublish2219362110.1007/s00204-011-0797-8
220813742012020620171116
1423-03803312012FebTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Reduced expression of DNA repair genes (XRCC1, XPD, and OGG1) in squamous cell carcinoma of head and neck in North India.111-910.1007/s13277-011-0253-7Squamous cell carcinoma of head and neck (SCCHN) is the sixth most common cancer globally, and in India, it accounts for 30% of all cancer cases. Epidemiological studies have shown a positive association between defective DNA repair capacity and SCCHN. The underlying mechanism of their involvement is not well understood. In the present study, we have analyzed the relationship between SCCHN and the expression of DNA repair genes namely X-ray repair cross-complementing group 1 (XRCC1), xeroderma pigmentosum group D (XPD), and 8-oxoguanine DNA glycosylase (OGG1) in 75 SCCHN cases and equal number of matched healthy controls. Additionally, levels of DNA adduct [8-hydroxyguanine (8-OHdG)] in 45 SCCHN cases and 45 healthy controls were also determined, to ascertain a link between mRNA expression of these three genes and DNA adducts. The relative expression of XRCC1, XPD, and OGG1 in head and neck cancer patients was found to be significantly low as compared to controls. The percent difference of mean relative expression between cases and controls demonstrated maximum lowering in OGG1 (47.3%) > XPD (30.7%) > XRCC1 (25.2%). A negative Spearmen correlation between XRCC1 vs. 8-OHdG in cases was observed. In multivariate logistic regression analysis (adjusting for age, gender, smoking status, and alcohol use), low expression of XRCC1, XPD, and OGG1 was associated with a statistically significant increased risk of SCCHN [crude odds ratios (ORs) (95%CI) OR 2.10; (1.06-4.17), OR 2.76; (1.39-5.49), and 5.24 (2.38-11.52), respectively]. In conclusion, our study demonstrated that reduced expression of XRCC1, XPD, and OGG1 is associated with more than twofold increased risk in SCCHN.KumarAnilACSIR-Indian Institute of Toxicology Research, CSIR-IITR, PO Box 80, MG Marg, Lucknow 226001, India.PantMohan ChandMCSinghHirdya ShankerHSKhandelwalShashiSengJournal ArticleResearch Support, Non-U.S. Gov't20111115
United StatesTumour Biol84099221010-42830DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanIMInt J Cancer. 1994 Sep 15;58(6):825-97523311J Biol Chem. 2003 Dec 26;278(52):52914-814578343Biogerontology. 2010 Jun;11(3):287-9719707883Mutat Res. 2011 Dec 24;726(2):227-3321986195Mutat Res. 2002 Nov 30;509(1-2):165-7412427537Cancer Sci. 2009 Jul;100(7):1261-619432884Carcinogenesis. 2009 Jan;30(1):78-8719029194Carcinogenesis. 1999 Nov;20(11):2125-910545415Mol Carcinog. 1997 Apr;18(4):232-439142218DNA Repair (Amst). 2002 Mar 28;1(3):237-5012509255Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1614-88434025Cancer Epidemiol Biomarkers Prev. 1998 Apr;7(4):309-149568786Mutat Res. 2001 Aug 9;486(3):207-1611459633Mutat Res. 2008 Dec 15;648(1-2):65-7218977234Oncogene. 1990 Oct;5(10):1603-101979160Pharmacogenet Genomics. 2007 Nov;17(11):897-90518075460Cancer Epidemiol Biomarkers Prev. 1998 Jun;7(6):465-89641488Science. 1999 Dec 3;286(5446):1897-90510583946DNA Repair (Amst). 2007 Sep 1;6(9):1264-7017403617Biochimie. 1999 Jan-Feb;81(1-2):39-4410214908Cell Biol Toxicol. 2009 Oct;25(5):489-9718787964Mutat Res. 2006 Jan 29;593(1-2):88-9616054657J Invest Dermatol. 2005 Feb;124(2):435-4215675965Carcinogenesis. 2000 Aug;21(8):1527-3010910954Toxicol Sci. 2009 Jan;107(1):165-7018948301Cell Biol Int. 2009 Mar;33(3):357-6319385033Carcinogenesis. 2006 May;27(5):997-100716308313J Genet. 2008 Apr;87(1):3-2018560169FEBS Lett. 1994 Mar 14;341(1):59-648137923Carcinogenesis. 2007 Mar;28(3):657-6417028303J Psychosom Res. 2009 Mar;66(3):259-6619232240Carcinogenesis. 2003 Nov;24(11):1847-5212919962Int J Cancer. 2003 Apr 10;104(3):263-812569548Mutat Res. 2011 Mar 15;708(1-2):11-2021277872Mol Biol Rep. 2011 Feb;38(2):1251-6120571908Nature. 1991 Jan 31;349(6308):431-41992344Cancer Biomark. 2005;1(2-3):201-517192041DNA Repair (Amst). 2005 Jul 12;4(7):826-3515927541Am J Respir Cell Mol Biol. 2010 Nov;43(5):576-8420008282Science. 1989 Nov 3;246(4930):629-342683079Pharmacogenomics. 2006 Sep;7(6):843-5216981845J Toxicol Environ Health A. 2007 Jun;70(11):956-6317479411Free Radic Biol Med. 1999 Aug;27(3-4):401-1010468215Mutat Res. 2012 Jan 3;729(1-2):24-3421945240Oncogene. 1998 Jun 25;16(25):3219-259681819Free Radic Biol Med. 2010 Aug 15;49(4):587-9620483371Cancer Res. 1992 Feb 1;52(3):734-61310070Cancer Res. 2006 Dec 15;66(24):11683-917178863Carcinogenesis. 2000 May;21(5):965-7110783319Mol Gen Genet. 1997 Mar 26;254(2):171-89108279Mutat Res. 2008 Mar 1;639(1-2):45-5418155253Anticancer Res. 2011 Apr;31(4):1411-521508394Mol Cancer. 2009 Mar 05;8:1319265534Int J Cancer. 2002 Jul 1;100(1):9-1312115580Am J Hematol. 2005 Feb;78(2):100-715682421Annu Rev Genet. 1995;29:69-1058825469Cancer. 2002 Jan 15;94(2):393-711900225J Radiat Res. 2003 Mar;44(1):31-512841596J Natl Cancer Inst. 2003 Sep 3;95(17):1263-512953074Trends Genet. 1993 Jul;9(7):246-98379000Carcinogenesis. 2000 Dec;21(12):2219-2311133811Cancer Res. 2001 Feb 15;61(4):1354-711245433J Exp Clin Cancer Res. 2009 Mar 13;28:3719284666Cancer Epidemiol Biomarkers Prev. 1999 Sep;8(9):801-710498399Kidney Int. 2004 Aug;66(2):820-3115253739Free Radic Biol Med. 2011 Jul 15;51(2):417-2321569841AdultAgedCarcinoma, Squamous CellgeneticsDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-Binding ProteinsgeneticsGene Expression Regulation, NeoplasticHead and Neck NeoplasmsgeneticsHumansMaleMiddle AgedX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
20110625201110182011111560201111156020122760ppublish2208137410.1007/s13277-011-0253-7
220572692012022720161125
1083-351X286522011Dec30The Journal of biological chemistryJ. Biol. Chem.Poly(ADP-ribose) polymerase 1 (PARP-1) binds to 8-oxoguanine-DNA glycosylase (OGG1).44679-9010.1074/jbc.M111.255869Human 8-oxoguanine-DNA glycosylase (OGG1) plays a major role in the base excision repair pathway by removing 8-oxoguanine base lesions generated by reactive oxygen species. Here we report a novel interaction between OGG1 and Poly(ADP-ribose) polymerase 1 (PARP-1), a DNA-damage sensor protein involved in DNA repair and many other cellular processes. We found that OGG1 binds directly to PARP-1 through the N-terminal region of OGG1, and this interaction is enhanced by oxidative stress. Furthermore, OGG1 binds to PARP-1 through its BRCA1 C-terminal (BRCT) domain. OGG1 stimulated the poly(ADP-ribosyl)ation activity of PARP-1, whereas decreased poly(ADP-ribose) levels were observed in OGG1(-/-) cells compared with wild-type cells in response to DNA damage. Importantly, activated PARP-1 inhibits OGG1. Although the OGG1 polymorphic variant proteins R229Q and S326C bind to PARP-1, these proteins were defective in activating PARP-1. Furthermore, OGG1(-/-) cells were more sensitive to PARP inhibitors alone or in combination with a DNA-damaging agent. These findings indicate that OGG1 binding to PARP-1 plays a functional role in the repair of oxidative DNA damage.Noren HootenNicoleNLaboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.KompaniezKariKBarnesJaniceJLohaniAlthafAEvansMichele KMKengIntramural NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Intramural20111104
United StatesJ Biol Chem2985121R0021-9258EC 2.4.2.30PARP1 protein, humanEC 2.4.2.30Parp1 protein, mouseEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 3.2.2.-oxoguanine glycosylase 1, humanIMCancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Nat Rev Cancer. 2010 Apr;10(4):293-30120200537J Biol Chem. 2003 Nov 7;278(45):44068-7412933815Mol Cell Biol. 2003 Dec;23(23):8601-1314612404DNA Repair (Amst). 2003 Dec 9;2(12):1337-5214642563Cancer Res. 2004 May 1;64(9):3096-10215126346Carcinogenesis. 2004 Sep;25(9):1689-9415073047Trends Neurosci. 2004 Oct;27(10):595-60015374670Br J Cancer Suppl. 1987 Jun;8:105-122820457Exp Cell Res. 1988 Mar;175(1):184-913345800Cancer Res. 1989 Sep 1;49(17):4682-92547513Radiat Res. 1990 Apr;122(1):86-942320728Nature. 1991 Jan 31;349(6308):431-41992344Free Radic Biol Med. 1991;10(3-4):225-421650738PLoS Genet. 2010 May;6(5):e100095120485567Mutat Res. 2011 Jun 3;711(1-2):100-1221167187Cancer Res. 1997 Jun 1;57(11):2151-69187114Oncogene. 1997 Jun 12;14(23):2857-619190902Curr Biol. 1997 Jun 1;7(6):397-4079197244Rev Physiol Biochem Pharmacol. 1997;131:1-879204689Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7303-79207086Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7429-349207108Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-59223305Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8016-209223306Genes Dev. 1997 Sep 15;11(18):2347-589308963Mol Cell Biol. 1998 Jun;18(6):3563-719584196Oncogene. 1998 Jun 25;16(25):3219-259681819Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2301-410051636Nucleic Acids Res. 1999 Oct 15;27(20):4001-710497264Annu Rev Genet. 2004;38:445-7615568983Mol Carcinog. 2005 Mar;42(3):127-4115584022Oncol Rep. 2005 Jun;13(6):1009-1615870915Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Mol Cell Biol. 2006 Mar;26(5):1654-6516478987Nucleic Acids Res. 2006;34(5):1620-3216549874FEBS J. 2006 Apr;273(8):1620-916623699Mutat Res. 2006 Jun 16;605(1-2):7-1616621680Nat Rev Mol Cell Biol. 2006 Jul;7(7):517-2816829982Nat Cell Biol. 2006 Aug;8(8):815-2516862147EMBO J. 2006 Sep 20;25(18):4305-1516957781Free Radic Res. 2006 Dec;40(12):1295-30217090419Nucleic Acids Res. 2007;35(8):2759-6617426120Nature. 2007 Jun 21;447(7147):941-5017581577Cancer Detect Prev. 2007;31(3):237-4317651912Anticancer Agents Med Chem. 2007 Sep;7(5):515-2317896912Cell Res. 2008 Jan;18(1):27-4718166975Carcinogenesis. 2008 Apr;29(4):722-818258604Biochem Biophys Res Commun. 2008 Nov 14;376(2):336-4018774780Methods Mol Biol. 2009;464:267-8318951190Cancer Res. 2000 Sep 1;60(17):4740-410987279Int J Cancer. 2000 Dec 15;88(6):932-711093817Nucleic Acids Res. 2001 Jan 15;29(2):430-811139613Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10469-7411517304Mol Biol (Mosk). 2008 Sep-Oct;42(5):891-90318988537Free Radic Biol Med. 2008 Dec 15;45(12):1631-4118845243Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18877-8219020090Mol Cell Biol. 2009 Aug;29(16):4441-5419506022DNA Repair (Amst). 2009 Oct 2;8(10):1190-20019615952Hum Mol Genet. 2009 Nov 1;18(21):4102-1719643912Cancer Res. 2003 Mar 1;63(5):902-512615700Amino Acid SubstitutionAnimalsDNA DamagephysiologyDNA GlycosylasesgeneticsmetabolismHeLa CellsHumansMiceMice, KnockoutMutation, MissensePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesgeneticsmetabolismProtein BindingphysiologyProtein Structure, Tertiary
20111186020111186020123160ppublish22057269M111.25586910.1074/jbc.M111.255869PMC3247967
220194392012041720131121
1873-45965212012Jan01Free radical biology & medicineFree Radic. Biol. Med.Influence of the OGG1 Ser326Cys polymorphism on oxidatively damaged DNA and repair activity.118-2510.1016/j.freeradbiomed.2011.09.038Oxidatively damaged DNA base lesions are considered to be mainly repaired by 8-oxoguanine DNA glycosylase (OGG1) mediated pathways. We investigated the effect of the OGG1 Ser326Cys polymorphism on the level and repair of oxidatively damaged DNA in mononuclear blood cells (MNBC) by means of the comet assay. We collected blood samples from 1,019 healthy subjects and genotyped for the OGG1 Ser326Cys polymorphism. We found 49 subjects homozygous for the variant genotype (Cys/Cys) and selected same numbers of age-matched subjects with the heterozygous (Ser/Cys) and homozygous wild-type genotype (Ser/Ser). Carriers of the Cys/Cys genotype had higher levels of formamidopyrimidine DNA glycosylase (FPG) sensitive sites in MNBC (0.31 ± 0.03 lesions/10(6)bp) compared to Ser/Ser (0.19 ± 0.02 lesions/10(6)bp, P<0.01). The level of hOGG1 sensitive sites in MNBC from the Ser326Cys carriers (0.19 ± 0.16 lesions/10(6) bp) was also higher compared to the Ser/Ser genotype (0.11 ± 0.09 lesions/10(6) bp, P<0.05). Still, there was no genotype-related difference in DNA repair incision activity of MNBC extracts on nucleoids with oxidatively damaged DNA induced by Ro19-8022/white light (P=0.20). In addition, there were no differences in the expression of OGG1 (P=0.69), ERCC1 (P=0.62), MUTYH (P=0.85), NEIL1 (P=0.17) or NUDT1 (P=0.48) in whole blood. Our results indicate that the OGG1 Ser326Cys polymorphism has limited influence on the DNA repair incisions by extracts of MNBC, whereas the apparent increased risk of cancer in subjects with the Cys/Cys genotype may be because of higher levels of oxidatively damaged DNA.Copyright © 2011 Elsevier Inc. All rights reserved.JensenAnnieADepartment of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.LøhrMilleMEriksenLouiseLGrønbækMortenMDorryEladELoftSteffenSMøllerPeterPengJournal ArticleResearch Support, Non-U.S. Gov't20111007
United StatesFree Radic Biol Med87091590891-58495614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanAdenocarcinoma of lungIMAdenocarcinomaenzymologygeneticsAdultAgedCase-Control StudiesComet AssayDNA DamagegeneticsDNA GlycosylasesgeneticsmetabolismDNA RepairgeneticsDenmarkFemaleGenetic Predisposition to DiseaseGenotypeGuanineanalogs & derivativesmetabolismHomozygoteHumansLeukocytes, MononuclearcytologymetabolismLung NeoplasmsenzymologygeneticsMaleMiddle AgedOxidation-ReductionOxidative StressPolymorphism, Single Nucleotide
20110614201109272011092720111025602011102560201241860ppublish22019439S0891-5849(11)00613-710.1016/j.freeradbiomed.2011.09.038
219861952012021320131121
0027-510772622011Dec24Mutation researchMutat. Res.Role of OGG1 Ser326Cys polymorphism and 8-oxoguanine DNA damage in risk assessment of squamous cell carcinoma of head and neck in North Indian population.227-3310.1016/j.mrgentox.2011.09.015Squamous cell carcinoma of head and neck (SCCHN), one of the leading cancers worldwide, is most prevalent in Indian sub-continent. The major risk factors involved are smoking and consumption of alcohol, since they provide high free radical generating environment. We studied 8-oxoguanine DNA-glycosylase (OGG1) Ser326Cys polymorphism in 278 SCCHN cases and 278 matched controls by PCR-RFLP and observed that the variant genotype Ser/Cys exhibited an enhanced risk of ∼1.7 folds (OR=1.71, 95% CI=1.20-2.93) and Cys/Cys ∼2.5 folds (OR=2.55, 95% CI=1.29-5.00). Furthermore, we found a significant increase in salivary cell 8-OHdG with respect to Ser/Cys and Cys/Cys genotypes of OGG1 in SCCHN cases, when compared to Ser/Ser and Ser/Cys genotypes of the control population. Our results demonstrate that Ser326Cys variant genotype is associated with an increased risk of SCCHN in north India. Ser326Cys variant genotype was found to accumulate more of 8-OHdG, which may serve as a biomarker for early diagnosis of SCCHN.Copyright © 2011 Elsevier B.V. All rights reserved.KumarAnilACSIR-Indian Institute of Toxicology Research, Lucknow, India.PantMohan ChandMCSinghHirdya ShankerHSKhandelwalShashiSengJournal ArticleResearch Support, Non-U.S. Gov't20111001
NetherlandsMutat Res04007630027-51070DNA Adducts5614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanCarcinoma, squamous cell of head and neckIMAdultAgedCarcinoma, Squamous CellgeneticsCase-Control StudiesDNA AdductsDNA DamageDNA GlycosylasesgeneticsFemaleGuanineanalogs & derivativesmetabolismHead and Neck NeoplasmsgeneticsHumansIndiaMaleMiddle AgedPolymorphism, GeneticRisk Assessment
20110709201109072011092520111012602011101260201221460ppublish21986195S1383-5718(11)00280-410.1016/j.mrgentox.2011.09.015
219833362012061120131121
1532-045615522012MarComparative biochemistry and physiology. Toxicology & pharmacology : CBPComp. Biochem. Physiol. C Toxicol. Pharmacol.8-Oxoguanine DNA glycosylase 1 (OGG1) from the copepod Tigriopus japonicus: molecular characterization and its expression in response to UV-B and heavy metals.290-910.1016/j.cbpc.2011.09.0108-Oxoguanine DNA glycosylase 1 (EC 3.2.2.23) is encoded by OGG1 gene and plays a key role in removing 8-oxo-7,8-dihydroguanine (8-oxoG) base in DNA lesion by reactive oxygen species (ROS). To identify and characterize OGG1 gene (TJ-OGG1) in the copepod Tigriopus japonicus, the full-length cDNA sequence, genomic structure, and promoter region was analyzed. In addition, to investigate transcriptional change of TJ-OGG1 mRNA under oxidative stress conditions, T. japonicus were exposed to environmental oxidative inducers, H(2)O(2), UV-B, and heavy metals (Cd, Cu, and Zn), respectively. The full-length cDNA of TJ-OGG1 gene was 1708 bp in length, encoding 343 amino acid residues. The deduced amino acid sequences of TJ-OGG1 showed a 56% similarity with human. Two conserved motifs (HhH and PVD loop) and two conserved residues (lysine and aspartic acid) in active sites were also observed. TJ-OGG1 genome structure contained six exons and five introns and putative transcription factor binding sites such as Nrf-2, p53, ERE-half sites, and XRE were detected on the promoter region. TJ-OGG1 mRNA level was increased at approximately three-fold (P<0.05) at 1mM and approximately 4-fold (P<0.01) at 10mM of H(2)O(2), respectively. UV-B enhanced the expression of TJ-OGG1 mRNA at 15kJ/m(2) (P<0.05) and more (P<0.001). In a time-course experiment, TJ-OGG1 gene was highly transcribed within 12h after exposure of 10 kJ/m(2) (P<0.01) and 20 kJ/m(2) (P<0.001). The expression of TJ-OGG1 mRNA after exposure to Cu and Cd for 96 h was significantly up-regulated at 0.1 μg/L and then remarkably reduced in a dose-dependent manner. Their transcript levels did not change at low dose (0.1 and 1 μg/L) but were dose-dependently down-regulated at high dose (10 and 100 μg/L). These findings suggest that H(2)O(2), UV-B, and heavy metals induce oxidative stress and generate oxidatively damaged DNA. Consequently, the enhanced TJ-OGG1 gene expression would be associated with active involvement of TJ-OGG1 gene in DNA repair process as a cellular protection mechanism. This is the first report on the cloning and characterization of OGG1 gene in aquatic animals. This study is helpful for a better understanding of the molecular mechanisms of cellular protection against various environmental oxidative stress inducers such as UV-B and heavy metals in aquatic invertebrates.Copyright © 2011 Elsevier Inc. All rights reserved.KimBo-MiBMDepartment of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791, South Korea.RheeJae-SungJSSeoJung SooJSKimIl-ChanICLeeYoung-MiYMLeeJae-SeongJSengGENBANKJN090125Journal ArticleResearch Support, Non-U.S. Gov't20111001
United StatesComp Biochem Physiol C Toxicol Pharmacol1009595001532-04560DNA, Complementary0Oxidants0Transcription Factors00BH33GNGHCadmium5614-64-28-hydroxyguanine5Z93L87A1RGuanine789U1901C5CopperBBX060AN9VHydrogen PeroxideEC 3.2.2.-DNA GlycosylasesIMAmino Acid SequenceAnimalsBase SequenceBinding SitesgeneticsCadmiumpharmacologyCloning, MolecularCopepodaenzymologygeneticsmetabolismCopperpharmacologyDNA GlycosylasesclassificationgeneticsmetabolismDNA, ComplementarychemistrygeneticsDose-Response Relationship, DrugGene Expression Regulation, Enzymologicdrug effectsradiation effectsGuanineanalogs & derivativesmetabolismHydrogen PeroxidepharmacologyMolecular Sequence DataOxidantspharmacologyPhylogenyPromoter Regions, GeneticgeneticsReverse Transcriptase Polymerase Chain ReactionSequence Analysis, DNASequence Homology, Amino AcidTranscription FactorsmetabolismUltraviolet Rays
20110802201109222011092320111011602011101160201261260ppublish21983336S1532-0456(11)00189-X10.1016/j.cbpc.2011.09.010
219191072012052520161118
1098-279578122011DecMolecular reproduction and developmentMol. Reprod. Dev.Age-related instability in spermatogenic cell nuclear and mitochondrial DNA obtained from Apex1 heterozygous mice.906-1910.1002/mrd.21374The prevalence of spontaneous mutations increases with age in the male germline; consequently, older men have an increased risk of siring children with genetic disease due to de novo mutations. The lacI transgenic mouse can be used to study paternal age effects, and in this system, the prevalence of de novo mutations increases in the male germline at old ages. Mutagenesis is linked with DNA repair capacity, and base excision repair (BER), which can ameliorate spontaneous DNA damage, decreases in nuclear extracts of spermatogenic cells from old mice. Mice heterozygous for a null allele of the Apex1 gene, which encodes apurinic/apyrimidinic endonuclease I (APEN), an essential BER enzyme, display an accelerated increase in spontaneous germline mutagenesis early in life. Here, the consequences of lifelong reduction of APEN on genetic instability in the male germline were examined, for the first time, at middle and old ages. Mutant frequency increased earlier in spermatogenic cells from Apex1(+/-) mice (by 6 months of age). Nuclear DNA damage increased with age in the spermatogenic lineage for both wild-type and Apex1(+/-) mice. By old age, mutant frequencies were similar for wild-type and APEN-deficient mice. Mitochondrial genome repair also depends on APEN, and novel analysis of mitochondrial DNA (mtDNA) damage revealed an increase in the Apex1(+/-) spermatogenic cells by middle age. Thus, Apex1 heterozygosity results in accelerated damage to mtDNA and spontaneous mutagenesis, consistent with an essential role for APEN in maintaining nuclear and mtDNA integrity in spermatogenic cells throughout life.Published 2011 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.VogelKristine SKSDepartment of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.PerezMarissaMMomandJamila RJRAcevedo-TorresKarinaKHildrethKimKGarciaRebecca ARATorres-RamosCarlos ACAAyala-TorresSylvetteSPrihodaThomas JTJMcMahanC AlexCAWalterChristi ACAengSC3 GM084759-03GMNIGMS NIH HHSUnited StatesU54 NS039408-10NSNINDS NIH HHSUnited StatesAG0211663AGNIA NIH HHSUnited StatesR01 AG024364-05AGNIA NIH HHSUnited States5R25GM061838GMNIGMS NIH HHSUnited StatesCA054174CANCI NIH HHSUnited States5SC3GM084759GMNIGMS NIH HHSUnited StatesR25 GM061838GMNIGMS NIH HHSUnited StatesG12 RR003051-25RRNCRR NIH HHSUnited StatesR01 AG024364AGNIA NIH HHSUnited StatesAG024364AGNIA NIH HHSUnited States5U54NS039408NSNINDS NIH HHSUnited StatesG12 RR003051RRNCRR NIH HHSUnited StatesR25 GM061838-12GMNIGMS NIH HHSUnited StatesG12RR03051RRNCRR NIH HHSUnited StatesR01 AG021163-05AGNIA NIH HHSUnited StatesP30 CA054174CANCI NIH HHSUnited StatesSC3 GM084759GMNIGMS NIH HHSUnited StatesU54 NS039408NSNINDS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20110914
United StatesMol Reprod Dev89033331040-452X0DNA, Mitochondrial9007-49-2DNAEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAndrologia. 2000 Sep;32(4-5):233-711021514Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Mutat Res. 2001 Mar 7;485(2):143-5211182545Sci Aging Knowledge Environ. 2004 Jan 21;2004(3):re114736914DNA Repair (Amst). 2004 May 4;3(5):495-50415084311Mol Cell Biol. 2004 Sep;24(18):8145-5315340075Anal Biochem. 1976 May 7;72:248-54942051J Cell Biol. 1977 Jul;74(1):68-85874003Am J Hum Genet. 1987 Aug;41(2):218-483618593J Biol Chem. 1988 Sep 5;263(25):12532-72457585Exp Cell Res. 1989 Mar;181(1):169-802917600Biol Reprod. 1992 Feb;46(2):201-71536896J Cell Biol. 1992 Nov;119(3):493-5011400587Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1614-88434025FASEB J. 1994 May;8(8):545-508181674Cell. 1994 Jul 29;78(2):335-427913883Nature. 1994 Sep 15;371(6494):252-48078586Nucleic Acids Res. 1994 Nov 25;22(23):4884-97800476Somat Cell Mol Genet. 1994 Nov;20(6):451-617892645Biol Reprod. 1995 Apr;52(4):729-367779994J Biol Chem. 1995 Jul 7;270(27):16002-77608159Nat Genet. 1996 May;13(1):48-538673103Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-99012815Am J Reprod Immunol. 2008 Jan;59(1):2-1118154591Cell Res. 2008 Jan;18(1):27-4718166975Mech Ageing Dev. 2008 Jul-Aug;129(7-8):366-8218423806Free Radic Biol Med. 2008 Sep 1;45(5):592-60118515104Biol Reprod. 2008 Nov;79(5):824-3118650495DNA Repair (Amst). 2009 Jan 1;8(1):126-3618935984Int J Androl. 2009 Feb;32(1):46-5619076252Carcinogenesis. 2009 Jan;30(1):2-1018978338Cell Mol Life Sci. 2009 Mar;66(6):981-9319153658Microsc Res Tech. 2010 Apr;73(4):364-40819941288Biol Reprod. 2010 Dec;83(6):979-8720739667Nucleic Acids Res. 2001 Mar 15;29(6):1366-7211239003Nat Rev Genet. 2000 Oct;1(1):40-711262873Cancer Res. 2001 Jul 15;61(14):5552-711454706Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10469-7411517304Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12566-7111606727Mol Cell Biol. 2002 Apr;22(7):2410-811884623Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14952-712397172J Androl. 2003 Mar-Apr;24(2):185-9112634304Fertil Steril. 2003 Dec;80(6):1420-3014667878Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-99207062Genetics. 1998 Apr;148(4):1567-789560376Mol Hum Reprod. 1998 Jul;4(7):657-669701788Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10015-99707592Mutat Res. 1998 Oct 21;409(1):17-299806499J Gerontol A Biol Sci Med Sci. 1999 May;54(5):B199-204; discussion B205-610361999Genetica. 2004 Sep;122(1):25-3615619958Semin Cell Dev Biol. 2005 Apr;16(2):245-5915797835Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6051-615840724Fertil Steril. 2005 Oct;84 Suppl 2:1191-816210011Nucleic Acids Res. 2006;34(7):2067-7616617147Methods Mol Biol. 2006;314:183-9916673882Mutat Res. 2006 Jun 25;598(1-2):164-9316542687Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9601-616766665J Radiat Res. 2006;47 Suppl B:B75-8217019055Hum Reprod. 2006 Nov;21(11):2901-1016982656Mutat Res. 2007 Jan 3;614(1-2):56-6816765995DNA Repair (Amst). 2007 Apr 1;6(4):461-917166779DNA Repair (Amst). 2007 Apr 1;6(4):410-2817208522Methods. 2000 Oct;22(2):135-4711020328Age FactorsAnimalsApoptosisCell NucleusgeneticsDNAgeneticsmetabolismDNA DamageDNA, MitochondrialgeneticsmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismHeterozygoteLogistic ModelsMaleMiceMice, TransgenicMutagenesisgeneticsSpermatogenesisgeneticsSpermatozoachemistryphysiology
2011031120110727201191660201191660201252660ppublish2191910710.1002/mrd.21374PMC3391697NIHMS318336
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1096-720610442011DecMolecular genetics and metabolismMol. Genet. Metab.The 8-hydroxydeoxyguanosine concentrations according to hormone therapy and S326C polymorphism of OGG1 gene in postmenopausal women.644-710.1016/j.ymgme.2011.08.016The 8-hydroxydeoxyguanosine (8-OHdG) is widely used for determination of DNA damage since it is excised from oxidative damaged DNA with endonuclease repair enzymes coded by 8-oxoguanine DNA N-glycosylase gene (OGG1). The present study aimed at investigating whether hormone therapy (HT) may influence on the blood/urinary 8-OHdG levels and whether the level of 8-OHdG is different according to OGG1 S326C polymorphism in postmenopausal women receiving HT.In 102 postmenopausal women receiving HT, the 8-OHdG levels were measured in the blood and urine using high performance liquid chromatography (HPLC) before HT and 3 months after HT. The genotyping of the S326C polymorphism of the OGG1 was performed by polymerase chain reaction (PCR) and restriction enzyme fragment length polymorphism (RFLP) analysis.After HT, mean blood 8-OHdG level significantly decreased compared to those before HT (P=0.003), while urinary 8-OHdG level did not show any difference according to HT. Pre-HT level of 8-OHdG was not different according to OGG1 genotypes and similar finding was demonstrated in post-HT 8-OHdG concentration.These findings imply that hormone therapy can reduce blood 8-OHdG concentration, one of the markers of oxidative damage. Further study is needed to confirm this association in larger population.Copyright © 2011 Elsevier Inc. All rights reserved.KimHoonHDepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.KuSeung-YupSYKangJong WonJWKimHeonHKimYong DaeYDKimSeok HyunSHChoiYoung MinYMKimJung GuJGMoonShin YongSYengJournal ArticleResearch Support, Non-U.S. Gov't20110824
United StatesMol Genet Metab98054561096-71920Biomarkers12133JR80SGuanosine3868-31-38-hydroxyguanosineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAmino Acid SubstitutionAmplified Fragment Length Polymorphism AnalysisBiomarkersbloodurineDNA DamageDNA GlycosylasesgeneticsFemaleGenetic Association StudiesGenotypeGuanosineanalogs & derivativesbloodurineHormone Replacement TherapyHumansMiddle AgedOxidative StressPolymorphism, GeneticPostmenopausemetabolism
201107082011081620110816201191360201191360201231660ppublish21908221S1096-7192(11)00269-110.1016/j.ymgme.2011.08.016
218455412011120720161021
1509-572X4922011Folia neuropathologicaFolia NeuropatholExpression of 8-oxoguanine DNA glycosylase 1 (OGG1) and the level of p53 and TNF-αlpha proteins in peripheral lymphocytes of patients with Alzheimer's disease.123-31The aim of the study was to determine the extent of oxidative DNA damage (levels of 8-oxo2dG) and expression of OGG1 and p53 and TNF-α proteins in lymphocytes of Alzheimer's disease (AD) patients and a control group. The studies were conducted on 41 patients with AD, including 25 women and 16 men aged 34-84 years. The control group included 51 individuals, 20 women and 31 men aged 22-83 years. The level of 8-oxo2dG was determined using HPLC/EC/UV, and the level of OGG1 and p53 and TNF-α proteins was determined with the Western blot method. The results showed that both proteins participating in DNA repair (OGG1, p53) and the inflammatory protein TNF-α are involved in pathogenesis of neurodegenerative diseases. It also seems that a specific system for DNA repair (OGG1) may contribute to downregulation of the inflammatory factor (TNF-α) level, especially in the early stages of dementia. Moreover, the results showed that p53 protein can fulfil its function in DNA damage repair only in early stages of dementia. It is possible that OGG1 and p53 and TNF-α proteins together or separately may be involved in pathogenesis of AD by repair of oxidative DNA damage and/or apoptosis.DezorMateuszMLaboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poland. dorszewskaj@yahoo.comDorszewskaJolantaJFlorczakJolantaJKempistyBartoszBJaroszewska-KoleckaJoannaJRozyckaAgataAPolrolniczakAnnaABugajRobertRJagodzinskiPaweł PPPKozubskiWojciechWengJournal Article
PolandFolia Neuropathol94374311509-572X0Biomarkers0TP53 protein, human0Tumor Necrosis Factor-alpha0Tumor Suppressor Protein p53EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultAgedAged, 80 and overAlzheimer DiseasebloodBiomarkersanalysisBlotting, WesternDNA GlycosylasesbiosynthesisbloodFemaleHumansLymphocytesmetabolismMaleMiddle AgedTumor Necrosis Factor-alphabloodTumor Suppressor Protein p53blood
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1873-54874232011AprArchives of medical researchArch. Med. Res.Genetic polymorphism of DNA base-excision repair genes (APE1, OGG1 and XRCC1) and their correlation with risk of lung cancer in a Chinese population.226-3410.1016/j.arcmed.2011.04.005Reactive oxygen species (ROS) and numerous carcinogens may cause DNA damage including oxidative base lesions that contribute to the risk of lung cancer. The base excision repair (BER) pathway could effectively remove oxidative lesions in which 8-oxoguanine glycosylase-1 (OGG1), x-ray repair cross-complementing 1 (XRCC1), and apurinic/apyimidinic endonuclease 1 (APE1) play key roles. The aim of this study was to analyze the polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of lung cancer.In a hospital-based, case-control study of 455 lung cancer cases and 443 cancer-free hospital controls, the SNPs of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their correlation with the risk of lung cancer in multivariate logistic regression models.Individuals homozygous for the variants APE1 -141GG showed a protective effect for lung cancer overall (OR=0.62; 95% CI: 0.42-0.91; p=0.02) and for lung adenocarcinoma (OR=0.65; 95% CI, 0.44-0.96; p=0.03). When analyzing the combined effects of variant alleles, 84 patients and controls were identified who were homozygous for two or three of the potential protective alleles (i.e., OGG1 326Cys, XRCC1 399Gln and APE1 -141G). ORs were significantly reduced when all patients were analyzed (OR=0.62; 95% CI: 0.38-0.99; p=0.05).The combined effects of polymorphisms within BER genes may contribute to the tumorigenesis of lung cancer.Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.LiZhengZDepartment of Pathology, Third Military Medical University, Chongqing, China.GuanWeiWLiMeng-xiaMXZhongZhao-yangZYQianCheng-yuanCYYangXue-qinXQLiaoLingLLiZeng-pengZPWangDongDengJournal ArticleResearch Support, Non-U.S. Gov't
United StatesArch Med Res93127060188-44090DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdenocarcinomageneticsAmino Acid SubstitutionAsian Continental Ancestry GroupCarcinoma, Small CellgeneticsCarcinoma, Squamous CellgeneticsCase-Control StudiesDNA GlycosylasesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGene FrequencyGenetic Association StudiesGenotypeHumansLogistic ModelsLung NeoplasmsgeneticsMaleMiddle AgedMultivariate AnalysisOdds RatioPolymorphism, GeneticSequence Analysis, DNASmokingX-ray Repair Cross Complementing Protein 1
20101227201103112011756020117560201111160ppublish21722819S0188-4409(11)00054-310.1016/j.arcmed.2011.04.005
216953872012030820170926
1432-126226122011DecInternational journal of colorectal diseaseInt J Colorectal DisAssociation of OGG1 Ser326Cys polymorphism with colorectal cancer risk: a meta-analysis.1525-3010.1007/s00384-011-1258-98-Oxoguanine DNA glycosylase 1 (OGG1), a key protein involved in the base excision repair pathway, can recognize and excise several lesions from oligodeoxynucleotides with single DNA damage. A C/G polymorphism at 1,245 bp (C1245G) in exon 7 of the OGG1 (Ser326Cys, rs1052133) is found to have a lower enzymatic activity. A variety of case-control studies have been published evaluating the association between OGG1 Ser326Cys polymorphism and colorectal cancer (CRC), though their conclusions were always contradictory.This meta-analysis enrolled 12 studies to estimate the overall risk of OGG1 Ser326Cys polymorphism associated with CRC. The pooled odds ratios (ORs) were performed for codominant model (Cys/Cys versus Ser/Ser; Ser/Cys versus Ser/Ser), dominant model (Ser/Cys + Cys/Cys versus Ser/Ser) and recessive model (Cys/Cys versus Ser/Cys + Ser/Ser).No significant associations were found for Cys/Cys versus Ser/Ser (OR = 1.19, 95% confidence interval (CI) 0.92-1.53), Ser/Cys versus Ser/Ser (OR = 1.04, 95% CI 0.95-1.13), Ser/Cys + Cys/Cys versus Ser/Ser (OR = 1.06, 95% CI 0.98-1.16) and Cys/Cys versus Ser/Cys + Ser/Ser (OR = 1.11, 95% CI 0.90-1.38); moreover, in the stratified analyses, no significantly increased risk was found for all genetic models.Our meta-analysis suggests that the OGG1 Ser326Cys polymorphism is not associated with CRC risk.ZhangYingYClinical Laboratory, Traditional Chinese Medicine Hospital of Kunshan, Kunshan, 215300, Jiangsu Province, China.HeBang-ShunBSPanYu-QinYQXuYe-QiongYQWangShu-KuiSKengJournal ArticleMeta-Analysis20110622
GermanyInt J Colorectal Dis86078990179-1958EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMInt J Cancer. 2001 May 20;95(3):140-311307145N Engl J Med. 1990 Dec 13;323(24):1664-722172820Am J Hum Genet. 2005 Jul;77(1):112-915931596Cancer Sci. 2006 Aug;97(8):724-816800823Arch Phys Med Rehabil. 2006 Jun;87(6):87516731227Tohoku J Exp Med. 2009 Jul;218(3):185-9119561388Cancer Epidemiol Biomarkers Prev. 2008 Jul;17(7):1739-4518628426Nucleic Acids Res. 2006 Mar 20;34(5):1620-3216549874Int J Cancer. 2002 Jun 1;99(4):624-711992556Nucleic Acids Res. 2000 Jul 15;28(14):2672-810908322Mol Aspects Med. 2007 Jun-Aug;28(3-4):258-7517628657J Natl Cancer Inst. 2004 Feb 18;96(4):261-814970275Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502Carcinogenesis. 2004 Sep;25(9):1689-9415073047FEBS J. 2009 Sep;276(18):5149-6219674107Mutat Res. 2008 Feb 1;638(1-2):146-5317991492J Biol Chem. 1992 Jan 5;267(1):166-721730583BMJ. 2003 Sep 6;327(7414):557-6012958120Antioxid Redox Signal. 2001 Aug;3(4):597-60911554447Science. 2001 Feb 16;291(5507):1284-911181991Nucleic Acids Res. 1999 Oct 15;27(20):4001-710497264J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060Science. 1997 Nov 7;278(5340):1043-509353177Contemp Clin Trials. 2007 Feb;28(2):105-1416807131World J Gastroenterol. 2003 May;9(5):956-6012717837Cancer Res. 2006 Dec 15;66(24):11683-917178863Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2101-816609022Br J Cancer. 1999 Mar;79(7-8):1283-710098773Carcinogenesis. 2002 Jul;23(7):1229-3412117782BMJ. 1997 Sep 13;315(7109):629-349310563Carcinogenesis. 2000 Mar;21(3):361-7010688856Cancer Lett. 2005 Nov 8;229(1):85-9115946795Cancer Res. 2003 Aug 15;63(16):4899-90212941813Nature. 2001 May 17;411(6835):366-7411357144Amino Acid SubstitutiongeneticsCase-Control StudiesColorectal NeoplasmsenzymologygeneticsDNA GlycosylasesgeneticsGenetic Association StudiesGenetic Predisposition to DiseaseHumansPolymorphism, Single NucleotidegeneticsPublication BiasRisk Factors
2011061020116236020116236020123960ppublish2169538710.1007/s00384-011-1258-9
216401552011093020111128
1879-31852871-32011Sep05ToxicologyToxicologyAn OGG1 polymorphism is associated with mitochondrial DNA content in pesticide-exposed fruit growers.8-1410.1016/j.tox.2011.05.001Exposure to pesticides has the capacity to cause mitochondrial dysfunction. An increase mitochondrial DNA (mtDNA) content has also been suggested to relate with DNA damaging agent. In mitochondria, the manganese superoxide dismutase (MnSOD) is a scavenger of reactive oxygen species, and the 8-oxoguanine DNA glycosylase (OGG1) is the major DNA glycosylase for the repair of 8-oxoG lesions. However, the alteration of mtDNA content elicited by pesticide exposure in people with genetic variations in MnSOD or OGG1 has not been investigated. In this study, the mitochondrial to nuclear DNA ratio was quantified in the peripheral blood of 120 fruit growers who experienced pesticide exposure and 106 unexposed controls by real-time quantitative polymerase chain reaction (real-time qPCR). Questionnaires were administered to obtain demographic data and occupational history. The MnSOD and OGG1 genotypes were identified by the PCR based restriction fragment length polymorphism analysis. After adjusting for confounding effects, multiple regression model revealed that subjects experiencing high or low pesticide exposure had a greater mtDNA content than that of controls. The OGG1 Ser-Ser genotype was also associated with an increased mtDNA content. No association between MnSOD genotype and mtDNA content was revealed. Thus, subjects experiencing pesticide exposure had greater mtDNA content and the OGG1 genotype may modulate mtDNA content in pesticide-exposed fruit growers.Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.HuangPei-LinPLDepartment of Occupational Safety and Health, China Medical University, Taichung, Taiwan.WangMing-FuuMFLeeHong-ShenHSLiuYi-JieYJChenChun-ChiehCCChenShiuan-ChihSCLaiJim-ShoungJSWongRuey-HongRHengJournal ArticleResearch Support, Non-U.S. Gov't20110512
IrelandToxicology03610550300-483X0DNA, Mitochondrial0PesticidesEC 1.15.1.1Superoxide DismutaseEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultAgricultureCross-Sectional StudiesDNA GlycosylasesgeneticsDNA, MitochondrialanalysisFemaleFruitGenotypeHumansMaleMiddle AgedOccupational Exposureadverse effectsPesticidestoxicityPolymorphism, GeneticSuperoxide Dismutasegenetics
2011020920110502201105042011676020116760201110160ppublish21640155S0300-483X(11)00165-X10.1016/j.tox.2011.05.001
216232572011092720111117
1556-1380642011AprJournal of thoracic oncology : official publication of the International Association for the Study of Lung CancerJ Thorac OncolContribution of the TP53, OGG1, CHRNA3, and HLA-DQA1 genes to the risk for lung squamous cell carcinoma.813-710.1097/JTO.0b013e3181ee80efRecent genome-wide association studies (GWASs) have identified polymorphisms in several genes associated with lung cancer risk. Nevertheless, functional polymorphisms in DNA repair and metabolic genes that had been reported as being associated with risk for lung cancer, particularly for lung squamous cell carcinoma (SQC), were not examined in those studies. Therefore, significance of these functional polymorphisms was evaluated in a population, in which polymorphisms in the GWAS genes showed associations with lung SQC risk.Polymorphisms in three DNA repair genes, TP53, MDM2, and OGG1, and two metabolic genes, CYP1A1 and GSTM1, were examined for associations with lung SQC risk in a hospital-based case-control study consisting of 377 cases and 325 controls, which had been previously subjected to association studies on GWAS genes, CHRNA3, TERT, and HLA-DQA1.Genotypes for two DNA repair genes, TP53 and OGG1, showed significant associations with SQC risk (p < 0.05), and those for two GWAS genes, CHRNA3 and HLA-DQA1, showed significant associations with SQC risk (P < 0.05) with odds ratios between 1.65 (95% confidence interval = 1.06-2.57 for OGG1) and 2.57 (95% confidence interval = 1.03-6.87 for CHRNA3). Marginally significant associations were also observed for MDM2 and CYP1A1 genes. Interactions among these polymorphisms on SQC risk were not observed.Association of functional polymorphisms in DNA repair and metabolic genes with lung SQC risk was appreciated. This result indicates the necessity of reevaluation for the significance of functional polymorphisms in DNA repair and metabolic genes on lung cancer risk in other populations subjected to GWASs.KohnoTakashiTBiology Division, National Cancer Center Research Institute; †Division of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.KunitohHideoHMimakiSachiyoSShiraishiKouyaKKuchibaAyaAYamamotoSeiichiroSYokotaJunJengComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't
United StatesJ Thorac Oncol1012742351556-08640DNA, Neoplasm0HLA-DQ Antigens0HLA-DQ alpha-Chains0HLA-DQA1 antigen0Receptors, Nicotinic0TP53 protein, human0Tumor Suppressor Protein p530nicotinic receptor subunit alpha3EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMCarcinoma, Squamous CelletiologymortalityCase-Control StudiesDNA GlycosylasesgeneticsDNA RepairDNA, NeoplasmgeneticsFemaleGenome-Wide Association StudyHLA-DQ AntigensgeneticsHLA-DQ alpha-ChainsHumansLung NeoplasmsetiologymortalityMaleMiddle AgedOdds RatioPolymerase Chain ReactionPolymorphism, GeneticgeneticsPrognosisReceptors, NicotinicgeneticsRisk FactorsSurvival RateTumor Suppressor Protein p53genetics
201153160201153160201192960ppublish2162325710.1097/JTO.0b013e3181ee80efS1556-0864(15)33400-6
215662592011092620171116
1945-4589352011MayAgingAging (Albany NY)Cockayne syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo.509-14OGG1 and MSH2/MSH3 promote CAG repeat expansion at Huntington's disease (HD) locusin vivo during removal of oxidized bases from DNA. CSB, a transcription-coupled repair (TCR) protein, facilitates repair of some of the same oxidative lesions. In vitro, a knock down CSB results in a reduction of transcription-induced deletions at CAG repeat tract. To test the role of CSB in vivo, we measured intergenerational and somatic expansion of CAG tracts in HD mice lacking CSB, OGG1, or both. We provide evidence that CSB protects CAG repeats from expansion by either active reduction of the tract length during parent-child transmission, or by antagonizing the action of OGG1, which tends to promote expansion in somatic cells. These results raise a possibility that actions of transcription-coupled and base excision repair pathways lead to different outcomes at CAG tracts in vivo.KovtunIrina VIVDepartment of Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Rochester, MN 55905, USA. kovtun.irina@mayo.eduJohnsonKurt OKOMcMurrayCynthia TCTengGM066359GMNIGMS NIH HHSUnited StatesR01 NS062384NSNINDS NIH HHSUnited StatesR01 NS040738NSNINDS NIH HHSUnited StatesR21 NS061998NSNINDS NIH HHSUnited StatesP01 CA092584CANCI NIH HHSUnited StatesNS40738NSNINDS NIH HHSUnited StatesNS062384NSNINDS NIH HHSUnited StatesNS061998NSNINDS NIH HHSUnited StatesR01 GM066359GMNIGMS NIH HHSUnited StatesCA092584CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural
United StatesAging (Albany NY)1015086171945-45890Poly-ADP-Ribose Binding ProteinsEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.-DNA HelicasesEC 3.6.4.12ERCC6 protein, humanEC 6.5.1.-DNA Repair EnzymesIMMol Cell Biol. 2007 Sep;27(17):6209-1717591697Nucleic Acids Res. 2007;35(12):4103-1317567611Mech Ageing Dev. 2008 Jul-Aug;129(7-8):441-818541289Neurobiol Dis. 2009 Jan;33(1):37-4718930147J Biol Chem. 2009 Apr 3;284(14):9270-919179336Mol Carcinog. 2009 Apr;48(4):350-6118973172Mol Cell. 2010 Jan 29;37(2):235-4620122405J Exp Med. 2010 Feb 15;207(2):379-9020100872Mol Cell. 2010 Apr 9;38(1):54-6620385089Mol Cell. 2010 Jun 11;38(5):637-4820541997FASEB J. 2010 Jul;24(7):2334-4620181933Nucleic Acids Res. 1999 Nov 15;27(22):4476-8210536158Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Nat Genet. 1999 Dec;23(4):471-310581038Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4156-6110725358Mol Cell Biol. 2000 Oct;20(20):7643-5311003660Nat Genet. 2001 Apr;27(4):407-1111279522Carcinogenesis. 2001 Sep;22(9):1459-6311532868J Biol Chem. 2001 Dec 7;276(49):45772-911581270Hum Mol Genet. 2002 Jan 15;11(2):191-811809728DNA Repair (Amst). 2003 Jan 2;2(1):13-2512509265Hum Mol Genet. 2003 Feb 1;12(3):273-8112554681FASEB J. 2003 Apr;17(6):668-7412665480Mol Cell Biol. 2004 Jan;24(2):629-3714701736Hum Mol Genet. 2004 Aug 15;13(16):1815-2515198993Cell. 1996 Nov 1;87(3):493-5068898202Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4306-119113985EMBO J. 1997 Oct 1;16(19):5955-659312053Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11205-99326587Mol Cell Biol. 1997 Dec;17(12):6803-149372911Nucleic Acids Res. 1999 Mar 1;27(5):1365-89973627Hum Mol Genet. 2004 Dec 15;13(24):3057-6815496421Nat Struct Mol Biol. 2005 Aug;12(8):663-7016025128Mol Cell Biol. 2005 Sep;25(17):7625-3616107709Nat Rev Genet. 2005 Oct;6(10):729-4216205713Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9613-816772382Science. 2007 Mar 30;315(5820):1857-917332375Nature. 2007 May 24;447(7143):447-5217450122Oncogene. 2007 Jun 7;26(27):4044-817213818Nature. 2007 Jun 21;447(7147):932-4017581576Cell Res. 2008 Jan;18(1):198-21318166978AnimalsDNA GlycosylasesgeneticsmetabolismDNA HelicasesgeneticsmetabolismDNA RepairDNA Repair EnzymesgeneticsmetabolismFemaleHumansHuntington DiseasegeneticsmetabolismMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPoly-ADP-Ribose Binding ProteinsTrinucleotide Repeat Expansion
201151460201151460201192960ppublish21566259100324PMC315660110.18632/aging.100324
215050902011120520141120
1096-092912212011JulToxicological sciences : an official journal of the Society of ToxicologyToxicol. Sci.Resistance of CD-1 and ogg1 DNA repair-deficient mice to thalidomide and hydrolysis product embryopathies in embryo culture.146-5610.1093/toxsci/kfr084Thalidomide (TD) displays remarkable species specificity, causing birth defects (teratogenesis) in humans and rabbits, but not rats or mice; yet, few determinants of species susceptibility have been identified. Also, certain mouse strains are susceptible to the embryopathic effects of some teratogens in embryo culture despite their resistance in vivo. Herein we show that CD-1 mouse embryos in culture are resistant to limb embryopathies caused by TD and two of its hydrolysis products, 2-phthalimidoglutaramic acid and 2-phthalimidoglutaric acid, although all three compounds cause these embryopathies in rabbit embryo culture. These results show that the resistance of CD-1 mice to TD teratogenesis is inherent to the embryo and is not dependent upon maternal factors, including differential in vivo exposure to the many hydrolysis products of TD. In utero TD exposure of rabbit but not mouse embryos elevates levels of the teratogenic oxidative DNA lesion 8-oxoguanine, which is repaired by oxoguanine glycosylase 1 (OGG1). However, DNA repair-deficient ogg1 knockout mice proved resistant to TD-initiated embryopathies in culture and teratogenesis in vivo, indicating that the resistance of mice is not due to a higher level of DNA repair.LeeCrystal J JCJFaculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.GonçalvesLuisa LLLWellsPeter GPGengCanadian Institutes of Health ResearchCanadaJournal ArticleResearch Support, Non-U.S. Gov't20110419
United StatesToxicol Sci98054611096-09290Proteins0Teratogens4Z8R6ORS6LThalidomideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMAbnormalities, Drug-InducedAnimalsDNA Damagedrug effectsDNA GlycosylasesgeneticsmetabolismDNA Repairdrug effectsDNA Repair-Deficiency DisordersgeneticspathologyEmbryo Culture TechniquesFemaleFetal Diseaseschemically inducedgeneticsGenotypeHydrolysisMaleMiceMice, Inbred StrainsMice, KnockoutOxidative Stressdrug effectsPregnancyProteinsdrug effectsTeratogenstoxicityThalidomidetoxicity
2011421602011421602011121300ppublish21505090kfr08410.1093/toxsci/kfr084
214415392011101720150204
1362-496239142011AugNucleic acids researchNucleic Acids Res.8-Oxo-7,8-dihydroguanine in DNA does not constitute a barrier to transcription, but is converted into transcription-blocking damage by OGG1.5926-3410.1093/nar/gkr163The common DNA base modification 8-oxo-7,8-dihydroguanine (8-oxo-G) affects the efficiency and fidelity of transcription. We constructed plasmid substrates carrying single 8-oxo-G residues, specifically positioned in the transcribed or the non-transcribed DNA strands, to investigate their effects on the expression of an EGFP reporter gene and to explore the role of base excision repair in the mechanism of transcription inhibition. We report that 8-oxo-G does not directly block transcription in cells, since a single 8-oxo-G in the transcribed DNA strand did not reduce the EGFP expression levels in repair-deficient (OGG1-null) mouse embryonic fibroblast cell lines. Rather, inhibition of transcription by 8-oxo-G fully depends on 8-oxoguanine DNA glycosylase (OGG1) and, at the same time, does not require the localization of the lesion in the transcribed DNA strand. We propose that the interruption of transcription is induced by base excision repair intermediates and, therefore, could be a common consequence of various DNA base modifications. Concordantly, the non-blocking DNA modification uracil was also found to inhibit transcription, but in an OGG1-independent manner.KitseraNataliyaNInstitute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, Staudingerweg 5, 55128 Mainz, Germany.StathisDimitriosDLühnsdorfBorkBMüllerHeikoHCarellThomasTEpeBerndBKhobtaAndriyAengJournal ArticleResearch Support, Non-U.S. Gov't20110325
EnglandNucleic Acids Res04110110305-10485614-64-28-hydroxyguanine56HH86ZVCTUracil5Z93L87A1RGuanine9007-49-2DNAEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMMutat Res. 2005 Sep 4;577(1-2):131-4515904937Annu Rev Genet. 2004;38:445-7615568983Chem Res Toxicol. 2006 Sep;19(9):1215-2016978026EMBO J. 2006 Nov 29;25(23):5481-9117110932DNA Repair (Amst). 2007 Jun 1;6(6):841-5117374514Nature. 2007 May 31;447(7144):606-817507928Mutagenesis. 2007 Sep;22(5):343-5117630408Cell Res. 2008 Jan;18(1):27-4718166975Science. 2008 Jan 11;319(5860):202-618187655DNA Repair (Amst). 2008 Oct 1;7(10):1670-918707026Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18877-8219020090DNA Repair (Amst). 2009 Mar 1;8(3):309-1719061977Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Nucleic Acids Res. 2000 Jan 1;28(1):29210592250Mol Cell. 2000 Jun;5(6):1059-6510912000Nucleic Acids Res. 2001 Mar 15;29(6):1285-9211238994Mol Biotechnol. 2001 Oct;19(2):133-4011725483Oncogene. 2002 Nov 28;21(54):8232-912447686J Biol Chem. 2003 Feb 28;278(9):7294-912466278DNA Repair (Amst). 2004 May 4;3(5):483-9415084310J Biol Chem. 2004 Apr 30;279(18):18511-2014978042Biochemistry. 2004 Sep 14;43(36):11596-60415350146Nature. 2004 Sep 9;431(7005):217-2115322558PLoS Genet. 2009 Jul;5(7):e100057719629170J Biol Chem. 2009 Nov 13;284(46):31658-6319758983Mol Cell Biol. 2010 Jan;30(1):146-5919841062Mol Cell Biol. 2010 Jul;30(13):3206-1520421413Nucleic Acids Res. 2010 Jul;38(13):4285-9520338881DNA Repair (Amst). 2010 Sep 4;9(9):985-9320674513DNA Repair (Amst). 2004 Nov 2;3(11):1457-6815380101J Biol Chem. 1990 Mar 5;265(7):3916-221689309Nature. 1991 Jan 31;349(6308):431-41992344Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8502-68078911Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7429-349207108Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-59223305EMBO J. 1997 Oct 15;16(20):6314-229321410Nucleic Acids Res. 1998 Feb 15;26(4):1084-919461472J Biol Chem. 1998 Aug 14;273(33):21276-819694887DNA Repair (Amst). 2006 Jan 5;5(1):13-2216129663AnimalsCell LineDNAchemistryDNA DamageDNA GlycosylasesgeneticsphysiologyDNA RepairGuanineanalogs & derivativesmetabolismMiceModels, GeneticPlasmidschemistryTranscription, GeneticUracilmetabolism
2011329602011329602011101860ppublish21441539gkr16310.1093/nar/gkr163PMC3152326
214202462011120720171116
1879-355X8132011Nov01International journal of radiation oncology, biology, physicsInt. J. Radiat. Oncol. Biol. Phys.Functional polymorphisms of base excision repair genes XRCC1 and APEX1 predict risk of radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.e67-7310.1016/j.ijrobp.2010.11.079To explore whether functional single nucleotide polymorphisms (SNPs) of base-excision repair genes are predictors of radiation treatment-related pneumonitis (RP), we investigated associations between functional SNPs of ADPRT, APEX1, and XRCC1 and RP development.We genotyped SNPs of ADPRT (rs1136410 [V762A]), XRCC1 (rs1799782 [R194W], rs25489 [R280H], and rs25487 [Q399R]), and APEX1 (rs1130409 [D148E]) in 165 patients with non-small cell lung cancer (NSCLC) who received definitive chemoradiation therapy. Results were assessed by both Logistic and Cox regression models for RP risk. Kaplan-Meier curves were generated for the cumulative RP probability by the genotypes.We found that SNPs of XRCC1 Q399R and APEX1 D148E each had a significant effect on the development of Grade ≥2 RP (XRCC1: AA vs. GG, adjusted hazard ratio [HR] = 0.48, 95% confidence interval [CI], 0.24-0.97; APEX1: GG vs. TT, adjusted HR = 3.61, 95% CI, 1.64-7.93) in an allele-dose response manner (Trend tests: p = 0.040 and 0.001, respectively). The number of the combined protective XRCC1 A and APEX1 T alleles (from 0 to 4) also showed a significant trend of predicting RP risk (p = 0.001).SNPs of the base-excision repair genes may be biomarkers for susceptibility to RP. Larger prospective studies are needed to validate our findings.Copyright © 2011 Elsevier Inc. All rights reserved.YinMingMDepartment of Epidemiology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.LiaoZhongxingZLiuZhenshengZWangLi-ELEGomezDanielDKomakiRitsukoRWeiQingyiQengR01 CA131274CANCI NIH HHSUnited StatesR01ES011740ESNIEHS NIH HHSUnited StatesP30 CA016672CANCI NIH HHSUnited StatesR01 ES011740ESNIEHS NIH HHSUnited StatesCA016672CANCI NIH HHSUnited StatesR01 CA131274-03CANCI NIH HHSUnited StatesCA131274CANCI NIH HHSUnited StatesR01 ES011740-08ESNIEHS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20110321
United StatesInt J Radiat Oncol Biol Phys76036160360-30160DNA-Binding Proteins0Genetic Markers0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 2.4.2.30PARP1 protein, humanEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMLung Cancer. 1994 Mar;10 Suppl 1:S67-727916253Nat Rev Cancer. 2006 Sep;6(9):702-1316929324Cancer Res. 2004 Sep 1;64(17):6344-815342424Cancer Res. 1999 Jun 1;59(11):2557-6110363972DNA Repair (Amst). 2003 Sep 18;2(9):955-6912967653Anticancer Res. 2008 Jul-Aug;28(4C):2421-3218751429Radiother Oncol. 2009 Jun;91(3):427-3218937989Radiat Res. 2001 Nov;156(5 Pt 2):577-8311604075J Clin Oncol. 2009 Jul 10;27(20):3370-819380441Radiat Res. 2005 Jul;164(1):27-3515966762Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Jpn J Clin Oncol. 1999 Apr;29(4):192-710340042Int J Radiat Oncol Biol Phys. 2006 Dec 1;66(5):1399-40716997503Cancer Res. 1998 Feb 15;58(4):604-89485007Carcinogenesis. 2001 Jun;22(6):917-2211375899Carcinogenesis. 2001 Sep;22(9):1437-4511532866Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):5-2415963660Cancer Cell Int. 2007 Sep 24;7:1517892593Radiographics. 2004 Jul-Aug;24(4):985-97; discussion 99815256622Int J Clin Exp Med. 2009;2(1):26-3519436829Mol Cell Biol. 2002 Apr;22(8):2556-6311909950Int J Radiat Biol. 1990 Jun;57(6):1141-501971840Environ Mol Mutagen. 2003;41(1):37-4212552590Radiother Oncol. 2010 Oct;97(1):26-3220170971J Clin Oncol. 1995 Oct;13(10):2606-127595714Cancer. 2007 Aug 15;110(4):867-7517614107Int J Cancer. 2002 Jul 1;100(1):9-1312115580Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Radiat Res. 2008 Jul;170(1):49-5918582155Radiat Prot Dosimetry. 2006;122(1-4):124-717351270Nucleic Acids Res. 2007;35(22):7676-8717982170AdultAgedAged, 80 and overCarcinoma, Non-Small-Cell LunggeneticsradiotherapyDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGenetic MarkersGenetic Predisposition to DiseasegeneticsGenotypeHumansLogistic ModelsLung Neoplasmsdrug therapygeneticsradiotherapyMaleMiddle AgedPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesgeneticsPolymorphism, Single NucleotidegeneticsProportional Hazards ModelsRadiation PneumonitisgeneticsRadiotherapy DosageX-ray Repair Cross Complementing Protein 1
2010061620100924201011292011323602011323602011121300ppublish21420246S0360-3016(11)00055-110.1016/j.ijrobp.2010.11.079PMC3136565NIHMS269981
214143272011062120171116
0027-5107709-7102011May10Mutation researchMutat. Res.Association studies of OGG1, XRCC1, XRCC2 and XRCC3 polymorphisms with differentiated thyroid cancer.67-7210.1016/j.mrfmmm.2011.03.003The role of the DNA repair genes OGG1, XRCC1, XRCC2 and XRCC3 on differentiated thyroid cancer (DTC) susceptibility was examined in 881 individuals (402 DTC and 479 controls). DNA repair genes were proposed as candidate genes, since the current data indicate that exposure to ionizing radiation is the only established factor in the development of thyroid cancer, especially when it occurs in early stages of life. We have genotyped DNA repair genes involved in base excision repair (BER) (OGG1, Ser326Cys; XRCC1, Arg280His and Arg399Gln), and homologous recombination repair (HRR) (XRCC2, Arg188His and XRCC3, ISV-14G). Genotyping was carried out using the iPLEX (Sequenom) technique. Multivariate logistic regression analyses were performed in a case-control study design. From all the studied polymorphism, only a positive association (OR=1.58, 95% CI 1.05-2.46, P=0.027) was obtained for XRCC1 (Arg280His). No associations were observed for the other polymorphisms. No effects of the histopathological type of tumor were found when the DTC patients were stratified according to the type of tumor. It must be emphasized that this study include the greater patients group, among the few studies carried out until now determining the role of DNA repair genes in thyroid cancer susceptibility.Copyright © 2011 Elsevier B.V. All rights reserved.García-QuispesWilser-AndrésWAGrup de Mutagènesi, Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Spain.Pérez-MachadoGiselleGAkdiAbdelmounaimAPastorSusanaSGalofréPerePBiarnésFinaFCastellJoanJVelázquezAntoniaAMarcosRicardRengJournal ArticleResearch Support, Non-U.S. Gov't20110321
NetherlandsMutat Res04007630027-51070DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10X-ray repair cross complementing protein 30XRCC1 protein, human0XRCC2 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultCase-Control StudiesDNA GlycosylasesgeneticsDNA RepairDNA-Binding ProteinsgeneticsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, GeneticThyroid NeoplasmsgeneticsX-ray Repair Cross Complementing Protein 1
201011182011022820110302201131960201131960201162260ppublish21414327S0027-5107(11)00053-410.1016/j.mrfmmm.2011.03.003
213767412011062120171116
0027-5107709-7102011May10Mutation researchMutat. Res.8-Oxoguanine incision activity is impaired in lung tissues of NSCLC patients with the polymorphism of OGG1 and XRCC1 genes.21-3110.1016/j.mrfmmm.2011.02.009Decreased repair of oxidative DNA damage is a risk factor for developing certain human malignancies. We have previously found that the capacity of 8-oxo-7,8-dihydroguanine repair was lower in leukocytes of NSCLC patients than in controls. To explain these observations, we searched for mutations and polymorphisms in the OGG1 gene among 88 NSCLC patients and 79 controls. One patient exhibited a heterozygous mutation in exon 1, which resulted in Arg46Gln substitution. Normal lung and tumor tissue carrying this mutation showed markedly lower 8-oxoG incision activity than the mean for all patients. The predominant polymorphism of OGG1 was Ser326Cys. A significant difference was observed in the frequencies of the OGG1 variants between populations of NSCLC patients and controls. The frequency of the Cys326 allele and the number of Cys326Cys homozygotes was higher among patients than controls. In individuals with either Ser326Cys or Cys326Cys genotype 8-oxoG incision rate was lower than in those with both Ser326 alleles, either in lung or leukocytes. Moreover, 8-oxodG level was higher in lung tissue and leukocytes of patients carrying two Cys326 alleles and in leukocytes of patients with the Ser326Cys genotype. We also screened for polymorphisms of the XRCC1 gene. Only heterozygotes of the XRCC1 variants Arg194Trp, Arg280His and Arg399Gln were found among patients and controls, with the frequency of Arg280His being significantly higher among patients. NSCLC patients with Arg280His or Arg399Gln polymorphism revealed lower 8-oxoG incision activity in their lung tissues, but not in leukocytes. We can conclude that the OGG1 Ser326Cys polymorphisms may have an impact on the efficiency of 8-oxoG incision in humans and the XRCC1 His280 and Gln399 may influence the OGG1 activity in tissues exposed to chronic oxidative/inflammatory stress. Higher frequency of the OGG1 Cys326 allele among NSCLC patients may partially explain the impairment of the 8-oxoG repair observed in their leukocytes.Copyright © 2011 Elsevier B.V. All rights reserved.JanikJustynaJDepartment of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.SwobodaMajaMJanowskaBeataBCieślaJarosław MJMGackowskiDanielDKowalewskiJanuszJOlinskiRyszardRTudekBarbaraBSpeinaElżbietaEengJournal ArticleResearch Support, Non-U.S. Gov't20110303
NetherlandsMutat Res04007630027-51070DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, human5614-64-28-hydroxyguanine5Z93L87A1RGuanine88847-89-68-oxo-7-hydrodeoxyguanosineG9481N71RODeoxyguanosineIMAdultAgedAged, 80 and overCarcinoma, Non-Small-Cell LunggeneticsCase-Control StudiesDNA RepairgeneticsDNA-Binding ProteinsgeneticsDeoxyguanosineanalogs & derivativesgeneticsFemaleGuanineanalogs & derivativesmetabolismHumansLeukocytesmetabolismLungLung NeoplasmsgeneticsMaleMiddle AgedPolymorphism, GeneticX-ray Repair Cross Complementing Protein 1
2010102020110124201102182011386020113860201162260ppublish21376741S0027-5107(11)00032-710.1016/j.mrfmmm.2011.02.009
213550732011072120161125
1078-04321772011Apr01Clinical cancer research : an official journal of the American Association for Cancer ResearchClin. Cancer Res.Analysis of the oxidative damage repair genes NUDT1, OGG1, and MUTYH in patients from mismatch repair proficient HNPCC families (MSS-HNPCC).1701-1210.1158/1078-0432.CCR-10-2491Several studies have described molecular differences between microsatellite stable hereditary nonpolyposis colorectal cancer (MSS-HNPCC) and microsatellite unstable Lynch syndrome tumors (MSI-HNPCC). These differences highlight the possibility that other instability forms could explain cancer susceptibility in this group of families. The base excision repair (BER) pathway is the major DNA repair pathway for oxidative DNA damage. A defect in this pathway can result in DNA transversion mutations and a subsequent increased cancer risk. Mutations in MUTYH have been associated with increased colorectal cancer (CRC) risk while no association has been described for OGG1 or NUDT1.We performed mutational screening of the three genes involved in defense against oxidative DNA damage in a set of 42 MSS-HNPCC families.Eight rare variants and 5 frequent variants were found in MSS-HNPCC patients. All variants were previously described by other authors except variant c.285C>T in OGG1. Segregation studies were done and in silico programs were used to estimate the level of amino acid conservation, protein damage prediction, and possible splicing alterations. Variants OGG1 c.137G>A; MUTYH c.1187G>A were detected in Amsterdam I families and cosegregate with cancer. Analysis of OGG1 c.137G>A transcripts showed an inactivation of the splicing donor of exon 1.Two rare variants (OGG1 c.137G>A; MUTYH c.1187G>A) and one common polymorphism (NUDT1 c.426C>T) were associated with CRC risk. We show that the BER pathway can play a significant role in a number of MSS-HNPCC colorectal cancers. More studies could be of interest in order to gain further understanding of yet unexplained CRC susceptibility cases.GarrePilarPLaboratorio de Oncología Molecular, Hospital Clinico San Carlos, Madrid, Spain.BriceñoVerónicaVXicolaRosa MRMDoyleBrian JBJde la HoyaMiguelMSanzJuliánJLlovetPatriciaPPescadorPaulaPPuenteJavierJDíaz-RubioEduardoELlorXavierXCaldésTrinidadTengJournal ArticleResearch Support, Non-U.S. Gov't20110225
United StatesClin Cancer Res95025001078-0432EC 3.1.3.2Phosphoric Monoester HydrolasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.1.558-oxodGTPaseEC 6.5.1.-DNA Repair EnzymesIMCase-Control StudiesColorectal Neoplasms, Hereditary NonpolyposisenzymologygeneticsmortalityDNA DamageDNA GlycosylasesgeneticsDNA Mismatch RepairDNA Repair EnzymesgeneticsDisease-Free SurvivalFemaleGene DosageGene FrequencyGenetic Association StudiesGenotypeHumansMaleMiddle AgedMutation, MissenseOxidation-ReductionPhosphoric Monoester HydrolasesgeneticsPoint MutationRestriction MappingSequence Analysis, DNA
2011316020113160201172260ppublish213550731078-0432.CCR-10-249110.1158/1078-0432.CCR-10-2491
213220942011052720110215
1099-04612512011 Jan-FebJournal of biochemical and molecular toxicologyJ. Biochem. Mol. Toxicol.Direct visualization of repair of oxidative damage by OGG1 in the nuclei of live cells.1-710.1002/jbt.20346Oxidative DNA damage caused by intracellular reactive oxygen species (ROS) is widely considered to be important in the pathology of a range of human diseases including cancer as well as in the aging process. A frequently occurring mutagenic base lesion produced by ROS is 8-oxo deoxyguanine (8-oxo dG) and the major enzyme for repair of 8-oxo dG is 8-oxoguanine-DNA glycosylase 1 (OGG1). There is now substantial evidence from bulk biochemical studies that a common human polymorphic variant of OGG1 (Ser326Cys) is repair deficient, and this has been linked to individual risk of pathologies related to oxidative stress. In the current study, we have used the technique of multiphoton microscopy to induce highly localized oxidative DNA damage in discrete regions of the nucleus of live cells. Cells transfected with GFP-tagged OGG1 proteins demonstrated rapid (<2 min) accumulation of OGG1 at sites of laser-induced damage as indicated by accumulation of GFP-fluorescence. This was followed by repair as evidenced by loss of the localized fluorescence over time. Quantification of the rate of repair confirmed that the Cys326 variant of OGG1 is repair deficient and that the initial repair rate of damage by Cys326 OGG1 was 3 to 4 fold slower than that observed for Ser326 OGG1. These values are in good agreement with kinetic data comparing the Ser326 and Cys326 proteins obtained by biochemical studies.Copyright © 2010 Wiley Periodicals, Inc.ZielinskaAgnieszkaASchool of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.DaviesOwain TOTMeldrumRosalind ARAHodgesNikolas JNJengJournal Article20101115
United StatesJ Biochem Mol Toxicol97172311095-66700Reactive Oxygen SpeciesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMAnimalsCell LineCell NucleusgeneticsmetabolismDNA DamagegeneticsDNA GlycosylasesgeneticsmetabolismDNA RepairgeneticsFibroblastsKineticsMiceMice, KnockoutMicroscopy, Fluorescence, MultiphotonmethodsMutagenesisgeneticsOxidative StressgeneticsPolymorphism, GeneticgeneticsReactive Oxygen Speciesmetabolism
200910262010011220100206201121660201121660201152860ppublish2132209410.1002/jbt.20346
212543232013050120131121
1522-727827102012OctEnvironmental toxicologyEnviron. Toxicol.Oxidative damage and OGG1 expression induced by a combined effect of titanium dioxide nanoparticles and lead acetate in human hepatocytes.590-710.1002/tox.20682Titanium dioxide (TiO(2)) is a widely used nanomaterial that can cause biological damage through oxidative stress. At low concentrations, TiO(2) can interact with lead acetate (PbAc) to produce different toxic responses, compared with TiO(2) or PbAc alone. In this study, we utilized the following as indicators of toxic responses in human embryo hepatocytes (L02): reactive oxygen species (ROS), reduced glutathione (GSH), superoxide dismutase (SOD), and the DNA adducts 8-hydroxydeoxyguanosine (8-OHdG) and 8-oxoguanine DNA glycosylase homolog 1 (OGG1). These were used to evaluate the oxidative stress of TiO(2) (at 0.001, 0.01, 0.1, 1, and 10 μg mL(-1)) mixed with PbAc (1 μg mL(-1)) on L02 cells without photoactivation. Compared with the negative control (1‰ dimethyl sulfoxide), TiO(2) mixed with PbAc induced increased release of ROS (at 0.001, 0.01, 0.1, 1, 10 μg mL(-1) TiO(2)), intracellular SOD activity (at 0.1 and 0.01 μg mL(-1) TiO(2)), GSH levels (at 0.01-1 μg mL(-1) TiO(2)), 8-OHdG levels (at 1 and 10 μg mL(-1) TiO(2)), OGG1 expression (at 0.001-1 μg mL(-1) TiO(2)), and cytotoxicity (at 0.1, 1, and 10 μg mL(-1) TiO(2)) in L02 cells. There were no significant changes in ROS, GSH, SOD, 8-OHdG, or OGG1 levels when L02 cells were treated with TiO(2) alone or PbAc alone. These findings indicate that TiO(2) and PbAc in combination induce cytotoxicity and oxidative stress in L02 cells in the absence of photoactivation.Copyright © 2011 Wiley Periodicals, Inc.DuHairongHMOE Key Lab of Environment and Health, Institute of Environmental Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.ZhuXiaolingXFanChuangangCXuSongSWangYoujieYZhouYikaiYengJournal ArticleResearch Support, Non-U.S. Gov't20110120
United StatesEnviron Toxicol1008853571520-40810Organometallic Compounds0Reactive Oxygen Species15FIX9V2JPtitanium dioxide88847-89-68-oxo-7-hydrodeoxyguanosineD1JT611TNETitaniumEC 1.15.1.1Superoxide DismutaseEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanG9481N71RODeoxyguanosineGAN16C9B8OGlutathioneRX077P88RYlead acetateIMCell LineCell SurvivalDNA GlycosylasesmetabolismDeoxyguanosineanalogs & derivativesanalysisGlutathionemetabolismHepatocytesdrug effectsmetabolismHumansNanoparticlestoxicityOrganometallic CompoundstoxicityOxidative Stressdrug effectsReactive Oxygen SpeciesmetabolismSuperoxide DismutasemetabolismTitaniumtoxicity
20100706201010272010110420111226020111226020135260ppublish2125432310.1002/tox.20682
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1437-160X3252012MayRheumatology internationalRheumatol. Int.Association of the C-285T and A5954G polymorphisms in the DNA repair gene OGG1 with the susceptibility of rheumatoid arthritis.1165-910.1007/s00296-010-1738-1Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. Previous study indicated that DNA repair system was involved in the pathology of RA. In this study, we investigated the association of two 8-oxoguanine glycosylase 1 (OGG1) gene polymorphisms (rs159153 and rs3219008) with the susceptibility to RA in 384 Taiwanese individuals (192 patients with RA and 192 controls). Our data showed that statistically significant difference in genotype frequency distributions was found at rs3219008 SNP between patients with RA and control groups (P = 5.6E-0.5). Our data also indicated that individuals with the AG genotype at rs3219008 SNP may have a higher risk of developing RA. We did not observe any statistically significant association of OGG1 haplotype frequencies (rs159153 and rs3219008) with RA progression. The study suggested that OGG1 polymorphisms (rs159153 and rs3219008) are associated with RA progression and that these may be used as molecular markers of RA.ChenShih-YinSYGenetic Center, Department of Medical Research, China Medical University Hospital, Graduate Institute of Chinese Medical Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan.WanLeiLHuangChung-MingCMHuangYu-ChuenYCSheuJim Jinn-ChyuanJJLinYing-JuYJLiuShih-PingSPLanYu-ChingYCLaiChih-HoCHLinCheng-WenCWTsaiChang-HaiCHTsaiFuu-JenFJengJournal ArticleResearch Support, Non-U.S. Gov't20110121
GermanyRheumatol Int82068850172-81720Genetic MarkersEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMJ Hum Genet. 2001;46(8):471-711501945Arthritis Rheum. 1991 Jul;34(7):822-302059230J Clin Invest. 2008 Jul;118(7):2516-2518521188FASEB J. 2003 Jul;17(10):1195-21412832285N Engl J Med. 1990 May 3;322(18):1277-892271017Nat Genet. 2002 Dec;32(4):650-412426569FASEB J. 2005 Feb;19(2):290-215677345J Rheumatol. 1995 Aug;22(8):1450-47473464Clin Exp Rheumatol. 2008 Jul-Aug;26(4):632-718799095J Exp Med. 2009 Jun 8;206(6):1435-4919451263Hum Genet. 2003 Jan;112(1):34-4112483297Arthritis Rheum. 1997 Feb;40(2):341-519041946Bioinformatics. 2005 Jan 15;21(2):263-515297300Nat Genet. 2003 Aug;34(4):395-40212833157J Rheumatol. 2008 Nov;35(11):2113-819004052J Rheumatol. 1990 Feb;17(2):127-332181124Hum Genet. 2007 Apr;121(2):233-4217203305Trends Mol Med. 2003 Oct;9(10):405-714557050Arthritis Rheum. 1988 Mar;31(3):315-243358796DNA Cell Biol. 2009 Nov;28(11):579-8819630534Cell. 1996 May 3;85(3):307-108616886Springer Semin Immunopathol. 1998;20(1-2):5-229836366Clin Exp Rheumatol. 2004 Mar-Apr;22(2):219-2215083890Am J Hum Genet. 1995 Jul;57(1):150-97611283Mutat Res. 2005 Jun 3;573(1-2):136-5115829243Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):811-516614128Arthritis, RheumatoidenzymologygeneticsmortalityCase-Control StudiesChi-Square DistributionDNA GlycosylasesgeneticsDNA RepairDisease ProgressionGene FrequencyGenetic MarkersGenetic Predisposition to DiseaseHaplotypesHumansKaplan-Meier EstimateLogistic ModelsOdds RatioPhenotypePolymorphism, Single NucleotideRisk AssessmentRisk FactorsTaiwan
2010073020101230201112260201112260201282260ppublish2125373710.1007/s00296-010-1738-1
211982602011100620171116
2476-762X1152010Asian Pacific journal of cancer prevention : APJCPAsian Pac. J. Cancer Prev.APEX1 Asp148Glu gene polymorphism is a risk factor for lung cancer in relation to smoking in Japanese.1181-6DNA repair enzymes play an important role in the development of various kinds of cancer. We here analyzed associations of XPD Lys751Gln, APEX1 Asp148Glu, XRCC1 Arg399Gln, and XRCC3 Thr241Met gene polymorphisms in DNA repair pathways in relation to the risk of lung cancer using PCR-RFLP. The study involved 104 lung cancer patients and 120 non-cancer controls divided into non-smokers and smokers. We found a statistically significant interaction between APEX1 Asp148Glu and the risk for lung cancer (adjusted OR 2.78, 95% CI 1.58-4.90, p=0.0004), of both adenocarcinoma (adjusted OR 2.24, 95%CI 1.18-4.25, p=0.014) and squamous cell carcinoma (adjusted OR 4.75, 95%CI 1.79-12.6, p=0.002) types. XRCC1 Arg399Gln showed a borderline significant association with adenocarcinoma (adjusted OR 1.89, 95%CI 1.00-3.57, p=0.051). The combined effect of smoking and presence of the APEX1 Asp148Glu demonstrated a significant association with risk of lung cancer (adjusted OR 3.61, 95% CI 1.74-7.50, p=0.001). The XPD Lys751Gln and XRCC3 Thr241Met genotypes displayed no statistically significant risk. Our findings suggest that the APEX1 Asp148Glu is associated with increased risk for primary lung cancer in Japanese individuals partaking in smoking.OsawaKayoKFaculty of Health Sciences, Kobe University Graduate School of Health Sciences, Kobe, Japan. osawak@kobe-u.ac.jpMiyaishiAikoAUchinoKazuyaKOsawaYasunoriYInoueNatsukoNNakaraiChiakiCTsutouAkimitsuAKidoYoshiakiYYoshimuraMasahiroMTsubotaNoriakiNTakahashiJuroJengJournal Article
ThailandAsian Pac J Cancer Prev1011306251513-73680DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10X-ray repair cross complementing protein 30XRCC1 protein, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 5.99.-ERCC2 protein, humanAdenocarcinoma of lungIMAdenocarcinomageneticsAgedAged, 80 and overCarcinoma, Squamous CellgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGenetic Predisposition to DiseasegeneticsGenotypeHumansJapanLung NeoplasmsgeneticsMaleMiddle AgedPolymorphism, Single NucleotideRisk FactorsSmokinggeneticsX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
2011156020111560201110760ppublish21198260
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1879-12988272011FebChemosphereChemosphereDNA repair gene polymorphisms at XRCC1, XRCC3, XPD, and OGG1 loci in Maharashtrian population of central India.941-610.1016/j.chemosphere.2010.10.100Reduction in DNA repair capacity is associated with increased rates of birth defects, cancer, and accelerated ageing. Genetic polymorphisms in DNA repair genes might influence the repair activities of the enzymes predisposing individuals to cancer risk. Owing to the presence of these genetic variants, inter-individual and ethnic differences in DNA repair capacity have been observed in various populations. India harbors enormous genetic, cultural and linguistic diversity. The present study was undertaken to determine the allele and genotype frequencies of four non-synonymous SNPs, XRCC1 Arg399Gln (C>T, rs25487), XRCC3 Thr241Met (G>A, rs861539), XPD Lys751Gln (T>G, rs13181), and OGG1 Ser326Cys (C>G, rs1052133) in the Maharashtrian population, residing in the Vidarbha region of central India and to compare them with HapMap and other Indian populations. The variant alleles of these polymorphisms have been found to be positively associated with different forms of cancer in several genetic epidemiological studies. The basic prevalence of these polymorphisms in the general population must be known to evaluate their significance in risk assessment in cancer and other phenotypes. About 215 healthy and unrelated individuals from the Maharashtrian population were genotyped for each of these four polymorphisms using PCR-RFLP. The allele and genotype frequency distribution at the four DNA repair gene loci among Maharashtrians revealed a characteristic pattern. To the best of our knowledge, this is the first report of these DNA repair gene polymorphisms in a central Indian population.Copyright © 2010 Elsevier Ltd. All rights reserved.PramanikSreemantaSNational Environmental Engineering Research Institute, Nehru Marg, Nagpur, India. sr_pramanik@neeri.res.inDeviSaravanaSChowdharySanghamitraSSurendranSubin TSTKrishnamurthiKannanKChakrabartiTapanTengJournal ArticleResearch Support, Non-U.S. Gov't20101222
EnglandChemosphere03206570045-65350DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10X-ray repair cross complementing protein 30XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanIMAdultDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-Binding ProteinsgeneticsmetabolismEthnic GroupsgeneticsGene FrequencyGenetic Predisposition to DiseaseHumansIndiaMiddle AgedPolymorphism, Single NucleotideX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D ProteingeneticsmetabolismYoung Adult
20100709201010272010102920101225602010122560201122560ppublish21183201S0045-6535(10)01367-610.1016/j.chemosphere.2010.10.100
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1573-49783842011AprMolecular biology reportsMol. Biol. Rep.The impact of OGG1, MTH1 and MnSOD gene polymorphisms on 8-hydroxy-2'-deoxyguanosine and cellular superoxide dismutase activity in myocardial ischemia-reperfusion.2427-3510.1007/s11033-010-0378-6Ischemia-reperfusion (I/R) injury, by inducing oxidative DNA damage, is one of the leading causes of increased patient morbidity and mortality in coronary artery by-pass grafting (CABG) surgery. 8-Hydroxyguanine (8-OHG) is an important oxidative base lesion. The 8-oxoguanine glycosylase (hOGG1) and hMTH1, which have several polymorphisms, remove 8-OHdG from the nucleotide pool. We investigated whether there are any correlations the biomarkers of oxidative stress (superoxide dismutase; SOD and 8-OHdG in serum) with genotype for two DNA repair genes (OGG1 and MTH1) and an antioxidant enzyme gene (manganese superoxide dismutase; MnSOD). Therefore, we measured DNA damage (8-hydroxy-2-deoxyguanosine; 8-OHdG) and endogenous antioxidant activity (SOD) at five different time points (T1, before anesthesia; T2, after anesthesia; T3, after ischemia; T4, after reperfusion and T5, after surgery). and also, MnSOD and MutT homolog 1 (MTH1) genes polymorphisms were genotyped by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) in patients undergoing coronary artery by-pass grafting (CABG) surgery. No statistically significant differences were detected in the levels of 8-OHdG and SOD in serum in terms of OGG1 Ser326Cys, MTH1 Val83Met and MnSOD Ala16Val genetic polymorphisms. Our results suggest that OGG1, MTH1 and MnSOD gene polymorphisms are not genetic risk factors for I/R injury.KarahalilBensuBToxicology Department, Faculty of Pharmacy, Ataturk Training and Research Hospital, Gazi University, Ankara, 06330, Turkey. bensuka@gmail.comKesimciElvinEEmerceEsraEGumusTulinTKanbakOrhanOengJournal ArticleResearch Support, Non-U.S. Gov't20101121
NetherlandsMol Biol Rep04032340301-485188847-89-68-oxo-7-hydrodeoxyguanosineEC 1.15.1.1Superoxide DismutaseEC 3.1.3.2Phosphoric Monoester HydrolasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.1.558-oxodGTPaseEC 6.5.1.-DNA Repair EnzymesG9481N71RODeoxyguanosineIMAnesthesiology. 2003 Oct;99(4):826-3314508313Cancer Epidemiol Biomarkers Prev. 2004 Oct;13(10):1680-115466987J Artif Organs. 2007;10(2):92-517574511Cancer Sci. 2006 Aug;97(8):724-816800823Anesth Analg. 2005 Nov;101(5):1275-8716243980J Natl Cancer Inst. 2003 Sep 3;95(17):1312-912953085J Natl Cancer Inst. 2005 Mar 2;97(5):384-9515741575Br J Pharmacol. 2008 Jan;153(1):21-3317952108EMBO Rep. 2003 May;4(5):479-8312717453Arh Hig Rada Toksikol. 2008 Dec;59(4):241-5019064361In Vivo. 2008 Jan-Feb;22(1):147-5118396798Arch Toxicol. 2005 Jul;79(7):377-8015834708Mutat Res. 2007 Jul 28;631(2):101-1017531525Toxicol Ind Health. 2010 Mar;26(2):67-7920056743Nature. 1991 Jan 31;349(6308):431-41992344Endocr J. 2004 Oct;51(5):493-815516784Am J Cardiol. 2005 Feb 15;95(4):514-715695143DNA Repair (Amst). 2003 Feb 3;2(2):211-2912531391Cancer Res. 1999 Feb 1;59(3):602-69973207Cancer Res. 2009 Apr 15;69(8):3642-919351836Anticancer Res. 2006 Nov-Dec;26(6C):4955-817214369J Mol Cell Cardiol. 2000 Jun;32(6):1053-910888257Curr Med Chem. 2007;14(14):1539-4917584062Antioxid Redox Signal. 2010 Sep 15;13(6):877-91820095865Cardiovasc Res. 2007 Jun 1;74(3):343-5517306241Eur J Cardiothorac Surg. 2005 Apr;27(4):611-615784359Cancer Res. 2002 Apr 15;62(8):2253-711956079BMC Med Genet. 2008 Apr 21;9:3018423055Crit Rev Clin Lab Sci. 2004;41(5-6):585-60715603512AdultAgedCoronary Artery Bypassadverse effectsDNA DamagegeneticsDNA GlycosylasesgeneticsDNA Repair EnzymesgeneticsDeoxyguanosineanalogs & derivativesmetabolismFemaleGenetic Predisposition to DiseasegeneticsGenotypeHumansMaleMiddle AgedMyocardial Reperfusion InjuryetiologymetabolismOxidative StressphysiologyPhosphoric Monoester HydrolasesgeneticsPolymorphism, Restriction Fragment LengthStatistics, NonparametricSuperoxide Dismutasegeneticsmetabolism
201004082010110820101125602010112660201172760ppublish2110414910.1007/s11033-010-0378-6
210629702011012720130603
1460-21803212011JanCarcinogenesisCarcinogenesisSpontaneous mutagenesis in Csb(m/m)Ogg1⁻(/)⁻ mice is attenuated by dietary resveratrol.80-510.1093/carcin/bgq196Oxidative DNA modifications such as 7,8-dihydro-8-oxoguanine (8-oxoG) are generated endogenously in apparently all living cells. The defect of the repair of 8-oxoG in Csb(m/m)Ogg1⁻(/)⁻ mice results in elevated basal levels of these lesions and increased frequencies of spontaneous mutations, which initiate tumorigenesis in the liver if cell proliferation is stimulated. Here, we describe that the phytoalexin resveratrol, applied either for 7 days per gavage (100 mg/kg body wt) or for 3-9 months in the diet (0.04% ad libitum), reduces the endogenous oxidative DNA base damage in the livers of the Csb(m/m)Ogg1⁻(/)⁻ mice by 20-30% (P < 0.01). A small but consistent effect is also observed in the wild-type animals. The spontaneous mutation frequencies determined in the lacI gene of BigBlue® Csb(m/m)Ogg1⁻(/)⁻ mice are concomitantly reduced by resveratrol to similar extents. Mechanistically, the protection is caused by an induction of the antioxidant defense system since (i) hepatocytes isolated from all resveratrol-treated animals were less susceptible to the generation of single-strand breaks and to cell killing by H₂O₂, (ii) messenger RNA levels of superoxide dismutases 1 and 2 (SOD1 and SOD2) heme oxygenase-1 and glutathione peroxidase were significantly upregulated after the short-term treatment and (iii) mutations primarily ascribed to the oxidative base modification 8-oxoG (G:C to T:A transversions) were more strongly suppressed than G:C to A:T transitions ascribed to spontaneous deamination. The results thus demonstrate that spontaneous somatic mutation rates resulting from endogenous oxidative DNA damage can be reduced by application of an exogenous agent.FusserMarkusMInstitute of Pharmacy and Biochemistry, University of Mainz, Germany.NesseGaute JGJKhobtaAndriyAXiaNingNLiHuigeHKlunglandArneAEpeBerndBengJournal ArticleResearch Support, Non-U.S. Gov't20101109
EnglandCarcinogenesis80080550143-33340Antimutagenic Agents0StilbenesQ369O8926LresveratrolIMAnimalsAntimutagenic Agentsadministration & dosageDNA Damagedrug effectsDietGene Expressiondrug effectsLiverdrug effectsMiceMice, TransgenicMutagenesisdrug effectsOxidative Stressdrug effectsphysiologyReverse Transcriptase Polymerase Chain ReactionStilbenesadministration & dosage
20101111602010111160201112960ppublish21062970bgq19610.1093/carcin/bgq196
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1873-45965092011May01Free radical biology & medicineFree Radic. Biol. Med.The DNA glycosylase Ogg1 defends against oxidant-induced mtDNA damage and apoptosis in pulmonary artery endothelial cells.1107-1310.1016/j.freeradbiomed.2010.10.692Emerging evidence suggests that mitochondrial (mt) DNA damage may be a trigger for apoptosis in oxidant-challenged pulmonary artery endothelial cells (PAECs). Understanding the rate-limiting determinants of mtDNA repair may point to new targets for intervention in acute lung injury. The base excision repair (BER) pathway is the only pathway for oxidative damage repair in mtDNA. One of the key BER enzymes is Ogg1, which excises the base oxidation product 8-oxoguanine. Previously we demonstrated that overexpression of mitochondrially targeted Ogg1 in PAECs attenuated apoptosis induced by xanthine oxidase (XO) treatment. To test the idea that Ogg1 is a potentially rate-limiting BER determinant protecting cells from oxidant-mediated death, PAECs transfected with siRNA to Ogg1 were challenged with XO and the extent of mitochondrial and nuclear DNA damage was determined along with indices of apoptosis. Transfected cells demonstrated significantly reduced Ogg1 activity, which was accompanied by delayed repair of XO-induced mtDNA damage and linked to increased XO-mediated apoptosis. The nuclear genome was undamaged by XO in either control PAECs or cells depleted of Ogg1. These observations suggest that Ogg1 plays a critical and possibly rate-limiting role in defending PAECs from oxidant-induced apoptosis by limiting the persistence of oxidative damage in the mitochondrial genome.Copyright © 2010 Elsevier Inc. All rights reserved.RuchkoMykhaylo VMVDepartment of Pharmacology and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, AL 36688, USA.GorodnyaOlena MOMZuletaAndresAPastukhViktor MVMGillespieMark NMNengR01 HL073244-05HLNHLBI NIH HHSUnited StatesP01 HL66299HLNHLBI NIH HHSUnited StatesP01 HL066299HLNHLBI NIH HHSUnited StatesR01 HL073244HLNHLBI NIH HHSUnited StatesP01 HL066299-050003HLNHLBI NIH HHSUnited StatesR01 HL058234HLNHLBI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20101020
United StatesFree Radic Biol Med87091590891-58490DNA, Mitochondrial0Oxidants0RNA, Small Interfering2TN51YD919Hypoxanthine5614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 1.17.3.2Xanthine OxidaseEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-OGG1 protein, ratIMCirc Res. 2000 May 12;86(9):960-610807868Mol Biol Rep. 2011 Jan;38(1):445-5120364408Circ Res. 2001 Mar 16;88(5):529-3511249877FASEB J. 2001 May;15(7):1267-911344109Am J Physiol Lung Cell Mol Physiol. 2001 Jun;280(6):L1300-811350811Cancer Res. 2001 Jul 15;61(14):5378-8111454679Prog Nucleic Acid Res Mol Biol. 2001;68:273-8411554303Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L205-1012060578Glia. 2003 Jun;42(4):370-812730957News Physiol Sci. 2003 Jun;18:89-9412750442Am J Physiol Lung Cell Mol Physiol. 2003 Nov;285(5):L1018-2512909582Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-99012815Am J Hum Genet. 1999 May;64(5):1276-8110205257Carcinogenesis. 1999 Sep;20(9):1863-810469635Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L530-515563690Diabetes. 2006 Apr;55(4):1022-816567524BMC Cancer. 2006;6:23517018150Glia. 2007 Nov 1;55(14):1416-2517674369Am J Physiol Cell Physiol. 2008 Feb;294(2):C413-2218077603Cell Mol Life Sci. 2008 May;65(10):1544-6518259689Cancer Lett. 2008 Jul 18;266(1):60-7218374480Adv Exp Med Biol. 2005;570:125-7318727500Carcinogenesis. 2009 Mar;30(3):500-519147860Cell Mol Life Sci. 2009 Mar;66(6):981-9319153658Free Radic Biol Med. 2009 Sep 15;47(6):750-919524665Gen Physiol Biophys. 2010 Jun;29(2):160-7420577028Free Radic Biol Med. 2000 Apr 15;28(8):1161-7410889445AnimalsApoptosisCell Culture TechniquesCytoprotectiongeneticsDNA DamageDNA Glycosylasesantagonists & inhibitorsgeneticsmetabolismDNA RepairDNA, MitochondrialmetabolismEndothelial CellscytologyenzymologyGene ExpressionGene SilencingGuanineanalogs & derivativesmetabolismHypoxanthineadverse effectsmetabolismMaleMitochondriageneticsmetabolismOxidantsadverse effectsmetabolismOxidative StressPulmonary ArterycytologyenzymologyRNA, Small InterferingpharmacologyRatsRats, Sprague-DawleyXanthine Oxidaseadverse effectsmetabolism
2010080320100917201010092010102660201010266020118960ppublish20969951S0891-5849(10)01315-810.1016/j.freeradbiomed.2010.10.692PMC3033972NIHMS247569
209516532012010320180425
1568-78561012011Jan02DNA repairDNA Repair (Amst.)Factors that influence telomeric oxidative base damage and repair by DNA glycosylase OGG1.34-4410.1016/j.dnarep.2010.09.008Telomeres are nucleoprotein complexes at the ends of linear chromosomes in eukaryotes, and are essential in preventing chromosome termini from being recognized as broken DNA ends. Telomere shortening has been linked to cellular senescence and human aging, with oxidative stress as a major contributing factor. 7,8-Dihydro-8-oxogaunine (8-oxodG) is one of the most abundant oxidative guanine lesions, and 8-oxoguanine DNA glycosylase (OGG1) is involved in its removal. In this study, we examined if telomeric DNA is particularly susceptible to oxidative base damage and if telomere-specific factors affect the incision of oxidized guanines by OGG1. We demonstrated that telomeric TTAGGG repeats were more prone to oxidative base damage and repaired less efficiently than non-telomeric TG repeats in vivo. We also showed that the 8-oxodG-incision activity of OGG1 is similar in telomeric and non-telomeric double-stranded substrates. In addition, telomere repeat binding factors TRF1 and TRF2 do not impair OGG1 incision activity. Yet, 8-oxodG in some telomere structures (e.g., fork-opening, 3'-overhang, and D-loop) were less effectively excised by OGG1, depending upon its position in these substrates. Collectively, our data indicate that the sequence context of telomere repeats and certain telomere configurations may contribute to telomere vulnerability to oxidative DNA damage processing.Published by Elsevier B.V.RheeDavid BDBLaboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States.GhoshAvikALuJianJBohrVilhelm AVALiuYieYengZIA AG000744-03NULLIntramural NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., IntramuralResearch Support, Non-U.S. Gov't20101016
NetherlandsDNA Repair (Amst)1011391381568-78560DNA, Single-Stranded0Recombinant Proteins0Telomeric Repeat Binding Protein 10Telomeric Repeat Binding Protein 288847-89-68-oxo-7-hydrodeoxyguanosine9007-49-2DNAEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanG9481N71RODeoxyguanosineIMNature. 1996 Aug 22;382(6593):731-58751447Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):258-627816828J Biol Chem. 1999 Jan 8;274(2):962-719873038Ann N Y Acad Sci. 1998 Nov 20;854:318-279928440Cell. 1999 May 14;97(4):503-1410338214FEBS Lett. 1999 Jun 25;453(3):365-810405177EMBO J. 1999 Oct 15;18(20):5735-4410523316EMBO Rep. 2005 Jan;6(1):39-4515608617Mol Cell Biol. 2005 Feb;25(3):1070-8015657433Nucleic Acids Res. 2005;33(2):497-51015659581Nucleic Acids Res. 2005;33(4):1230-915731343Nucleic Acids Res. 2005;33(15):4849-5616129732Biophys Chem. 2005 Oct 22;118(1):31-4116039038Genes Dev. 2005 Sep 15;19(18):2100-1016166375Biochimie. 2005 Dec;87(12):1079-8815979229Chem Res Toxicol. 2006 Apr;19(4):491-50516608160Nature. 2007 Feb 1;445(7127):506-1017237768DNA Repair (Amst). 2007 Apr 1;6(4):454-6017123872DNA Repair (Amst). 2007 Apr 1;6(4):481-817127104Mech Ageing Dev. 2007 Apr;128(4):340-517395247Genes Dev. 2008 Jan 15;22(2):125-4018198332Biochemistry. 2008 Aug 26;47(34):8970-618672903Cell Mol Life Sci. 2009 Mar;66(6):981-9319153658Annu Rev Genet. 2008;42:301-3418680434Genes Cells. 2008 Oct;13(10):1045-5918761675Cell. 2009 Jul 10;138(1):90-10319596237Mol Cell Biol. 2009 Aug;29(16):4441-5419506022Nature. 2009 Aug 13;460(7257):914-819633651EMBO J. 2009 Aug 19;28(16):2309-2219629031J Biol Chem. 2009 Nov 6;284(45):31074-8419734539EMBO J. 2010 Jan 20;29(2):398-40919942858Nature. 2010 Mar 25;464(7288):520-820336134PLoS Genet. 2010 May;6(5):e100095120485567Cell. 2010 Jul 23;142(2):230-4220655466Biochemistry. 1999 Dec 21;38(51):16733-910606504J Biol Chem. 2000 Feb 18;275(7):4956-6410671534Mutat Res. 2000 Jun 30;451(1-2):39-5110915864Nature. 2001 Jul 19;412(6844):318-2011460159EMBO J. 2001 Oct 1;20(19):5532-4011574485J Am Chem Soc. 2002 Feb 27;124(8):1625-3111853436Free Radic Biol Med. 2002 Apr 15;32(8):678-8211937293Photochem Photobiol. 2002 Nov;76(5):467-7212462639Nucleic Acids Res. 2003 Apr 1;31(7):1897-90312655006Mol Cell. 2003 Dec;12(6):1489-9814690602Exp Cell Res. 2004 Aug 1;298(1):17-2715242758Ann N Y Acad Sci. 2004 Jun;1019:278-8415247029Genes Dev. 2004 Aug 1;18(15):1781-9915289453Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4690-42052552Nucleic Acids Res. 1998 Apr 1;26(7):1731-409512546AnimalsCells, CulturedDNAchemistrymetabolismDNA DamageDNA GlycosylasesgeneticsmetabolismDNA RepairDNA, Single-StrandedmetabolismDeoxyguanosineanalogs & derivativesmetabolismHumansMiceOxidative StressRecombinant ProteinsgeneticsmetabolismTelomerechemistrymetabolismTelomeric Repeat Binding Protein 1metabolismTelomeric Repeat Binding Protein 2metabolismTrinucleotide Repeats
2010070620100908201009172010101960201010196020121460ppublish20951653S1568-7864(10)00313-710.1016/j.dnarep.2010.09.008PMC3010491NIHMS247224
208529422011052320171116
1573-49783832011MarMolecular biology reportsMol. Biol. Rep.Base excision repair genes XRCC1 and APEX1 and the risk for prostate cancer.1585-9110.1007/s11033-010-0267-zProstate cancer is the second cause of cancer death in Brazilian men. One of the relevant phenomena to the inherited susceptibility is the presence of allelic variants in genes involved with the DNA repair pathway. The aim of this study was to analyze the frequencies of prevalent, heterozygous and rare genotypes of the base excision repair genes APEX1 and XRCC1 in a case-control study and relate the genotypes with tumoral aggressiveness. DNA from peripheral blood of 172 patients and 172 controls were analyzed by RFLP-PCR method. The polymorphisms were also evaluated in relation to clinical and pathological parameters. The OR (Odds Ratio) and confidence interval (CI = 95%) were used in the association study and the Chi-square and ANOVA tests for the evaluation of histopathological parameters. The rare genotypes frequencies of the gene APEX1 increased the risk for the development of prostate cancer (OR = 1.68 95% CI 1.10-2.58). No association was found for the gene XRCC1 (OR = 0.82 95% CI 0.53-1.27). The combined analysis for both genes did not show association with this neoplasia (OR = 1.27 95% CI 0.79-20.5). The relationship of XRCC1 and APEX1 genotypes with cancer aggressiveness through the correlation with histopathological parameters, did not find any association. Our results suggest that the polymorphism in the gene APEX1 may be indicated as a potential marker for prostate cancer risk.KuasneHHDepartment of General Biology, Biological Science Center, Londrina State University, Londrina, PR, Brazil. khellenk@yahoo.com.brRodriguesI SISLosi-GuembarovskiRRReisM BMBFugantiP EPEGregórioE PEPLibos JuniorFFMatsudaH MHMRodriguesM A FMAKishimaM OMOCólusI M SIMengJournal ArticleResearch Support, Non-U.S. Gov't20100918
NetherlandsMol Biol Rep04032340301-48510DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.4.21.77Prostate-Specific AntigenEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMEur J Cancer. 2007 Jan;43(2):231-717196815EMBO J. 2001 Nov 15;20(22):6530-911707423Annu Rev Biochem. 1994;63:915-487979257Cancer Treat Rev. 2001 Jun;27(3):143-5111417964Urology. 2009 Sep;74(3):648-5319428062IARC Sci Publ. 1996;(139):189-2018923031Mutat Res. 2000 Oct 16;461(2):83-10811018583Hum Pathol. 1992 Mar;23(3):273-91555838Mol Cancer Ther. 2008 May;7(5):1246-5018483312Cancer Res. 1999 Jun 1;59(11):2557-6110363972J Urol. 2006 Jan;175(1):108-12; discussion 11216406883Mutat Res. 2003 Jul 25;528(1-2):19-2712873719Nucleic Acids Res. 1988 Feb 11;16(3):12153344216Nucleic Acids Res. 1991 Nov 11;19(21):5907-141719484Nucleic Acids Res. 1996 Nov 15;24(22):4387-948948628Blood. 1990 Aug 15;76(4):655-632200535Cancer Res. 1998 Feb 15;58(4):604-89485007Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):23-914744728Carcinogenesis. 2001 Jun;22(6):917-2211375899Neoplasma. 2008;55(4):330-718505345J Exp Clin Cancer Res. 2008 Sep 30;27:4918823566Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):177-8212509516Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Carcinogenesis. 2004 Aug;25(8):1395-40115044328Mutagenesis. 2009 Nov;24(6):507-1219762350Genomics. 2004 Jun;83(6):970-915177551Carcinogenesis. 2000 May;21(5):965-7110783319Mutat Res. 2000 Feb 16;459(1):1-1810677679EMBO J. 1996 Dec 2;15(23):6662-708978692Bull Cancer. 2002 Jun;89(6):619-3412135863Cancer Lett. 2001 May 10;166(1):65-911295288J Urol. 1998 Dec;160(6 Pt 1):2096-1019817331Clin Cancer Res. 2001 Apr;7(4):824-3011309329Mutat Res. 1988 Mar;204(3):379-4063347212Asian J Androl. 2007 May;9(3):331-817486273Case-Control StudiesDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsGene FrequencygeneticsGenetic Predisposition to DiseaseHumansMaleNeoplasm StagingProstate-Specific AntigenmetabolismProstatic NeoplasmsgeneticspathologyRisk FactorsX-ray Repair Cross Complementing Protein 1
2010022720100902201092160201092160201152460ppublish2085294210.1007/s11033-010-0267-z
208376002010111620170220
1460-218031112010NovCarcinogenesisCarcinogenesisNovel mechanism of regulation of the DNA repair enzyme OGG1 in tuberin-deficient cells.2022-3010.1093/carcin/bgq189Tuberin (protein encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease in the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in tumour kidney of tuberous sclerosis complex (TSC) patients. The purpose of this study was to elucidate the mechanisms by which tuberin regulates OGG1. The partial deficiency in tuberin expression that occurs in the renal proximal tubular cells and kidney cortex of the Eker rat is associated with decreased activator protein 4 (AP4) and OGG1 expression. A complete deficiency in tuberin is associated with loss of AP4 and OGG1 expression in kidney tumour from Eker rats and the accumulation of significant levels of 8-oxo-deoxyguanosine. Knockdown of tuberin expression in human renal epithelial cells (HEK293) with small interfering RNA (siRNA) also resulted in a marked decrease in the expression of AP4 and OGG1. In contrast, overexpression of tuberin in HEK293 cells increased the expression of AP4 and OGG1 proteins. Downregulation of AP4 expression using siRNA resulted in a significant decrease in the protein expression of OGG1. Immunoprecipitation studies show that AP4 is associated with tuberin in cells. Gel shift analysis and chromatin immunoprecipitation identified the transcription factor AP4 as a positive regulator of the OGG1 promoter. AP4 DNA-binding activity is significantly reduced in Tsc2(-/-) as compared with Tsc2(+/+) cells. Transcriptional activity of the OGG1 promoter is also decreased in tuberin-null cells compared with wild-type cells. These data indicate a novel role for tuberin in the regulation of OGG1 through the transcription factor AP4. This regulation may be important in the pathogenesis of kidney tumours in patients with TSC disease.HabibSamy LSLDepartment of Geriatrics, Geriatric Research, Education, and Clinical Center, South Texas Veterans Healthcare System, San Antonio, TX 78229, USA. habib@uthscsa.eduBhandariBesant KBKSadekNahedNAbboud-WernerSherry LSLAbboudHanna EHEengR01 AR042306ARNIAMS NIH HHSUnited StatesR01 DK078971DKNIDDK NIH HHSUnited StatesJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.20100913
EnglandCarcinogenesis80080550143-33340DNA-Binding Proteins0RNA, Messenger0Transcription Factors0Tumor Suppressor Proteins0enhancer-binding protein AP-44JG2LF96VFtuberous sclerosis complex 2 protein88847-89-68-oxo-7-hydrodeoxyguanosineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseG9481N71RODeoxyguanosineIMNat Cell Biol. 2002 Sep;4(9):658-6512172554Arch Biochem Biophys. 2000 May 1;377(1):1-810775435Am J Physiol Renal Physiol. 2008 Jan;294(1):F281-9017989114Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):669-7410744126Genes Dev. 1990 Oct;4(10):1741-522123466Oncogene. 2005 Nov 14;24(50):7475-8116288294Pharmacogenetics. 2004 Feb;14(2):103-915077011Cancer Epidemiol Biomarkers Prev. 2008 Jul;17(7):1739-4518628426Int J Cancer. 2008 Jul 1;123(1):51-518366059Carcinogenesis. 2003 Mar;24(3):573-8212663520Mol Cell Biol. 2004 Sep;24(18):7965-7515340059J Biol Chem. 2002 Sep 20;277(38):35364-7012167664Mutat Res. 2003 Oct 29;531(1-2):127-3914637250J Biol Chem. 1995 Jul 7;270(27):16409-147608212Mol Cancer. 2009;8:1319265534Mol Cell. 2002 Jul;10(1):151-6212150915Br J Cancer. 2001 Oct 19;85(8):1226-3011710839Cancer. 1998 Nov 15;83(10):2208-169827727Int J Cancer. 2007 Aug 1;121(3):501-517417784J Biol Chem. 2006 May 5;281(18):12495-50516540471Cancer Res. 2000 Sep 1;60(17):4740-410987279Biochimie. 2000 Jan;82(1):59-6410717388Cancer Res. 2003 May 15;63(10):2675-8012750296Mutat Res. 2000 Oct 16;461(2):109-1811018584Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):327-318419937J Biol Chem. 2006 Sep 1;281(35):25447-5616803888Methods Mol Med. 2000;36:197-20521340976J Urol. 1987 Sep;138(3):477-813625844Oncogene. 1998 Jun 11;16(23):3083-69662341Jpn J Clin Oncol. 2008 Mar;38(3):186-9118272472Carcinogenesis. 2002 Jul;23(7):1229-3412117782Cell. 2005 Apr 22;121(2):179-9315851026Cancer Lett. 2001 May 10;166(1):65-911295288Anal Biochem. 1976 May 7;72:248-54942051Nat Cell Biol. 2002 Sep;4(9):648-5712172553Nature. 1988 Apr 7;332(6164):557-612833704Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4156-6110725358Mutat Res. 2005 Sep 4;577(1-2):55-7615941573Toxicol Pathol. 2002 Nov-Dec;30(6):675-8012512868Int J Cancer. 2006 Jan 1;118(1):1-516206276J Biol Chem. 2003 Sep 26;278(39):37288-9612867426Cancer Biol Ther. 2008 Jan;7(1):23-717932460Proc Natl Acad Sci U S A. 1988 Aug;85(16):5789-932901089Mol Cancer. 2008;7:1018218111AnimalsBlotting, WesternCell ProliferationCells, CulturedChromatin ImmunoprecipitationDNA GlycosylasesmetabolismDNA RepairDNA-Binding ProteinsmetabolismDeoxyguanosineanalogs & derivativesmetabolismEmbryo, MammaliancytologymetabolismFibroblastscytologymetabolismHumansImmunoenzyme TechniquesKidneycytologymetabolismKidney NeoplasmsgeneticsmetabolismpathologyKidney Tubules, ProximalcytologyenzymologyMaleMiceMice, KnockoutPromoter Regions, GeneticgeneticsRNA, MessengergeneticsRatsRats, Long-EvansReverse Transcriptase Polymerase Chain ReactionTranscription FactorsmetabolismTumor Suppressor Proteinsphysiology
2010915602010915602010111760ppublish20837600bgq18910.1093/carcin/bgq189PMC3105579
207369622011031720161019
1559-70163122011FebJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and MetabolismJ. Cereb. Blood Flow Metab.Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions.680-9210.1038/jcbfm.2010.1477,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1(-/-)) mice to examine the possible roles of OGG1 in the vulnerability of neurons to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential. Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA base lesions (8-oxoG, FapyAde, and FapyGua) were elevated in response to ischemia in both the ipsilateral and contralateral hemispheres, and to a greater extent in the contralateral cortex of OGG1(-/-) mice compared with OGG1(+/+) mice. Ischemia-induced elevation of 8-oxoG incision activity involved increased levels of a nuclear isoform OGG1, suggesting an adaptive response to oxidative nuclear DNA damage. Thus, OGG1 has a pivotal role in repairing oxidative damage to nuclear DNA under ischemic conditions, thereby reducing brain damage and improving functional outcome.LiuDongDLaboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224, USA.CroteauDeborah LDLSouza-PintoNadjaNPittaMichaelMTianJingyanJWuChristopherCJiangHaiyangHMustafaKhadijaKKeijzersGuidoGBohrVilhelm AVAMattsonMark PMPengIntramural NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Intramural20100825
United StatesJ Cereb Blood Flow Metab81125660271-678X0DNA, MitochondrialEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMTrends Neurosci. 2004 Oct;27(10):595-60015374670J Clin Invest. 2004 Jun;113(12):1711-2115199406J Biol Chem. 1997 Oct 24;272(43):27338-449341184Science. 1999 Apr 2;284(5411):159-6210102819Brain Res Mol Brain Res. 1999 May 7;68(1-2):29-4110320781J Neurosci Res. 1999 Oct 15;58(2):308-1710502287Free Radic Biol Med. 2005 Mar 15;38(6):737-4515721984Neuroscience. 2005;136(1):135-4616182450J Biol Chem. 2005 Dec 9;280(49):40544-5116221681J Cereb Blood Flow Metab. 2006 Feb;26(2):181-9816001017Oncogene. 2006 Apr 20;25(17):2425-3216369492Neuromolecular Med. 2006;8(3):389-41416775390Mutat Res. 2006 Jul 25;599(1-2):88-9716574166Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1583-9616987013DNA Repair (Amst). 2007 Apr 1;6(4):544-5917112792J Biol Chem. 2007 Aug 17;282(33):23788-9817537722Nucleic Acids Res. 2007;35(16):5545-5517704129EMBO J. 2008 Jan 23;27(2):421-3218188152Nucleic Acids Res. 2008 Sep;36(15):5111-2118682529Free Radic Biol Med. 2008 Sep 15;45(6):813-918598755Ann N Y Acad Sci. 2008 Dec;1147:283-9219076450Neuron. 2008 Dec 10;60(5):748-6619081372Neuromolecular Med. 2009;11(1):28-4219288225Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Nucleic Acids Res. 2000 Mar 15;28(6):E1610684948J Cereb Blood Flow Metab. 2001 Jan;21(1):2-1411149664Cancer Res. 2001 Jul 15;61(14):5378-8111454679Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10469-7411517304J Cereb Blood Flow Metab. 2002 Apr;22(4):431-4311919514Biochemistry. 2002 Dec 31;41(52):15838-4412501213J Biol Chem. 2003 May 23;278(21):19541-812644468Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10670-512960370J Cereb Blood Flow Metab. 2003 Nov;23(11):1324-3914600440Mutat Res. 2003 Oct 29;531(1-2):109-2614637249Ann N Y Acad Sci. 2004 Apr;1011:101-1115126288Methods Cell Biol. 1995;46:187-2167541884AnimalsBehavior, AnimalphysiologyBlotting, WesternBrain IschemiapathologypsychologyCell DeathphysiologyCell NucleusmetabolismCell SurvivalphysiologyCells, CulturedDNA DamageDNA GlycosylasesgeneticsphysiologyDNA RepairDNA, MitochondrialmetabolismFluorescent Antibody TechniqueIn Situ Nick-End LabelingMiceMice, KnockoutMitochondriadrug effectsNeuronsphysiologyOxidative StressphysiologyStrokepathologypsychology
201082660201082660201131860ppublish20736962jcbfm201014710.1038/jcbfm.2010.147PMC3049522
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1879-085246152010OctEuropean journal of cancer (Oxford, England : 1990)Eur. J. CancerNovel mechanism of reducing tumourigenesis: upregulation of the DNA repair enzyme OGG1 by rapamycin-mediated AMPK activation and mTOR inhibition.2806-2010.1016/j.ejca.2010.06.117Inhibition of mTOR by rapamycin is an important approach in cancer therapy. In early clinical trials, tuberous sclerosis complex (TSC)-related kidney tumours were found to regress following rapamycin treatment. Since loss of function of the DNA repair OGG1 enzyme has a major role in multistep carcinogenesis of the kidney and other organs, we investigated the effect of rapamycin on OGG1 regulation. Treatment of HK2 cells, mouse Tsc-deficient cells and human VHL-deficient cells (786-O) with rapamycin resulted in decrease in p70S6K phosphorylation at Thr(389), and increase in the expression of NF-YA and OGG1 proteins. In addition, rapamycin increased OGG1 promoter activity in cells transfected with OGG1 promoter construct. Furthermore, rapamycin increased the phosphorylation at Thr(172) of the energy sensor AMPK. Downregulation of AMPK phosphorylation by high glucose (HG) increases the phosphorylation of p70S6K and decreases the protein expression of NF-YA and OGG1. Pretreatment of the cells with rapamycin before exposure to HG reversed the effects of HG. However, downregulation of AMPK by dominant negative (DN)-AMPK in Tsc2(+/-) cells abolished AMPK and decreased OGG1 expression. In contrast, transfection of Tsc2(+/-) cells with DN-S6K abolished p70S6K phosphorylation and increased OGG1 expression, a response enhanced by rapamycin. Treatment of Tsc2(+/-) mice with rapamycin resulted in activation of AMPK, downregulation of phospho-p70S6K and enhanced OGG1 expression. Our data show that inhibition of mTOR can activate AMPK and lead to upregulation of DNA repair enzyme OGG1. These data comprise the first report to provide one mechanism whereby rapamycin might prevent or inhibit the formation and progression of certain cancers.Copyright © 2010 Elsevier Ltd. All rights reserved.HabibSamy LSLGeriatric Research Education and Clinical Center, South Texas Veterans Healthcare System, TX, USA. habib@uthscsa.eduKasinathBalakuntalam SBSAryaRuth RectorRRVexlerSandraSVelagapudiChakradharCengR01 DK077295DKNIDDK NIH HHSUnited StatesJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.20100723
EnglandEur J Cancer90053730959-80490Antibiotics, AntineoplasticEC 2.7.-Protein KinasesEC 2.7.1.-AMP-activated protein kinase kinaseEC 2.7.1.1MTOR protein, humanEC 2.7.1.1TOR Serine-Threonine KinasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 6.5.1.-DNA Repair EnzymesW36ZG6FT64SirolimusIMAnimalsAntibiotics, AntineoplasticpharmacologyDNA GlycosylasesmetabolismDNA Repair EnzymesmetabolismDrug Screening Assays, AntitumorEpithelial CellsHumansImmunoblottingKidney Neoplasmsdrug therapymetabolismKidney Tubules, ProximalMaleMiceProtein KinasesmetabolismSirolimuspharmacologyTOR Serine-Threonine Kinasesantagonists & inhibitorsTumor Cells, CulturedUp-Regulation
201004152010061120100618201072760201072760201112060ppublish20656472S0959-8049(10)00633-710.1016/j.ejca.2010.06.117
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1945-02571442010AugGenetic testing and molecular biomarkersGenet Test Mol BiomarkersOxidative stress, Helicobacter pylori, and OGG1 Ser326Cys, XPC Lys939Gln, and XPD Lys751Gln polymorphisms in a Turkish population with colorectal carcinoma.559-6410.1089/gtmb.2009.0195The contribution of polymorphisms of DNA repair genes OGG1 Ser326Cys, XPC Lys939Gln, and XPD Lys751Gln in developing colorectal carcinoma is controversial. Whether the group 1A carcinogen Helicobacter pylori is a risk factor or not in these patients could not be clearly elucidated. One hundred ten colorectal cancer patients and 116 cancer-free individuals constituted the test and control groups, respectively. The association of OGG1 Ser326Cys, XPC Lys939Gln, and XPD Lys751Gln polymorphisms and the susceptibility to colorectal carcinoma with or without oxidative stress were evaluated. DNA was extracted from peripheral blood cells and genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. For serum nitric oxide and total antioxidant status assay, spectrophotometric analyses were used. Serum albumin measurements were performed using an autoanalyzer. H. pylori IgG was measured by ELISA. The serum albumin concentrations of cancer patients were significantly lower than those of the controls (p < 0.05). The carriers of the variant genotype of OGG1 (odds ratio: 0.963; 95% confidence interval: 0.446-2.079), XPC (0.789, 0.366-1.700), or XPD (0.532, 0.259-1.094) did not associate with the increased risk of cancer progression, despite the increased oxidative stress in cancer patients. Seropositivity of H. pylori IgG has been found to increase the risk of colorectal carcinoma by 2.2-fold.EnginAyse BasakABDepartment of Toxicology, Faculty of Pharmacy, Gazi University, Ankara, Turkey. abengin@gmail.comKarahalilBensuBEnginAtillaAKarakayaAli EsatAEengJournal ArticleResearch Support, Non-U.S. Gov't
United StatesGenet Test Mol Biomarkers1014942101945-02570DNA-Binding Proteins0RH81L854JGlutamine156533-34-5XPC protein, human452VLY9402SerineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanK3Z4F929H6LysineK848JZ4886CysteineIMAdultAgedAmino Acid SubstitutiongeneticsphysiologyColorectal NeoplasmscomplicationsgeneticsimmunologymetabolismCysteinegeneticsDNA GlycosylasesgeneticsDNA-Binding ProteinsgeneticsGenetics, PopulationGlutaminegeneticsHelicobacter InfectionsbloodcomplicationsgeneticsimmunologyHelicobacter pyloriimmunologyHumansLysinegeneticsMiddle AgedMutation, MissensephysiologyOxidative StressgeneticsphysiologyPolymorphism, Single NucleotidephysiologySerinegeneticsTurkeyXeroderma Pigmentosum Group D Proteingenetics
2010724602010724602010121460ppublish2064943310.1089/gtmb.2009.0195
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1423-00627022010Human heredityHum. Hered.The Ser(326)Cys polymorphism of 8-oxoguanine glycosylase 1 (OGG1) is associated with type 2 diabetes in Mexican Americans.97-10110.1159/000291964Human 8-oxoguanine glycosylase 1 (OGG1) excises oxidatively damaged promutagenic base 8-oxoguanine, a lesion previously observed in a rat model of type 2 diabetes (T2DM). The objective of the present study is to determine whether genetic variation in OGG1 is associated with type 2 diabetes (T2DM) in a Mexican American cohort.Ten SNPs including two tagging SNPs (rs1052133, rs2072668) across the OGG1 gene region were selected from the Hapmap database and genotyped in the entire cohort (n = 670; 29% diabetes; 39 families) by TaqMan assay. Association analyses between the SNPs and T2DM were performed using the measured genotype approach as implemented in the program SOLAR.Of the ten SNPs genotyped, only five were polymorphic. The minor allele frequencies of these 5 SNPs ranged from 1-38%. Of the SNPs examined for association, the Ser(326)Cys (rs1052133) exhibited significant association with T2DM (p = 0.016) after accounting for age and sex effects. Another intronic variant (rs2072668), which was in strong linkage disequilibrium (r(2) = 0.96) with Ser(326)Cys also exhibited significant association with T2DM (p = 0.031).These results suggest for the first time that the variants in OGG1 could influence diabetes risk in these Mexican American families and support a role for alterations of OGG1 in the pathogenesis of T2DM.Copyright © 2010 S. Karger AG, Basel.ThameemFarookFDivision of Nephrology, University of Texas Health Science Center, San Antonio, Tex., USA.PuppalaSobhaSLehmanDonna MDMSternMichael PMPBlangeroJohnJAbboudHanna EHEDuggiralaRavindranathRHabibSamy LSLengR01 DK042273-10DKNIDDK NIH HHSUnited StatesR01 DK047482DKNIDDK NIH HHSUnited StatesDK53889DKNIDDK NIH HHSUnited StatesDK42273DKNIDDK NIH HHSUnited StatesR01 DK047482-15DKNIDDK NIH HHSUnited StatesDK47482DKNIDDK NIH HHSUnited StatesR01 DK053889-10DKNIDDK NIH HHSUnited StatesR01 DK053889DKNIDDK NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20100703
SwitzerlandHum Hered02005250001-5652EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMFEBS Lett. 1997 Nov 3;417(1):150-29395094Biochem Biophys Res Commun. 2009 Aug 14;386(1):26-919486888Lancet. 1996 Feb 17;347(8999):444-58618487Free Radic Biol Med. 1994 Feb;16(2):271-48005523Ann Hum Genet. 1986 May;50(Pt 2):181-943435047Nature. 1987 May 7-13;327(6117):77-93574469Behav Genet. 2004 Mar;34(2):173-714755182Diabetologia. 2002 Jan;45(1):85-9611845227Eur J Hum Genet. 2000 Jul;8(7):545-5110909856Diabetes Res Clin Pract. 1999 Sep;45(2-3):161-810588369Acta Histochem. 2009;111(2):138-4418676009Am J Hum Genet. 2006 Mar;78(3):377-9216400619J Hum Genet. 2006;51(2):124-816333523Heredity (Edinb). 2005 Sep;95(3):221-716077740Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):497-50515734978Mol Carcinog. 2005 Mar;42(3):127-4115584022Hum Genet. 1999 Jul-Aug;105(1-2):179-8010480377Nitric Oxide. 1998;2(6):429-4110342486Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8016-209223306AdultDNA GlycosylasesgeneticsDiabetes Mellitus, Type 2geneticsFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansLinkage DisequilibriumgeneticsMaleMexican AmericansgeneticsPolymorphism, Single NucleotidegeneticsTexas
20090414200912222010786020107860201561960ppublish2060645600029196410.1159/000291964PMC3083264
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2476-762X1112010Asian Pacific journal of cancer prevention : APJCPAsian Pac. J. Cancer Prev.Lack of influence of DNA repair gene OGG1 codon 326 polymorphisms of gastric cancer risk in the Kashmir valley.165-8Damage to DNA may lead to carcinogenesis but is repaired through activation of pathways involving polymorphic enzymes, including human 8-oxoguanine glycosylase 1 (OGG1). The present study aimed to assess the role of genetic variants of DNA repair gene OGG1 Ser326Cys in susceptibility to gastric cancer in Kashmir valley. A case control study was performed in 303 subjects (108 gastric cancer and 195 healthy controls), all genotyped through the polymerase chain reaction (PCR). Data were statistically analyzed using the chi-square test and the logistic regression model. The distribution of OGG1 genotypes among controls and gastric cancer cases did not show any significant differences. Although smokers and high salted tea drinkers themselves were at higher risk for gastric cancer (OR=8.975, P=0.0001; OR=14.778, P=0.0001), interaction with OGG1 Ser326Cys did not further modulate the risk. In conclusion, our findings suggest that the OGG1 polymorphism does not influence either gastric cancer risk independently or by interaction with smoking or salted-tea consumption in the Kashmir valley.MalikM AMADepartment of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.ZargarS ASAMittalBalrajBengComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't
ThailandAsian Pac J Cancer Prev1011306251513-73680CodonEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdenocarcinomageneticspathologyCarcinoma, Squamous CellgeneticspathologyCase-Control StudiesCodongeneticsDNA GlycosylasesgeneticsDNA RepairFemaleGenetic Predisposition to DiseaseGenotypeHumansIndiaMiddle AgedPolymorphism, Single NucleotidegeneticsPrognosisRisk FactorsStomach Neoplasmsgeneticspathology
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1573-49783822011FebMolecular biology reportsMol. Biol. Rep.MUTYH Tyr165Cys, OGG1 Ser326Cys and XPD Lys751Gln polymorphisms and head neck cancer susceptibility: a case control study.1251-6110.1007/s11033-010-0224-xIn the present study we investigated the association between three polymorphisms of the MUTYH (Tyr165Cys, rs34612342), the OGG1 (Ser326Cys, rs1052133) and the XPD (Lys751Gln, rs13181) genes with head and neck cancer risk. Genotypes were determined in DNA from peripheral blood lymphocytes of 265 patients with head and neck squamous cell carcinoma (HNSCC) as well as 280 cancer-free controls by PCR-restriction fragment length polymorphisms. We found an association between HNSCC and the Ser326Cys (OR 1.69; 95% CI 1.19-2.45) as well as Cys326Cys (OR 4.56; 95% CI 2.07-10.05) variants of the OGG1 gene. The gene-gene interaction between MUTYH and OGG1 as well as OGG1 and XPD polymorphic variants may contribute to higher prevalence of HNSCC. We also found an association between Ser326Cys and Cys326Cys variants of OGG1 gene and smoking status in HNSCC patients (OR 1.97; 95% CI 1.25-3.11), (OR 3.54; 95% CI 1.39-9.04), respectively. Moreover, we also observed a protective association between Tyr165Cys variant of the MUTYH gene and non-smoking status in HNSCC (OR 0.34; 95% CI 0.17-0.66). We also found a link between gene-gene interaction (MUTYH and OGG1 or OGG1 and XPD) and smoking (ORs 2.17-4.20 and 2.18-5.23) or non-smoking status (ORs 0.11 and 7.61) in HNSCC patients, respectively. In conclusion our data showed that the Ser326Cys polymorphism of the OGG1 gene may modify the risk of HNSCC associated with smoking. Finally we suggested that this polymorphism might be used as predictive factor for head and neck cancer in Polish population.SliwinskiTomaszTDepartment of Molecular Genetics, University of Lodz, 12/16, 90-237, Lodz, Poland.PrzybylowskaKarolinaKMarkiewiczLukaszLRusinPawelPPietruszewskaWiolettaWZelinska-BlizniewskaHannaHOlszewskiJurekJMorawiec-SztanderaAlinaAMlynarskiWojciechWMajsterekIreneuszIengJournal ArticleResearch Support, Non-U.S. Gov't20100623
NetherlandsMol Biol Rep04032340301-4851EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanIMAnnu Rev Genet. 2004;38:445-7615568983Int J Cancer. 2001 May 20;95(3):140-311307145Cancer Sci. 2008 Feb;99(2):355-6018271935Cancer Epidemiol Biomarkers Prev. 2004 Oct;13(10):1680-115466987Carcinogenesis. 2006 Sep;27(9):1835-4116571649Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):669-7410744126Cancer Res. 2004 Feb 1;64(3):1197-20114871857Mutat Res. 2005 Dec 11;591(1-2):60-7316081110Mutagenesis. 2002 Nov;17(6):463-912435843CA Cancer J Clin. 2004 Jan-Feb;54(1):8-2914974761Crit Rev Toxicol. 1996;26(2):183-988688160Environ Mol Mutagen. 1999;33(1):3-2010037319Cancer Res. 1999 Jun 1;59(11):2557-6110363972Mol Carcinog. 2005 Apr;42(4):222-815754315Mutat Res. 2007 Jun 1;619(1-2):68-8017363013Nucleic Acids Res. 2006 Mar 20;34(5):1620-3216549874Carcinogenesis. 2005 Sep;26(9):1536-4115878910Carcinogenesis. 2004 Sep;25(9):1695-70015090466Cancer Sci. 2004 Dec;95(12):977-8315596047Int J Cancer. 2002 Jun 1;99(4):624-711992556Carcinogenesis. 2007 Jun;28(6):1254-817264068Int J Cancer. 2002 Aug 10;100(5):600-512124811N Engl J Med. 2003 Feb 27;348(9):845-712606740Tohoku J Exp Med. 2009 Dec;219(4):269-7519966524Am J Epidemiol. 2005 Jan 1;161(1):1-1415615908Oral Oncol. 2007 Sep;43(8):791-517207658Otolaryngol Pol. 2008;62(5):540-419004253Cancer Epidemiol Biomarkers Prev. 2008 Mar;17(3):736-918349297Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2526-3217164380Int J Oncol. 2005 Nov;27(5):1315-2016211227Rev Laryngol Otol Rhinol (Bord). 2005;126(3):135-4016366378Carcinogenesis. 2001 Aug;22(8):1185-811470747Mol Carcinog. 2006 May;45(5):344-816381036Science. 2001 Feb 16;291(5507):1284-911181991Free Radic Res. 2004 May;38(5):423-915293549Nucleic Acids Res. 1999 Oct 15;27(20):4001-710497264Chem Biol Interact. 2006 Mar 10;160(1):1-4016430879FEBS Lett. 2000 Jun 30;476(1-2):73-710878254Genes Dev. 2001 Jan 1;15(1):15-2311156600Int J Cancer. 1993 Jun 19;54(4):594-6068514451Carcinogenesis. 2002 Jul;23(7):1229-3412117782Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2384-9017164360Histol Histopathol. 2002;17 (3):909-1412168802Carcinogenesis. 2004 Dec;25(12):2433-4115333465Cancer Res. 2002 Apr 15;62(8):2253-711956079Trends Genet. 1993 Jun;9(6):211-78337762Int J Cancer. 2008 Apr 1;122(7):1630-818059021Carcinogenesis. 2000 Apr;21(4):551-510753184Clin Chem. 2006 Apr;52(4):739-4316455870Mol Biol Rep. 2011 Jan;38(1):445-5120364408Cancer Causes Control. 2008 Dec;19(10):1077-8318478337Mol Immunol. 2008 Jul;45(12):3321-918533267Cancer Res. 2001 Feb 15;61(4):1354-711245433J Exp Clin Cancer Res. 2009 Mar 13;28:3719284666Exp Oncol. 2009 Mar;31(1):57-919300419Chin J Physiol. 2007 Dec 31;50(6):294-30018442012Environ Health Perspect. 2003 Nov;111(15):1843-5014630517AdultAgedAged, 80 and overCase-Control StudiesDNA GlycosylasesgeneticsFemaleGenetic Predisposition to DiseaseGenotypeHead and Neck NeoplasmsgeneticsHumansMaleMiddle AgedPolymerase Chain ReactionmethodsSmokingXeroderma Pigmentosum Group D Proteingenetics
2010051220100611201062460201062460201152760ppublish2057190810.1007/s11033-010-0224-x
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0008-543X116132010Jul01CancerCancerPolymorphisms in ERCC2, MSH2, and OGG1 DNA repair genes and gallbladder cancer risk in a population of Northern India.3160-910.1002/cncr.25063Genetic variants of DNA repair enzymes may lead to genetic instability and contribute to gallbladder (GB) carcinogenesis.A case-control study (230 GB carcinogenesis patients and 230 controls) was undertaken to evaluate whether genetic variations in 3 DNA repair genes ERCC2 (Asp312Asn [rs1799793] and Lys751Gln [rs13181]), MSH2 (-118T > C [rs2303425] and IVS1 + 9G>C [rs2303426]), and OGG1 (Ser326Cys [rs1052133] and 748-15C > G [rs2072668]) are associated with GB carcinogenesis risk in a North Indian population.The authors found that the ERCC2 Asp312Asn AA, MSH2 IVS1 + 9G > C CC, OGG1 Ser326Cys GG and CG + GG, and OGG1 748-15C > G GG and CG + GG genotypes were significantly associated with an increased risk of GB carcinogenesis (odds ratio [OR], 2.1, 1.8, 2.5, 1.8, 2.0, and 1.6, respectively). In contrast, ERCC2 Lys751Gln, and MSH2 -118T > C markers showed no significant associations with GB carcinogenesis risk, although because of the small sample size their effects cannot be ruled out. Female GB carcinogenesis patients with the OGG1 748-15C > G GG, OGG1 Ser326Cys GG, and ERCC2 Asp312Asn genotypes had a greater risk for developing the disease (OR, 3.6, 7.7, and 2.7, respectively). There was a significant interaction between MSH2 IVS1 + 9G > C and OGG1 748-15C > G polymorphisms (P = .001). Furthermore, individuals with > 6 variant alleles of the studied polymorphisms were at 4-fold increased risk for developing GB carcinogenesis. Classification and Regression Tree analysis revealed potential higher-order gene-gene interactions and categorized a few higher-risk subgroups for GB carcinogenesis.These results suggest that genetic variants in the DNA repair pathways may be involved in GB carcinogenesis etiology.SrivastavaKshitijKDepartment of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.SrivastavaAnveshaAMittalBalrajBengJournal ArticleResearch Support, Non-U.S. Gov't
United StatesCancer03742360008-543X786N6370WK2-amino-5-hydroxy-4-oxopentanoic acid88755TAZ87Aminolevulinic AcidEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.1.3MSH2 protein, humanEC 3.6.1.3MutS Homolog 2 ProteinEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanAIMIMAminolevulinic Acidanalogs & derivativesCase-Control StudiesDNA GlycosylasesgeneticsFemaleGallbladder NeoplasmsgeneticsGallstonescomplicationsGene FrequencyGenetic Predisposition to DiseaseHaplotypesHumansIndiaMaleMiddle AgedMutS Homolog 2 ProteingeneticsPolymorphism, Single NucleotideRiskXeroderma Pigmentosum Group D Proteingenetics
201062260201062260201071660ppublish2056462410.1002/cncr.25063
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1756-9966292010Jun12Journal of experimental & clinical cancer research : CRJ. Exp. Clin. Cancer Res.The association of 18F-deoxyglucose (FDG) uptake of PET with polymorphisms in the glucose transporter gene (SLC2A1) and hypoxia-related genes (HIF1A, VEGFA, APEX1) in non-small cell lung cancer. SLC2A1 polymorphisms and FDG-PET in NSCLC patients.6910.1186/1756-9966-29-69Positron emission tomography imaging of lung cancers with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose is a non-invasive diagnostic, and prognostic tool that measures tumor metabolism. We have analyzed the effect of solute carrier family 2 (facilitated glucose transporter), member 1 polymorphisms on 2-[fluorine-18]-fluoro-2-deoxy-D-glucose-uptake with a combination of polymorphisms of hypoxia-inducible factor 1 alpha, apurinic/apyimidinic endonuclease, and vascular endothelial growth factor A in a hypoxia-related pathway.We investigated the association between solute carrier family 2 (facilitated glucose transporter), member 1 -2841A>T, hypoxia-inducible factor 1 alpha Pro582Ser, Ala588Thr, apurinic/apyimidinic endonuclease Asp148Glu, or vascular endothelial growth factor A +936C>T and 2-[fluorine-18]-fluoro-2-deoxy-D-glucose-uptake among 154 patients with non-small-cell lung cancer.The solute carrier family 2 (facilitated glucose transporter), member 1 -2841A>T polymorphism was significantly associated with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose-uptake in combination with the apurinic/apyimidinic endonuclease Asp148Glu (T>G) polymorphism in the squamous cell type of non-small-cell lung cancer. The solute carrier family 2 (facilitated glucose transporter), member 1 TT genotype had a higher maximum standardized uptake values than the AA + AT genotype when the apurinic/apyimidinic endonuclease genotype was TT (mean maximum standardized uptake values, 12.47 +/- 1.33 versus 8.46 +/- 2.90, respectively; P = 0.028). The mean maximum standardized uptake values were not statistically different with respect to vascular endothelial growth factor A and hypoxia-inducible factor 1 alpha polymorphisms.A glucose transporter gene polymorphism was shown to be statistically associated with glucose-uptake when the apurinic/apyimidinic endonuclease genotype is TT in patients with the squamous cell type of non-small-cell lung cancer. Our findings suggest that a newly developed tracer for positron emission tomography could be affected by genetic polymorphisms.KimSeong-JangSJDepartments of Laboratory Medicine, Pusan National University Hospital, School of Medicine Pusan National University, Busan, Korea. mindcatch@hanmail.netHwangSang-HyunSHKimIn JooIJLeeMin KiMKLeeChang HunCHLeeSang-YullSYLeeEun YupEYengJournal ArticleResearch Support, Non-U.S. Gov't20100612
EnglandJ Exp Clin Cancer Res83086470392-90780Biomarkers, Tumor0DNA, Neoplasm0Glucose Transporter Type 10HIF1A protein, human0Hypoxia-Inducible Factor 1, alpha Subunit0Radiopharmaceuticals0SLC2A1 protein, human0VEGFA protein, human0Vascular Endothelial Growth Factor A0Z5B2CJX4DFluorodeoxyglucose F18EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMKidney Int. 2001 Feb;59(2):631-611168944Nephrol Dial Transplant. 2001 Aug;16(8):1653-611477169Trends Mol Med. 2002;8(4 Suppl):S62-711927290Oncol Rep. 2004 Nov;12(5):1033-715492789Cancer. 1994 Oct 15;74(8):2239-447922975Ann Thorac Surg. 1995 Nov;60(5):1348-528526625Curr Opin Genet Dev. 1998 Oct;8(5):588-949794818J Nucl Med. 1999 Apr;40(4):556-6510210213Cancer Res. 1999 Nov 15;59(22):5830-510582706FEBS Lett. 2000 Jun 30;476(1-2):73-710878254Cancer Sci. 2009 Apr;100(4):753-819141127J Exp Clin Cancer Res. 2008;27:4918823566Am J Clin Oncol. 2008 Aug;31(4):352-6218845994Anticancer Res. 2008 Mar-Apr;28(2B):1271-618505065Cancer Biomark. 2008;4(2):63-7118503157Lung Cancer. 2008 May;60(2):277-8418061304Eur J Cardiothorac Surg. 2008 May;33(5):819-2318374589J Clin Oncol. 2008 Feb 20;26(6):856-6218281657Clin Cancer Res. 2008 Jan 15;14(2):612-718223238DNA Repair (Amst). 2008 Feb 1;7(2):177-8617974506Hum Mol Genet. 2007 Oct 1;16(19):2333-4017855454Eur J Cancer. 2007 Jun;43(9):1392-817512190Lung Cancer. 2006 Sep;53(3):257-6216837101Prostate. 2005 May 15;63(3):215-2115538748J Diabetes Complications. 2005 Mar-Apr;19(2):65-915745834Breast Cancer Res Treat. 2004 Dec;88(3):205-815609122Kidney Int. 1999 May;55(5):1843-810231446Am J Pathol. 2000 Aug;157(2):411-2110934146Mutat Res. 2000 Oct 16;461(2):83-10811018583J Vasc Res. 2000 Nov-Dec;37(6):443-811146397Adenocarcinomadiagnostic imaginggeneticspathologyAdultAgedAged, 80 and overBiomarkers, TumorgeneticsCarcinoma, Non-Small-Cell Lungdiagnostic imaginggeneticspathologyCarcinoma, Squamous Celldiagnostic imaginggeneticspathologyDNA, NeoplasmgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleFluorodeoxyglucose F18GenotypeGlucose Transporter Type 1geneticsHumansHypoxiadiagnostic imagingHypoxia-Inducible Factor 1, alpha SubunitgeneticsLung Neoplasmsdiagnostic imaginggeneticspathologyMaleMiddle AgedPolymerase Chain ReactionPolymorphism, Single NucleotidegeneticsPositron-Emission TomographyPrognosisProspective StudiesRadiopharmaceuticalsVascular Endothelial Growth Factor Agenetics
20100331201006122010615602010615602010102960epublish205407861756-9966-29-6910.1186/1756-9966-29-69PMC2898683
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1364-67531142010OctNeurogeneticsNeurogeneticsAge at onset in Huntington's disease: replication study on the associations of ADORA2A, HAP1 and OGG1.435-910.1007/s10048-010-0248-3In previous candidate gene studies, associations of the age at onset (AO) in Huntington disease (HD) have been reported with genetic variations in the genes encoding adenosinergic A(2A) receptor (ADORA2A), human huntingtin-associated protein-1 (HAP1) and the single base excision repair enzyme, 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1). Here, we sought to replicate these associations in an established study population of 419 unrelated German HD patients. AO was defined as the age at which the first motor signs of HD appeared, motor AO (mAO). For 215 patients, also information about the first behavioural or cognitive signs of HD was available, so that we also tested for an association with the earliest AO. No association was found with OGG1. For HAP1, we found modest evidence for association with the same risk allele as in the original sample and mAO. Yet, we replicated the previously reported association between the original ADORA2A polymorphism when using the earliest AO. Additionally, we identified new associations in the same gene, thus further supporting the potential contribution of ADORA2A to the pathogenesis of HD.Taherzadeh-FardElaheEDepartment of Human Genetics, Ruhr-University Bochum, 44780, Bochum, Germany.SaftCarstenCWieczorekStefanSEpplenJörg TJTArningLarissaLengJournal Article20100530
United StatesNeurogenetics97097141364-67450HAP1 protein, human0Nerve Tissue Proteins0Receptor, Adenosine A2AEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMArch Biochem Biophys. 2000 May 1;377(1):1-810775435BMC Med Genet. 2006 Nov 10;7:7917096834Mutat Res. 2001 Aug 9;486(3):207-1611459633Nature. 1995 Nov 23;378(6555):398-4027477378Mol Neurodegener. 2009 Jan 08;4:319133136Science. 2002 Jun 21;296(5576):2225-912029063J Med Genet. 2007 Jan;44(1):44-5017018562Nature. 2007 May 24;447(7143):447-5217450122Mol Neurodegener. 2009 Feb 06;4:1019200361Neurobiol Dis. 2009 Sep;35(3):474-619591938Neuropsychopharmacology. 2008 Nov;33(12):2791-80018305461Genome Med. 2009 Aug 21;1(8):8019725930J Biol Chem. 1998 Jul 24;273(30):19220-79668110Cancer Res. 2009 Apr 15;69(8):3642-919351836Neurogenetics. 2005 Feb;6(1):25-815742215Hum Mol Genet. 2008 Apr 15;17(8):1137-4618192679J Radiat Res. 2003 Mar;44(1):31-512841596J Biol Chem. 2010 Feb 19;285(8):5614-2319996106Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):497-50515734978Cell Adh Migr. 2009 Jan-Mar;3(1):71-619262167AdolescentAdultAge of OnsetAgedAllelesCognitionCohort StudiesDNA GlycosylasesgeneticsGenetic Predisposition to DiseaseGenetic VariationHumansHuntington DiseasegeneticsMiddle AgedNerve Tissue ProteinsgeneticsPolymorphism, GeneticReceptor, Adenosine A2AgeneticsRisk
20100324201005172010616020106160201111960ppublish2051260610.1007/s10048-010-0248-3
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1573-49783812011JanMolecular biology reportsMol. Biol. Rep.The association of polymorphisms in DNA base excision repair genes XRCC1, OGG1 and MUTYH with the risk of childhood acute lymphoblastic leukemia.445-5110.1007/s11033-010-0127-xThe aim of this study was to evaluate the association of polymorphisms in genes encoding three key proteins of DNA base excision repair (BER): the OGG1 Ser326Cys, the MUTYH Tyr165Cys and the XRCC1 Arg399Gln with the risk of childhood acute lymphoblastic leukemia (ALL). Our study included 97 children patients with ALL (mean age 5.4±2.5) and 131 healthy children (mean age 6.2±2.8) used as controls. Genetic polymorphisms in BER pathway genes were examined using PCR and restriction fragment length polymorphism (RFLP). We have demonstrated that the OGG1 Cys/Cys genotype increases the risk of ALL (OR 5.36) whereas the Ser/Ser genotype variant strongly reduces the risk of this cancer among Polish children (OR 0.45). Although we did not observe the differences in single nucleotide polymorphisms (SNPs) in MUTYH and XRCC1 genes between control group and children with ALL, we have shown that the combined genotypes of examined genes can modulate the risk of childhood ALL in Polish population. We found that the combined genotype Arg/Gln-Cys/Cys of XRCC1/OGG1 (OR 3.83) as well as the Cys/Cys-Tyr/Tyr of OGG1/MUTYH (OR 6.75) increases the risk of ALL. In contrast, the combined genotype Arg/Arg-Ser/Ser of XRCC1/OGG1 (OR 0.40) as well as the Ser/Ser-Tyr/Tyr of OGG1/MUTYH (OR 0.43) played a protective role against this malignant disease. In conclusion, we suggest that polymorphisms of BER genes may be used as an important predictive factor for acute lymphoblastic leukemia in children.StanczykMMDepartment of Molecular Genetics, University of Lodz, Banacha 12/16 St, 90-237, Lodz, Poland.SliwinskiTTCuchraMMZubowskaMMBielecka-KowalskaAAKowalskiMMSzemrajJJMlynarskiWWMajsterekIIengJournal ArticleResearch Support, Non-U.S. Gov't20100404
NetherlandsMol Biol Rep04032340301-48510DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanIMCancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1810-816030121Mol Biol Rep. 2008 Dec;35(4):669-7217874204Cancer Epidemiol Biomarkers Prev. 2003 Feb;12(2):170-112582029J Genet. 2008 Aug;87(2):181-618776649Mutat Res. 2005 Dec 11;591(1-2):60-7316081110J Natl Cancer Inst. 2004 Nov 3;96(21):1631-415523092Leuk Res. 2009 Jun;33(6):759-6319101034Cancer Cell. 2004 Dec;6(6):539-4515607958Tohoku J Exp Med. 2009 Jul;218(3):185-9119561388Mol Biol Rep. 2011 Jun;38(5):2911-820127182Cancer Detect Prev. 2007;31(3):237-4317651912Ann Surg Oncol. 2009 Jun;16(6):1695-70319266243Best Pract Res Clin Haematol. 2002 Dec;15(4):597-62112617866Mol Aspects Med. 2007 Jun-Aug;28(3-4):258-7517628657Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502J Biol Chem. 2004 May 21;279(21):22585-9415020594J Exp Clin Cancer Res. 2008 Sep 30;27:4918823566Pediatr Blood Cancer. 2009 Mar;52(3):318-2318989891Mol Biol Rep. 2010 Jun;37(5):2471-619763880Cancer Epidemiol Biomarkers Prev. 2002 Jan;11(1):23-711815397Cancer Lett. 2005 Jan 10;217(1):17-2415596292Eur J Cancer. 2001 Jun;37(9):1173-8011378349Blood. 2002 Nov 15;100(10):3761-612393447Cancer Lett. 2000 Oct 16;159(1):79-8610974409J Biol Chem. 2001 Feb 23;276(8):5547-5511092888Jpn J Clin Oncol. 2008 Mar;38(3):186-9118272472Cancer Genet Cytogenet. 2007 Sep;177(2):89-9417854660Leuk Res. 2007 Mar;31(3):387-9316949154Pediatr Blood Cancer. 2007 Jan;48(1):16-2016435384Best Pract Res Clin Haematol. 2001 Sep;14(3):593-60711640871Anticancer Res. 2007 Jul-Aug;27(4B):2453-617695538Exp Oncol. 2009 Mar;31(1):57-919300419ChildDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-Binding ProteinsgeneticsFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansMalePolymorphism, Single NucleotidegeneticsPrecursor Cell Lymphoblastic Leukemia-LymphomaenzymologygeneticsRisk FactorsX-ray Repair Cross Complementing Protein 1
20100112201003232010466020104760201132260ppublish2036440810.1007/s11033-010-0127-x
202187382010061420170214
1533-0338922010AprTechnology in cancer research & treatmentTechnol. Cancer Res. Treat.APEX1 gene amplification and its protein overexpression in osteosarcoma: correlation with recurrence, metastasis, and survival.161-9The expression of apurinic/apyrimidinic exonuclease 1 (APEX1) in tumors has been linked with chemoresistance, radioresistance, and shorter patient survival times. We sought to gain insight into the role of APEX1 in human osteosarcoma by evaluation of gene copy number alterations and its protein expression in osteosarcoma patients treated at the Sarcoma Center of Tianjin Cancer Hospital (Tianjin, China). To evaluate the gene copy number alterations of APEX1, we acquired 10 fresh tissue samples from 9 patients and performed whole-genome array-based comparative genomic hybridization (aCGH). We next acquired formalin-fixed and paraffin embedded tissues from 57 well-annotated osteosarcoma cases and performed immunohistochemical analyses for APEX1. APEX1 gene amplification was observed in 50% (5/10) of the osteosarcoma samples. The overexpression of APEX1 protein was detected in 64.9% (37/57) of the osteosarcomas ranging from negative (35.1%, 20/57), weakly positive (35.1%, 20/57), moderate (14%, 8/57) and strongly positive (15.8%, 9/57). The APEX1 expression had significant correlation with osteosarcoma local recurrence and/or metastasis. Moreover, multivariate analysis showed that APEX1 expression was an independent molecular predictor for disease-free survival of patients with osteosarcomas. Our study for the first time showed that APEX1 gene was amplified in osteosarcomas and that APEX1 expression was an independent predictor of the osteosarcoma local recurrence and/or metastasis. Thus, APEX1 may serve as a prognostic marker and potential therapeutic target for osteosarcoma.YangJilongJDepartment of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Hospital and Institute, Tianjin, 30060, China. jilongyang2003@yahoo.com.cnYangDaDCogdellDavidDDuXiaolingXLiHaixinHPangYiYSunYanYHuLimeiLSunBaocunBTrentJonathanJChenKexinKZhangWeiWengJournal ArticleResearch Support, Non-U.S. Gov't
United StatesTechnol Cancer Res Treat1011409411533-03380Biomarkers, TumorEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdolescentAdultBiomarkers, TumoranalysisBone NeoplasmsgeneticsmortalitypathologyChildDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisgeneticsDisease-Free SurvivalFemaleGene AmplificationGene DosageHumansIn Situ Hybridization, FluorescenceKaplan-Meier EstimateMaleNeoplasm Recurrence, LocalgeneticsmortalitypathologyNeoplasm StagingOsteosarcomageneticsmortalitypathologyPrognosisYoung Adult
201031260201031260201061560ppublish20218738c4306/APEX1-Gene-Amplification-and-Its-Protein-Overexpression-in-Osteosarcoma-Correlation-with-Recurrence-Metastasis-and-Survival-161-170-p17777.html10.1177/153303461000900205
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1098-22805212011JanEnvironmental and molecular mutagenesisEnviron. Mol. Mutagen.BER gene polymorphisms (OGG1 Ser326Cys and XRCC1 Arg194Trp) and modulation of DNA damage due to pesticides exposure.20-710.1002/em.20562The susceptibility of individuals to the genotoxic effect of pesticides can be modulated by genetic variations in the xenobiotic detoxification and DNA repair processes. This study evaluates if the two BER polymorphisms (XRCC1Arg194Trp and OGG1Ser326Cys) or the combined genotypes of these polymorphisms with PON1Gln192Arg could modify individual susceptibility to pesticide exposure in vineyard workers, as measured by micronucleus formation and DNA damage induction in peripheral leukocytes. The study population comprised 108 agricultural workers exposed to pesticides and 65 nonexposed. Our results demonstrate that individuals with the variant allele (OGG1Cys) showed higher DNA damage, detected by the comet assay, in relation to individuals carrying the wild-type OGG1Ser allele. Considering the combined influence of metabolizing PON1 and the DNA repair OGG1 genes, we observed significantly higher DNA damage in the comet assay in the exposed group when a less efficient OGG1Cys allele was acting independently of the PON1 genotype, reinforcing the importance of the OGG1 repair enzyme in the response to DNA damage by pesticide exposure. The association of the PONGln/Gln genotype with higher MN frequency suggests that the PON1 genotype is a major determinant of genotoxic risk in individuals exposed to pesticides. Analysis of the compared effect of XRCC1 and PON1 genotypes in the exposed group suggested that, among the poorly metabolizing PON1Gln/Gln individuals, the XRCC1Arg/Trp genotype has a protective effect with respect to MN formation. These results indicate that enhanced XRCC1 function may provide some protection from the enhanced genotoxic risk associated with inefficient xenobiotic detoxification in the studied population.Copyright © 2010 Wiley-Liss, Inc.RohrPaulaPDepartamento de Genética e Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre-RS, Brazil.da SilvaJulianaJErdtmannBernardoBSaffiJeniferJGuechevaTemenouga NikolovaTNAntônio Pêgas HenriquesJoãoJKvitkoKátiaKengJournal ArticleResearch Support, Non-U.S. Gov't
United StatesEnviron Mol Mutagen88001090893-66920DNA-Binding Proteins0Pesticides0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.1.8.1AryldialkylphosphataseEC 3.1.8.1PON1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultAryldialkylphosphatasegeneticsComet AssayDNA Damagedrug effectsgeneticsDNA GlycosylasesgeneticsDNA-Binding ProteinsgeneticsGenetic Predisposition to DiseasegeneticsGenotypeHumansMaleMicronucleus TestsMiddle AgedPesticidestoxicityPolymorphism, GeneticgeneticsX-ray Repair Cross Complementing Protein 1
201039602010396020112960ppublish2020964710.1002/em.20562
201271822011102120171030
1573-49783852011JunMolecular biology reportsMol. Biol. Rep.Associations between GSTM1 and OGG1 Ser326Cys polymorphisms and smoking on chromosomal damage and birth growth in mothers.2911-810.1007/s11033-010-9953-0The presenting study was investigated the associations between individual susceptibility and cigarette smoke on maternal chromosomal damage and neonatal birth growth in smoking mothers since little known about genetic susceptibility to cigarette smoke in relation to adverse pregnancy outcome such as birth growth. Sixty-one pregnant women who completed a questionnaire at Ankara Education and Research Hospital, Department of Obstetrics and Gynecology have enrolled in this study. GSTM1 and OGG1 ser326Cys gene polymorphisms were analysed by RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction) as possible genetic factors affecting susceptibility to such health effects of smoking and chromosomal damage was performed by chromosomal aberration assay (CAA) in maternal blood lymphocytes. Maternal self-reported history of pregnancy smoking was informed by questionnaire declaration. Our results showed that maternal smoking had significant effect on chromosomal damage, birth weight, and length. The frequencies of CA in smokers was significantly higher than that of the nonsmokers (3.46 ± 2.06 and 2.00 ± 1.3, P = 0.001). Birth weight and length in smokers were significantly higher that of nonsmokers (3,355 g and 49.57 cm, P = 0.001; 3,639 g and 50.79 cm, P = 0.002). On the other hand, there was a slightly increased in the frequencies of CA and reduction birth weight and length in GSTM1 null and length in OGG1 variant genotypes, those differences were not statistically significant (P > 0.05); likely due to small sample size. Larger sample size needs to reach significance.KarahalilBensuBDepartment of Toxicology, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey. bensuka@gmail.comEmerceEsraEKocabaşNeslihan AygünNAAkkaşElifEengJournal Article20100202
NetherlandsMol Biol Rep04032340301-4851EC 2.5.1.18Glutathione TransferaseEC 2.5.1.18glutathione S-transferase M1EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMInt J Epidemiol. 1999 Oct;28(5):829-3510597978DNA Repair (Amst). 2006 Nov 8;5(11):1337-4516861056Hum Genet. 2008 May;123(4):359-6918320229Carcinogenesis. 1997 Sep;18(9):1763-69328173Med J Aust. 2008 Nov 3;189(9):490-418976189Hiroshima J Med Sci. 2008 Jun;57(2):61-718717188Birth Defects Res C Embryo Today. 2006 Dec;78(4):326-3217315246Pediatr Int. 2002 Feb;44(1):55-911982872FASEB J. 2004 Mar;18(3):595-714734635Cancer Lett. 2005 Mar 10;219(2):191-515723719Early Hum Dev. 2000 Feb;57(2):137-4710735460Mutat Res. 2000 Feb 16;465(1-2):101-1110708975Arh Hig Rada Toksikol. 2008 Dec;59(4):241-5019064361Mutat Res. 2000 Sep 20;469(2):199-20510984680Mutat Res. 2005 Mar 7;581(1-2):181-615725617Environ Health Perspect. 2004 Jul;112(10 ):1133-615238289Mutat Res. 2004 Nov;567(2-3):447-7415572290Sci Total Environ. 2007 Nov 1;386(1-3):124-3317610937J Occup Environ Med. 2003 May;45(5):492-812762073Br J Obstet Gynaecol. 1996 Aug;103(8):806-138760712Clin Sci (Lond). 1998 Aug;95(2):115-289680492J Mol Med (Berl). 2003 Aug;81(8):488-9412811412Methods Mol Biol. 2009;472:103-3719107431Mutat Res. 2006 Sep 28;608(2):136-5616829162Free Radic Biol Med. 2002 Jun 1;32(11):1102-1512031895Epidemiology. 2000 Jul;11(4):427-3310874550Mol Cell Biochem. 2000 Dec;215(1-2):11-911204445Anticancer Res. 2006 Nov-Dec;26(6C):4955-817214369Mutat Res. 1995 Oct;338(1-6):95-1067565886Am J Med Genet. 2001 Jul 22;102(1):21-411471167JAMA. 2002 Jan 9;287(2):195-20211779261Am J Perinatol. 2009 Feb;26(2):117-2118850517Arch Environ Health. 1998 May-Jun;53(3):214-219814718Eur J Obstet Gynecol Reprod Biol. 2009 Mar;143(1):38-4219147266Mol Hum Reprod. 2006 Feb;12(2):77-8316481407Mutat Res. 1998 May 25;400(1-2):467-789685705AdultBirth WeightgeneticsChromosome Aberrationschemically inducedDNA DamageDNA GlycosylasesgeneticsFemaleGenotypeGlutathione TransferasegeneticsHumansMothersPolymorphism, GeneticPregnancyPregnancy Complicationschemically inducedgeneticsSmokingadverse effectsTobaccoadverse effectsYoung Adult
200908132010011520102460201024602011102260ppublish2012718210.1007/s11033-010-9953-0
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1941-66364122010JunJournal of gastrointestinal cancerJ Gastrointest CancerOGG1 Ser326Cys polymorphism and susceptibility to esophageal cancer in low and high at-risk populations of northern India.110-510.1007/s12029-009-9124-5Esophageal cancer has diverse incidence worldwide, and genetic/environmental risk factors are supposed to be responsible for it. OGG1 Ser326Cys gene polymorphism (rs1052133) has been found to be associated with different cancer susceptibilities and interaction with different environmental factors.The aim of this study is to detect the role of OGG1 Ser326Cys polymorphism in susceptibility to esophageal cancer in two Northern Indian populations having different incidence rates.A total of 737 cases and controls from two high and low at-risk populations were selected for the study. All the subjects were genotyped by PCR with confronting two-pair primers.No significant association was found between OGG1 Ser326Cys genotypes and esophageal cancer risk in both of the populations. Gene-environment analysis revealed no significant interaction between OGG1 Ser326Cys genotypes and smoking/high-salted tea intake habits.OGG1 Ser326Cys polymorphism does not have a role in determining susceptibility to esophageal cancer either in high or in low at-risk populations of Northern India.UpadhyayRohitRDepartment of Genetics, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, 226014, India.MalikManzoor AhmedMAZargarShowkat AliSAMittalBalrajBengJournal ArticleResearch Support, Non-U.S. Gov't
United StatesJ Gastrointest Cancer1014796270DNA PrimersEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMOncol Rep. 2005 Jun;13(6):1009-1615870915Int J Cancer. 2001 May 20;95(3):140-311307145Arch Biochem Biophys. 2000 May 1;377(1):1-810775435Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Cancer Epidemiol Biomarkers Prev. 2003 Feb;12(2):170-112582029Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):669-7410744126Carcinogenesis. 2008 Jan;29(1):100-517984110Arch Med Res. 2009 Jul;40(5):416-2319766908Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1470-918559563CA Cancer J Clin. 2005 Mar-Apr;55(2):74-10815761078Carcinogenesis. 1992 Aug;13(8):1331-51499084Mutat Res. 2005 Apr 4;582(1-2):53-6015781210Int J Cancer. 2002 Jun 1;99(4):624-711992556Gut. 1992 Jan;33(1):11-51740265Nucleic Acids Res. 1988 Feb 11;16(3):12153344216Carcinogenesis. 2007 Mar;28(3):691-717056606Mutat Res. 2007 Jul 28;631(2):101-1017531525Cancer Epidemiol Biomarkers Prev. 2004 Jun;13(6):1081-315184269Carcinogenesis. 2004 Sep;25(9):1689-9415073047J Biol Chem. 1992 Jan 5;267(1):166-721730583Cancer Epidemiol Biomarkers Prev. 2008 Mar;17(3):736-918349297Int J Cancer. 2000 Dec 15;88(6):932-711093817Gynecol Oncol. 2005 Oct;99(1):43-915990162J Am Chem Soc. 2009 Jul 15;131(27):9506-1519537786Carcinogenesis. 2001 Sep;22(9):1355-6211532855Jpn J Cancer Res. 1998 Aug;89(8):825-89765618Oncogene. 1998 Jun 25;16(25):3219-259681819Cancer Lett. 2001 Sep 10;170(1):53-6111448535Science. 1997 Nov 7;278(5340):1043-509353177Carcinogenesis. 2002 Jul;23(7):1229-3412117782Prog Nucleic Acid Res Mol Biol. 2001;68:193-20511554297J Epidemiol. 2002 May;12(3):258-6512164330Carcinogenesis. 2000 Mar;21(3):361-7010688856Cancer Lett. 2005 Nov 8;229(1):85-9115946795AgedCase-Control StudiesDNA GlycosylasesanalysisgeneticsDNA PrimersEsophageal NeoplasmsepidemiologygeneticsFemaleGenotypeHumansIndiaepidemiologyInterviews as TopicLogistic ModelsMaleMiddle AgedPolymerase Chain ReactionPolymorphism, GeneticRisk Factors
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200567432010050620151119
1477-03932622010MarToxicology and industrial healthToxicol Ind HealthThe role of oxidative DNA damage, DNA repair, GSTM1, SOD2 and OGG1 polymorphisms in individual susceptibility to Barrett's esophagus.67-7910.1177/0748233709359278Determination of the genetic alterations, which play a role in the etiology of Barrett's esophagus (BE), could help identify high-risk individuals for esophageal adenocarcinoma (EA). The aim of the present study was to investigate the role of oxidative DNA damage, glutathione (GSH) concentration as oxidative stress parameters and DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic polymorphisms as individual susceptibility parameters in the etiology of BE. The study groups comprised BE patients who were clinically diagnosed (n = 40) and a healthy control group (n = 40). Basal DNA damage, pyrimidine and purine base damage after H(2)O(2) induction, H( 2)O(2) sensitivity, DNA repair capacity, oxidized pyrimidine and purine base damage repair were evaluated in peripheral blood lymphocytes with a modified comet assay using specific endonucleases (Endo III and Fpg). Polymerase chain reaction-restriction length polymorphism (PCR-RFLP)-based assays were used for genotyping. The patient group showed elevated levels of basal DNA damage, pyrimidine base damage and H(2)O(2) sensitivity as compared to controls (p < .05). DNA repair capacity, oxidized pyrimidine and purine base damage repair capacity, were not statistically different between patients and controls. GSH concentration was found to be significantly lower in smoking patients than in the controls (p < .05). None of the genetic variations changed the risk of having BE disease. However, patients carrying the variant OGG1 Cys allele showed elevated levels of pyrimidine base damage as compared to patients carrying the wild-type OGG1 Ser (p < .05). The results of this study point to a role of oxidative DNA damage in BE. However, DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic polymorphisms appeared to play no role in the individual susceptibility to this disease.KadiogluElaEToxicology Department, Faculty of Pharmacy, Gazi University, Ankara, Turkey. ela1015@hotmail.comSardasSemraSErgunMeltemMUnalSelahattinSKarakayaAli EsatAEengJournal ArticleResearch Support, Non-U.S. Gov't20100107
EnglandToxicol Ind Health86027020748-23370BiomarkersBBX060AN9VHydrogen PeroxideEC 1.15.1.1Superoxide DismutaseEC 1.15.1.1superoxide dismutase 2EC 2.5.1.18Glutathione TransferaseEC 2.5.1.18glutathione S-transferase M1EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanGAN16C9B8OGlutathioneIMAdolescentAdultAgedAnalysis of VarianceBarrett EsophagusenzymologygeneticsBiomarkersmetabolismCase-Control StudiesComet AssayDNA DamagephysiologyDNA GlycosylasesgeneticsDNA RepairFemaleGenetic Predisposition to DiseaseGlutathionemetabolismGlutathione TransferasegeneticsHumansHydrogen PeroxideMaleMiddle AgedStatistics, NonparametricSuperoxide Dismutasegenetics
201019602010196020105760ppublish20056743074823370935927810.1177/0748233709359278
200423772010050320170922
1568-7856922010Feb04DNA repairDNA Repair (Amst.)Use of a molecular beacon to track the activity of base excision repair protein OGG1 in live cells.144-5210.1016/j.dnarep.2009.11.009An abundant form of DNA damage caused by reactive oxygen species is 8-oxo-7,8-dihydroguanine for which the base excision repair protein 8-oxoguanine-DNA glycosylase 1 (OGG1) is a major repair enzyme. To assess the location and intracellular activity of the OGG1 protein in response to oxidative stress, we have utilised a fluorescence-quench molecular beacon switch containing a 8-oxo-dG:C base pair and a fluorescent and quencher molecule at opposite ends of a hairpin oligonucleotide. Oxidative stress was induced by treatment with potassium bromate. Flow cytometry demonstrated a concentration-dependent increase in the activity of OGG1 that was detected by the fluorescence produced when the oligonucleotide was cleaved in the cells treated with potassium bromate. This signal is highly specific and not detectable in OGG1 knock out cells. Induction of OGG1 activity is not a result of induction of OGG1 gene expression as assessed by qPCR suggesting a role for protein stabilisation or increased OGG1 catalytic activity. High resolution confocal microscopy pinpointed the location of the fluorescent molecular beacon in live cells to perinuclear regions that were identified as mitochondria by co-staining with mitotracker dye. There is no evidence of cut beacon within the nuclear compartment of the cell. Control experiments with a positive control beacon (G:C base pair and lacking the DAB quencher) did not result in mitochondrial localisation of fluorescence signal indicating that the dye does not accumulate in mitochondria independent of OGG1 activity. Furthermore, faint nuclear staining was apparent confirming that the beacon structure is able to enter the nucleus. In conclusion, these data indicate that the mitochondria are the major site for OGG1 repair activity under conditions of oxidative stress.Copyright 2009 Elsevier B.V. All rights reserved.MirbahaiLedaLSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.KershawRachael MRMGreenRichard MRMHaydenRachel EREMeldrumRosalind ARAHodgesNikolas JNJengG0400648Medical Research CouncilUnited KingdomJournal Article20091229
NetherlandsDNA Repair (Amst)1011391381568-78560Bromates0Molecular Probes04MB35W6ZApotassium bromate88847-89-68-oxo-7-hydrodeoxyguanosineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseG9481N71RODeoxyguanosineGAN16C9B8OGlutathioneIMAnimalsBase SequenceBromatespharmacologyCell Deathdrug effectsCell Survivaldrug effectsDNA GlycosylasesgeneticsmetabolismDNA Repairdrug effectsDeoxyguanosineanalogs & derivativesmetabolismEnzyme Inductiondrug effectsFibroblastscytologyenzymologyGlutathionemetabolismMiceMicroscopy, ConfocalMitochondriadrug effectsenzymologyMolecular ProbesgeneticsmetabolismMolecular Sequence DataOxidative Stressdrug effectsProtein Transportdrug effectsReverse Transcriptase Polymerase Chain ReactionTranscriptional Activationdrug effects
200905132009111920091119201011602010116020105460ppublish20042377S1568-7864(09)00310-310.1016/j.dnarep.2009.11.009
200237022010042320151119
1476-559429132010Apr01OncogeneOncogeneOGG1 is a novel prognostic indicator in acute myeloid leukaemia.2005-1210.1038/onc.2009.462OGG1 (8-oxoguanine DNA glycosylase) constitutes a key component of the DNA base excision repair pathway, catalysing the removal of 8-oxoguanine nucleotides from DNA, thereby suppressing mutagenesis and cell death. We found that OGG1 expression was significantly downregulated by the RUNX1-ETO fusion protein product of the t(8;21) chromosome translocation in normal haematopoietic progenitor cells and in patients with acute myeloid leukaemia (AML). Further examination of OGG1 expression in 174 AML trial patients using Affymetrix microarrays showed that the prevalence rate of OGG1 expression was 33% and correlated strongly with adverse cytogenetics. OGG1-expressing patients had a worse relapse-free survival and overall survival and an increased risk of relapse at 5-years of follow-up. There remained a trend towards increased relapse rate among OGG1-expressing patients, even after adjusting for other known risk factors in comprehensive stratified analyses. We also determined a trend for OGG1 expression to have a more adverse impact on disease outcome in the context of the FLT3-ITD mutation. This study highlights OGG1 as a valuable prognostic marker that could be used to sub-stratify AML patients to predict those likely to fail conventional chemotherapies but those likely to benefit from novel therapeutic approaches that modulate DNA repair activity.LiddiardKKDepartment of Haematology, School of Medicine, Cardiff University, Cardiff, UK.HillsRRBurnettA KAKDarleyR LRLTonksAAengMedical Research CouncilUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20091221
EnglandOncogene87115620950-92320Biomarkers, Tumor5614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMBiomarkers, TumorgeneticsmetabolismDNA GlycosylasesgeneticsmetabolismFollow-Up StudiesGuanineanalogs & derivativesmetabolismHumansLeukemia, Myeloid, AcutediagnosisenzymologymetabolismMutationPrognosis
20091222602009122260201042460ppublish20023702onc200946210.1038/onc.2009.462
199428582010020520161019
1460-20752922010Jan20The EMBO journalEMBO J.Deletion of Ogg1 DNA glycosylase results in telomere base damage and length alteration in yeast.398-40910.1038/emboj.2009.355Telomeres consist of short guanine-rich repeats. Guanine can be oxidized to 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). 8-oxoguanine DNA glycosylase (Ogg1) repairs these oxidative guanine lesions through the base excision repair (BER) pathway. Here we show that in Saccharomyces cerevisiae ablation of Ogg1p leads to an increase in oxidized guanine level in telomeric DNA. The ogg1 deletion (ogg1Delta) strain shows telomere lengthening that is dependent on telomerase and/or Rad52p-mediated homologous recombination. 8-oxoG in telomeric repeats attenuates the binding of the telomere binding protein, Rap1p, to telomeric DNA in vitro. Moreover, the amount of telomere-bound Rap1p and Rif2p is reduced in ogg1Delta strain. These results suggest that oxidized guanines may perturb telomere length equilibrium by attenuating telomere protein complex to function in telomeres, which in turn impedes their regulation of pathways engaged in telomere length maintenance. We propose that Ogg1p is critical in maintaining telomere length homoeostasis through telomere guanine damage repair, and that interfering with telomere length homoeostasis may be one of the mechanism(s) by which oxidative DNA damage inflicts the genome.LuJianJLaboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.LiuYieYengIntramural NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Intramural20091126
EnglandEMBO J82086640261-41890RAP1 protein, S cerevisiae0RIF2 protein, S cerevisiae0Saccharomyces cerevisiae Proteins0Telomere-Binding Proteins0Transcription Factors5Z93L87A1RGuanine9007-49-2DNAEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, S cerevisiaeIMCell. 2001 Sep 21;106(6):661-7311572773Nucleic Acids Res. 2007;35(17):5809-1817720711Mol Cell Biol. 2008 Jan;28(1):20-917967889Genetics. 2008 Feb;178(2):693-70118245359Mol Cell Biol. 2008 Apr;28(7):2380-9018212041Cell. 1990 Nov 16;63(4):739-502225074Nucleic Acids Res. 1992 Mar 25;20(6):14251561104Genes Dev. 1992 May;6(5):801-141577274Cell. 1993 Apr 23;73(2):347-608477448Genes Dev. 1993 Jul;7(7A):1146-598319907Cell. 1994 Jan 14;76(1):145-558287473Science. 1994 Oct 21;266(5184):404-97545955Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12213-77991608Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):258-627816828Nature. 1995 Aug 3;376(6539):403-97630414Science. 1995 Dec 8;270(5242):1601-77502069Cell. 1996 Apr 5;85(1):125-368620531Nature. 1996 Sep 26;383(6598):354-78848051Annu Rev Biochem. 1996;65:337-658811183Genetics. 1996 Dec;144(4):1399-4128978029Science. 1997 Feb 14;275(5302):986-909020083Nature. 1997 Feb 20;385(6618):740-39034193Genes Dev. 1997 Mar 15;11(6):748-609087429Science. 1997 Apr 25;276(5312):561-79110970Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9202-79256460Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12486-919770512J Biol Chem. 1998 Dec 11;273(50):33360-69837911J Biol Chem. 1999 Jan 8;274(2):962-719873038Yeast. 1999 Feb;15(3):205-1810077187Mol Cell Biol. 1999 Apr;19(4):2929-3510082560Genetics. 1999 May;152(1):143-5210224249EMBO J. 1999 Jun 15;18(12):3509-1910369690FEBS Lett. 1999 Jun 25;453(3):365-810405177Mol Cell Biol. 2004 Dec;24(24):10857-6715572688Nucleic Acids Res. 2005;33(4):1230-915731343Methods Mol Biol. 2006;313:265-31616118440Nature. 2005 Nov 3;438(7064):57-6116121131J Biol Chem. 2005 Dec 9;280(49):40544-5116221681Nucleic Acids Res. 2006;34(5):1393-40416522649PLoS Biol. 2006 Jan;4(1):e1116379496Nature. 2006 Apr 6;440(7085):824-816598261Genome Res. 2006 May;16(5):567-7516651663Mol Cell Biol. 2007 Jan;27(1):297-31117074814DNA Repair (Amst). 2007 Apr 1;6(4):481-817127104PLoS Genet. 2007 Jun;3(6):e10517590086Mol Cell. 2007 Sep 7;27(5):851-817803948Mol Cell Biol. 1999 Dec;19(12):8083-9310567534Biochemistry. 1999 Dec 21;38(51):16733-910606504Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15044-910611335Mol Cell Biol. 2000 Mar;20(5):1659-6810669743J Biol Chem. 2000 Feb 25;275(8):5723-3210681558Ann N Y Acad Sci. 2000 Jun;908:99-11010911951Mol Cell. 2008 Jul 25;31(2):153-6518657499Annu Rev Genet. 2008;42:301-3418680434Free Radic Biol Med. 2008 Dec 15;45(12):1610-2118692130Mol Cell. 2009 Feb 13;33(3):312-2219217405Mol Cell Biol. 2009 Aug;29(16):4441-5419506022Mol Cell Biol. 2002 Jan;22(1):332-4211739745Free Radic Biol Med. 2002 Jun 15;32(12):1244-5312057762Cell. 2004 Apr 30;117(3):323-3515109493Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8658-6315161972Mol Cell Biol. 2004 Nov;24(22):9887-9815509791Cell. 1983 Jun;33(2):563-736345000Cell. 1984 Nov;39(1):191-2016091911Genetics. 1990 Mar;124(3):533-452179052Mutat Res. 2000 Jun 30;451(1-2):39-5110915864Curr Biol. 2000 Oct 19;10(20):1299-30211069113Nucleic Acids Res. 2001 Mar 15;29(6):1381-811239005Nat Genet. 2001 Aug;28(4):327-3411455386DNAmetabolismDNA GlycosylasesgeneticsmetabolismGene DeletionGuaninemetabolismOxidation-ReductionProtein BindingSaccharomyces cerevisiaegeneticsmetabolismSaccharomyces cerevisiae ProteinsgeneticsmetabolismTelomerechemistrymetabolismTelomere-Binding ProteinsmetabolismTranscription Factorsmetabolism
20090304200911042009112860200911286020102660ppublish19942858emboj200935510.1038/emboj.2009.355PMC2824463
192428242011011220171108
1559-131X2722010JunMedical oncology (Northwood, London, England)Med. Oncol.Impact of nucleotide excision repair ERCC2 and base excision repair APEX1 genes polymorphism and its association with recurrence after adjuvant BCG immunotherapy in bladder cancer patients of North India.159-6610.1007/s12032-009-9187-yAltered DNA repair capacity due to polymorphisms in DNA repair genes may modify response to Bacillus Calmette-Guerin (BCG) immunotherapy for high risk superficial bladder cancer (SBC).We evaluated the prospective outcome of exicision repair cross complementing group 2 (ERCC2) and apurinic/apyriminidic endonuclease (APEX1) gene in tumor recurrence after BCG immunotherapy in SBC patients.The study included 135 SBC patients, of which BCG immunotherapy was received by 74 patients. Genotyping was performed for ERCC2 Asp(312)Asn (G > A), Lys751Gln (A > C), and APEX1 Asp(148)Glu (T > G) polymorphisms by restriction fragment length polymorphism PCR and amplification refractory mutation system (ARMS) methods.Multiple Cox regression analysis demonstrated association of variant genotype of ERCC2 (312)AA polymorphism with high risk of recurrence in BCG treated patients (HR = 3.07, P = 0.016, P ( c ) = 0.048). Patients with the ERCC2 (312)AA polymorphic genotypes showed shorter recurrence free survival (log-rank, P = 0.005; AA/GA + AA = 14/44) who received BCG treatment. Overall, risk of recurrence in bladder cancer was observed with smokers and size of tumors (1-3 cm) (HR = 1.86, P = 0.023 and HR = 3.19, P = 0.031, respectively). Smokers were identified to be at elevated risk in BCG treated patients (HR = 2.84, P = 0.005). No association was observed with the (ERCC2 Lys(751)Gln and APEX1 Asp(148)Glu) polymorphisms and risk of recurrence.Our data suggested variant (AA) of ERCC2 312 AA genotype to be associated with high risk of tumor recurrence and reduced recurrence free survival in superficial bladder cancer patients.GangawarRuchikaRDepartment of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014, India.AhirwarDineshDMandhaniAnilAMittalRama DeviRDengComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't20090226
United StatesMed Oncol94355121357-05600Adjuvants, Immunologic0BCG VaccineEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 5.99.-ERCC2 protein, humanIMCancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039J Clin Oncol. 2005 Aug 20;23(24):5746-5616110031Cancer Pract. 2002 Nov-Dec;10(6):311-2212406054Carcinogenesis. 2002 Apr;23(4):599-60311960912Acta Oncol. 2007;46(1):31-4117438703Mutat Res. 2007 Jun 1;619(1-2):68-8017363013Int J Epidemiol. 2008 Dec;37(6):1316-2518641418Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-99207062Ann Oncol. 2006 Apr;17(4):668-7516407418Cell Biochem Biophys. 2001;35(2):141-7011892789Nucleic Acids Res. 1988 Feb 11;16(3):12153344216Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):23-914744728Cancer Epidemiol Biomarkers Prev. 2003 Apr;12(4):359-6512692111Carcinogenesis. 2006 May;27(5):1030-716311243Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):84-9117220334Carcinogenesis. 2004 Aug;25(8):1395-40115044328Clin Cancer Res. 2005 Feb 15;11(4):1408-1515746040Br J Urol. 1995 Feb;75(2):180-47850322EMBO J. 1994 May 15;13(10):2388-928194528Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):878-8415824159Cancer Epidemiol Biomarkers Prev. 2008 Mar;17(3):507-1718349268Postgrad Med J. 2002 Aug;78(922):449-5412185215Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1004-1112376500Br J Cancer. 2006 Sep 4;95(5):561-7016880786Gynecol Oncol. 2007 Oct;107(1 Suppl 1):S223-917825393Genetica. 2009 May;136(1):163-918946634Carcinogenesis. 2004 May;25(5):729-3414688016J Urol. 2003 Sep;170(3):964-912913751EMBO J. 1999 Mar 1;18(5):1357-6610064601Environ Mol Mutagen. 2001;38(2-3):180-9011746753Cancer Res. 2001 Feb 15;61(4):1354-711245433Adjuvants, Immunologictherapeutic useAgedBCG Vaccinetherapeutic useCase-Control StudiesDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleFollow-Up StudiesHumansImmunotherapymethodsIndiaepidemiologyMaleMiddle AgedNeoplasm Recurrence, Localdrug therapyepidemiologygeneticsPolymorphism, Single NucleotidegeneticsProspective StudiesUrinary Bladder Neoplasmsdrug therapyepidemiologygeneticsXeroderma Pigmentosum Group D Proteingenetics
2008111920090210200922790200922790201111360ppublish1924282410.1007/s12032-009-9187-y
184827812010031520091216
1558-14973122010FebNeurobiology of agingNeurobiol. AgingLack of association between the APEX1 Asp148Glu polymorphism and sporadic amyotrophic lateral sclerosis.353-510.1016/j.neurobiolaging.2008.03.018Impairments in DNA repair enzymes have been observed in amyotrophic lateral sclerosis (ALS) tissues, particularly in the activity of the apurinic/apyrimidinic endonuclease 1 (APEX1). Moreover, it was suggested that the common APEX1 Asp148Glu polymorphism might be associated with ALS risk. To further address this question we performed the present study aimed at evaluating the contribution of the APEX1 Asp148Glu polymorphism in sporadic ALS (sALS) risk and clinical presentation, including age and site of onset and disease progression. We screened 134 sALS Italian patients and 129 matched controls for the presence of the APEX1 Asp148Glu polymorphism. No difference in APEX1 Asp148Glu allele and genotype frequencies was found between the groups, nor was the polymorphism associated with age and site of onset or disease progression. Present results do not support a role for the APEX1 Asp148Glu polymorphism in sALS pathogenesis in the Italian population.CoppedèFabioFDepartment of Neuroscience, Neurological Clinic, University of Pisa, 56126 Pisa, Italy. f.coppede@geog.unipi.itLo GerfoAnnalisaACarlesiCeciliaCPiazzaSelinaSMancusoMichelangeloMPasqualiLiviaLMurriLuigiLMiglioreLuciaLSicilianoGabrieleGengJournal Article
United StatesNeurobiol Aging81004370197-4580EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdultAge of OnsetAgedAged, 80 and overAmyotrophic Lateral SclerosisgeneticsCase-Control StudiesCohort StudiesDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDisease ProgressionEuropean Continental Ancestry GroupgeneticsFemaleGene FrequencyGenetic Predisposition to DiseaseGenotypeHumansItalyMaleMiddle AgedMutation, MissensePolymorphism, GeneticSequence Analysis, DNA
200801092008031120080329200851790201031760200851790ppublish18482781S0197-4580(08)00115-210.1016/j.neurobiolaging.2008.03.018
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"EDirect for PubMed: Part 1: Getting PubMed Data" Sample Code

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Below you will find sample code for the examples, in-class exercises and homework presented in the first session of the “EDirect for PubMed” Insider’s Guide class. These examples are written for use with EDirect in a Unix environment. If you need help installing and setting up EDirect, please see our “Installing EDirect” page.

For more examples, please see the sample code from the other parts of “EDirect for PubMed”:

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The code below is lightly annotated to explain how it works, but if you are looking for more information, we suggest you review our EDirect documentation.

There are many different ways to answer the questions discussed in class. The sample code below provides some options, but by no means the only options. Feel free to modify, adapt, edit, re-use or completely discard any of the suggestions below when trying to find a solution that works best for you.

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esearch

Conduct a simple search of PubMed for articles on seasonal affective disorder

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esearch -db pubmed -query "seasonal affective disorder"
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This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "seasonal affective disorder").

If you want to see the query translation for your search (like you would see in the Search Details box with the web version of PubMed), you can add an additional argument to your command:

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esearch -db pubmed -query "seasonal affective disorder" -log
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By adding the -log argument to esearch, the command will also output the E-utilities URL and query translation for your search.

Conduct a simple search of PubMed for articles on malaria in the journal JAMA

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esearch -db pubmed -query "malaria AND jama[journal]"
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This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "malaria AND jama[journal]"). Note that the search query can include Boolean operators (AND) and search field tags ([journal]) to help focus our search, just as we can in the web version of PubMed.

Restrict search results by publication date

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esearch -db pubmed -query "malaria AND jama[journal]" \
+-datetype PDAT -mindate 2015 -maxdate 2017
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The first line of code is the same as our previous example, though the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting.

The second line limits the search results by publication date (-datetype PDAT), including only articles published between 2015 and 2017 (-mindate 2015 -maxdate 2017).

Conduct a PubMed search with a search string that includes quotation marks

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esearch -db pubmed -query "cancer AND \"science\"[journal]"
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This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "cancer AND \"science\"[journal]"). We need to “escape” the double quotation marks (“) in our search query by putting a ”\" before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the -query argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched.

efetch

Retrieve a single PubMed record in text abstract format

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efetch -db pubmed -id 25359968 -format abstract
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This line of code uses the efetch command to retrieve a record from PubMed (-db pubmed). We specify that we will retrieve the record for PMID 25359968 (-id 25359968) and that we want the results in the text abstract format (-format abstract).

Retrieve multiple PubMed records in text abstract format

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efetch -db pubmed -id 24102982,21171099,17150207 -format abstract
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This line of code uses the efetch command to retrieve records from PubMed (-db pubmed). We specify that we will retrieve the records for PMID 24102982,21171099,17150207 (-id 24102982,21171099,17150207) and that we want the results in the text abstract format (-format abstract).

Creating a data pipeline

Conduct a PubMed search and retrieve the results as a list of PMIDs

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esearch -db pubmed -query "asthenopia[mh] AND nursing[sh]" | efetch -format uid
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This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "asthenopia[mh] AND nursing[sh]"), and then pipes the resulting PMIDs into an efetch command (| efetch), which retrieves the PubMed records, but outputs only the PMIDs (-format uid). For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.

In-class exercise solutions

Exercise 1: esearch

How many Spanish-language articles about diabetes are in PubMed?

Solution:

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esearch -db pubmed -query "diabetes AND spanish[lang]"
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This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "diabetes AND spanish[lang]"). Note that the search query can include Boolean operators (AND) and search field tags ([lang]) to help focus our search, just as we can in the web version of PubMed.

Exercise 2: esearch

How many articles were written by BH Smith between 2012 and 2017, inclusive?

Solutions:

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esearch -db pubmed -query "smith bh[author]" -datetype PDAT -mindate 2012 -maxdate 2017
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There are multiple possible solutions to this exercise. This solution uses the esearch command to search PubMed (-db pubmed) for our search query (-query "smith bh[author]"). Note that the search query can include search field tags ([author]) to help focus our search, just as we can in the web version of PubMed. The esearch command also limits the search results by publication date (-datetype PDAT), including only articles published between 2012 and 2017 (-mindate 2012 -maxdate 2017).

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esearch -db pubmed -query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat])"
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The second solution is largely the same as the first. Rather than use the -datetype, -mindate, and -maxdate arguments to limit the search by publication date, this solution incorporates the date restriction into the search string itself (-query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat])"), just as you would include a date restriction in a search string in the web version of PubMed.

Exercise 3: efetch

Who is the first author listed on the PubMed record 26287646?

Solution:

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efetch -db pubmed -id 26287646 -format abstract
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This line of code uses the efetch command to retrieve a record from PubMed (-db pubmed). We specify that we will retrieve the record for PMID 25359968 (-id 25359968). The command retrieves the record in the text abstract format (-format abstract), which allows us to easily see that the first author of the article is PF Brennan. Rather than using the abstract format, we could instead use -format medline or -format xml to retrieve the record in the MEDLINE or XML formats, if we prefer.

Exercise 4: Combining Commands

How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017?

Solutions:

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esearch -db pubmed -query "smith bh[author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \
+efetch -format uid
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This solution begins the same as the first solution for Exercise 2. The first line concludes by piping (|) the results of the esearch command into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records, but outputs only the PMIDs (-format uid).

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esearch -db pubmed -query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat])" | \
+efetch -format uid
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Similarly, this solution begins the same as the second solution for Exercise 2, and then pipes the results of the esearch into the efetch, which retrieves the PubMed records, but outputs only the PMIDs (-format uid).

For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.

Homework solutions

Question 1

Using EDirect, write a command to find out how many citations are in PubMed for articles about using melatonin to treat sleep disorders.

Solution:

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esearch -db pubmed -query "melatonin sleep disorder"
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This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "melatonin sleep disorder").

Question 2

How many of the PubMed citations identified in question 2 were added to PubMed (i.e. created) between January 1, 2015 and July 1, 2017?

Solution:

There are multiple possible solutions to this question.

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esearch -db pubmed -query "melatonin sleep disorder" -datetype CRDT -mindate 2015/01/01 -maxdate 2017/07/01
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Both of these solutions use the esearch command to search PubMed (-db pubmed) for our search query (-query "melatonin sleep disorder"). In the first solution, the esearch command also limits the search results by the date citations were added to PubMed, using the “CRDT” date type (-datetype CRDT), including only articles created between January 1, 2015 and July 1, 2017 (-mindate 2015/01/01 -maxdate 2017/07/01).

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esearch -db pubmed -query "melatonin sleep disorder"  AND (2015/01/01[crdt] : 2017/07/01[crdt])"
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The second solution is largely the same as the first. Rather than use the -datetype, -mindate, and -maxdate arguments to limit the search by create date, this solution incorporates the date restriction into the search string itself (-query "melatonin sleep disorder" AND (2015/01/01[crdt] : 2017/07/01[crdt])"), just as you would include a date restriction in a search string in the web version of PubMed.

Question 3

Write a command to retreive the abstracts of the following PubMed records:

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27240713,27027883,22468771,20121990
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Solution:

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efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format abstract
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This line of code uses the efetch command to retrieve records from PubMed (-db pubmed). We specify that we will retrieve the records for four PMIDs: 27240713, 27027883, 22468771, and 20121990 (-id 27240713,27027883,22468771,20121990). The command retrieves the records in the text abstract format (-format abstract).

Question 4

Modify your answer to Question 3 to retrieve the full XML of all four records.

Solution:

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efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format xml
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This solution is largely the same as the solution for Question 3, but the -format argument has been changed to retrieve XML instead of the text Abstract format (-format xml).

Question 5

Write a series of commands that retrieves a list of PMIDs for all citations for papers written by the author with the ORCID 0000-0002-1141-6306.

Solution:

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esearch -db pubmed -query "0000-0002-1141-6306[auid]" | \
+efetch -format uid
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This solution begins by using the esearch command to search PubMed (-db pubmed) for citations including an author identifier of “0000-0002-1141-6306” (-query "0000-0002-1141-6306[auid]"). The first line concludes by piping (|) the results of the esearch command into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records, but outputs only the PMIDs (-format uid).

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"EDirect for PubMed: Part 2: Extracting Data from XML" Sample Code

+ +

Below you will find sample code for the examples, in-class exercises and homework presented in the second session of the “EDirect for PubMed” Insider’s Guide class. These examples are written for use with EDirect in a Unix environment. If you need help installing and setting up EDirect, please see our “Installing EDirect” page.

For more examples, please see the sample code from the other parts of “EDirect for PubMed”:

+

The code below is lightly annotated to explain how it works, but if you are looking for more information, we suggest you review our EDirect documentation.

There are many different ways to answer the questions discussed in class. The sample code below provides some options, but by no means the only options. Feel free to modify, adapt, edit, re-use or completely discard any of the suggestions below when trying to find a solution that works best for you.

+

xtract Basics

For an introduction to the xtract command, see the xtract section of our EDirect documentation.

Retrieve the article titles for a list of PubMed records

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element ArticleTitle
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row in our output table for every PubMed record (-pattern PubmedArticle). The -element argument indicates that the table should include a single column, containing the article title for the given record (-element ArticleTitle).

Retrieve the list of authors for a series of PubMed records

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern Author -element LastName
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row in our output table for every author (-pattern Author). The -element argument indicates that the table should include a single column, containing the last name for the given author (-element LastName).

Retrieve the PMID and year of publication for a PubMed record

In order to retrieve the PMID and the year of publication for a PubMed record, we might try to use code such as the following:

+
efetch -db pubmed -id 27101380 -format xml | \
+xtract -pattern PubmedArticle -element PMID Year
+

The first line of this code uses the efetch command to retrieve a record from PubMed (-db pubmed -id 27101380) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle; in this case, the table will only have a single row). The line then uses the -element argument to create two columns, one for PMID and one for Year. (-element PMID Year). However, the output of this series of commands is not what we expect:

+
27101380        27619336        27619799        27746956        27747057        2016    2016    2016      2016    2015    2016    2016    2016    2016
+

Rather than getting a single PMID and a single year, we get 5 PMIDs and 9 Years. This is because, while the -element argument is designed to create a new column for each element or attribute specified, it populates each column with the contents of every occurrence of the specified element or attribute in the -pattern. This means that if there are multiple occurrences of the <PMID> or <Year> elements in a PubMed record, the contents of all occurrences will be displayed. As a result, we see not only the PMID for the record, but also the PMIDs used to link it to other records which contain related comments or corrections. Furthermore, in addition to the publication year, we also the year for the other eight dates associated with the PubMed record.

We can avoid this by using Parent/Child construction to specify that we only want the contents of the <PMID> element that is a direct child of the <MedlineCitation> element, and that we only want the <Year> element that is a child of the <PubDate> element:

+
efetch -db pubmed -id 27101380 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID PubDate/Year
+

This version of the code gives us the output we expect:

+
27101380        2016
+

Retrieve three data elements for a list of PubMed records

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation ArticleTitle    
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one for the journal title abbreviation, and one for the article title (-element MedlineCitation/PMID ISOAbbreviation ArticleTitle).

sort-uniq-count-rank and head

Sort a list of authors by the frequency they appear in your results set

+
esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern Author -element LastName,Initials | \
+sort-uniq-count-rank | \
+head -n 10  
+

This series of commands searches PubMed for the string “traumatic brain injury athletes”, restricts results to those published in 2016 and 2017, retrieves the full XML records for each of the search results, extracts the last name and initials of every author on every record, sorts the authors by frequency of occurrence in the results set, and presents the top ten most frequently-occurring authors, along with the number of times that author appeared.

+
esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "traumatic brain injury athletes"). The line also restricts the search results to articles that were published in 2016 or 2017 (-datetype PDAT -mindate 2016 -maxdate 2017).

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern Author -element LastName,Initials | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials). This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line.

+
sort-uniq-count-rank | \
+

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set.

+
head -n 10
+

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set:

+
14      Iverson     GL
+11      Guskiewicz  KM
+10      Meehan   WP
+9       Kerr       ZY
+9       Kontos   AP
+9       Solomon     GS
+9       Zuckerman   SL
+8       Zafonte     R
+7       Broglio     SP
+7       Covassin    T
+

(Note: Your output may vary slightly, as additional citations are added to PubMed and the “most frequent” authors change.)

To show more or fewer rows, adjust the “10” up or down. If you want to see all of the authors, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the “|” and “\” characters from the previous line. Otherwise, the system will wait for you to finish entering your command.)

In-class exercise solutions

Note: The first three exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data.

Exercise 1

Write an xtract command that creates a table with one row per PubMed article. Each row should have two columns: volume number and issue number.

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element Volume Issue
+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with columns for volume number and issue number (-element Volume Issue).

Exercise 2

Write an xtract command that creates a table with one row per PubMed record. Each row should have three columns: PMID, journal ISSN, and citation status.

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISSN MedlineCitation@Status
+

This xtract command begins the same as the solution for Exercise 1 (xtract -pattern PubmedArticle). When creating the first column, this command uses Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (like as a child of a <CommentsCorrections> element; -element MedlineCitation/PMID).

Similarly, the second column is also created using Parent/Child construction. This is probably not strictly necessary, as the <ISSN> element only appears in one location in the PubMed XML structure. However, this demonstrates that there may be multiple valid EDirect solutions to a given question (Journal/ISSN).

Finally, the citation status, which is found in the “Status” attribute of the <MedlineCitation> element, is placed in the third column (MedlineCitation@Status).

Exercise 3

Find out which authors have been writing about traumatic brain injuries in athletes, with publications in 2016 and 2017. The output should be a list of author names, one per line, with each author’s last name and initials.

Solution:

+
esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern Author -element LastName,Initials
+

This series of commands searches PubMed for the string “traumatic brain injury athletes”, restricts results to those published in 2016 and 2017, retrieves the full XML records for each of the search results, and extracts the last name and initials of every author on every record.

+
esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
+

The first line of code uses esearch to search PubMed (-db pubmed) for our search query (-query "traumatic brain injury athletes"). The line also restricts the search results to articles that were published in 2016 or 2017 (-datetype PDAT -mindate 2016 -maxdate 2017).

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern Author -element LastName,Initials
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line.

The command then extracts each author’s last name and initials (-element LastName,Initials).

Homework solutions

Question 1

Using the efetch command below to retrieve PubMed XML, write an xtract command to extract specific elements and arrange them into a table. The table should have one PubMed record per row, with columns for PMID, Journal Title Abbreviation, Publication Year, Volume, Issue and Page Numbers.

+
efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml
+

Solution:

+
efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation PubDate/Year Volume Issue MedlinePgn
+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). When creating the first column, this command uses Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (like as a child of a <CommentsCorrections> element; -element MedlineCitation/PMID).

The second column is created without Parent/Child construction, as the <ISOAbbreviation> element is not repeated in a single PubMed XML record (ISOAbbreviation).

The third column also uses Parent/Child construction to retrieve the publication year (as opposed to other <Year> elements; PubDate/Year); the remaining elements only appear in one location in the PubMed XML structure, so Parent/Child construction is unnecessary (Volume Issue MedlinePgn).

Question 2

Create a table of the authors attached to PubMed record 28341696. The table should include each author’s last name, initials, and affiliation information (if listed).

Solution:

+
efetch -db pubmed -id 28341696 -format xml | \
+xtract -pattern Author -element LastName Initials Affiliation
+

This first line of this solution uses the efetch command to retrieve a record from PubMed (-db pubmed). We specify that we will retrieve the record for PMID 28341696 (-id 28341696) and that we want the results in XML (-format xml).

+
xtract -pattern Author -element LastName Initials Affiliation
+

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name, initials, and affiliation information (-element LastName Initials Affiliation).

Question 3

Write a series of commands to generate a table of PubMed records for review articles about the Paleolithic diet. The table should have one row per citation, and should include columns for the PMID, the citation status, and the article title.

Solution:

+
esearch -db pubmed -query "review[pt] paleolithic diet" | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID MedlineCitation@Status ArticleTitle
+

This series of commands searches PubMed for the string “review[pt] paleolithic diet”, retrieves the full XML records for each of the search results, and extracts the last name and initials of every author on every record.

+
esearch -db pubmed -query "review[pt] paleolithic diet" | \
+

The first line of code uses esearch to search PubMed (-db pubmed) for our search query (-query "review[pt] paleolithic diet"). Note that the search query can include search field tags ([pt]) to help focus our search, just as we can in the web version of PubMed.

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern PubmedArticle -element MedlineCitation/PMID MedlineCitation@Status ArticleTitle
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every PubMed record (-pattern PubmedArticle).

The command then extracts each record’s PMID (using Parent/Child construction; -element MedlineCitation/PMID), citation status (using “@” to retrieve the attribute value for “Status”; MedlineCitation@Status), and article title (ArticleTitle).

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"EDirect for PubMed: Part 3: Formatting Results and Unix Tools" Sample Code

+ +

Below you will find sample code for the examples, in-class exercises and homework presented in the third session of the “EDirect for PubMed” Insider’s Guide class. These examples are written for use with EDirect in a Unix environment. If you need help installing and setting up EDirect, please see our “Installing EDirect” page.

For more examples, please see the sample code from the other parts of “EDirect for PubMed”:

+

The code below is lightly annotated to explain how it works, but if you are looking for more information, we suggest you review our EDirect documentation.

There are many different ways to answer the questions discussed in class. The sample code below provides some options, but by no means the only options. Feel free to modify, adapt, edit, re-use or completely discard any of the suggestions below when trying to find a solution that works best for you.

+

xtract Formatting arguments

For an introduction to xtract Formatting arguments, see the Customizing separators section of our EDirect documentation.

Change the separators in an xtract output table

We can use the -tab and -sep arguments to modify the separators in an xtract output table. We will start with a basic xtract statement with no customized separators:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISSN LastName
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one for the journal ISSN, and one for author last name (-element MedlineCitation/PMID ISSN LastName). For articles with more than one author, we will see multiple author last names in the third column:

+
24102982        1742-4658       Wu      Doyle   Barry   Beauvais        Rozkalne        Piao    Lawlor    Kopin   Walsh   Gussoni
+21171099        1097-4598       Wu      Gussoni
+17150207        0012-1606       Yoon    Molloy  Wu      Cowan   Gussoni
+

By default, xtract separates columns in the output table with tabs (indicated in Unix as \t). Additionally, by default, xtract separates multiple values in the same column with tabs. So the following series of commands:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "\t" -sep "\t" -element MedlineCitation/PMID ISSN LastName
+

produces the same output as before, since we are telling xtract to use a tab to separate between columns (-tab "\t") and between multiple values in the same column (-sep "\t"), which xtract is already doing by default:

+
24102982        1742-4658       Wu      Doyle   Barry   Beauvais        Rozkalne        Piao    Lawlor    Kopin   Walsh   Gussoni
+21171099        1097-4598       Wu      Gussoni
+17150207        0012-1606       Yoon    Molloy  Wu      Cowan   Gussoni
+

We can modify the output by modifying the -sep argument:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "\t" -sep " " -element MedlineCitation/PMID ISSN LastName
+

This series of commands tells xtract to keep the separators between columns the same, but to separate multiple values in the same column (such as the multiple author last names in our third column) by spaces instead of tabs:

+
24102982        1742-4658       Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni
+21171099        1097-4598       Wu Gussoni
+17150207        0012-1606       Yoon Molloy Wu Cowan Gussoni
+

We can further modify the output by modifying the -tab argument:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep " " -element MedlineCitation/PMID ISSN LastName
+

This time, the separators between columns have been changed from tabs to pipes (-tab "|"), while multiple values in the same column are still separated by spaces:

+
24102982|1742-4658|Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni
+21171099|1097-4598|Wu Gussoni
+17150207|0012-1606|Yoon Molloy Wu Cowan Gussoni
+

The -tab and -sep arguments also allow you to specify separators of more than one character:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep ", " -element MedlineCitation/PMID ISSN LastName
+

This series of commands uses pipes to separate the columns (-tab "|"), but uses a comma followed by a space to separate the last names (-sep ", "):

+
24102982|1742-4658|Wu, Doyle, Barry, Beauvais, Rozkalne, Piao, Lawlor, Kopin, Walsh, Gussoni
+21171099|1097-4598|Wu, Gussoni
+17150207|0012-1606|Yoon, Molloy, Wu, Cowan, Gussoni
+

xtract Exploration arguments

For an introduction to xtract Exploration arguments, see the Exploration arguments section of our EDirect documentation.

Retrieve author names for a list of PubMed records

In order to retrieve the author names (including last name and initials) for all of the authors associated with each of several PubMed records, we might try to use code such as the following:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID LastName Initials
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one for author last name, and one for author initials (-element MedlineCitation/PMID LastName Initials). However, the output of this series of commands is not what we expect:

+
24102982        Wu      Doyle   Barry   Beauvais        Rozkalne        Piao    Lawlor  Kopin   Walsh     Gussoni MP      JR      B       A       A       X       MW      AS    CA      E
+21171099        Wu      Gussoni MP      E
+17150207        Yoon    Molloy  Wu      Cowan   Gussoni S       MJ      MP      DB      E
+

The PMID appears as we expect, as does the first author last name. However, rather than following the first author’s last name with the corresponding initials, our output lists all of the authors’ last names for a PubMed record first, before listing all of the authors’ initials.

To retain the relationship between last name and initials, we could use the following series of commands:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -element LastName Initials
+

The second line of this code creates a column for the PMID as before (xtract -pattern PubmedArticle -element MedlineCitation/PMID). However, the code then uses the -block argument to direct xtract to look for an <Author> element, then to look within that <Author> for <LastName> and <Initials> elements (-block Author -element LastName Initials). Because each author has only one last name and one set of initials, xtract outputs a corresponding pair of last name and initials, before moving on to find the next author. This process is then repeated for each author, giving us the output we expect:

+
24102982        Wu      MP      Doyle   JR      Barry   B       Beauvais        A       Rozkalne        A       Piao    X       Lawlor  MW      Kopin   AS   Walsh    CA      Gussoni E
+21171099        Wu      MP      Gussoni E
+17150207        Yoon    S       Molloy  MJ      Wu      MP      Cowan   DB      Gussoni E
+

Putting values from multiple elements in the same column

Separate author last name and initials with a space, while separating columns with a tab

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -sep " " -element LastName,Initials
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and creates a column for the PMID (xtract -pattern PubmedArticle -element MedlineCitation/PMID). As seen in previous examples, the code than uses the -block argument to direct xtract to look for an <Author> element (-block Author), then to look within that <Author> for <LastName> and <Initials> elements.

Because each author has only one last name and one set of initials, xtract outputs a corresponding pair of last name and initials, before moving on to find the next author. However, rather than putting the last name and initials in separate columns, this command uses a comma to group together both the last name and initials in the same column (-element LastName,Initials). This tells xtract to separate the last name and initials with the character we define in the -sep argument (which we have defined as a single space: -sep " "), instead of using the separator between columns (which is still the default tab), and gives us the output we desire:

+
24102982        Wu MP   Doyle JR        Barry B Beauvais A      Rozkalne A      Piao X  Lawlor MW       Kopin AS        Walsh CA      Gussoni E
+21171099        Wu MP   Gussoni E
+17150207        Yoon S  Molloy MJ       Wu MP   Cowan DB        Gussoni E
+

Working with files

Saving results to a file

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.txt
+

This line of code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and redirects the XML output to a file named “testfile.txt” (> testfile.txt).

Using a search string saved in a file to search PubMed

+
esearch -db pubmed -query "$(cat searchstring.txt)"
+

This line of code uses the esearch command to search PubMed (-db pubmed). The search query is stored in a text file (“searchstring.txt”), and the cat command is used to access the contents of the file for use as a search query (-query "$(cat searchstring.txt)"). The dollar-sign and parentheses around cat searchstring.txt indicate that Unix should use the value of cat searchstring.txt (i.e. the contents of the file “searchstring.txt”), rather than simply the words “cat searchstring.txt”.

epost

Post two PMIDs to the History server

+
epost -db pubmed -id 24102982,21171099
+

This line of code uses the epost command to post two unique identifiers (UIDs) to the History server (-id 24102982,21171099), indicating that the UIDs are for records in the PubMed database (i.e. that the UIDs are actually PMIDs; -db pubmed).

For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.

Post two PMIDs to the History server and retrieve the corresponding PubMed records in abstract format

+
epost -db pubmed -id 24102982,21171099 | efetch -format abstract
+

This line of code uses the epost command to post two unique identifiers (UIDs) to the History server (-id 24102982,21171099), indicating that the UIDs are for records in the PubMed database (i.e. that the UIDs are actually PMIDs; -db pubmed). The line then pipes information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract). For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.

Retrieve PubMed records in abstract format for a list of PMIDs contained in a CSV file

+
cat pmids.csv | epost -db pubmed | efetch -format abstract
+

This line of code uses cat to open a CSV file (“pmids.csv”) which contains a list of PMIDs (cat pmids.csv). Rather than displaying the contents of the file on the screen, this line of code pipes the contents of the file into an epost command (| epost). The epost command stores the PMIDs on the History server, indicating to the History server that they are PMIDs, and not UIDs from a different database (-db pubmed). Finally, the line pipes the information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract).

+
epost -db pubmed -input pmids.csv | efetch -format abstract
+

This line of code is another way of accomplishing the same task as the previous example. Rather than use cat to open the file “pmids.csv”, this line uses the epost command’s -input argument, which is a new feature of EDirect, added in version 4.90 (released on September 14, 2016). The epost command stores the PMIDs on the History server, indicating to the History server that they are PMIDs, and not UIDs from a different database (-db pubmed). Finally, the line pipes the information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract).

For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.

In-class exercise solutions

Note: The first two exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data.

Exercise 1

Write an xtract command that generates a new row for each PubMed record, and has columns for PMID, journal title abbreviation, and author-supplied keywords. Each column should be separated by “|”. Multiple keywords in the last column should be separated with commas.

Sample Output:

+
26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology
+

Solution:

+
efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep "," -element MedlineCitation/PMID ISOAbbreviation Keyword
+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with columns for PMID (specified using Parent/Child construction), journal title abbreviation, and author-supplied keywords (-element MedlineCitation/PMID ISOAbbreviation Keyword).

Instead of separating the columns by tabs, the command uses the -tab argument to specify pipe (“|”) as a separator (-tab "|"). Because each record could have multiple author-supplied keywords, the command uses the -sep argument to specify a separator between multiple values in a column (i.e. multiple author-supplied keywords in the third column; -sep ",").

Exercise 2

Write an xtract command that creates a table with a new row for each PubMed record. Each row should have the record’s PMID, as well as a list of all the MeSH headings for the records, separated by “|”. If a MeSH heading has subheadings attached, separate the heading and subheadings with “/”. For example:

+
24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology
+

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \
+-block MeshHeading -tab "|" -sep "/" -element DescriptorName,QualifierName
+

This xtract command begins the same as the solution for Exercise 1 (xtract -pattern PubmedArticle). The command then specifies a separator between columns (-tab "|") and the first column in the output table (using Parent/Child construction; -element MedlineCitation/PMID). The “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

The command continues on the next line, using -block to maintain the relationship between MeSH headings and related subheadings. The -block argument directs xtract to look for a <MeshHeading> element (-block MeshHeading) then to look within that <MeshHeading> for <DescriptorName> and <QualifierName> elements. Another argument is needed to respecify the separator between columns (-tab "|"), as the separators are reset to default by -block.

Each <MeshHeading> element contains one <DescriptorName>, but may contain zero or more <QualifierName> elements. For each -block, the -element argument populates a column with the <DescriptorName> and all of the <QualifierName> elements, if there are any (-element DescriptorName,QualifierName). For MeSH headings with subheadings, this will place multiple values in the same column (one <DescriptorName> and one or more <QualifierName> elements), so we establish “/” as a separator between multiple values in the same column (-sep "/").

Exercise 3

How can we get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil? Save your results to a file.

Solution:

+
esearch -db pubmed -query "zika virus microcephaly brazil" | \
+efetch -format xml > zika.xml
+

This solution begins by using the esearch command to search PubMed (-db pubmed) for our search query (-query "zika virus microcephaly brazil"). The first line concludes by piping (|) the results of the esearch command into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records in full XML (-format xml). The results of the command is then redirected to a file (> zika.xml).

Homework solutions

Question 1

In the PubMed XML of each record, there is a <History> element, with one or more elements which provide dates for various stages in each article’s life cycle. These can include when the article was submitted to the publisher for review, when the article was accepted by the publisher for publication, when it was added to PubMed, and/or when it was indexed for MEDLINE, among others. Not all citations will include entries for each type of date.

For the following list of PMIDs

+
22389010,20060130,14678125,19750182,19042713,18586245
+

write a series of commands that retrieves each record and extracts all of these different dates, along with the labels that indicate which type of date is which.

Each PubMed record should appear on a separate line. Each line should start with the PMID, followed by a tab, followed by the list of dates. For each date, include the label, followed by a “:”, followed by the year, month and day, separated by slashes. Separate each date with a “|”.

Example output:

+
18586245        received:2008/01/21|revised:2008/05/05|accepted:2008/05/07|pubmed:2008/7/1|medline:2008/10/28|entrez:2008/7/1
+

Solution:

+
efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block PubMedPubDate -tab ":" -sep "/" -element PubMedPubDate@PubStatus \
+-tab "|" -element Year,Month,Day
+

Question 2

Identify your “working directory”. Write a series of commands that retrieve PubMed data, redirect the output to a file, and locate the file on your computer.

Solution:

The solution to this question may vary, depending on what type of Unix system you are using to run EDirect. One possible solution for identifying your “working directory” is:

+
pwd
+

The pwd command prints to the screen the name of your working directory. Depending on your system, this may give you all of the information you need to find your working directory. If not, please review the material presented in “EDirect for PubMed: Part 3: Formatting Results and Unix Tools”.

The second part of this question may also have many solutions. One possible solution is:

+
efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format abstract > abstracts.txt
+

This solution uses a basic efetch command to retrieve the six PubMed records specified in the the text abstract format (-format abstract). The command then redirects the output to a text file (> abstracts.txt). Provided you have found your working directory, you can find your new file and open it in a text editor.

Question 3

Write a series of commands that identifies the top ten agencies that have most frequently funded published research on diabetes and pregnancy over the last year and a half. Your script should start with a search for articles about diabetes and pregnancy that were published between January 1, 2016 and June 30, 2017, should extract the agencies listed as funders on each citation, and should output a list of the ten most frequently occuring agencies. Save the results to a file.

Note: This script may take some time to run. As you build it, consider testing with small set of PubMed records, or with a search that has a smaller date range.

Solution:

+
esearch -db pubmed -query "diabetes AND pregnancy" -datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30 | \
+efetch -format xml | \
+xtract -pattern Grant -element Agency | \
+sort-uniq-count-rank | \
+head -n 10
+

This series of commands searches PubMed for the string “diabetes AND pregnancy” with a publication date between January 1, 2016 and June 30, 2017; retrieves the full XML records for each of the search results, extracts the funding agency for every grant listed on every record, sorts the funding agencies by frequency of occurrence in the results set, and presents the top ten most frequently-occurring agencies, along with the number of times that agency appeared.

+
esearch -db pubmed -query "diabetes AND pregnancy" -datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30 | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "diabetes AND pregnancy"). We use the -datetype, -mindate, and -maxdate arguments to add our date restriction (-datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30). Alternatively, we could include the date restriction in our search string, as part of our -query argument.

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern Grant -element Agency | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every grant (-pattern Grant). Even if there are multiple grants on a single citation, each grant will be on a new line, rather than putting all grants for the same citation on the same line. The command then extracts each grant’s funding agency (-element Agency). This will output a list of agencies, one agency per line, and will pipe the list to the next line.

+
sort-uniq-count-rank | \
+

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of agencies received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique agency, removes the duplicate agencies, and then sorts the list of unique agencies by how frequently they occur, with the most frequent agencies at the top. The function also returns the numerical count, making it easier to quantify how frequently each agency occurs in the data set.

+
head -n 10
+

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set.

Question 4

Write a PubMed search strategy and save it to a file. Write a series of commands to search PubMed using the search string contained in the file and retrieve a list of PMIDs for all records which meet the search criteria.

Solution:

The solution to this may vary, based on your strategy and the name of the file to which you save it. For this example, our search strategy is saved to a file named “searchstring.txt”.

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format uid
+

The first line uses esearch to search PubMed (-db pubmed). The line uses the Unix command cat to read the entire contents of a file (searchstring.txt) and use it as the search query (-query "$(cat searchstring.txt)").

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format uid
+

The second line takes the esearch result from our first line and uses efetch to retrieve the PMIDs for all of the records in our results set. (efetch -format uid).

Question 5

Save the following list of PMIDs in a .csv file:

+
22389010,20060130,14678125,19750182,19042713,18586245
+

Write a series of commands to retrieve the full PubMed XML records for all of the PMIDs in the file, and save the resulting XML to a .xml file.

Solution:

The solution to this may vary, based on how you choose to save your PMIDs to a file, and on the name of that file. To begin, you could save your PMIDs to a file using efetch:

+
efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format uid > pmids.csv
+

Regardless of how you get the PMIDs into a .csv file, you can use epost -input and efetch to retrieve the records.

+
epost -db pubmed -input pmids.csv | \
+efetch -format xml > records.xml
+

The first line of this solution uses epost to retrieve the numbers from the “pmids.csv” file (-input pmids.csv) and save them to the history server, along with the indication that the numbers are PMIDs, and refer to records in PubMed (-db pubmed)

The “|” character pipes the WebEnv and QueryKey output of our epost into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

The efetch command on the second line receiveds the WebEnv and QueryKey from the epost and uses the information to locate on the history server the specific set of PMIDs posted by our epost command. The efetch command then retrieves the full records for each of those PMIDs in full PubMed XML (-format xml), and saves the output to a new file (> records.xml).

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"EDirect for PubMed: Part 4: xtract Conditional Arguments" Sample Code

+ +

Below you will find sample code for the examples, in-class exercises and homework presented in the fourth session of the “EDirect for PubMed” Insider’s Guide class. These examples are written for use with EDirect in a Unix environment. If you need help installing and setting up EDirect, please see our “Installing EDirect” page.

For more examples, please see the sample code from the other parts of “EDirect for PubMed”:

+

The code below is lightly annotated to explain how it works, but if you are looking for more information, we suggest you review our EDirect documentation.

There are many different ways to answer the questions discussed in class. The sample code below provides some options, but by no means the only options. Feel free to modify, adapt, edit, re-use or completely discard any of the suggestions below when trying to find a solution that works best for you.

+

xtract Conditional arguments

For an introduction to the xtract Conditional arguments, see the Filtering output with Conditional arguments section of our EDirect documentation.

Include only authors with ORCID IDs in the output table

+
efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml | \
+xtract -pattern Author -if Identifier -sep " " -element LastName,Initials Identifier
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27298442,27392493,27363997,27298443) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each <Author> element (-pattern Author), but only if the <Author> element contains an <Identifier> element (which is the where an author’s ORCID ID is stored). If an author does not have an ORCID ID, the author will not have an <Identifier> element; no row is created for the author, and xtract skips to the next author (-if Identifier).

The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " "), and one with the author’s ORCID ID (Identifier).

Include only articles from the journal JAMA in the output table

+
efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
+xtract -pattern PubmedArticle -if ISOAbbreviation -equals JAMA -element Volume Issue
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the article’s journal title abbreviation (<ISOAbbreviation>) is “JAMA”. If a citation is from a different journal, no row is created for the record, and xtract skips to the next record (-if ISOAbbreviation -equals JAMA).

The command creates two columns for each row: one with the article’s Volume number, one with the article’s Issue number (-element Volume Issue).

Include only MEDLINE articles in the output table

+
efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
+xtract -pattern PubmedArticle -if MedlineCitation@Status -equals MEDLINE -element MedlineCitation/PMID
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the record’s citation status (which is found in the “Status” attribute of the <MedlineCitation> element) is “MEDLINE”. If a citation is not in “MEDLINE” status, no row is created for the record, and xtract skips to the next record (-if MedlineCitation@Status -equals MEDLINE).

The command creates a single column for each row, containing the record’s PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element; -element MedlineCitation/PMID)

Include only authors whose affiliation mentions Japan in the output table

+
efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
+xtract -pattern Author -if Affiliation -contains Japan -sep " " -element LastName,Initials Affiliation
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each <Author> element (-pattern Author), but only if the <Author> element contains an <Affiliation> element which includes the word “Japan”. If an author does not have affiliation data, or the author’s affiliation data does not contain Japan, no row is created for the author, and xtract skips to the next author (-if Affiliation -contains Japan).

The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " "), and one with the author’s affiliation data (Affiliation).

Output a list of PMIDs and corresponding DOIs

+
efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block ArticleId -if ArticleId@IdType -equals doi -element ArticleId
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 16940437,16049336,11972038) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (e.g. as a child of a <CommentsCorrections> element; -element MedlineCitation/PMID).

The xtract command continues on the third line by checking each <ArticleId> element in a PubMed record (-block ArticleId). If an <ArticleId> element contains a DOI (indicated by the “IdType” attribute for the <ArticleId> equaling “doi”; -if ArticleId@IdType -equals doi), then the command puts the DOI in the second column (-element ArticleId). If not, the second column is left blank.

The result of this command will be a two column table, where the first column is always a PMID, and the second column is either the corresponding DOI (if there is one), or is blank (if there is no DOI).

Combining multiple Conditional arguments

Output a list of PMIDs and corresponding DOIs and PMCIDs

+
efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block ArticleId -if ArticleId@IdType -equals doi \
+-or ArticleId@IdType -equals pmc -element ArticleId
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 16940437,16049336,11972038) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (e.g. as a child of a <CommentsCorrections> element; -element MedlineCitation/PMID).

The xtract command continues on the third line by checking each <ArticleId> element in a PubMed record (-block ArticleId). If an <ArticleId> element contains a DOI (indicated by the “IdType” attribute for the <ArticleId> equaling “doi”; -if ArticleId@IdType -equals doi) OR a PMC ID (indicated by the “IdType” attribute for the <ArticleId> equaling “pmc”; -or ArticleId@IdType -equals pmc), then the command puts the contents of the <ArticleId> element in the second column (-element ArticleId).

Because a PubMed record can have multiple <ArticleId> elements, and because the -block argument checks each <ArticleId> separately, this command may result in both a DOI and a PMC ID appearing the second column of some rows.

Include only authors with the last name Kamal and with affiliation data in the output table

+
efetch -db pubmed -id 27798514,24372221,24332497,24307782 -format xml | \
+xtract -pattern Author -if LastName -equals Kamal -and Affiliation \
+-sep " " -element LastName,Initials Affiliation
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27798514,24372221,24332497,24307782) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each <Author> element (-pattern Author), but only if the <LastName> element for the <Author> is “Kamal”, AND the <Author> element contains an <Affiliation> element (-if LastName -equals Kamal -and Affiliation). If an author’s last name is not “Kamal” or the author does not have affiliation data, no row is created for the author, and xtract skips to the next author.

The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " "), and one with the author’s affiliation data (Affiliation).

Include only PubMed records indexed with the MeSH heading “Microcephaly”, and with any MeSH heading containing the words “Zika Virus” in the output table

+
efetch -db pubmed -id 27582188,27417495,27409810,27306170,18142192 -format xml | \
+xtract -pattern PubmedArticle -if DescriptorName -contains "Zika Virus" \
+-and DescriptorName -equals Microcephaly -element MedlineCitation/PMID ArticleTitle
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27582188,27417495,27409810,27306170,18142192) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the record has a <DescriptorName> element that contains the words “Zika Virus” (-if DescriptorName -contains "Zika Virus"), AND a <DescriptorName> element that equals “Microcephaly” (-and DescriptorName -equals Microcephaly). If a record does not have MeSH headings assigned that meet those criteria, no row is created for the author, and xtract skips to the next author. Note that, because of the use of -contains, both the MeSH heading “Zika Virus” and the MeSH heading “Zika Virus Infection” will satisfy the first condition in this command.

The command creates two columns for each row: one with the record’s PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one with the article’s title (-element MedlineCitation/PMID ArticleTitle).

xtract and the -position argument

Include only the First Author in the output table

+
efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block Author -position first -sep " " -element LastName,Initials
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (e.g. as a child of a <CommentsCorrections> element; -element MedlineCitation/PMID).

In the third line, xtract looks through each PubMed record for an <Author> element (-block Author). When it finds the first <Author> (-position first), it populates the second column in the row with the first author’s last name and initials, separated by a space (-sep " " -element LastName,Initials).

Dealing with blanks

Specify a placeholder to replace blank spaces in the output table

+
efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block Author -position first -sep " " -def "N/A" -element LastName,Initials Identifier
+

This series of commands is largely the same as the “Include only the First Author in the output table” example presented above. However, in the third line, we have added the -def argument to specify the placeholder value (“N/A”) for any blank cells in the output table (-def "N/A").

In-class exercise solutions

Note: The first two exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data.

Exercise 1

Write an xtract command that creates a table with one row per PubMed record, but that only includes PubMed records if they have MeSH headings. Each row should have two columns: PMID and citation status.

Solution:

+
efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml | \
+xtract -pattern PubmedArticle -if MeshHeading -element MedlineCitation/PMID MedlineCitation@Status
+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record contains a <MeshHeading> element (-if MeshHeading). If a record does not have MeSH headings attached, no row is created for the record, and xtract skips to the next record.

For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one with the record’s citation status (-element MedlineCitation/PMID MedlineCitation@Status).

Exercise 2

Write an xtract command that creates a table with one row per PubMed record, but that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.). Each row should have two columns: PMID and journal title abbreviation.

Solution:

+
efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml | \
+xtract -pattern PubmedArticle -if ISOAbbreviation -starts-with JAMA -element MedlineCitation/PMID ISOAbbreviation
+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record has a journal title abbreviation that begins with “JAMA” (-if ISOAbbreviation -starts-with JAMA).

For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one with the article’s journal title abbreviation (-element MedlineCitation/PMID ISOAbbreviation).

Exercise 3

Write a series of commands that generates a list of the different affiliation data used by author BH Smith between 2012 and 2017. The script should output the PMID for each article published by BH Smith in that time frame, along with the BH Smith’s affiliation data for each article.

Solution:

+
esearch -db pubmed -query "smith bh[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block Author -if LastName -equals Smith -and Initials -equals BH -element LastName,Initials Affiliation
+

This series of commands searches for publications by the author BH Smith that were published between 2012 and 2017, retrieves the full XML records for each of the search results, extracts the PMID and BH Smith’s affiliation data from each record, and displays the results in a table.

+
esearch -db pubmed -query "smith bh[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \
+

The first line of code uses esearch to search PubMed (-db pubmed) for articles where “smith bh” is the author (-query "smith bh[Author]"). The line also restricts the search results to articles that were published between 2011 and 2016 (-datetype PDAT -mindate 2012 -maxdate 2017).

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+

Beginning on the third line, the xtract command creates a table with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with three columns. The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (e.g. as a child of a <CommentsCorrections> element).

+
-block Author -if LastName -equals Smith -and Initials -equals BH -sep " " -element LastName,Initials Affiliation
+

The xtract command continues on the fourth line by checking each <Author> element in a PubMed record (-block Author). If a given author’s <LastName> is Smith AND <Initials> are BH (-if LastName -equals Smith -and Initials -equals BH), the xtract command populates the second column with the author’s last name and initials (separated by a space), and the third column with the author’s affiliation (-sep " " -element LastName,Initials Affiliation). Outputting the last name and initials into the second column is slightly redundant, as we know that they will always be “Smith BH”. However, it is helpful as a confirmation that our Conditional arguments are correct.

Homework solutions

Question 1

Fetch the records for the following list of PMIDs:

+
28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139
+

Write an xtract command that outputs the PMID and Article Title, but only for records that have a structured abstract. Hint: in PubMed records, structured abstracts are broken up into multiple AbstractText elements, each with their own “NlmCategory” attribute.

Solution:

+
efetch -db pubmed -id 28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139 -format xml | \
+xtract -pattern PubmedArticle -if AbstractText@NlmCategory -element MedlineCitation/PMID ArticleTitle
+

The first line of this solution uses efetch to retrieve several records from PubMed in XML format.

The “|” character pipes the results of our efetch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record has one or more “AbstractText” elements that contain an “NlmCategory” attribute (-if AbstractText@NlmCategory). This will ensure that only PubMed records with structured abstracts are included.

For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one with the article title (-element MedlineCitation/PMID ArticleTitle).

Question 2

Modify your command from Question 1 to display the “RESULTS” section of each structured abstract, if there is one, in place of the Article Title. If there is no “RESULTS” section, display just the PMID, leaving the second column blank. Hint: Use the “NlmCategory” attribute to determine whether a particular AbstractText element contains “RESULTS”.

Solution:

+
efetch -db pubmed -id 28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139 -format xml | \
+xtract -pattern PubmedArticle -if AbstractText@NlmCategory -element MedlineCitation/PMID \
+-block AbstractText -if AbstractText@NlmCategory -equals RESULTS -element AbstractText
+

This solution begins the same as the solution for Question 2. However, rather than including the article title in the first -element argument, the xtract command continues on the third line (with the “\” character at the end of the second line allowing us to continue our string of commands on the next line, for easier-to-read formatting.

+
-block AbstractText -if AbstractText@NlmCategory -equals RESULTS -element AbstractText
+

In the third line, the command uses -block to look for an <AbstractText> element (-block AbstractText), then looks within that <AbstractText> element to see if it has an “NlmCategory” attribute with the value “RESULTS” (-if AbstractText@NlmCategory -equals RESULTS). If it does, the command then outputs the contents of the <AbstractText> element in the second column. If the <AbstractText> element does not have an “NlmCategory” with the value “RESULTS”, the command proceeds to check the next <AbstractText> element in the record. The process repeats for each <AbstractText> element in the record.

Question 3

When indexing a record for MEDLINE, indexers can assign MeSH headings (descriptors) to represent concepts found in an article, and MeSH subheadings (qualifiers) to describe a specific aspect of a concept. Indexers denote some of MeSH headings as “Major Topics” (i.e. one of the primary topics of the article). When assigning a “Major Topic”, the indexer can determine that heading itself is a major topic, or that a specific heading/subheading pair is a major topic. When a heading/subheading pair is assigned as a Major Topic, only the subheading will be labeled as Major in the PubMed XML.

Write an xtract command that outputs one PubMed record per row. Each row should have the record’s PMID and a pipe-delimited list of all of the MeSH Headings the indexers have determined are Major Topics. Note: the list should only include headings (descriptors), not subheadings (qualifiers). However, if a heading/subheading pair is assigned as major, the list should include that heading.

You can use the following efetch command to retrieve some sample records:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block MeshHeading -if DescriptorName@MajorTopicYN -equals Y -or QualifierName@MajorTopicYN -equals Y \
+-tab "|" -element DescriptorName
+

This solution uses the example efetch command to retrieve three PubMed records in XML, then outputs a table with one row per PubMed record. Each row begins with the record’s PMID, followed by a pipe-delimited list of all of the MeSH Headings that the indexers have determined are Major Topics.

+
xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle) with the record’s PMID (-element MedlineCitation/PMID) and additional data, which is specified on the subsequent lines.

+
-block MeshHeading -if DescriptorName@MajorTopicYN -equals Y -or QualifierName@MajorTopicYN -equals Y \
+

In the third line, we start to check each <MeshHeading> element to determine if it has been labeled Major. The command uses -block to look for the first <MeshHeading> element in the record (-block MeshHeading). The command then looks within that <MeshHeading> element to see if its child <DescriptorName> element has a “MajorTopicYN” attribute with a value of “Y” (-if DescriptorName@MajorTopicYN -equals Y), or if any of its child <QualifierName> elements have a “MajorTopicYN” attribute with a value of “Y” (-or QualifierName@MajorTopicYN -equals Y). If either of these are true, the MeSH heading has been labeled as a Major Topic, and the command will continue on the next line (see below). If neither of these conditions are true, the command will proceed to the next <MeshHeading> element and repeat the process, looking for MeSH Headings which are Major Topics.

+
-tab "|" -element DescriptorName
+

The fourth line specifies that the DescriptorName will appear in the second column of our table (-element DescriptorName). Each indexed record will have at least one Major Topic assigned, and probably more than one. We use the -tab argument to specify a separator between the multiple MeSH descriptors (-tab "|"). It is important to place the -tab argument after the -block, as -block resets any -tab arguments that have been previously specified. We use -tab instead of -sep, as -block automatically creates a new column at the end of each block, so by specifying “|” in our -tab argument, we insure that our blocks are pipe-delimited.

Question 4

Write a series of commands to search for articles reporting on clinical trials relating to tularemia and output a table of citations. Each row should include the PMID for an article, as well as the name and affiliation information (if any) for the last author. If the last author does not have affiliation information, put “Not Available” in the last column instead.

Solution:

+
esearch -db pubmed -query "tularemia clinical trial" | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block Author -position last -sep " " -def "Not Available" -element LastName,Initials Affiliation
+

This solution of commands searches PubMed for the string “tularemia clinical trial”, retrieves the full XML records and outputs the PMID as well as the last name, initials affiliation information (if any) of each article’s last author.

+
esearch -db pubmed -query "tularemia clinical trial" | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "tularemia clinical trial").

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
-pattern PubmedArticle -element MedlineCitation/PMID \
+

Beginning on the third line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle) with the record’s PMID (-element MedlineCitation/PMID) and additional data, which is specified on the subsequent lines.

+
-block Author -position last -sep " " -def "Not Available" -element LastName,Initials Affiliation
+

The fourth line uses the -block and -position arguments to identify the last <Author> element in each record (-block Author -position last). The last name and initials of the last author, separated by a space (-sep " "), are placed in the second column, with the last author’s affiliation information (if present) is placed in the third column (-element LastName,Initials Affiliation). If the last author has no affiliation information, the third column will contain the default value of “Not Available” instead of being left blank (-def "Not Available")

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"EDirect for PubMed: Part 5: Developing and Building Scripts" Sample Code

+ +

Below you will find sample code for the examples, in-class exercises and homework presented in the fifth session of the “EDirect for PubMed” Insider’s Guide class. These examples are written for use with EDirect in a Unix environment. If you need help installing and setting up EDirect, please see our “Installing EDirect” page.

For more examples, please see the sample code from the other parts of “EDirect for PubMed”:

+

The code below is lightly annotated to explain how it works, but if you are looking for more information, we suggest you review our EDirect documentation.

There are many different ways to answer the questions discussed in class. The sample code below provides some options, but by no means the only options. Feel free to modify, adapt, edit, re-use or completely discard any of the suggestions below when trying to find a solution that works best for you.

Case study

Retrieve a list of articles published in between March 1, 2017 and February 28, 2018 about breast cancer that include clinical trial information from ClinicalTrials.gov. Include the PMID, journal title abbreviation, first author’s last name and initials, and ClinicalTrials.gov NCT number(s) for each record. Save the entire output to a text file.

Solution

+
esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \
+-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \
+-block Author -position first -sep " " -element LastName,Initials \
+-block DataBank -if DataBankName -equals ClinicalTrials.gov \
+-sep "|" -element AccessionNumber > clinicaltrials.txt
+

Discussion

+
esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "breast cancer AND clinicaltrials.gov[si]"). The “clinicaltrials.gov[si]” portion of the query ensures that only records with ClinicalTrials.gov NCT numbers are included in our results. The “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 | \
+

The second line restricts the search results to articles that were published between March 1, 2017 and February 28, 2018 (-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28). The “|” character pipes the results of our esearch into our next command.

+
efetch -format xml | \
+

The third line takes the esearch results from our first two lines and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \
+

Beginning on the fourth line, the xtract command creates a table with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with four columns. The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (e.g. as a child of a <CommentsCorrections> element), while the second column will contain the article’s journal title abbreviation (-element MedlineCitation/PMID ISOAbbreviation).

+
-block Author -position 1 -sep " " -element LastName,Initials \
+

In the fifth line, xtract looks through each PubMed record for an <Author> element (-block Author). When it finds the first <Author> (-position 1), it populates the third column in the row with the first author’s last name and initials, separated by a space (-sep " " -element LastName,Initials).

+
-block DataBank -if DataBankName -equals ClinicalTrials.gov \
+

In the sixth line, xtract looks through each PubMed record for <DataBank> elements which have a child <DataBankName> element that equals “ClinicalTrials.gov” (-block DataBank -if DataBankName -equals ClinicalTrials.gov). This will ensure that only ClinicalTrials.gov data is included, while data from non-ClinicalTrials.gov <DataBank> elements is excluded.

+
-sep "|" -element AccessionNumber > clinicaltrials.txt
+

In the seventh line, xtract specifies that the fourth column should be populated with the <AccessionNumber> (i.e. NCT number) from the included <DataBank> elements (-element AccessionNumber). If a record has multiple NCT numbers attached, they will be separated by pipes (-sep "|").

Finally, the results of the script are saved to a file (> clinicaltrials.txt).

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+ + \ No newline at end of file diff --git a/e-utilities-lecture-notes/Ekran Resmi 2018-03-12 20.09.56.png b/e-utilities-lecture-notes/Ekran Resmi 2018-03-12 20.09.56.png new file mode 100644 index 0000000..1226dc3 Binary files /dev/null and b/e-utilities-lecture-notes/Ekran Resmi 2018-03-12 20.09.56.png differ diff --git a/e-utilities-lecture-notes/Evaluation of Pathology Literature using E-utilities EDirect for PubMed.Rmd b/e-utilities-lecture-notes/Evaluation of Pathology Literature using E-utilities EDirect for PubMed.Rmd new file mode 100644 index 0000000..a47d644 --- /dev/null +++ b/e-utilities-lecture-notes/Evaluation of Pathology Literature using E-utilities EDirect for PubMed.Rmd @@ -0,0 +1,3222 @@ +--- +title: "Evaluation of Pathology Literature using E-utilities & EDirect for PubMed" +author: "Serdar Balcı, MD, Pathologist" +date: "`r format(Sys.Date())`" +output: + html_notebook: + code_folding: hide + df_print: kable + highlight: kate + number_sections: yes + theme: cerulean + toc: yes + toc_float: yes + html_document: + df_print: paged + toc: yes +subtitle: Codes and Pages are Copied & Modified from "E-utilities & EDirect for PubMed" + lectures +--- + +NLMTrainers@nih.gov + + +```{r necessary packages, include=FALSE} +library(rstudioapi) +library(tidyverse) +``` + + +```{r eval=FALSE, include=FALSE} +# https://cran.r-project.org/web/packages/rstudioapi/vignettes/terminal.html +# myTerm <- rstudioapi::terminalCreate() +# EdirectCall <- "esearch -db pubmed -query 'seasonal affective disorder' > myquery.txt \n" +# rstudioapi::terminalSend(myTerm, EdirectCall) +# rstudioapi::terminalKill(myTerm) +# readLines("myquery.txt") +``` + + + +# The Insider's Guide to Accessing NLM Data + +[The Insider's Guide to Accessing NLM Data](https://dataguide.nlm.nih.gov/) + + +# EDirect installation + +[Installing EDirect](https://dataguide.nlm.nih.gov/edirect/install.html) + + +To install EDirect, open your Unix terminal and execute the following commands. (The easiest way to do this is to copy the whole block and paste it directly into your terminal window.) + + cd ~ + /bin/bash + perl -MNet::FTP -e \ + '$ftp = new Net::FTP("ftp.ncbi.nlm.nih.gov", Passive => 1); + $ftp->login; $ftp->binary; + $ftp->get("/entrez/entrezdirect/edirect.tar.gz");' + gunzip -c edirect.tar.gz | tar xf - + rm edirect.tar.gz + builtin exit + export PATH=$PATH:$HOME/edirect >& /dev/null || setenv PATH "${PATH}:$HOME/edirect" + ./edirect/setup.sh + + +This installs the EDirect software and gets it ready to use. Depending on your system’s configuration, you may see the following message: + + In order to complete the configuration process, please execute the following: + +followed by a command that looks something like: + + echo "export PATH=\$PATH:\$HOME/edirect" >> $HOME/.bash_profile + +If you see this prompt, copy the command provided and paste it into your terminal. + +Once the installation is complete, you will see the following message in your terminal window: + + Entrez Direct has been successfully downloaded and installed. + +You can confirm EDirect is installed correctly by using the testing script below. + +## Test your EDirect installation + +To confirm that EDirect is installed and working properly, you can run your first EDirect script! Just type (or copy and paste) the following code into your terminal window, and press Enter. + + echo "***********************" > installconfirm + echo "esearch version:" >> installconfirm + esearch -version >> installconfirm + echo "xtract version:" >> installconfirm + xtract -version >> installconfirm + echo "EDirect install status:" >> installconfirm + esearch -db pubmed -query "Babalobi OO[au] AND 2008[pdat]" | \ + efetch -format xml | \ + xtract -pattern Author -if Affiliation -contains Medicine \ + -element Initials >> installconfirm + echo "***********************" >> installconfirm + cat installconfirm + rm installconfirm + +The result should be a message similar to the following: + + *********************** + esearch version: + 8.00 + xtract version: + 8.00 + EDirect install status: + OK + *********************** + +If you see this output, you have installed EDirect successfully! + +--- + + + + + +# "Welcome to E-utilities for PubMed" Sample Code for Class Exercises + +Below you will find sample code for the examples presented in the “Welcome to E-utilities for PubMed” Insider’s Guide course. These examples are written for use with EDirect in a Unix environment. If you need help installing and setting up EDirect, please see our “Installing EDirect” page. + +There are many different ways to answer the questions discussed in class. The sample code below provides one option, but by no means the only option, and not even necessarily the best option. + +**Feel free to modify, adapt, edit, re-use or completely discard any of the suggestions below when trying to find the solution that works best for you.**^[That is why I am preparing this page.] + +* Find the current “most active” authors for a given topic +* Generate list of funding agencies who are most active in funding a particular topic +* Create a customized version of the Discovery Bar “Results By Year” histogram, comparing two searches +* Find the most commonly-discussed topics of articles written by authors from a specific institution + * Version 1: Basic + * Version 2: Intermediate + * Version 3: Advanced + * Version 4: ??? + + +### Find the current “most active” authors for a given topic + +**Goal:** + +Find out who the “hot” authors are on a given topic. We are looking for authors that have written the most papers recently (i.e. in the last two years), on a specific subject. (For this example, we are looking at papers about diabetes and pregnancy.) + +**Solution:** + + esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \ + efetch -format xml | \ + xtract -pattern Author -sep " " -element LastName,Initials | \ + sort-uniq-count-rank | \ + head -n 10 + + + +```{r} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query '(diabetes AND pregnancy) AND (\"2017/01/01\"[PDAT] : \"2017/12/31\"[PDAT])' | \n") +rstudioapi::terminalSend(myTerm, "efetch -format xml | \n") +rstudioapi::terminalSend(myTerm, "xtract -pattern Grant -element Agency | \n") +rstudioapi::terminalSend(myTerm, "sort-uniq-count-rank | \n") +rstudioapi::terminalSend(myTerm, "head -n 10 > myquery.txt \n") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} + +``` + +```{r} +readLines("myquery.txt") +``` + + +```{r} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query '(diabetes AND pregnancy) AND (\"2017/01/01\"[PDAT] : \"2017/12/31\"[PDAT])' | efetch -format xml | xtract -pattern Grant -element Agency | sort-uniq-count-rank | head -n 10 > myquery.txt \n") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} +``` + + +This series of commands searches PubMed for the string `“(diabetes AND pregnancy) AND (”2015/01/01“[PDAT] : ”2017/12/31“[PDAT])”`, retrieves the full XML records for each of the search results, extracts the last name and initials of every author on every record, sorts the authors by frequency of occurrence in the results set, and presents the top ten most frequently-occurring authors, along with the number of times that author appeared. +Discussion: + + esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \ + +The first line of this command uses esearch to search PubMed `(-db pubmed)` for our search query `(-query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])")`. Our search query is constructed almost exactly like we would construct it in PubMed: we have a topic string `(“diabetes AND pregnancy”)` enclosed in parentheses and ANDed together with a date range. However, the double quotation marks (“) in our search string pose a problem. We need to ”escape“ the double quotation marks (”) in our search query by putting a `“\”` before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the -query argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched. + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format xml | \ + +The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format `(-format xml)`, and pipes the XML output to the next line. + + xtract -pattern Author -sep " " -element LastName,Initials | \ + +The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The `-pattern` command indicates that we should start a new row for every author `(-pattern Author)`. Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials) and separates the two elements with a single space `(-sep " ")`. This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line. + + sort-uniq-count-rank | \ + +The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set. + + head -n 10 + +The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the authors, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the `“|”` and `“\”` characters from the previous line. Otherwise, the system will wait for you to finish entering your command.) +Generate list of funding agencies who are most active in funding a particular topic +Goal: + +Find out which funding agencies have been funding research on a given topic. We are looking for agencies that are associated with papers published recently (i.e. in the last two years), on a specific subject. (For this example, we are looking at papers about diabetes and pregnancy.) + + +**Solution:** + + esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \ + efetch -format xml | \ + xtract -pattern Grant -element Agency | \ + sort-uniq-count-rank | \ + head -n 10 + +This series of commands searches PubMed for the string “(diabetes AND pregnancy) AND (”2015/01/01“[PDAT] : ”2017/12/31“[PDAT])”, retrieves the full XML records for each of the search results, extracts the funding agency for every grant listed on every record, sorts the funding agencies by frequency of occurrence in the results set, and presents the top ten most frequently-occurring agencies, along with the number of times that agency appeared. +Discussion: + + esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \ + +The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])"). Our search query is constructed almost exactly like we would construct it in PubMed: we have a topic string (“diabetes AND pregnancy”) enclosed in parentheses and ANDed together with a date range. However, the double quotation marks (“) in our search string pose a problem. We need to ”escape“ the double quotation marks (”) in our search query by putting a `“\”` before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the -query argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched. + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format xml | \ + +The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line. + + xtract -pattern Grant -element Agency | \ + +The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every grant (-pattern Grant). Even if there are multiple grants on a single citation, each grant will be on a new line, rather than putting all grants for the same citation on the same line. The command then extracts each grant’s funding agency (-element Agency). This will output a list of agencies, one agency per line, and will pipe the list to the next line. + + sort-uniq-count-rank | \ + +The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of agencies received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique agency, removes the duplicate agencies, and then sorts the list of unique agencies by how frequently they occur, with the most frequent agencies at the top. The function also returns the numerical count, making it easier to quantify how frequently each agency occurs in the data set. + + head -n 10 + +The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring agencies first, this will show us only the ten most frequently occurring agencies in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the agencies, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the `“|”` and `“\”` characters from the previous line. Otherwise, the system will wait for you to finish entering your command.) +Create a customized version of the Discovery Bar “Results By Year” histogram, comparing two searches +Goal: + +In order to recreate the “Results By Year” histogram available in the PubMed Discovery Bar for a given search, we need to count how many occurrences of each Publication Year there are in the results set, then sort those counts by year. To compare the “Results By Year” for two searches, we need to do this twice, and combine the two outputs. For this example, the searches we are doing relate to abuse of specific opioids (“fentanyl abuse” vs. “oxycodone abuse”), and we will restrict our results to articles published between 1988 and 2017. + + +**Solution:** + + esearch -db pubmed -query "fentanyl abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \ + efetch -format xml | \ + xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \ + cut -c -4 | \ + sort-uniq-count-rank | \ + sort -n -t $'\t' -k 2 > fentanyl_abuse.txt + + esearch -db pubmed -query "oxycodone abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \ + efetch -format xml | \ + xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \ + cut -c -4 | \ + sort-uniq-count-rank | \ + sort -n -t $'\t' -k 2 > oxycodone_abuse.txt + + join -j 2 -o 0,1.1,2.1 -a1 -a2 -e0 -t $'\t' <(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt) > abuse_compare.txt + +This series of commands searches PubMed for the string “fentanyl abuse” (restricted to publication dates between 1988 and 2017), retrieves the full XML records for each of the search results, extracts the year of publication from each record, counts how frequently each publication year appears in the results, then re-sorts by chronologically by year. The results are then saved to a file. The process is repeated for the string “oxycodone abuse”, and the two files are merged together. + +(This example uses some Unix tools like sort, cut, and join that were not discussed in detail in “Welcome to E-utilities for PubMed”. We will address some of them in greater detail in our follow-up class, “EDirect for PubMed”, but you can find a brief description of some of these tools in the appendices of NCBI’s EDirect documentation, under the heading “UNIX Utilities.”) +Discussion: + + esearch -db pubmed -query "fentanyl abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \ + +The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "fentanyl abuse"). Our search query is constructed exactly like we would construct it in PubMed: no tags, no punctuation, no Boolean operators. We simply put in our terms and they are automatically ANDed together. We use a few more arguments to restict our results based on publication date (-datetype PDAT -mindate 1988 -maxdate 2017). + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format xml | \ + +The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line. + + xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \ + +The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for each PubMed record (-pattern PubmedArticle). We then want to look in the PubDate element for each record, and extract either the Year element or the MedlineDate element (each citation should only have one or the other; -block PubDate -element Year MedlineDate). Each line in the output will have either a publication year (from the Year element), or a publication year followed by a month or other, more specific date information (from the MedlineDate element). The output will then be piped to the next line. + + cut -c -4 | \ + +The fourth line cuts off each line after the fourth character, leaving only the four digits of the year on each row (cut -c -4). The list of years is then piped to the next line. + + sort-uniq-count-rank | \ + +The fifth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of years received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique year, removes the duplicate years, and then sorts the list of unique years by how frequently they occur, with the most frequently occurring years at the top. The function also returns the numerical count for each year. + + sort -n -t $'\t' -k 2 > fentanyl_abuse.txt + +The sixth line then re-sorts the results numerically by the second column of data (sort -n -t $'\t' -k 2), which is the list of unique years (the first column of data is the frequency counts generated on the previous line). The list of years and frequency counts is now sorted chronologically, and the result is then sent to a file (> fentanyl_abuse.txt). + + esearch -db pubmed -query "oxycodone abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \ + efetch -format xml | \ + xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \ + cut -c -4 | \ + sort-uniq-count-rank | \ + sort -n -t $'\t' -k 2 > oxycodone_abuse.txt + +The first six lines are then repeated, substituting out “fentanyl” for “oxycodone” in both the search string and the output file name. + + join -j 2 -o 0,1.1,2.1 -a1 -a2 -e0 -t $'\t' <(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt) > abuse_compare.txt + +The final line uses a more advanced Unix command, join, that will allow us to merge together the two output files according to the values of a “key” column (in our case, the publication year). Both of our output files have the publication year in the second column, so we will join the two files using the second column of each file (join -j 2). We specify that the “key” column should be output first, followed by the first column of each file (-o 0,1.1,2.1). We want to make sure to include all of the publication years that were listed in either results set, even if they don’t appear in the other (with SQL or other database querying techniques, this is sometimes referred to as a “full outer join”; -a1 -a2). If one of the files has no results for a given publication year, we will output a 0 instead of a blank, and we will separate the columns in our output by tabs (-e0 -t $'\t'). + +The last part of the final line tells the join command which files to merge (<(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt)) and where to save the output (> abuse_compare.txt). If you want to instead view the results in your terminal window, you can omit the “>” and everything that follows it on the last line. +Find the most commonly-discussed topics of articles written by authors from a specific institution +Goal: + +Find the most common topics for articles written by any author from a specific institution. For the purposes of this exercise, we will find the “most common topics” by determining which MeSH headings are most frequently attached to the records from our institution. This exercise assumes that the institution has many authors (or many research components with different names), and that searching for all of the authors (or all papers with any of the institution’s names listed in the affiliation data) involves creating a long and complicated search string. +Solutions: + +As mentioned before, most use cases have multiple solutions. There is almost always a way to accomplish 100% of your goal in a single script. However, there are usually also ways of accomplishing 90%, 75% or 50% of your goal in a single script, and doing the remaining 10%, 25% or 50% manually. Each individual user should decide whether the additional time and effort it will take to get from 90% to 100% is more or less efficient than simply doing the remaining 10% manually. + +With that in mind, we have presented three different solutions below. Each solution is closer and closer to “perfect.” However, each solution adds new complexity and new commands which are more powerful, but also increasingly complicated. We encourage you to read through all three examples and see if one of them meets your needs, or if one of them could be adapted to meet your needs. +Version 1: Basic + + esearch -db pubmed -query "$(cat searchstring.txt)" | \ + efetch -format xml | \ + xtract -pattern DescriptorName -element DescriptorName | \ + sort-uniq-count-rank | \ + head -n 10 + +This series of commands searches PubMed for a string defined in the text file “searchstring.txt”, retrieves the full XML records for each of the search results, extracts each of the MeSH descriptors associated with every record in the results set, sorts the MeSH headings by frequency of occurrence in the results set, and presents the top ten most frequently-occurring MeSH headings, along with the number of times that heading appears. +Discussion: + + esearch -db pubmed -query "$(cat searchstring.txt)" | \ + +The first line uses esearch to search PubMed (-db pubmed). The line uses the Unix command cat to read the entire contents of a file (searchstring.txt) and use it as the search query (-query "$(cat searchstring.txt)"). This allows us to use a long and complex search strategy (involving many author names, many institutional names, or both), and to keep that search string in a separate file. Over time, we can update the search strategy without having to edit our actual script. Additionally, it makes the script more readable. + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format xml | \ + +The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line. + + xtract -pattern DescriptorName -element DescriptorName | \ + +The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every MeSH heading in the results set (-pattern DescriptorName). Even if there are multiple MeSH headings on a single citation (which there likely will be), each MeSH heading will be on a new line, rather than putting all MeSH headings for the same citation on the same line. The command then extracts the name of each MeSH heading (-element DescriptorName). This will output a list of MeSH headings, one per line, and will pipe the list to the next line. + + sort-uniq-count-rank | \ + +The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of MeSH headings received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique MeSH heading, removes the duplicate headings, and then sorts the list of unique headings by how frequently they occur, with the most frequent headings at the top. The function also returns the numerical count for each heading. + + head -n 10 + +The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring MeSH headings first, this will show us only the ten most frequently occurring headings in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the headings, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the `“|”` and `“\”` characters from the previous line. Otherwise, the system will wait for you to finish entering your command.) +Version 2: Intermediate + + esearch -db pubmed -query "$(cat searchstring.txt)" | \ + efetch -format xml | \ + xtract -pattern DescriptorName -element DescriptorName | \ + grep -vxf checktags.txt | \ + sort-uniq-count-rank | \ + head -n 10 + +As you may have noticed in Version 1 (depending on your search terms), “Humans” was probably among the most common MeSH headings in your output. Virtually every biomedical article will describe subjects of research (human or animal; mice or rats, etc.). Clinical articles will describe treatment, diagnosis, etc. of diseases in patients. These articles will almost always mention the number of patients, their sex and age. Experimental articles will almost always mention the species and sex of the animal subjects. + +These concepts, which are mentioned in almost every article, are designated as “check tags”. Check tags are routinely added to articles even if they are just mentioned in the article. If you like, you could just ignore these MeSH headings in your results. However, Version 2 of this code includes some lines which will automatically remove any headings that are check tags from your output. +Discussion: + + esearch -db pubmed -query "$(cat searchstring.txt)" | \ + efetch -format xml | \ + xtract -pattern DescriptorName -element DescriptorName | \ + +The first three lines are the same as Version 1, ending with the xtract command which outputs a list of MeSH headings, one per line, and will pipe the list to the next line. + + grep -vxf checktags.txt | \ + +The fourth line uses a very powerful Unix command, grep, which specializes in matching patterns in text. This line compares each line of text being piped in from our xtract command against every line in a specified file, and removes any lines from our xtract which match any of the lines in the file. The file (“checktags.txt”) contains a list of all of the MeSH headings which are check tags, with one heading on each line. You can download the checktags.txt file and use it as is, or you can modify it to filter out a different set of MeSH headings. The filtered list of MeSH headings is now piped to the next line. + + sort-uniq-count-rank | \ + head -n 10 + +The remaining lines of Version 2 are the same as Version 1. +Version 3: Advanced + + esearch -db pubmed -query "$(cat searchstring.txt)" | \ + efetch -format xml | \ + xtract -pattern DescriptorName -sep "" -element DescriptorName@MajorTopicYN,DescriptorName | \ + grep -vxf nchecktags.txt | \ + cut -c 2- | \ + sort-uniq-count-rank | \ + head -n 10 + +Version 2 filtered out the check tags from our result. However, while check tags are often added even if they are just mentioned in an article, those MeSH headings can sometimes be more central topics to the article. For example, “pregnancy” is a check tag, which is used to refer to research involving pregnant subjects. However, “pregnancy” can also be the main subject of an article. When it is, it will be denoted as a Major Topic. If we want to be even more precise than Version 2, we could make sure that we only filter out check tags when they are not the Major Topic of an article. +Discussion: + + esearch -db pubmed -query "$(cat searchstring.txt)" | \ + efetch -format xml | \ + xtract -pattern DescriptorName -sep "" -element DescriptorName@MajorTopicYN,DescriptorName | \ + +Again, most of Version 3 is the same as Version 2. The first difference is in the third line. In addition to extracting the DescriptorName, we are also going to be extracting the attribute “MajorTopicYN” for each DescriptorName element (-element DescriptorName@MajorTopicYN,DescriptorName). The MajorTopicYN indicator (which is always either a “Y” if the MeSH heading is a Major Topic, or “N” if it is not) will be appended to the beginning of the descriptor name, because we have eliminated the separator between elements (-sep ""). + + grep -vxf nchecktags.txt | \ + +Since the output from our xtract now consists of MeSH headings with either “Y” or “N” in front of them, we also need to edit the file that contains the check tags we are filtering out (grep -vxf nchecktags.txt). The new file (nchecktags.txt) is almost identical to the old file, with the exception that each heading in the file now starts with “N” (e.g. “Humans” becomes “NHumans”). If any of the headings in the output from our xtract are Major Topics, they will have a “Y” in front of them, and will not be filtered out by our N-prefixed check tag file. As before, the remaining, non-check tag MeSH headings are piped to the next line. + + cut -c 2- | \ + +Finally, we need to remove our extraneous “Y” and “N” characters from the front of the remaining MeSH headings (cut -c 2-). + + sort-uniq-count-rank | \ + head -n 10 + +The remaining lines of Version 3 are the same as Version 2. +Version 4: ??? + +Version 3 solved many of the problems, but is still not perfect. It does not handle MeSH subheadings, for example, and adding “N” to the front of each of the Check Tags in our filter file is inelegant. There are still more ways to improve this script, but the 90% of the task that this accomplishes will hopefully meet your needs. If it doesn’t, feel free to keep improving it! + + + +# EDirect for PubMed" Class Materials + +[EDirect for PubMed" Class Materials](https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/materials.html) + + + +## Part One "EDirect for PubMed: Part 1: Getting PubMed Data" Sample Code + +### Part One + + +https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode1.html + + +#### esearch + +**Conduct a simple search of PubMed for articles on seasonal affective disorder** + + esearch -db pubmed -query "seasonal affective disorder" + + +```{r part1-1.txt} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query \"seasonal affective disorder\" > part1-1.txt \n") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} + + +readLines("part1-1.txt") + +``` + + + +This line of code uses the esearch command to search PubMed (`-db pubmed`) for our search query `(-query "seasonal affective disorder")`. + +If you want to see the query translation for your search (like you would see in the Search Details box with the web version of PubMed), you can add an additional argument to your command: + + esearch -db pubmed -query "seasonal affective disorder" -log + +By adding the -log argument to esearch, the command will also output the E-utilities URL and query translation for your search. + + +```{r part1-2} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query 'seasonal affective disorder' -log &> part1-2.txt \n ") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} + +rstudioapi::terminalKill(myTerm) +readLines("part1-2.txt") + +# Problem in saving with > + +``` + + + +**Conduct a simple search of PubMed for articles on malaria in the journal JAMA** + + esearch -db pubmed -query "malaria AND jama[journal]" + +This line of code uses the esearch command to search PubMed `(-db pubmed)` for our search query `(-query "malaria AND jama[journal]")`. Note that the search query can include Boolean operators (AND) and search field tags ([journal]) to help focus our search, just as we can in the web version of PubMed. + +```{r part1-3} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query \"malaria AND jama[journal]\" &> part1-3.txt \n") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} +readLines("part1-3.txt") +``` + + + + +**Restrict search results by publication date** + + esearch -db pubmed -query "malaria AND jama[journal]" \ + -datetype PDAT -mindate 2015 -maxdate 2017 + +The first line of code is the same as our previous example, though the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting. + +The second line limits the search results by publication date `-datetype PDAT`, including only articles published between 2015 and 2017 `-mindate 2015 -maxdate 2017`. + + +**`“\”` does not work as a second line in `rstudioapi::` functions** + +```{r part1-4} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query \"malaria AND jama[journal]\" -datetype PDAT -mindate 2015 -maxdate 2017 &> part1-4.txt \n") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} +readLines("part1-4.txt") +``` + + + +**Conduct a PubMed search with a search string that includes quotation marks** + + esearch -db pubmed -query "cancer AND \"science\"[journal]" + +This line of code uses the esearch command to search PubMed `-db pubmed` for our search query `-query "cancer AND \"science\"[journal]"`. We need to “escape” the double quotation marks `“` in our search query by putting a `\` before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the `-query` argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched. + +```{r part1-5} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query 'cancer AND \"science\"[journal]' &> part1-5.txt \n") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} +readLines("part1-5.txt") +``` + + + + + +#### efetch + +**Retrieve a single PubMed record in text abstract format** + + efetch -db pubmed -id 25359968 -format abstract + +This line of code uses the efetch command to retrieve a record from PubMed `-db pubmed`. We specify that we will retrieve the record for PMID 25359968 `-id 25359968` and that we want the results in the text abstract format `-format abstract`. + + +```{r part1-6} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, "efetch -db pubmed -id 25359968 -format abstract -log > part1-6.txt \n") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} +readLines("part1-6.txt") +``` + + efetch -db pubmed -id 25359968 -format medline + + efetch -db pubmed -id 25359968 -format xml + + efetch -db pubmed -id 25359968 -format uid + +Retrieve multiple PubMed records in text abstract format + + efetch -db pubmed -id 24102982,21171099,17150207 -format abstract + +This line of code uses the efetch command to retrieve records from PubMed (-db pubmed). We specify that we will retrieve the records for PMID 24102982,21171099,17150207 (-id 24102982,21171099,17150207) and that we want the results in the text abstract format (-format abstract). + + +**Creating a data pipeline** + +**Conduct a PubMed search and retrieve the results as a list of PMIDs** + +```{r part1-pipe} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, " esearch -db pubmed -query \"asthenopia[mh] AND nursing[sh]\" | efetch -format uid &> part1-pipe.txt \n") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} +readLines("part1-pipe.txt") +``` + + + + + + esearch -db pubmed -query "asthenopia[mh] AND nursing[sh]" | efetch -format uid + +This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "asthenopia[mh] AND nursing[sh]"), and then pipes the resulting PMIDs into an efetch command (| efetch), which retrieves the PubMed records, but outputs only the PMIDs (-format uid). For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview. + + +**In-class exercise solutions** + + +**Exercise 1: esearch** + +How many Spanish-language articles about diabetes are in PubMed? + +**Solution:** + + esearch -db pubmed -query "diabetes AND spanish[lang]" + + +```{r part1-e1} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query \"diabetes AND spanish[lang]\" &> part1-e1.txt \n") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} +readLines("part1-e1.txt") +``` + + + +This line of code uses the esearch command to search PubMed `-db pubmed` for our search query `-query "diabetes AND spanish[lang]"`. Note that the search query can include Boolean operators `AND` and search field tags `[lang]` to help focus our search, just as we can in the web version of PubMed. + +**Exercise 2: esearch** + +How many articles were written by BH Smith between 2012 and 2017, inclusive? + +**Solutions:** + + esearch -db pubmed -query "smith bh[author]" -datetype PDAT -mindate 2012 -maxdate 2017 + + +```{r part1-e2} +myTerm <- rstudioapi::terminalCreate(show = FALSE) +rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query \"smith bh[author]\" -datetype PDAT -mindate 2012 -maxdate 2017 &> part1-e2.txt \n") +Sys.sleep(1) +repeat{ + Sys.sleep(0.1) + if(rstudioapi::terminalBusy(myTerm) == FALSE){ + print("Code Executed") + break + } +} +readLines("part1-e2.txt") +``` + + + + +There are multiple possible solutions to this exercise. This solution uses the esearch command to search PubMed (-db pubmed) for our search query (-query "smith bh[author]"). Note that the search query can include search field tags ([author]) to help focus our search, just as we can in the web version of PubMed. The esearch command also limits the search results by publication date (-datetype PDAT), including only articles published between 2012 and 2017 (-mindate 2012 -maxdate 2017). + + esearch -db pubmed -query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat])" + +The second solution is largely the same as the first. Rather than use the -datetype, -mindate, and -maxdate arguments to limit the search by publication date, this solution incorporates the date restriction into the search string itself (-query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat])"), just as you would include a date restriction in a search string in the web version of PubMed. + + +**Exercise 3: efetch** + +Who is the first author listed on the PubMed record 26287646? + +**Solution:** + + efetch -db pubmed -id 26287646 -format abstract + +This line of code uses the efetch command to retrieve a record from PubMed (-db pubmed). We specify that we will retrieve the record for PMID 25359968 (-id 25359968). The command retrieves the record in the text abstract format (-format abstract), which allows us to easily see that the first author of the article is PF Brennan. Rather than using the abstract format, we could instead use -format medline or -format xml to retrieve the record in the MEDLINE or XML formats, if we prefer. +Exercise 4: Combining Commands + +How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017? + +**Solutions:** + + esearch -db pubmed -query "smith bh[author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \ + efetch -format uid + +This solution begins the same as the first solution for Exercise 2. The first line concludes by piping (|) the results of the esearch command into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records, but outputs only the PMIDs (-format uid). + + esearch -db pubmed -query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat]" | \ + efetch -format uid + + +Similarly, this solution begins the same as the second solution for Exercise 2, and then pipes the results of the esearch into the efetch, which retrieves the PubMed records, but outputs only the PMIDs (-format uid). + +For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview. + +**Homework solutions** + +**Question 1** + +Using EDirect, write a command to find out how many citations are in PubMed for articles about using melatonin to treat sleep disorders. + +**Solution:** + + esearch -db pubmed -query "melatonin sleep disorder" + +This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "melatonin sleep disorder"). +Question 2 + +How many of the PubMed citations identified in question 2 were added to PubMed (i.e. created) between January 1, 2015 and July 1, 2017? + +**Solution:** + +There are multiple possible solutions to this question. + + esearch -db pubmed -query "melatonin sleep disorder" -datetype CRDT -mindate 2015/01/01 -maxdate 2017/07/01 + +Both of these solutions use the esearch command to search PubMed (-db pubmed) for our search query (-query "melatonin sleep disorder"). In the first solution, the esearch command also limits the search results by the date citations were added to PubMed, using the “CRDT” date type (-datetype CRDT), including only articles created between January 1, 2015 and July 1, 2017 (-mindate 2015/01/01 -maxdate 2017/07/01). + + esearch -db pubmed -query "melatonin sleep disorder" AND (2015/01/01[crdt] : 2017/07/01[crdt])" + +The second solution is largely the same as the first. Rather than use the -datetype, -mindate, and -maxdate arguments to limit the search by create date, this solution incorporates the date restriction into the search string itself (-query "melatonin sleep disorder" AND (2015/01/01[crdt] : 2017/07/01[crdt])"), just as you would include a date restriction in a search string in the web version of PubMed. + +**Question 3** + +Write a command to retreive the abstracts of the following PubMed records: + + 27240713,27027883,22468771,20121990 + +**Solution:** + + efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format abstract + +This line of code uses the efetch command to retrieve records from PubMed (-db pubmed). We specify that we will retrieve the records for four PMIDs: 27240713, 27027883, 22468771, and 20121990 (-id 27240713,27027883,22468771,20121990). The command retrieves the records in the text abstract format (-format abstract). + +**Question 4** + +Modify your answer to Question 3 to retrieve the full XML of all four records. + +**Solution:** + + efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format xml + +This solution is largely the same as the solution for Question 3, but the -format argument has been changed to retrieve XML instead of the text Abstract format (-format xml). + +**Question 5** + +Write a series of commands that retrieves a list of PMIDs for all citations for papers written by the author with the ORCID 0000-0002-1141-6306. + +**Solution:** + + esearch -db pubmed -query "0000-0002-1141-6306[auid]" | \ + efetch -format uid + +This solution begins by using the esearch command to search PubMed (-db pubmed) for citations including an author identifier of “0000-0002-1141-6306” (-query "0000-0002-1141-6306[auid]"). The first line concludes by piping (|) the results of the esearch command into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records, but outputs only the PMIDs (-format uid). + +### Part One + +https://dataguide.nlm.nih.gov/edirect-for-pubmed-1.txt + +The Insider's Guide to Accessing NLM Data: EDirect for PubMed +Part One: Getting PubMed Data + +Course Materials + +NOTE: Solutions to all exercises are at the bottom of this document. + + +Commands are instructions given by a user telling a computer to do something + +Arguments provide input data or modify the behavior of a command + + +TIPS FOR CYGWIN USERS: + +Copy: Ctrl + Insert +(NOT Ctrl + C!) + +Paste: Shift + Insert +(NOT Ctrl + V!) + + + +TIPS FOR ALL USERS: + +Ctrl + C "cancels" and gets you back to a prompt + +Up and Down arrow keys allow you to cycle through your recent commands + +clear: clears your screen + + +**esearch** + +esearch searches a database and returns the unique identifier of every record that meets the search criteria - in this case, PMIDs. + + -db to specify database: -db pubmed + -query to enter your query in quotes: -query "seasonal affective disorder" + + +COMMAND STRING: + + esearch -db pubmed -query "seasonal affective disorder" + +PUBMED SEARCH: + + seasonal affective disorder + + + +Show PubMed's translation of your search terms like you receive in the Search Details in PubMed + +COMMAND STRING: + + esearch -db pubmed -query "seasonal affective disorder" -log + +Details display at end of XML snippit + + "seasonal affective disorder"[MeSH Terms] OR ("seasonal"[All Fields] AND "affective"[All Fields] AND "disorder"[All Fields]) OR "seasonal affective disorder"[All Fields] + + +Search like you do in PubMed with uppercase Boolean AND/OR/NOT and field tags as needed. + +PUBMED SEARCH: + + malaria AND jama[journal] + +COMMAND STRING: + + esearch -db pubmed -query "malaria AND jama[journal]" + + +Restricting by Date + + -datetype specifies date field: -datetype PDAT + -mindate -maxdate specifies range: -mindate 2015 -maxdate 2017 + +COMMAND STRING: + + esearch -db pubmed -query "malaria AND jama[journal]" -datetype PDAT -mindate 2015 -maxdate 2017 + + +Use backslash `"\"` to indicate that you have not finished writing the command - it is continued on the next line. + +COMMAND STRING: + + esearch -db pubmed -query "malaria AND jama[journal]" \ + -datetype PDAT -mindate 2015 -maxdate 2017 + + + +Be Careful with Quotes + +PUBMED SEARCH: + + cancer AND science[journal] + + cancer AND "science"[journal] + + +COMMAND STRING: + + esearch -db pubmed -query "cancer AND \"science\"[journal]" + + + +**EXERCISE 1: esearch** + +How many Spanish-language articles about diabetes are in PubMed? +Hint: use the [lang] field tag + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + + +**EXERCISE 2: esearch** + +How many articles were written by BH Smith between 2012 and 2017, inclusive? + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + + + +**efetch** + +efetch retrieves the complete record in the format that you specify. + + -db to specify database: -db pubmed + -id to specify PMID: -id 25359968 + -format to specify format: -format abstract + +COMMAND STRING: + + efetch -db pubmed -id 25359968 -format abstract + + + + +efetch Formats + + -format options: + +MEDLINE + + -format medline + +XML + + -format xml + +PMID list + + -format uid + +Summary + + -format docsum + + +efetch Multiple Records + +Separate multiple PMIDs in the -id argument with commas. + +COMMAND STRING: + + efetch -db pubmed -id 24102982,21171099,17150207 -format abstract + + efetch -db pubmed -id 26024162 -format abstract + + + +EXERCISE 3: efetch +Who is the first author listed on the PubMed record 26287646? + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + + + +Creating a data pipeline + +Use pipe "|" [Shift + \] to "pipe" the results of one command into the next + +COMMAND STRING: + + esearch -db pubmed -query "asthenopia[mh] AND nursing[sh]" | efetch -format uid + + + +EXERCISE 4: Combining Commands +How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017? +Hint: Use the up arrow to access your previous commands +Hint: Remember -format uid + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + + +HOMEWORK FOR PART ONE + +(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode1.html) + + +**Question 1:** + +Using EDirect, write a command to find out how many citations are in PubMed for articles about using melatonin to treat sleep disorders. + + +**Question 2:** + +How many of the PubMed citations identified in question 2 were added to PubMed (i.e. created) between January 1, 2015 and July 1, 2017? + + +**Question 3:** + +Write a command to retrieve the abstracts of the following PubMed records: + + 27240713 + 27027883 + 22468771 + 20121990 + + +**Question 4:** + +Modify your answer to Question 3 to retrieve the full XML of all four records. + + +**Question 5:** + +Write a series of commands that retrieves a list of PMIDs for all citations for papers written by the author with the ORCID 0000-0002-1141-6306. + + +EXERCISE SOLUTIONS: + +EXERCISE 1: esearch +How many Spanish-language articles about diabetes are in PubMed? +Hint: use the [lang] field tag + +**Solution:** + + esearch -db pubmed -query "diabetes AND spanish[lang]" + + +EXERCISE 2: esearch +How many articles were written by BH Smith between 2012 and 2017, inclusive? +Hint: use the [author] field tag + +SOLUTIONS: + + esearch -db pubmed -query "smith bh[author]" \ + -datetype PDAT -mindate 2012 -maxdate 2017 + + esearch -db pubmed -query "smith bh[author] \ + AND (2012/01/01[pdat] : 2017/12/31[pdat])" + + +EXERCISE 3: efetch +Who is the first author listed on the PubMed record 26287646? + +**Solution:** + + efetch -db pubmed -id 26287646 -format abstract + +The first author is Brennan PF + + + +EXERCISE 4: Combining Commands +How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017? +Hint: Use the up arrow to access your previous commands +Hint: Remember -format uid + +SOLUTIONS: + + esearch -db pubmed -query "smith bh[author] AND \ + (2012/01/01[pdat] : 2017/12/31[pdat]" | \ + efetch -format uid + + + + esearch -db pubmed -query "smith bh[author]" \ + -datetype PDAT -mindate 2012 -maxdate 2017 | \ + efetch -format uid + + +## Part Two "EDirect for PubMed: Part 2: Extracting Data from XML" Sample Code + +### Part Two + +https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode2.html + + +**xtract Basics** + +For an introduction to the xtract command, see the xtract section of our EDirect documentation. +Retrieve the article titles for a list of PubMed records + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element ArticleTitle + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row in our output table for every PubMed record (-pattern PubmedArticle). The -element argument indicates that the table should include a single column, containing the article title for the given record (-element ArticleTitle). +Retrieve the list of authors for a series of PubMed records + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern Author -element LastName + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row in our output table for every author (-pattern Author). The -element argument indicates that the table should include a single column, containing the last name for the given author (-element LastName). +Retrieve the PMID and year of publication for a PubMed record + +In order to retrieve the PMID and the year of publication for a PubMed record, we might try to use code such as the following: + + efetch -db pubmed -id 27101380 -format xml | \ + xtract -pattern PubmedArticle -element PMID Year + +The first line of this code uses the efetch command to retrieve a record from PubMed (-db pubmed -id 27101380) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle; in this case, the table will only have a single row). The line then uses the -element argument to create two columns, one for PMID and one for Year. (-element PMID Year). However, the output of this series of commands is not what we expect: + + 27101380 27619336 27619799 27746956 27747057 2016 2016 2016 2016 2015 2016 2016 2016 2016 + +Rather than getting a single PMID and a single year, we get 5 PMIDs and 9 Years. This is because, while the -element argument is designed to create a new column for each element or attribute specified, it populates each column with the contents of every occurrence of the specified element or attribute in the -pattern. This means that if there are multiple occurrences of the or elements in a PubMed record, the contents of all occurrences will be displayed. As a result, we see not only the PMID for the record, but also the PMIDs used to link it to other records which contain related comments or corrections. Furthermore, in addition to the publication year, we also the year for the other eight dates associated with the PubMed record. + +We can avoid this by using Parent/Child construction to specify that we only want the contents of the element that is a direct child of the element, and that we only want the element that is a child of the element: + + efetch -db pubmed -id 27101380 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID PubDate/Year + +This version of the code gives us the output we expect: + + 27101380 2016 + +Retrieve three data elements for a list of PubMed records + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation ArticleTitle + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the element that is a child of the element), one for the journal title abbreviation, and one for the article title (-element MedlineCitation/PMID ISOAbbreviation ArticleTitle). +sort-uniq-count-rank and head +Sort a list of authors by the frequency they appear in your results set + + esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \ + efetch -format xml | \ + xtract -pattern Author -element LastName,Initials | \ + sort-uniq-count-rank | \ + head -n 10 + +This series of commands searches PubMed for the string “traumatic brain injury athletes”, restricts results to those published in 2016 and 2017, retrieves the full XML records for each of the search results, extracts the last name and initials of every author on every record, sorts the authors by frequency of occurrence in the results set, and presents the top ten most frequently-occurring authors, along with the number of times that author appeared. + + esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \ + +The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "traumatic brain injury athletes"). The line also restricts the search results to articles that were published in 2016 or 2017 (-datetype PDAT -mindate 2016 -maxdate 2017). + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format xml | \ + +The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line. + + xtract -pattern Author -element LastName,Initials | \ + +The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials). This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line. + + sort-uniq-count-rank | \ + +The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set. + + head -n 10 + +The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set: + + 14 Iverson GL + 11 Guskiewicz KM + 10 Meehan WP + 9 Kerr ZY + 9 Kontos AP + 9 Solomon GS + 9 Zuckerman SL + 8 Zafonte R + 7 Broglio SP + 7 Covassin T + +(Note: Your output may vary slightly, as additional citations are added to PubMed and the “most frequent” authors change.) + +To show more or fewer rows, adjust the “10” up or down. If you want to see all of the authors, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the `“|”` and `“\”` characters from the previous line. Otherwise, the system will wait for you to finish entering your command.) +In-class exercise solutions + +Note: The first three exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data. +Exercise 1 + +Write an xtract command that creates a table with one row per PubMed article. Each row should have two columns: volume number and issue number. + +**Solution:** + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element Volume Issue + +This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with columns for volume number and issue number (-element Volume Issue). +Exercise 2 + +Write an xtract command that creates a table with one row per PubMed record. Each row should have three columns: PMID, journal ISSN, and citation status. + +**Solution:** + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISSN MedlineCitation@Status + +This xtract command begins the same as the solution for Exercise 1 (xtract -pattern PubmedArticle). When creating the first column, this command uses Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (like as a child of a element; -element MedlineCitation/PMID). + +Similarly, the second column is also created using Parent/Child construction. This is probably not strictly necessary, as the element only appears in one location in the PubMed XML structure. However, this demonstrates that there may be multiple valid EDirect solutions to a given question (Journal/ISSN). + +Finally, the citation status, which is found in the “Status” attribute of the element, is placed in the third column (MedlineCitation@Status). +Exercise 3 + +Find out which authors have been writing about traumatic brain injuries in athletes, with publications in 2016 and 2017. The output should be a list of author names, one per line, with each author’s last name and initials. + +**Solution:** + + esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \ + efetch -format xml | \ + xtract -pattern Author -element LastName,Initials + +This series of commands searches PubMed for the string “traumatic brain injury athletes”, restricts results to those published in 2016 and 2017, retrieves the full XML records for each of the search results, and extracts the last name and initials of every author on every record. + + esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \ + + +The first line of code uses esearch to search PubMed (-db pubmed) for our search query (-query "traumatic brain injury athletes"). The line also restricts the search results to articles that were published in 2016 or 2017 (-datetype PDAT -mindate 2016 -maxdate 2017). + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format xml | \ + +The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line. + + xtract -pattern Author -element LastName,Initials + +The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. + +The command then extracts each author’s last name and initials (-element LastName,Initials). +Homework solutions + +**Question 1** + +Using the efetch command below to retrieve PubMed XML, write an xtract command to extract specific elements and arrange them into a table. The table should have one PubMed record per row, with columns for PMID, Journal Title Abbreviation, Publication Year, Volume, Issue and Page Numbers. + + efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml + +**Solution:** + + efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation PubDate/Year Volume Issue MedlinePgn + +This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). When creating the first column, this command uses Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (like as a child of a element; -element MedlineCitation/PMID). + +The second column is created without Parent/Child construction, as the element is not repeated in a single PubMed XML record (ISOAbbreviation). + +The third column also uses Parent/Child construction to retrieve the publication year (as opposed to other elements; PubDate/Year); the remaining elements only appear in one location in the PubMed XML structure, so Parent/Child construction is unnecessary (Volume Issue MedlinePgn). + +**Question 2** + +Create a table of the authors attached to PubMed record 28341696. The table should include each author’s last name, initials, and affiliation information (if listed). + +**Solution:** + + efetch -db pubmed -id 28341696 -format xml | \ + xtract -pattern Author -element LastName Initials Affiliation + +This first line of this solution uses the efetch command to retrieve a record from PubMed (-db pubmed). We specify that we will retrieve the record for PMID 28341696 (-id 28341696) and that we want the results in XML (-format xml). + + xtract -pattern Author -element LastName Initials Affiliation + +The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name, initials, and affiliation information (-element LastName Initials Affiliation). + +**Question 3** + +Write a series of commands to generate a table of PubMed records for review articles about the Paleolithic diet. The table should have one row per citation, and should include columns for the PMID, the citation status, and the article title. + + +**Solution:** + + esearch -db pubmed -query "review[pt] paleolithic diet" | \ + efetch -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID MedlineCitation@Status ArticleTitle + +This series of commands searches PubMed for the string “review[pt] paleolithic diet”, retrieves the full XML records for each of the search results, and extracts the last name and initials of every author on every record. + + esearch -db pubmed -query "review[pt] paleolithic diet" | \ + +The first line of code uses esearch to search PubMed (-db pubmed) for our search query (-query "review[pt] paleolithic diet"). Note that the search query can include search field tags ([pt]) to help focus our search, just as we can in the web version of PubMed. + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format xml | \ + +The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line. + +xtract -pattern PubmedArticle -element MedlineCitation/PMID MedlineCitation@Status ArticleTitle + +The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every PubMed record (-pattern PubmedArticle). + +The command then extracts each record’s PMID (using Parent/Child construction; -element MedlineCitation/PMID), citation status (using “@” to retrieve the attribute value for “Status”; MedlineCitation@Status), and article title (ArticleTitle). + + + +### Part Two + +https://dataguide.nlm.nih.gov/edirect-for-pubmed-2.txt + + +The Insider's Guide to Accessing NLM Data: EDirect for PubMed +Part Two: Extracting Data from XML +Course Materials + +NOTE: Solutions to all exercises are at the bottom of this document. + + +REMINDERS FROM PART ONE + +esearch: Searches a database and returns PMIDs + +efetch: Retrieves PubMed records in a variety of formats + +Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next + + + + +TIPS FOR CYGWIN USERS: + +Copy: Ctrl + Insert +(NOT Ctrl + C!) + +Paste: Shift + Insert +(NOT Ctrl + V!) + + + + +TIPS FOR ALL USERS: + +Ctrl + C "cancels" and gets you back to a prompt + +Up and Down arrow keys allow you to cycle through your recent commands + +clear: clears your screen + +---------------------------------------------------------------------- + + +xtract + +Extracts specific elements from XML and arranges them in a customized tabular format. + +---------------------------------------------------------------------- + +Getting XML + +From efetch: + +[...] | efetch -format xml | xtract [...] + +From a file on your computer using "-input": + +xtract -input file.xml [...] + +---------------------------------------------------------------------- + +XML Element Descriptions +https://www.nlm.nih.gov/bsd/licensee/elements_descriptions.html + +PubMed DTD Documentation +https://dtd.nlm.nih.gov/ncbi/pubmed/out/doc/2018/ + +---------------------------------------------------------------------- + +Before you start xtract-ing... + +Look at some PubMed XML by searching PubMed for a few PMIDs: + +24102982,21171099,17150207 + +---------------------------------------------------------------------- + +Getting a small sample dataset + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml + +---------------------------------------------------------------------- + +-pattern to identify which element will create a new row in the output table + +-element to identify which element(s) or attribute(s) will create columns in the output table + + +A basic xtract Command: + +COMMAND STRING: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element ArticleTitle + + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern Author -element LastName + +---------------------------------------------------------------------- + +Creating multiple columns + +Create multiple columns using the same -element argument by including multiple XML element names. +Separate the names with spaces. + +Example: + + xtract -pattern PubmedArticle -element Agency GrantID + +---------------------------------------------------------------------- + +EXERCISE 1: +Write an xtract command that: +* creates a table with one row per PubMed article. +* Each row should have two columns: + * Volume + * Issue Number + +Use the following efetch as input: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + +---------------------------------------------------------------------- +Isolating the elements we need + +COMMAND STRING: + + efetch -db pubmed -id 27101380 -format xml | \ + xtract -pattern PubmedArticle -element PMID Year + +---------------------------------------------------------------------- + +Parent/Child construction + +Retrieves only elements that are the child of a specific parent. + +Format: ParentElement/ChildElement + +Example: + + -element MedlineCitation/PMID + +---------------------------------------------------------------------- + +Solving xtract Example 1 +We have a set of records +We want a tabular list with PMID, Journal Title Abbreviation, and Article Title + +COMMAND STRING: +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISOAbbreviation ArticleTitle + +---------------------------------------------------------------------- + +xtract-ing attribute values + +Format: ElementName@AttributeName + +Example: + + -element DescriptorName@MajorTopicYN + +---------------------------------------------------------------------- + +EXERCISE 2 +Write an xtract command that: +* Has one row per PubMed records +* Has three columns: + * PMID + * Journal ISSN + * Citation status + +Use the following efetch as input: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + +---------------------------------------------------------------------- + +EXERCISE 3: Putting it all together + +We want to find out which authors have been writing about traumatic brain injuries in athletes +* Limit to publications from 2016 and 2017. +We want to see just the author names, one per line. +We want the last name and initials, separated by a space. +We want the whole script (not just the xtract command). + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + + +---------------------------------------------------------------------- + +sort-uniq-count-rank + +Four steps of sort-uniq-count-rank +1. Sorts all of the lines in your input alphabetically by the full contents of the line +2. Eliminates all duplicates, leaving only unique values. +3. Counts up how many of each unique value there were in your input, and provides that frequency count next to each unique value. +4. Re-sorts the unique values in descending order by frequency, so the most frequently occurring values are at the top. + +COMMAND STRING: + +esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \ +efetch -format xml | \ +xtract -pattern Author -element LastName Initials | \ +sort-uniq-count-rank + +---------------------------------------------------------------------- + +head + +Limits output to only the first few lines of input. + +Example: + + head -n 10 + +Outputs only the first ten lines of the input. + +COMMAND STRING: + + esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \ + efetch -format xml | \ + xtract -pattern Author -element LastName Initials | \ + sort-uniq-count-rank | \ + head -n 10 + + +HOMEWORK FOR PART TWO) + +(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode2.html) + +**Question 1:** + +Using the efetch command below to retrieve PubMed XML, write an xtract command with one record per row, with columns for PMID, Journal Title Abbreviation, Publication Year, Volume, Issue and Page Numbers. + + efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml + + +**Question 2:** + +Create a table of the authors attached to PubMed record 28341696. The table should include each author's last name, initials, and affiliation information (if listed). + + +**Question 3:** + +Write a series of commands to generate a table of PubMed records for review articles about the paleolithic diet. The table should have one row per citation, and should include columns for the PMID, the citation status, and the article title. + + +EXERCISE SOLUTIONS: + +**EXERCISE 1:** +Write an xtract command that: +* creates a table with one row per PubMed article. +* Each row should have two columns: + * Volume + * Issue Number + +**Solution:** + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element Volume Issue + + + +**EXERCISE 2:** +Write an xtract command that: +* Has one row per PubMed records +* Has three columns: + * PMID + * Journal ISSN + * Citation status + +**Solution:** + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISSN MedlineCitation@Status + + + +**EXERCISE 3: Putting it all together** + +We want to find out which authors have been writing about traumatic brain injuries in athletes +* Limit to publications from 2016 and 2017. +We want to see just the author names, one per line. +We want the last name and initials, separated by a space. +We want the whole script (not just the xtract command). + +**Solution:** + + esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \ + efetch -format xml | \ + xtract -pattern Author -element LastName Initials + + +## Part Three "EDirect for PubMed: Part 3: Formatting Results and Unix Tools" Sample Code + +### Part Three + +https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode3.html + + +xtract Formatting arguments + +For an introduction to xtract Formatting arguments, see the Customizing separators section of our EDirect documentation. +Change the separators in an xtract output table + +We can use the -tab and -sep arguments to modify the separators in an xtract output table. We will start with a basic xtract statement with no customized separators: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID ISSN LastName + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the element that is a child of the element), one for the journal ISSN, and one for author last name (-element MedlineCitation/PMID ISSN LastName). For articles with more than one author, we will see multiple author last names in the third column: + + 24102982 1742-4658 Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni + 21171099 1097-4598 Wu Gussoni + 17150207 0012-1606 Yoon Molloy Wu Cowan Gussoni + +By default, xtract separates columns in the output table with tabs (indicated in Unix as `\t`). Additionally, by default, xtract separates multiple values in the same column with tabs. So the following series of commands: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "\t" -sep "\t" -element MedlineCitation/PMID ISSN LastName + +produces the same output as before, since we are telling xtract to use a tab to separate between columns `(-tab "\t")` and between multiple values in the same column (-sep "\t"), which xtract is already doing by default: + + 24102982 1742-4658 Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni + 21171099 1097-4598 Wu Gussoni + 17150207 0012-1606 Yoon Molloy Wu Cowan Gussoni + +We can modify the output by modifying the -sep argument: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "\t" -sep " " -element MedlineCitation/PMID ISSN LastName + +This series of commands tells xtract to keep the separators between columns the same, but to separate multiple values in the same column (such as the multiple author last names in our third column) by spaces instead of tabs: + + 24102982 1742-4658 Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni + 21171099 1097-4598 Wu Gussoni + 17150207 0012-1606 Yoon Molloy Wu Cowan Gussoni + +We can further modify the output by modifying the -tab argument: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -sep " " -element MedlineCitation/PMID ISSN LastName + +This time, the separators between columns have been changed from tabs to pipes (-tab "|"), while multiple values in the same column are still separated by spaces: + + 24102982|1742-4658|Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni + 21171099|1097-4598|Wu Gussoni + 17150207|0012-1606|Yoon Molloy Wu Cowan Gussoni + +The -tab and -sep arguments also allow you to specify separators of more than one character: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -sep ", " -element MedlineCitation/PMID ISSN LastName + +This series of commands uses pipes to separate the columns (-tab "|"), but uses a comma followed by a space to separate the last names (-sep ", "): + + 24102982|1742-4658|Wu, Doyle, Barry, Beauvais, Rozkalne, Piao, Lawlor, Kopin, Walsh, Gussoni + 21171099|1097-4598|Wu, Gussoni + 17150207|0012-1606|Yoon, Molloy, Wu, Cowan, Gussoni + +xtract Exploration arguments + +For an introduction to xtract Exploration arguments, see the Exploration arguments section of our EDirect documentation. +Retrieve author names for a list of PubMed records + +In order to retrieve the author names (including last name and initials) for all of the authors associated with each of several PubMed records, we might try to use code such as the following: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID LastName Initials + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the element that is a child of the element), one for author last name, and one for author initials (-element MedlineCitation/PMID LastName Initials). However, the output of this series of commands is not what we expect: + + 24102982 Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni MP JR B A A X MW AS CA E + 21171099 Wu Gussoni MP E + 17150207 Yoon Molloy Wu Cowan Gussoni S MJ MP DB E + +The PMID appears as we expect, as does the first author last name. However, rather than following the first author’s last name with the corresponding initials, our output lists all of the authors’ last names for a PubMed record first, before listing all of the authors’ initials. + +To retain the relationship between last name and initials, we could use the following series of commands: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -element LastName Initials + +The second line of this code creates a column for the PMID as before (xtract -pattern PubmedArticle -element MedlineCitation/PMID). However, the code then uses the -block argument to direct xtract to look for an element, then to look within that for and elements (-block Author -element LastName Initials). Because each author has only one last name and one set of initials, xtract outputs a corresponding pair of last name and initials, before moving on to find the next author. This process is then repeated for each author, giving us the output we expect: + + 24102982 Wu MP Doyle JR Barry B Beauvais A Rozkalne A Piao X Lawlor MW Kopin AS Walsh CA Gussoni E + 21171099 Wu MP Gussoni E + 17150207 Yoon S Molloy MJ Wu MP Cowan DB Gussoni E + +Putting values from multiple elements in the same column +Separate author last name and initials with a space, while separating columns with a tab + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -sep " " -element LastName,Initials + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and creates a column for the PMID (xtract -pattern PubmedArticle -element MedlineCitation/PMID). As seen in previous examples, the code than uses the -block argument to direct xtract to look for an element (-block Author), then to look within that for and elements. + +Because each author has only one last name and one set of initials, xtract outputs a corresponding pair of last name and initials, before moving on to find the next author. However, rather than putting the last name and initials in separate columns, this command uses a comma to group together both the last name and initials in the same column (-element LastName,Initials). This tells xtract to separate the last name and initials with the character we define in the -sep argument (which we have defined as a single space: -sep " "), instead of using the separator between columns (which is still the default tab), and gives us the output we desire: + + 24102982 Wu MP Doyle JR Barry B Beauvais A Rozkalne A Piao X Lawlor MW Kopin AS Walsh CA Gussoni E + 21171099 Wu MP Gussoni E + 17150207 Yoon S Molloy MJ Wu MP Cowan DB Gussoni E + +Working with files +Saving results to a file + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.txt + +This line of code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and redirects the XML output to a file named “testfile.txt” (> testfile.txt). +Using a search string saved in a file to search PubMed + + esearch -db pubmed -query "$(cat searchstring.txt)" + +This line of code uses the esearch command to search PubMed (-db pubmed). The search query is stored in a text file (“searchstring.txt”), and the cat command is used to access the contents of the file for use as a search query (-query "$(cat searchstring.txt)"). The dollar-sign and parentheses around cat searchstring.txt indicate that Unix should use the value of cat searchstring.txt (i.e. the contents of the file “searchstring.txt”), rather than simply the words “cat searchstring.txt”. +epost +Post two PMIDs to the History server + + epost -db pubmed -id 24102982,21171099 + +This line of code uses the epost command to post two unique identifiers (UIDs) to the History server (-id 24102982,21171099), indicating that the UIDs are for records in the PubMed database (i.e. that the UIDs are actually PMIDs; -db pubmed). + +For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview. +Post two PMIDs to the History server and retrieve the corresponding PubMed records in abstract format + + epost -db pubmed -id 24102982,21171099 | efetch -format abstract + +This line of code uses the epost command to post two unique identifiers (UIDs) to the History server (-id 24102982,21171099), indicating that the UIDs are for records in the PubMed database (i.e. that the UIDs are actually PMIDs; -db pubmed). The line then pipes information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract). For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview. +Retrieve PubMed records in abstract format for a list of PMIDs contained in a CSV file + + cat pmids.csv | epost -db pubmed | efetch -format abstract + +This line of code uses cat to open a CSV file (“pmids.csv”) which contains a list of PMIDs (cat pmids.csv). Rather than displaying the contents of the file on the screen, this line of code pipes the contents of the file into an epost command (| epost). The epost command stores the PMIDs on the History server, indicating to the History server that they are PMIDs, and not UIDs from a different database (-db pubmed). Finally, the line pipes the information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract). + + epost -db pubmed -input pmids.csv | efetch -format abstract + +This line of code is another way of accomplishing the same task as the previous example. Rather than use cat to open the file “pmids.csv”, this line uses the epost command’s -input argument, which is a new feature of EDirect, added in version 4.90 (released on September 14, 2016). The epost command stores the PMIDs on the History server, indicating to the History server that they are PMIDs, and not UIDs from a different database (-db pubmed). Finally, the line pipes the information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract). + +For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview. +In-class exercise solutions + +Note: The first two exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data. +Exercise 1 + +Write an xtract command that generates a new row for each PubMed record, and has columns for PMID, journal title abbreviation, and author-supplied keywords. Each column should be separated by `“|”`. Multiple keywords in the last column should be separated with commas. + +Sample Output: + + 26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology + +**Solution:** + + efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -sep "," -element MedlineCitation/PMID ISOAbbreviation Keyword + +This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with columns for PMID (specified using Parent/Child construction), journal title abbreviation, and author-supplied keywords (-element MedlineCitation/PMID ISOAbbreviation Keyword). + +Instead of separating the columns by tabs, the command uses the -tab argument to specify pipe (``“|”``) as a separator (-tab "|"). Because each record could have multiple author-supplied keywords, the command uses the -sep argument to specify a separator between multiple values in a column (i.e. multiple author-supplied keywords in the third column; -sep ","). +Exercise 2 + +Write an xtract command that creates a table with a new row for each PubMed record. Each row should have the record’s PMID, as well as a list of all the MeSH headings for the records, separated by ``“|”``. If a MeSH heading has subheadings attached, separate the heading and subheadings with “/”. For example: + + 24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology + +**Solution:** + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \ + -block MeshHeading -tab "|" -sep "/" -element DescriptorName,QualifierName + +This xtract command begins the same as the solution for Exercise 1 (xtract -pattern PubmedArticle). The command then specifies a separator between columns (-tab "|") and the first column in the output table (using Parent/Child construction; -element MedlineCitation/PMID). The `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + +The command continues on the next line, using -block to maintain the relationship between MeSH headings and related subheadings. The -block argument directs xtract to look for a element (-block MeshHeading) then to look within that for and elements. Another argument is needed to respecify the separator between columns (-tab "|"), as the separators are reset to default by -block. + +Each element contains one , but may contain zero or more elements. For each -block, the -element argument populates a column with the and all of the elements, if there are any (-element DescriptorName,QualifierName). For MeSH headings with subheadings, this will place multiple values in the same column (one and one or more elements), so we establish “/” as a separator between multiple values in the same column (-sep "/"). + +**Exercise 3** + +How can we get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil? Save your results to a file. + +**Solution:** + + esearch -db pubmed -query "zika virus microcephaly brazil" | \ + efetch -format xml > zika.xml + +This solution begins by using the esearch command to search PubMed (-db pubmed) for our search query (-query "zika virus microcephaly brazil"). The first line concludes by piping (|) the results of the esearch command into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records in full XML (-format xml). The results of the command is then redirected to a file (> zika.xml). +Homework solutions + +Question 1 + +In the PubMed XML of each record, there is a element, with one or more elements which provide dates for various stages in each article’s life cycle. These can include when the article was submitted to the publisher for review, when the article was accepted by the publisher for publication, when it was added to PubMed, and/or when it was indexed for MEDLINE, among others. Not all citations will include entries for each type of date. + +For the following list of PMIDs + + 22389010,20060130,14678125,19750182,19042713,18586245 + +write a series of commands that retrieves each record and extracts all of these different dates, along with the labels that indicate which type of date is which. + +Each PubMed record should appear on a separate line. Each line should start with the PMID, followed by a tab, followed by the list of dates. For each date, include the label, followed by a “:”, followed by the year, month and day, separated by slashes. Separate each date with a `“|”`. + +Example output: + + 18586245 received:2008/01/21|revised:2008/05/05|accepted:2008/05/07|pubmed:2008/7/1|medline:2008/10/28|entrez:2008/7/1 + +**Solution:** + + efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block PubMedPubDate -tab ":" -sep "/" -element PubMedPubDate@PubStatus \ + -tab "|" -element Year,Month,Day + +Question 2 + +Identify your “working directory”. Write a series of commands that retrieve PubMed data, redirect the output to a file, and locate the file on your computer. + +**Solution:** + +The solution to this question may vary, depending on what type of Unix system you are using to run EDirect. One possible solution for identifying your “working directory” is: + + pwd + +The pwd command prints to the screen the name of your working directory. Depending on your system, this may give you all of the information you need to find your working directory. If not, please review the material presented in “EDirect for PubMed: Part 3: Formatting Results and Unix Tools”. + +The second part of this question may also have many solutions. One possible solution is: + + efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format abstract > abstracts.txt + +This solution uses a basic efetch command to retrieve the six PubMed records specified in the the text abstract format (-format abstract). The command then redirects the output to a text file (> abstracts.txt). Provided you have found your working directory, you can find your new file and open it in a text editor. +Question 3 + +Write a series of commands that identifies the top ten agencies that have most frequently funded published research on diabetes and pregnancy over the last year and a half. Your script should start with a search for articles about diabetes and pregnancy that were published between January 1, 2016 and June 30, 2017, should extract the agencies listed as funders on each citation, and should output a list of the ten most frequently occuring agencies. Save the results to a file. + +Note: This script may take some time to run. As you build it, consider testing with small set of PubMed records, or with a search that has a smaller date range. + +**Solution:** + + esearch -db pubmed -query "diabetes AND pregnancy" -datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30 | \ + efetch -format xml | \ + xtract -pattern Author -sep " " -element LastName,Initials | \ + sort-uniq-count-rank | \ + head -n 10 + +This series of commands searches PubMed for the string “diabetes AND pregnancy” with a publication date between January 1, 2016 and June 30, 2017; retrieves the full XML records for each of the search results; extracts the last name and initials of every author on every record; sorts the authors by frequency of occurence in the results set; and presents the top ten most frequently-occuring authors, along with the number of times that author appeared. + + esearch -db pubmed -query "diabetes AND pregnancy" -datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30 | \ + +The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "diabetes AND pregnancy"). We use the -datetype, -mindate, and -maxdate arguments to add our date restriction (-datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30). Alternatively, we could include the date restriction in our search string, as part of our -query argument. + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format xml | \ + +The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line. + + xtract -pattern Author -sep " " -element LastName,Initials | \ + +The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials) and separates the two elements with a single space (-sep " "). This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line. + + sort-uniq-count-rank | \ + +The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set. + + head -n 10 + +The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set. +Question 4 + +Write a PubMed search strategy and save it to a file. Write a series of commands to search PubMed using the search string contained in the file and retrieve a list of PMIDs for all records which meet the search criteria. + +**Solution:** + +The solution to this may vary, based on your strategy and the name of the file to which you save it. For this example, our search strategy is saved to a file named “searchstring.txt”. + + esearch -db pubmed -query "$(cat searchstring.txt)" | \ + efetch -format uid + +The first line uses esearch to search PubMed (-db pubmed). The line uses the Unix command cat to read the entire contents of a file (searchstring.txt) and use it as the search query (-query "$(cat searchstring.txt)"). + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format uid + +The second line takes the esearch result from our first line and uses efetch to retrieve the PMIDs for all of the records in our results set. (efetch -format uid). + +**Question 5** + +Save the following list of PMIDs in a .csv file: + + 22389010,20060130,14678125,19750182,19042713,18586245 + +Write a series of commands to retrieve the full PubMed XML records for all of the PMIDs in the file, and save the resulting XML to a .xml file. + +**Solution:** + +The solution to this may vary, based on how you choose to save your PMIDs to a file, and on the name of that file. To begin, you could save your PMIDs to a file using efetch: + + efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format uid > pmids.csv + +Regardless of how you get the PMIDs into a .csv file, you can use epost -input and efetch to retrieve the records. + + epost -db pubmed -input pmids.csv | \ + efetch -format xml > records.xml + +The first line of this solution uses epost to retrieve the numbers from the “pmids.csv” file (-input pmids.csv) and save them to the history server, along with the indication that the numbers are PMIDs, and refer to records in PubMed (-db pubmed) + +The `“|”` character pipes the WebEnv and QueryKey output of our epost into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + +The efetch command on the second line receiveds the WebEnv and QueryKey from the epost and uses the information to locate on the history server the specific set of PMIDs posted by our epost command. The efetch command then retrieves the full records for each of those PMIDs in full PubMed XML (-format xml), and saves the output to a new file (> records.xml). + +### Part Three + +https://dataguide.nlm.nih.gov/edirect-for-pubmed-3.txt + + +The Insider's Guide to Accessing NLM Data: EDirect for PubMed +Part Three: Formatting Results and Unix tools +Course Materials + +NOTE: Solutions to all exercises are at the bottom of this document. + + +REMINDERS FROM PART ONE + +esearch: Searches a database and returns PMIDs + +efetch: Retrieves PubMed records in a variety of formats + +Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next + + +---------------------------------------------------------------------- + +REMINDERS FROM PART TWO + +xtract: Pulls data from XML and arranges it in a table + +-pattern: Defines rows for xtract + +-element: Defines columns for xtract + +Identify XML elements by name (e.g. ArticleTitle) + +Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID) + +Identify attributes with "@" (e.g. MedlineCitation@Status) + +---------------------------------------------------------------------- + +TIPS FOR CYGWIN USERS: + +Copy: Ctrl + Insert +(NOT Ctrl + C!) + +Paste: Shift + Insert +(NOT Ctrl + V!) + +---------------------------------------------------------------------- + +TIPS FOR ALL USERS: + +Ctrl + C "cancels" and gets you back to a prompt + +Up and Down arrow keys allow you to cycle through your recent commands + +clear: clears your screen + +---------------------------------------------------------------------- + +-tab and -sep + +-tab defines the separator between columns +-sep defines the separator between multiple values in the same columns + +The default for both -tab and -sep is "\t" (the tab character) +Changes to -tab and -sep only affect subsequent -element/-first/-last arguments + +COMMAND STRING: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID ISSN LastName + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "\t" -sep "\t" \ + -element MedlineCitation/PMID ISSN LastName + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "\t" -sep " " \ + -element MedlineCitation/PMID ISSN LastName + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -sep " " \ + -element MedlineCitation/PMID ISSN LastName + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -sep "," \ + -element MedlineCitation/PMID ISSN LastName + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -sep ", " \ + -element MedlineCitation/PMID ISSN LastName + + + +With -tab/-sep, order matters! + +-tab/-sep only affect subsequent -elements + +Later -tab/-sep overwrite earlier ones + + + + +**EXERCISE 1** + +Write an xtract command that: +* has a new row for each PubMed record +* has columns for PMID, Journal Title Abbreviation, and Author-supplied Keywords +Each column should be separated by "|" +Multiple keywords in the last column should be separated with commas +Sample Output: + + + 26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology + +Use the following efetch as input: + + efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \ + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + + + +Authors: First Draft + +COMMAND STRING: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID LastName Initials + +---------------------------------------------------------------------- + +-block + +-block associates multiple child elements of the same parent element in the results + +COMMAND STRING: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -element LastName Initials + +---------------------------------------------------------------------- + +What we know so far... + + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -sep ", " \ + -element MedlineCitation/PMID ISSN LastName + +---------------------------------------------------------------------- + +Putting two different elements in the same column + +Separate multiple -element values with a comma instead of a space. + +COMMAND STRING: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -sep " " -element LastName,Initials + + + +"-block" resets -tab/-sep to default + +COMMAND STRING: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \ + -block Author -sep " " -element LastName,Initials + + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \ + -block Author -tab "|" -sep " " -element LastName,Initials + +---------------------------------------------------------------------- + +**EXERCISE 2** + +Write an xtract command that: +* Has a new row for each PubMed record +* Has a column for PMID +* Lists all of the MeSH headings, separated by "|" + * If a heading has multiple subheadings attached, separate the heading and subheadings with "/" +Sample Output: + + + 24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology + +Use the following efetch as input: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + +---------------------------------------------------------------------- + +Saving results to a file + +Use ">" to save the output to a file + +COMMAND STRING: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.txt + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.xml + + + +But where is my file!? + +Use "pwd" to "Print the Working Directory" (a.k.a display on the screen the name of the directory you are working in). This is where your file was saved. + +CYGWIN USERS: + +Your working directory is probably a subfolder of the folder where you installed Cygwin. In Cygwin, try: + +cygpath -w ~ + +MAC USERS: + +Your working directory is probably in your Users folder: + +Users/ + +---------------------------------------------------------------------- + +Another way to find your files + +COMMAND STRING: + +efetch -db pubmed -id 24102982,21171099,25359968,17150207 -format uid > specialname.csv + +Use "ls" to list the files in your current directory. + +---------------------------------------------------------------------- + +EXERCISE 3: Retrieving XML +How can I get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil? Save your results to a file. + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + +---------------------------------------------------------------------- + +cat + +Short for concatenate, "cat" opens files to display them on the screen. "cat" can also combine/append files + + +---------------------------------------------------------------------- + +Reading a search string from a file + +Use "$(cat filename)" to use the contents of a file in a command + +COMMAND STRING: + + esearch -db pubmed -query "$(cat searchstring.txt)" + +---------------------------------------------------------------------- + +epost uploads a list of PMIDs to the history server + +COMMAND STRING: + + epost -db pubmed -id 24102982,21171099 + + epost -db pubmed -id 24102982,21171099 | efetch -format abstract + + + +An epost-efetch pipeline + + cat specialname.csv | epost -db pubmed | efetch -format abstract + +Using the -input argument + + epost -db pubmed -input specialname.csv | efetch -format abstract + + +HOMEWORK FOR PART THREE + +(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode3.html) + + +**Question 1:** + +In the PubMed XML of each record, there is a element, with one or more elements which provide dates for various stages in each article's life cycle. These can include when the article was submitted to the publisher for review, when the article was accepted by the publisher for publication, when it was added to PubMed, and/or when it was indexed for MEDLINE, among others. Not all citations will include entries for each type of date. + +For the following list of PMIDs + + 22389010 + 20060130 + 14678125 + 19750182 + 19042713 + 18586245 + +write a series of commands that retrieves each record and extracts all of these different dates, along with the labels that indicate which type of date is which. + +Each PubMed record should appear on a separate line. Each line should start with the PMID, followed by a tab, followed by the list of dates. For each date, include the label, followed by a ":", followed by the year, month and day, separated by slashes. Separate each date with a "|". + +Example output: + + 18586245 received:2008/01/21|revised:2008/05/05|accepted:2008/05/07|pubmed:2008/7/1|medline:2008/10/28|entrez:2008/7/1 + + +**Question 2:** + +Identify your "working directory". Write a series of commands that retrieve PubMed data, redirect the output to a file, and locate the file on your computer. + + +**Question 3:** + +Write a series of commands that identifies the top ten agencies that have most frequently funded published research on diabetes and pregnancy over the last year and a half. Your script should start with a search for articles about diabetes and pregnancy that were published between January 1, 2016 and June 30, 2017, should extract the agencies listed as funders on each citation, and should output a list of the ten most frequently occurring agencies. Save the results to a file. + +Note: This script may take some time to run. As you build it, consider testing with small set of PubMed records, or with a search that has a smaller date range. + + +**Question 4:** + +Write a PubMed search strategy and save it to a file. Write a series of commands to search PubMed using the search string contained in the file and retrieve a list of PMIDs for all records which meet the search criteria. + + +**Question 5:** + +Save the following list of PMIDs in a .csv file: + + 22389010 + 20060130 + 14678125 + 19750182 + 19042713 + 18586245 + +Write a series of commands to retrieve the full PubMed XML records for all of the PMIDs in the file, and save the resulting XML to a .xml file. + +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE SOLUTIONS: +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- + +EXERCISE 1 +Write an xtract command that: +* has a new row for each PubMed recprd +* has columns for PMID, Journal Title Abbreviation, and Author-supplied Keywords +Each column should be separated by "|" +Multiple keywords in the last column should be separated with commas +Sample Output: + +26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology + + +**Solution:** + + efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -sep "," -element MedlineCitation/PMID ISOAbbreviation Keyword + +-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE 2: +Write an xtract command that: +* Has a new row for each PubMed record +* Has a column for PMID +* Lists all of the MeSH headings, separated by "|" + * If a heading has multiple subheadings attached, separate the heading and subheadings with "/" +Sample Output: + + + 24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology + +**Solution:** + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \ + -block MeshHeading -tab "|" -sep "/" -element DescriptorName,QualifierName + +-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE 3: Retrieving XML +How can I get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil? Save your results to a file. + +**Solution:** + + esearch -db pubmed \ + -query "zika virus microcephaly brazil" | \ + efetch -format xml > zika.xml + + +## Part Four "EDirect for PubMed: Part 4: xtract Conditional Arguments" Sample Code + +### Part Four + +https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode4.html + + + + +xtract Conditional arguments + +For an introduction to the xtract Conditional arguments, see the Filtering output with Conditional arguments section of our EDirect documentation. +Include only authors with ORCID IDs in the output table + + efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml | \ + xtract -pattern Author -if Identifier -sep " " -element LastName,Initials Identifier + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27298442,27392493,27363997,27298443) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each element (-pattern Author), but only if the element contains an element (which is the where an author’s ORCID ID is stored). If an author does not have an ORCID ID, the author will not have an element; no row is created for the author, and xtract skips to the next author (-if Identifier). + +The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " "), and one with the author’s ORCID ID (Identifier). +Include only articles from the journal JAMA in the output table + + efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \ + xtract -pattern PubmedArticle -if ISOAbbreviation -equals JAMA -element Volume Issue + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the article’s journal title abbreviation () is “JAMA”. If a citation is from a different journal, no row is created for the record, and xtract skips to the next record (-if ISOAbbreviation -equals JAMA). + +The command creates two columns for each row: one with the article’s Volume number, one with the article’s Issue number (-element Volume Issue). +Include only MEDLINE articles in the output table + + efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \ + xtract -pattern PubmedArticle -if MedlineCitation@Status -equals MEDLINE -element MedlineCitation/PMID + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the record’s citation status (which is found in the “Status” attribute of the element) is “MEDLINE”. If a citation is not in “MEDLINE” status, no row is created for the record, and xtract skips to the next record (-if MedlineCitation@Status -equals MEDLINE). + +The command creates a single column for each row, containing the record’s PMID (specifically, the contents of the element that is a child of the element; -element MedlineCitation/PMID) +Include only authors whose affiliation mentions Japan in the output table + + efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \ + xtract -pattern Author -if Affiliation -contains Japan -sep " " -element LastName,Initials Affiliation + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each element (-pattern Author), but only if the element contains an element which includes the word “Japan”. If an author does not have affiliation data, or the author’s affiliation data does not contain Japan, no row is created for the author, and xtract skips to the next author (-if Affiliation -contains Japan). + +The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " "), and one with the author’s affiliation data (Affiliation). +Output a list of PMIDs and corresponding DOIs + + efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block ArticleId -if ArticleId@IdType -equals doi -element ArticleId + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 16940437,16049336,11972038) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (e.g. as a child of a element; -element MedlineCitation/PMID). + +The xtract command continues on the third line by checking each element in a PubMed record (-block ArticleId). If an element contains a DOI (indicated by the “IdType” attribute for the equaling “doi”; -if ArticleId@IdType -equals doi), then the command puts the DOI in the second column (-element ArticleId). If not, the second column is left blank. + +The result of this command will be a two column table, where the first column is always a PMID, and the second column is either the corresponding DOI (if there is one), or is blank (if there is no DOI). +Combining multiple Conditional arguments +Output a list of PMIDs and corresponding DOIs and PMCIDs + + efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block ArticleId -if ArticleId@IdType -equals doi \ + -or ArticleId@IdType -equals pmc -element ArticleId + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 16940437,16049336,11972038) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (e.g. as a child of a element; -element MedlineCitation/PMID). + +The xtract command continues on the third line by checking each element in a PubMed record (-block ArticleId). If an element contains a DOI (indicated by the “IdType” attribute for the equaling “doi”; -if ArticleId@IdType -equals doi) OR a PMC ID (indicated by the “IdType” attribute for the equaling “pmc”; -or ArticleId@IdType -equals pmc), then the command puts the contents of the element in the second column (-element ArticleId). + +Because a PubMed record can have multiple elements, and because the -block argument checks each separately, this command may result in both a DOI and a PMC ID appearing the second column of some rows. +Include only authors with the last name Kamal and with affiliation data in the output table + + efetch -db pubmed -id 27798514,24372221,24332497,24307782 -format xml | \ + xtract -pattern Author -if LastName -equals Kamal -and Affiliation \ + -sep " " -element LastName,Initials Affiliation + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27798514,24372221,24332497,24307782) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each element (-pattern Author), but only if the element for the is “Kamal”, AND the element contains an element (-if LastName -equals Kamal -and Affiliation). If an author’s last name is not “Kamal” or the author does not have affiliation data, no row is created for the author, and xtract skips to the next author. + +The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " "), and one with the author’s affiliation data (Affiliation). +Include only PubMed records indexed with the MeSH heading “Microcephaly”, and with any MeSH heading containing the words “Zika Virus” in the output table + + efetch -db pubmed -id 27582188,27417495,27409810,27306170,18142192 -format xml | \ + xtract -pattern PubmedArticle -if DescriptorName -contains "Zika Virus" \ + -and DescriptorName -equals Microcephaly -element MedlineCitation/PMID ArticleTitle + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27582188,27417495,27409810,27306170,18142192) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the record has a element that contains the words “Zika Virus” (-if DescriptorName -contains "Zika Virus"), AND a element that equals “Microcephaly” (-and DescriptorName -equals Microcephaly). If a record does not have MeSH headings assigned that meet those criteria, no row is created for the author, and xtract skips to the next author. Note that, because of the use of -contains, both the MeSH heading “Zika Virus” and the MeSH heading “Zika Virus Infection” will satisfy the first condition in this command. + +The command creates two columns for each row: one with the record’s PMID (specifically, the contents of the element that is a child of the element), one with the article’s title (-element MedlineCitation/PMID ArticleTitle). +xtract and the -position argument +Include only the First Author in the output table + + efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -position first -sep " " -element LastName,Initials + +The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting). + +Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (e.g. as a child of a element; -element MedlineCitation/PMID). + +In the third line, xtract looks through each PubMed record for an element (-block Author). When it finds the first (-position first), it populates the second column in the row with the first author’s last name and initials, separated by a space (-sep " " -element LastName,Initials). +Dealing with blanks +Specify a placeholder to replace blank spaces in the output table + + efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -position first -sep " " -def "N/A" -element LastName,Initials Identifier + +This series of commands is largely the same as the “Include only the First Author in the output table” example presented above. However, in the third line, we have added the -def argument to specify the placeholder value (“N/A”) for any blank cells in the output table (-def "N/A"). +In-class exercise solutions + +Note: The first two exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data. +Exercise 1 + +Write an xtract command that creates a table with one row per PubMed record, but that only includes PubMed records if they have MeSH headings. Each row should have two columns: PMID and citation status. + +**Solution:** + + efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml | \ + xtract -pattern PubmedArticle -if MeshHeading -element MedlineCitation/PMID MedlineCitation@Status + +This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record contains a element (-if MeshHeading). If a record does not have MeSH headings attached, no row is created for the record, and xtract skips to the next record. + +For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the element that is a child of the element), one with the record’s citation status (-element MedlineCitation/PMID MedlineCitation@Status). + +Exercise 2 + +Write an xtract command that creates a table with one row per PubMed record, but that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.). Each row should have two columns: PMID and journal title abbreviation. + +**Solution:** + + efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml | \ + xtract -pattern PubmedArticle -if ISOAbbreviation -starts-with JAMA -element MedlineCitation/PMID ISOAbbreviation + +This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record has a journal title abbreviation that begins with “JAMA” (-if ISOAbbreviation -starts-with JAMA). + +For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the element that is a child of the element), one with the article’s journal title abbreviation (-element MedlineCitation/PMID ISOAbbreviation). +Exercise 3 + +Write a series of commands that generates a list of the different affiliation data used by author BH Smith between 2012 and 2017. The script should output the PMID for each article published by BH Smith in that time frame, along with the BH Smith’s affiliation data for each article. + +**Solution:** + + esearch -db pubmed -query "smith bh[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \ + efetch -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -if LastName -equals Smith -and Initials -equals BH -element LastName,Initials Affiliation + +This series of commands searches for publications by the author BH Smith that were published between 2012 and 2017, retrieves the full XML records for each of the search results, extracts the PMID and BH Smith’s affiliation data from each record, and displays the results in a table. + + esearch -db pubmed -query "smith bh[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \ + +The first line of code uses esearch to search PubMed (-db pubmed) for articles where “smith bh” is the author (-query "smith bh[Author]"). The line also restricts the search results to articles that were published between 2011 and 2016 (-datetype PDAT -mindate 2012 -maxdate 2017). + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format xml | \ + +The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line. + + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + +Beginning on the third line, the xtract command creates a table with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with three columns. The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (e.g. as a child of a element). + + -block Author -if LastName -equals Smith -and Initials -equals BH -sep " " -element LastName,Initials Affiliation + +The xtract command continues on the fourth line by checking each element in a PubMed record (-block Author). If a given author’s is Smith AND are BH (-if LastName -equals Smith -and Initials -equals BH), the xtract command populates the second column with the author’s last name and initials (separated by a space), and the third column with the author’s affiliation (-sep " " -element LastName,Initials Affiliation). Outputting the last name and initials into the second column is slightly redundant, as we know that they will always be “Smith BH”. However, it is helpful as a confirmation that our Conditional arguments are correct. +Homework solutions + +Question 1 + +Fetch the records for the following list of PMIDs: + + 28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139 + +Write an xtract command that outputs the PMID and Article Title, but only for records that have a structured abstract. Hint: in PubMed records, structured abstracts are broken up into multiple AbstractText elements, each with their own “NlmCategory” attribute. + +**Solution:** + + efetch -db pubmed -id 28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139 -format xml | \ + xtract -pattern PubmedArticle -if AbstractText@NlmCategory -element MedlineCitation/PMID ArticleTitle + +The first line of this solution uses efetch to retrieve several records from PubMed in XML format. + +The `“|”` character pipes the results of our efetch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + +This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record has one or more “AbstractText” elements that contain an “NlmCategory” attribute (-if AbstractText@NlmCategory). This will ensure that only PubMed records with structured abstracts are included. + +For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the element that is a child of the element), one with the article title (-element MedlineCitation/PMID ArticleTitle). + +Question 2 + +Modify your command from Question 1 to display the “RESULTS” section of each structured abstract, if there is one, in place of the Article Title. If there is no “RESULTS” section, display just the PMID, leaving the second column blank. Hint: Use the “NlmCategory” attribute to determine whether a particular AbstractText element contains “RESULTS”. + +**Solution:** + + efetch -db pubmed -id 28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139 -format xml | \ + xtract -pattern PubmedArticle -if AbstractText@NlmCategory -element MedlineCitation/PMID \ + -block AbstractText -if AbstractText@NlmCategory -equals RESULTS -element AbstractText + +This solution begins the same as the solution for Question 2. However, rather than including the article title in the first -element argument, the xtract command continues on the third line (with the `“\”` character at the end of the second line allowing us to continue our string of commands on the next line, for easier-to-read formatting. + + -block AbstractText -if AbstractText@NlmCategory -equals RESULTS -element AbstractText + +In the third line, the command uses -block to look for an element (-block AbstractText), then looks within that element to see if it has an “NlmCategory” attribute with the value “RESULTS” (-if AbstractText@NlmCategory -equals RESULTS). If it does, the command then outputs the contents of the element in the second column. If the element does not have an “NlmCategory” with the value “RESULTS”, the command proceeds to check the next element in the record. The process repeats for each element in the record. + +Question 3 + +When indexing a record for MEDLINE, indexers can assign MeSH headings (descriptors) to represent concepts found in an article, and MeSH subheadings (qualifiers) to describe a specific aspect of a concept. Indexers denote some of MeSH headings as “Major Topics” (i.e. one of the primary topics of the article). When assigning a “Major Topic”, the indexer can determine that heading itself is a major topic, or that a specific heading/subheading pair is a major topic. When a heading/subheading pair is assigned as a Major Topic, only the subheading will be labeled as Major in the PubMed XML. + +Write an xtract command that outputs one PubMed record per row. Each row should have the record’s PMID and a pipe-delimited list of all of the MeSH Headings the indexers have determined are Major Topics. Note: the list should only include headings (descriptors), not subheadings (qualifiers). However, if a heading/subheading pair is assigned as major, the list should include that heading. + +You can use the following efetch command to retrieve some sample records: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + +**Solution:** + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block MeshHeading -if DescriptorName@MajorTopicYN -equals Y -or QualifierName@MajorTopicYN -equals Y \ + -tab "|" -element DescriptorName + +This solution uses the example efetch command to retrieve three PubMed records in XML, then outputs a table with one row per PubMed record. Each row begins with the record’s PMID, followed by a pipe-delimited list of all of the MeSH Headings that the indexers have determined are Major Topics. + + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + +Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle) with the record’s PMID (-element MedlineCitation/PMID) and additional data, which is specified on the subsequent lines. + + -block MeshHeading -if DescriptorName@MajorTopicYN -equals Y -or QualifierName@MajorTopicYN -equals Y \ + +In the third line, we start to check each element to determine if it has been labeled Major. The command uses -block to look for the first element in the record (-block MeshHeading). The command then looks within that element to see if its child element has a “MajorTopicYN” attribute with a value of “Y” (-if DescriptorName@MajorTopicYN -equals Y), or if any of its child elements have a “MajorTopicYN” attribute with a value of “Y” (-or QualifierName@MajorTopicYN -equals Y). If either of these are true, the MeSH heading has been labeled as a Major Topic, and the command will continue on the next line (see below). If neither of these conditions are true, the command will proceed to the next element and repeat the process, looking for MeSH Headings which are Major Topics. + + -tab "|" -element DescriptorName + +The fourth line specifies that the DescriptorName will appear in the second column of our table (-element DescriptorName). Each indexed record will have at least one Major Topic assigned, and probably more than one. We use the -tab argument to specify a separator between the multiple MeSH descriptors (-tab "|"). It is important to place the -tab argument after the -block, as -block resets any -tab arguments that have been previously specified. We use -tab instead of -sep, as -block automatically creates a new column at the end of each block, so by specifying `“|”` in our -tab argument, we insure that our blocks are pipe-delimited. + +Question 4 + +Write a series of commands to search for articles reporting on clinical trials relating to tularemia and output a table of citations. Each row should include the PMID for an article, as well as the name and affiliation information (if any) for the last author. If the last author does not have affiliation information, put “Not Available” in the last column instead. + +**Solution:** + + esearch -db pubmed -query "tularemia clinical trial" | \ + efetch -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -position last -sep " " -def "Not Available" -element LastName,Initials Affiliation + +This solution of commands searches PubMed for the string “tularemia clinical trial”, retrieves the full XML records and outputs the PMID as well as the last name, initials affiliation information (if any) of each article’s last author. + + esearch -db pubmed -query "tularemia clinical trial" | \ + +The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "tularemia clinical trial"). + +The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + efetch -format xml | \ + +The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line. + + -pattern PubmedArticle -element MedlineCitation/PMID \ + +Beginning on the third line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle) with the record’s PMID (-element MedlineCitation/PMID) and additional data, which is specified on the subsequent lines. + + -block Author -position last -sep " " -def "Not Available" -element LastName,Initials Affiliation + +The fourth line uses the -block and -position arguments to identify the last element in each record (-block Author -position last). The last name and initials of the last author, separated by a space (-sep " "), are placed in the second column, with the last author’s affiliation information (if present) is placed in the third column (-element LastName,Initials Affiliation). If the last author has no affiliation information, the third column will contain the default value of “Not Available” instead of being left blank (-def "Not Available") + +### Part Four + +https://dataguide.nlm.nih.gov/edirect-for-pubmed-4.txt + +---------------------------------------------------------------------- +The Insider's Guide to Accessing NLM Data: EDirect for PubMed +Part Four: xtract Conditional Arguments +Course Materials + + +NOTE: Solutions to all exercises are at the bottom of this document. + + + +REMINDERS FROM PART ONE + +esearch: Searches a database and returns PMIDs + +efetch: Retrieves PubMed records in a variety of formats + +Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next + + + +REMINDERS FROM PART TWO + +xtract: Pulls data from XML and arranges it in a table + +-pattern: Defines rows for xtract + +-element: Defines columns for xtract + +Identify XML elements by name (e.g. ArticleTitle) + +Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID) + +Identify attributes with "@" (e.g. MedlineCitation@Status) + + + +REMINDERS FROM PART THREE + +-block: Selects and groups child elements of the same parent + +-tab: Defines the separator between columns (default is tab, "\t") + +-sep: Defines the separator between values in the same column (default is tab, "\t") + +Use ">" to save the output to a file + +Use "cat" to pull the contents of a file into the EDirect command + +epost: Stores PMIDs to the History Server + + + +TIPS FOR CYGWIN USERS: + +Ctrl + C does not Copy +(Cygwin default for Copy is Ctrl + Insert) + +Ctrl + V does not Paste +(Cygwin default for Paste is Shift + Insert) + + + + +TIPS FOR ALL USERS: + +Ctrl + C "cancels" and gets you back to a prompt + +Up and Down arrow keys allow you to cycle through your recent commands + +clear: clears your screen + + + +If-Then + +If the condition is met... +Then, create a new row for the pattern and populate the specified columns. +(If not, skip the pattern and move on to the next one.) + + + +-if + +COMMAND STRING: + + efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml + + efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml | \ + xtract -pattern Author -sep " " -element LastName,Initials Identifier + + efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml | \ + xtract -pattern Author -if Identifier -sep " " -element LastName,Initials Identifier + + + +EXERCISE 1: + +Write an xtract command that only includes PubMed records if they have MeSH headings +* One row per PubMed record +* Two columns: PMID, Citation Status +Hint: Use this efetch to test: + + + efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml | \ + + + +-if/-equals + +COMMAND STRING: + + efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \ + xtract -pattern PubmedArticle -if ISOAbbreviation -equals JAMA -element Volume Issue + + + +-if/-equals: Attributes + +COMMAND STRING: + + efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \ + xtract -pattern PubmedArticle -if MedlineCitation@Status -equals MEDLINE \ + -element MedlineCitation/PMID + + + +Alternatives to -equals + +-contains: Element or attribute contains this string +-starts-with: Element or attribute starts with this string +-ends-with: Element or attribute ends with this string +-is-not: Element or attribute does not match this string + + + +-if/-contains + +COMMAND STRING: + + efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \ + xtract -pattern Author -if Affiliation -contains Japan \ + -sep " " -element LastName,Initials Affiliation + + + + +EXERCISE 2: +Write an xtract command that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.) +* One row per PubMed record +* Two Columns: PMID, ISOAbbreviation +* ISOAbbreviation should start with "JAMA" +Hint: Use this efetch to test: + + + efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml | \ + + + + +-if in a -block + +COMMAND STRING: + + efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block ArticleId -if ArticleId@IdType -equals doi -element ArticleId + + + + +Combining multiple conditions + +-or: at least one condition must be true + +-and: all conditions must be true + + + + +-or + +COMMAND STRING: + + efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block ArticleId -if ArticleId@IdType -equals doi \ + -or ArticleId@IdType -equals pmc -element ArticleId + + + + +-and + +COMMAND STRING: + + efetch -db pubmed -id 27798514,24372221,24332497,24307782 -format xml | \ + xtract -pattern Author -if LastName -equals Kamal -and Affiliation \ + -sep " " -element LastName,Initials Affiliation + + + efetch -db pubmed -id 27582188,27417495,27409810,27306170,18142192 -format xml | \ + xtract -pattern PubmedArticle -if DescriptorName -contains "Zika Virus" \ + -and DescriptorName -equals Microcephaly -element MedlineCitation/PMID ArticleTitle + + + + +EXERCISE 3 +We want to do a search for author BH Smith, and see the different affiliations that are listed for that author +* Limit to publications from 2012 through 2017 + +We only want to see affiliation data for BH Smith, no other authors. + +We want our output to be a table of citations with specific data: +* PMID +* Author Last Name/Initials (should always be BH Smith) +* Affiliation Data + +Write the whole script (not just the xtract command). + + + + +-position + +Include a -block based on its position: + + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -position first -sep " " -element LastName,Initials + +Use -position with an integer, "first" or "last": + +-position 3 + +-position first + +-position last + +COMMAND STRING: + + efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -sep " " -element LastName,Initials + + + efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -position first -sep " " -element LastName,Initials + + + efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -position last -sep " " -element LastName,Initials + + + +Dealing with blanks + +Use -def to define a placeholder to replace blank cells + +Placement for -def is the same as for -tab/-sep. +* Subsequent -def arguments overwrite earlier ones. +* -block arguments clear previous -def arguments. + +COMMAND STRING: + + efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -position first -sep " " -element LastName,Initials Identifier + + efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -position first -sep " " -def "N/A" -element LastName,Initials Identifier + + +HOMEWORK FOR PART FOUR + +(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode4.html) + + +Question 1: + +Fetch the records for the following list of PMIDs: + + 28197844 + 28176235 + 28161874 + 28183232 + 28164731 + 27937077 + 28118756 + 27845598 + 27049596 + 27710139 + +Write an xtract command that outputs the PMID and Article Title, but only for records that have a structured abstract. Hint: in PubMed records, structured abstracts are broken up into multiple AbstractText elements, each with their own "NlmCategory" attribute. + + +Question 2: + +Modify your command from Question 1 to display the "RESULTS" section of each structured abstract, if there is one, in place of the Article Title. If there is no "RESULTS" section, display just the PMID, leaving the second column blank. Hint: Use the "NlmCategory" attribute to determine whether a particular AbstractText element contains "RESULTS". + + +Question 3: + +When indexing a record for MEDLINE, indexers can assign MeSH headings (descriptors) to represent concepts found in an article, and MeSH subheadings (qualifiers) to describe a specific aspect of a concept. Indexers denote some of the assigned MeSH headings as "Major Topics" (i.e. one of the primary topics of the article). When assigning a "Major Topic", the indexer can determine that the heading itself is a major topic, or that a specific heading/subheading pair is a major topic. When a heading/subheading pair is assigned as a Major Topic, only the subheading will be labeled as Major in the PubMed XML. + +Write an xtract command that outputs one PubMed record per row. Each row should have the record's PMID and a pipe-delimited list of all of the MeSH Headings the indexers have determined are Major Topics. Note: the list should only include headings (descriptors), not subheadings (qualifiers). However, if a heading/subheading pair is assigned as major, the list should include that heading. + +You can use the following efetch command to retrieve some sample records: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + + + +Question 4: + +Write a series of commands to search for articles reporting on clinical trials relating to tularemia and output a table of citations. Each row should include the PMID for an article, as well as the name and affiliation information (if any) for the last author. If the last author does not have affiliation information, put "Not Available" in the last column instead. + +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE SOLUTIONS: +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE 1: +Write an xtract command that only includes PubMed records if they have MeSH headings +* One row per PubMed record +* Two columns: PMID, Citation Status +Hint: Use this efetch to test: + + + efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml + +**Solution:** + + efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml | \ + xtract -pattern PubmedArticle -if MeshHeading \ + -element MedlineCitation/PMID MedlineCitation@Status + +-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE 2: +Write an xtract command that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.) +* One row per PubMed record +* Two Columns: PMID, ISOAbbreviation +* ISOAbbreviation should start with "JAMA" + +efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml + +**Solution:** + + efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml | \ + xtract -pattern PubmedArticle -if ISOAbbreviation -starts-with JAMA \ + -element MedlineCitation/PMID ISOAbbreviation + +-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE 3 +We want to do a search for author BH Smith, and see the different affiliations that are listed for that author +* Limit to publications from 2012 through 2017 + +We only want to see affiliation data for BH Smith, no other authors. + +We want our output to be a table of citations with specific data: +* PMID +* Author Last Name/Initials (should always be BH Smith) +* Affiliation Data + +Write the whole script (not just the xtract command). + +**Solution:** + + esearch -db pubmed -query "smith bh[Author]" \ + -datetype PDAT -mindate 2012 -maxdate 2017 | \ + efetch -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID \ + -block Author -if LastName -equals Smith -and Initials -equals BH -sep " " -element LastName,Initials Affiliation + + + +## Part Five "EDirect for PubMed: Part 5: Developing and Building Scripts" Sample Code + +### Part Five + +https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode5.html + + +Case study + +Retrieve a list of articles published in between March 1, 2017 and February 28, 2018 about breast cancer that include clinical trial information from ClinicalTrials.gov. Include the PMID, journal title abbreviation, first author’s last name and initials, and ClinicalTrials.gov NCT number(s) for each record. Save the entire output to a text file. + +**Solution** + + esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \ + -datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 | \ + efetch -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \ + -block Author -position first -sep " " -element LastName,Initials \ + -block DataBank -if DataBankName -equals ClinicalTrials.gov \ + -sep "|" -element AccessionNumber > clinicaltrials.txt + +Discussion + + esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \ + +The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "breast cancer AND clinicaltrials.gov[si]"). The “clinicaltrials.gov[si]” portion of the query ensures that only records with ClinicalTrials.gov NCT numbers are included in our results. The `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting. + + -datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 | \ + +The second line restricts the search results to articles that were published between March 1, 2017 and February 28, 2018 (-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28). The `“|”` character pipes the results of our esearch into our next command. + + efetch -format xml | \ + +The third line takes the esearch results from our first two lines and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line. + + xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \ + +Beginning on the fourth line, the xtract command creates a table with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with four columns. The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (e.g. as a child of a element), while the second column will contain the article’s journal title abbreviation (-element MedlineCitation/PMID ISOAbbreviation). + + -block Author -position 1 -sep " " -element LastName,Initials \ + +In the fifth line, xtract looks through each PubMed record for an element (-block Author). When it finds the first (-position 1), it populates the third column in the row with the first author’s last name and initials, separated by a space (-sep " " -element LastName,Initials). + + -block DataBank -if DataBankName -equals ClinicalTrials.gov \ + +In the sixth line, xtract looks through each PubMed record for elements which have a child element that equals “ClinicalTrials.gov” (-block DataBank -if DataBankName -equals ClinicalTrials.gov). This will ensure that only ClinicalTrials.gov data is included, while data from non-ClinicalTrials.gov elements is excluded. + + -sep "|" -element AccessionNumber > clinicaltrials.txt + +In the seventh line, xtract specifies that the fourth column should be populated with the (i.e. NCT number) from the included elements (-element AccessionNumber). If a record has multiple NCT numbers attached, they will be separated by pipes (-sep "|"). + +Finally, the results of the script are saved to a file (> clinicaltrials.txt). + +### Part Five + +https://dataguide.nlm.nih.gov/edirect-for-pubmed-5.txt + + + +The Insider's Guide to Accessing NLM Data: EDirect for PubMed +Part Five: Developing and Building Scripts +Course Materials + +NOTE: Solutions to all exercises are at the bottom of this document. + + + +REMINDERS FROM PART ONE + +esearch: Searches a database and returns PMIDs + +efetch: Retrieves PubMed records in a variety of formats + +Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next + + + +REMINDERS FROM PART TWO + +xtract: Pulls data from XML and arranges it in a table + +-pattern: Defines rows for xtract + +-element: Defines columns for xtract + +Identify XML elements by name (e.g. ArticleTitle) + +Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID) + +Identify attributes with "@" (e.g. MedlineCitation@Status) + + + +REMINDERS FROM PART THREE + +-block: Selects and groups child elements of the same parent + +-tab: Defines the separator between columns (default is tab, "\t") + +-sep: Defines the separator between values in the same column (default is tab, "\t") + +Use ">" to save the output to a file + +Use "cat" to pull the contents of a file into the EDirect command + +epost: Stores PMIDs to the History Server + + + +REMINDERS FROM PART FOUR + +-if: Defines an element/attribute that must be present in order to include a pattern/block. +(e.g. "If is present in the pattern/block, include pattern/block in the output.") + +-if/-equals: Defines a specific element/attribute that must be equal to a specific value in order to include a pattern/block, +(e.g. "If an equals [value] in the pattern/block, include pattern/block in the output.") + + +Alternatives to -equals: let you define more specific conditions +-contains: Element or attribute must contain this string +-starts-with: Element or attribute must start with this string +-ends-with: Element or attribute must end with this string +-is-not: Element or attribute must not match this string + + +Alternatives to -if: let you combine multiple conditions +-or: at least one condition must be true +-and: all conditions must be true + + +-position: Includes a block based on its position in a series of blocks. +Use -position with an integer, "first" or "last": + + + +Tips for Developing a Script + +1. Identify your goal. + * Identify your input + * Identify your output + * Identify your format +2. Choose your tool. +3. Decide how much to automate. +4. Build one step at a time. + + + +E-utilities Usage Guidelines and Requirements from NCBI +https://www.ncbi.nlm.nih.gov/books/NBK25497/#chapter2.Usage_Guidelines_and_Requiremen + +NLM Data Distribution: Download MEDLINE/PubMed Data +https://www.nlm.nih.gov/databases/download/pubmed_medline.html + +Using EDirect to create a local copy of PubMed +https://dataguide.nlm.nih.gov/edirect/archive.html + +NCBI Documentation: EDirect: Local Data Cache +https://www.ncbi.nlm.nih.gov/books/NBK179288/#chapter6.Local_Data_Cache + +---------------------------------------------------------------------- + +Case 1: Simple table of data elements + +We want a list of articles about breast cancer that were published in 2016 and the first half of 2017 and are linked to ClinicalTrials.gov entries. + +For each article we want: +* PMID +* NCT Number(s) +* First Author +* Journal + +---------------------------------------------------------------------- + +Case Study + +COMMAND STRING: + + esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" + + esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \ + -datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 + + esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \ + -datetype PDAT -mindate 2018/01/01 -maxdate 2018/02/28 + + efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml + + efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation + + efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \ + -block Author -position first -sep " " -element LastName,Initials + + efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \ + -block Author -position first -sep " " -element LastName,Initials \ + -block DataBank -if DataBankName -equals ClinicalTrials.gov \ + -sep "|" -element AccessionNumber + +CASE STUDY **Solution:** + + esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \ + -datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 | \ + efetch -format xml | \ + xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \ + -block Author -position first -sep " " -element LastName,Initials \ + -block DataBank -if DataBankName -equals ClinicalTrials.gov \ + -sep "|" -element AccessionNumber > clinicaltrials.txt + +---------------------------------------------------------------------- + +EDirect Cookbook on GitHub +https://ncbi-hackathons.github.io/EDirectCookbook/ + + + + + + +# Materials and Methods Used For This Analyses + +## The Insider's Guide to Accessing NLM Data + +### "Welcome to E-utilities for PubMed" Class Materials +https://dataguide.nlm.nih.gov/classes/intro/materials.html + +> Webinar Recording +> https://dataguide.nlm.nih.gov/classes/intro/recording.html + +> "Welcome to E-utilities for PubMed" Sample Code for Class Exercises +> https://dataguide.nlm.nih.gov/classes/intro/samplecode.html + + +> Entrez Programming Utilities Help +> https://www.ncbi.nlm.nih.gov/books/NBK25501/ + +> Entrez Direct: E-utilities on the UNIX Command Line +> https://www.ncbi.nlm.nih.gov/books/NBK179288/ + +### Installing EDirect +https://dataguide.nlm.nih.gov/edirect/install.html + + + +### The 9 E-utilities and Associated Parameters +https://dataguide.nlm.nih.gov/eutilities/utilities.html + diff --git a/e-utilities-lecture-notes/Evaluation of Pathology Literature using E-utilities EDirect for PubMed.nb.html b/e-utilities-lecture-notes/Evaluation of Pathology Literature using E-utilities EDirect for PubMed.nb.html new file mode 100644 index 0000000..ac27ff8 --- /dev/null +++ b/e-utilities-lecture-notes/Evaluation of Pathology Literature using E-utilities EDirect for PubMed.nb.html @@ -0,0 +1,5124 @@ + + + + + + + + + + + + + + + +Evaluation of Pathology Literature using E-utilities & EDirect for PubMed + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
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NLMTrainers@nih.gov

+ + + + +
+

1 The Insider’s Guide to Accessing NLM Data

+

The Insider’s Guide to Accessing NLM Data

+
+
+

2 EDirect installation

+

Installing EDirect

+

To install EDirect, open your Unix terminal and execute the following commands. (The easiest way to do this is to copy the whole block and paste it directly into your terminal window.)

+
cd ~
+/bin/bash
+perl -MNet::FTP -e \
+    '$ftp = new Net::FTP("ftp.ncbi.nlm.nih.gov", Passive => 1);
+    $ftp->login; $ftp->binary;
+    $ftp->get("/entrez/entrezdirect/edirect.tar.gz");'
+gunzip -c edirect.tar.gz | tar xf -
+rm edirect.tar.gz
+builtin exit
+export PATH=$PATH:$HOME/edirect >& /dev/null || setenv PATH "${PATH}:$HOME/edirect"
+./edirect/setup.sh
+

This installs the EDirect software and gets it ready to use. Depending on your system’s configuration, you may see the following message:

+
In order to complete the configuration process, please execute the following:
+

followed by a command that looks something like:

+
echo "export PATH=\$PATH:\$HOME/edirect" >> $HOME/.bash_profile
+

If you see this prompt, copy the command provided and paste it into your terminal.

+

Once the installation is complete, you will see the following message in your terminal window:

+
Entrez Direct has been successfully downloaded and installed.
+

You can confirm EDirect is installed correctly by using the testing script below.

+
+

2.1 Test your EDirect installation

+

To confirm that EDirect is installed and working properly, you can run your first EDirect script! Just type (or copy and paste) the following code into your terminal window, and press Enter.

+
echo "***********************" > installconfirm
+echo "esearch version:" >> installconfirm
+esearch -version >> installconfirm
+echo "xtract version:" >> installconfirm
+xtract -version >> installconfirm
+echo "EDirect install status:" >> installconfirm
+esearch -db pubmed -query "Babalobi OO[au] AND 2008[pdat]" | \
+efetch -format xml | \
+xtract -pattern Author -if Affiliation -contains Medicine \
+-element Initials >> installconfirm
+echo "***********************" >> installconfirm
+cat installconfirm
+rm installconfirm
+

The result should be a message similar to the following:

+
***********************
+esearch version:
+8.00
+xtract version:
+8.00
+EDirect install status:
+OK
+***********************
+

If you see this output, you have installed EDirect successfully!

+
+
+
+
+

3 “Welcome to E-utilities for PubMed” Sample Code for Class Exercises

+

Below you will find sample code for the examples presented in the “Welcome to E-utilities for PubMed” Insider’s Guide course. These examples are written for use with EDirect in a Unix environment. If you need help installing and setting up EDirect, please see our “Installing EDirect” page.

+

There are many different ways to answer the questions discussed in class. The sample code below provides one option, but by no means the only option, and not even necessarily the best option.

+

Feel free to modify, adapt, edit, re-use or completely discard any of the suggestions below when trying to find the solution that works best for you.1

+
    +
  • Find the current “most active” authors for a given topic
  • +
  • Generate list of funding agencies who are most active in funding a particular topic
  • +
  • Create a customized version of the Discovery Bar “Results By Year” histogram, comparing two searches
  • +
  • Find the most commonly-discussed topics of articles written by authors from a specific institution +
      +
    • Version 1: Basic
    • +
    • Version 2: Intermediate
    • +
    • Version 3: Advanced
    • +
    • Version 4: ???
    • +
  • +
+
+

3.0.1 Find the current “most active” authors for a given topic

+

Goal:

+

Find out who the “hot” authors are on a given topic. We are looking for authors that have written the most papers recently (i.e. in the last two years), on a specific subject. (For this example, we are looking at papers about diabetes and pregnancy.)

+

Solution:

+
esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \
+efetch -format xml | \
+xtract -pattern Author -sep " " -element LastName,Initials | \
+sort-uniq-count-rank | \
+head -n 10
+ + + + + + + + + + + + + + + + + + + + + +

This series of commands searches PubMed for the string “(diabetes AND pregnancy) AND (”2015/01/01“[PDAT] : ”2017/12/31“[PDAT])”, retrieves the full XML records for each of the search results, extracts the last name and initials of every author on every record, sorts the authors by frequency of occurrence in the results set, and presents the top ten most frequently-occurring authors, along with the number of times that author appeared. Discussion:

+
esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])"). Our search query is constructed almost exactly like we would construct it in PubMed: we have a topic string (“diabetes AND pregnancy”) enclosed in parentheses and ANDed together with a date range. However, the double quotation marks (“) in our search string pose a problem. We need to”escape“ the double quotation marks (”) in our search query by putting a “\” before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the -query argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched.

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern Author -sep " " -element LastName,Initials | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials) and separates the two elements with a single space (-sep " "). This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line.

+
sort-uniq-count-rank | \
+

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set.

+
head -n 10
+

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the authors, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the “|” and “\” characters from the previous line. Otherwise, the system will wait for you to finish entering your command.) Generate list of funding agencies who are most active in funding a particular topic Goal:

+

Find out which funding agencies have been funding research on a given topic. We are looking for agencies that are associated with papers published recently (i.e. in the last two years), on a specific subject. (For this example, we are looking at papers about diabetes and pregnancy.)

+

Solution:

+
esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \
+efetch -format xml | \
+xtract -pattern Grant -element Agency | \
+sort-uniq-count-rank | \
+head -n 10
+

This series of commands searches PubMed for the string “(diabetes AND pregnancy) AND (”2015/01/01“[PDAT] :”2017/12/31“[PDAT])”, retrieves the full XML records for each of the search results, extracts the funding agency for every grant listed on every record, sorts the funding agencies by frequency of occurrence in the results set, and presents the top ten most frequently-occurring agencies, along with the number of times that agency appeared. Discussion:

+
esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query “(diabetes AND pregnancy) AND ("2015/01/01"[PDAT] : "2017/12/31"[PDAT])”). Our search query is constructed almost exactly like we would construct it in PubMed: we have a topic string (“diabetes AND pregnancy”) enclosed in parentheses and ANDed together with a date range. However, the double quotation marks (“) in our search string pose a problem. We need to”escape“ the double quotation marks (”) in our search query by putting a “\” before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the -query argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched.

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern Grant -element Agency | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every grant (-pattern Grant). Even if there are multiple grants on a single citation, each grant will be on a new line, rather than putting all grants for the same citation on the same line. The command then extracts each grant’s funding agency (-element Agency). This will output a list of agencies, one agency per line, and will pipe the list to the next line.

+
sort-uniq-count-rank | \
+

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of agencies received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique agency, removes the duplicate agencies, and then sorts the list of unique agencies by how frequently they occur, with the most frequent agencies at the top. The function also returns the numerical count, making it easier to quantify how frequently each agency occurs in the data set.

+
head -n 10
+

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring agencies first, this will show us only the ten most frequently occurring agencies in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the agencies, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the “|” and “\” characters from the previous line. Otherwise, the system will wait for you to finish entering your command.) Create a customized version of the Discovery Bar “Results By Year” histogram, comparing two searches Goal:

+

In order to recreate the “Results By Year” histogram available in the PubMed Discovery Bar for a given search, we need to count how many occurrences of each Publication Year there are in the results set, then sort those counts by year. To compare the “Results By Year” for two searches, we need to do this twice, and combine the two outputs. For this example, the searches we are doing relate to abuse of specific opioids (“fentanyl abuse” vs. “oxycodone abuse”), and we will restrict our results to articles published between 1988 and 2017.

+

Solution:

+
esearch -db pubmed -query "fentanyl abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
+cut -c -4 | \
+sort-uniq-count-rank | \
+sort -n -t $'\t' -k 2 > fentanyl_abuse.txt
+
+esearch -db pubmed -query "oxycodone abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
+cut -c -4 | \
+sort-uniq-count-rank | \
+sort -n -t $'\t' -k 2 > oxycodone_abuse.txt
+
+join -j 2 -o 0,1.1,2.1 -a1 -a2 -e0 -t $'\t' <(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt) > abuse_compare.txt
+

This series of commands searches PubMed for the string “fentanyl abuse” (restricted to publication dates between 1988 and 2017), retrieves the full XML records for each of the search results, extracts the year of publication from each record, counts how frequently each publication year appears in the results, then re-sorts by chronologically by year. The results are then saved to a file. The process is repeated for the string “oxycodone abuse”, and the two files are merged together.

+

(This example uses some Unix tools like sort, cut, and join that were not discussed in detail in “Welcome to E-utilities for PubMed”. We will address some of them in greater detail in our follow-up class, “EDirect for PubMed”, but you can find a brief description of some of these tools in the appendices of NCBI’s EDirect documentation, under the heading “UNIX Utilities.”) Discussion:

+
esearch -db pubmed -query "fentanyl abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query “fentanyl abuse”). Our search query is constructed exactly like we would construct it in PubMed: no tags, no punctuation, no Boolean operators. We simply put in our terms and they are automatically ANDed together. We use a few more arguments to restict our results based on publication date (-datetype PDAT -mindate 1988 -maxdate 2017).

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for each PubMed record (-pattern PubmedArticle). We then want to look in the PubDate element for each record, and extract either the Year element or the MedlineDate element (each citation should only have one or the other; -block PubDate -element Year MedlineDate). Each line in the output will have either a publication year (from the Year element), or a publication year followed by a month or other, more specific date information (from the MedlineDate element). The output will then be piped to the next line.

+
cut -c -4 | \
+

The fourth line cuts off each line after the fourth character, leaving only the four digits of the year on each row (cut -c -4). The list of years is then piped to the next line.

+
sort-uniq-count-rank | \
+

The fifth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of years received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique year, removes the duplicate years, and then sorts the list of unique years by how frequently they occur, with the most frequently occurring years at the top. The function also returns the numerical count for each year.

+
sort -n -t $'\t' -k 2 > fentanyl_abuse.txt
+

The sixth line then re-sorts the results numerically by the second column of data (sort -n -t $‘’ -k 2), which is the list of unique years (the first column of data is the frequency counts generated on the previous line). The list of years and frequency counts is now sorted chronologically, and the result is then sent to a file (> fentanyl_abuse.txt).

+
esearch -db pubmed -query "oxycodone abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
+cut -c -4 | \
+sort-uniq-count-rank | \
+sort -n -t $'\t' -k 2 > oxycodone_abuse.txt
+

The first six lines are then repeated, substituting out “fentanyl” for “oxycodone” in both the search string and the output file name.

+
join -j 2 -o 0,1.1,2.1 -a1 -a2 -e0 -t $'\t' <(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt) > abuse_compare.txt
+

The final line uses a more advanced Unix command, join, that will allow us to merge together the two output files according to the values of a “key” column (in our case, the publication year). Both of our output files have the publication year in the second column, so we will join the two files using the second column of each file (join -j 2). We specify that the “key” column should be output first, followed by the first column of each file (-o 0,1.1,2.1). We want to make sure to include all of the publication years that were listed in either results set, even if they don’t appear in the other (with SQL or other database querying techniques, this is sometimes referred to as a “full outer join”; -a1 -a2). If one of the files has no results for a given publication year, we will output a 0 instead of a blank, and we will separate the columns in our output by tabs (-e0 -t $‘’).

+

The last part of the final line tells the join command which files to merge (<(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt)) and where to save the output (> abuse_compare.txt). If you want to instead view the results in your terminal window, you can omit the “>” and everything that follows it on the last line. Find the most commonly-discussed topics of articles written by authors from a specific institution Goal:

+

Find the most common topics for articles written by any author from a specific institution. For the purposes of this exercise, we will find the “most common topics” by determining which MeSH headings are most frequently attached to the records from our institution. This exercise assumes that the institution has many authors (or many research components with different names), and that searching for all of the authors (or all papers with any of the institution’s names listed in the affiliation data) involves creating a long and complicated search string. Solutions:

+

As mentioned before, most use cases have multiple solutions. There is almost always a way to accomplish 100% of your goal in a single script. However, there are usually also ways of accomplishing 90%, 75% or 50% of your goal in a single script, and doing the remaining 10%, 25% or 50% manually. Each individual user should decide whether the additional time and effort it will take to get from 90% to 100% is more or less efficient than simply doing the remaining 10% manually.

+

With that in mind, we have presented three different solutions below. Each solution is closer and closer to “perfect.” However, each solution adds new complexity and new commands which are more powerful, but also increasingly complicated. We encourage you to read through all three examples and see if one of them meets your needs, or if one of them could be adapted to meet your needs. Version 1: Basic

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format xml | \
+xtract -pattern DescriptorName -element DescriptorName | \
+sort-uniq-count-rank | \
+head -n 10
+

This series of commands searches PubMed for a string defined in the text file “searchstring.txt”, retrieves the full XML records for each of the search results, extracts each of the MeSH descriptors associated with every record in the results set, sorts the MeSH headings by frequency of occurrence in the results set, and presents the top ten most frequently-occurring MeSH headings, along with the number of times that heading appears. Discussion:

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+

The first line uses esearch to search PubMed (-db pubmed). The line uses the Unix command cat to read the entire contents of a file (searchstring.txt) and use it as the search query (-query “$(cat searchstring.txt)”). This allows us to use a long and complex search strategy (involving many author names, many institutional names, or both), and to keep that search string in a separate file. Over time, we can update the search strategy without having to edit our actual script. Additionally, it makes the script more readable.

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern DescriptorName -element DescriptorName | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every MeSH heading in the results set (-pattern DescriptorName). Even if there are multiple MeSH headings on a single citation (which there likely will be), each MeSH heading will be on a new line, rather than putting all MeSH headings for the same citation on the same line. The command then extracts the name of each MeSH heading (-element DescriptorName). This will output a list of MeSH headings, one per line, and will pipe the list to the next line.

+
sort-uniq-count-rank | \
+

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of MeSH headings received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique MeSH heading, removes the duplicate headings, and then sorts the list of unique headings by how frequently they occur, with the most frequent headings at the top. The function also returns the numerical count for each heading.

+
head -n 10
+

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring MeSH headings first, this will show us only the ten most frequently occurring headings in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the headings, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the “|” and “\” characters from the previous line. Otherwise, the system will wait for you to finish entering your command.) Version 2: Intermediate

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format xml | \
+xtract -pattern DescriptorName -element DescriptorName | \
+grep -vxf checktags.txt | \
+sort-uniq-count-rank | \
+head -n 10
+

As you may have noticed in Version 1 (depending on your search terms), “Humans” was probably among the most common MeSH headings in your output. Virtually every biomedical article will describe subjects of research (human or animal; mice or rats, etc.). Clinical articles will describe treatment, diagnosis, etc. of diseases in patients. These articles will almost always mention the number of patients, their sex and age. Experimental articles will almost always mention the species and sex of the animal subjects.

+

These concepts, which are mentioned in almost every article, are designated as “check tags”. Check tags are routinely added to articles even if they are just mentioned in the article. If you like, you could just ignore these MeSH headings in your results. However, Version 2 of this code includes some lines which will automatically remove any headings that are check tags from your output. Discussion:

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format xml | \
+xtract -pattern DescriptorName -element DescriptorName | \
+

The first three lines are the same as Version 1, ending with the xtract command which outputs a list of MeSH headings, one per line, and will pipe the list to the next line.

+
grep -vxf checktags.txt | \
+

The fourth line uses a very powerful Unix command, grep, which specializes in matching patterns in text. This line compares each line of text being piped in from our xtract command against every line in a specified file, and removes any lines from our xtract which match any of the lines in the file. The file (“checktags.txt”) contains a list of all of the MeSH headings which are check tags, with one heading on each line. You can download the checktags.txt file and use it as is, or you can modify it to filter out a different set of MeSH headings. The filtered list of MeSH headings is now piped to the next line.

+
sort-uniq-count-rank | \
+head -n 10
+

The remaining lines of Version 2 are the same as Version 1. Version 3: Advanced

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format xml | \
+xtract -pattern DescriptorName -sep "" -element DescriptorName@MajorTopicYN,DescriptorName | \
+grep -vxf nchecktags.txt | \
+cut -c 2- | \
+sort-uniq-count-rank | \
+head -n 10
+

Version 2 filtered out the check tags from our result. However, while check tags are often added even if they are just mentioned in an article, those MeSH headings can sometimes be more central topics to the article. For example, “pregnancy” is a check tag, which is used to refer to research involving pregnant subjects. However, “pregnancy” can also be the main subject of an article. When it is, it will be denoted as a Major Topic. If we want to be even more precise than Version 2, we could make sure that we only filter out check tags when they are not the Major Topic of an article. Discussion:

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format xml | \
+xtract -pattern DescriptorName -sep "" -element DescriptorName@MajorTopicYN,DescriptorName | \  
+

Again, most of Version 3 is the same as Version 2. The first difference is in the third line. In addition to extracting the DescriptorName, we are also going to be extracting the attribute “MajorTopicYN” for each DescriptorName element (-element DescriptorName@MajorTopicYN,DescriptorName). The MajorTopicYN indicator (which is always either a “Y” if the MeSH heading is a Major Topic, or “N” if it is not) will be appended to the beginning of the descriptor name, because we have eliminated the separator between elements (-sep “”).

+
grep -vxf nchecktags.txt | \
+

Since the output from our xtract now consists of MeSH headings with either “Y” or “N” in front of them, we also need to edit the file that contains the check tags we are filtering out (grep -vxf nchecktags.txt). The new file (nchecktags.txt) is almost identical to the old file, with the exception that each heading in the file now starts with “N” (e.g. “Humans” becomes “NHumans”). If any of the headings in the output from our xtract are Major Topics, they will have a “Y” in front of them, and will not be filtered out by our N-prefixed check tag file. As before, the remaining, non-check tag MeSH headings are piped to the next line.

+
cut -c 2- | \
+

Finally, we need to remove our extraneous “Y” and “N” characters from the front of the remaining MeSH headings (cut -c 2-).

+
sort-uniq-count-rank | \
+head -n 10
+

The remaining lines of Version 3 are the same as Version 2. Version 4: ???

+

Version 3 solved many of the problems, but is still not perfect. It does not handle MeSH subheadings, for example, and adding “N” to the front of each of the Check Tags in our filter file is inelegant. There are still more ways to improve this script, but the 90% of the task that this accomplishes will hopefully meet your needs. If it doesn’t, feel free to keep improving it!

+
+
+
+

4 EDirect for PubMed" Class Materials

+

EDirect for PubMed" Class Materials

+
+

4.1 Part One “EDirect for PubMed: Part 1: Getting PubMed Data” Sample Code

+
+

4.1.1 Part One

+

https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode1.html

+
+

4.1.1.1 esearch

+

Conduct a simple search of PubMed for articles on seasonal affective disorder

+
esearch -db pubmed -query "seasonal affective disorder"
+ + + + + + +
[1] "Code Executed"
+ + + + + +
[1] "<ENTREZ_DIRECT>"                                                                                   
+[2] "  <Db>pubmed</Db>"                                                                                 
+[3] "  <WebEnv>NCID_1_203517608_130.14.18.34_9001_1520427561_1688902671_0MetA0_S_MegaStore_F_1</WebEnv>"
+[4] "  <QueryKey>1</QueryKey>"                                                                          
+[5] "  <Count>1695</Count>"                                                                             
+[6] "  <Step>1</Step>"                                                                                  
+[7] "</ENTREZ_DIRECT>"                                                                                  
+ + + +

This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "seasonal affective disorder").

+

If you want to see the query translation for your search (like you would see in the Search Details box with the web version of PubMed), you can add an additional argument to your command:

+
esearch -db pubmed -query "seasonal affective disorder" -log
+

By adding the -log argument to esearch, the command will also output the E-utilities URL and query translation for your search.

+ + + + + + +
[1] "Code Executed"
+ + + + + +
 [1] "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=seasonal%20affective%20disorder&retmax=0&usehistory=y&edirect_os=darwin&edirect=7.90&tool=edirect&email=serdarbalciold@cf1-2.local"
+ [2] "\"seasonal affective disorder\"[MeSH Terms] OR (\"seasonal\"[All Fields] AND \"affective\"[All Fields] AND \"disorder\"[All Fields]) OR \"seasonal affective disorder\"[All Fields]"                         
+ [3] "<ENTREZ_DIRECT>"                                                                                                                                                                                             
+ [4] "  <Db>pubmed</Db>"                                                                                                                                                                                           
+ [5] "  <WebEnv>NCID_1_54189898_130.14.22.215_9001_1520434167_1415535048_0MetA0_S_MegaStore_F_1</WebEnv>"                                                                                                          
+ [6] "  <QueryKey>1</QueryKey>"                                                                                                                                                                                    
+ [7] "  <Count>1695</Count>"                                                                                                                                                                                       
+ [8] "  <Step>1</Step>"                                                                                                                                                                                            
+ [9] "  <Log>Y</Log>"                                                                                                                                                                                              
+[10] "</ENTREZ_DIRECT>"                                                                                                                                                                                            
+ + + + + + +

Conduct a simple search of PubMed for articles on malaria in the journal JAMA

+
esearch -db pubmed -query "malaria AND jama[journal]"
+

This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "malaria AND jama[journal]"). Note that the search query can include Boolean operators (AND) and search field tags ([journal]) to help focus our search, just as we can in the web version of PubMed.

+ + + + + + +
[1] "Code Executed"
+ + + + + +
[1] "<ENTREZ_DIRECT>"                                                                                   
+[2] "  <Db>pubmed</Db>"                                                                                 
+[3] "  <WebEnv>NCID_1_54194188_130.14.22.215_9001_1520434183_1404976732_0MetA0_S_MegaStore_F_1</WebEnv>"
+[4] "  <QueryKey>1</QueryKey>"                                                                          
+[5] "  <Count>212</Count>"                                                                              
+[6] "  <Step>1</Step>"                                                                                  
+[7] "</ENTREZ_DIRECT>"                                                                                  
+ + + +

Restrict search results by publication date

+
esearch -db pubmed -query "malaria AND jama[journal]" \
+-datetype PDAT -mindate 2015 -maxdate 2017
+

The first line of code is the same as our previous example, though the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting.

+

The second line limits the search results by publication date -datetype PDAT, including only articles published between 2015 and 2017 -mindate 2015 -maxdate 2017.

+

“\” does not work as a second line in rstudioapi:: functions

+ + + + + + +
[1] "Code Executed"
+ + + + + +
[1] "<ENTREZ_DIRECT>"                                                                                  
+[2] "  <Db>pubmed</Db>"                                                                                
+[3] "  <WebEnv>NCID_1_205204336_130.14.18.34_9001_1520434198_944619105_0MetA0_S_MegaStore_F_1</WebEnv>"
+[4] "  <QueryKey>1</QueryKey>"                                                                         
+[5] "  <Count>12</Count>"                                                                              
+[6] "  <Step>1</Step>"                                                                                 
+[7] "</ENTREZ_DIRECT>"                                                                                 
+ + + +

Conduct a PubMed search with a search string that includes quotation marks

+
esearch -db pubmed -query "cancer AND \"science\"[journal]"
+

This line of code uses the esearch command to search PubMed -db pubmed for our search query -query "cancer AND \"science\"[journal]". We need to “escape” the double quotation marks in our search query by putting a \ before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the -query argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched.

+ + + + + + +
[1] "Code Executed"
+ + + + + +
[1] "<ENTREZ_DIRECT>"                                                                                   
+[2] "  <Db>pubmed</Db>"                                                                                 
+[3] "  <WebEnv>NCID_1_205243067_130.14.18.34_9001_1520434348_1018590557_0MetA0_S_MegaStore_F_1</WebEnv>"
+[4] "  <QueryKey>1</QueryKey>"                                                                          
+[5] "  <Count>5429</Count>"                                                                             
+[6] "  <Step>1</Step>"                                                                                  
+[7] "</ENTREZ_DIRECT>"                                                                                  
+ + + +
+
+

4.1.1.2 efetch

+

Retrieve a single PubMed record in text abstract format

+
efetch -db pubmed -id 25359968 -format abstract
+

This line of code uses the efetch command to retrieve a record from PubMed -db pubmed. We specify that we will retrieve the record for PMID 25359968 -id 25359968 and that we want the results in the text abstract format -format abstract.

+ + + + + + + +
efetch -db pubmed -id 25359968 -format medline
+
+efetch -db pubmed -id 25359968 -format xml
+
+efetch -db pubmed -id 25359968 -format uid
+

Retrieve multiple PubMed records in text abstract format

+
efetch -db pubmed -id 24102982,21171099,17150207 -format abstract
+

This line of code uses the efetch command to retrieve records from PubMed (-db pubmed). We specify that we will retrieve the records for PMID 24102982,21171099,17150207 (-id 24102982,21171099,17150207) and that we want the results in the text abstract format (-format abstract).

+

Creating a data pipeline

+

Conduct a PubMed search and retrieve the results as a list of PMIDs

+ + + + + + +
[1] "Code Executed"
+ + + + + +
[1] "26306366" "8097056"  "2447467" 
+ + + +
esearch -db pubmed -query "asthenopia[mh] AND nursing[sh]" | efetch -format uid
+

This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query “asthenopia[mh] AND nursing[sh]”), and then pipes the resulting PMIDs into an efetch command (| efetch), which retrieves the PubMed records, but outputs only the PMIDs (-format uid). For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.

+

In-class exercise solutions

+

Exercise 1: esearch

+

How many Spanish-language articles about diabetes are in PubMed?

+

Solution:

+
esearch -db pubmed -query "diabetes AND spanish[lang]"
+ + + + + + + +

This line of code uses the esearch command to search PubMed -db pubmed for our search query -query "diabetes AND spanish[lang]". Note that the search query can include Boolean operators AND and search field tags [lang] to help focus our search, just as we can in the web version of PubMed.

+

Exercise 2: esearch

+

How many articles were written by BH Smith between 2012 and 2017, inclusive?

+

Solutions:

+
esearch -db pubmed -query "smith bh[author]" -datetype PDAT -mindate 2012 -maxdate 2017
+ + + + + + + +

There are multiple possible solutions to this exercise. This solution uses the esearch command to search PubMed (-db pubmed) for our search query (-query “smith bh[author]”). Note that the search query can include search field tags ([author]) to help focus our search, just as we can in the web version of PubMed. The esearch command also limits the search results by publication date (-datetype PDAT), including only articles published between 2012 and 2017 (-mindate 2012 -maxdate 2017).

+
esearch -db pubmed -query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat])"
+

The second solution is largely the same as the first. Rather than use the -datetype, -mindate, and -maxdate arguments to limit the search by publication date, this solution incorporates the date restriction into the search string itself (-query “smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat])”), just as you would include a date restriction in a search string in the web version of PubMed.

+

Exercise 3: efetch

+

Who is the first author listed on the PubMed record 26287646?

+

Solution:

+
efetch -db pubmed -id 26287646 -format abstract
+

This line of code uses the efetch command to retrieve a record from PubMed (-db pubmed). We specify that we will retrieve the record for PMID 25359968 (-id 25359968). The command retrieves the record in the text abstract format (-format abstract), which allows us to easily see that the first author of the article is PF Brennan. Rather than using the abstract format, we could instead use -format medline or -format xml to retrieve the record in the MEDLINE or XML formats, if we prefer. Exercise 4: Combining Commands

+

How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017?

+

Solutions:

+
esearch -db pubmed -query "smith bh[author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \
+efetch -format uid
+

This solution begins the same as the first solution for Exercise 2. The first line concludes by piping (|) the results of the esearch command into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records, but outputs only the PMIDs (-format uid).

+
esearch -db pubmed -query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat]" | \
+efetch -format uid
+

Similarly, this solution begins the same as the second solution for Exercise 2, and then pipes the results of the esearch into the efetch, which retrieves the PubMed records, but outputs only the PMIDs (-format uid).

+

For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.

+

Homework solutions

+

Question 1

+

Using EDirect, write a command to find out how many citations are in PubMed for articles about using melatonin to treat sleep disorders.

+

Solution:

+
esearch -db pubmed -query "melatonin sleep disorder"
+

This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query “melatonin sleep disorder”). Question 2

+

How many of the PubMed citations identified in question 2 were added to PubMed (i.e. created) between January 1, 2015 and July 1, 2017?

+

Solution:

+

There are multiple possible solutions to this question.

+
esearch -db pubmed -query "melatonin sleep disorder" -datetype CRDT -mindate 2015/01/01 -maxdate 2017/07/01
+

Both of these solutions use the esearch command to search PubMed (-db pubmed) for our search query (-query “melatonin sleep disorder”). In the first solution, the esearch command also limits the search results by the date citations were added to PubMed, using the “CRDT” date type (-datetype CRDT), including only articles created between January 1, 2015 and July 1, 2017 (-mindate 2015/01/01 -maxdate 2017/07/01).

+
esearch -db pubmed -query "melatonin sleep disorder"  AND (2015/01/01[crdt] : 2017/07/01[crdt])"
+

The second solution is largely the same as the first. Rather than use the -datetype, -mindate, and -maxdate arguments to limit the search by create date, this solution incorporates the date restriction into the search string itself (-query “melatonin sleep disorder” AND (2015/01/01[crdt] : 2017/07/01[crdt])“), just as you would include a date restriction in a search string in the web version of PubMed.

+

Question 3

+

Write a command to retreive the abstracts of the following PubMed records:

+
27240713,27027883,22468771,20121990
+

Solution:

+
efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format abstract
+

This line of code uses the efetch command to retrieve records from PubMed (-db pubmed). We specify that we will retrieve the records for four PMIDs: 27240713, 27027883, 22468771, and 20121990 (-id 27240713,27027883,22468771,20121990). The command retrieves the records in the text abstract format (-format abstract).

+

Question 4

+

Modify your answer to Question 3 to retrieve the full XML of all four records.

+

Solution:

+
efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format xml
+

This solution is largely the same as the solution for Question 3, but the -format argument has been changed to retrieve XML instead of the text Abstract format (-format xml).

+

Question 5

+

Write a series of commands that retrieves a list of PMIDs for all citations for papers written by the author with the ORCID 0000-0002-1141-6306.

+

Solution:

+
esearch -db pubmed -query "0000-0002-1141-6306[auid]" | \
+efetch -format uid
+

This solution begins by using the esearch command to search PubMed (-db pubmed) for citations including an author identifier of “0000-0002-1141-6306” (-query “0000-0002-1141-6306[auid]”). The first line concludes by piping (|) the results of the esearch command into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records, but outputs only the PMIDs (-format uid).

+
+
+
+

4.1.2 Part One

+

https://dataguide.nlm.nih.gov/edirect-for-pubmed-1.txt

+

The Insider’s Guide to Accessing NLM Data: EDirect for PubMed Part One: Getting PubMed Data

+

Course Materials

+

NOTE: Solutions to all exercises are at the bottom of this document.

+

Commands are instructions given by a user telling a computer to do something

+

Arguments provide input data or modify the behavior of a command

+

TIPS FOR CYGWIN USERS:

+

Copy: Ctrl + Insert (NOT Ctrl + C!)

+

Paste: Shift + Insert (NOT Ctrl + V!)

+

TIPS FOR ALL USERS:

+

Ctrl + C “cancels” and gets you back to a prompt

+

Up and Down arrow keys allow you to cycle through your recent commands

+

clear: clears your screen

+

esearch

+

esearch searches a database and returns the unique identifier of every record that meets the search criteria - in this case, PMIDs.

+
-db to specify database: -db pubmed
+-query to enter your query in quotes: -query "seasonal affective disorder"
+

COMMAND STRING:

+
esearch -db pubmed -query "seasonal affective disorder"
+

PUBMED SEARCH:

+
seasonal affective disorder
+

Show PubMed’s translation of your search terms like you receive in the Search Details in PubMed

+

COMMAND STRING:

+
esearch -db pubmed -query "seasonal affective disorder" -log
+

Details display at end of XML snippit

+
"seasonal affective disorder"[MeSH Terms] OR ("seasonal"[All Fields] AND "affective"[All Fields] AND "disorder"[All Fields]) OR "seasonal affective disorder"[All Fields]
+

Search like you do in PubMed with uppercase Boolean AND/OR/NOT and field tags as needed.

+

PUBMED SEARCH:

+
malaria AND jama[journal]
+

COMMAND STRING:

+
esearch -db pubmed -query "malaria AND jama[journal]"
+

Restricting by Date

+
-datetype specifies date field: -datetype PDAT
+-mindate -maxdate specifies range: -mindate 2015 -maxdate 2017 
+

COMMAND STRING:

+
esearch -db pubmed -query "malaria AND jama[journal]" -datetype PDAT -mindate 2015 -maxdate 2017
+

Use backslash "\" to indicate that you have not finished writing the command - it is continued on the next line.

+

COMMAND STRING:

+
esearch -db pubmed -query "malaria AND jama[journal]" \
+-datetype PDAT -mindate 2015 -maxdate 2017
+

Be Careful with Quotes

+

PUBMED SEARCH:

+
cancer AND science[journal]
+
+cancer AND "science"[journal]
+

COMMAND STRING:

+
esearch -db pubmed -query "cancer AND \"science\"[journal]"
+

EXERCISE 1: esearch

+

How many Spanish-language articles about diabetes are in PubMed? Hint: use the [lang] field tag

+

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

+

EXERCISE 2: esearch

+

How many articles were written by BH Smith between 2012 and 2017, inclusive?

+

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

+

efetch

+

efetch retrieves the complete record in the format that you specify.

+
-db to specify database: -db pubmed
+-id to specify PMID: -id 25359968
+-format to specify format: -format abstract
+

COMMAND STRING:

+
efetch -db pubmed -id 25359968 -format abstract
+

efetch Formats

+
-format options:
+

MEDLINE

+
-format medline
+

XML

+
-format xml
+

PMID list

+
-format uid
+

Summary

+
-format docsum
+

efetch Multiple Records

+

Separate multiple PMIDs in the -id argument with commas.

+

COMMAND STRING:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format abstract
+
+efetch -db pubmed -id 26024162 -format abstract
+

EXERCISE 3: efetch Who is the first author listed on the PubMed record 26287646?

+

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

+

Creating a data pipeline

+

Use pipe “|” [Shift + ] to “pipe” the results of one command into the next

+

COMMAND STRING:

+
esearch -db pubmed -query "asthenopia[mh] AND nursing[sh]" | efetch -format uid
+

EXERCISE 4: Combining Commands How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017? Hint: Use the up arrow to access your previous commands Hint: Remember -format uid

+

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

+

HOMEWORK FOR PART ONE

+

(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode1.html)

+

Question 1:

+

Using EDirect, write a command to find out how many citations are in PubMed for articles about using melatonin to treat sleep disorders.

+

Question 2:

+

How many of the PubMed citations identified in question 2 were added to PubMed (i.e. created) between January 1, 2015 and July 1, 2017?

+

Question 3:

+

Write a command to retrieve the abstracts of the following PubMed records:

+
27240713
+27027883
+22468771
+20121990
+

Question 4:

+

Modify your answer to Question 3 to retrieve the full XML of all four records.

+

Question 5:

+

Write a series of commands that retrieves a list of PMIDs for all citations for papers written by the author with the ORCID 0000-0002-1141-6306.

+

EXERCISE SOLUTIONS:

+

EXERCISE 1: esearch How many Spanish-language articles about diabetes are in PubMed? Hint: use the [lang] field tag

+

Solution:

+
esearch -db pubmed -query "diabetes AND spanish[lang]"
+

EXERCISE 2: esearch How many articles were written by BH Smith between 2012 and 2017, inclusive? Hint: use the [author] field tag

+

SOLUTIONS:

+
esearch -db pubmed -query "smith bh[author]" \
+-datetype PDAT -mindate 2012 -maxdate 2017
+
+esearch -db pubmed -query "smith bh[author] \
+AND (2012/01/01[pdat] : 2017/12/31[pdat])"
+

EXERCISE 3: efetch Who is the first author listed on the PubMed record 26287646?

+

Solution:

+
efetch -db pubmed -id 26287646 -format abstract
+

The first author is Brennan PF

+

EXERCISE 4: Combining Commands How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017? Hint: Use the up arrow to access your previous commands Hint: Remember -format uid

+

SOLUTIONS:

+
esearch -db pubmed -query "smith bh[author] AND \
+(2012/01/01[pdat] : 2017/12/31[pdat]" | \
+efetch -format uid
+
+
+
+esearch -db pubmed -query "smith bh[author]" \
+-datetype PDAT -mindate 2012 -maxdate 2017 | \
+efetch -format uid
+
+
+
+

4.2 Part Two “EDirect for PubMed: Part 2: Extracting Data from XML” Sample Code

+
+

4.2.1 Part Two

+

https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode2.html

+

xtract Basics

+

For an introduction to the xtract command, see the xtract section of our EDirect documentation. Retrieve the article titles for a list of PubMed records

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element ArticleTitle
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row in our output table for every PubMed record (-pattern PubmedArticle). The -element argument indicates that the table should include a single column, containing the article title for the given record (-element ArticleTitle). Retrieve the list of authors for a series of PubMed records

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern Author -element LastName
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row in our output table for every author (-pattern Author). The -element argument indicates that the table should include a single column, containing the last name for the given author (-element LastName). Retrieve the PMID and year of publication for a PubMed record

+

In order to retrieve the PMID and the year of publication for a PubMed record, we might try to use code such as the following:

+
efetch -db pubmed -id 27101380 -format xml | \
+xtract -pattern PubmedArticle -element PMID Year
+

The first line of this code uses the efetch command to retrieve a record from PubMed (-db pubmed -id 27101380) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle; in this case, the table will only have a single row). The line then uses the -element argument to create two columns, one for PMID and one for Year. (-element PMID Year). However, the output of this series of commands is not what we expect:

+
27101380        27619336        27619799        27746956        27747057        2016    2016    2016      2016    2015    2016    2016    2016    2016
+

Rather than getting a single PMID and a single year, we get 5 PMIDs and 9 Years. This is because, while the -element argument is designed to create a new column for each element or attribute specified, it populates each column with the contents of every occurrence of the specified element or attribute in the -pattern. This means that if there are multiple occurrences of the or elements in a PubMed record, the contents of all occurrences will be displayed. As a result, we see not only the PMID for the record, but also the PMIDs used to link it to other records which contain related comments or corrections. Furthermore, in addition to the publication year, we also the year for the other eight dates associated with the PubMed record.

+

We can avoid this by using Parent/Child construction to specify that we only want the contents of the element that is a direct child of the element, and that we only want the element that is a child of the element:

+
efetch -db pubmed -id 27101380 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID PubDate/Year
+

This version of the code gives us the output we expect:

+
27101380        2016
+

Retrieve three data elements for a list of PubMed records

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation ArticleTitle    
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the element that is a child of the element), one for the journal title abbreviation, and one for the article title (-element MedlineCitation/PMID ISOAbbreviation ArticleTitle). sort-uniq-count-rank and head Sort a list of authors by the frequency they appear in your results set

+
esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern Author -element LastName,Initials | \
+sort-uniq-count-rank | \
+head -n 10  
+

This series of commands searches PubMed for the string “traumatic brain injury athletes”, restricts results to those published in 2016 and 2017, retrieves the full XML records for each of the search results, extracts the last name and initials of every author on every record, sorts the authors by frequency of occurrence in the results set, and presents the top ten most frequently-occurring authors, along with the number of times that author appeared.

+
esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query “traumatic brain injury athletes”). The line also restricts the search results to articles that were published in 2016 or 2017 (-datetype PDAT -mindate 2016 -maxdate 2017).

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern Author -element LastName,Initials | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials). This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line.

+
sort-uniq-count-rank | \
+

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set.

+
head -n 10
+

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set:

+
14      Iverson     GL
+11      Guskiewicz  KM
+10      Meehan   WP
+9       Kerr       ZY
+9       Kontos   AP
+9       Solomon     GS
+9       Zuckerman   SL
+8       Zafonte     R
+7       Broglio     SP
+7       Covassin    T
+

(Note: Your output may vary slightly, as additional citations are added to PubMed and the “most frequent” authors change.)

+

To show more or fewer rows, adjust the “10” up or down. If you want to see all of the authors, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the “|” and “\” characters from the previous line. Otherwise, the system will wait for you to finish entering your command.) In-class exercise solutions

+

Note: The first three exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data. Exercise 1

+

Write an xtract command that creates a table with one row per PubMed article. Each row should have two columns: volume number and issue number.

+

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element Volume Issue
+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with columns for volume number and issue number (-element Volume Issue). Exercise 2

+

Write an xtract command that creates a table with one row per PubMed record. Each row should have three columns: PMID, journal ISSN, and citation status.

+

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISSN MedlineCitation@Status
+

This xtract command begins the same as the solution for Exercise 1 (xtract -pattern PubmedArticle). When creating the first column, this command uses Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (like as a child of a element; -element MedlineCitation/PMID).

+

Similarly, the second column is also created using Parent/Child construction. This is probably not strictly necessary, as the element only appears in one location in the PubMed XML structure. However, this demonstrates that there may be multiple valid EDirect solutions to a given question (Journal/ISSN).

+

Finally, the citation status, which is found in the “Status” attribute of the element, is placed in the third column (MedlineCitation@Status). Exercise 3

+

Find out which authors have been writing about traumatic brain injuries in athletes, with publications in 2016 and 2017. The output should be a list of author names, one per line, with each author’s last name and initials.

+

Solution:

+
esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern Author -element LastName,Initials
+

This series of commands searches PubMed for the string “traumatic brain injury athletes”, restricts results to those published in 2016 and 2017, retrieves the full XML records for each of the search results, and extracts the last name and initials of every author on every record.

+
esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
+

The first line of code uses esearch to search PubMed (-db pubmed) for our search query (-query “traumatic brain injury athletes”). The line also restricts the search results to articles that were published in 2016 or 2017 (-datetype PDAT -mindate 2016 -maxdate 2017).

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern Author -element LastName,Initials
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line.

+

The command then extracts each author’s last name and initials (-element LastName,Initials). Homework solutions

+

Question 1

+

Using the efetch command below to retrieve PubMed XML, write an xtract command to extract specific elements and arrange them into a table. The table should have one PubMed record per row, with columns for PMID, Journal Title Abbreviation, Publication Year, Volume, Issue and Page Numbers.

+
efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml
+

Solution:

+
efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation PubDate/Year Volume Issue MedlinePgn
+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). When creating the first column, this command uses Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (like as a child of a element; -element MedlineCitation/PMID).

+

The second column is created without Parent/Child construction, as the element is not repeated in a single PubMed XML record (ISOAbbreviation).

+

The third column also uses Parent/Child construction to retrieve the publication year (as opposed to other elements; PubDate/Year); the remaining elements only appear in one location in the PubMed XML structure, so Parent/Child construction is unnecessary (Volume Issue MedlinePgn).

+

Question 2

+

Create a table of the authors attached to PubMed record 28341696. The table should include each author’s last name, initials, and affiliation information (if listed).

+

Solution:

+
efetch -db pubmed -id 28341696 -format xml | \
+xtract -pattern Author -element LastName Initials Affiliation
+

This first line of this solution uses the efetch command to retrieve a record from PubMed (-db pubmed). We specify that we will retrieve the record for PMID 28341696 (-id 28341696) and that we want the results in XML (-format xml).

+
xtract -pattern Author -element LastName Initials Affiliation
+

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name, initials, and affiliation information (-element LastName Initials Affiliation).

+

Question 3

+

Write a series of commands to generate a table of PubMed records for review articles about the Paleolithic diet. The table should have one row per citation, and should include columns for the PMID, the citation status, and the article title.

+

Solution:

+
esearch -db pubmed -query "review[pt] paleolithic diet" | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID MedlineCitation@Status ArticleTitle
+

This series of commands searches PubMed for the string “review[pt] paleolithic diet”, retrieves the full XML records for each of the search results, and extracts the last name and initials of every author on every record.

+
esearch -db pubmed -query "review[pt] paleolithic diet" | \
+

The first line of code uses esearch to search PubMed (-db pubmed) for our search query (-query “review[pt] paleolithic diet”). Note that the search query can include search field tags ([pt]) to help focus our search, just as we can in the web version of PubMed.

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+

xtract -pattern PubmedArticle -element MedlineCitation/PMID MedlineCitation@Status ArticleTitle

+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every PubMed record (-pattern PubmedArticle).

+

The command then extracts each record’s PMID (using Parent/Child construction; -element MedlineCitation/PMID), citation status (using “@” to retrieve the attribute value for “Status”; MedlineCitation@Status), and article title (ArticleTitle).

+
+
+

4.2.2 Part Two

+

https://dataguide.nlm.nih.gov/edirect-for-pubmed-2.txt

+

The Insider’s Guide to Accessing NLM Data: EDirect for PubMed Part Two: Extracting Data from XML Course Materials

+

NOTE: Solutions to all exercises are at the bottom of this document.

+

REMINDERS FROM PART ONE

+

esearch: Searches a database and returns PMIDs

+

efetch: Retrieves PubMed records in a variety of formats

+

Use “|” (Shift + , pronounced “pipe”) to “pipe” the results of one command into the next

+

TIPS FOR CYGWIN USERS:

+

Copy: Ctrl + Insert (NOT Ctrl + C!)

+

Paste: Shift + Insert (NOT Ctrl + V!)

+

TIPS FOR ALL USERS:

+

Ctrl + C “cancels” and gets you back to a prompt

+

Up and Down arrow keys allow you to cycle through your recent commands

+

clear: clears your screen

+
+

xtract

+

Extracts specific elements from XML and arranges them in a customized tabular format.

+
+

Getting XML

+

From efetch:

+

[…] | efetch -format xml | xtract […]

+

From a file on your computer using “-input”:

+

xtract -input file.xml […]

+
+

XML Element Descriptions https://www.nlm.nih.gov/bsd/licensee/elements_descriptions.html

+

PubMed DTD Documentation https://dtd.nlm.nih.gov/ncbi/pubmed/out/doc/2018/

+
+

Before you start xtract-ing…

+

Look at some PubMed XML by searching PubMed for a few PMIDs:

+

24102982,21171099,17150207

+
+

Getting a small sample dataset

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml
+
+

-pattern to identify which element will create a new row in the output table

+

-element to identify which element(s) or attribute(s) will create columns in the output table

+

A basic xtract Command:

+

COMMAND STRING:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element ArticleTitle
+
+
+efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern Author -element LastName
+
+

Creating multiple columns

+

Create multiple columns using the same -element argument by including multiple XML element names. Separate the names with spaces.

+

Example:

+
xtract -pattern PubmedArticle -element Agency GrantID
+
+

EXERCISE 1: Write an xtract command that: * creates a table with one row per PubMed article. * Each row should have two columns: * Volume * Issue Number

+

Use the following efetch as input:

+

efetch -db pubmed -id 24102982,21171099,17150207 -format xml |  

+

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

+ +++ + + + + + + + + + + + +
Isolating the elements we need
COMMAND STRING:
efetch -db pubmed -id 27101380 -format xml |
+xtract -pattern PubmedArticle -element PMID Year
+

Parent/Child construction

+

Retrieves only elements that are the child of a specific parent.

+

Format: ParentElement/ChildElement

+

Example:

+
-element MedlineCitation/PMID
+
+

Solving xtract Example 1 We have a set of records We want a tabular list with PMID, Journal Title Abbreviation, and Article Title

+

COMMAND STRING: efetch -db pubmed -id 24102982,21171099,17150207 -format xml |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISOAbbreviation ArticleTitle

+
+

xtract-ing attribute values

+

Format: ElementName@AttributeName

+

Example:

+
-element DescriptorName@MajorTopicYN
+
+

EXERCISE 2 Write an xtract command that: * Has one row per PubMed records * Has three columns: * PMID * Journal ISSN * Citation status

+

Use the following efetch as input:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

+
+

EXERCISE 3: Putting it all together

+

We want to find out which authors have been writing about traumatic brain injuries in athletes * Limit to publications from 2016 and 2017. We want to see just the author names, one per line. We want the last name and initials, separated by a space. We want the whole script (not just the xtract command).

+

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

+
+

sort-uniq-count-rank

+

Four steps of sort-uniq-count-rank 1. Sorts all of the lines in your input alphabetically by the full contents of the line 2. Eliminates all duplicates, leaving only unique values. 3. Counts up how many of each unique value there were in your input, and provides that frequency count next to each unique value. 4. Re-sorts the unique values in descending order by frequency, so the most frequently occurring values are at the top.

+

COMMAND STRING:

+

esearch -db pubmed -query “traumatic brain injury athletes” -datetype PDAT -mindate 2016 -maxdate 2017 |
+efetch -format xml |
+xtract -pattern Author -element LastName Initials |
+sort-uniq-count-rank

+
+

head

+

Limits output to only the first few lines of input.

+

Example:

+
head -n 10
+

Outputs only the first ten lines of the input.

+

COMMAND STRING:

+
esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern Author -element LastName Initials | \
+sort-uniq-count-rank | \
+head -n 10
+

HOMEWORK FOR PART TWO)

+

(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode2.html)

+

Question 1:

+

Using the efetch command below to retrieve PubMed XML, write an xtract command with one record per row, with columns for PMID, Journal Title Abbreviation, Publication Year, Volume, Issue and Page Numbers.

+
efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml
+

Question 2:

+

Create a table of the authors attached to PubMed record 28341696. The table should include each author’s last name, initials, and affiliation information (if listed).

+

Question 3:

+

Write a series of commands to generate a table of PubMed records for review articles about the paleolithic diet. The table should have one row per citation, and should include columns for the PMID, the citation status, and the article title.

+

EXERCISE SOLUTIONS:

+

EXERCISE 1: Write an xtract command that: * creates a table with one row per PubMed article. * Each row should have two columns: * Volume * Issue Number

+

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element Volume Issue
+

EXERCISE 2: Write an xtract command that: * Has one row per PubMed records * Has three columns: * PMID * Journal ISSN * Citation status

+

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISSN MedlineCitation@Status
+

EXERCISE 3: Putting it all together

+

We want to find out which authors have been writing about traumatic brain injuries in athletes * Limit to publications from 2016 and 2017. We want to see just the author names, one per line. We want the last name and initials, separated by a space. We want the whole script (not just the xtract command).

+

Solution:

+
esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern Author -element LastName Initials
+
+
+
+

4.3 Part Three “EDirect for PubMed: Part 3: Formatting Results and Unix Tools” Sample Code

+
+

4.3.1 Part Three

+

https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode3.html

+

xtract Formatting arguments

+

For an introduction to xtract Formatting arguments, see the Customizing separators section of our EDirect documentation. Change the separators in an xtract output table

+

We can use the -tab and -sep arguments to modify the separators in an xtract output table. We will start with a basic xtract statement with no customized separators:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISSN LastName
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the element that is a child of the element), one for the journal ISSN, and one for author last name (-element MedlineCitation/PMID ISSN LastName). For articles with more than one author, we will see multiple author last names in the third column:

+
24102982        1742-4658       Wu      Doyle   Barry   Beauvais        Rozkalne        Piao    Lawlor    Kopin   Walsh   Gussoni
+21171099        1097-4598       Wu      Gussoni
+17150207        0012-1606       Yoon    Molloy  Wu      Cowan   Gussoni
+

By default, xtract separates columns in the output table with tabs (indicated in Unix as \t). Additionally, by default, xtract separates multiple values in the same column with tabs. So the following series of commands:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "\t" -sep "\t" -element MedlineCitation/PMID ISSN LastName
+

produces the same output as before, since we are telling xtract to use a tab to separate between columns (-tab "\t") and between multiple values in the same column (-sep “”), which xtract is already doing by default:

+
24102982        1742-4658       Wu      Doyle   Barry   Beauvais        Rozkalne        Piao    Lawlor    Kopin   Walsh   Gussoni
+21171099        1097-4598       Wu      Gussoni
+17150207        0012-1606       Yoon    Molloy  Wu      Cowan   Gussoni
+

We can modify the output by modifying the -sep argument:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "\t" -sep " " -element MedlineCitation/PMID ISSN LastName
+

This series of commands tells xtract to keep the separators between columns the same, but to separate multiple values in the same column (such as the multiple author last names in our third column) by spaces instead of tabs:

+
24102982        1742-4658       Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni
+21171099        1097-4598       Wu Gussoni
+17150207        0012-1606       Yoon Molloy Wu Cowan Gussoni
+

We can further modify the output by modifying the -tab argument:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep " " -element MedlineCitation/PMID ISSN LastName
+

This time, the separators between columns have been changed from tabs to pipes (-tab “|”), while multiple values in the same column are still separated by spaces:

+
24102982|1742-4658|Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni
+21171099|1097-4598|Wu Gussoni
+17150207|0012-1606|Yoon Molloy Wu Cowan Gussoni
+

The -tab and -sep arguments also allow you to specify separators of more than one character:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep ", " -element MedlineCitation/PMID ISSN LastName
+

This series of commands uses pipes to separate the columns (-tab “|”), but uses a comma followed by a space to separate the last names (-sep “,”):

+
24102982|1742-4658|Wu, Doyle, Barry, Beauvais, Rozkalne, Piao, Lawlor, Kopin, Walsh, Gussoni
+21171099|1097-4598|Wu, Gussoni
+17150207|0012-1606|Yoon, Molloy, Wu, Cowan, Gussoni
+

xtract Exploration arguments

+

For an introduction to xtract Exploration arguments, see the Exploration arguments section of our EDirect documentation. Retrieve author names for a list of PubMed records

+

In order to retrieve the author names (including last name and initials) for all of the authors associated with each of several PubMed records, we might try to use code such as the following:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID LastName Initials
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the element that is a child of the element), one for author last name, and one for author initials (-element MedlineCitation/PMID LastName Initials). However, the output of this series of commands is not what we expect:

+
24102982        Wu      Doyle   Barry   Beauvais        Rozkalne        Piao    Lawlor  Kopin   Walsh     Gussoni MP      JR      B       A       A       X       MW      AS    CA      E
+21171099        Wu      Gussoni MP      E
+17150207        Yoon    Molloy  Wu      Cowan   Gussoni S       MJ      MP      DB      E
+

The PMID appears as we expect, as does the first author last name. However, rather than following the first author’s last name with the corresponding initials, our output lists all of the authors’ last names for a PubMed record first, before listing all of the authors’ initials.

+

To retain the relationship between last name and initials, we could use the following series of commands:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -element LastName Initials
+

The second line of this code creates a column for the PMID as before (xtract -pattern PubmedArticle -element MedlineCitation/PMID). However, the code then uses the -block argument to direct xtract to look for an element, then to look within that for and elements (-block Author -element LastName Initials). Because each author has only one last name and one set of initials, xtract outputs a corresponding pair of last name and initials, before moving on to find the next author. This process is then repeated for each author, giving us the output we expect:

+
24102982        Wu      MP      Doyle   JR      Barry   B       Beauvais        A       Rozkalne        A       Piao    X       Lawlor  MW      Kopin   AS   Walsh    CA      Gussoni E
+21171099        Wu      MP      Gussoni E
+17150207        Yoon    S       Molloy  MJ      Wu      MP      Cowan   DB      Gussoni E
+

Putting values from multiple elements in the same column Separate author last name and initials with a space, while separating columns with a tab

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -sep " " -element LastName,Initials
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and creates a column for the PMID (xtract -pattern PubmedArticle -element MedlineCitation/PMID). As seen in previous examples, the code than uses the -block argument to direct xtract to look for an element (-block Author), then to look within that for and elements.

+

Because each author has only one last name and one set of initials, xtract outputs a corresponding pair of last name and initials, before moving on to find the next author. However, rather than putting the last name and initials in separate columns, this command uses a comma to group together both the last name and initials in the same column (-element LastName,Initials). This tells xtract to separate the last name and initials with the character we define in the -sep argument (which we have defined as a single space: -sep " “), instead of using the separator between columns (which is still the default tab), and gives us the output we desire:

+
24102982        Wu MP   Doyle JR        Barry B Beauvais A      Rozkalne A      Piao X  Lawlor MW       Kopin AS        Walsh CA      Gussoni E
+21171099        Wu MP   Gussoni E
+17150207        Yoon S  Molloy MJ       Wu MP   Cowan DB        Gussoni E
+

Working with files Saving results to a file

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.txt
+

This line of code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and redirects the XML output to a file named “testfile.txt” (> testfile.txt). Using a search string saved in a file to search PubMed

+
esearch -db pubmed -query "$(cat searchstring.txt)"
+

This line of code uses the esearch command to search PubMed (-db pubmed). The search query is stored in a text file (“searchstring.txt”), and the cat command is used to access the contents of the file for use as a search query (-query “$(cat searchstring.txt)”). The dollar-sign and parentheses around cat searchstring.txt indicate that Unix should use the value of cat searchstring.txt (i.e. the contents of the file “searchstring.txt”), rather than simply the words “cat searchstring.txt”. epost Post two PMIDs to the History server

+
epost -db pubmed -id 24102982,21171099
+

This line of code uses the epost command to post two unique identifiers (UIDs) to the History server (-id 24102982,21171099), indicating that the UIDs are for records in the PubMed database (i.e. that the UIDs are actually PMIDs; -db pubmed).

+

For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview. Post two PMIDs to the History server and retrieve the corresponding PubMed records in abstract format

+
epost -db pubmed -id 24102982,21171099 | efetch -format abstract
+

This line of code uses the epost command to post two unique identifiers (UIDs) to the History server (-id 24102982,21171099), indicating that the UIDs are for records in the PubMed database (i.e. that the UIDs are actually PMIDs; -db pubmed). The line then pipes information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract). For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview. Retrieve PubMed records in abstract format for a list of PMIDs contained in a CSV file

+
cat pmids.csv | epost -db pubmed | efetch -format abstract
+

This line of code uses cat to open a CSV file (“pmids.csv”) which contains a list of PMIDs (cat pmids.csv). Rather than displaying the contents of the file on the screen, this line of code pipes the contents of the file into an epost command (| epost). The epost command stores the PMIDs on the History server, indicating to the History server that they are PMIDs, and not UIDs from a different database (-db pubmed). Finally, the line pipes the information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract).

+
epost -db pubmed -input pmids.csv | efetch -format abstract
+

This line of code is another way of accomplishing the same task as the previous example. Rather than use cat to open the file “pmids.csv”, this line uses the epost command’s -input argument, which is a new feature of EDirect, added in version 4.90 (released on September 14, 2016). The epost command stores the PMIDs on the History server, indicating to the History server that they are PMIDs, and not UIDs from a different database (-db pubmed). Finally, the line pipes the information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract).

+

For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview. In-class exercise solutions

+

Note: The first two exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data. Exercise 1

+

Write an xtract command that generates a new row for each PubMed record, and has columns for PMID, journal title abbreviation, and author-supplied keywords. Each column should be separated by “|”. Multiple keywords in the last column should be separated with commas.

+

Sample Output:

+
26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology
+

Solution:

+
efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep "," -element MedlineCitation/PMID ISOAbbreviation Keyword
+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with columns for PMID (specified using Parent/Child construction), journal title abbreviation, and author-supplied keywords (-element MedlineCitation/PMID ISOAbbreviation Keyword).

+

Instead of separating the columns by tabs, the command uses the -tab argument to specify pipe (“|”) as a separator (-tab “|”). Because each record could have multiple author-supplied keywords, the command uses the -sep argument to specify a separator between multiple values in a column (i.e. multiple author-supplied keywords in the third column; -sep “,”). Exercise 2

+

Write an xtract command that creates a table with a new row for each PubMed record. Each row should have the record’s PMID, as well as a list of all the MeSH headings for the records, separated by “|”. If a MeSH heading has subheadings attached, separate the heading and subheadings with “/”. For example:

+
24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology
+

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \
+-block MeshHeading -tab "|" -sep "/" -element DescriptorName,QualifierName
+

This xtract command begins the same as the solution for Exercise 1 (xtract -pattern PubmedArticle). The command then specifies a separator between columns (-tab “|”) and the first column in the output table (using Parent/Child construction; -element MedlineCitation/PMID). The “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+

The command continues on the next line, using -block to maintain the relationship between MeSH headings and related subheadings. The -block argument directs xtract to look for a element (-block MeshHeading) then to look within that for and elements. Another argument is needed to respecify the separator between columns (-tab “|”), as the separators are reset to default by -block.

+

Each element contains one , but may contain zero or more elements. For each -block, the -element argument populates a column with the and all of the elements, if there are any (-element DescriptorName,QualifierName). For MeSH headings with subheadings, this will place multiple values in the same column (one and one or more elements), so we establish “/” as a separator between multiple values in the same column (-sep “/”).

+

Exercise 3

+

How can we get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil? Save your results to a file.

+

Solution:

+
esearch -db pubmed -query "zika virus microcephaly brazil" | \
+efetch -format xml > zika.xml
+

This solution begins by using the esearch command to search PubMed (-db pubmed) for our search query (-query “zika virus microcephaly brazil”). The first line concludes by piping (|) the results of the esearch command into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records in full XML (-format xml). The results of the command is then redirected to a file (> zika.xml). Homework solutions

+

Question 1

+

In the PubMed XML of each record, there is a element, with one or more elements which provide dates for various stages in each article’s life cycle. These can include when the article was submitted to the publisher for review, when the article was accepted by the publisher for publication, when it was added to PubMed, and/or when it was indexed for MEDLINE, among others. Not all citations will include entries for each type of date.

+

For the following list of PMIDs

+
22389010,20060130,14678125,19750182,19042713,18586245
+

write a series of commands that retrieves each record and extracts all of these different dates, along with the labels that indicate which type of date is which.

+

Each PubMed record should appear on a separate line. Each line should start with the PMID, followed by a tab, followed by the list of dates. For each date, include the label, followed by a “:”, followed by the year, month and day, separated by slashes. Separate each date with a “|”.

+

Example output:

+
18586245        received:2008/01/21|revised:2008/05/05|accepted:2008/05/07|pubmed:2008/7/1|medline:2008/10/28|entrez:2008/7/1
+

Solution:

+
efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block PubMedPubDate -tab ":" -sep "/" -element PubMedPubDate@PubStatus \
+-tab "|" -element Year,Month,Day
+

Question 2

+

Identify your “working directory”. Write a series of commands that retrieve PubMed data, redirect the output to a file, and locate the file on your computer.

+

Solution:

+

The solution to this question may vary, depending on what type of Unix system you are using to run EDirect. One possible solution for identifying your “working directory” is:

+
pwd
+

The pwd command prints to the screen the name of your working directory. Depending on your system, this may give you all of the information you need to find your working directory. If not, please review the material presented in “EDirect for PubMed: Part 3: Formatting Results and Unix Tools”.

+

The second part of this question may also have many solutions. One possible solution is:

+
efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format abstract > abstracts.txt
+

This solution uses a basic efetch command to retrieve the six PubMed records specified in the the text abstract format (-format abstract). The command then redirects the output to a text file (> abstracts.txt). Provided you have found your working directory, you can find your new file and open it in a text editor. Question 3

+

Write a series of commands that identifies the top ten agencies that have most frequently funded published research on diabetes and pregnancy over the last year and a half. Your script should start with a search for articles about diabetes and pregnancy that were published between January 1, 2016 and June 30, 2017, should extract the agencies listed as funders on each citation, and should output a list of the ten most frequently occuring agencies. Save the results to a file.

+

Note: This script may take some time to run. As you build it, consider testing with small set of PubMed records, or with a search that has a smaller date range.

+

Solution:

+
esearch -db pubmed -query "diabetes AND pregnancy" -datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30 | \
+efetch -format xml | \
+xtract -pattern Author -sep " " -element LastName,Initials | \
+sort-uniq-count-rank | \
+head -n 10
+

This series of commands searches PubMed for the string “diabetes AND pregnancy” with a publication date between January 1, 2016 and June 30, 2017; retrieves the full XML records for each of the search results; extracts the last name and initials of every author on every record; sorts the authors by frequency of occurence in the results set; and presents the top ten most frequently-occuring authors, along with the number of times that author appeared.

+
esearch -db pubmed -query "diabetes AND pregnancy" -datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30 | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query “diabetes AND pregnancy”). We use the -datetype, -mindate, and -maxdate arguments to add our date restriction (-datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30). Alternatively, we could include the date restriction in our search string, as part of our -query argument.

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern Author -sep " " -element LastName,Initials | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials) and separates the two elements with a single space (-sep " “). This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line.

+
sort-uniq-count-rank | \
+

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set.

+
head -n 10
+

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set. Question 4

+

Write a PubMed search strategy and save it to a file. Write a series of commands to search PubMed using the search string contained in the file and retrieve a list of PMIDs for all records which meet the search criteria.

+

Solution:

+

The solution to this may vary, based on your strategy and the name of the file to which you save it. For this example, our search strategy is saved to a file named “searchstring.txt”.

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format uid
+

The first line uses esearch to search PubMed (-db pubmed). The line uses the Unix command cat to read the entire contents of a file (searchstring.txt) and use it as the search query (-query “$(cat searchstring.txt)”).

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format uid
+

The second line takes the esearch result from our first line and uses efetch to retrieve the PMIDs for all of the records in our results set. (efetch -format uid).

+

Question 5

+

Save the following list of PMIDs in a .csv file:

+
22389010,20060130,14678125,19750182,19042713,18586245
+

Write a series of commands to retrieve the full PubMed XML records for all of the PMIDs in the file, and save the resulting XML to a .xml file.

+

Solution:

+

The solution to this may vary, based on how you choose to save your PMIDs to a file, and on the name of that file. To begin, you could save your PMIDs to a file using efetch:

+
efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format uid > pmids.csv
+

Regardless of how you get the PMIDs into a .csv file, you can use epost -input and efetch to retrieve the records.

+
epost -db pubmed -input pmids.csv | \
+efetch -format xml > records.xml
+

The first line of this solution uses epost to retrieve the numbers from the “pmids.csv” file (-input pmids.csv) and save them to the history server, along with the indication that the numbers are PMIDs, and refer to records in PubMed (-db pubmed)

+

The “|” character pipes the WebEnv and QueryKey output of our epost into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+

The efetch command on the second line receiveds the WebEnv and QueryKey from the epost and uses the information to locate on the history server the specific set of PMIDs posted by our epost command. The efetch command then retrieves the full records for each of those PMIDs in full PubMed XML (-format xml), and saves the output to a new file (> records.xml).

+
+
+

4.3.2 Part Three

+

https://dataguide.nlm.nih.gov/edirect-for-pubmed-3.txt

+

The Insider’s Guide to Accessing NLM Data: EDirect for PubMed Part Three: Formatting Results and Unix tools Course Materials

+

NOTE: Solutions to all exercises are at the bottom of this document.

+

REMINDERS FROM PART ONE

+

esearch: Searches a database and returns PMIDs

+

efetch: Retrieves PubMed records in a variety of formats

+

Use “|” (Shift + , pronounced “pipe”) to “pipe” the results of one command into the next

+
+

REMINDERS FROM PART TWO

+

xtract: Pulls data from XML and arranges it in a table

+

-pattern: Defines rows for xtract

+

-element: Defines columns for xtract

+

Identify XML elements by name (e.g. ArticleTitle)

+

Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID)

+

Identify attributes with “@” (e.g. MedlineCitation@Status)

+
+

TIPS FOR CYGWIN USERS:

+

Copy: Ctrl + Insert (NOT Ctrl + C!)

+

Paste: Shift + Insert (NOT Ctrl + V!)

+
+

TIPS FOR ALL USERS:

+

Ctrl + C “cancels” and gets you back to a prompt

+

Up and Down arrow keys allow you to cycle through your recent commands

+

clear: clears your screen

+
+

-tab and -sep

+

-tab defines the separator between columns -sep defines the separator between multiple values in the same columns

+

The default for both -tab and -sep is “” (the tab character) Changes to -tab and -sep only affect subsequent -element/-first/-last arguments

+

COMMAND STRING:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISSN LastName
+
+efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "\t" -sep "\t" \
+-element MedlineCitation/PMID ISSN LastName
+
+efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "\t" -sep " " \
+-element MedlineCitation/PMID ISSN LastName
+
+efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep " " \
+-element MedlineCitation/PMID ISSN LastName
+
+efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep "," \
+-element MedlineCitation/PMID ISSN LastName
+
+efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep ", " \
+-element MedlineCitation/PMID ISSN LastName
+

With -tab/-sep, order matters!

+

-tab/-sep only affect subsequent -elements

+

Later -tab/-sep overwrite earlier ones

+

EXERCISE 1

+

Write an xtract command that: * has a new row for each PubMed record * has columns for PMID, Journal Title Abbreviation, and Author-supplied Keywords Each column should be separated by “|” Multiple keywords in the last column should be separated with commas Sample Output:

+
26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology
+

Use the following efetch as input:

+
efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \
+

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

+

Authors: First Draft

+

COMMAND STRING:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID LastName Initials
+
+

-block

+

-block associates multiple child elements of the same parent element in the results

+

COMMAND STRING:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -element LastName Initials
+
+

What we know so far…

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep ", " \
+-element MedlineCitation/PMID ISSN LastName
+
+

Putting two different elements in the same column

+

Separate multiple -element values with a comma instead of a space.

+

COMMAND STRING:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block Author -sep " " -element LastName,Initials
+

“-block” resets -tab/-sep to default

+

COMMAND STRING:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \
+-block Author -sep " " -element LastName,Initials
+
+
+efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \
+-block Author -tab "|" -sep " " -element LastName,Initials
+
+

EXERCISE 2

+

Write an xtract command that: * Has a new row for each PubMed record * Has a column for PMID * Lists all of the MeSH headings, separated by “|” * If a heading has multiple subheadings attached, separate the heading and subheadings with “/” Sample Output:

+
24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology
+

Use the following efetch as input:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

+
+

Saving results to a file

+

Use “>” to save the output to a file

+

COMMAND STRING:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.txt
+
+efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.xml
+

But where is my file!?

+

Use “pwd” to “Print the Working Directory” (a.k.a display on the screen the name of the directory you are working in). This is where your file was saved.

+

CYGWIN USERS:

+

Your working directory is probably a subfolder of the folder where you installed Cygwin. In Cygwin, try:

+

cygpath -w ~

+

MAC USERS:

+

Your working directory is probably in your Users folder:

+

Users/

+
+

Another way to find your files

+

COMMAND STRING:

+

efetch -db pubmed -id 24102982,21171099,25359968,17150207 -format uid > specialname.csv

+

Use “ls” to list the files in your current directory.

+
+

EXERCISE 3: Retrieving XML How can I get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil? Save your results to a file.

+

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

+
+

cat

+

Short for concatenate, “cat” opens files to display them on the screen. “cat” can also combine/append files

+
+

Reading a search string from a file

+

Use “$(cat filename)” to use the contents of a file in a command

+

COMMAND STRING:

+
esearch -db pubmed -query "$(cat searchstring.txt)"
+
+

epost uploads a list of PMIDs to the history server

+

COMMAND STRING:

+
epost -db pubmed -id 24102982,21171099
+
+epost -db pubmed -id 24102982,21171099 | efetch -format abstract
+

An epost-efetch pipeline

+
cat specialname.csv | epost -db pubmed | efetch -format abstract
+

Using the -input argument

+
epost -db pubmed -input specialname.csv | efetch -format abstract
+

HOMEWORK FOR PART THREE

+

(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode3.html)

+

Question 1:

+

In the PubMed XML of each record, there is a element, with one or more elements which provide dates for various stages in each article’s life cycle. These can include when the article was submitted to the publisher for review, when the article was accepted by the publisher for publication, when it was added to PubMed, and/or when it was indexed for MEDLINE, among others. Not all citations will include entries for each type of date.

+

For the following list of PMIDs

+
22389010
+20060130
+14678125
+19750182
+19042713
+18586245
+

write a series of commands that retrieves each record and extracts all of these different dates, along with the labels that indicate which type of date is which.

+

Each PubMed record should appear on a separate line. Each line should start with the PMID, followed by a tab, followed by the list of dates. For each date, include the label, followed by a “:”, followed by the year, month and day, separated by slashes. Separate each date with a “|”.

+

Example output:

+
18586245        received:2008/01/21|revised:2008/05/05|accepted:2008/05/07|pubmed:2008/7/1|medline:2008/10/28|entrez:2008/7/1
+

Question 2:

+

Identify your “working directory”. Write a series of commands that retrieve PubMed data, redirect the output to a file, and locate the file on your computer.

+

Question 3:

+

Write a series of commands that identifies the top ten agencies that have most frequently funded published research on diabetes and pregnancy over the last year and a half. Your script should start with a search for articles about diabetes and pregnancy that were published between January 1, 2016 and June 30, 2017, should extract the agencies listed as funders on each citation, and should output a list of the ten most frequently occurring agencies. Save the results to a file.

+

Note: This script may take some time to run. As you build it, consider testing with small set of PubMed records, or with a search that has a smaller date range.

+

Question 4:

+

Write a PubMed search strategy and save it to a file. Write a series of commands to search PubMed using the search string contained in the file and retrieve a list of PMIDs for all records which meet the search criteria.

+

Question 5:

+

Save the following list of PMIDs in a .csv file:

+
22389010
+20060130
+14678125
+19750182
+19042713
+18586245
+

Write a series of commands to retrieve the full PubMed XML records for all of the PMIDs in the file, and save the resulting XML to a .xml file.

+

-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- EXERCISE SOLUTIONS: -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-

+

EXERCISE 1 Write an xtract command that: * has a new row for each PubMed recprd * has columns for PMID, Journal Title Abbreviation, and Author-supplied Keywords Each column should be separated by “|” Multiple keywords in the last column should be separated with commas Sample Output:

+

26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology

+

Solution:

+
efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -sep "," -element MedlineCitation/PMID ISOAbbreviation Keyword
+

-=-=-=-=-=-=-=-=-=-=-=-=- EXERCISE 2: Write an xtract command that: * Has a new row for each PubMed record * Has a column for PMID * Lists all of the MeSH headings, separated by “|” * If a heading has multiple subheadings attached, separate the heading and subheadings with “/” Sample Output:

+
24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology
+

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \
+-block MeshHeading -tab "|" -sep "/" -element DescriptorName,QualifierName
+

-=-=-=-=-=-=-=-=-=-=-=-=- EXERCISE 3: Retrieving XML How can I get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil? Save your results to a file.

+

Solution:

+
esearch -db pubmed \
+-query "zika virus microcephaly brazil" | \
+efetch -format xml > zika.xml
+
+
+
+

4.4 Part Four “EDirect for PubMed: Part 4: xtract Conditional Arguments” Sample Code

+
+

4.4.1 Part Four

+

https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode4.html

+

xtract Conditional arguments

+

For an introduction to the xtract Conditional arguments, see the Filtering output with Conditional arguments section of our EDirect documentation. Include only authors with ORCID IDs in the output table

+
efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml | \
+xtract -pattern Author -if Identifier -sep " " -element LastName,Initials Identifier
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27298442,27392493,27363997,27298443) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each element (-pattern Author), but only if the element contains an element (which is the where an author’s ORCID ID is stored). If an author does not have an ORCID ID, the author will not have an element; no row is created for the author, and xtract skips to the next author (-if Identifier).

+

The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " “), and one with the author’s ORCID ID (Identifier). Include only articles from the journal JAMA in the output table

+
efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
+xtract -pattern PubmedArticle -if ISOAbbreviation -equals JAMA -element Volume Issue
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the article’s journal title abbreviation () is “JAMA”. If a citation is from a different journal, no row is created for the record, and xtract skips to the next record (-if ISOAbbreviation -equals JAMA).

+

The command creates two columns for each row: one with the article’s Volume number, one with the article’s Issue number (-element Volume Issue). Include only MEDLINE articles in the output table

+
efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
+xtract -pattern PubmedArticle -if MedlineCitation@Status -equals MEDLINE -element MedlineCitation/PMID
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the record’s citation status (which is found in the “Status” attribute of the element) is “MEDLINE”. If a citation is not in “MEDLINE” status, no row is created for the record, and xtract skips to the next record (-if MedlineCitation@Status -equals MEDLINE).

+

The command creates a single column for each row, containing the record’s PMID (specifically, the contents of the element that is a child of the element; -element MedlineCitation/PMID) Include only authors whose affiliation mentions Japan in the output table

+
efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
+xtract -pattern Author -if Affiliation -contains Japan -sep " " -element LastName,Initials Affiliation
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each element (-pattern Author), but only if the element contains an element which includes the word “Japan”. If an author does not have affiliation data, or the author’s affiliation data does not contain Japan, no row is created for the author, and xtract skips to the next author (-if Affiliation -contains Japan).

+

The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " “), and one with the author’s affiliation data (Affiliation). Output a list of PMIDs and corresponding DOIs

+
efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block ArticleId -if ArticleId@IdType -equals doi -element ArticleId
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 16940437,16049336,11972038) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (e.g. as a child of a element; -element MedlineCitation/PMID).

+

The xtract command continues on the third line by checking each element in a PubMed record (-block ArticleId). If an element contains a DOI (indicated by the “IdType” attribute for the equaling “doi”; -if ArticleId@IdType -equals doi), then the command puts the DOI in the second column (-element ArticleId). If not, the second column is left blank.

+

The result of this command will be a two column table, where the first column is always a PMID, and the second column is either the corresponding DOI (if there is one), or is blank (if there is no DOI). Combining multiple Conditional arguments Output a list of PMIDs and corresponding DOIs and PMCIDs

+
efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block ArticleId -if ArticleId@IdType -equals doi \
+-or ArticleId@IdType -equals pmc -element ArticleId
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 16940437,16049336,11972038) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (e.g. as a child of a element; -element MedlineCitation/PMID).

+

The xtract command continues on the third line by checking each element in a PubMed record (-block ArticleId). If an element contains a DOI (indicated by the “IdType” attribute for the equaling “doi”; -if ArticleId@IdType -equals doi) OR a PMC ID (indicated by the “IdType” attribute for the equaling “pmc”; -or ArticleId@IdType -equals pmc), then the command puts the contents of the element in the second column (-element ArticleId).

+

Because a PubMed record can have multiple elements, and because the -block argument checks each separately, this command may result in both a DOI and a PMC ID appearing the second column of some rows. Include only authors with the last name Kamal and with affiliation data in the output table

+
efetch -db pubmed -id 27798514,24372221,24332497,24307782 -format xml | \
+xtract -pattern Author -if LastName -equals Kamal -and Affiliation \
+-sep " " -element LastName,Initials Affiliation
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27798514,24372221,24332497,24307782) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each element (-pattern Author), but only if the element for the is “Kamal”, AND the element contains an element (-if LastName -equals Kamal -and Affiliation). If an author’s last name is not “Kamal” or the author does not have affiliation data, no row is created for the author, and xtract skips to the next author.

+

The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " “), and one with the author’s affiliation data (Affiliation). Include only PubMed records indexed with the MeSH heading “Microcephaly”, and with any MeSH heading containing the words “Zika Virus” in the output table

+
efetch -db pubmed -id 27582188,27417495,27409810,27306170,18142192 -format xml | \
+xtract -pattern PubmedArticle -if DescriptorName -contains "Zika Virus" \
+-and DescriptorName -equals Microcephaly -element MedlineCitation/PMID ArticleTitle
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27582188,27417495,27409810,27306170,18142192) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the record has a element that contains the words “Zika Virus” (-if DescriptorName -contains “Zika Virus”), AND a element that equals “Microcephaly” (-and DescriptorName -equals Microcephaly). If a record does not have MeSH headings assigned that meet those criteria, no row is created for the author, and xtract skips to the next author. Note that, because of the use of -contains, both the MeSH heading “Zika Virus” and the MeSH heading “Zika Virus Infection” will satisfy the first condition in this command.

+

The command creates two columns for each row: one with the record’s PMID (specifically, the contents of the element that is a child of the element), one with the article’s title (-element MedlineCitation/PMID ArticleTitle). xtract and the -position argument Include only the First Author in the output table

+
efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block Author -position first -sep " " -element LastName,Initials
+

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the “\” character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

+

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (e.g. as a child of a element; -element MedlineCitation/PMID).

+

In the third line, xtract looks through each PubMed record for an element (-block Author). When it finds the first (-position first), it populates the second column in the row with the first author’s last name and initials, separated by a space (-sep " " -element LastName,Initials). Dealing with blanks Specify a placeholder to replace blank spaces in the output table

+
efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block Author -position first -sep " " -def "N/A" -element LastName,Initials Identifier
+

This series of commands is largely the same as the “Include only the First Author in the output table” example presented above. However, in the third line, we have added the -def argument to specify the placeholder value (“N/A”) for any blank cells in the output table (-def “N/A”). In-class exercise solutions

+

Note: The first two exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data. Exercise 1

+

Write an xtract command that creates a table with one row per PubMed record, but that only includes PubMed records if they have MeSH headings. Each row should have two columns: PMID and citation status.

+

Solution:

+
efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml | \
+xtract -pattern PubmedArticle -if MeshHeading -element MedlineCitation/PMID MedlineCitation@Status
+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record contains a element (-if MeshHeading). If a record does not have MeSH headings attached, no row is created for the record, and xtract skips to the next record.

+

For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the element that is a child of the element), one with the record’s citation status (-element MedlineCitation/PMID MedlineCitation@Status).

+

Exercise 2

+

Write an xtract command that creates a table with one row per PubMed record, but that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.). Each row should have two columns: PMID and journal title abbreviation.

+

Solution:

+
efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml | \
+xtract -pattern PubmedArticle -if ISOAbbreviation -starts-with JAMA -element MedlineCitation/PMID ISOAbbreviation
+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record has a journal title abbreviation that begins with “JAMA” (-if ISOAbbreviation -starts-with JAMA).

+

For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the element that is a child of the element), one with the article’s journal title abbreviation (-element MedlineCitation/PMID ISOAbbreviation). Exercise 3

+

Write a series of commands that generates a list of the different affiliation data used by author BH Smith between 2012 and 2017. The script should output the PMID for each article published by BH Smith in that time frame, along with the BH Smith’s affiliation data for each article.

+

Solution:

+
esearch -db pubmed -query "smith bh[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block Author -if LastName -equals Smith -and Initials -equals BH -element LastName,Initials Affiliation
+

This series of commands searches for publications by the author BH Smith that were published between 2012 and 2017, retrieves the full XML records for each of the search results, extracts the PMID and BH Smith’s affiliation data from each record, and displays the results in a table.

+
esearch -db pubmed -query "smith bh[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \
+

The first line of code uses esearch to search PubMed (-db pubmed) for articles where “smith bh” is the author (-query “smith bh[Author]”). The line also restricts the search results to articles that were published between 2011 and 2016 (-datetype PDAT -mindate 2012 -maxdate 2017).

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+

Beginning on the third line, the xtract command creates a table with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with three columns. The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (e.g. as a child of a element).

+
-block Author -if LastName -equals Smith -and Initials -equals BH -sep " " -element LastName,Initials Affiliation
+

The xtract command continues on the fourth line by checking each element in a PubMed record (-block Author). If a given author’s is Smith AND are BH (-if LastName -equals Smith -and Initials -equals BH), the xtract command populates the second column with the author’s last name and initials (separated by a space), and the third column with the author’s affiliation (-sep " " -element LastName,Initials Affiliation). Outputting the last name and initials into the second column is slightly redundant, as we know that they will always be “Smith BH”. However, it is helpful as a confirmation that our Conditional arguments are correct. Homework solutions

+

Question 1

+

Fetch the records for the following list of PMIDs:

+
28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139
+

Write an xtract command that outputs the PMID and Article Title, but only for records that have a structured abstract. Hint: in PubMed records, structured abstracts are broken up into multiple AbstractText elements, each with their own “NlmCategory” attribute.

+

Solution:

+
efetch -db pubmed -id 28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139 -format xml | \
+xtract -pattern PubmedArticle -if AbstractText@NlmCategory -element MedlineCitation/PMID ArticleTitle
+

The first line of this solution uses efetch to retrieve several records from PubMed in XML format.

+

The “|” character pipes the results of our efetch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record has one or more “AbstractText” elements that contain an “NlmCategory” attribute (-if AbstractText@NlmCategory). This will ensure that only PubMed records with structured abstracts are included.

+

For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the element that is a child of the element), one with the article title (-element MedlineCitation/PMID ArticleTitle).

+

Question 2

+

Modify your command from Question 1 to display the “RESULTS” section of each structured abstract, if there is one, in place of the Article Title. If there is no “RESULTS” section, display just the PMID, leaving the second column blank. Hint: Use the “NlmCategory” attribute to determine whether a particular AbstractText element contains “RESULTS”.

+

Solution:

+
efetch -db pubmed -id 28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139 -format xml | \
+xtract -pattern PubmedArticle -if AbstractText@NlmCategory -element MedlineCitation/PMID \
+-block AbstractText -if AbstractText@NlmCategory -equals RESULTS -element AbstractText
+

This solution begins the same as the solution for Question 2. However, rather than including the article title in the first -element argument, the xtract command continues on the third line (with the “\” character at the end of the second line allowing us to continue our string of commands on the next line, for easier-to-read formatting.

+
-block AbstractText -if AbstractText@NlmCategory -equals RESULTS -element AbstractText
+

In the third line, the command uses -block to look for an element (-block AbstractText), then looks within that element to see if it has an “NlmCategory” attribute with the value “RESULTS” (-if AbstractText@NlmCategory -equals RESULTS). If it does, the command then outputs the contents of the element in the second column. If the element does not have an “NlmCategory” with the value “RESULTS”, the command proceeds to check the next element in the record. The process repeats for each element in the record.

+

Question 3

+

When indexing a record for MEDLINE, indexers can assign MeSH headings (descriptors) to represent concepts found in an article, and MeSH subheadings (qualifiers) to describe a specific aspect of a concept. Indexers denote some of MeSH headings as “Major Topics” (i.e. one of the primary topics of the article). When assigning a “Major Topic”, the indexer can determine that heading itself is a major topic, or that a specific heading/subheading pair is a major topic. When a heading/subheading pair is assigned as a Major Topic, only the subheading will be labeled as Major in the PubMed XML.

+

Write an xtract command that outputs one PubMed record per row. Each row should have the record’s PMID and a pipe-delimited list of all of the MeSH Headings the indexers have determined are Major Topics. Note: the list should only include headings (descriptors), not subheadings (qualifiers). However, if a heading/subheading pair is assigned as major, the list should include that heading.

+

You can use the following efetch command to retrieve some sample records:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+

Solution:

+
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block MeshHeading -if DescriptorName@MajorTopicYN -equals Y -or QualifierName@MajorTopicYN -equals Y \
+-tab "|" -element DescriptorName
+

This solution uses the example efetch command to retrieve three PubMed records in XML, then outputs a table with one row per PubMed record. Each row begins with the record’s PMID, followed by a pipe-delimited list of all of the MeSH Headings that the indexers have determined are Major Topics.

+
xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle) with the record’s PMID (-element MedlineCitation/PMID) and additional data, which is specified on the subsequent lines.

+
-block MeshHeading -if DescriptorName@MajorTopicYN -equals Y -or QualifierName@MajorTopicYN -equals Y \
+

In the third line, we start to check each element to determine if it has been labeled Major. The command uses -block to look for the first element in the record (-block MeshHeading). The command then looks within that element to see if its child element has a “MajorTopicYN” attribute with a value of “Y” (-if DescriptorName@MajorTopicYN -equals Y), or if any of its child elements have a “MajorTopicYN” attribute with a value of “Y” (-or QualifierName@MajorTopicYN -equals Y). If either of these are true, the MeSH heading has been labeled as a Major Topic, and the command will continue on the next line (see below). If neither of these conditions are true, the command will proceed to the next element and repeat the process, looking for MeSH Headings which are Major Topics.

+
-tab "|" -element DescriptorName
+

The fourth line specifies that the DescriptorName will appear in the second column of our table (-element DescriptorName). Each indexed record will have at least one Major Topic assigned, and probably more than one. We use the -tab argument to specify a separator between the multiple MeSH descriptors (-tab “|”). It is important to place the -tab argument after the -block, as -block resets any -tab arguments that have been previously specified. We use -tab instead of -sep, as -block automatically creates a new column at the end of each block, so by specifying “|” in our -tab argument, we insure that our blocks are pipe-delimited.

+

Question 4

+

Write a series of commands to search for articles reporting on clinical trials relating to tularemia and output a table of citations. Each row should include the PMID for an article, as well as the name and affiliation information (if any) for the last author. If the last author does not have affiliation information, put “Not Available” in the last column instead.

+

Solution:

+
esearch -db pubmed -query "tularemia clinical trial" | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID \
+-block Author -position last -sep " " -def "Not Available" -element LastName,Initials Affiliation
+

This solution of commands searches PubMed for the string “tularemia clinical trial”, retrieves the full XML records and outputs the PMID as well as the last name, initials affiliation information (if any) of each article’s last author.

+
esearch -db pubmed -query "tularemia clinical trial" | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query “tularemia clinical trial”).

+

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
-pattern PubmedArticle -element MedlineCitation/PMID \
+

Beginning on the third line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle) with the record’s PMID (-element MedlineCitation/PMID) and additional data, which is specified on the subsequent lines.

+
-block Author -position last -sep " " -def "Not Available" -element LastName,Initials Affiliation
+

The fourth line uses the -block and -position arguments to identify the last element in each record (-block Author -position last). The last name and initials of the last author, separated by a space (-sep " “), are placed in the second column, with the last author’s affiliation information (if present) is placed in the third column (-element LastName,Initials Affiliation). If the last author has no affiliation information, the third column will contain the default value of “Not Available” instead of being left blank (-def”Not Available“)

+
+
+

4.4.2 Part Four

+

https://dataguide.nlm.nih.gov/edirect-for-pubmed-4.txt

+ +++ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
The Insider’s Guide to Accessing NLM Data: EDirect for PubMed Part Four: xtract Conditional Arguments Course Materials
NOTE: Solutions to all exercises are at the bottom of this document.
REMINDERS FROM PART ONE
esearch: Searches a database and returns PMIDs
efetch: Retrieves PubMed records in a variety of formats
Use “|” (Shift + , pronounced “pipe”) to “pipe” the results of one command into the next
REMINDERS FROM PART TWO
xtract: Pulls data from XML and arranges it in a table
-pattern: Defines rows for xtract
-element: Defines columns for xtract
Identify XML elements by name (e.g. ArticleTitle)
Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID)
Identify attributes with “@” (e.g. MedlineCitation@Status)
REMINDERS FROM PART THREE
-block: Selects and groups child elements of the same parent
-tab: Defines the separator between columns (default is tab, “”)
-sep: Defines the separator between values in the same column (default is tab, “”)
Use “>” to save the output to a file
Use “cat” to pull the contents of a file into the EDirect command
epost: Stores PMIDs to the History Server
TIPS FOR CYGWIN USERS:
Ctrl + C does not Copy (Cygwin default for Copy is Ctrl + Insert)
Ctrl + V does not Paste (Cygwin default for Paste is Shift + Insert)
TIPS FOR ALL USERS:
Ctrl + C “cancels” and gets you back to a prompt
Up and Down arrow keys allow you to cycle through your recent commands
clear: clears your screen
If-Then
If the condition is met… Then, create a new row for the pattern and populate the specified columns. (If not, skip the pattern and move on to the next one.)
-if
COMMAND STRING:
efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml
efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml |
+xtract -pattern Author -sep " " -element LastName,Initials Identifier
efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml |
+xtract -pattern Author -if Identifier -sep " " -element LastName,Initials Identifier
EXERCISE 1:
Write an xtract command that only includes PubMed records if they have MeSH headings * One row per PubMed record * Two columns: PMID, Citation Status Hint: Use this efetch to test:
efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml |
+
-if/-equals
COMMAND STRING:
efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml |
+xtract -pattern PubmedArticle -if ISOAbbreviation -equals JAMA -element Volume Issue
-if/-equals: Attributes
COMMAND STRING:
efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml |
+xtract -pattern PubmedArticle -if MedlineCitation@Status -equals MEDLINE
+-element MedlineCitation/PMID
Alternatives to -equals
-contains: Element or attribute contains this string -starts-with: Element or attribute starts with this string -ends-with: Element or attribute ends with this string -is-not: Element or attribute does not match this string
-if/-contains
COMMAND STRING:
efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml |
+xtract -pattern Author -if Affiliation -contains Japan
+-sep " " -element LastName,Initials Affiliation
EXERCISE 2: Write an xtract command that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.) * One row per PubMed record * Two Columns: PMID, ISOAbbreviation * ISOAbbreviation should start with “JAMA” Hint: Use this efetch to test:
efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml |
+
-if in a -block
COMMAND STRING:
efetch -db pubmed -id 16940437,16049336,11972038 -format xml |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID
+-block ArticleId -if ArticleId@IdType -equals doi -element ArticleId
Combining multiple conditions
-or: at least one condition must be true
-and: all conditions must be true
-or
COMMAND STRING:
efetch -db pubmed -id 16940437,16049336,11972038 -format xml |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID
+-block ArticleId -if ArticleId@IdType -equals doi
+-or ArticleId@IdType -equals pmc -element ArticleId
-and
COMMAND STRING:
efetch -db pubmed -id 27798514,24372221,24332497,24307782 -format xml |
+xtract -pattern Author -if LastName -equals Kamal -and Affiliation
+-sep " " -element LastName,Initials Affiliation
efetch -db pubmed -id 27582188,27417495,27409810,27306170,18142192 -format xml |
+xtract -pattern PubmedArticle -if DescriptorName -contains “Zika Virus”
+-and DescriptorName -equals Microcephaly -element MedlineCitation/PMID ArticleTitle
EXERCISE 3 We want to do a search for author BH Smith, and see the different affiliations that are listed for that author * Limit to publications from 2012 through 2017
We only want to see affiliation data for BH Smith, no other authors.
We want our output to be a table of citations with specific data: * PMID * Author Last Name/Initials (should always be BH Smith) * Affiliation Data
Write the whole script (not just the xtract command).
-position
Include a -block based on its position:
xtract -pattern PubmedArticle -element MedlineCitation/PMID
+-block Author -position first -sep " " -element LastName,Initials
Use -position with an integer, “first” or “last”:
-position 3
-position first
-position last
COMMAND STRING:
efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID
+-block Author -sep " " -element LastName,Initials
efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID
+-block Author -position first -sep " " -element LastName,Initials
efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID
+-block Author -position last -sep " " -element LastName,Initials
Dealing with blanks
Use -def to define a placeholder to replace blank cells
Placement for -def is the same as for -tab/-sep. * Subsequent -def arguments overwrite earlier ones. * -block arguments clear previous -def arguments.
COMMAND STRING:
efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID
+-block Author -position first -sep " " -element LastName,Initials Identifier
efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID
+-block Author -position first -sep " " -def “N/A” -element LastName,Initials Identifier
HOMEWORK FOR PART FOUR
(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode4.html)
Question 1:
Fetch the records for the following list of PMIDs:
28197844 28176235 28161874 28183232 28164731 27937077 28118756 27845598 27049596 27710139
Write an xtract command that outputs the PMID and Article Title, but only for records that have a structured abstract. Hint: in PubMed records, structured abstracts are broken up into multiple AbstractText elements, each with their own “NlmCategory” attribute.
Question 2:
Modify your command from Question 1 to display the “RESULTS” section of each structured abstract, if there is one, in place of the Article Title. If there is no “RESULTS” section, display just the PMID, leaving the second column blank. Hint: Use the “NlmCategory” attribute to determine whether a particular AbstractText element contains “RESULTS”.
Question 3:
When indexing a record for MEDLINE, indexers can assign MeSH headings (descriptors) to represent concepts found in an article, and MeSH subheadings (qualifiers) to describe a specific aspect of a concept. Indexers denote some of the assigned MeSH headings as “Major Topics” (i.e. one of the primary topics of the article). When assigning a “Major Topic”, the indexer can determine that the heading itself is a major topic, or that a specific heading/subheading pair is a major topic. When a heading/subheading pair is assigned as a Major Topic, only the subheading will be labeled as Major in the PubMed XML.
Write an xtract command that outputs one PubMed record per row. Each row should have the record’s PMID and a pipe-delimited list of all of the MeSH Headings the indexers have determined are Major Topics. Note: the list should only include headings (descriptors), not subheadings (qualifiers). However, if a heading/subheading pair is assigned as major, the list should include that heading.
You can use the following efetch command to retrieve some sample records:
efetch -db pubmed -id 24102982,21171099,17150207 -format xml |
+
Question 4:
Write a series of commands to search for articles reporting on clinical trials relating to tularemia and output a table of citations. Each row should include the PMID for an article, as well as the name and affiliation information (if any) for the last author. If the last author does not have affiliation information, put “Not Available” in the last column instead.
-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- EXERCISE SOLUTIONS: -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- EXERCISE 1: Write an xtract command that only includes PubMed records if they have MeSH headings * One row per PubMed record * Two columns: PMID, Citation Status Hint: Use this efetch to test:
efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml
Solution:
efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml |
+xtract -pattern PubmedArticle -if MeshHeading
+-element MedlineCitation/PMID MedlineCitation@Status
-=-=-=-=-=-=-=-=-=-=-=-=- EXERCISE 2: Write an xtract command that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.) * One row per PubMed record * Two Columns: PMID, ISOAbbreviation * ISOAbbreviation should start with “JAMA”
efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml
Solution:
efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml |
+xtract -pattern PubmedArticle -if ISOAbbreviation -starts-with JAMA
+-element MedlineCitation/PMID ISOAbbreviation
-=-=-=-=-=-=-=-=-=-=-=-=- EXERCISE 3 We want to do a search for author BH Smith, and see the different affiliations that are listed for that author * Limit to publications from 2012 through 2017
We only want to see affiliation data for BH Smith, no other authors.
We want our output to be a table of citations with specific data: * PMID * Author Last Name/Initials (should always be BH Smith) * Affiliation Data
Write the whole script (not just the xtract command).
Solution:
esearch -db pubmed -query “smith bh[Author]”
+-datetype PDAT -mindate 2012 -maxdate 2017 |
+efetch -format xml |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID
+-block Author -if LastName -equals Smith -and Initials -equals BH -sep " " -element LastName,Initials Affiliation
## Part Five “EDirect for PubMed: Part 5: Developing and Building Scripts” Sample Code
### Part Five
https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode5.html
Case study
Retrieve a list of articles published in between March 1, 2017 and February 28, 2018 about breast cancer that include clinical trial information from ClinicalTrials.gov. Include the PMID, journal title abbreviation, first author’s last name and initials, and ClinicalTrials.gov NCT number(s) for each record. Save the entire output to a text file.
Solution
esearch -db pubmed -query “breast cancer AND clinicaltrials.gov[si]”
+-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 |
+efetch -format xml |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation
+-block Author -position first -sep " " -element LastName,Initials
+-block DataBank -if DataBankName -equals ClinicalTrials.gov
+-sep “|” -element AccessionNumber > clinicaltrials.txt
Discussion
esearch -db pubmed -query “breast cancer AND clinicaltrials.gov[si]”
+
The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query “breast cancer AND clinicaltrials.gov[si]”). The “clinicaltrials.gov[si]” portion of the query ensures that only records with ClinicalTrials.gov NCT numbers are included in our results. The “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.
-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 |
+
The second line restricts the search results to articles that were published between March 1, 2017 and February 28, 2018 (-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28). The “|” character pipes the results of our esearch into our next command.
efetch -format xml |
+
The third line takes the esearch results from our first two lines and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.
xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation
+
Beginning on the fourth line, the xtract command creates a table with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with four columns. The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the element that is the child of the element, and not another element elsewhere in the PubMed record (e.g. as a child of a element), while the second column will contain the article’s journal title abbreviation (-element MedlineCitation/PMID ISOAbbreviation).
-block Author -position 1 -sep " " -element LastName,Initials
+
In the fifth line, xtract looks through each PubMed record for an element (-block Author). When it finds the first (-position 1), it populates the third column in the row with the first author’s last name and initials, separated by a space (-sep " " -element LastName,Initials).
-block DataBank -if DataBankName -equals ClinicalTrials.gov
+
In the sixth line, xtract looks through each PubMed record for elements which have a child element that equals “ClinicalTrials.gov” (-block DataBank -if DataBankName -equals ClinicalTrials.gov). This will ensure that only ClinicalTrials.gov data is included, while data from non-ClinicalTrials.gov elements is excluded.
-sep “|” -element AccessionNumber > clinicaltrials.txt
In the seventh line, xtract specifies that the fourth column should be populated with the (i.e. NCT number) from the included elements (-element AccessionNumber). If a record has multiple NCT numbers attached, they will be separated by pipes (-sep “|”).
Finally, the results of the script are saved to a file (> clinicaltrials.txt).
### Part Five
https://dataguide.nlm.nih.gov/edirect-for-pubmed-5.txt
The Insider’s Guide to Accessing NLM Data: EDirect for PubMed Part Five: Developing and Building Scripts Course Materials
NOTE: Solutions to all exercises are at the bottom of this document.
REMINDERS FROM PART ONE
esearch: Searches a database and returns PMIDs
efetch: Retrieves PubMed records in a variety of formats
Use “|” (Shift + , pronounced “pipe”) to “pipe” the results of one command into the next
REMINDERS FROM PART TWO
xtract: Pulls data from XML and arranges it in a table
-pattern: Defines rows for xtract
-element: Defines columns for xtract
Identify XML elements by name (e.g. ArticleTitle)
Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID)
Identify attributes with “@” (e.g. MedlineCitation@Status)
REMINDERS FROM PART THREE
-block: Selects and groups child elements of the same parent
-tab: Defines the separator between columns (default is tab, “”)
-sep: Defines the separator between values in the same column (default is tab, “”)
Use “>” to save the output to a file
Use “cat” to pull the contents of a file into the EDirect command
epost: Stores PMIDs to the History Server
REMINDERS FROM PART FOUR
-if: Defines an element/attribute that must be present in order to include a pattern/block. (e.g. “If is present in the pattern/block, include pattern/block in the output.”)
-if/-equals: Defines a specific element/attribute that must be equal to a specific value in order to include a pattern/block, (e.g. “If an equals [value] in the pattern/block, include pattern/block in the output.”)
Alternatives to -equals: let you define more specific conditions -contains: Element or attribute must contain this string -starts-with: Element or attribute must start with this string -ends-with: Element or attribute must end with this string -is-not: Element or attribute must not match this string
Alternatives to -if: let you combine multiple conditions -or: at least one condition must be true -and: all conditions must be true
-position: Includes a block based on its position in a series of blocks. Use -position with an integer, “first” or “last”:
Tips for Developing a Script
1. Identify your goal. * Identify your input * Identify your output * Identify your format 2. Choose your tool. 3. Decide how much to automate. 4. Build one step at a time.
E-utilities Usage Guidelines and Requirements from NCBI https://www.ncbi.nlm.nih.gov/books/NBK25497/#chapter2.Usage_Guidelines_and_Requiremen
NLM Data Distribution: Download MEDLINE/PubMed Data https://www.nlm.nih.gov/databases/download/pubmed_medline.html
Using EDirect to create a local copy of PubMed https://dataguide.nlm.nih.gov/edirect/archive.html
NCBI Documentation: EDirect: Local Data Cache https://www.ncbi.nlm.nih.gov/books/NBK179288/#chapter6.Local_Data_Cache
+

Case 1: Simple table of data elements

+

We want a list of articles about breast cancer that were published in 2016 and the first half of 2017 and are linked to ClinicalTrials.gov entries.

+

For each article we want: * PMID * NCT Number(s) * First Author * Journal

+
+

Case Study

+

COMMAND STRING:

+
esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]"
+
+esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \
+-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28
+
+esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \
+-datetype PDAT -mindate 2018/01/01 -maxdate 2018/02/28
+
+efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml
+
+efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation
+
+efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \
+-block Author -position first -sep " " -element LastName,Initials
+
+efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \
+-block Author -position first -sep " " -element LastName,Initials \
+-block DataBank -if DataBankName -equals ClinicalTrials.gov \
+-sep "|" -element AccessionNumber
+

CASE STUDY Solution:

+
esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \
+-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \
+-block Author -position first -sep " " -element LastName,Initials \
+-block DataBank -if DataBankName -equals ClinicalTrials.gov \
+-sep "|" -element AccessionNumber > clinicaltrials.txt
+
+

EDirect Cookbook on GitHub https://ncbi-hackathons.github.io/EDirectCookbook/

+
+
+
+
+

5 Materials and Methods Used For This Analyses

+
+

5.1 The Insider’s Guide to Accessing NLM Data

+
+

5.1.1 “Welcome to E-utilities for PubMed” Class Materials

+

https://dataguide.nlm.nih.gov/classes/intro/materials.html

+
+

Webinar Recording https://dataguide.nlm.nih.gov/classes/intro/recording.html

+
+
+

“Welcome to E-utilities for PubMed” Sample Code for Class Exercises https://dataguide.nlm.nih.gov/classes/intro/samplecode.html

+
+
+

Entrez Programming Utilities Help https://www.ncbi.nlm.nih.gov/books/NBK25501/

+
+
+

Entrez Direct: E-utilities on the UNIX Command Line https://www.ncbi.nlm.nih.gov/books/NBK179288/

+
+
+ +
+

5.1.3 The 9 E-utilities and Associated Parameters

+

https://dataguide.nlm.nih.gov/eutilities/utilities.html

+ +
+
+
+
+
+
    +
  1. That is why I am preparing this page.

  2. +
+
+ +
---
title: "Evaluation of Pathology Literature using E-utilities & EDirect for PubMed"
author: "Serdar Balcı, MD, Pathologist"
date: "`r format(Sys.Date())`"
output:
  html_notebook:
    code_folding: hide
    df_print: kable
    highlight: kate
    number_sections: yes
    theme: cerulean
    toc: yes
    toc_float: yes
  html_document:
    df_print: paged
    toc: yes
subtitle: Codes and Pages are Copied & Modified from "E-utilities & EDirect for PubMed"
  lectures
---

NLMTrainers@nih.gov


```{r necessary packages, include=FALSE}
library(rstudioapi)
library(tidyverse)
```


```{r eval=FALSE, include=FALSE}
# https://cran.r-project.org/web/packages/rstudioapi/vignettes/terminal.html
# myTerm <- rstudioapi::terminalCreate()
# EdirectCall <- "esearch -db pubmed -query 'seasonal affective disorder' > myquery.txt \n"
# rstudioapi::terminalSend(myTerm, EdirectCall)
# rstudioapi::terminalKill(myTerm)
# readLines("myquery.txt")
```



# The Insider's Guide to Accessing NLM Data

[The Insider's Guide to Accessing NLM Data](https://dataguide.nlm.nih.gov/)


# EDirect installation

[Installing EDirect](https://dataguide.nlm.nih.gov/edirect/install.html)


To install EDirect, open your Unix terminal and execute the following commands. (The easiest way to do this is to copy the whole block and paste it directly into your terminal window.)

    cd ~
    /bin/bash
    perl -MNet::FTP -e \
        '$ftp = new Net::FTP("ftp.ncbi.nlm.nih.gov", Passive => 1);
        $ftp->login; $ftp->binary;
        $ftp->get("/entrez/entrezdirect/edirect.tar.gz");'
    gunzip -c edirect.tar.gz | tar xf -
    rm edirect.tar.gz
    builtin exit
    export PATH=$PATH:$HOME/edirect >& /dev/null || setenv PATH "${PATH}:$HOME/edirect"
    ./edirect/setup.sh


This installs the EDirect software and gets it ready to use. Depending on your system’s configuration, you may see the following message:

    In order to complete the configuration process, please execute the following:

followed by a command that looks something like:

    echo "export PATH=\$PATH:\$HOME/edirect" >> $HOME/.bash_profile

If you see this prompt, copy the command provided and paste it into your terminal.

Once the installation is complete, you will see the following message in your terminal window:

    Entrez Direct has been successfully downloaded and installed.

You can confirm EDirect is installed correctly by using the testing script below.

## Test your EDirect installation

To confirm that EDirect is installed and working properly, you can run your first EDirect script! Just type (or copy and paste) the following code into your terminal window, and press Enter.

    echo "***********************" > installconfirm
    echo "esearch version:" >> installconfirm
    esearch -version >> installconfirm
    echo "xtract version:" >> installconfirm
    xtract -version >> installconfirm
    echo "EDirect install status:" >> installconfirm
    esearch -db pubmed -query "Babalobi OO[au] AND 2008[pdat]" | \
    efetch -format xml | \
    xtract -pattern Author -if Affiliation -contains Medicine \
    -element Initials >> installconfirm
    echo "***********************" >> installconfirm
    cat installconfirm
    rm installconfirm

The result should be a message similar to the following:

    ***********************
    esearch version:
    8.00
    xtract version:
    8.00
    EDirect install status:
    OK
    ***********************

If you see this output, you have installed EDirect successfully! 

---





# "Welcome to E-utilities for PubMed" Sample Code for Class Exercises

Below you will find sample code for the examples presented in the “Welcome to E-utilities for PubMed” Insider’s Guide course. These examples are written for use with EDirect in a Unix environment. If you need help installing and setting up EDirect, please see our “Installing EDirect” page.

There are many different ways to answer the questions discussed in class. The sample code below provides one option, but by no means the only option, and not even necessarily the best option. 

**Feel free to modify, adapt, edit, re-use or completely discard any of the suggestions below when trying to find the solution that works best for you.**^[That is why I am preparing this page.]

* Find the current “most active” authors for a given topic
* Generate list of funding agencies who are most active in funding a particular topic
* Create a customized version of the Discovery Bar “Results By Year” histogram, comparing two searches
* Find the most commonly-discussed topics of articles written by authors from a specific institution
    * Version 1: Basic
    * Version 2: Intermediate
    * Version 3: Advanced
    * Version 4: ???


### Find the current “most active” authors for a given topic

**Goal:**

Find out who the “hot” authors are on a given topic. We are looking for authors that have written the most papers recently (i.e. in the last two years), on a specific subject. (For this example, we are looking at papers about diabetes and pregnancy.)

**Solution:**

    esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \
    efetch -format xml | \
    xtract -pattern Author -sep " " -element LastName,Initials | \
    sort-uniq-count-rank | \
    head -n 10



```{r}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query '(diabetes AND pregnancy) AND (\"2017/01/01\"[PDAT] : \"2017/12/31\"[PDAT])' | \n")
rstudioapi::terminalSend(myTerm, "efetch -format xml | \n")
rstudioapi::terminalSend(myTerm, "xtract -pattern Grant -element Agency | \n")
rstudioapi::terminalSend(myTerm, "sort-uniq-count-rank | \n")
rstudioapi::terminalSend(myTerm, "head -n 10 > myquery.txt \n")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}

```

```{r}
readLines("myquery.txt")
```


```{r}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query '(diabetes AND pregnancy) AND (\"2017/01/01\"[PDAT] : \"2017/12/31\"[PDAT])' | efetch -format xml | xtract -pattern Grant -element Agency | sort-uniq-count-rank | head -n 10 > myquery.txt \n")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}
```


This series of commands searches PubMed for the string `“(diabetes AND pregnancy) AND (”2015/01/01“[PDAT] : ”2017/12/31“[PDAT])”`, retrieves the full XML records for each of the search results, extracts the last name and initials of every author on every record, sorts the authors by frequency of occurrence in the results set, and presents the top ten most frequently-occurring authors, along with the number of times that author appeared.
Discussion:

    esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \

The first line of this command uses esearch to search PubMed `(-db pubmed)` for our search query `(-query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])")`. Our search query is constructed almost exactly like we would construct it in PubMed: we have a topic string `(“diabetes AND pregnancy”)` enclosed in parentheses and ANDed together with a date range. However, the double quotation marks (“) in our search string pose a problem. We need to ”escape“ the double quotation marks (”) in our search query by putting a `“\”` before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the -query argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched.

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format xml | \

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format `(-format xml)`, and pipes the XML output to the next line.

    xtract -pattern Author -sep " " -element LastName,Initials | \

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The `-pattern` command indicates that we should start a new row for every author `(-pattern Author)`. Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials) and separates the two elements with a single space `(-sep " ")`. This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line.

    sort-uniq-count-rank | \

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set.

    head -n 10

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the authors, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the `“|”` and `“\”` characters from the previous line. Otherwise, the system will wait for you to finish entering your command.)
Generate list of funding agencies who are most active in funding a particular topic
Goal:

Find out which funding agencies have been funding research on a given topic. We are looking for agencies that are associated with papers published recently (i.e. in the last two years), on a specific subject. (For this example, we are looking at papers about diabetes and pregnancy.)


**Solution:**

    esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \
    efetch -format xml | \
    xtract -pattern Grant -element Agency | \
    sort-uniq-count-rank | \
    head -n 10

This series of commands searches PubMed for the string “(diabetes AND pregnancy) AND (”2015/01/01“[PDAT] : ”2017/12/31“[PDAT])”, retrieves the full XML records for each of the search results, extracts the funding agency for every grant listed on every record, sorts the funding agencies by frequency of occurrence in the results set, and presents the top ten most frequently-occurring agencies, along with the number of times that agency appeared.
Discussion:

    esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])"). Our search query is constructed almost exactly like we would construct it in PubMed: we have a topic string (“diabetes AND pregnancy”) enclosed in parentheses and ANDed together with a date range. However, the double quotation marks (“) in our search string pose a problem. We need to ”escape“ the double quotation marks (”) in our search query by putting a `“\”` before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the -query argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched.

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format xml | \

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

    xtract -pattern Grant -element Agency | \

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every grant (-pattern Grant). Even if there are multiple grants on a single citation, each grant will be on a new line, rather than putting all grants for the same citation on the same line. The command then extracts each grant’s funding agency (-element Agency). This will output a list of agencies, one agency per line, and will pipe the list to the next line.

    sort-uniq-count-rank | \

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of agencies received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique agency, removes the duplicate agencies, and then sorts the list of unique agencies by how frequently they occur, with the most frequent agencies at the top. The function also returns the numerical count, making it easier to quantify how frequently each agency occurs in the data set.

    head -n 10

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring agencies first, this will show us only the ten most frequently occurring agencies in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the agencies, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the `“|”` and `“\”` characters from the previous line. Otherwise, the system will wait for you to finish entering your command.)
Create a customized version of the Discovery Bar “Results By Year” histogram, comparing two searches
Goal:

In order to recreate the “Results By Year” histogram available in the PubMed Discovery Bar for a given search, we need to count how many occurrences of each Publication Year there are in the results set, then sort those counts by year. To compare the “Results By Year” for two searches, we need to do this twice, and combine the two outputs. For this example, the searches we are doing relate to abuse of specific opioids (“fentanyl abuse” vs. “oxycodone abuse”), and we will restrict our results to articles published between 1988 and 2017.


**Solution:**

    esearch -db pubmed -query "fentanyl abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
    efetch -format xml | \
    xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
    cut -c -4 | \
    sort-uniq-count-rank | \
    sort -n -t $'\t' -k 2 > fentanyl_abuse.txt

    esearch -db pubmed -query "oxycodone abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
    efetch -format xml | \
    xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
    cut -c -4 | \
    sort-uniq-count-rank | \
    sort -n -t $'\t' -k 2 > oxycodone_abuse.txt

    join -j 2 -o 0,1.1,2.1 -a1 -a2 -e0 -t $'\t' <(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt) > abuse_compare.txt

This series of commands searches PubMed for the string “fentanyl abuse” (restricted to publication dates between 1988 and 2017), retrieves the full XML records for each of the search results, extracts the year of publication from each record, counts how frequently each publication year appears in the results, then re-sorts by chronologically by year. The results are then saved to a file. The process is repeated for the string “oxycodone abuse”, and the two files are merged together.

(This example uses some Unix tools like sort, cut, and join that were not discussed in detail in “Welcome to E-utilities for PubMed”. We will address some of them in greater detail in our follow-up class, “EDirect for PubMed”, but you can find a brief description of some of these tools in the appendices of NCBI’s EDirect documentation, under the heading “UNIX Utilities.”)
Discussion:

    esearch -db pubmed -query "fentanyl abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "fentanyl abuse"). Our search query is constructed exactly like we would construct it in PubMed: no tags, no punctuation, no Boolean operators. We simply put in our terms and they are automatically ANDed together. We use a few more arguments to restict our results based on publication date (-datetype PDAT -mindate 1988 -maxdate 2017).

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format xml | \

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

    xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for each PubMed record (-pattern PubmedArticle). We then want to look in the PubDate element for each record, and extract either the Year element or the MedlineDate element (each citation should only have one or the other; -block PubDate -element Year MedlineDate). Each line in the output will have either a publication year (from the Year element), or a publication year followed by a month or other, more specific date information (from the MedlineDate element). The output will then be piped to the next line.

    cut -c -4 | \

The fourth line cuts off each line after the fourth character, leaving only the four digits of the year on each row (cut -c -4). The list of years is then piped to the next line.

    sort-uniq-count-rank | \

The fifth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of years received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique year, removes the duplicate years, and then sorts the list of unique years by how frequently they occur, with the most frequently occurring years at the top. The function also returns the numerical count for each year.

    sort -n -t $'\t' -k 2 > fentanyl_abuse.txt

The sixth line then re-sorts the results numerically by the second column of data (sort -n -t $'\t' -k 2), which is the list of unique years (the first column of data is the frequency counts generated on the previous line). The list of years and frequency counts is now sorted chronologically, and the result is then sent to a file (> fentanyl_abuse.txt).

    esearch -db pubmed -query "oxycodone abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
    efetch -format xml | \
    xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
    cut -c -4 | \
    sort-uniq-count-rank | \
    sort -n -t $'\t' -k 2 > oxycodone_abuse.txt

The first six lines are then repeated, substituting out “fentanyl” for “oxycodone” in both the search string and the output file name.

    join -j 2 -o 0,1.1,2.1 -a1 -a2 -e0 -t $'\t' <(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt) > abuse_compare.txt

The final line uses a more advanced Unix command, join, that will allow us to merge together the two output files according to the values of a “key” column (in our case, the publication year). Both of our output files have the publication year in the second column, so we will join the two files using the second column of each file (join -j 2). We specify that the “key” column should be output first, followed by the first column of each file (-o 0,1.1,2.1). We want to make sure to include all of the publication years that were listed in either results set, even if they don’t appear in the other (with SQL or other database querying techniques, this is sometimes referred to as a “full outer join”; -a1 -a2). If one of the files has no results for a given publication year, we will output a 0 instead of a blank, and we will separate the columns in our output by tabs (-e0 -t $'\t').

The last part of the final line tells the join command which files to merge (<(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt)) and where to save the output (> abuse_compare.txt). If you want to instead view the results in your terminal window, you can omit the “>” and everything that follows it on the last line.
Find the most commonly-discussed topics of articles written by authors from a specific institution
Goal:

Find the most common topics for articles written by any author from a specific institution. For the purposes of this exercise, we will find the “most common topics” by determining which MeSH headings are most frequently attached to the records from our institution. This exercise assumes that the institution has many authors (or many research components with different names), and that searching for all of the authors (or all papers with any of the institution’s names listed in the affiliation data) involves creating a long and complicated search string.
Solutions:

As mentioned before, most use cases have multiple solutions. There is almost always a way to accomplish 100% of your goal in a single script. However, there are usually also ways of accomplishing 90%, 75% or 50% of your goal in a single script, and doing the remaining 10%, 25% or 50% manually. Each individual user should decide whether the additional time and effort it will take to get from 90% to 100% is more or less efficient than simply doing the remaining 10% manually.

With that in mind, we have presented three different solutions below. Each solution is closer and closer to “perfect.” However, each solution adds new complexity and new commands which are more powerful, but also increasingly complicated. We encourage you to read through all three examples and see if one of them meets your needs, or if one of them could be adapted to meet your needs.
Version 1: Basic

    esearch -db pubmed -query "$(cat searchstring.txt)" | \
    efetch -format xml | \
    xtract -pattern DescriptorName -element DescriptorName | \
    sort-uniq-count-rank | \
    head -n 10

This series of commands searches PubMed for a string defined in the text file “searchstring.txt”, retrieves the full XML records for each of the search results, extracts each of the MeSH descriptors associated with every record in the results set, sorts the MeSH headings by frequency of occurrence in the results set, and presents the top ten most frequently-occurring MeSH headings, along with the number of times that heading appears.
Discussion:

    esearch -db pubmed -query "$(cat searchstring.txt)" | \

The first line uses esearch to search PubMed (-db pubmed). The line uses the Unix command cat to read the entire contents of a file (searchstring.txt) and use it as the search query (-query "$(cat searchstring.txt)"). This allows us to use a long and complex search strategy (involving many author names, many institutional names, or both), and to keep that search string in a separate file. Over time, we can update the search strategy without having to edit our actual script. Additionally, it makes the script more readable.

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format xml | \

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

    xtract -pattern DescriptorName -element DescriptorName | \

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every MeSH heading in the results set (-pattern DescriptorName). Even if there are multiple MeSH headings on a single citation (which there likely will be), each MeSH heading will be on a new line, rather than putting all MeSH headings for the same citation on the same line. The command then extracts the name of each MeSH heading (-element DescriptorName). This will output a list of MeSH headings, one per line, and will pipe the list to the next line.

    sort-uniq-count-rank | \

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of MeSH headings received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique MeSH heading, removes the duplicate headings, and then sorts the list of unique headings by how frequently they occur, with the most frequent headings at the top. The function also returns the numerical count for each heading.

    head -n 10

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring MeSH headings first, this will show us only the ten most frequently occurring headings in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the headings, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the `“|”` and `“\”` characters from the previous line. Otherwise, the system will wait for you to finish entering your command.)
Version 2: Intermediate

    esearch -db pubmed -query "$(cat searchstring.txt)" | \
    efetch -format xml | \
    xtract -pattern DescriptorName -element DescriptorName | \
    grep -vxf checktags.txt | \
    sort-uniq-count-rank | \
    head -n 10

As you may have noticed in Version 1 (depending on your search terms), “Humans” was probably among the most common MeSH headings in your output. Virtually every biomedical article will describe subjects of research (human or animal; mice or rats, etc.). Clinical articles will describe treatment, diagnosis, etc. of diseases in patients. These articles will almost always mention the number of patients, their sex and age. Experimental articles will almost always mention the species and sex of the animal subjects.

These concepts, which are mentioned in almost every article, are designated as “check tags”. Check tags are routinely added to articles even if they are just mentioned in the article. If you like, you could just ignore these MeSH headings in your results. However, Version 2 of this code includes some lines which will automatically remove any headings that are check tags from your output.
Discussion:

    esearch -db pubmed -query "$(cat searchstring.txt)" | \
    efetch -format xml | \
    xtract -pattern DescriptorName -element DescriptorName | \

The first three lines are the same as Version 1, ending with the xtract command which outputs a list of MeSH headings, one per line, and will pipe the list to the next line.

    grep -vxf checktags.txt | \

The fourth line uses a very powerful Unix command, grep, which specializes in matching patterns in text. This line compares each line of text being piped in from our xtract command against every line in a specified file, and removes any lines from our xtract which match any of the lines in the file. The file (“checktags.txt”) contains a list of all of the MeSH headings which are check tags, with one heading on each line. You can download the checktags.txt file and use it as is, or you can modify it to filter out a different set of MeSH headings. The filtered list of MeSH headings is now piped to the next line.

    sort-uniq-count-rank | \
    head -n 10

The remaining lines of Version 2 are the same as Version 1.
Version 3: Advanced

    esearch -db pubmed -query "$(cat searchstring.txt)" | \
    efetch -format xml | \
    xtract -pattern DescriptorName -sep "" -element DescriptorName@MajorTopicYN,DescriptorName | \
    grep -vxf nchecktags.txt | \
    cut -c 2- | \
    sort-uniq-count-rank | \
    head -n 10

Version 2 filtered out the check tags from our result. However, while check tags are often added even if they are just mentioned in an article, those MeSH headings can sometimes be more central topics to the article. For example, “pregnancy” is a check tag, which is used to refer to research involving pregnant subjects. However, “pregnancy” can also be the main subject of an article. When it is, it will be denoted as a Major Topic. If we want to be even more precise than Version 2, we could make sure that we only filter out check tags when they are not the Major Topic of an article.
Discussion:

    esearch -db pubmed -query "$(cat searchstring.txt)" | \
    efetch -format xml | \
    xtract -pattern DescriptorName -sep "" -element DescriptorName@MajorTopicYN,DescriptorName | \  

Again, most of Version 3 is the same as Version 2. The first difference is in the third line. In addition to extracting the DescriptorName, we are also going to be extracting the attribute “MajorTopicYN” for each DescriptorName element (-element DescriptorName@MajorTopicYN,DescriptorName). The MajorTopicYN indicator (which is always either a “Y” if the MeSH heading is a Major Topic, or “N” if it is not) will be appended to the beginning of the descriptor name, because we have eliminated the separator between elements (-sep "").

    grep -vxf nchecktags.txt | \

Since the output from our xtract now consists of MeSH headings with either “Y” or “N” in front of them, we also need to edit the file that contains the check tags we are filtering out (grep -vxf nchecktags.txt). The new file (nchecktags.txt) is almost identical to the old file, with the exception that each heading in the file now starts with “N” (e.g. “Humans” becomes “NHumans”). If any of the headings in the output from our xtract are Major Topics, they will have a “Y” in front of them, and will not be filtered out by our N-prefixed check tag file. As before, the remaining, non-check tag MeSH headings are piped to the next line.

    cut -c 2- | \

Finally, we need to remove our extraneous “Y” and “N” characters from the front of the remaining MeSH headings (cut -c 2-).

    sort-uniq-count-rank | \
    head -n 10

The remaining lines of Version 3 are the same as Version 2.
Version 4: ???

Version 3 solved many of the problems, but is still not perfect. It does not handle MeSH subheadings, for example, and adding “N” to the front of each of the Check Tags in our filter file is inelegant. There are still more ways to improve this script, but the 90% of the task that this accomplishes will hopefully meet your needs. If it doesn’t, feel free to keep improving it!



# EDirect for PubMed" Class Materials

[EDirect for PubMed" Class Materials](https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/materials.html)



## Part One "EDirect for PubMed: Part 1: Getting PubMed Data" Sample Code

### Part One


https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode1.html


#### esearch

**Conduct a simple search of PubMed for articles on seasonal affective disorder**

    esearch -db pubmed -query "seasonal affective disorder"


```{r part1-1.txt}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query \"seasonal affective disorder\" > part1-1.txt \n")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}


readLines("part1-1.txt")

```



This line of code uses the esearch command to search PubMed (`-db pubmed`) for our search query `(-query "seasonal affective disorder")`.

If you want to see the query translation for your search (like you would see in the Search Details box with the web version of PubMed), you can add an additional argument to your command:

    esearch -db pubmed -query "seasonal affective disorder" -log

By adding the -log argument to esearch, the command will also output the E-utilities URL and query translation for your search.


```{r part1-2}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query 'seasonal affective disorder' -log &> part1-2.txt \n ")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}

rstudioapi::terminalKill(myTerm)
readLines("part1-2.txt")

# Problem in saving with >

```



**Conduct a simple search of PubMed for articles on malaria in the journal JAMA**

    esearch -db pubmed -query "malaria AND jama[journal]"

This line of code uses the esearch command to search PubMed `(-db pubmed)` for our search query `(-query "malaria AND jama[journal]")`. Note that the search query can include Boolean operators (AND) and search field tags ([journal]) to help focus our search, just as we can in the web version of PubMed.

```{r part1-3}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query \"malaria AND jama[journal]\" &> part1-3.txt \n")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}
readLines("part1-3.txt")
```




**Restrict search results by publication date**

    esearch -db pubmed -query "malaria AND jama[journal]" \
    -datetype PDAT -mindate 2015 -maxdate 2017

The first line of code is the same as our previous example, though the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting.

The second line limits the search results by publication date `-datetype PDAT`, including only articles published between 2015 and 2017 `-mindate 2015 -maxdate 2017`.


**`“\”` does not work as a second line in `rstudioapi::` functions**

```{r part1-4}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query \"malaria AND jama[journal]\" -datetype PDAT -mindate 2015 -maxdate 2017 &> part1-4.txt \n")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}
readLines("part1-4.txt")
```



**Conduct a PubMed search with a search string that includes quotation marks**

    esearch -db pubmed -query "cancer AND \"science\"[journal]"

This line of code uses the esearch command to search PubMed `-db pubmed` for our search query `-query "cancer AND \"science\"[journal]"`. We need to “escape” the double quotation marks `“` in our search query by putting a `\` before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the `-query` argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched.

```{r part1-5}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query 'cancer AND \"science\"[journal]' &> part1-5.txt \n")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}
readLines("part1-5.txt")
```





#### efetch

**Retrieve a single PubMed record in text abstract format**

    efetch -db pubmed -id 25359968 -format abstract

This line of code uses the efetch command to retrieve a record from PubMed `-db pubmed`. We specify that we will retrieve the record for PMID 25359968 `-id 25359968` and that we want the results in the text abstract format `-format abstract`.


```{r part1-6}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, "efetch -db pubmed -id 25359968 -format abstract -log > part1-6.txt \n")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}
readLines("part1-6.txt")
```

    efetch -db pubmed -id 25359968 -format medline
    
    efetch -db pubmed -id 25359968 -format xml
    
    efetch -db pubmed -id 25359968 -format uid

Retrieve multiple PubMed records in text abstract format

    efetch -db pubmed -id 24102982,21171099,17150207 -format abstract

This line of code uses the efetch command to retrieve records from PubMed (-db pubmed). We specify that we will retrieve the records for PMID 24102982,21171099,17150207 (-id 24102982,21171099,17150207) and that we want the results in the text abstract format (-format abstract).


**Creating a data pipeline**

**Conduct a PubMed search and retrieve the results as a list of PMIDs**

```{r part1-pipe}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, " esearch -db pubmed -query \"asthenopia[mh] AND nursing[sh]\" | efetch -format uid &> part1-pipe.txt \n")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}
readLines("part1-pipe.txt")
```





    esearch -db pubmed -query "asthenopia[mh] AND nursing[sh]" | efetch -format uid

This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "asthenopia[mh] AND nursing[sh]"), and then pipes the resulting PMIDs into an efetch command (| efetch), which retrieves the PubMed records, but outputs only the PMIDs (-format uid). For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.


**In-class exercise solutions**


**Exercise 1: esearch**

How many Spanish-language articles about diabetes are in PubMed?

**Solution:**

    esearch -db pubmed -query "diabetes AND spanish[lang]"


```{r part1-e1}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query \"diabetes AND spanish[lang]\" &> part1-e1.txt \n")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}
readLines("part1-e1.txt")
```



This line of code uses the esearch command to search PubMed `-db pubmed` for our search query `-query "diabetes AND spanish[lang]"`. Note that the search query can include Boolean operators `AND` and search field tags `[lang]` to help focus our search, just as we can in the web version of PubMed.

**Exercise 2: esearch**

How many articles were written by BH Smith between 2012 and 2017, inclusive?

**Solutions:**

    esearch -db pubmed -query "smith bh[author]" -datetype PDAT -mindate 2012 -maxdate 2017


```{r part1-e2}
myTerm <- rstudioapi::terminalCreate(show = FALSE)
rstudioapi::terminalSend(myTerm, "esearch -db pubmed -query \"smith bh[author]\" -datetype PDAT -mindate 2012 -maxdate 2017 &> part1-e2.txt \n")
Sys.sleep(1)
repeat{
    Sys.sleep(0.1)
    if(rstudioapi::terminalBusy(myTerm) == FALSE){
        print("Code Executed")
        break
    }
}
readLines("part1-e2.txt")
```




There are multiple possible solutions to this exercise. This solution uses the esearch command to search PubMed (-db pubmed) for our search query (-query "smith bh[author]"). Note that the search query can include search field tags ([author]) to help focus our search, just as we can in the web version of PubMed. The esearch command also limits the search results by publication date (-datetype PDAT), including only articles published between 2012 and 2017 (-mindate 2012 -maxdate 2017).

    esearch -db pubmed -query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat])"

The second solution is largely the same as the first. Rather than use the -datetype, -mindate, and -maxdate arguments to limit the search by publication date, this solution incorporates the date restriction into the search string itself (-query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat])"), just as you would include a date restriction in a search string in the web version of PubMed.


**Exercise 3: efetch**

Who is the first author listed on the PubMed record 26287646?

**Solution:**

    efetch -db pubmed -id 26287646 -format abstract

This line of code uses the efetch command to retrieve a record from PubMed (-db pubmed). We specify that we will retrieve the record for PMID 25359968 (-id 25359968). The command retrieves the record in the text abstract format (-format abstract), which allows us to easily see that the first author of the article is PF Brennan. Rather than using the abstract format, we could instead use -format medline or -format xml to retrieve the record in the MEDLINE or XML formats, if we prefer.
Exercise 4: Combining Commands

How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017?

**Solutions:**

    esearch -db pubmed -query "smith bh[author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \
    efetch -format uid

This solution begins the same as the first solution for Exercise 2. The first line concludes by piping (|) the results of the esearch command into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records, but outputs only the PMIDs (-format uid).

    esearch -db pubmed -query "smith bh[author] AND (2012/01/01[pdat] : 2017/12/31[pdat]" | \
    efetch -format uid


Similarly, this solution begins the same as the second solution for Exercise 2, and then pipes the results of the esearch into the efetch, which retrieves the PubMed records, but outputs only the PMIDs (-format uid).

For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.

**Homework solutions**

**Question 1**

Using EDirect, write a command to find out how many citations are in PubMed for articles about using melatonin to treat sleep disorders.

**Solution:**

    esearch -db pubmed -query "melatonin sleep disorder"

This line of code uses the esearch command to search PubMed (-db pubmed) for our search query (-query "melatonin sleep disorder").
Question 2

How many of the PubMed citations identified in question 2 were added to PubMed (i.e. created) between January 1, 2015 and July 1, 2017?

**Solution:**

There are multiple possible solutions to this question.

    esearch -db pubmed -query "melatonin sleep disorder" -datetype CRDT -mindate 2015/01/01 -maxdate 2017/07/01

Both of these solutions use the esearch command to search PubMed (-db pubmed) for our search query (-query "melatonin sleep disorder"). In the first solution, the esearch command also limits the search results by the date citations were added to PubMed, using the “CRDT” date type (-datetype CRDT), including only articles created between January 1, 2015 and July 1, 2017 (-mindate 2015/01/01 -maxdate 2017/07/01).

    esearch -db pubmed -query "melatonin sleep disorder"  AND (2015/01/01[crdt] : 2017/07/01[crdt])"

The second solution is largely the same as the first. Rather than use the -datetype, -mindate, and -maxdate arguments to limit the search by create date, this solution incorporates the date restriction into the search string itself (-query "melatonin sleep disorder" AND (2015/01/01[crdt] : 2017/07/01[crdt])"), just as you would include a date restriction in a search string in the web version of PubMed.

**Question 3**

Write a command to retreive the abstracts of the following PubMed records:

    27240713,27027883,22468771,20121990

**Solution:**

    efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format abstract

This line of code uses the efetch command to retrieve records from PubMed (-db pubmed). We specify that we will retrieve the records for four PMIDs: 27240713, 27027883, 22468771, and 20121990 (-id 27240713,27027883,22468771,20121990). The command retrieves the records in the text abstract format (-format abstract).

**Question 4**

Modify your answer to Question 3 to retrieve the full XML of all four records.

**Solution:**

    efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format xml

This solution is largely the same as the solution for Question 3, but the -format argument has been changed to retrieve XML instead of the text Abstract format (-format xml).

**Question 5**

Write a series of commands that retrieves a list of PMIDs for all citations for papers written by the author with the ORCID 0000-0002-1141-6306.

**Solution:**

    esearch -db pubmed -query "0000-0002-1141-6306[auid]" | \
    efetch -format uid

This solution begins by using the esearch command to search PubMed (-db pubmed) for citations including an author identifier of “0000-0002-1141-6306” (-query "0000-0002-1141-6306[auid]"). The first line concludes by piping (|) the results of the esearch command into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records, but outputs only the PMIDs (-format uid).

### Part One

https://dataguide.nlm.nih.gov/edirect-for-pubmed-1.txt

The Insider's Guide to Accessing NLM Data: EDirect for PubMed
Part One: Getting PubMed Data

Course Materials

NOTE: Solutions to all exercises are at the bottom of this document.


Commands are instructions given by a user telling a computer to do something

Arguments provide input data or modify the behavior of a command


TIPS FOR CYGWIN USERS:

Copy: Ctrl + Insert
(NOT Ctrl + C!)

Paste: Shift + Insert
(NOT Ctrl + V!)



TIPS FOR ALL USERS:

Ctrl + C "cancels" and gets you back to a prompt

Up and Down arrow keys allow you to cycle through your recent commands

clear: clears your screen


**esearch**

esearch searches a database and returns the unique identifier of every record that meets the search criteria - in this case, PMIDs.

    -db to specify database: -db pubmed
    -query to enter your query in quotes: -query "seasonal affective disorder"


COMMAND STRING:

    esearch -db pubmed -query "seasonal affective disorder"

PUBMED SEARCH:

    seasonal affective disorder



Show PubMed's translation of your search terms like you receive in the Search Details in PubMed

COMMAND STRING:

    esearch -db pubmed -query "seasonal affective disorder" -log

Details display at end of XML snippit 

    "seasonal affective disorder"[MeSH Terms] OR ("seasonal"[All Fields] AND "affective"[All Fields] AND "disorder"[All Fields]) OR "seasonal affective disorder"[All Fields]


Search like you do in PubMed with uppercase Boolean AND/OR/NOT and field tags as needed.

PUBMED SEARCH:

    malaria AND jama[journal]

COMMAND STRING:

    esearch -db pubmed -query "malaria AND jama[journal]"


Restricting by Date

    -datetype specifies date field: -datetype PDAT
    -mindate -maxdate specifies range: -mindate 2015 -maxdate 2017 

COMMAND STRING:

    esearch -db pubmed -query "malaria AND jama[journal]" -datetype PDAT -mindate 2015 -maxdate 2017


Use backslash `"\"` to indicate that you have not finished writing the command - it is continued on the next line.

COMMAND STRING:

    esearch -db pubmed -query "malaria AND jama[journal]" \
    -datetype PDAT -mindate 2015 -maxdate 2017



Be Careful with Quotes

PUBMED SEARCH:

    cancer AND science[journal]

    cancer AND "science"[journal]


COMMAND STRING:

    esearch -db pubmed -query "cancer AND \"science\"[journal]"



**EXERCISE 1: esearch**

How many Spanish-language articles about diabetes are in PubMed?
Hint: use the [lang] field tag

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)


**EXERCISE 2: esearch**

How many articles were written by BH Smith between 2012 and 2017, inclusive?

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)



**efetch**

efetch retrieves the complete record in the format that you specify.

    -db to specify database: -db pubmed
    -id to specify PMID: -id 25359968
    -format to specify format: -format abstract

COMMAND STRING:

    efetch -db pubmed -id 25359968 -format abstract




efetch Formats

    -format options:

MEDLINE

    -format medline

XML

    -format xml

PMID list

    -format uid

Summary

    -format docsum


efetch Multiple Records

Separate multiple PMIDs in the -id argument with commas.

COMMAND STRING:

    efetch -db pubmed -id 24102982,21171099,17150207 -format abstract

    efetch -db pubmed -id 26024162 -format abstract



EXERCISE 3: efetch
Who is the first author listed on the PubMed record 26287646?

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)



Creating a data pipeline

Use pipe "|" [Shift + \] to "pipe" the results of one command into the next

COMMAND STRING:

    esearch -db pubmed -query "asthenopia[mh] AND nursing[sh]" | efetch -format uid



EXERCISE 4: Combining Commands
How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017?
Hint: Use the up arrow to access your previous commands
Hint: Remember -format uid

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)


HOMEWORK FOR PART ONE

(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode1.html)


**Question 1:**

Using EDirect, write a command to find out how many citations are in PubMed for articles about using melatonin to treat sleep disorders.


**Question 2:**

How many of the PubMed citations identified in question 2 were added to PubMed (i.e. created) between January 1, 2015 and July 1, 2017?


**Question 3:**

Write a command to retrieve the abstracts of the following PubMed records:

    27240713
    27027883
    22468771
    20121990


**Question 4:**

Modify your answer to Question 3 to retrieve the full XML of all four records.	


**Question 5:**

Write a series of commands that retrieves a list of PMIDs for all citations for papers written by the author with the ORCID 0000-0002-1141-6306.


EXERCISE SOLUTIONS:

EXERCISE 1: esearch
How many Spanish-language articles about diabetes are in PubMed?
Hint: use the [lang] field tag

**Solution:**

    esearch -db pubmed -query "diabetes AND spanish[lang]"


EXERCISE 2: esearch
How many articles were written by BH Smith between 2012 and 2017, inclusive?
Hint: use the [author] field tag

SOLUTIONS:

    esearch -db pubmed -query "smith bh[author]" \
    -datetype PDAT -mindate 2012 -maxdate 2017

    esearch -db pubmed -query "smith bh[author] \
    AND (2012/01/01[pdat] : 2017/12/31[pdat])"


EXERCISE 3: efetch
Who is the first author listed on the PubMed record 26287646?

**Solution:**

    efetch -db pubmed -id 26287646 -format abstract

The first author is Brennan PF



EXERCISE 4: Combining Commands
How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017?
Hint: Use the up arrow to access your previous commands
Hint: Remember -format uid

SOLUTIONS:

    esearch -db pubmed -query "smith bh[author] AND \
    (2012/01/01[pdat] : 2017/12/31[pdat]" | \
    efetch -format uid



    esearch -db pubmed -query "smith bh[author]" \
    -datetype PDAT -mindate 2012 -maxdate 2017 | \
    efetch -format uid


## Part Two "EDirect for PubMed: Part 2: Extracting Data from XML" Sample Code

### Part Two

https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode2.html


**xtract Basics**

For an introduction to the xtract command, see the xtract section of our EDirect documentation.
Retrieve the article titles for a list of PubMed records

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element ArticleTitle

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row in our output table for every PubMed record (-pattern PubmedArticle). The -element argument indicates that the table should include a single column, containing the article title for the given record (-element ArticleTitle).
Retrieve the list of authors for a series of PubMed records

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern Author -element LastName

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row in our output table for every author (-pattern Author). The -element argument indicates that the table should include a single column, containing the last name for the given author (-element LastName).
Retrieve the PMID and year of publication for a PubMed record

In order to retrieve the PMID and the year of publication for a PubMed record, we might try to use code such as the following:

    efetch -db pubmed -id 27101380 -format xml | \
    xtract -pattern PubmedArticle -element PMID Year

The first line of this code uses the efetch command to retrieve a record from PubMed (-db pubmed -id 27101380) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle; in this case, the table will only have a single row). The line then uses the -element argument to create two columns, one for PMID and one for Year. (-element PMID Year). However, the output of this series of commands is not what we expect:

    27101380        27619336        27619799        27746956        27747057        2016    2016    2016      2016    2015    2016    2016    2016    2016

Rather than getting a single PMID and a single year, we get 5 PMIDs and 9 Years. This is because, while the -element argument is designed to create a new column for each element or attribute specified, it populates each column with the contents of every occurrence of the specified element or attribute in the -pattern. This means that if there are multiple occurrences of the <PMID> or <Year> elements in a PubMed record, the contents of all occurrences will be displayed. As a result, we see not only the PMID for the record, but also the PMIDs used to link it to other records which contain related comments or corrections. Furthermore, in addition to the publication year, we also the year for the other eight dates associated with the PubMed record.

We can avoid this by using Parent/Child construction to specify that we only want the contents of the <PMID> element that is a direct child of the <MedlineCitation> element, and that we only want the <Year> element that is a child of the <PubDate> element:

    efetch -db pubmed -id 27101380 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID PubDate/Year

This version of the code gives us the output we expect:

    27101380        2016

Retrieve three data elements for a list of PubMed records

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation ArticleTitle    

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one for the journal title abbreviation, and one for the article title (-element MedlineCitation/PMID ISOAbbreviation ArticleTitle).
sort-uniq-count-rank and head
Sort a list of authors by the frequency they appear in your results set

    esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
    efetch -format xml | \
    xtract -pattern Author -element LastName,Initials | \
    sort-uniq-count-rank | \
    head -n 10  

This series of commands searches PubMed for the string “traumatic brain injury athletes”, restricts results to those published in 2016 and 2017, retrieves the full XML records for each of the search results, extracts the last name and initials of every author on every record, sorts the authors by frequency of occurrence in the results set, and presents the top ten most frequently-occurring authors, along with the number of times that author appeared.

    esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "traumatic brain injury athletes"). The line also restricts the search results to articles that were published in 2016 or 2017 (-datetype PDAT -mindate 2016 -maxdate 2017).

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format xml | \

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

    xtract -pattern Author -element LastName,Initials | \

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials). This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line.

    sort-uniq-count-rank | \

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set.

    head -n 10

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set:

    14      Iverson     GL
    11      Guskiewicz  KM
    10      Meehan   WP
    9       Kerr       ZY
    9       Kontos   AP
    9       Solomon     GS
    9       Zuckerman   SL
    8       Zafonte     R
    7       Broglio     SP
    7       Covassin    T

(Note: Your output may vary slightly, as additional citations are added to PubMed and the “most frequent” authors change.)

To show more or fewer rows, adjust the “10” up or down. If you want to see all of the authors, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the `“|”` and `“\”` characters from the previous line. Otherwise, the system will wait for you to finish entering your command.)
In-class exercise solutions

Note: The first three exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data.
Exercise 1

Write an xtract command that creates a table with one row per PubMed article. Each row should have two columns: volume number and issue number.

**Solution:**

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element Volume Issue

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with columns for volume number and issue number (-element Volume Issue).
Exercise 2

Write an xtract command that creates a table with one row per PubMed record. Each row should have three columns: PMID, journal ISSN, and citation status.

**Solution:**

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISSN MedlineCitation@Status

This xtract command begins the same as the solution for Exercise 1 (xtract -pattern PubmedArticle). When creating the first column, this command uses Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (like as a child of a <CommentsCorrections> element; -element MedlineCitation/PMID).

Similarly, the second column is also created using Parent/Child construction. This is probably not strictly necessary, as the <ISSN> element only appears in one location in the PubMed XML structure. However, this demonstrates that there may be multiple valid EDirect solutions to a given question (Journal/ISSN).

Finally, the citation status, which is found in the “Status” attribute of the <MedlineCitation> element, is placed in the third column (MedlineCitation@Status).
Exercise 3

Find out which authors have been writing about traumatic brain injuries in athletes, with publications in 2016 and 2017. The output should be a list of author names, one per line, with each author’s last name and initials.

**Solution:**

    esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
    efetch -format xml | \
    xtract -pattern Author -element LastName,Initials

This series of commands searches PubMed for the string “traumatic brain injury athletes”, restricts results to those published in 2016 and 2017, retrieves the full XML records for each of the search results, and extracts the last name and initials of every author on every record.

    esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \


The first line of code uses esearch to search PubMed (-db pubmed) for our search query (-query "traumatic brain injury athletes"). The line also restricts the search results to articles that were published in 2016 or 2017 (-datetype PDAT -mindate 2016 -maxdate 2017).

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format xml | \

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

    xtract -pattern Author -element LastName,Initials

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line.

The command then extracts each author’s last name and initials (-element LastName,Initials).
Homework solutions

**Question 1**

Using the efetch command below to retrieve PubMed XML, write an xtract command to extract specific elements and arrange them into a table. The table should have one PubMed record per row, with columns for PMID, Journal Title Abbreviation, Publication Year, Volume, Issue and Page Numbers.

    efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml

**Solution:**

    efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation PubDate/Year Volume Issue MedlinePgn

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). When creating the first column, this command uses Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (like as a child of a <CommentsCorrections> element; -element MedlineCitation/PMID).

The second column is created without Parent/Child construction, as the <ISOAbbreviation> element is not repeated in a single PubMed XML record (ISOAbbreviation).

The third column also uses Parent/Child construction to retrieve the publication year (as opposed to other <Year> elements; PubDate/Year); the remaining elements only appear in one location in the PubMed XML structure, so Parent/Child construction is unnecessary (Volume Issue MedlinePgn).

**Question 2**

Create a table of the authors attached to PubMed record 28341696. The table should include each author’s last name, initials, and affiliation information (if listed).

**Solution:**

    efetch -db pubmed -id 28341696 -format xml | \
    xtract -pattern Author -element LastName Initials Affiliation

This first line of this solution uses the efetch command to retrieve a record from PubMed (-db pubmed). We specify that we will retrieve the record for PMID 28341696 (-id 28341696) and that we want the results in XML (-format xml).

    xtract -pattern Author -element LastName Initials Affiliation

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name, initials, and affiliation information (-element LastName Initials Affiliation).

**Question 3**

Write a series of commands to generate a table of PubMed records for review articles about the Paleolithic diet. The table should have one row per citation, and should include columns for the PMID, the citation status, and the article title.


**Solution:**

    esearch -db pubmed -query "review[pt] paleolithic diet" | \
    efetch -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID MedlineCitation@Status ArticleTitle

This series of commands searches PubMed for the string “review[pt] paleolithic diet”, retrieves the full XML records for each of the search results, and extracts the last name and initials of every author on every record.

    esearch -db pubmed -query "review[pt] paleolithic diet" | \

The first line of code uses esearch to search PubMed (-db pubmed) for our search query (-query "review[pt] paleolithic diet"). Note that the search query can include search field tags ([pt]) to help focus our search, just as we can in the web version of PubMed.

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format xml | \

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

xtract -pattern PubmedArticle -element MedlineCitation/PMID MedlineCitation@Status ArticleTitle

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for every PubMed record (-pattern PubmedArticle).

The command then extracts each record’s PMID (using Parent/Child construction; -element MedlineCitation/PMID), citation status (using “@” to retrieve the attribute value for “Status”; MedlineCitation@Status), and article title (ArticleTitle).



### Part Two

https://dataguide.nlm.nih.gov/edirect-for-pubmed-2.txt


The Insider's Guide to Accessing NLM Data: EDirect for PubMed
Part Two: Extracting Data from XML
Course Materials

NOTE: Solutions to all exercises are at the bottom of this document.


REMINDERS FROM PART ONE

esearch: Searches a database and returns PMIDs

efetch: Retrieves PubMed records in a variety of formats

Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next




TIPS FOR CYGWIN USERS:

Copy: Ctrl + Insert
(NOT Ctrl + C!)

Paste: Shift + Insert
(NOT Ctrl + V!)




TIPS FOR ALL USERS:

Ctrl + C "cancels" and gets you back to a prompt

Up and Down arrow keys allow you to cycle through your recent commands

clear: clears your screen

----------------------------------------------------------------------


xtract

Extracts specific elements from XML and arranges them in a customized tabular format.

----------------------------------------------------------------------

Getting XML

From efetch:

[...] | efetch -format xml | xtract [...]

From a file on your computer using "-input":

xtract -input file.xml [...]

----------------------------------------------------------------------

XML Element Descriptions 
https://www.nlm.nih.gov/bsd/licensee/elements_descriptions.html 

PubMed DTD Documentation
https://dtd.nlm.nih.gov/ncbi/pubmed/out/doc/2018/ 

----------------------------------------------------------------------

Before you start xtract-ing...

Look at some PubMed XML by searching PubMed for a few PMIDs:

24102982,21171099,17150207

----------------------------------------------------------------------

Getting a small sample dataset

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml

----------------------------------------------------------------------

-pattern to identify which element will create a new row in the output table

-element to identify which element(s) or attribute(s) will create columns in the output table


A basic xtract Command:

COMMAND STRING:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element ArticleTitle


    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern Author -element LastName

----------------------------------------------------------------------

Creating multiple columns

Create multiple columns using the same -element argument by including multiple XML element names.
Separate the names with spaces.

Example:

    xtract -pattern PubmedArticle -element Agency GrantID

----------------------------------------------------------------------

EXERCISE 1:
Write an xtract command that:
*	creates a table with one row per PubMed article.
*	Each row should have two columns:
	*	Volume
	*	Issue Number

Use the following efetch as input:

efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \	

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)
	
----------------------------------------------------------------------
Isolating the elements we need

COMMAND STRING:

    efetch -db pubmed -id 27101380 -format xml | \
    xtract -pattern PubmedArticle -element PMID Year 

----------------------------------------------------------------------

Parent/Child construction

Retrieves only elements that are the child of a specific parent.

Format: ParentElement/ChildElement

Example:

    -element MedlineCitation/PMID

----------------------------------------------------------------------

Solving xtract Example 1
We have a set of records
We want a tabular list with PMID, Journal Title Abbreviation, and Article Title

COMMAND STRING:
efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISOAbbreviation ArticleTitle

----------------------------------------------------------------------

xtract-ing attribute values

Format: ElementName@AttributeName

Example:

    -element DescriptorName@MajorTopicYN

----------------------------------------------------------------------

EXERCISE 2
Write an xtract command that:
*	Has one row per PubMed records
*	Has three columns:
	*	PMID
	*	Journal ISSN
	*	Citation status

Use the following efetch as input:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)
	
----------------------------------------------------------------------

EXERCISE 3: Putting it all together

We want to find out which authors have been writing about traumatic brain injuries in athletes
*	Limit to publications from 2016 and 2017.
We want to see just the author names, one per line.
We want the last name and initials, separated by a space.
We want the whole script (not just the xtract command).

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)


----------------------------------------------------------------------

sort-uniq-count-rank

Four steps of sort-uniq-count-rank
1. Sorts all of the lines in your input alphabetically by the full contents of the line
2. Eliminates all duplicates, leaving only unique values.
3. Counts up how many of each unique value there were in your input, and provides that frequency count next to each unique value.
4. Re-sorts the unique values in descending order by frequency, so the most frequently occurring values are at the top.

COMMAND STRING:

esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
efetch -format xml | \
xtract -pattern Author -element LastName Initials | \
sort-uniq-count-rank

----------------------------------------------------------------------

head

Limits output to only the first few lines of input.

Example:

    head -n 10

Outputs only the first ten lines of the input.

COMMAND STRING:

    esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
    efetch -format xml | \
    xtract -pattern Author -element LastName Initials | \
    sort-uniq-count-rank | \
    head -n 10


HOMEWORK FOR PART TWO)

(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode2.html)

**Question 1:**

Using the efetch command below to retrieve PubMed XML, write an xtract command with one record per row, with columns for PMID, Journal Title Abbreviation, Publication Year, Volume, Issue and Page Numbers.

    efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml


**Question 2:**

Create a table of the authors attached to PubMed record 28341696. The table should include each author's last name, initials, and affiliation information (if listed).


**Question 3:**

Write a series of commands to generate a table of PubMed records for review articles about the paleolithic diet. The table should have one row per citation, and should include columns for the PMID, the citation status, and the article title.


EXERCISE SOLUTIONS:

**EXERCISE 1:**
Write an xtract command that:
*	creates a table with one row per PubMed article.
*	Each row should have two columns:
	*	Volume
	*	Issue Number

**Solution:**

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element Volume Issue



**EXERCISE 2:**
Write an xtract command that:
*	Has one row per PubMed records
*	Has three columns:
	*	PMID
	*	Journal ISSN
	*	Citation status

**Solution:**

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISSN MedlineCitation@Status



**EXERCISE 3: Putting it all together**

We want to find out which authors have been writing about traumatic brain injuries in athletes
*	Limit to publications from 2016 and 2017.
We want to see just the author names, one per line.
We want the last name and initials, separated by a space.
We want the whole script (not just the xtract command).

**Solution:**

    esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \
    efetch -format xml | \
    xtract -pattern Author -element LastName Initials


## Part Three "EDirect for PubMed: Part 3: Formatting Results and Unix Tools" Sample Code

### Part Three

https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode3.html


xtract Formatting arguments

For an introduction to xtract Formatting arguments, see the Customizing separators section of our EDirect documentation.
Change the separators in an xtract output table

We can use the -tab and -sep arguments to modify the separators in an xtract output table. We will start with a basic xtract statement with no customized separators:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID ISSN LastName

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one for the journal ISSN, and one for author last name (-element MedlineCitation/PMID ISSN LastName). For articles with more than one author, we will see multiple author last names in the third column:

    24102982        1742-4658       Wu      Doyle   Barry   Beauvais        Rozkalne        Piao    Lawlor    Kopin   Walsh   Gussoni
    21171099        1097-4598       Wu      Gussoni
    17150207        0012-1606       Yoon    Molloy  Wu      Cowan   Gussoni

By default, xtract separates columns in the output table with tabs (indicated in Unix as `\t`). Additionally, by default, xtract separates multiple values in the same column with tabs. So the following series of commands:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "\t" -sep "\t" -element MedlineCitation/PMID ISSN LastName

produces the same output as before, since we are telling xtract to use a tab to separate between columns `(-tab "\t")` and between multiple values in the same column (-sep "\t"), which xtract is already doing by default:

    24102982        1742-4658       Wu      Doyle   Barry   Beauvais        Rozkalne        Piao    Lawlor    Kopin   Walsh   Gussoni
    21171099        1097-4598       Wu      Gussoni
    17150207        0012-1606       Yoon    Molloy  Wu      Cowan   Gussoni

We can modify the output by modifying the -sep argument:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "\t" -sep " " -element MedlineCitation/PMID ISSN LastName

This series of commands tells xtract to keep the separators between columns the same, but to separate multiple values in the same column (such as the multiple author last names in our third column) by spaces instead of tabs:

    24102982        1742-4658       Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni
    21171099        1097-4598       Wu Gussoni
    17150207        0012-1606       Yoon Molloy Wu Cowan Gussoni

We can further modify the output by modifying the -tab argument:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -sep " " -element MedlineCitation/PMID ISSN LastName

This time, the separators between columns have been changed from tabs to pipes (-tab "|"), while multiple values in the same column are still separated by spaces:

    24102982|1742-4658|Wu Doyle Barry Beauvais Rozkalne Piao Lawlor Kopin Walsh Gussoni
    21171099|1097-4598|Wu Gussoni
    17150207|0012-1606|Yoon Molloy Wu Cowan Gussoni

The -tab and -sep arguments also allow you to specify separators of more than one character:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -sep ", " -element MedlineCitation/PMID ISSN LastName

This series of commands uses pipes to separate the columns (-tab "|"), but uses a comma followed by a space to separate the last names (-sep ", "):

    24102982|1742-4658|Wu, Doyle, Barry, Beauvais, Rozkalne, Piao, Lawlor, Kopin, Walsh, Gussoni
    21171099|1097-4598|Wu, Gussoni
    17150207|0012-1606|Yoon, Molloy, Wu, Cowan, Gussoni

xtract Exploration arguments

For an introduction to xtract Exploration arguments, see the Exploration arguments section of our EDirect documentation.
Retrieve author names for a list of PubMed records

In order to retrieve the author names (including last name and initials) for all of the authors associated with each of several PubMed records, we might try to use code such as the following:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID LastName Initials

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and with three columns: one for PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one for author last name, and one for author initials (-element MedlineCitation/PMID LastName Initials). However, the output of this series of commands is not what we expect:

    24102982        Wu      Doyle   Barry   Beauvais        Rozkalne        Piao    Lawlor  Kopin   Walsh     Gussoni MP      JR      B       A       A       X       MW      AS    CA      E
    21171099        Wu      Gussoni MP      E
    17150207        Yoon    Molloy  Wu      Cowan   Gussoni S       MJ      MP      DB      E

The PMID appears as we expect, as does the first author last name. However, rather than following the first author’s last name with the corresponding initials, our output lists all of the authors’ last names for a PubMed record first, before listing all of the authors’ initials.

To retain the relationship between last name and initials, we could use the following series of commands:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -element LastName Initials

The second line of this code creates a column for the PMID as before (xtract -pattern PubmedArticle -element MedlineCitation/PMID). However, the code then uses the -block argument to direct xtract to look for an <Author> element, then to look within that <Author> for <LastName> and <Initials> elements (-block Author -element LastName Initials). Because each author has only one last name and one set of initials, xtract outputs a corresponding pair of last name and initials, before moving on to find the next author. This process is then repeated for each author, giving us the output we expect:

    24102982        Wu      MP      Doyle   JR      Barry   B       Beauvais        A       Rozkalne        A       Piao    X       Lawlor  MW      Kopin   AS   Walsh    CA      Gussoni E
    21171099        Wu      MP      Gussoni E
    17150207        Yoon    S       Molloy  MJ      Wu      MP      Cowan   DB      Gussoni E

Putting values from multiple elements in the same column
Separate author last name and initials with a space, while separating columns with a tab

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -sep " " -element LastName,Initials

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to create a table, with one row for every PubMed record in our XML (xtract -pattern PubmedArticle), and creates a column for the PMID (xtract -pattern PubmedArticle -element MedlineCitation/PMID). As seen in previous examples, the code than uses the -block argument to direct xtract to look for an <Author> element (-block Author), then to look within that <Author> for <LastName> and <Initials> elements.

Because each author has only one last name and one set of initials, xtract outputs a corresponding pair of last name and initials, before moving on to find the next author. However, rather than putting the last name and initials in separate columns, this command uses a comma to group together both the last name and initials in the same column (-element LastName,Initials). This tells xtract to separate the last name and initials with the character we define in the -sep argument (which we have defined as a single space: -sep " "), instead of using the separator between columns (which is still the default tab), and gives us the output we desire:

    24102982        Wu MP   Doyle JR        Barry B Beauvais A      Rozkalne A      Piao X  Lawlor MW       Kopin AS        Walsh CA      Gussoni E
    21171099        Wu MP   Gussoni E
    17150207        Yoon S  Molloy MJ       Wu MP   Cowan DB        Gussoni E

Working with files
Saving results to a file

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.txt

This line of code uses the efetch command to retrieve records from PubMed (-db pubmed -id 24102982,21171099,17150207) in XML format (-format xml), and redirects the XML output to a file named “testfile.txt” (> testfile.txt).
Using a search string saved in a file to search PubMed

    esearch -db pubmed -query "$(cat searchstring.txt)"

This line of code uses the esearch command to search PubMed (-db pubmed). The search query is stored in a text file (“searchstring.txt”), and the cat command is used to access the contents of the file for use as a search query (-query "$(cat searchstring.txt)"). The dollar-sign and parentheses around cat searchstring.txt indicate that Unix should use the value of cat searchstring.txt (i.e. the contents of the file “searchstring.txt”), rather than simply the words “cat searchstring.txt”.
epost
Post two PMIDs to the History server

    epost -db pubmed -id 24102982,21171099

This line of code uses the epost command to post two unique identifiers (UIDs) to the History server (-id 24102982,21171099), indicating that the UIDs are for records in the PubMed database (i.e. that the UIDs are actually PMIDs; -db pubmed).

For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.
Post two PMIDs to the History server and retrieve the corresponding PubMed records in abstract format

    epost -db pubmed -id 24102982,21171099 | efetch -format abstract

This line of code uses the epost command to post two unique identifiers (UIDs) to the History server (-id 24102982,21171099), indicating that the UIDs are for records in the PubMed database (i.e. that the UIDs are actually PMIDs; -db pubmed). The line then pipes information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract). For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.
Retrieve PubMed records in abstract format for a list of PMIDs contained in a CSV file

    cat pmids.csv | epost -db pubmed | efetch -format abstract

This line of code uses cat to open a CSV file (“pmids.csv”) which contains a list of PMIDs (cat pmids.csv). Rather than displaying the contents of the file on the screen, this line of code pipes the contents of the file into an epost command (| epost). The epost command stores the PMIDs on the History server, indicating to the History server that they are PMIDs, and not UIDs from a different database (-db pubmed). Finally, the line pipes the information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract).

    epost -db pubmed -input pmids.csv | efetch -format abstract

This line of code is another way of accomplishing the same task as the previous example. Rather than use cat to open the file “pmids.csv”, this line uses the epost command’s -input argument, which is a new feature of EDirect, added in version 4.90 (released on September 14, 2016). The epost command stores the PMIDs on the History server, indicating to the History server that they are PMIDs, and not UIDs from a different database (-db pubmed). Finally, the line pipes the information to an efetch command (| efetch), which allows the efetch command to retrieve the correct PMIDs from the History server. The efetch command then retrieves the corresponding PubMed records in text abstract format (-format abstract).

For more information about piping data from one EDirect command to another, please review the page on Making data pipelines with the History server in our EDirect overview.
In-class exercise solutions

Note: The first two exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data.
Exercise 1

Write an xtract command that generates a new row for each PubMed record, and has columns for PMID, journal title abbreviation, and author-supplied keywords. Each column should be separated by `“|”`. Multiple keywords in the last column should be separated with commas.

Sample Output:

    26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology

**Solution:**

    efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -sep "," -element MedlineCitation/PMID ISOAbbreviation Keyword

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with columns for PMID (specified using Parent/Child construction), journal title abbreviation, and author-supplied keywords (-element MedlineCitation/PMID ISOAbbreviation Keyword).

Instead of separating the columns by tabs, the command uses the -tab argument to specify pipe (``“|”``) as a separator (-tab "|"). Because each record could have multiple author-supplied keywords, the command uses the -sep argument to specify a separator between multiple values in a column (i.e. multiple author-supplied keywords in the third column; -sep ",").
Exercise 2

Write an xtract command that creates a table with a new row for each PubMed record. Each row should have the record’s PMID, as well as a list of all the MeSH headings for the records, separated by ``“|”``. If a MeSH heading has subheadings attached, separate the heading and subheadings with “/”. For example:

    24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology

**Solution:**

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \
    -block MeshHeading -tab "|" -sep "/" -element DescriptorName,QualifierName

This xtract command begins the same as the solution for Exercise 1 (xtract -pattern PubmedArticle). The command then specifies a separator between columns (-tab "|") and the first column in the output table (using Parent/Child construction; -element MedlineCitation/PMID). The `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

The command continues on the next line, using -block to maintain the relationship between MeSH headings and related subheadings. The -block argument directs xtract to look for a <MeshHeading> element (-block MeshHeading) then to look within that <MeshHeading> for <DescriptorName> and <QualifierName> elements. Another argument is needed to respecify the separator between columns (-tab "|"), as the separators are reset to default by -block.

Each <MeshHeading> element contains one <DescriptorName>, but may contain zero or more <QualifierName> elements. For each -block, the -element argument populates a column with the <DescriptorName> and all of the <QualifierName> elements, if there are any (-element DescriptorName,QualifierName). For MeSH headings with subheadings, this will place multiple values in the same column (one <DescriptorName> and one or more <QualifierName> elements), so we establish “/” as a separator between multiple values in the same column (-sep "/").

**Exercise 3**

How can we get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil? Save your results to a file.

**Solution:**

    esearch -db pubmed -query "zika virus microcephaly brazil" | \
    efetch -format xml > zika.xml

This solution begins by using the esearch command to search PubMed (-db pubmed) for our search query (-query "zika virus microcephaly brazil"). The first line concludes by piping (|) the results of the esearch command into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The efetch command in the second line accepts the PMIDs piped from the previous line, and retrieves the PubMed records in full XML (-format xml). The results of the command is then redirected to a file (> zika.xml).
Homework solutions

Question 1

In the PubMed XML of each record, there is a <History> element, with one or more elements which provide dates for various stages in each article’s life cycle. These can include when the article was submitted to the publisher for review, when the article was accepted by the publisher for publication, when it was added to PubMed, and/or when it was indexed for MEDLINE, among others. Not all citations will include entries for each type of date.

For the following list of PMIDs

    22389010,20060130,14678125,19750182,19042713,18586245

write a series of commands that retrieves each record and extracts all of these different dates, along with the labels that indicate which type of date is which.

Each PubMed record should appear on a separate line. Each line should start with the PMID, followed by a tab, followed by the list of dates. For each date, include the label, followed by a “:”, followed by the year, month and day, separated by slashes. Separate each date with a `“|”`.

Example output:

    18586245        received:2008/01/21|revised:2008/05/05|accepted:2008/05/07|pubmed:2008/7/1|medline:2008/10/28|entrez:2008/7/1

**Solution:**

    efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block PubMedPubDate -tab ":" -sep "/" -element PubMedPubDate@PubStatus \
    -tab "|" -element Year,Month,Day

Question 2

Identify your “working directory”. Write a series of commands that retrieve PubMed data, redirect the output to a file, and locate the file on your computer.

**Solution:**

The solution to this question may vary, depending on what type of Unix system you are using to run EDirect. One possible solution for identifying your “working directory” is:

    pwd

The pwd command prints to the screen the name of your working directory. Depending on your system, this may give you all of the information you need to find your working directory. If not, please review the material presented in “EDirect for PubMed: Part 3: Formatting Results and Unix Tools”.

The second part of this question may also have many solutions. One possible solution is:

    efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format abstract > abstracts.txt

This solution uses a basic efetch command to retrieve the six PubMed records specified in the the text abstract format (-format abstract). The command then redirects the output to a text file (> abstracts.txt). Provided you have found your working directory, you can find your new file and open it in a text editor.
Question 3

Write a series of commands that identifies the top ten agencies that have most frequently funded published research on diabetes and pregnancy over the last year and a half. Your script should start with a search for articles about diabetes and pregnancy that were published between January 1, 2016 and June 30, 2017, should extract the agencies listed as funders on each citation, and should output a list of the ten most frequently occuring agencies. Save the results to a file.

Note: This script may take some time to run. As you build it, consider testing with small set of PubMed records, or with a search that has a smaller date range.

**Solution:**

    esearch -db pubmed -query "diabetes AND pregnancy" -datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30 | \
    efetch -format xml | \
    xtract -pattern Author -sep " " -element LastName,Initials | \
    sort-uniq-count-rank | \
    head -n 10

This series of commands searches PubMed for the string “diabetes AND pregnancy” with a publication date between January 1, 2016 and June 30, 2017; retrieves the full XML records for each of the search results; extracts the last name and initials of every author on every record; sorts the authors by frequency of occurence in the results set; and presents the top ten most frequently-occuring authors, along with the number of times that author appeared.

    esearch -db pubmed -query "diabetes AND pregnancy" -datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30 | \

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "diabetes AND pregnancy"). We use the -datetype, -mindate, and -maxdate arguments to add our date restriction (-datetype PDAT -mindate 2016/01/01 -maxdate 2017/06/30). Alternatively, we could include the date restriction in our search string, as part of our -query argument.

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format xml | \

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

    xtract -pattern Author -sep " " -element LastName,Initials | \

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials) and separates the two elements with a single space (-sep " "). This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line.

    sort-uniq-count-rank | \

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set.

    head -n 10

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set.
Question 4

Write a PubMed search strategy and save it to a file. Write a series of commands to search PubMed using the search string contained in the file and retrieve a list of PMIDs for all records which meet the search criteria.

**Solution:**

The solution to this may vary, based on your strategy and the name of the file to which you save it. For this example, our search strategy is saved to a file named “searchstring.txt”.

    esearch -db pubmed -query "$(cat searchstring.txt)" | \
    efetch -format uid

The first line uses esearch to search PubMed (-db pubmed). The line uses the Unix command cat to read the entire contents of a file (searchstring.txt) and use it as the search query (-query "$(cat searchstring.txt)").

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format uid

The second line takes the esearch result from our first line and uses efetch to retrieve the PMIDs for all of the records in our results set. (efetch -format uid).

**Question 5**

Save the following list of PMIDs in a .csv file:

    22389010,20060130,14678125,19750182,19042713,18586245

Write a series of commands to retrieve the full PubMed XML records for all of the PMIDs in the file, and save the resulting XML to a .xml file.

**Solution:**

The solution to this may vary, based on how you choose to save your PMIDs to a file, and on the name of that file. To begin, you could save your PMIDs to a file using efetch:

    efetch -db pubmed -id 22389010,20060130,14678125,19750182,19042713,18586245 -format uid > pmids.csv

Regardless of how you get the PMIDs into a .csv file, you can use epost -input and efetch to retrieve the records.

    epost -db pubmed -input pmids.csv | \
    efetch -format xml > records.xml

The first line of this solution uses epost to retrieve the numbers from the “pmids.csv” file (-input pmids.csv) and save them to the history server, along with the indication that the numbers are PMIDs, and refer to records in PubMed (-db pubmed)

The `“|”` character pipes the WebEnv and QueryKey output of our epost into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

The efetch command on the second line receiveds the WebEnv and QueryKey from the epost and uses the information to locate on the history server the specific set of PMIDs posted by our epost command. The efetch command then retrieves the full records for each of those PMIDs in full PubMed XML (-format xml), and saves the output to a new file (> records.xml).

### Part Three

https://dataguide.nlm.nih.gov/edirect-for-pubmed-3.txt


The Insider's Guide to Accessing NLM Data: EDirect for PubMed
Part Three: Formatting Results and Unix tools
Course Materials

NOTE: Solutions to all exercises are at the bottom of this document.


REMINDERS FROM PART ONE

esearch: Searches a database and returns PMIDs

efetch: Retrieves PubMed records in a variety of formats

Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next


----------------------------------------------------------------------

REMINDERS FROM PART TWO

xtract: Pulls data from XML and arranges it in a table

-pattern: Defines rows for xtract

-element: Defines columns for xtract

Identify XML elements by name (e.g. ArticleTitle)

Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID)

Identify attributes with "@" (e.g. MedlineCitation@Status)

----------------------------------------------------------------------

TIPS FOR CYGWIN USERS:

Copy: Ctrl + Insert
(NOT Ctrl + C!)

Paste: Shift + Insert
(NOT Ctrl + V!)

----------------------------------------------------------------------

TIPS FOR ALL USERS:

Ctrl + C "cancels" and gets you back to a prompt

Up and Down arrow keys allow you to cycle through your recent commands

clear: clears your screen

----------------------------------------------------------------------

-tab and -sep

-tab defines the separator between columns
-sep defines the separator between multiple values in the same columns

The default for both -tab and -sep is "\t" (the tab character)
Changes to -tab and -sep only affect subsequent -element/-first/-last arguments

COMMAND STRING:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID ISSN LastName

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "\t" -sep "\t" \
    -element MedlineCitation/PMID ISSN LastName

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "\t" -sep " " \
    -element MedlineCitation/PMID ISSN LastName

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -sep " " \
    -element MedlineCitation/PMID ISSN LastName

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -sep "," \
    -element MedlineCitation/PMID ISSN LastName

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -sep ", " \
    -element MedlineCitation/PMID ISSN LastName



With -tab/-sep, order matters!

-tab/-sep only affect subsequent -elements

Later -tab/-sep overwrite earlier ones




**EXERCISE 1**

Write an xtract command that:
*	has a new row for each PubMed record
*	has columns for PMID, Journal Title Abbreviation, and Author-supplied Keywords
Each column should be separated by "|"
Multiple keywords in the last column should be separated with commas
Sample Output:


    26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology

Use the following efetch as input:

    efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)



Authors: First Draft

COMMAND STRING:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID LastName Initials

----------------------------------------------------------------------

-block

-block associates multiple child elements of the same parent element in the results

COMMAND STRING:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -element LastName Initials

----------------------------------------------------------------------

What we know so far...


    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -sep ", " \
    -element MedlineCitation/PMID ISSN LastName

----------------------------------------------------------------------

Putting two different elements in the same column

Separate multiple -element values with a comma instead of a space.

COMMAND STRING:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -sep " " -element LastName,Initials



"-block" resets -tab/-sep to default

COMMAND STRING:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \
    -block Author -sep " " -element LastName,Initials


    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \
    -block Author -tab "|" -sep " " -element LastName,Initials

----------------------------------------------------------------------

**EXERCISE 2**

Write an xtract command that:
*	Has a new row for each PubMed record
*	Has a column for PMID
*	Lists all of the MeSH headings, separated by "|"
	*	If a heading has multiple subheadings attached, separate the heading and subheadings with "/"
Sample Output:


    24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology

Use the following efetch as input:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

----------------------------------------------------------------------

Saving results to a file

Use ">" to save the output to a file

COMMAND STRING:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.txt

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.xml



But where is my file!?

Use "pwd" to "Print the Working Directory" (a.k.a display on the screen the name of the directory you are working in). This is where your file was saved.

CYGWIN USERS:

Your working directory is probably a subfolder of the folder where you installed Cygwin. In Cygwin, try:

cygpath -w ~

MAC USERS:

Your working directory is probably in your Users folder:

Users/<your user name>

----------------------------------------------------------------------

Another way to find your files

COMMAND STRING:

efetch -db pubmed -id 24102982,21171099,25359968,17150207 -format uid > specialname.csv

Use "ls" to list the files in your current directory.

----------------------------------------------------------------------

EXERCISE 3: Retrieving XML 
How can I get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil?  Save your results to a file.

(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.)

----------------------------------------------------------------------

cat

Short for concatenate, "cat" opens files to display them on the screen. "cat" can also combine/append files


----------------------------------------------------------------------

Reading a search string from a file 

Use "$(cat filename)" to use the contents of a file in a command

COMMAND STRING:

    esearch -db pubmed -query "$(cat searchstring.txt)"

----------------------------------------------------------------------

epost uploads a list of PMIDs to the history server

COMMAND STRING:

    epost -db pubmed -id 24102982,21171099

    epost -db pubmed -id 24102982,21171099 | efetch -format abstract



An epost-efetch pipeline

    cat specialname.csv | epost -db pubmed | efetch -format abstract

Using the -input argument

    epost -db pubmed -input specialname.csv | efetch -format abstract


HOMEWORK FOR PART THREE

(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode3.html)


**Question 1:**

In the PubMed XML of each record, there is a <History> element, with one or more <PubmedPubDate> elements which provide dates for various stages in each article's life cycle. These can include when the article was submitted to the publisher for review, when the article was accepted by the publisher for publication, when it was added to PubMed, and/or when it was indexed for MEDLINE, among others. Not all citations will include entries for each type of date.

For the following list of PMIDs

    22389010
    20060130
    14678125
    19750182
    19042713
    18586245

write a series of commands that retrieves each record and extracts all of these different dates, along with the labels that indicate which type of date is which.

Each PubMed record should appear on a separate line. Each line should start with the PMID, followed by a tab, followed by the list of dates. For each date, include the label, followed by a ":", followed by the year, month and day, separated by slashes. Separate each date with a "|".

Example output:

    18586245        received:2008/01/21|revised:2008/05/05|accepted:2008/05/07|pubmed:2008/7/1|medline:2008/10/28|entrez:2008/7/1


**Question 2:**

Identify your "working directory". Write a series of commands that retrieve PubMed data, redirect the output to a file, and locate the file on your computer.


**Question 3:**

Write a series of commands that identifies the top ten agencies that have most frequently funded published research on diabetes and pregnancy over the last year and a half. Your script should start with a search for articles about diabetes and pregnancy that were published between January 1, 2016 and June 30, 2017, should extract the agencies listed as funders on each citation, and should output a list of the ten most frequently occurring agencies. Save the results to a file.

Note: This script may take some time to run. As you build it, consider testing with small set of PubMed records, or with a search that has a smaller date range.


**Question 4:**

Write a PubMed search strategy and save it to a file. Write a series of commands to search PubMed using the search string contained in the file and retrieve a list of PMIDs for all records which meet the search criteria.


**Question 5:**

Save the following list of PMIDs in a .csv file:

    22389010
    20060130
    14678125
    19750182
    19042713
    18586245

Write a series of commands to retrieve the full PubMed XML records for all of the PMIDs in the file, and save the resulting XML to a .xml file.

-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-
EXERCISE SOLUTIONS:
-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-

EXERCISE 1
Write an xtract command that:
*	has a new row for each PubMed recprd
*	has columns for PMID, Journal Title Abbreviation, and Author-supplied Keywords
Each column should be separated by "|"
Multiple keywords in the last column should be separated with commas
Sample Output:

26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology


**Solution:**

    efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -sep "," -element MedlineCitation/PMID ISOAbbreviation Keyword

-=-=-=-=-=-=-=-=-=-=-=-=-
EXERCISE 2:
Write an xtract command that:
*	Has a new row for each PubMed record
*	Has a column for PMID
*	Lists all of the MeSH headings, separated by "|"
	*	If a heading has multiple subheadings attached, separate the heading and subheadings with "/"
Sample Output:


    24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology

**Solution:**

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \
    -block MeshHeading -tab "|" -sep "/" -element DescriptorName,QualifierName

-=-=-=-=-=-=-=-=-=-=-=-=-
EXERCISE 3: Retrieving XML 
How can I get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil?  Save your results to a file.

**Solution:**

    esearch -db pubmed \
    -query "zika virus microcephaly brazil" | \
    efetch -format xml > zika.xml


## Part Four "EDirect for PubMed: Part 4: xtract Conditional Arguments" Sample Code

### Part Four

https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode4.html




xtract Conditional arguments

For an introduction to the xtract Conditional arguments, see the Filtering output with Conditional arguments section of our EDirect documentation.
Include only authors with ORCID IDs in the output table

    efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml | \
    xtract -pattern Author -if Identifier -sep " " -element LastName,Initials Identifier

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27298442,27392493,27363997,27298443) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each <Author> element (-pattern Author), but only if the <Author> element contains an <Identifier> element (which is the where an author’s ORCID ID is stored). If an author does not have an ORCID ID, the author will not have an <Identifier> element; no row is created for the author, and xtract skips to the next author (-if Identifier).

The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " "), and one with the author’s ORCID ID (Identifier).
Include only articles from the journal JAMA in the output table

    efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
    xtract -pattern PubmedArticle -if ISOAbbreviation -equals JAMA -element Volume Issue

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the article’s journal title abbreviation (<ISOAbbreviation>) is “JAMA”. If a citation is from a different journal, no row is created for the record, and xtract skips to the next record (-if ISOAbbreviation -equals JAMA).

The command creates two columns for each row: one with the article’s Volume number, one with the article’s Issue number (-element Volume Issue).
Include only MEDLINE articles in the output table

    efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
    xtract -pattern PubmedArticle -if MedlineCitation@Status -equals MEDLINE -element MedlineCitation/PMID

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the record’s citation status (which is found in the “Status” attribute of the <MedlineCitation> element) is “MEDLINE”. If a citation is not in “MEDLINE” status, no row is created for the record, and xtract skips to the next record (-if MedlineCitation@Status -equals MEDLINE).

The command creates a single column for each row, containing the record’s PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element; -element MedlineCitation/PMID)
Include only authors whose affiliation mentions Japan in the output table

    efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
    xtract -pattern Author -if Affiliation -contains Japan -sep " " -element LastName,Initials Affiliation

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27460563,27532912,27392493,27363997,24108526) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each <Author> element (-pattern Author), but only if the <Author> element contains an <Affiliation> element which includes the word “Japan”. If an author does not have affiliation data, or the author’s affiliation data does not contain Japan, no row is created for the author, and xtract skips to the next author (-if Affiliation -contains Japan).

The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " "), and one with the author’s affiliation data (Affiliation).
Output a list of PMIDs and corresponding DOIs

    efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block ArticleId -if ArticleId@IdType -equals doi -element ArticleId

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 16940437,16049336,11972038) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (e.g. as a child of a <CommentsCorrections> element; -element MedlineCitation/PMID).

The xtract command continues on the third line by checking each <ArticleId> element in a PubMed record (-block ArticleId). If an <ArticleId> element contains a DOI (indicated by the “IdType” attribute for the <ArticleId> equaling “doi”; -if ArticleId@IdType -equals doi), then the command puts the DOI in the second column (-element ArticleId). If not, the second column is left blank.

The result of this command will be a two column table, where the first column is always a PMID, and the second column is either the corresponding DOI (if there is one), or is blank (if there is no DOI).
Combining multiple Conditional arguments
Output a list of PMIDs and corresponding DOIs and PMCIDs

    efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block ArticleId -if ArticleId@IdType -equals doi \
    -or ArticleId@IdType -equals pmc -element ArticleId

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 16940437,16049336,11972038) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (e.g. as a child of a <CommentsCorrections> element; -element MedlineCitation/PMID).

The xtract command continues on the third line by checking each <ArticleId> element in a PubMed record (-block ArticleId). If an <ArticleId> element contains a DOI (indicated by the “IdType” attribute for the <ArticleId> equaling “doi”; -if ArticleId@IdType -equals doi) OR a PMC ID (indicated by the “IdType” attribute for the <ArticleId> equaling “pmc”; -or ArticleId@IdType -equals pmc), then the command puts the contents of the <ArticleId> element in the second column (-element ArticleId).

Because a PubMed record can have multiple <ArticleId> elements, and because the -block argument checks each <ArticleId> separately, this command may result in both a DOI and a PMC ID appearing the second column of some rows.
Include only authors with the last name Kamal and with affiliation data in the output table

    efetch -db pubmed -id 27798514,24372221,24332497,24307782 -format xml | \
    xtract -pattern Author -if LastName -equals Kamal -and Affiliation \
    -sep " " -element LastName,Initials Affiliation

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27798514,24372221,24332497,24307782) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each <Author> element (-pattern Author), but only if the <LastName> element for the <Author> is “Kamal”, AND the <Author> element contains an <Affiliation> element (-if LastName -equals Kamal -and Affiliation). If an author’s last name is not “Kamal” or the author does not have affiliation data, no row is created for the author, and xtract skips to the next author.

The command creates two columns for each row: one with the author’s last name and initials (-element LastName,Initials) separated with a single space (-sep " "), and one with the author’s affiliation data (Affiliation).
Include only PubMed records indexed with the MeSH heading “Microcephaly”, and with any MeSH heading containing the words “Zika Virus” in the output table

    efetch -db pubmed -id 27582188,27417495,27409810,27306170,18142192 -format xml | \
    xtract -pattern PubmedArticle -if DescriptorName -contains "Zika Virus" \
    -and DescriptorName -equals Microcephaly -element MedlineCitation/PMID ArticleTitle

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 27582188,27417495,27409810,27306170,18142192) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

The second line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern argument indicates that we should start a new row for each PubMed record (-pattern PubmedArticle), but only if the record has a <DescriptorName> element that contains the words “Zika Virus” (-if DescriptorName -contains "Zika Virus"), AND a <DescriptorName> element that equals “Microcephaly” (-and DescriptorName -equals Microcephaly). If a record does not have MeSH headings assigned that meet those criteria, no row is created for the author, and xtract skips to the next author. Note that, because of the use of -contains, both the MeSH heading “Zika Virus” and the MeSH heading “Zika Virus Infection” will satisfy the first condition in this command.

The command creates two columns for each row: one with the record’s PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one with the article’s title (-element MedlineCitation/PMID ArticleTitle).
xtract and the -position argument
Include only the First Author in the output table

    efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -position first -sep " " -element LastName,Initials

The first line of this code uses the efetch command to retrieve records from PubMed (-db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957) in XML format (-format xml), and concludes by piping (|) the resulting XML into a command on the next line (the `“\”` character at the end of the line allows us to continue our command on the next line, for easier-to-read formatting).

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle). The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (e.g. as a child of a <CommentsCorrections> element; -element MedlineCitation/PMID).

In the third line, xtract looks through each PubMed record for an <Author> element (-block Author). When it finds the first <Author> (-position first), it populates the second column in the row with the first author’s last name and initials, separated by a space (-sep " " -element LastName,Initials).
Dealing with blanks
Specify a placeholder to replace blank spaces in the output table

    efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -position first -sep " " -def "N/A" -element LastName,Initials Identifier

This series of commands is largely the same as the “Include only the First Author in the output table” example presented above. However, in the third line, we have added the -def argument to specify the placeholder value (“N/A”) for any blank cells in the output table (-def "N/A").
In-class exercise solutions

Note: The first two exercises ask for an xtract command. The solutions below start with efetch commands that retrieve a sample set of PubMed records in XML, which are then piped into the xtract command. This allows us to test and verify the solutions using appropriate sample data.
Exercise 1

Write an xtract command that creates a table with one row per PubMed record, but that only includes PubMed records if they have MeSH headings. Each row should have two columns: PMID and citation status.

**Solution:**

    efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml | \
    xtract -pattern PubmedArticle -if MeshHeading -element MedlineCitation/PMID MedlineCitation@Status

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record contains a <MeshHeading> element (-if MeshHeading). If a record does not have MeSH headings attached, no row is created for the record, and xtract skips to the next record.

For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one with the record’s citation status (-element MedlineCitation/PMID MedlineCitation@Status).

Exercise 2

Write an xtract command that creates a table with one row per PubMed record, but that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.). Each row should have two columns: PMID and journal title abbreviation.

**Solution:**

    efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml | \
    xtract -pattern PubmedArticle -if ISOAbbreviation -starts-with JAMA -element MedlineCitation/PMID ISOAbbreviation

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record has a journal title abbreviation that begins with “JAMA” (-if ISOAbbreviation -starts-with JAMA).

For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one with the article’s journal title abbreviation (-element MedlineCitation/PMID ISOAbbreviation).
Exercise 3

Write a series of commands that generates a list of the different affiliation data used by author BH Smith between 2012 and 2017. The script should output the PMID for each article published by BH Smith in that time frame, along with the BH Smith’s affiliation data for each article.

**Solution:**

    esearch -db pubmed -query "smith bh[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \
    efetch -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -if LastName -equals Smith -and Initials -equals BH -element LastName,Initials Affiliation

This series of commands searches for publications by the author BH Smith that were published between 2012 and 2017, retrieves the full XML records for each of the search results, extracts the PMID and BH Smith’s affiliation data from each record, and displays the results in a table.

    esearch -db pubmed -query "smith bh[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 | \

The first line of code uses esearch to search PubMed (-db pubmed) for articles where “smith bh” is the author (-query "smith bh[Author]"). The line also restricts the search results to articles that were published between 2011 and 2016 (-datetype PDAT -mindate 2012 -maxdate 2017).

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format xml | \

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

    xtract -pattern PubmedArticle -element MedlineCitation/PMID \

Beginning on the third line, the xtract command creates a table with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with three columns. The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (e.g. as a child of a <CommentsCorrections> element).

    -block Author -if LastName -equals Smith -and Initials -equals BH -sep " " -element LastName,Initials Affiliation

The xtract command continues on the fourth line by checking each <Author> element in a PubMed record (-block Author). If a given author’s <LastName> is Smith AND <Initials> are BH (-if LastName -equals Smith -and Initials -equals BH), the xtract command populates the second column with the author’s last name and initials (separated by a space), and the third column with the author’s affiliation (-sep " " -element LastName,Initials Affiliation). Outputting the last name and initials into the second column is slightly redundant, as we know that they will always be “Smith BH”. However, it is helpful as a confirmation that our Conditional arguments are correct.
Homework solutions

Question 1

Fetch the records for the following list of PMIDs:

    28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139

Write an xtract command that outputs the PMID and Article Title, but only for records that have a structured abstract. Hint: in PubMed records, structured abstracts are broken up into multiple AbstractText elements, each with their own “NlmCategory” attribute.

**Solution:**

    efetch -db pubmed -id 28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139 -format xml | \
    xtract -pattern PubmedArticle -if AbstractText@NlmCategory -element MedlineCitation/PMID ArticleTitle

The first line of this solution uses efetch to retrieve several records from PubMed in XML format.

The `“|”` character pipes the results of our efetch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

This xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), but only if the record has one or more “AbstractText” elements that contain an “NlmCategory” attribute (-if AbstractText@NlmCategory). This will ensure that only PubMed records with structured abstracts are included.

For each row in the output, xtract creates two columns: one with the record’s PMID (specifically, the contents of the <PMID> element that is a child of the <MedlineCitation> element), one with the article title (-element MedlineCitation/PMID ArticleTitle).

Question 2

Modify your command from Question 1 to display the “RESULTS” section of each structured abstract, if there is one, in place of the Article Title. If there is no “RESULTS” section, display just the PMID, leaving the second column blank. Hint: Use the “NlmCategory” attribute to determine whether a particular AbstractText element contains “RESULTS”.

**Solution:**

    efetch -db pubmed -id 28197844,28176235,28161874,28183232,28164731,27937077,28118756,27845598,27049596,27710139 -format xml | \
    xtract -pattern PubmedArticle -if AbstractText@NlmCategory -element MedlineCitation/PMID \
    -block AbstractText -if AbstractText@NlmCategory -equals RESULTS -element AbstractText

This solution begins the same as the solution for Question 2. However, rather than including the article title in the first -element argument, the xtract command continues on the third line (with the `“\”` character at the end of the second line allowing us to continue our string of commands on the next line, for easier-to-read formatting.

    -block AbstractText -if AbstractText@NlmCategory -equals RESULTS -element AbstractText

In the third line, the command uses -block to look for an <AbstractText> element (-block AbstractText), then looks within that <AbstractText> element to see if it has an “NlmCategory” attribute with the value “RESULTS” (-if AbstractText@NlmCategory -equals RESULTS). If it does, the command then outputs the contents of the <AbstractText> element in the second column. If the <AbstractText> element does not have an “NlmCategory” with the value “RESULTS”, the command proceeds to check the next <AbstractText> element in the record. The process repeats for each <AbstractText> element in the record.

Question 3

When indexing a record for MEDLINE, indexers can assign MeSH headings (descriptors) to represent concepts found in an article, and MeSH subheadings (qualifiers) to describe a specific aspect of a concept. Indexers denote some of MeSH headings as “Major Topics” (i.e. one of the primary topics of the article). When assigning a “Major Topic”, the indexer can determine that heading itself is a major topic, or that a specific heading/subheading pair is a major topic. When a heading/subheading pair is assigned as a Major Topic, only the subheading will be labeled as Major in the PubMed XML.

Write an xtract command that outputs one PubMed record per row. Each row should have the record’s PMID and a pipe-delimited list of all of the MeSH Headings the indexers have determined are Major Topics. Note: the list should only include headings (descriptors), not subheadings (qualifiers). However, if a heading/subheading pair is assigned as major, the list should include that heading.

You can use the following efetch command to retrieve some sample records:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \

**Solution:**

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block MeshHeading -if DescriptorName@MajorTopicYN -equals Y -or QualifierName@MajorTopicYN -equals Y \
    -tab "|" -element DescriptorName

This solution uses the example efetch command to retrieve three PubMed records in XML, then outputs a table with one row per PubMed record. Each row begins with the record’s PMID, followed by a pipe-delimited list of all of the MeSH Headings that the indexers have determined are Major Topics.

    xtract -pattern PubmedArticle -element MedlineCitation/PMID \

Beginning on the second line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle) with the record’s PMID (-element MedlineCitation/PMID) and additional data, which is specified on the subsequent lines.

    -block MeshHeading -if DescriptorName@MajorTopicYN -equals Y -or QualifierName@MajorTopicYN -equals Y \

In the third line, we start to check each <MeshHeading> element to determine if it has been labeled Major. The command uses -block to look for the first <MeshHeading> element in the record (-block MeshHeading). The command then looks within that <MeshHeading> element to see if its child <DescriptorName> element has a “MajorTopicYN” attribute with a value of “Y” (-if DescriptorName@MajorTopicYN -equals Y), or if any of its child <QualifierName> elements have a “MajorTopicYN” attribute with a value of “Y” (-or QualifierName@MajorTopicYN -equals Y). If either of these are true, the MeSH heading has been labeled as a Major Topic, and the command will continue on the next line (see below). If neither of these conditions are true, the command will proceed to the next <MeshHeading> element and repeat the process, looking for MeSH Headings which are Major Topics.

    -tab "|" -element DescriptorName

The fourth line specifies that the DescriptorName will appear in the second column of our table (-element DescriptorName). Each indexed record will have at least one Major Topic assigned, and probably more than one. We use the -tab argument to specify a separator between the multiple MeSH descriptors (-tab "|"). It is important to place the -tab argument after the -block, as -block resets any -tab arguments that have been previously specified. We use -tab instead of -sep, as -block automatically creates a new column at the end of each block, so by specifying `“|”` in our -tab argument, we insure that our blocks are pipe-delimited.

Question 4

Write a series of commands to search for articles reporting on clinical trials relating to tularemia and output a table of citations. Each row should include the PMID for an article, as well as the name and affiliation information (if any) for the last author. If the last author does not have affiliation information, put “Not Available” in the last column instead.

**Solution:**

    esearch -db pubmed -query "tularemia clinical trial" | \
    efetch -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -position last -sep " " -def "Not Available" -element LastName,Initials Affiliation

This solution of commands searches PubMed for the string “tularemia clinical trial”, retrieves the full XML records and outputs the PMID as well as the last name, initials affiliation information (if any) of each article’s last author.

    esearch -db pubmed -query "tularemia clinical trial" | \

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "tularemia clinical trial").

The `“|”` character pipes the results of our esearch into our next command, and the `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    efetch -format xml | \

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

    -pattern PubmedArticle -element MedlineCitation/PMID \

Beginning on the third line, the xtract command creates a table, with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle) with the record’s PMID (-element MedlineCitation/PMID) and additional data, which is specified on the subsequent lines.

    -block Author -position last -sep " " -def "Not Available" -element LastName,Initials Affiliation

The fourth line uses the -block and -position arguments to identify the last <Author> element in each record (-block Author -position last). The last name and initials of the last author, separated by a space (-sep " "), are placed in the second column, with the last author’s affiliation information (if present) is placed in the third column (-element LastName,Initials Affiliation). If the last author has no affiliation information, the third column will contain the default value of “Not Available” instead of being left blank (-def "Not Available")

### Part Four

https://dataguide.nlm.nih.gov/edirect-for-pubmed-4.txt

----------------------------------------------------------------------
The Insider's Guide to Accessing NLM Data: EDirect for PubMed
Part Four: xtract Conditional Arguments
Course Materials


NOTE: Solutions to all exercises are at the bottom of this document.



REMINDERS FROM PART ONE

esearch: Searches a database and returns PMIDs

efetch: Retrieves PubMed records in a variety of formats

Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next



REMINDERS FROM PART TWO

xtract: Pulls data from XML and arranges it in a table

-pattern: Defines rows for xtract

-element: Defines columns for xtract

Identify XML elements by name (e.g. ArticleTitle)

Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID)

Identify attributes with "@" (e.g. MedlineCitation@Status)



REMINDERS FROM PART THREE

-block: Selects and groups child elements of the same parent

-tab: Defines the separator between columns (default is tab, "\t")

-sep: Defines the separator between values in the same column (default is tab, "\t")

Use ">" to save the output to a file

Use "cat" to pull the contents of a file into the EDirect command

epost: Stores PMIDs to the History Server



TIPS FOR CYGWIN USERS:

Ctrl + C does not Copy
(Cygwin default for Copy is Ctrl + Insert)

Ctrl + V does not Paste
(Cygwin default for Paste is Shift + Insert)




TIPS FOR ALL USERS:

Ctrl + C "cancels" and gets you back to a prompt

Up and Down arrow keys allow you to cycle through your recent commands

clear: clears your screen



If-Then

If the condition is met...
Then, create a new row for the pattern and populate the specified columns.
(If not, skip the pattern and move on to the next one.)



-if

COMMAND STRING:

    efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml

    efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml | \
    xtract -pattern Author -sep " " -element LastName,Initials Identifier

    efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml | \
    xtract -pattern Author -if Identifier -sep " " -element LastName,Initials Identifier



EXERCISE 1:

Write an xtract command that only includes PubMed records if they have MeSH headings
*	One row per PubMed record
*	Two columns: PMID, Citation Status
Hint: Use this efetch to test:


    efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml | \



-if/-equals

COMMAND STRING:

    efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
    xtract -pattern PubmedArticle -if ISOAbbreviation -equals JAMA -element Volume Issue



-if/-equals: Attributes

COMMAND STRING:

    efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
    xtract -pattern PubmedArticle -if MedlineCitation@Status -equals MEDLINE \
    -element MedlineCitation/PMID



Alternatives to -equals

-contains: Element or attribute contains this string
-starts-with: Element or attribute starts with this string
-ends-with: Element or attribute ends with this string
-is-not: Element or attribute does not match this string



-if/-contains

COMMAND STRING:

    efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \
    xtract -pattern Author -if Affiliation -contains Japan \
    -sep " " -element LastName,Initials Affiliation




EXERCISE 2:
Write an xtract command that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.)
*	One row per PubMed record
*	Two Columns: PMID, ISOAbbreviation
*	ISOAbbreviation should start with "JAMA"
Hint: Use this efetch to test:


    efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml | \




-if in a -block

COMMAND STRING:

    efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block ArticleId -if ArticleId@IdType -equals doi -element ArticleId




Combining multiple conditions

-or: at least one condition must be true

-and: all conditions must be true




-or

COMMAND STRING:

    efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block ArticleId -if ArticleId@IdType -equals doi \
    -or ArticleId@IdType -equals pmc -element ArticleId




-and

COMMAND STRING:

    efetch -db pubmed -id 27798514,24372221,24332497,24307782 -format xml | \
    xtract -pattern Author -if LastName -equals Kamal -and Affiliation \
    -sep " " -element LastName,Initials Affiliation


    efetch -db pubmed -id 27582188,27417495,27409810,27306170,18142192 -format xml | \
    xtract -pattern PubmedArticle -if DescriptorName -contains "Zika Virus" \
    -and DescriptorName -equals Microcephaly -element MedlineCitation/PMID ArticleTitle




EXERCISE 3
We want to do a search for author BH Smith, and see the different affiliations that are listed for that author
*	Limit to publications from 2012 through 2017

We only want to see affiliation data for BH Smith, no other authors.

We want our output to be a table of citations with specific data:
*	PMID
*	Author Last Name/Initials (should always be BH Smith)
*	Affiliation Data

Write the whole script (not just the xtract command).




-position

Include a -block based on its position:

    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -position first -sep " " -element LastName,Initials

Use -position with an integer, "first" or "last":

-position 3

-position first

-position last

COMMAND STRING:

    efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -sep " " -element LastName,Initials


    efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -position first -sep " " -element LastName,Initials


    efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -position last -sep " " -element LastName,Initials



Dealing with blanks

Use -def to define a placeholder to replace blank cells

Placement for -def is the same as for -tab/-sep.
*	Subsequent -def arguments overwrite earlier ones.
*	-block arguments clear previous -def arguments.

COMMAND STRING:

    efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -position first -sep " " -element LastName,Initials Identifier

    efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -position first -sep " " -def "N/A" -element LastName,Initials Identifier


HOMEWORK FOR PART FOUR

(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode4.html)


Question 1: 

Fetch the records for the following list of PMIDs:

    28197844
    28176235
    28161874
    28183232
    28164731
    27937077
    28118756
    27845598
    27049596
    27710139

Write an xtract command that outputs the PMID and Article Title, but only for records that have a structured abstract. Hint: in PubMed records, structured abstracts are broken up into multiple AbstractText elements, each with their own "NlmCategory" attribute.


Question 2:

Modify your command from Question 1 to display the "RESULTS" section of each structured abstract, if there is one, in place of the Article Title. If there is no "RESULTS" section, display just the PMID, leaving the second column blank. Hint: Use the "NlmCategory" attribute to determine whether a particular AbstractText element contains "RESULTS".


Question 3:

When indexing a record for MEDLINE, indexers can assign MeSH headings (descriptors) to represent concepts found in an article, and MeSH subheadings (qualifiers) to describe a specific aspect of a concept. Indexers denote some of the assigned MeSH headings as "Major Topics" (i.e. one of the primary topics of the article). When assigning a "Major Topic", the indexer can determine that the heading itself is a major topic, or that a specific heading/subheading pair is a major topic. When a heading/subheading pair is assigned as a Major Topic, only the subheading will be labeled as Major in the PubMed XML.

Write an xtract command that outputs one PubMed record per row. Each row should have the record's PMID and a pipe-delimited list of all of the MeSH Headings the indexers have determined are Major Topics. Note: the list should only include headings (descriptors), not subheadings (qualifiers). However, if a heading/subheading pair is assigned as major, the list should include that heading. 

You can use the following efetch command to retrieve some sample records:

    efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \



Question 4:

Write a series of commands to search for articles reporting on clinical trials relating to tularemia and output a table of citations. Each row should include the PMID for an article, as well as the name and affiliation information (if any) for the last author. If the last author does not have affiliation information, put "Not Available" in the last column instead.

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EXERCISE SOLUTIONS:
-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-
EXERCISE 1:
Write an xtract command that only includes PubMed records if they have MeSH headings
*	One row per PubMed record
*	Two columns: PMID, Citation Status
Hint: Use this efetch to test:


    efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml

**Solution:**

    efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml | \
    xtract -pattern PubmedArticle -if MeshHeading \
    -element MedlineCitation/PMID MedlineCitation@Status

-=-=-=-=-=-=-=-=-=-=-=-=-
EXERCISE 2:
Write an xtract command that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.)
*	One row per PubMed record
*	Two Columns: PMID, ISOAbbreviation
*	ISOAbbreviation should start with "JAMA"

efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml

**Solution:**

    efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml | \
    xtract -pattern PubmedArticle -if ISOAbbreviation -starts-with JAMA \
    -element MedlineCitation/PMID ISOAbbreviation

-=-=-=-=-=-=-=-=-=-=-=-=-
EXERCISE 3
We want to do a search for author BH Smith, and see the different affiliations that are listed for that author
*	Limit to publications from 2012 through 2017

We only want to see affiliation data for BH Smith, no other authors.

We want our output to be a table of citations with specific data:
*	PMID
*	Author Last Name/Initials (should always be BH Smith)
*	Affiliation Data

Write the whole script (not just the xtract command).

**Solution:**

    esearch -db pubmed -query "smith bh[Author]" \
    -datetype PDAT -mindate 2012 -maxdate 2017 | \
    efetch -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID \
    -block Author -if LastName -equals Smith -and Initials -equals BH -sep " " -element LastName,Initials Affiliation



## Part Five "EDirect for PubMed: Part 5: Developing and Building Scripts" Sample Code

### Part Five

https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode5.html


Case study

Retrieve a list of articles published in between March 1, 2017 and February 28, 2018 about breast cancer that include clinical trial information from ClinicalTrials.gov. Include the PMID, journal title abbreviation, first author’s last name and initials, and ClinicalTrials.gov NCT number(s) for each record. Save the entire output to a text file.

**Solution**

    esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \
    -datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 | \
    efetch -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \
    -block Author -position first -sep " " -element LastName,Initials \
    -block DataBank -if DataBankName -equals ClinicalTrials.gov \
    -sep "|" -element AccessionNumber > clinicaltrials.txt

Discussion

    esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "breast cancer AND clinicaltrials.gov[si]"). The “clinicaltrials.gov[si]” portion of the query ensures that only records with ClinicalTrials.gov NCT numbers are included in our results. The `“\”` character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

    -datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 | \

The second line restricts the search results to articles that were published between March 1, 2017 and February 28, 2018 (-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28). The `“|”` character pipes the results of our esearch into our next command.

    efetch -format xml | \

The third line takes the esearch results from our first two lines and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

    xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \

Beginning on the fourth line, the xtract command creates a table with each PubMed record in our input populating its own row (xtract -pattern PubmedArticle), and with four columns. The first column of each row will contain the record’s PMID, using Parent/Child construction to specify that we want the <PMID> element that is the child of the <MedlineCitation> element, and not another <PMID> element elsewhere in the PubMed record (e.g. as a child of a <CommentsCorrections> element), while the second column will contain the article’s journal title abbreviation (-element MedlineCitation/PMID ISOAbbreviation).

    -block Author -position 1 -sep " " -element LastName,Initials \

In the fifth line, xtract looks through each PubMed record for an <Author> element (-block Author). When it finds the first <Author> (-position 1), it populates the third column in the row with the first author’s last name and initials, separated by a space (-sep " " -element LastName,Initials).

    -block DataBank -if DataBankName -equals ClinicalTrials.gov \

In the sixth line, xtract looks through each PubMed record for <DataBank> elements which have a child <DataBankName> element that equals “ClinicalTrials.gov” (-block DataBank -if DataBankName -equals ClinicalTrials.gov). This will ensure that only ClinicalTrials.gov data is included, while data from non-ClinicalTrials.gov <DataBank> elements is excluded.

    -sep "|" -element AccessionNumber > clinicaltrials.txt

In the seventh line, xtract specifies that the fourth column should be populated with the <AccessionNumber> (i.e. NCT number) from the included <DataBank> elements (-element AccessionNumber). If a record has multiple NCT numbers attached, they will be separated by pipes (-sep "|").

Finally, the results of the script are saved to a file (> clinicaltrials.txt).

### Part Five

https://dataguide.nlm.nih.gov/edirect-for-pubmed-5.txt



The Insider's Guide to Accessing NLM Data: EDirect for PubMed
Part Five: Developing and Building Scripts
Course Materials

NOTE: Solutions to all exercises are at the bottom of this document.



REMINDERS FROM PART ONE

esearch: Searches a database and returns PMIDs

efetch: Retrieves PubMed records in a variety of formats

Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next



REMINDERS FROM PART TWO

xtract: Pulls data from XML and arranges it in a table

-pattern: Defines rows for xtract

-element: Defines columns for xtract

Identify XML elements by name (e.g. ArticleTitle)

Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID)

Identify attributes with "@" (e.g. MedlineCitation@Status)



REMINDERS FROM PART THREE

-block: Selects and groups child elements of the same parent

-tab: Defines the separator between columns (default is tab, "\t")

-sep: Defines the separator between values in the same column (default is tab, "\t")

Use ">" to save the output to a file

Use "cat" to pull the contents of a file into the EDirect command

epost: Stores PMIDs to the History Server



REMINDERS FROM PART FOUR

-if: Defines an element/attribute that must be present in order to include a pattern/block.
(e.g. "If <element> is present in the pattern/block, include pattern/block in the output.")

-if/-equals: Defines a specific element/attribute that must be equal to a specific value in order to include a pattern/block,
(e.g. "If an <element> equals [value] in the pattern/block, include pattern/block in the output.")


Alternatives to -equals: let you define more specific conditions
-contains: Element or attribute must contain this string
-starts-with: Element or attribute must start with this string
-ends-with: Element or attribute must end with this string
-is-not: Element or attribute must not match this string


Alternatives to -if: let you combine multiple conditions
-or: at least one condition must be true
-and: all conditions must be true


-position: Includes a block based on its position in a series of blocks.
Use -position with an integer, "first" or "last":



Tips for Developing a Script

1. Identify your goal.
	* Identify your input
	* Identify your output
	* Identify your format
2. Choose your tool.
3. Decide how much to automate.
4. Build one step at a time.



E-utilities Usage Guidelines and Requirements from NCBI
https://www.ncbi.nlm.nih.gov/books/NBK25497/#chapter2.Usage_Guidelines_and_Requiremen

NLM Data Distribution: Download MEDLINE/PubMed Data
https://www.nlm.nih.gov/databases/download/pubmed_medline.html

Using EDirect to create a local copy of PubMed
https://dataguide.nlm.nih.gov/edirect/archive.html

NCBI Documentation: EDirect: Local Data Cache
https://www.ncbi.nlm.nih.gov/books/NBK179288/#chapter6.Local_Data_Cache

----------------------------------------------------------------------

Case 1: Simple table of data elements

We want a list of articles about breast cancer that were published in 2016 and the first half of 2017 and are linked to ClinicalTrials.gov entries.

For each article we want:
*	PMID
*	NCT Number(s)
*	First Author
*	Journal

----------------------------------------------------------------------

Case Study

COMMAND STRING:

    esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]"
    
    esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \
    -datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28
    
    esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \
    -datetype PDAT -mindate 2018/01/01 -maxdate 2018/02/28
    
    efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml
    
    efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation
    
    efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \
    -block Author -position first -sep " " -element LastName,Initials
    
    efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \
    -block Author -position first -sep " " -element LastName,Initials \
    -block DataBank -if DataBankName -equals ClinicalTrials.gov \
    -sep "|" -element AccessionNumber

CASE STUDY **Solution:**

    esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \
    -datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 | \
    efetch -format xml | \
    xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \
    -block Author -position first -sep " " -element LastName,Initials \
    -block DataBank -if DataBankName -equals ClinicalTrials.gov \
    -sep "|" -element AccessionNumber > clinicaltrials.txt

----------------------------------------------------------------------

EDirect Cookbook on GitHub
https://ncbi-hackathons.github.io/EDirectCookbook/






# Materials and Methods Used For This Analyses

## The Insider's Guide to Accessing NLM Data

### "Welcome to E-utilities for PubMed" Class Materials
https://dataguide.nlm.nih.gov/classes/intro/materials.html

> Webinar Recording
> https://dataguide.nlm.nih.gov/classes/intro/recording.html

> "Welcome to E-utilities for PubMed" Sample Code for Class Exercises
> https://dataguide.nlm.nih.gov/classes/intro/samplecode.html


> Entrez Programming Utilities Help
> https://www.ncbi.nlm.nih.gov/books/NBK25501/

> Entrez Direct: E-utilities on the UNIX Command Line
> https://www.ncbi.nlm.nih.gov/books/NBK179288/

### Installing EDirect
https://dataguide.nlm.nih.gov/edirect/install.html



### The 9 E-utilities and Associated Parameters
https://dataguide.nlm.nih.gov/eutilities/utilities.html


+ + +
+
+ +
+ + + + + + + + diff --git a/e-utilities-lecture-notes/RJ-2017-058.zip b/e-utilities-lecture-notes/RJ-2017-058.zip new file mode 100644 index 0000000..ed01205 Binary files /dev/null and b/e-utilities-lecture-notes/RJ-2017-058.zip differ diff --git a/e-utilities-lecture-notes/Untitled.sh b/e-utilities-lecture-notes/Untitled.sh new file mode 100644 index 0000000..39064fe --- /dev/null +++ b/e-utilities-lecture-notes/Untitled.sh @@ -0,0 +1 @@ +esearch -version diff --git a/e-utilities-lecture-notes/Untitled2.sh b/e-utilities-lecture-notes/Untitled2.sh new file mode 100644 index 0000000..d2edefc --- /dev/null +++ b/e-utilities-lecture-notes/Untitled2.sh @@ -0,0 +1 @@ +esearch -db pubmed -query "seasonal affective disorder" \ No newline at end of file diff --git a/e-utilities-lecture-notes/Using EDirect to create a local copy of PubMed.Rmd b/e-utilities-lecture-notes/Using EDirect to create a local copy of PubMed.Rmd new file mode 100644 index 0000000..a091376 --- /dev/null +++ b/e-utilities-lecture-notes/Using EDirect to create a local copy of PubMed.Rmd @@ -0,0 +1,137 @@ +--- +title: "Using EDirect to create a local copy of PubMed" +output: html_notebook +--- + + +https://dataguide.nlm.nih.gov/edirect/archive.html + + + +Using EDirect to create a local copy of PubMed + +This documentation reflects EDirect version 8.00, released on 2/26/2018. + +We strive to keep this documentation up-to-date with the latest release. If you are looking for documentation on a more recent version of EDirect, or to find out more about new EDirect releases, please see the Release Notes of NCBI's EDirect documentation. + +EDirect is designed to help you get the PubMed data you need, and only the PubMed data you need, in the exact format you specify. You can use esearch to search for PubMed records, efetch to download records in XML, and xtract to output the specific data elements you need. + +But what if you need a lot of data? + +If you are trying to download tens or hundreds of thousands of PubMed records, you may find that the downloading process takes an impractically long time (especially during peak hours). Additionally, if your job is very large, you may run afoul of the E-utilities Usage Guidelines and Requirements. + +For users who routinely use EDirect to retrieve very large sets of PubMed records, NCBI has introduced a new tool and technique that lets you create your own local copy of PubMed, which may speed up the process of bulk retrieval substantially. Newer versions of EDirect (starting with version 8.00) include a suite of scripts and commands that help you: + + download the entirety of PubMed through the NLM Data Distribution program, + extract and de-duplicate individual PubMed records, + create a local archive of PubMed, and + retrieve large sets of PubMed records from your local archive for use by xtract. + +Note: This technique is only recommended for advanced EDirect users, who have some prior experience working in Unix. Creating and using a local PubMed archive does require certain minimum hardware specifications and technical expertise, and initial setup can take some time. However, once the archive is created, you will be able to retrieve records from the archive much faster than you can using traditional efetch. Exact speeds will vary based on your hardware and software configuration, but tests of retrieving records from a properly configured archive have shown speeds of 3,000 or more records per second (compared to about 50 records per second using traditional efetch). +System Requirements +A current version of EDirect + +The archive creation process relies on scripts and commands included in EDirect version 8.00 and later. If you do not yet have EDirect installed, please see our installation page. If you already have EDirect installed, you can check your current version using our testing script. If your version is earlier than 8.00, you can update your installation by re-installing EDirect using our installation script. +A Solid State Drive (SSD) + +Creating and retrieving from a PubMed archive is only practical on a Solid State Drive (SSD). The techniques described below will technically work on a spinning-disk hard drive, but at speeds so slow as to render the process impractical. An external SSD will work fine, though you will see even greater speed increases with an internal SSD. Currently, an external SSD of 250 GB or more should be more than sufficient to hold a complete PubMed archive (though larger drives may be necessary in the future, as PubMed continues to grow). +Recommended: MacOS 10.13 + +When building a local PubMed archive, the EDirect scripts build a hierarchy of 1 million folders to organize the 28 million records. While you can create and use a PubMed archive in any Unix-like environment that can run EDirect (including the MacOS terminal, a Cygwin emulator on a Windows computer, a Linux machine, etc.), the process is designed to take advantage of the new APFS file system, available in MacOS version 10.13 and later, which is specifically built to work with gigantic folder hierarchies. Using other file systems (like NTFS) will certainly work, but the speed benefits may not be as great. +Before you begin +Format your archive drive + +Starting with a freshly formatted SSD will help ensure the archive creation process goes smoothly. If you are using MacOS 10.13 or later, format your drive using the new APFS file system. If you are using another operating system, make sure you are using the NTFS file system, with a cluster size (also sometimes called an “allocation unit size”) of 4 KB. Formatting with a different cluster size will have an impact on performance, and on the space required to hold the completed archive: increasing the cluster size increases speed and required disk space, while decreasing the cluster size decreases speed and required disk space. +Set aside some time + +Depending on the configuration of your system, building the archive may take quite a while. Downloading the baseline and update files for the first time could take several hours, while the creation of the archive could take anywhere from two to more than thirty hours, depending on your hardware. Fortunately, the full archive creation process only needs to be executed once a year, and can be interrupted and restarted at any time. +Building the archive + +Building a local archive of PubMed takes several steps, but the archive-pubmed command, included in EDirect versions 8.00 and later, automatically performs each of the necessary steps in the correct order. From your Unix terminal, execute the following command: + +archive-pubmed -path /Volumes/myssd + +This starts the process of building the local archive in the directory /Volumes/myssd (replace the /Volumes/myssd with the directory on your SSD where you would like to hold your archive). The archive-pubmed command then performs the following steps: + + Creates subdirectories of /Volumes/myssd to store the archive, as well as the raw baseline and update files which will be used to build the archive. + Analyzes your system and displays messages to suggest steps you can take to improve the archive creation process. + Downloads all of the baseline and update files from the NLM Data Distribution FTP server and saves them in the /Volumes/myssd/Pubmed subdirectory. + Opens each baseline file in turn, decompresses the XML file contained within, and extracts each individual PubMed record into its own, individual XML file. These individual record XML files are then re-compressed and saved into a new directory structure (within the /Volumes/myssd/Archive subdirectory) which is built to facilitate rapid access. + Opens each update file in turn, processing them like the baseline files, overwriting previous versions of a PubMed record with newer ones, and deleting records from your archive which have been deleted from PubMed. + +As this command finishes processing each baseline and update file, it creates a sentinel file as a flag to indicate which files have already been processed. If the archive-pubmed command is interrupted in the middle, simply execute the command again to restart it; the sentinel files will automatically indicate where to start back up again. + +Note: while the archive-pubmed command is processing update files, you may occasionally see error messages that look like this: + +rm: cannot remove 'XX/XX/XX/XXXXXXXX.xml.gz': No such file or directory + +These messages occur when an update file contains a delete message for a record that is not yet in your archive. This will happen when a PubMed record was created in error, then deleted on the same day. These messages can be ignored. +Maintaining the archive +Updating an archive with the latest files + +New update files are released to the FTP server on a daily basis. To make sure your local archive mirrors the current state of the PubMed database as closely as possible, you will want to update your local archive before attempting any major projects. To do this, simply re-run the archive-pubmed command (substituting /Volumes/myssd with the directory that contains your archive): + +archive-pubmed -path /Volumes/myssd + +This should only take a few minutes, as it will only need to download the new update files and add those records to your archive. +Re-archive for the new baseline + +Once a year, usually around late November, NLM releases a new set of baseline files. These files are updated to reflect changes in the PubMed DTD, and any changes to the MeSH terminology for the new year. Once the new baseline is released, you will need to rebuild your archive from the ground up in order to make sure your archive reflects the current state of the PubMed database. + +Before rebuilding your archive, make sure you delete the entire contents of the directory that contains your archive and the downloaded baseline and update files (i.e. /Volumes/myssd). The easiest way to accomplish this is to reformat your SSD as described above, which will delete the entire archive in minutes instead of hours. Even if you do delete your archive in a different way, it is probably a good idea to reformat your SSD as described above before trying to build your new archive. Once your drive is ready, follow the steps above to build the archive from the new baseline files. +Retrieving from the archive +Retrieve records based on a list of PMIDs + +If you have a list of PMIDs saved in a file, you can retrieve the full XML for all of those records from your archive by using the fetch-pubmed command. Remember to replace Volumes/myssd/Archive with the directory that contains your archive. + +cat lycopene.txt | \ +fetch-pubmed -path /Volumes/myssd/Archive > lycopene.xml + +This will save the full XML records for all of the PMIDs listed in the file lycopene.txt to the file lycopene.xml. +Retrieve records based on a PubMed search + +Other EDirect commands are completely interoperable with the archive. You can use esearch to find relevant records in the live PubMed database using the normal search algorithm, but retrieve the records from your local archive using fetch-pubmed. Remember to replace Volumes/myssd/Archive with the directory that contains your archive. + +esearch -db pubmed -query "breast cancer" | \ +efetch -format uid | \ +fetch-pubmed -path /Volumes/myssd/Archive > breastcancer.xml + +The first line of this script uses esearch to search the PubMed database for the query “breast cancer.” The esearch command uses the E-utilities API to search the live PubMed database. + +The second line uses efetch -format uid to retrieve the PMIDs for all of the records that matched the search criteria from our initial search. Rather than retrieving full XML records for all of these records, we are only retrieving the PMIDs, which takes much less time. + +Our third line receives the PMIDs piped in from the second line and retrieves full XML records for each of the PMIDs from the local archive, and saves the resulting XML to a file. +Extract specific elements from a group of archived records + +You can pipe the output of a fetch-pubmed command into xtract just as you would with efetch. Remember to replace Volumes/myssd/Pubmed with the directory that contains your archive. + +esearch -db pubmed -query "breast cancer" | \ +efetch -format uid | \ +fetch-pubmed -path /Volumes/myssd/Archive | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation Volume Issue PubDate/Year + +Additional Information +Differences between your local archive and PubMed + +As explained above, the local archive is based on the export files from the NLM Data Distribution program. While export files closely mirror the contents of the live PubMed database, there are a few categories of records which are not included in the exports. As a result, while your local PubMed archive should be a very close match to the live PubMed database, there are likely to be a few discrepancies: + + The local archive will not contain the small number of records in PubMed (approximately 13,000) for books and book chapters. + For the small number of versioned citations in PubMed (approximately 800), the local archive will contain only the most recent version. + +You can find a good representation of the contents of your local archive by searching PubMed (using either the web version of PubMed or esearch) for the following string: + +all[sb] NOT pmcbook NOT ispreviousversion + +(In fact, if you are retrieving records based on a PubMed search using esearch, you may find it useful to add “NOT pmcbook NOT ispreviousversion” to the end of your search string. This will minimize the number of absent records fetch-pubmed attempts to retrieve.) + +Additionally, you may see some further discrepancies, depending on when you update your local archive and when you search. New records are being added to PubMed all the time by publishers submitting citation data. However, the indexes that power PubMed search are updated once a day (usually around 6 AM ET), and new export files are only generated once a day (usually around 2 PM ET). As a result, even a completely up-to-date local archive may include a handful of records that are not yet included in the PubMed search indexes, or vice versa. +Set an environment variable to save time + +You can make using archive-pubmed and fetch-pubmed commands a little easier by setting up your local archive directory as an environment variable. Add the following line to each user’s .bash_profile configuration file (substituting /Volumes/myssd with the directory that contains your archive): + +export EDIRECT_PUBMED_MASTER=/Volumes/myssd + +After you have set this variable, you can omit the -path argument from both archive-pubmed and fetch-pubmed: These commands will check the environment variable, and know exactly where your local archive is located. +For more information + +Additional information and documentation on the local archiving process can be found on NCBI’s EDirect documentation page, “Entrez Direct: E-utilities on the UNIX Command Line” (look for the section labeled “Local Data Cache”). diff --git a/e-utilities-lecture-notes/Using EDirect to create a local copy of PubMed.nb.html b/e-utilities-lecture-notes/Using EDirect to create a local copy of PubMed.nb.html new file mode 100644 index 0000000..6394a8b --- /dev/null +++ b/e-utilities-lecture-notes/Using EDirect to create a local copy of PubMed.nb.html @@ -0,0 +1,1805 @@ + + + + + + + + + + + + + +Using EDirect to create a local copy of PubMed + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + + + + + + + + + + + +

https://dataguide.nlm.nih.gov/edirect/archive.html

+

Using EDirect to create a local copy of PubMed

+

This documentation reflects EDirect version 8.00, released on 2/26/2018.

+

We strive to keep this documentation up-to-date with the latest release. If you are looking for documentation on a more recent version of EDirect, or to find out more about new EDirect releases, please see the Release Notes of NCBI’s EDirect documentation.

+

EDirect is designed to help you get the PubMed data you need, and only the PubMed data you need, in the exact format you specify. You can use esearch to search for PubMed records, efetch to download records in XML, and xtract to output the specific data elements you need.

+

But what if you need a lot of data?

+

If you are trying to download tens or hundreds of thousands of PubMed records, you may find that the downloading process takes an impractically long time (especially during peak hours). Additionally, if your job is very large, you may run afoul of the E-utilities Usage Guidelines and Requirements.

+

For users who routinely use EDirect to retrieve very large sets of PubMed records, NCBI has introduced a new tool and technique that lets you create your own local copy of PubMed, which may speed up the process of bulk retrieval substantially. Newer versions of EDirect (starting with version 8.00) include a suite of scripts and commands that help you:

+
download the entirety of PubMed through the NLM Data Distribution program,
+extract and de-duplicate individual PubMed records,
+create a local archive of PubMed, and
+retrieve large sets of PubMed records from your local archive for use by xtract.
+

Note: This technique is only recommended for advanced EDirect users, who have some prior experience working in Unix. Creating and using a local PubMed archive does require certain minimum hardware specifications and technical expertise, and initial setup can take some time. However, once the archive is created, you will be able to retrieve records from the archive much faster than you can using traditional efetch. Exact speeds will vary based on your hardware and software configuration, but tests of retrieving records from a properly configured archive have shown speeds of 3,000 or more records per second (compared to about 50 records per second using traditional efetch). System Requirements A current version of EDirect

+

The archive creation process relies on scripts and commands included in EDirect version 8.00 and later. If you do not yet have EDirect installed, please see our installation page. If you already have EDirect installed, you can check your current version using our testing script. If your version is earlier than 8.00, you can update your installation by re-installing EDirect using our installation script. A Solid State Drive (SSD)

+

Creating and retrieving from a PubMed archive is only practical on a Solid State Drive (SSD). The techniques described below will technically work on a spinning-disk hard drive, but at speeds so slow as to render the process impractical. An external SSD will work fine, though you will see even greater speed increases with an internal SSD. Currently, an external SSD of 250 GB or more should be more than sufficient to hold a complete PubMed archive (though larger drives may be necessary in the future, as PubMed continues to grow). Recommended: MacOS 10.13

+

When building a local PubMed archive, the EDirect scripts build a hierarchy of 1 million folders to organize the 28 million records. While you can create and use a PubMed archive in any Unix-like environment that can run EDirect (including the MacOS terminal, a Cygwin emulator on a Windows computer, a Linux machine, etc.), the process is designed to take advantage of the new APFS file system, available in MacOS version 10.13 and later, which is specifically built to work with gigantic folder hierarchies. Using other file systems (like NTFS) will certainly work, but the speed benefits may not be as great. Before you begin Format your archive drive

+

Starting with a freshly formatted SSD will help ensure the archive creation process goes smoothly. If you are using MacOS 10.13 or later, format your drive using the new APFS file system. If you are using another operating system, make sure you are using the NTFS file system, with a cluster size (also sometimes called an “allocation unit size”) of 4 KB. Formatting with a different cluster size will have an impact on performance, and on the space required to hold the completed archive: increasing the cluster size increases speed and required disk space, while decreasing the cluster size decreases speed and required disk space. Set aside some time

+

Depending on the configuration of your system, building the archive may take quite a while. Downloading the baseline and update files for the first time could take several hours, while the creation of the archive could take anywhere from two to more than thirty hours, depending on your hardware. Fortunately, the full archive creation process only needs to be executed once a year, and can be interrupted and restarted at any time. Building the archive

+

Building a local archive of PubMed takes several steps, but the archive-pubmed command, included in EDirect versions 8.00 and later, automatically performs each of the necessary steps in the correct order. From your Unix terminal, execute the following command:

+

archive-pubmed -path /Volumes/myssd

+

This starts the process of building the local archive in the directory /Volumes/myssd (replace the /Volumes/myssd with the directory on your SSD where you would like to hold your archive). The archive-pubmed command then performs the following steps:

+
Creates subdirectories of /Volumes/myssd to store the archive, as well as the raw baseline and update files which will be used to build the archive.
+Analyzes your system and displays messages to suggest steps you can take to improve the archive creation process.
+Downloads all of the baseline and update files from the NLM Data Distribution FTP server and saves them in the /Volumes/myssd/Pubmed subdirectory.
+Opens each baseline file in turn, decompresses the XML file contained within, and extracts each individual PubMed record into its own, individual XML file. These individual record XML files are then re-compressed and saved into a new directory structure (within the /Volumes/myssd/Archive subdirectory) which is built to facilitate rapid access.
+Opens each update file in turn, processing them like the baseline files, overwriting previous versions of a PubMed record with newer ones, and deleting records from your archive which have been deleted from PubMed.
+

As this command finishes processing each baseline and update file, it creates a sentinel file as a flag to indicate which files have already been processed. If the archive-pubmed command is interrupted in the middle, simply execute the command again to restart it; the sentinel files will automatically indicate where to start back up again.

+

Note: while the archive-pubmed command is processing update files, you may occasionally see error messages that look like this:

+

rm: cannot remove ‘XX/XX/XX/XXXXXXXX.xml.gz’: No such file or directory

+

These messages occur when an update file contains a delete message for a record that is not yet in your archive. This will happen when a PubMed record was created in error, then deleted on the same day. These messages can be ignored. Maintaining the archive Updating an archive with the latest files

+

New update files are released to the FTP server on a daily basis. To make sure your local archive mirrors the current state of the PubMed database as closely as possible, you will want to update your local archive before attempting any major projects. To do this, simply re-run the archive-pubmed command (substituting /Volumes/myssd with the directory that contains your archive):

+

archive-pubmed -path /Volumes/myssd

+

This should only take a few minutes, as it will only need to download the new update files and add those records to your archive. Re-archive for the new baseline

+

Once a year, usually around late November, NLM releases a new set of baseline files. These files are updated to reflect changes in the PubMed DTD, and any changes to the MeSH terminology for the new year. Once the new baseline is released, you will need to rebuild your archive from the ground up in order to make sure your archive reflects the current state of the PubMed database.

+

Before rebuilding your archive, make sure you delete the entire contents of the directory that contains your archive and the downloaded baseline and update files (i.e. /Volumes/myssd). The easiest way to accomplish this is to reformat your SSD as described above, which will delete the entire archive in minutes instead of hours. Even if you do delete your archive in a different way, it is probably a good idea to reformat your SSD as described above before trying to build your new archive. Once your drive is ready, follow the steps above to build the archive from the new baseline files. Retrieving from the archive Retrieve records based on a list of PMIDs

+

If you have a list of PMIDs saved in a file, you can retrieve the full XML for all of those records from your archive by using the fetch-pubmed command. Remember to replace Volumes/myssd/Archive with the directory that contains your archive.

+

cat lycopene.txt |
+fetch-pubmed -path /Volumes/myssd/Archive > lycopene.xml

+

This will save the full XML records for all of the PMIDs listed in the file lycopene.txt to the file lycopene.xml. Retrieve records based on a PubMed search

+

Other EDirect commands are completely interoperable with the archive. You can use esearch to find relevant records in the live PubMed database using the normal search algorithm, but retrieve the records from your local archive using fetch-pubmed. Remember to replace Volumes/myssd/Archive with the directory that contains your archive.

+

esearch -db pubmed -query “breast cancer” |
+efetch -format uid |
+fetch-pubmed -path /Volumes/myssd/Archive > breastcancer.xml

+

The first line of this script uses esearch to search the PubMed database for the query “breast cancer.” The esearch command uses the E-utilities API to search the live PubMed database.

+

The second line uses efetch -format uid to retrieve the PMIDs for all of the records that matched the search criteria from our initial search. Rather than retrieving full XML records for all of these records, we are only retrieving the PMIDs, which takes much less time.

+

Our third line receives the PMIDs piped in from the second line and retrieves full XML records for each of the PMIDs from the local archive, and saves the resulting XML to a file. Extract specific elements from a group of archived records

+

You can pipe the output of a fetch-pubmed command into xtract just as you would with efetch. Remember to replace Volumes/myssd/Pubmed with the directory that contains your archive.

+

esearch -db pubmed -query “breast cancer” |
+efetch -format uid |
+fetch-pubmed -path /Volumes/myssd/Archive |
+xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation Volume Issue PubDate/Year

+

Additional Information Differences between your local archive and PubMed

+

As explained above, the local archive is based on the export files from the NLM Data Distribution program. While export files closely mirror the contents of the live PubMed database, there are a few categories of records which are not included in the exports. As a result, while your local PubMed archive should be a very close match to the live PubMed database, there are likely to be a few discrepancies:

+
The local archive will not contain the small number of records in PubMed (approximately 13,000) for books and book chapters.
+For the small number of versioned citations in PubMed (approximately 800), the local archive will contain only the most recent version.
+

You can find a good representation of the contents of your local archive by searching PubMed (using either the web version of PubMed or esearch) for the following string:

+

all[sb] NOT pmcbook NOT ispreviousversion

+

(In fact, if you are retrieving records based on a PubMed search using esearch, you may find it useful to add “NOT pmcbook NOT ispreviousversion” to the end of your search string. This will minimize the number of absent records fetch-pubmed attempts to retrieve.)

+

Additionally, you may see some further discrepancies, depending on when you update your local archive and when you search. New records are being added to PubMed all the time by publishers submitting citation data. However, the indexes that power PubMed search are updated once a day (usually around 6 AM ET), and new export files are only generated once a day (usually around 2 PM ET). As a result, even a completely up-to-date local archive may include a handful of records that are not yet included in the PubMed search indexes, or vice versa. Set an environment variable to save time

+

You can make using archive-pubmed and fetch-pubmed commands a little easier by setting up your local archive directory as an environment variable. Add the following line to each user’s .bash_profile configuration file (substituting /Volumes/myssd with the directory that contains your archive):

+

export EDIRECT_PUBMED_MASTER=/Volumes/myssd

+

After you have set this variable, you can omit the -path argument from both archive-pubmed and fetch-pubmed: These commands will check the environment variable, and know exactly where your local archive is located. For more information

+

Additional information and documentation on the local archiving process can be found on NCBI’s EDirect documentation page, “Entrez Direct: E-utilities on the UNIX Command Line” (look for the section labeled “Local Data Cache”).

+ + +
---
title: "Using EDirect to create a local copy of PubMed"
output: html_notebook
---


https://dataguide.nlm.nih.gov/edirect/archive.html



Using EDirect to create a local copy of PubMed

This documentation reflects EDirect version 8.00, released on 2/26/2018.

We strive to keep this documentation up-to-date with the latest release. If you are looking for documentation on a more recent version of EDirect, or to find out more about new EDirect releases, please see the Release Notes of NCBI's EDirect documentation.

EDirect is designed to help you get the PubMed data you need, and only the PubMed data you need, in the exact format you specify. You can use esearch to search for PubMed records, efetch to download records in XML, and xtract to output the specific data elements you need.

But what if you need a lot of data?

If you are trying to download tens or hundreds of thousands of PubMed records, you may find that the downloading process takes an impractically long time (especially during peak hours). Additionally, if your job is very large, you may run afoul of the E-utilities Usage Guidelines and Requirements.

For users who routinely use EDirect to retrieve very large sets of PubMed records, NCBI has introduced a new tool and technique that lets you create your own local copy of PubMed, which may speed up the process of bulk retrieval substantially. Newer versions of EDirect (starting with version 8.00) include a suite of scripts and commands that help you:

    download the entirety of PubMed through the NLM Data Distribution program,
    extract and de-duplicate individual PubMed records,
    create a local archive of PubMed, and
    retrieve large sets of PubMed records from your local archive for use by xtract.

Note: This technique is only recommended for advanced EDirect users, who have some prior experience working in Unix. Creating and using a local PubMed archive does require certain minimum hardware specifications and technical expertise, and initial setup can take some time. However, once the archive is created, you will be able to retrieve records from the archive much faster than you can using traditional efetch. Exact speeds will vary based on your hardware and software configuration, but tests of retrieving records from a properly configured archive have shown speeds of 3,000 or more records per second (compared to about 50 records per second using traditional efetch).
System Requirements
A current version of EDirect

The archive creation process relies on scripts and commands included in EDirect version 8.00 and later. If you do not yet have EDirect installed, please see our installation page. If you already have EDirect installed, you can check your current version using our testing script. If your version is earlier than 8.00, you can update your installation by re-installing EDirect using our installation script.
A Solid State Drive (SSD)

Creating and retrieving from a PubMed archive is only practical on a Solid State Drive (SSD). The techniques described below will technically work on a spinning-disk hard drive, but at speeds so slow as to render the process impractical. An external SSD will work fine, though you will see even greater speed increases with an internal SSD. Currently, an external SSD of 250 GB or more should be more than sufficient to hold a complete PubMed archive (though larger drives may be necessary in the future, as PubMed continues to grow).
Recommended: MacOS 10.13

When building a local PubMed archive, the EDirect scripts build a hierarchy of 1 million folders to organize the 28 million records. While you can create and use a PubMed archive in any Unix-like environment that can run EDirect (including the MacOS terminal, a Cygwin emulator on a Windows computer, a Linux machine, etc.), the process is designed to take advantage of the new APFS file system, available in MacOS version 10.13 and later, which is specifically built to work with gigantic folder hierarchies. Using other file systems (like NTFS) will certainly work, but the speed benefits may not be as great.
Before you begin
Format your archive drive

Starting with a freshly formatted SSD will help ensure the archive creation process goes smoothly. If you are using MacOS 10.13 or later, format your drive using the new APFS file system. If you are using another operating system, make sure you are using the NTFS file system, with a cluster size (also sometimes called an “allocation unit size”) of 4 KB. Formatting with a different cluster size will have an impact on performance, and on the space required to hold the completed archive: increasing the cluster size increases speed and required disk space, while decreasing the cluster size decreases speed and required disk space.
Set aside some time

Depending on the configuration of your system, building the archive may take quite a while. Downloading the baseline and update files for the first time could take several hours, while the creation of the archive could take anywhere from two to more than thirty hours, depending on your hardware. Fortunately, the full archive creation process only needs to be executed once a year, and can be interrupted and restarted at any time.
Building the archive

Building a local archive of PubMed takes several steps, but the archive-pubmed command, included in EDirect versions 8.00 and later, automatically performs each of the necessary steps in the correct order. From your Unix terminal, execute the following command:

archive-pubmed -path /Volumes/myssd

This starts the process of building the local archive in the directory /Volumes/myssd (replace the /Volumes/myssd with the directory on your SSD where you would like to hold your archive). The archive-pubmed command then performs the following steps:

    Creates subdirectories of /Volumes/myssd to store the archive, as well as the raw baseline and update files which will be used to build the archive.
    Analyzes your system and displays messages to suggest steps you can take to improve the archive creation process.
    Downloads all of the baseline and update files from the NLM Data Distribution FTP server and saves them in the /Volumes/myssd/Pubmed subdirectory.
    Opens each baseline file in turn, decompresses the XML file contained within, and extracts each individual PubMed record into its own, individual XML file. These individual record XML files are then re-compressed and saved into a new directory structure (within the /Volumes/myssd/Archive subdirectory) which is built to facilitate rapid access.
    Opens each update file in turn, processing them like the baseline files, overwriting previous versions of a PubMed record with newer ones, and deleting records from your archive which have been deleted from PubMed.

As this command finishes processing each baseline and update file, it creates a sentinel file as a flag to indicate which files have already been processed. If the archive-pubmed command is interrupted in the middle, simply execute the command again to restart it; the sentinel files will automatically indicate where to start back up again.

Note: while the archive-pubmed command is processing update files, you may occasionally see error messages that look like this:

rm: cannot remove 'XX/XX/XX/XXXXXXXX.xml.gz': No such file or directory

These messages occur when an update file contains a delete message for a record that is not yet in your archive. This will happen when a PubMed record was created in error, then deleted on the same day. These messages can be ignored.
Maintaining the archive
Updating an archive with the latest files

New update files are released to the FTP server on a daily basis. To make sure your local archive mirrors the current state of the PubMed database as closely as possible, you will want to update your local archive before attempting any major projects. To do this, simply re-run the archive-pubmed command (substituting /Volumes/myssd with the directory that contains your archive):

archive-pubmed -path /Volumes/myssd

This should only take a few minutes, as it will only need to download the new update files and add those records to your archive.
Re-archive for the new baseline

Once a year, usually around late November, NLM releases a new set of baseline files. These files are updated to reflect changes in the PubMed DTD, and any changes to the MeSH terminology for the new year. Once the new baseline is released, you will need to rebuild your archive from the ground up in order to make sure your archive reflects the current state of the PubMed database.

Before rebuilding your archive, make sure you delete the entire contents of the directory that contains your archive and the downloaded baseline and update files (i.e. /Volumes/myssd). The easiest way to accomplish this is to reformat your SSD as described above, which will delete the entire archive in minutes instead of hours. Even if you do delete your archive in a different way, it is probably a good idea to reformat your SSD as described above before trying to build your new archive. Once your drive is ready, follow the steps above to build the archive from the new baseline files.
Retrieving from the archive
Retrieve records based on a list of PMIDs

If you have a list of PMIDs saved in a file, you can retrieve the full XML for all of those records from your archive by using the fetch-pubmed command. Remember to replace Volumes/myssd/Archive with the directory that contains your archive.

cat lycopene.txt | \
fetch-pubmed -path /Volumes/myssd/Archive > lycopene.xml

This will save the full XML records for all of the PMIDs listed in the file lycopene.txt to the file lycopene.xml.
Retrieve records based on a PubMed search

Other EDirect commands are completely interoperable with the archive. You can use esearch to find relevant records in the live PubMed database using the normal search algorithm, but retrieve the records from your local archive using fetch-pubmed. Remember to replace Volumes/myssd/Archive with the directory that contains your archive.

esearch -db pubmed -query "breast cancer" | \
efetch -format uid | \
fetch-pubmed -path /Volumes/myssd/Archive > breastcancer.xml

The first line of this script uses esearch to search the PubMed database for the query “breast cancer.” The esearch command uses the E-utilities API to search the live PubMed database.

The second line uses efetch -format uid to retrieve the PMIDs for all of the records that matched the search criteria from our initial search. Rather than retrieving full XML records for all of these records, we are only retrieving the PMIDs, which takes much less time.

Our third line receives the PMIDs piped in from the second line and retrieves full XML records for each of the PMIDs from the local archive, and saves the resulting XML to a file.
Extract specific elements from a group of archived records

You can pipe the output of a fetch-pubmed command into xtract just as you would with efetch. Remember to replace Volumes/myssd/Pubmed with the directory that contains your archive.

esearch -db pubmed -query "breast cancer" | \
efetch -format uid | \
fetch-pubmed -path /Volumes/myssd/Archive | \
xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation Volume Issue PubDate/Year

Additional Information
Differences between your local archive and PubMed

As explained above, the local archive is based on the export files from the NLM Data Distribution program. While export files closely mirror the contents of the live PubMed database, there are a few categories of records which are not included in the exports. As a result, while your local PubMed archive should be a very close match to the live PubMed database, there are likely to be a few discrepancies:

    The local archive will not contain the small number of records in PubMed (approximately 13,000) for books and book chapters.
    For the small number of versioned citations in PubMed (approximately 800), the local archive will contain only the most recent version.

You can find a good representation of the contents of your local archive by searching PubMed (using either the web version of PubMed or esearch) for the following string:

all[sb] NOT pmcbook NOT ispreviousversion

(In fact, if you are retrieving records based on a PubMed search using esearch, you may find it useful to add “NOT pmcbook NOT ispreviousversion” to the end of your search string. This will minimize the number of absent records fetch-pubmed attempts to retrieve.)

Additionally, you may see some further discrepancies, depending on when you update your local archive and when you search. New records are being added to PubMed all the time by publishers submitting citation data. However, the indexes that power PubMed search are updated once a day (usually around 6 AM ET), and new export files are only generated once a day (usually around 2 PM ET). As a result, even a completely up-to-date local archive may include a handful of records that are not yet included in the PubMed search indexes, or vice versa.
Set an environment variable to save time

You can make using archive-pubmed and fetch-pubmed commands a little easier by setting up your local archive directory as an environment variable. Add the following line to each user’s .bash_profile configuration file (substituting /Volumes/myssd with the directory that contains your archive):

export EDIRECT_PUBMED_MASTER=/Volumes/myssd

After you have set this variable, you can omit the -path argument from both archive-pubmed and fetch-pubmed: These commands will check the environment variable, and know exactly where your local archive is located.
For more information

Additional information and documentation on the local archiving process can be found on NCBI’s EDirect documentation page, “Entrez Direct: E-utilities on the UNIX Command Line” (look for the section labeled “Local Data Cache”).

+ + + +
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"Welcome to E-utilities for PubMed" Sample Code for Class Exercises

+ +

Below you will find sample code for the examples presented in the “Welcome to E-utilities for PubMed” Insider’s Guide course. These examples are written for use with EDirect in a Unix environment. If you need help installing and setting up EDirect, please see our “Installing EDirect” page.

There are many different ways to answer the questions discussed in class. The sample code below provides one option, but by no means the only option, and not even necessarily the best option. Feel free to modify, adapt, edit, re-use or completely discard any of the suggestions below when trying to find the solution that works best for you.

+

Find the current “most active” authors for a given topic

Goal:

Find out who the “hot” authors are on a given topic. We are looking for authors that have written the most papers recently (i.e. in the last two years), on a specific subject. (For this example, we are looking at papers about diabetes and pregnancy.)

Solution:

+
esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \
+efetch -format xml | \
+xtract -pattern Author -sep " " -element LastName,Initials | \
+sort-uniq-count-rank | \
+head -n 10
+

This series of commands searches PubMed for the string “(diabetes AND pregnancy) AND (”2015/01/01“[PDAT] : ”2017/12/31“[PDAT])”, retrieves the full XML records for each of the search results, extracts the last name and initials of every author on every record, sorts the authors by frequency of occurrence in the results set, and presents the top ten most frequently-occurring authors, along with the number of times that author appeared.

Discussion:

+
esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])"). Our search query is constructed almost exactly like we would construct it in PubMed: we have a topic string (“diabetes AND pregnancy”) enclosed in parentheses and ANDed together with a date range. However, the double quotation marks (“) in our search string pose a problem. We need to ”escape“ the double quotation marks (”) in our search query by putting a “\” before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the -query argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched.

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern Author -sep " " -element LastName,Initials | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every author (-pattern Author). Even if there are multiple authors on a single citation, each author will be on a new line, rather than putting all authors for the same citation on the same line. The command then extracts each author’s last name and initials (-element LastName,Initials) and separates the two elements with a single space (-sep " "). This will output a list of authors’ names and initials, one author per line, and will pipe the list to the next line.

+
sort-uniq-count-rank | \
+

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of authors received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique author, removes the duplicate authors, and then sorts the list of unique authors by how frequently they occur, with the most frequent authors at the top. The function also returns the numerical count, making it easier to quantify how frequently each author occurs in the data set.

+
head -n 10
+

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring authors first, this will show us only the ten most frequently occurring authors in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the authors, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the “|” and “\” characters from the previous line. Otherwise, the system will wait for you to finish entering your command.)

+

Generate list of funding agencies who are most active in funding a particular topic

Goal:

Find out which funding agencies have been funding research on a given topic. We are looking for agencies that are associated with papers published recently (i.e. in the last two years), on a specific subject. (For this example, we are looking at papers about diabetes and pregnancy.)

Solution:

+
esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \
+efetch -format xml | \
+xtract -pattern Grant -element Agency | \
+sort-uniq-count-rank | \
+head -n 10
+

This series of commands searches PubMed for the string “(diabetes AND pregnancy) AND (”2015/01/01“[PDAT] : ”2017/12/31“[PDAT])”, retrieves the full XML records for each of the search results, extracts the funding agency for every grant listed on every record, sorts the funding agencies by frequency of occurrence in the results set, and presents the top ten most frequently-occurring agencies, along with the number of times that agency appeared.

Discussion:

+
esearch -db pubmed -query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])" | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "(diabetes AND pregnancy) AND (\"2015/01/01\"[PDAT] : \"2017/12/31\"[PDAT])"). Our search query is constructed almost exactly like we would construct it in PubMed: we have a topic string (“diabetes AND pregnancy”) enclosed in parentheses and ANDed together with a date range. However, the double quotation marks (“) in our search string pose a problem. We need to ”escape“ the double quotation marks (”) in our search query by putting a “\” before them. This tells EDirect to interpret the quotation marks as just another character, and not a special character that marks the end of the -query argument. Otherwise, EDirect would interpret the double quotation marks before the first date as marking the end of the search query, and the rest of the query would not be searched.

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern Grant -element Agency | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every grant (-pattern Grant). Even if there are multiple grants on a single citation, each grant will be on a new line, rather than putting all grants for the same citation on the same line. The command then extracts each grant’s funding agency (-element Agency). This will output a list of agencies, one agency per line, and will pipe the list to the next line.

+
sort-uniq-count-rank | \
+

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of agencies received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique agency, removes the duplicate agencies, and then sorts the list of unique agencies by how frequently they occur, with the most frequent agencies at the top. The function also returns the numerical count, making it easier to quantify how frequently each agency occurs in the data set.

+
head -n 10
+

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring agencies first, this will show us only the ten most frequently occurring agencies in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the agencies, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the “|” and “\” characters from the previous line. Otherwise, the system will wait for you to finish entering your command.)

+

Create a customized version of the Discovery Bar “Results By Year” histogram, comparing two searches

Goal:

In order to recreate the “Results By Year” histogram available in the PubMed Discovery Bar for a given search, we need to count how many occurrences of each Publication Year there are in the results set, then sort those counts by year. To compare the “Results By Year” for two searches, we need to do this twice, and combine the two outputs. For this example, the searches we are doing relate to abuse of specific opioids (“fentanyl abuse” vs. “oxycodone abuse”), and we will restrict our results to articles published between 1988 and 2017.

Solution:

+
esearch -db pubmed -query "fentanyl abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
+cut -c -4 | \
+sort-uniq-count-rank | \
+sort -n -t $'\t' -k 2 > fentanyl_abuse.txt
+
+esearch -db pubmed -query "oxycodone abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
+cut -c -4 | \
+sort-uniq-count-rank | \
+sort -n -t $'\t' -k 2 > oxycodone_abuse.txt
+
+join -j 2 -o 0,1.1,2.1 -a1 -a2 -e0 -t $'\t' <(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt) > abuse_compare.txt
+

This series of commands searches PubMed for the string “fentanyl abuse” (restricted to publication dates between 1988 and 2017), retrieves the full XML records for each of the search results, extracts the year of publication from each record, counts how frequently each publication year appears in the results, then re-sorts by chronologically by year. The results are then saved to a file. The process is repeated for the string “oxycodone abuse”, and the two files are merged together.

(This example uses some Unix tools like sort, cut, and join that were not discussed in detail in “Welcome to E-utilities for PubMed”. We will address some of them in greater detail in our follow-up class, “EDirect for PubMed”, but you can find a brief description of some of these tools in the appendices of NCBI’s EDirect documentation, under the heading “UNIX Utilities.”)

Discussion:

+
esearch -db pubmed -query "fentanyl abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
+

The first line of this command uses esearch to search PubMed (-db pubmed) for our search query (-query "fentanyl abuse"). Our search query is constructed exactly like we would construct it in PubMed: no tags, no punctuation, no Boolean operators. We simply put in our terms and they are automatically ANDed together. We use a few more arguments to restict our results based on publication date (-datetype PDAT -mindate 1988 -maxdate 2017).

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for each PubMed record (-pattern PubmedArticle). We then want to look in the PubDate element for each record, and extract either the Year element or the MedlineDate element (each citation should only have one or the other; -block PubDate -element Year MedlineDate). Each line in the output will have either a publication year (from the Year element), or a publication year followed by a month or other, more specific date information (from the MedlineDate element). The output will then be piped to the next line.

+
cut -c -4 | \
+

The fourth line cuts off each line after the fourth character, leaving only the four digits of the year on each row (cut -c -4). The list of years is then piped to the next line.

+
sort-uniq-count-rank | \
+

The fifth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of years received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique year, removes the duplicate years, and then sorts the list of unique years by how frequently they occur, with the most frequently occurring years at the top. The function also returns the numerical count for each year.

+
sort -n -t $'\t' -k 2 > fentanyl_abuse.txt
+

The sixth line then re-sorts the results numerically by the second column of data (sort -n -t $'\t' -k 2), which is the list of unique years (the first column of data is the frequency counts generated on the previous line). The list of years and frequency counts is now sorted chronologically, and the result is then sent to a file (> fentanyl_abuse.txt).

+
esearch -db pubmed -query "oxycodone abuse" -datetype PDAT -mindate 1988 -maxdate 2017 | \
+efetch -format xml | \
+xtract -pattern PubmedArticle -block PubDate -element Year MedlineDate | \
+cut -c -4 | \
+sort-uniq-count-rank | \
+sort -n -t $'\t' -k 2 > oxycodone_abuse.txt
+

The first six lines are then repeated, substituting out “fentanyl” for “oxycodone” in both the search string and the output file name.

+
join -j 2 -o 0,1.1,2.1 -a1 -a2 -e0 -t $'\t' <(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt) > abuse_compare.txt
+

The final line uses a more advanced Unix command, join, that will allow us to merge together the two output files according to the values of a “key” column (in our case, the publication year). Both of our output files have the publication year in the second column, so we will join the two files using the second column of each file (join -j 2). We specify that the “key” column should be output first, followed by the first column of each file (-o 0,1.1,2.1). We want to make sure to include all of the publication years that were listed in either results set, even if they don’t appear in the other (with SQL or other database querying techniques, this is sometimes referred to as a “full outer join”; -a1 -a2). If one of the files has no results for a given publication year, we will output a 0 instead of a blank, and we will separate the columns in our output by tabs (-e0 -t $'\t').

The last part of the final line tells the join command which files to merge (<(cat fentanyl_abuse.txt) <(cat oxycodone_abuse.txt)) and where to save the output (> abuse_compare.txt). If you want to instead view the results in your terminal window, you can omit the “>” and everything that follows it on the last line.

+

Find the most commonly-discussed topics of articles written by authors from a specific institution

Goal:

Find the most common topics for articles written by any author from a specific institution. For the purposes of this exercise, we will find the “most common topics” by determining which MeSH headings are most frequently attached to the records from our institution. This exercise assumes that the institution has many authors (or many research components with different names), and that searching for all of the authors (or all papers with any of the institution’s names listed in the affiliation data) involves creating a long and complicated search string.

Solutions:

As mentioned before, most use cases have multiple solutions. There is almost always a way to accomplish 100% of your goal in a single script. However, there are usually also ways of accomplishing 90%, 75% or 50% of your goal in a single script, and doing the remaining 10%, 25% or 50% manually. Each individual user should decide whether the additional time and effort it will take to get from 90% to 100% is more or less efficient than simply doing the remaining 10% manually.

With that in mind, we have presented three different solutions below. Each solution is closer and closer to “perfect.” However, each solution adds new complexity and new commands which are more powerful, but also increasingly complicated. We encourage you to read through all three examples and see if one of them meets your needs, or if one of them could be adapted to meet your needs.

Version 1: Basic

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format xml | \
+xtract -pattern DescriptorName -element DescriptorName | \
+sort-uniq-count-rank | \
+head -n 10
+

This series of commands searches PubMed for a string defined in the text file “searchstring.txt”, retrieves the full XML records for each of the search results, extracts each of the MeSH descriptors associated with every record in the results set, sorts the MeSH headings by frequency of occurrence in the results set, and presents the top ten most frequently-occurring MeSH headings, along with the number of times that heading appears.

Discussion:

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+

The first line uses esearch to search PubMed (-db pubmed). The line uses the Unix command cat to read the entire contents of a file (searchstring.txt) and use it as the search query (-query "$(cat searchstring.txt)"). This allows us to use a long and complex search strategy (involving many author names, many institutional names, or both), and to keep that search string in a separate file. Over time, we can update the search strategy without having to edit our actual script. Additionally, it makes the script more readable.

The “|” character pipes the results of our esearch into our next command, and the “\” character at the end of the line allows us to continue our string of commands on the next line, for easier-to-read formatting.

+
efetch -format xml | \
+

The second line takes the esearch results from our first line and uses efetch to retrieve the full records for each of our results in the XML format (-format xml), and pipes the XML output to the next line.

+
xtract -pattern DescriptorName -element DescriptorName | \
+

The third line uses the xtract command to retrieve only the elements we need from the XML output, and display those elements in a tabular format. The -pattern command indicates that we should start a new row for every MeSH heading in the results set (-pattern DescriptorName). Even if there are multiple MeSH headings on a single citation (which there likely will be), each MeSH heading will be on a new line, rather than putting all MeSH headings for the same citation on the same line. The command then extracts the name of each MeSH heading (-element DescriptorName). This will output a list of MeSH headings, one per line, and will pipe the list to the next line.

+
sort-uniq-count-rank | \
+

The fourth line uses a special EDirect function (sort-uniq-count-rank) to sort the list of MeSH headings received from the previous line, grouping together the duplicates. The function then counts how many occurrences there are of each unique MeSH heading, removes the duplicate headings, and then sorts the list of unique headings by how frequently they occur, with the most frequent headings at the top. The function also returns the numerical count for each heading.

+
head -n 10
+

The fifth line, which is optional, shows us only the first ten rows from the output of the sort-uniq-count-rank function (head -n 10). Because this function puts the most frequently occurring MeSH headings first, this will show us only the ten most frequently occurring headings in our search results set. To show more or fewer rows, adjust the “10” up or down. If you want to see all of the headings, regardless of how frequently they appear, remove this line entirely. (If you do choose to remove this line, make sure you also remove the “|” and “\” characters from the previous line. Otherwise, the system will wait for you to finish entering your command.)

Version 2: Intermediate

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format xml | \
+xtract -pattern DescriptorName -element DescriptorName | \
+grep -vxf checktags.txt | \
+sort-uniq-count-rank | \
+head -n 10
+

As you may have noticed in Version 1 (depending on your search terms), “Humans” was probably among the most common MeSH headings in your output. Virtually every biomedical article will describe subjects of research (human or animal; mice or rats, etc.). Clinical articles will describe treatment, diagnosis, etc. of diseases in patients. These articles will almost always mention the number of patients, their sex and age. Experimental articles will almost always mention the species and sex of the animal subjects.

These concepts, which are mentioned in almost every article, are designated as “check tags”. Check tags are routinely added to articles even if they are just mentioned in the article. If you like, you could just ignore these MeSH headings in your results. However, Version 2 of this code includes some lines which will automatically remove any headings that are check tags from your output.

Discussion:

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format xml | \
+xtract -pattern DescriptorName -element DescriptorName | \
+

The first three lines are the same as Version 1, ending with the xtract command which outputs a list of MeSH headings, one per line, and will pipe the list to the next line.

+
grep -vxf checktags.txt | \
+

The fourth line uses a very powerful Unix command, grep, which specializes in matching patterns in text. This line compares each line of text being piped in from our xtract command against every line in a specified file, and removes any lines from our xtract which match any of the lines in the file. The file (“checktags.txt”) contains a list of all of the MeSH headings which are check tags, with one heading on each line. You can download the checktags.txt file and use it as is, or you can modify it to filter out a different set of MeSH headings. The filtered list of MeSH headings is now piped to the next line.

+
sort-uniq-count-rank | \
+head -n 10
+

The remaining lines of Version 2 are the same as Version 1.

Version 3: Advanced

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format xml | \
+xtract -pattern DescriptorName -sep "" -element DescriptorName@MajorTopicYN,DescriptorName | \
+grep -vxf nchecktags.txt | \
+cut -c 2- | \
+sort-uniq-count-rank | \
+head -n 10
+

Version 2 filtered out the check tags from our result. However, while check tags are often added even if they are just mentioned in an article, those MeSH headings can sometimes be more central topics to the article. For example, “pregnancy” is a check tag, which is used to refer to research involving pregnant subjects. However, “pregnancy” can also be the main subject of an article. When it is, it will be denoted as a Major Topic. If we want to be even more precise than Version 2, we could make sure that we only filter out check tags when they are not the Major Topic of an article.

Discussion:

+
esearch -db pubmed -query "$(cat searchstring.txt)" | \
+efetch -format xml | \
+xtract -pattern DescriptorName -sep "" -element DescriptorName@MajorTopicYN,DescriptorName | \  
+

Again, most of Version 3 is the same as Version 2. The first difference is in the third line. In addition to extracting the DescriptorName, we are also going to be extracting the attribute “MajorTopicYN” for each DescriptorName element (-element DescriptorName@MajorTopicYN,DescriptorName). The MajorTopicYN indicator (which is always either a “Y” if the MeSH heading is a Major Topic, or “N” if it is not) will be appended to the beginning of the descriptor name, because we have eliminated the separator between elements (-sep "").

+
grep -vxf nchecktags.txt | \
+

Since the output from our xtract now consists of MeSH headings with either “Y” or “N” in front of them, we also need to edit the file that contains the check tags we are filtering out (grep -vxf nchecktags.txt). The new file (nchecktags.txt) is almost identical to the old file, with the exception that each heading in the file now starts with “N” (e.g. “Humans” becomes “NHumans”). If any of the headings in the output from our xtract are Major Topics, they will have a “Y” in front of them, and will not be filtered out by our N-prefixed check tag file. As before, the remaining, non-check tag MeSH headings are piped to the next line.

+
cut -c 2- | \
+

Finally, we need to remove our extraneous “Y” and “N” characters from the front of the remaining MeSH headings (cut -c 2-).

+
sort-uniq-count-rank | \
+head -n 10
+

The remaining lines of Version 3 are the same as Version 2.

Version 4: ???

Version 3 solved many of the problems, but is still not perfect. It does not handle MeSH subheadings, for example, and adding “N” to the front of each of the Check Tags in our filter file is inelegant. There are still more ways to improve this script, but the 90% of the task that this accomplishes will hopefully meet your needs. If it doesn’t, feel free to keep improving it!

+
+
+
+
+ +
+ + +
+ + \ No newline at end of file diff --git a/e-utilities-lecture-notes/checktags.txt b/e-utilities-lecture-notes/checktags.txt new file mode 100644 index 0000000..4a21f31 --- /dev/null +++ b/e-utilities-lecture-notes/checktags.txt @@ -0,0 +1,33 @@ +Pregnancy +Infant, Newborn +Infant +Child, Preschool +Child +Adolescent +Young Adult +Adult +Middle Aged +Aged +Aged, 80 and over +Cats +Cattle +Chick Embryo +Dogs +Guinea Pigs +Cricetinae +Mice +Rabbits +Rats +Animals +Humans +Male +Female +History, Ancient +History, Medieval +History, 15th Century +History, 16th Century +History, 17th Century +History, 18th Century +History, 19th Century +History, 20th Century +History, 21st Century \ No newline at end of file diff --git a/e-utilities-lecture-notes/edirect-for-pubmed-1.sh b/e-utilities-lecture-notes/edirect-for-pubmed-1.sh new file mode 100644 index 0000000..239cb3a --- /dev/null +++ b/e-utilities-lecture-notes/edirect-for-pubmed-1.sh @@ -0,0 +1,350 @@ +# ---------------------------------------------------------------------- +# The Insider's Guide to Accessing NLM Data: EDirect for PubMed +# Part One: Getting PubMed Data +# Course Materials +# https://dataguide.nlm.nih.gov/edirect-for-pubmed-1.txt +# ---------------------------------------------------------------------- +# NOTE: Solutions to all exercises are at the bottom of this document. +# ---------------------------------------------------------------------- +# +# Commands are instructions given by a user telling a computer to do something +# +# Arguments provide input data or modify the behavior of a command +# +# ---------------------------------------------------------------------- +# +# TIPS FOR CYGWIN USERS: +# +# Copy: Ctrl + Insert +# (NOT Ctrl + C!) +# +# Paste: Shift + Insert +# (NOT Ctrl + V!) +# +# +# ---------------------------------------------------------------------- +# +# TIPS FOR ALL USERS: +# +# Ctrl + C "cancels" and gets you back to a prompt +# +# Up and Down arrow keys allow you to cycle through your recent commands +# +# clear: clears your screen + +clear +esearch -version +# ---------------------------------------------------------------------- +# +# esearch +# +# esearch searches a database and returns the unique identifier of every record that meets the search criteria - in this case, PMIDs. +# +# -db to specify database: -db pubmed +# -query to enter your query in quotes: -query "seasonal affective disorder" +# +# +# COMMAND STRING: + +esearch -db pubmed -query "seasonal affective disorder" + +# PUBMED SEARCH: + +# seasonal affective disorder + +# ---------------------------------------------------------------------- + +# Show PubMed's translation of your search terms like you receive in the Search Details in PubMed +# +# COMMAND STRING: +# + esearch -db pubmed -query "seasonal affective disorder" -log +# +# Details display at end of XML snippit +# +# "seasonal affective disorder"[MeSH Terms] OR ("seasonal"[All Fields] AND "affective"[All Fields] AND "disorder"[All Fields]) OR "seasonal affective disorder"[All Fields] +# +# ---------------------------------------------------------------------- +# +# Search like you do in PubMed with uppercase Boolean AND/OR/NOT and field tags as needed. +# +# PUBMED SEARCH: +# +# malaria AND jama[journal] +# +# COMMAND STRING: +# + esearch -db pubmed -query "malaria AND jama[journal]" + + + esearch -db pubmed -query "malaria AND jama[journal]" -log + + +# +# ---------------------------------------------------------------------- +# +# Restricting by Date +# +# -datetype specifies date field: -datetype PDAT +# -mindate -maxdate specifies range: -mindate 2015 -maxdate 2017 +# +# COMMAND STRING: +# + esearch -db pubmed -query "malaria AND jama[journal]" -datetype PDAT -mindate 2015 -maxdate 2017 +# +# +# Use backslash "\" to indicate that you have not finished writing the command - it is continued on the next line. +# +# COMMAND STRING: +# +# esearch -db pubmed -query "malaria AND jama[journal]" \ +# -datetype PDAT -mindate 2015 -maxdate 2017 +# +# ---------------------------------------------------------------------- +# +# Be Careful with Quotes +# +# PUBMED SEARCH: +# +# cancer AND science[journal] +# +# cancer AND "science"[journal] +# +# +# COMMAND STRING: +# + esearch -db pubmed -query "cancer AND \"science\"[journal]" +# +# +# ---------------------------------------------------------------------- +# +# EXERCISE 1: esearch +# How many Spanish-language articles about diabetes are in PubMed? +# Hint: use the [lang] field tag +# +# (ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + +esearch -db pubmed -query "diabetes AND Spanish[lang]" + +esearch -db pubmed -query "diabetes AND Spanish[lang]" -log + +esearch -db pubmed -query "diabetes AND Turkish[lang]" + + +# ---------------------------------------------------------------------- +# +# EXERCISE 2: esearch +# How many articles were written by BH Smith between 2012 and 2017, inclusive? + +esearch -db pubmed -query "BH Smith[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 + +esearch -db pubmed -query "bh smith[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 + +esearch -db pubmed -query "Balci Serdar[Author]" + +esearch -db pubmed -query "Balci Serdar[Author]" -log + +# (ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) +# +# ---------------------------------------------------------------------- +# +# efetch +# +# efetch retrieves the complete record in the format that you specify. +# +# -db to specify database: -db pubmed +# -id to specify PMID: -id 25359968 +# -format to specify format: -format abstract +# +# COMMAND STRING: +# + efetch -db pubmed -id 25359968 -format abstract + + efetch -db pubmed -id 25359968 -format medline + + efetch -db pubmed -id 25359968 -format xml + + efetch -db pubmed -id 25359968 -format uid + +# +# ---------------------------------------------------------------------- +# +# efetch Formats +# +# -format options: +# +# MEDLINE +# -format medline +# +# XML +# -format xml +# +# PMID list +# -format uid +# +# Summary +# -format docsum +# ---------------------------------------------------------------------- +# +# efetch Multiple Records +# +# Separate multiple PMIDs in the -id argument with commas. +# +# COMMAND STRING: +# + efetch -db pubmed -id 24102982,21171099,17150207 -format abstract + + efetch -db pubmed -id 26024162 -format abstract + +# +# efetch -db pubmed -id 26024162 -format abstract +# +# ---------------------------------------------------------------------- +# +# EXERCISE 3: efetch +# Who is the first author listed on the PubMed record 26287646? +# +# (ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + + +efetch -db pubmed -id 26287646 -format abstract + + + + +# ---------------------------------------------------------------------- +# +# Creating a data pipeline +# +# Use pipe "|" [Shift + \] to "pipe" the results of one command into the next +# +# COMMAND STRING: +# + esearch -db pubmed -query "asthenopia[mh] AND nursing[sh]" | efetch -format uid + +# +# ---------------------------------------------------------------------- +# +# EXERCISE 4: Combining Commands +# How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017? +# Hint: Use the up arrow to access your previous commands +# Hint: Remember -format uid +# +# (ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + +esearch -db pubmed -query "BH Smith[Author]" -datetype PDAT \ +-mindate 2012 -maxdate 2017 | efetch -format uid + +esearch -db pubmed -query "BH Smith[Author]" -datetype PDAT -mindate 2012 -maxdate 2017 | efetch -format uid + +# -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +# HOMEWORK FOR PART ONE +# -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +# (Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode1.html) +# ----------------------------------------------------------------------- +# Question 1: +# +# Using EDirect, write a command to find out how many citations are in PubMed for articles about using melatonin to treat sleep disorders. + +esearch -db pubmed -query "melatonin AND sleep disorders" + +esearch -db pubmed -query "melatonin sleep disorder" + +# ----------------------------------------------------------------------- +# Question 2: +# +# How many of the PubMed citations identified in question 2 were added to PubMed (i.e. created) between January 1, 2015 and July 1, 2017? + +esearch -db pubmed -query "melatonin AND sleep disorders" -datetype PDAT -mindate 2015/01/01 -maxdate 2017/07/01 + +esearch -db pubmed -query "melatonin sleep disorder" -datetype CRDT -mindate 2015/01/01 -maxdate 2017/07/01 + +esearch -db pubmed -query "melatonin sleep disorder" AND (2015/01/01[crdt] : 2017/07/01[crdt])" + + + +# ----------------------------------------------------------------------- +# Question 3: +# +# Write a command to retrieve the abstracts of the following PubMed records: +# +# 27240713 +# 27027883 +# 22468771 +# 20121990 + +efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format abstract + +efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format abstract + +# ----------------------------------------------------------------------- +# Question 4: +# +# Modify your answer to Question 3 to retrieve the full XML of all four records. + +efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format xml + +efetch -db pubmed -id 27240713,27027883,22468771,20121990 -format xml + + +# ----------------------------------------------------------------------- +# Question 5: +# +# Write a series of commands that retrieves a list of PMIDs for all citations for papers written by the author with the ORCID 0000-0002-1141-6306. + +esearch -db pubmed -query "0000-0002-1141-6306" | efetch -db pubmed -format uid + +esearch -db pubmed -query "0000-0002-1141-6306[auid]" | \ +efetch -format uid + + +# -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +# EXERCISE SOLUTIONS: +# ----------------------------------------------------------------------- +# EXERCISE 1: esearch +# How many Spanish-language articles about diabetes are in PubMed? +# Hint: use the [lang] field tag +# +# SOLUTION: +# +# esearch -db pubmed -query "diabetes AND spanish[lang]" +# +# -=-=-=-=-=-=-=-=-=-=-=-=- +# EXERCISE 2: esearch +# How many articles were written by BH Smith between 2012 and 2017, inclusive? +# Hint: use the [author] field tag +# +# SOLUTIONS: +# +# esearch -db pubmed -query "smith bh[author]" \ +# -datetype PDAT -mindate 2012 -maxdate 2017 +# +# esearch -db pubmed -query "smith bh[author] \ +# AND (2012/01/01[pdat] : 2017/12/31[pdat])" +# +# -=-=-=-=-=-=-=-=-=-=-=-=- +# EXERCISE 3: efetch +# Who is the first author listed on the PubMed record 26287646? +# +# SOLUTION: +# +# efetch -db pubmed -id 26287646 -format abstract +# +# The first author is Brennan PF +# +# -=-=-=-=-=-=-=-=-=-=-=-=- +# EXERCISE 4: Combining Commands +# How do we get a list of PMIDs for all of the articles written by BH Smith between 2012 and 2017? +# Hint: Use the up arrow to access your previous commands +# Hint: Remember -format uid +# +# SOLUTIONS: +# +# esearch -db pubmed -query "smith bh[author] AND \ +# (2012/01/01[pdat] : 2017/12/31[pdat]" | \ +# efetch -format uid +# +# esearch -db pubmed -query "smith bh[author]" \ +# -datetype PDAT -mindate 2012 -maxdate 2017 | \ +# efetch -format uid +# diff --git a/e-utilities-lecture-notes/edirect-for-pubmed-2.sh b/e-utilities-lecture-notes/edirect-for-pubmed-2.sh new file mode 100644 index 0000000..baf6dc9 --- /dev/null +++ b/e-utilities-lecture-notes/edirect-for-pubmed-2.sh @@ -0,0 +1,329 @@ +# ---------------------------------------------------------------------- +# The Insider's Guide to Accessing NLM Data: EDirect for PubMed +# Part Two: Extracting Data from XML +# Course Materials +# https://dataguide.nlm.nih.gov/edirect-for-pubmed-2.txt +# ---------------------------------------------------------------------- +# NOTE: Solutions to all exercises are at the bottom of this document. +# ---------------------------------------------------------------------- +# +# REMINDERS FROM PART ONE +# +# esearch: Searches a database and returns PMIDs +# +# efetch: Retrieves PubMed records in a variety of formats +# +# Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next +# +# +# ---------------------------------------------------------------------- +# +# TIPS FOR CYGWIN USERS: +# +# Copy: Ctrl + Insert +# (NOT Ctrl + C!) +# +# Paste: Shift + Insert +# (NOT Ctrl + V!) +# +# +# ---------------------------------------------------------------------- +# +# TIPS FOR ALL USERS: +# +# Ctrl + C "cancels" and gets you back to a prompt +# +# Up and Down arrow keys allow you to cycle through your recent commands +# +# clear: clears your screen +# +# ---------------------------------------------------------------------- +# +# +# xtract +# +# Extracts specific elements from XML and arranges them in a customized tabular format. +# +# ---------------------------------------------------------------------- +# +# Getting XML +# +# From efetch: +# +# [...] | efetch -format xml | xtract [...] +# +# From a file on your computer using "-input": +# +# xtract -input file.xml [...] +# +# ---------------------------------------------------------------------- +# +# XML Element Descriptions +# https://www.nlm.nih.gov/bsd/licensee/elements_descriptions.html +# +# PubMed DTD Documentation +# https://dtd.nlm.nih.gov/ncbi/pubmed/out/doc/2018/ +# +# ---------------------------------------------------------------------- +# +# Before you start xtract-ing... +# +# Look at some PubMed XML by searching PubMed for a few PMIDs: +# +# 24102982,21171099,17150207 +# +# ---------------------------------------------------------------------- +# +# Getting a small sample dataset + + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml &> pubmed2.txt + + +# ---------------------------------------------------------------------- +# +# -pattern to identify which element will create a new row in the output table +# +# -element to identify which element(s) or attribute(s) will create columns in the output table +# +# +# A basic xtract Command: +# +# COMMAND STRING: +# +# **pattern for row, element for column** + + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element ArticleTitle + + + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern Author -element LastName + + + + +---------------------------------------------------------------------- + +Creating multiple columns + +Create multiple columns using the same -element argument by including multiple XML element names. +Separate the names with spaces. + +Example: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element Agency GrantID + + + +---------------------------------------------------------------------- + +EXERCISE 1: +Write an xtract command that: +* creates a table with one row per PubMed article. +* Each row should have two columns: + * Volume + * Issue Number + +Use the following efetch as input: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element Volume Issue + +efetch -db pubmed -id 27101380 -format xml | \ +xtract -pattern PubmedArticle -element PMID Year + +PMID references, Year multiple + +efetch -db pubmed -id 27101380 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID Year + + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + +---------------------------------------------------------------------- +Isolating the elements we need + +COMMAND STRING: +efetch -db pubmed -id 27101380 -format xml | \ +xtract -pattern PubmedArticle -element PMID Year + +---------------------------------------------------------------------- + +Parent/Child construction + +Retrieves only elements that are the child of a specific parent. + +Format: ParentElement/ChildElement + +Example: +-element MedlineCitation/PMID + +---------------------------------------------------------------------- + +Solving xtract Example 1 +We have a set of records +We want a tabular list with PMID, Journal Title Abbreviation, and Article Title + +COMMAND STRING: +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISOAbbreviation ArticleTitle + +---------------------------------------------------------------------- + +xtract-ing attribute values + +Format: ElementName@AttributeName + +Example: + +-element DescriptorName@MajorTopicYN + +---------------------------------------------------------------------- + +EXERCISE 2 +Write an xtract command that: +* Has one row per PubMed records +* Has three columns: + * PMID + * Journal ISSN + * Citation status + +Use the following efetch as input: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISSN MedlineCitation@Status + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISSN MedlineCitation@Status Author/LastName + + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + +---------------------------------------------------------------------- + +EXERCISE 3: Putting it all together + +We want to find out which authors have been writing about traumatic brain injuries in athletes +* Limit to publications from 2016 and 2017. +We want to see just the author names, one per line. +We want the last name and initials, separated by a space. +We want the whole script (not just the xtract command). + +esearch -db pubmed -query "traumatic brain injuries athletes" \ +-datetype PDAT -mindate 2016 -maxdate 2017 | \ +efetch -format xml | \ +xtract -pattern Author -element Author/LastName Author/Initials + + + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + + +---------------------------------------------------------------------- + +sort-uniq-count-rank + +Four steps of sort-uniq-count-rank +1. Sorts all of the lines in your input alphabetically by the full contents of the line +2. Eliminates all duplicates, leaving only unique values. +3. Counts up how many of each unique value there were in your input, and provides that frequency count next to each unique value. +4. Re-sorts the unique values in descending order by frequency, so the most frequently occurring values are at the top. + +COMMAND STRING: + +esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \ +efetch -format xml | \ +xtract -pattern Author -element LastName Initials | \ +sort-uniq-count-rank + +---------------------------------------------------------------------- + +head + +Limits output to only the first few lines of input. + +Example: + +head -n 10 +Outputs only the first ten lines of the input. + +COMMAND STRING: + +esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \ +efetch -format xml | \ +xtract -pattern Author -element LastName Initials | \ +sort-uniq-count-rank | \ +head -n 10 + +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +HOMEWORK FOR PART TWO) +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode2.html) +----------------------------------------------------------------------- +Question 1: + +Using the efetch command below to retrieve PubMed XML, write an xtract command with one record per row, with columns for PMID, Journal Title Abbreviation, Publication Year, Volume, Issue and Page Numbers. + +efetch -db pubmed -id 12312644,12262899,11630826,22074095,22077608,21279770,22084910 -format xml + +----------------------------------------------------------------------- +Question 2: + +Create a table of the authors attached to PubMed record 28341696. The table should include each author's last name, initials, and affiliation information (if listed). + +----------------------------------------------------------------------- +Question 3: + +Write a series of commands to generate a table of PubMed records for review articles about the paleolithic diet. The table should have one row per citation, and should include columns for the PMID, the citation status, and the article title. + +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE SOLUTIONS: +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE 1: +Write an xtract command that: +* creates a table with one row per PubMed article. +* Each row should have two columns: + * Volume + * Issue Number + +SOLUTION: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element Volume Issue + +-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE 2: +Write an xtract command that: +* Has one row per PubMed records +* Has three columns: + * PMID + * Journal ISSN + * Citation status + +SOLUTION: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID Journal/ISSN MedlineCitation@Status + + +-=-=-=-=-=-=-=-=-=-=-=-=- +EXERCISE 3: Putting it all together + +We want to find out which authors have been writing about traumatic brain injuries in athletes +* Limit to publications from 2016 and 2017. +We want to see just the author names, one per line. +We want the last name and initials, separated by a space. +We want the whole script (not just the xtract command). + +SOLUTION: + +esearch -db pubmed -query "traumatic brain injury athletes" -datetype PDAT -mindate 2016 -maxdate 2017 | \ +efetch -format xml | \ +xtract -pattern Author -element LastName Initials + diff --git a/e-utilities-lecture-notes/edirect-for-pubmed-3.sh b/e-utilities-lecture-notes/edirect-for-pubmed-3.sh new file mode 100644 index 0000000..4c51ad8 --- /dev/null +++ b/e-utilities-lecture-notes/edirect-for-pubmed-3.sh @@ -0,0 +1,385 @@ +# ---------------------------------------------------------------------- +# The Insider's Guide to Accessing NLM Data: EDirect for PubMed +# Part Three: Formatting Results and Unix tools +# Course Materials +# https://dataguide.nlm.nih.gov/edirect-for-pubmed-3.txt +# ---------------------------------------------------------------------- +# NOTE: Solutions to all exercises are at the bottom of this document. +# ---------------------------------------------------------------------- +# +# REMINDERS FROM PART ONE +# +# esearch: Searches a database and returns PMIDs +# +# efetch: Retrieves PubMed records in a variety of formats +# +# Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next +# +# +# ---------------------------------------------------------------------- +# +# REMINDERS FROM PART TWO +# +# xtract: Pulls data from XML and arranges it in a table +# +# -pattern: Defines rows for xtract +# +# -element: Defines columns for xtract +# +# Identify XML elements by name (e.g. ArticleTitle) +# +# Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID) +# +# Identify attributes with "@" (e.g. MedlineCitation@Status) +# +# ---------------------------------------------------------------------- +# +# TIPS FOR CYGWIN USERS: +# +# Copy: Ctrl + Insert +# (NOT Ctrl + C!) +# +# Paste: Shift + Insert +# (NOT Ctrl + V!) +# +# ---------------------------------------------------------------------- +# +# TIPS FOR ALL USERS: +# +# Ctrl + C "cancels" and gets you back to a prompt +# +# Up and Down arrow keys allow you to cycle through your recent commands +# +# clear: clears your screen +# +# ---------------------------------------------------------------------- + +-tab and -sep + +-tab defines the separator between columns +-sep defines the separator between multiple values in the same columns + +The default for both -tab and -sep is "\t" (the tab character) +Changes to -tab and -sep only affect subsequent -element/-first/-last arguments + +COMMAND STRING: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID ISSN LastName + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "\t" -sep "\t" \ +-element MedlineCitation/PMID ISSN LastName + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "\t" -sep " " \ +-element MedlineCitation/PMID ISSN LastName + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -sep " " \ +-element MedlineCitation/PMID ISSN LastName + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -sep "," \ +-element MedlineCitation/PMID ISSN LastName + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -sep ", " \ +-element MedlineCitation/PMID ISSN LastName + +# ---------------------------------------------------------------------- +# +# With -tab/-sep, order matters! +# +# -tab/-sep only affect subsequent -elements +# +# Later -tab/-sep overwrite earlier ones +# +# ---------------------------------------------------------------------- + +EXERCISE 1 +Write an xtract command that: +* has a new row for each PubMed record +* has columns for PMID, Journal Title Abbreviation, and Author-supplied Keywords +Each column should be separated by "|" +Multiple keywords in the last column should be separated with commas +Sample Output: + +26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology + +Use the following efetch as input: + +efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -sep "," \ +-element MedlineCitation/PMID ISOAbbreviation Keyword + + + + +# (ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) +# +# ---------------------------------------------------------------------- + +Authors: First Draft + +COMMAND STRING: +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID LastName Initials + +---------------------------------------------------------------------- + +-block + +-block associates multiple child elements of the same parent element in the results + +COMMAND STRING: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID -block Author -element LastName Initials + +---------------------------------------------------------------------- + +What we know so far... + + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -sep ", " \ +-element MedlineCitation/PMID ISSN LastName + +---------------------------------------------------------------------- + +Putting two different elements in the same column + +Separate multiple -element values with a comma instead of a space. + +COMMAND STRING: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -sep " " -element LastName,Initials + +---------------------------------------------------------------------- + +"-block" resets -tab/-sep to default + +COMMAND STRING: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \ +-block Author -sep " " -element LastName,Initials + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \ +-block Author -tab "|" -sep " " -element LastName,Initials + +---------------------------------------------------------------------- + +EXERCISE 2 +Write an xtract command that: +* Has a new row for each PubMed record +* Has a column for PMID +* Lists all of the MeSH headings, separated by "|" +* If a heading has multiple subheadings attached, separate the heading and subheadings with "/" +Sample Output: +24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology + +Use the following efetch as input: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \ +-block MeshHeading -tab "|" -sep "/" -element MeshHeading/DescriptorName, MeshHeading/QualifierName + + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \ +-block MeshHeading -tab "|" -sep "/" -element DescriptorName,QualifierName + + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + +---------------------------------------------------------------------- + +Saving results to a file + +Use ">" to save the output to a file + +COMMAND STRING: + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.txt + +efetch -db pubmed -id 24102982,21171099,17150207 -format xml > testfile.xml + +---------------------------------------------------------------------- + +But where is my file!? + +Use "pwd" to "Print the Working Directory" (a.k.a display on the screen the name of the directory you are working in). This is where your file was saved. + +CYGWIN USERS: + +Your working directory is probably a subfolder of the folder where you installed Cygwin. In Cygwin, try: + +cygpath -w ~ + +MAC USERS: + +Your working directory is probably in your Users folder: + +Users/ + +---------------------------------------------------------------------- + +Another way to find your files + +COMMAND STRING: + +efetch -db pubmed -id 24102982,21171099,25359968,17150207 -format uid > specialname.csv + +Use "ls" to list the files in your current directory. + +---------------------------------------------------------------------- + +EXERCISE 3: Retrieving XML +How can I get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil? Save your results to a file. + +(ANSWERS TO ALL EXERCISES ARE AT THE BOTTOM OF THIS HANDOUT.) + +---------------------------------------------------------------------- + +cat + +Short for concatenate, "cat" opens files to display them on the screen. "cat" can also combine/append files + + +---------------------------------------------------------------------- + +Reading a search string from a file + +Use "$(cat filename)" to use the contents of a file in a command + +COMMAND STRING: + +esearch -db pubmed -query "$(cat searchstring.txt)" + +---------------------------------------------------------------------- + +epost uploads a list of PMIDs to the history server + +COMMAND STRING: + +epost -db pubmed -id 24102982,21171099 + +epost -db pubmed -id 24102982,21171099 | efetch -format abstract + +---------------------------------------------------------------------- + +An epost-efetch pipeline + +cat specialname.csv | epost -db pubmed | efetch -format abstract + +Using the -input argument + +epost -db pubmed -input specialname.csv | efetch -format abstract +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- + +HOMEWORK FOR PART THREE +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode3.html) +----------------------------------------------------------------------- +Question 1: + +In the PubMed XML of each record, there is a element, with one or more elements which provide dates for various stages in each article's life cycle. These can include when the article was submitted to the publisher for review, when the article was accepted by the publisher for publication, when it was added to PubMed, and/or when it was indexed for MEDLINE, among others. Not all citations will include entries for each type of date. + +For the following list of PMIDs + +22389010 +20060130 +14678125 +19750182 +19042713 +18586245 + +write a series of commands that retrieves each record and extracts all of these different dates, along with the labels that indicate which type of date is which. + +Each PubMed record should appear on a separate line. Each line should start with the PMID, followed by a tab, followed by the list of dates. For each date, include the label, followed by a ":", followed by the year, month and day, separated by slashes. Separate each date with a "|". + +Example output: + + 18586245 received:2008/01/21|revised:2008/05/05|accepted:2008/05/07|pubmed:2008/7/1|medline:2008/10/28|entrez:2008/7/1 + +----------------------------------------------------------------------- + Question 2: + + Identify your "working directory". Write a series of commands that retrieve PubMed data, redirect the output to a file, and locate the file on your computer. + +----------------------------------------------------------------------- + Question 3: + + Write a series of commands that identifies the top ten agencies that have most frequently funded published research on diabetes and pregnancy over the last year and a half. Your script should start with a search for articles about diabetes and pregnancy that were published between January 1, 2016 and June 30, 2017, should extract the agencies listed as funders on each citation, and should output a list of the ten most frequently occurring agencies. Save the results to a file. + +Note: This script may take some time to run. As you build it, consider testing with small set of PubMed records, or with a search that has a smaller date range. + +----------------------------------------------------------------------- + Question 4: + + Write a PubMed search strategy and save it to a file. Write a series of commands to search PubMed using the search string contained in the file and retrieve a list of PMIDs for all records which meet the search criteria. + +----------------------------------------------------------------------- + Question 5: + + Save the following list of PMIDs in a .csv file: + + 22389010 +20060130 +14678125 +19750182 +19042713 +18586245 + +Write a series of commands to retrieve the full PubMed XML records for all of the PMIDs in the file, and save the resulting XML to a .xml file. + +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- + EXERCISE SOLUTIONS: + -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- + + EXERCISE 1 +Write an xtract command that: + * has a new row for each PubMed recprd +* has columns for PMID, Journal Title Abbreviation, and Author-supplied Keywords +Each column should be separated by "|" +Multiple keywords in the last column should be separated with commas +Sample Output: + + 26359634|Elife|Argonaute,RNA silencing,biochemistry,biophysics,human,microRNA,structural biology + + +SOLUTION: + + efetch -db pubmed -id 26359634,24102982,28194521,27794519 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -sep "," -element MedlineCitation/PMID ISOAbbreviation Keyword + +-=-=-=-=-=-=-=-=-=-=-=-=- + EXERCISE 2: + Write an xtract command that: + * Has a new row for each PubMed record +* Has a column for PMID +* Lists all of the MeSH headings, separated by "|" +* If a heading has multiple subheadings attached, separate the heading and subheadings with "/" +Sample Output: + 24102982|Cell Fusion|Myoblasts/cytology/metabolism|Muscle Development/physiology + +SOLUTION: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ +xtract -pattern PubmedArticle -tab "|" -element MedlineCitation/PMID \ +-block MeshHeading -tab "|" -sep "/" -element DescriptorName,QualifierName + +-=-=-=-=-=-=-=-=-=-=-=-=- + EXERCISE 3: Retrieving XML +How can I get the full XML of all articles about the relationship of Zika Virus to microcephaly in Brazil? Save your results to a file. + +SOLUTION: + + esearch -db pubmed \ +-query "zika virus microcephaly brazil" | \ +efetch -format xml > zika.xml \ No newline at end of file diff --git a/e-utilities-lecture-notes/edirect-for-pubmed-4.sh b/e-utilities-lecture-notes/edirect-for-pubmed-4.sh new file mode 100644 index 0000000..e1a112b --- /dev/null +++ b/e-utilities-lecture-notes/edirect-for-pubmed-4.sh @@ -0,0 +1,377 @@ +# ---------------------------------------------------------------------- +# The Insider's Guide to Accessing NLM Data: EDirect for PubMed +# Part Four: xtract Conditional Arguments +# Course Materials +# https://dataguide.nlm.nih.gov/edirect-for-pubmed-4.txt +# ---------------------------------------------------------------------- +# NOTE: Solutions to all exercises are at the bottom of this document. +# ---------------------------------------------------------------------- + +REMINDERS FROM PART ONE + +esearch: Searches a database and returns PMIDs + +efetch: Retrieves PubMed records in a variety of formats + +Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next + +---------------------------------------------------------------------- + +REMINDERS FROM PART TWO + +xtract: Pulls data from XML and arranges it in a table + +-pattern: Defines rows for xtract + +-element: Defines columns for xtract + +Identify XML elements by name (e.g. ArticleTitle) + +Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID) + +Identify attributes with "@" (e.g. MedlineCitation@Status) + +---------------------------------------------------------------------- + +REMINDERS FROM PART THREE + +-block: Selects and groups child elements of the same parent + +-tab: Defines the separator between columns (default is tab, "\t") + +-sep: Defines the separator between values in the same column (default is tab, "\t") + +Use ">" to save the output to a file + +Use "cat" to pull the contents of a file into the EDirect command + +epost: Stores PMIDs to the History Server + +---------------------------------------------------------------------- + +TIPS FOR CYGWIN USERS: + +Ctrl + C does not Copy +(Cygwin default for Copy is Ctrl + Insert) + +Ctrl + V does not Paste +(Cygwin default for Paste is Shift + Insert) + + +---------------------------------------------------------------------- + +TIPS FOR ALL USERS: + +Ctrl + C "cancels" and gets you back to a prompt + +Up and Down arrow keys allow you to cycle through your recent commands + +clear: clears your screen + +---------------------------------------------------------------------- + +If-Then + +If the condition is met... +Then, create a new row for the pattern and populate the specified columns. +(If not, skip the pattern and move on to the next one.) + +---------------------------------------------------------------------- + +-if + +COMMAND STRING: + +efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml + +efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml | \ +xtract -pattern Author -sep " " -element LastName,Initials Identifier + +efetch -db pubmed -id 27460563,27298442,27392493,27363997,27298443 -format xml | \ +xtract -pattern Author -if Identifier -sep " " -element LastName,Initials Identifier + +---------------------------------------------------------------------- + +EXERCISE 1: + +Write an xtract command that only includes PubMed records if they have MeSH headings +* One row per PubMed record +* Two columns: PMID, Citation Status +Hint: Use this efetch to test: + +efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml | \ +xtract -pattern PubmedArticle -if MeshHeading \ +-element MedlineCitation/PMID, MedlineCitation@Status + + +---------------------------------------------------------------------- + +-if/-equals + +COMMAND STRING: + +efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \ +xtract -pattern PubmedArticle -if ISOAbbreviation -equals JAMA -element Volume Issue + +---------------------------------------------------------------------- + +-if/-equals: Attributes + +COMMAND STRING: + +efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \ +xtract -pattern PubmedArticle -if MedlineCitation@Status -equals MEDLINE \ +-element MedlineCitation/PMID + +---------------------------------------------------------------------- + +Alternatives to -equals + +-contains: Element or attribute contains this string +-starts-with: Element or attribute starts with this string +-ends-with: Element or attribute ends with this string +-is-not: Element or attribute does not match this string + +---------------------------------------------------------------------- + +-if/-contains + +COMMAND STRING: + +efetch -db pubmed -id 27460563,27532912,27392493,27363997,24108526 -format xml | \ +xtract -pattern Author -if Affiliation -contains Japan \ +-sep " " -element LastName,Initials Affiliation + +---------------------------------------------------------------------- + +EXERCISE 2: +Write an xtract command that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.) +* One row per PubMed record +* Two Columns: PMID, ISOAbbreviation +* ISOAbbreviation should start with "JAMA" +Hint: Use this efetch to test: + +efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml | \ +xtract -pattern PubmedArticle -if ISOAbbreviation -starts-with JAMA \ +-element MedlineCitation/PMID ISOAbbreviation + +---------------------------------------------------------------------- + +-if in a -block + +COMMAND STRING: + +efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block ArticleId -if ArticleId@IdType -equals doi -element ArticleId + +---------------------------------------------------------------------- + +Combining multiple conditions + +-or: at least one condition must be true + +-and: all conditions must be true + +---------------------------------------------------------------------- + +-or + +COMMAND STRING: + +efetch -db pubmed -id 16940437,16049336,11972038 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block ArticleId -if ArticleId@IdType -equals doi \ +-or ArticleId@IdType -equals pmc -element ArticleId + +---------------------------------------------------------------------- + +-and + +COMMAND STRING: + +efetch -db pubmed -id 27798514,24372221,24332497,24307782 -format xml | \ +xtract -pattern Author -if LastName -equals Kamal -and Affiliation \ +-sep " " -element LastName,Initials Affiliation + +efetch -db pubmed -id 27582188,27417495,27409810,27306170,18142192 -format xml | \ +xtract -pattern PubmedArticle -if DescriptorName -contains "Zika Virus" \ +-and DescriptorName -equals Microcephaly -element MedlineCitation/PMID ArticleTitle + +---------------------------------------------------------------------- + +EXERCISE 3 +We want to do a search for author BH Smith, and see the different affiliations that are listed for that author +* Limit to publications from 2012 through 2017 + +We only want to see affiliation data for BH Smith, no other authors. + +We want our output to be a table of citations with specific data: +* PMID +* Author Last Name/Initials (should always be BH Smith) +* Affiliation Data + +Write the whole script (not just the xtract command). + + +esearch -db pubmed -query "smith bh[Author]" \ +-datetype PDAT -mindate 2012 -maxdate 2017 | \ +efetch -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -if LastName -equals Smith -and Initials -equals BH -sep " " -element LastName,Initials Affiliation + + + +---------------------------------------------------------------------- + +-position + +Include a -block based on its position: + +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -position first -sep " " -element LastName,Initials + +Use -position with an integer, "first" or "last": + +-position 3 + +-position first + +-position last + +COMMAND STRING: + +efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -sep " " -element LastName,Initials + +efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -position first -sep " " -element LastName,Initials + +efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -position last -sep " " -element LastName,Initials + +---------------------------------------------------------------------- + +Dealing with blanks + +Use -def to define a placeholder to replace blank cells + +Placement for -def is the same as for -tab/-sep. +* Subsequent -def arguments overwrite earlier ones. +* -block arguments clear previous -def arguments. + +COMMAND STRING: + +efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -position first -sep " " -element LastName,Initials Identifier + +efetch -db pubmed -id 28594955,28594944,28594945,28594943,28594948,28594957 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -position first -sep " " -def "N/A" -element LastName,Initials Identifier + + +---------- +**Yes exactly. Suppose I search articles from an institution, then I want to get the position of author from that institution.** +---------- + + +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +HOMEWORK FOR PART FOUR +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- +(Answers are available at: https://dataguide.nlm.nih.gov/classes/edirect-for-pubmed/samplecode4.html) +----------------------------------------------------------------------- +Question 1: + +Fetch the records for the following list of PMIDs: + +28197844 +28176235 +28161874 +28183232 +28164731 +27937077 +28118756 +27845598 +27049596 +27710139 + +Write an xtract command that outputs the PMID and Article Title, but only for records that have a structured abstract. Hint: in PubMed records, structured abstracts are broken up into multiple AbstractText elements, each with their own "NlmCategory" attribute. + +----------------------------------------------------------------------- +Question 2: + +Modify your command from Question 1 to display the "RESULTS" section of each structured abstract, if there is one, in place of the Article Title. If there is no "RESULTS" section, display just the PMID, leaving the second column blank. Hint: Use the "NlmCategory" attribute to determine whether a particular AbstractText element contains "RESULTS". + +----------------------------------------------------------------------- +Question 3: + +When indexing a record for MEDLINE, indexers can assign MeSH headings (descriptors) to represent concepts found in an article, and MeSH subheadings (qualifiers) to describe a specific aspect of a concept. Indexers denote some of the assigned MeSH headings as "Major Topics" (i.e. one of the primary topics of the article). When assigning a "Major Topic", the indexer can determine that the heading itself is a major topic, or that a specific heading/subheading pair is a major topic. When a heading/subheading pair is assigned as a Major Topic, only the subheading will be labeled as Major in the PubMed XML. + +Write an xtract command that outputs one PubMed record per row. Each row should have the record's PMID and a pipe-delimited list of all of the MeSH Headings the indexers have determined are Major Topics. Note: the list should only include headings (descriptors), not subheadings (qualifiers). However, if a heading/subheading pair is assigned as major, the list should include that heading. + +You can use the following efetch command to retrieve some sample records: + + efetch -db pubmed -id 24102982,21171099,17150207 -format xml | \ + +----------------------------------------------------------------------- + Question 4: + + Write a series of commands to search for articles reporting on clinical trials relating to tularemia and output a table of citations. Each row should include the PMID for an article, as well as the name and affiliation information (if any) for the last author. If the last author does not have affiliation information, put "Not Available" in the last column instead. + +-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- + EXERCISE SOLUTIONS: + -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- + EXERCISE 1: + Write an xtract command that only includes PubMed records if they have MeSH headings +* One row per PubMed record +* Two columns: PMID, Citation Status +Hint: Use this efetch to test: + + efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml + +SOLUTION: + + efetch -db pubmed -id 26277396,29313986,19649173,21906097,25380814 -format xml | \ +xtract -pattern PubmedArticle -if MeshHeading \ +-element MedlineCitation/PMID MedlineCitation@Status + +-=-=-=-=-=-=-=-=-=-=-=-=- + EXERCISE 2: + Write an xtract command that only includes PubMed records for articles published in one of the JAMA journals (e.g. JAMA cardiology, JAMA oncology, etc.) +* One row per PubMed record +* Two Columns: PMID, ISOAbbreviation +* ISOAbbreviation should start with "JAMA" + +efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml + +SOLUTION: + + efetch -db pubmed -id 27829097,27829076,19649173,21603067,25380814 -format xml | \ +xtract -pattern PubmedArticle -if ISOAbbreviation -starts-with JAMA \ +-element MedlineCitation/PMID ISOAbbreviation + +-=-=-=-=-=-=-=-=-=-=-=-=- + EXERCISE 3 +We want to do a search for author BH Smith, and see the different affiliations that are listed for that author +* Limit to publications from 2012 through 2017 + +We only want to see affiliation data for BH Smith, no other authors. + +We want our output to be a table of citations with specific data: + * PMID +* Author Last Name/Initials (should always be BH Smith) +* Affiliation Data + +Write the whole script (not just the xtract command). + +SOLUTION: + + esearch -db pubmed -query "smith bh[Author]" \ +-datetype PDAT -mindate 2012 -maxdate 2017 | \ +efetch -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -if LastName -equals Smith -and Initials -equals BH -sep " " -element LastName,Initials Affiliation diff --git a/e-utilities-lecture-notes/edirect-for-pubmed-5-supplemental.sh b/e-utilities-lecture-notes/edirect-for-pubmed-5-supplemental.sh new file mode 100644 index 0000000..135e198 --- /dev/null +++ b/e-utilities-lecture-notes/edirect-for-pubmed-5-supplemental.sh @@ -0,0 +1,110 @@ +# ----------------------------------------------------------------------- +# The Insider's Guide to Accessing NLM Data: EDirect for PubMed +# Part Five: Developing and Building Scripts +# Supplemental Course Materials +# ----------------------------------------------------------------------- +# This file contains code blocks and information about Case Studies 2 & 3 +# +# For Case Study 1, see the Part Five handout: edirect-for-pubmed-5.txt +# +# https://dataguide.nlm.nih.gov/edirect-for-pubmed-5-supplemental.txt +# +# ----------------------------------------------------------------------- + +CASE STUDY 2: +Goal: Look at a single author ("Eric D. Peterson") and identify his most frequent co-authors. + +CODE BLOCKS: + +Phase One: Author Disambiguation + +esearch -db pubmed -query "peterson ed[au]" + +esearch -db pubmed -query "peterson ed[au]" | \ +efetch -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -if LastName -equals Peterson -and Initials -equals ED \ +-def "N/A" -element LastName ForeName Identifier + +esearch -db pubmed -query "peterson ed[au]" | \ +efetch -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -if LastName -equals peterson -and Initials -equals ed \ +-and ForeName -is-not "Erik D" \ +-element LastName ForeName + +esearch -db pubmed -query "peterson ed[au] NOT (peterson erik[fau])" + +esearch -db pubmed -query "peterson ed[au] NOT (peterson erik[fau])" | \ +efetch -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -if LastName -equals peterson -and Initials -equals ed \ +-element LastName ForeName \ +-block Investigator -if LastName -equals peterson -and Initials -equals ed \ +-element LastName ForeName + +esearch -db pubmed -query "peterson ed[au] NOT (peterson erik[fau])" | \ +efetch -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -if LastName -equals peterson -and Initials -equals ed \ +-element Affiliation \ +-block Investigator -if LastName -equals peterson -and Initials -equals ed \ +-element Affiliation + +Phase Two: Identifying Co-authors + +esearch -db pubmed -query "peterson ed[au] NOT (peterson erik[fau])" | \ +efetch -format xml | \ +xtract -pattern Author -if LastName -is-not Peterson -and Initials -is-not ED -tab " " -element LastName Initials | \ +sort-uniq-count-rank + +----------------------------------------------------------------------- + +CASE STUDY 3: +Goal: Analyze a complex search strategy to identify gaps in the existing strategy and find new search terms to include. + +About the strategy: The search is run each week to capture new citations. It searches a list of 300+ veterinary journals, as well as a handful of MeSH subject terms. Both parts of the stratgegy are updated periodically. + + + +CODE BLOCKS: +(NOTE: The following code blocks require having a search strategy saved to a file named "vetjournals.txt" in your home directory. The code will not work properly without that file.) + +esearch -db pubmed -query "$(cat vetjournals.txt)" -datetype PDAT -mindate 2017 -maxdate 2017 + +esearch -db pubmed -query "$(cat vetjournals.txt)" -datetype PDAT -mindate 2017 -maxdate 2017 | \ +efetch -format uid + +efetch -db pubmed -id 25426834,25319380,24899544 -format xml | \ +xtract -pattern MeshHeading -element DescriptorName + +DO NOT RUN THE FOLLOWING CODE! +(It will take several minutes to download such a large set of records in XML!) +*************************************** +esearch -db pubmed -query "$(cat vetjournals.txt)" -datetype PDAT -mindate 2017 -maxdate 2017 | \ +efetch -format xml | \ +xtract -pattern MeshHeading -element DescriptorName | \ +sort-uniq-count-rank > descriptors.txt +*************************************** +esearch -db pubmed -query "$(cat vetjournals.txt)" -datetype PDAT -mindate 2017 -maxdate 2017 | \ +efetch -format xml > vet.xml +*************************************** + +Note: The following code will only run successfully if you have a file named "vet.xml" that contains PubMed XML in your home directory. + +xtract -input vet.xml -pattern MeshHeading -element DescriptorName | sort-uniq-count-rank > descriptors.txt + +xtract -input vet.xml -pattern MeshHeading \ +-if DescriptorName@MajorTopicYN -equals Y \ +-or QualifierName@MajorTopicYN -equals Y -element DescriptorName | \ +sort-uniq-count-rank > majortopics.txt + +xtract -input vet.xml -pattern Keyword -element Keyword | sort-uniq-count-rank > authorkeywords.txt + + +xtract vet.xml -pattern Keyword -element Keyword | sort-uniq-count-rank > authorkeywords.txt + + + + + diff --git a/e-utilities-lecture-notes/edirect-for-pubmed-5.sh b/e-utilities-lecture-notes/edirect-for-pubmed-5.sh new file mode 100644 index 0000000..40410bc --- /dev/null +++ b/e-utilities-lecture-notes/edirect-for-pubmed-5.sh @@ -0,0 +1,180 @@ +# ---------------------------------------------------------------------- +# The Insider's Guide to Accessing NLM Data: EDirect for PubMed +# Part Five: Developing and Building Scripts +# Course Materials +# https://dataguide.nlm.nih.gov/edirect-for-pubmed-5.txt +# ---------------------------------------------------------------------- +# NOTE: Solutions to all exercises are at the bottom of this document. +# ---------------------------------------------------------------------- +# +# REMINDERS FROM PART ONE +# +# esearch: Searches a database and returns PMIDs +# +# efetch: Retrieves PubMed records in a variety of formats +# +# Use "|" (Shift + \, pronounced "pipe") to "pipe" the results of one command into the next +# +# ---------------------------------------------------------------------- +# +# REMINDERS FROM PART TWO +# +# xtract: Pulls data from XML and arranges it in a table +# +# -pattern: Defines rows for xtract +# +# -element: Defines columns for xtract +# +# Identify XML elements by name (e.g. ArticleTitle) +# +# Identify specific child elements with Parent/Child construction (e.g. MedlineCitation/PMID) +# +# Identify attributes with "@" (e.g. MedlineCitation@Status) +# +# ---------------------------------------------------------------------- +# +# REMINDERS FROM PART THREE +# +# -block: Selects and groups child elements of the same parent +# +# -tab: Defines the separator between columns (default is tab, "\t") +# +# -sep: Defines the separator between values in the same column (default is tab, "\t") +# +# Use ">" to save the output to a file +# +# Use "cat" to pull the contents of a file into the EDirect command +# +# epost: Stores PMIDs to the History Server +# +# ---------------------------------------------------------------------- +# +# REMINDERS FROM PART FOUR +# +# -if: Defines an element/attribute that must be present in order to include a pattern/block. +# (e.g. "If is present in the pattern/block, include pattern/block in the output.") +# +# -if/-equals: Defines a specific element/attribute that must be equal to a specific value in order to include a pattern/block, +# (e.g. "If an equals [value] in the pattern/block, include pattern/block in the output.") +# +# +# Alternatives to -equals: let you define more specific conditions +# -contains: Element or attribute must contain this string +# -starts-with: Element or attribute must start with this string +# -ends-with: Element or attribute must end with this string +# -is-not: Element or attribute must not match this string +# +# +# Alternatives to -if: let you combine multiple conditions +# -or: at least one condition must be true +# -and: all conditions must be true +# +# +# -position: Includes a block based on its position in a series of blocks. +# Use -position with an integer, "first" or "last": +# +# ---------------------------------------------------------------------- +# +# TIPS FOR CYGWIN USERS: +# +# Ctrl + C does not Copy +# (Cygwin default for Copy is Ctrl + Insert) +# +# Ctrl + V does not Paste +# (Cygwin default for Paste is Shift + Insert) +# +# ---------------------------------------------------------------------- +# +# TIPS FOR ALL USERS: +# +# Ctrl + C "cancels" and gets you back to a prompt +# +# Up and Down arrow keys allow you to cycle through your recent commands +# +# clear: clears your screen +# +# ---------------------------------------------------------------------- +# +# Tips for Developing a Script +# +# 1. Identify your goal. +# * Identify your input +# * Identify your output +# * Identify your format +# 2. Choose your tool. +# 3. Decide how much to automate. +# 4. Build one step at a time. +# +# ---------------------------------------------------------------------- +# +# E-utilities Usage Guidelines and Requirements from NCBI +# https://www.ncbi.nlm.nih.gov/books/NBK25497/#chapter2.Usage_Guidelines_and_Requiremen +# +# NLM Data Distribution: Download MEDLINE/PubMed Data +# https://www.nlm.nih.gov/databases/download/pubmed_medline.html +# +# Using EDirect to create a local copy of PubMed +# https://dataguide.nlm.nih.gov/edirect/archive.html +# +# NCBI Documentation: EDirect: Local Data Cache +# https://www.ncbi.nlm.nih.gov/books/NBK179288/#chapter6.Local_Data_Cache +# +# ---------------------------------------------------------------------- + +Case 1: Simple table of data elements + +We want a list of articles about breast cancer that were published in 2016 and the first half of 2017 and are linked to ClinicalTrials.gov entries. + +For each article we want: +* PMID +* NCT Number(s) +* First Author +* Journal + +---------------------------------------------------------------------- + +Case Study + +COMMAND STRING: + +esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" + +esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \ +-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 + +esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \ +-datetype PDAT -mindate 2018/01/01 -maxdate 2018/02/28 + +efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml + +efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation + +efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \ +-block Author -position first -sep " " -element LastName,Initials + +efetch -db pubmed -id 29172605,29158011,29136523,29045554,29045543,28918548,28741175,28702218 -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \ +-block Author -position first -sep " " -element LastName,Initials \ +-block DataBank -if DataBankName -equals ClinicalTrials.gov \ +-sep "|" -element AccessionNumber + +CASE STUDY SOLUTION: +esearch -db pubmed -query "breast cancer AND clinicaltrials.gov[si]" \ +-datetype PDAT -mindate 2017/03/01 -maxdate 2018/02/28 | \ +efetch -format xml | \ +xtract -pattern PubmedArticle -element MedlineCitation/PMID ISOAbbreviation \ +-block Author -position first -sep " " -element LastName,Initials \ +-block DataBank -if DataBankName -equals ClinicalTrials.gov \ +-sep "|" -element AccessionNumber > clinicaltrials.txt + + +---------------------------------------------------------------------- + +**hacettepe different affiliations** + + + +EDirect Cookbook on GitHub +https://ncbi-hackathons.github.io/EDirectCookbook/ \ No newline at end of file diff --git a/e-utilities-lecture-notes/edirect-for-pubmed-final-exam-march-2018.txt b/e-utilities-lecture-notes/edirect-for-pubmed-final-exam-march-2018.txt new file mode 100644 index 0000000..9681747 --- /dev/null +++ b/e-utilities-lecture-notes/edirect-for-pubmed-final-exam-march-2018.txt @@ -0,0 +1,64 @@ +EDirect for PubMed Final Exam +DUE: 11:59 PM EDT, March 26, 2018 + +Instructions: +This exam is completely "open-book" and untimed. Feel free to review any of the recordings, handouts, sample code and/or documentation while answering these questions. + +In a text file, write scripts that will answer each of the questions posed below. + +If you get stuck, remember that the instructors will be available to answer questions in our office hours session on Thursday, March 22, at 1 PM ET. If you have questions at any other time, please e-mail us at NLMtrainers@nih.gov. + +To submit your exam, save your text file as edirect-march18-XXXXXXX.txt (where XXXXXXX is your last name). + +Attach the file to an e-mail, and send it to NLMtrainers@nih.gov no later than the due date specified above. Even if you are unable to answer every question perfectly, we encourage you to submit what you have, so we can provide feedback to help you figure out the rest. + +We will review each submission as quickly as possible, and will reply with feedback, and with instructions on how to claim your MLA CE credit. + +Thanks for participating in EDirect for PubMed! + + +Question 1: + +This is a multi-part question that will have you create a series of short scripts to help you analyze and evaluate the research output of an institution or organization. For the sake of example, we will evaluate the Scripps Research Institute, but if you would prefer to use your own institution or organization, feel free! + +A. One way of evaluating the research output of an organization is by topic. Write a script that will find articles published in the last two years by authors affiliated with the Scripps Research Institute, and will generate a list of the top 20 MeSH descriptors most frequently assigned to those articles by indexers. + +B. Your output for part A may include many MeSH descriptors that don't seem specifically relevant to this institution (e.g. Humans, Animals, Male, Female, etc.). Create another script that will find articles published in the last two years by authors affiliated with the Scripps Research Institute, and generates a list of the top 20 MeSH descriptors most frequently assigned to those articles as Major Topics. Hint: You may want to review the homework questions from Session 4, which may give you some ideas as to how to accomplish this. + +C. Not all articles in PubMed are indexed with MeSH terms. Another way to evaluate the topical portfolio of an institution is by looking at the author-supplied keywords. Create another script that will find articles published in the last two years by authors affiliated with the Scripps Research Institute, and generates a list of the top 20 keywords most frequently assigned to those articles by their authors. (Note: Because author-supplied keywords are author-supplied, and are not drawn from a controlled vocabulary, this method may be less practical as a real-world solution, without further post-processing. However, it's still a good exercise!) + +D. We can also evaluate the output of an institution by seeing which agencies are funding grants which eventually leads to published research from its authors. Create another script that will find articles published in the last two years by authors affiliated with the Scripps Research Institute, and generates a list of the top 20 funding agencies most frequently associated with those records. + +E. Say that instead of evaluating an institution's output, we instead want to evaluate a group of authors. We know that we will want to re-run this evaluation periodically, but that our author list might change. We want to save our search strategy in a text file instead of including it as part of our script, so we can modify it more easily. Modify your script from part D to pull the search strategy from a text file. + + + +Question 2: + +This question tests your ability to output exactly the data you need from PubMed in a specific format. We strongly suggest you read the entire question before you begin. + +Write a script that generates a list of articles published in 2016 or 2017 that have been retracted. Make sure that the output is formatted according to the following guidelines: + +A. For each retracted article, the list should include the PMID for the retracted article, the name of the retracted article's first author, the PMID of the retraction notice and the citation information of the retraction notice. + +B. Not every PubMed record includes listed authors. If a retracted article has no authors listed, exclude it from your results. + +C. Some PubMed records list collective or corporate names for some authors, instead of personal names. If a retracted article has a first author with a collective name, output the collective name for the first author. If a retracted article has a first author with a personal name, output the last name and initials, separated by a space. + +D. If the retraction notice does not have a PMID, the output table should have "XXXXXXXX" in place of the retraction notice PMID. + +E. Save the output to a text file, so you can open it in Microsoft Excel or another application. (PLEASE DO NOT SUBMIT YOUR OUTPUT FILE WITH YOUR EXAM.) + +Your solution to this question should be a single script that meets all of the above conditions. To help you get started, here are some resources that might help you navigate the relevant portions of PubMed data. + +Information about searching PubMed for retractions: +https://www.ncbi.nlm.nih.gov/books/NBK3827/#pubmedhelp.Comment_Correction_Type + +Information about how retractions are represented in PubMed XML: +https://www.nlm.nih.gov/bsd/licensee/elements_descriptions.html#commentscorrections + +Information about how author names (personal and collective) are represented in PubMed XML: +https://www.nlm.nih.gov/bsd/licensee/elements_descriptions.html#authorlist + +Fact Sheet: Errata, Retractions, and Other Linked Citations in PubMed +https://www.nlm.nih.gov/pubs/factsheets/errata.html diff --git a/e-utilities-lecture-notes/edirect-march18-Balci.sh b/e-utilities-lecture-notes/edirect-march18-Balci.sh new file mode 100644 index 0000000..06ea7f5 --- /dev/null +++ b/e-utilities-lecture-notes/edirect-march18-Balci.sh @@ -0,0 +1,199 @@ +EDirect for PubMed Final Exam +DUE: 11:59 PM EDT, March 26, 2018 + +Serdar Balci + +Instructions: +This exam is completely "open-book" and untimed. Feel free to review any of the recordings, handouts, sample code and/or documentation while answering these questions. + +In a text file, write scripts that will answer each of the questions posed below. + +If you get stuck, remember that the instructors will be available to answer questions in our office hours session on Thursday, March 22, at 1 PM ET. If you have questions at any other time, please e-mail us at NLMtrainers@nih.gov. + +To submit your exam, save your text file as edirect-march18-XXXXXXX.txt (where XXXXXXX is your last name). + +Attach the file to an e-mail, and send it to NLMtrainers@nih.gov no later than the due date specified above. Even if you are unable to answer every question perfectly, we encourage you to submit what you have, so we can provide feedback to help you figure out the rest. + +We will review each submission as quickly as possible, and will reply with feedback, and with instructions on how to claim your MLA CE credit. + +Thanks for participating in EDirect for PubMed! + + +Question 1: + +Scripps Research Institute + + +A. One way of evaluating the research output of an organization is by topic. +Write a script that will find articles published in the last two years by +authors affiliated with the Scripps Research Institute, +and will generate a list of the top 20 MeSH descriptors +most frequently assigned to those articles by indexers. + +esearch -db pubmed -query "'Scripps Research Institute'[Affiliation]" \ +-datetype PDAT -mindate 2016/03/01 | \ +efetch -format xml | \ +xtract -pattern DescriptorName -element DescriptorName | \ +sort-uniq-count-rank | \ +head -n 20 + + + +B. Your output for part A may include many MeSH descriptors +that dont seem specifically relevant to this institution +(e.g. Humans, Animals, Male, Female, etc.). +Create another script that will find articles published in the +last two years by authors affiliated with the Scripps Research Institute, +and generates a list of the top 20 MeSH descriptors most frequently assigned +to those articles as Major Topics. +Hint: You may want to review the homework questions from Session 4, +which may give you some ideas as to how to accomplish this. + +esearch -db pubmed -query "'Scripps Research Institute'[Affiliation]" \ +-datetype PDAT -mindate 2016/03/01 | \ +efetch -format xml | \ +xtract -pattern DescriptorName -element DescriptorName | \ +grep -vxf checktags.txt | \ +sort-uniq-count-rank | \ +head -n 20 + + + + + + +C. Not all articles in PubMed are indexed with MeSH terms. +Another way to evaluate the topical portfolio of an institution +is by looking at the author-supplied keywords. +Create another script that will find articles published +in the last two years by authors affiliated with the Scripps Research Institute, +and generates a list of the top 20 keywords most frequently assigned to those +articles by their authors. +(Note: Because author-supplied keywords are author-supplied, +and are not drawn from a controlled vocabulary, +this method may be less practical as a real-world solution, +without further post-processing. However, its still a good exercise!) + +esearch -db pubmed -query "'Scripps Research Institute'[Affiliation]" \ +-datetype PDAT -mindate 2016/03/01 | \ +efetch -format xml | \ +xtract -pattern Keyword -element Keyword | \ +sort-uniq-count-rank | \ +head -n 20 + + +D. We can also evaluate the output of an institution +by seeing which agencies are funding grants which eventually +leads to published research from its authors. Create +another script that will find articles published in the last two +years by authors affiliated with the Scripps Research Institute, +and generates a list of the top 20 funding agencies most frequently +associated with those records. + + +esearch -db pubmed -query "'Scripps Research Institute'[Affiliation]" \ +-datetype PDAT -mindate 2016/03/01 | \ +efetch -format xml | \ +xtract -pattern Agency -element Agency | \ +sort-uniq-count-rank | \ +head -n 20 + + + +E. Say that instead of evaluating an institution output, +we instead want to evaluate a group of authors. +We know that we will want to re-run this evaluation periodically, +but that our author list might change. We want to save our search strategy +in a text file instead of including it as part of our script, +so we can modify it more easily. +Modify your script from part D to pull the search strategy from a text file. + +esearch -db pubmed -query "$(cat authorlist.txt)" \ +-datetype PDAT -mindate 2016/03/01 | \ +efetch -format xml | \ +xtract -pattern Agency -element Agency | \ +sort-uniq-count-rank | \ +head -n 20 + + + + +Question 2: + +This question tests your ability to output exactly +the data you need from PubMed in a specific format. +We strongly suggest you read the entire question before you begin. + +Write a script that generates a list of articles published +in 2016 or 2017 that have been retracted. +Make sure that the output is formatted according to the following guidelines: + + + +A. For each retracted article, the list should include the PMID for the retracted article, +the name of the retracted article first author, the PMID of the retraction notice and +the citation information of the retraction notice. + +esearch -db pubmed -query "hasretractionin" \ +-datetype PDAT -mindate 2016 -maxdate 2017 | \ +efetch -format xml |\ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -position first -sep " " -element LastName,Initials \ +-block CommentsCorrections -if CommentsCorrections@RefType -equals RetractionIn -element CommentsCorrections/PMID CommentsCorrections/RefSource \ +>retractionlist.csv + + + +B. Not every PubMed record includes listed authors. +If a retracted article has no authors listed, exclude it from your results. + + +C. Some PubMed records list collective or corporate names for some authors, +instead of personal names. If a retracted article has a first author with a collective name, +output the collective name for the first author. If a retracted article has a first author +with a personal name, output the last name and initials, separated by a space. + + + + + +D. If the retraction notice does not have a PMID, +the output table should have "XXXXXXXX" in place of the retraction notice PMID. + +esearch -db pubmed -query "hasretractionin" \ +-datetype PDAT -mindate 2016 -maxdate 2017 | \ +efetch -format xml |\ +xtract -pattern PubmedArticle -element MedlineCitation/PMID \ +-block Author -position first -sep " " -element LastName,Initials \ +-block CommentsCorrections -if CommentsCorrections@RefType -equals RetractionIn -def "XXXXXXXX" -element CommentsCorrections/PMID -element CommentsCorrections/RefSource \ +>retractionlist.csv + + +E. Save the output to a text file, +so you can open it in Microsoft Excel or another application. +(PLEASE DO NOT SUBMIT YOUR OUTPUT FILE WITH YOUR EXAM.) + +esearch -db pubmed -query "hasretractionin" \ +-datetype PDAT -mindate 2016 -maxdate 2017 | \ +efetch -format xml |\ +xtract -pattern PubmedArticle -if Author -element MedlineCitation/PMID \ +-block Author -if Author/CollectiveName -element CollectiveName -block Author -position first -sep " " -element LastName,Initials \ +-block CommentsCorrections -if CommentsCorrections@RefType -equals RetractionIn -def "XXXXXXXX" -element CommentsCorrections/PMID -element CommentsCorrections/RefSource \ +>retractionlist.txt + + +Your solution to this question should be a single script +that meets all of the above conditions. To help you get started, +here are some resources that might help you navigate the relevant portions of PubMed data. + +Information about searching PubMed for retractions: +https://www.ncbi.nlm.nih.gov/books/NBK3827/#pubmedhelp.Comment_Correction_Type + +Information about how retractions are represented in PubMed XML: +https://www.nlm.nih.gov/bsd/licensee/elements_descriptions.html#commentscorrections + +Information about how author names (personal and collective) are represented in PubMed XML: +https://www.nlm.nih.gov/bsd/licensee/elements_descriptions.html#authorlist + +Fact Sheet: Errata, Retractions, and Other Linked Citations in PubMed +https://www.nlm.nih.gov/pubs/factsheets/errata.html diff --git a/e-utilities-lecture-notes/edirect-march18-Balci.txt b/e-utilities-lecture-notes/edirect-march18-Balci.txt new file mode 100644 index 0000000..cca6afa --- /dev/null +++ b/e-utilities-lecture-notes/edirect-march18-Balci.txt @@ -0,0 +1,78 @@ +EDirect for PubMed Final Exam +DUE: 11:59 PM EDT, March 26, 2018 + +Serdar Balci + + +Question 1: + +A. + +esearch -db pubmed -query "'Scripps Research Institute'[Affiliation]" \ +-datetype PDAT -mindate 2016/03/01 | \ +efetch -format xml | \ +xtract -pattern DescriptorName -element DescriptorName | \ +sort-uniq-count-rank | \ +head -n 20 + + +B. + +esearch -db pubmed -query "'Scripps Research Institute'[Affiliation]" \ +-datetype PDAT -mindate 2016/03/01 | \ +efetch -format xml | \ +xtract -pattern DescriptorName -element DescriptorName | \ +grep -vxf checktags.txt | \ +sort-uniq-count-rank | \ +head -n 20 + + +C. + +esearch -db pubmed -query "'Scripps Research Institute'[Affiliation]" \ +-datetype PDAT -mindate 2016/03/01 | \ +efetch -format xml | \ +xtract -pattern Keyword -element Keyword | \ +sort-uniq-count-rank | \ +head -n 20 + + +D. + +esearch -db pubmed -query "'Scripps Research Institute'[Affiliation]" \ +-datetype PDAT -mindate 2016/03/01 | \ +efetch -format xml | \ +xtract -pattern Agency -element Agency | \ +sort-uniq-count-rank | \ +head -n 20 + + +E. + +esearch -db pubmed -query "$(cat authorlist.txt)" \ +-datetype PDAT -mindate 2016/03/01 | \ +efetch -format xml | \ +xtract -pattern Agency -element Agency | \ +sort-uniq-count-rank | \ +head -n 20 + + + +Question 2: + +esearch -db pubmed -query "hasretractionin" \ +-datetype PDAT -mindate 2016 -maxdate 2017 | \ +efetch -format xml |\ +xtract -pattern PubmedArticle -if Author -element MedlineCitation/PMID \ +-block Author -if Author/CollectiveName -element CollectiveName -block Author -position first -sep " " -element LastName,Initials \ +-block CommentsCorrections -if CommentsCorrections@RefType -equals RetractionIn -def "XXXXXXXX" -element CommentsCorrections/PMID -element CommentsCorrections/RefSource \ +>retractionlist.txt + + +esearch -db pubmed -query "hasretractionin" \ +-datetype PDAT -mindate 2016 -maxdate 2017 | \ +efetch -format xml |\ +xtract -pattern PubmedArticle -if Author -element MedlineCitation/PMID \ +-block Author -if Author/CollectiveName -element CollectiveName -block Author -position first -sep " " -element LastName,Initials \ +-block CommentsCorrections -if CommentsCorrections@RefType -equals RetractionIn -def "XXXXXXXX" -element CommentsCorrections/PMID -element CommentsCorrections/RefSource \ +>retractionlist.txt diff --git a/e-utilities-lecture-notes/myquery.txt b/e-utilities-lecture-notes/myquery.txt new file mode 100644 index 0000000..9bab272 --- /dev/null +++ b/e-utilities-lecture-notes/myquery.txt @@ -0,0 +1,10 @@ +240 NICHD NIH HHS +215 NIDDK NIH HHS +71 NHLBI NIH HHS +70 NIEHS NIH HHS +56 Medical Research Council +45 NCATS NIH HHS +17 NIGMS NIH HHS +16 NCRR NIH HHS +15 NIMH NIH HHS +14 NIA NIH HHS diff --git a/e-utilities-lecture-notes/part1-1.txt b/e-utilities-lecture-notes/part1-1.txt new file mode 100644 index 0000000..9934f85 --- /dev/null +++ b/e-utilities-lecture-notes/part1-1.txt @@ -0,0 +1,7 @@ + + pubmed + NCID_1_203517608_130.14.18.34_9001_1520427561_1688902671_0MetA0_S_MegaStore_F_1 + 1 + 1695 + 1 + diff --git a/e-utilities-lecture-notes/part1-2.txt b/e-utilities-lecture-notes/part1-2.txt new file mode 100644 index 0000000..0d355f1 --- /dev/null +++ b/e-utilities-lecture-notes/part1-2.txt @@ -0,0 +1,7 @@ + + pubmed + NCID_1_54233261_130.14.22.215_9001_1520434333_518150207_0MetA0_S_MegaStore_F_1 + 1 + 5429 + 1 + diff --git a/e-utilities-lecture-notes/part1-3.txt b/e-utilities-lecture-notes/part1-3.txt new file mode 100644 index 0000000..63d720b --- /dev/null +++ b/e-utilities-lecture-notes/part1-3.txt @@ -0,0 +1,7 @@ + + pubmed + NCID_1_54194188_130.14.22.215_9001_1520434183_1404976732_0MetA0_S_MegaStore_F_1 + 1 + 212 + 1 + diff --git a/e-utilities-lecture-notes/part1-4.txt b/e-utilities-lecture-notes/part1-4.txt new file mode 100644 index 0000000..cf17c31 --- /dev/null +++ b/e-utilities-lecture-notes/part1-4.txt @@ -0,0 +1,7 @@ + + pubmed + NCID_1_205204336_130.14.18.34_9001_1520434198_944619105_0MetA0_S_MegaStore_F_1 + 1 + 12 + 1 + diff --git a/e-utilities-lecture-notes/part1-5.txt b/e-utilities-lecture-notes/part1-5.txt new file mode 100644 index 0000000..162949d --- /dev/null +++ b/e-utilities-lecture-notes/part1-5.txt @@ -0,0 +1,7 @@ + + pubmed + NCID_1_205243067_130.14.18.34_9001_1520434348_1018590557_0MetA0_S_MegaStore_F_1 + 1 + 5429 + 1 + diff --git a/e-utilities-lecture-notes/part1-6.txt b/e-utilities-lecture-notes/part1-6.txt new file mode 100644 index 0000000..4b2f8cf --- /dev/null +++ b/e-utilities-lecture-notes/part1-6.txt @@ -0,0 +1,37 @@ + +1. Science. 2014 Oct 31;346(6209):608-13. doi: 10.1126/science.1258040. + +Structural basis for microRNA targeting. + +Schirle NT(1), Sheu-Gruttadauria J(1), MacRae IJ(2). + +Author information: +(1)Department of Integrative Structural and Computational Biology, The Scripps +Research Institute, La Jolla, CA 92037, USA. +(2)Department of Integrative Structural and Computational Biology, The Scripps +Research Institute, La Jolla, CA 92037, USA. macrae@scripps.edu. + +Comment in + Science. 2014 Oct 31;346(6209):542-3. + +MicroRNAs (miRNAs) control expression of thousands of genes in plants and +animals. miRNAs function by guiding Argonaute proteins to complementary sites in +messenger RNAs (mRNAs) targeted for repression. We determined crystal structures +of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target +RNAs representing miRNA recognition sites. These structures suggest a stepwise +mechanism, in which Ago2 primarily exposes guide nucleotides (nt) 2 to 5 for +initial target pairing. Pairing to nt 2 to 5 promotes conformational changes that +expose nt 2 to 8 and 13 to 16 for further target recognition. Interactions with +the guide-target minor groove allow Ago2 to interrogate target RNAs in a +sequence-independent manner, whereas an adenosine binding-pocket opposite guide +nt 1 further facilitates target recognition. Spurious slicing of miRNA targets is +avoided through an inhibitory coordination of one catalytic magnesium ion. These +results explain the conserved nucleotide-pairing patterns in animal miRNA target +sites first observed over two decades ago. + +Copyright © 2014, American Association for the Advancement of Science. + +DOI: 10.1126/science.1258040 +PMCID: PMC4313529 +PMID: 25359968 [Indexed for MEDLINE] + diff --git a/e-utilities-lecture-notes/part1-e1.txt b/e-utilities-lecture-notes/part1-e1.txt new file mode 100644 index 0000000..1688bfc --- /dev/null +++ b/e-utilities-lecture-notes/part1-e1.txt @@ -0,0 +1,31 @@ +500 Can't connect to eutils.ncbi.nlm.nih.gov:443 +No do_post output returned from 'https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=diabetes%20AND%20spanish%5Blang%5D&retmax=0&usehistory=y&edirect_os=darwin&edirect=7.90&tool=edirect&email=serdarbalciold@cf1-2.local' +Result of do_post http request is +$VAR1 = bless( { + '_headers' => bless( { + 'content-type' => 'text/plain', + 'client-warning' => 'Internal response', + '::std_case' => { + 'client-date' => 'Client-Date', + 'client-warning' => 'Client-Warning' + }, + 'client-date' => 'Wed, 07 Mar 2018 16:52:57 GMT' + }, 'HTTP::Headers' ), + '_request' => bless( { + '_uri' => bless( do{\(my $o = 'https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi')}, 'URI::https' ), + '_headers' => bless( { + 'content-type' => 'application/x-www-form-urlencoded', + 'user-agent' => 'libwww-perl/6.05' + }, 'HTTP::Headers' ), + '_content' => 'db=pubmed&term=diabetes%20AND%20spanish%5Blang%5D&retmax=0&usehistory=y&edirect_os=darwin&edirect=7.90&tool=edirect&email=serdarbalciold@cf1-2.local', + '_method' => 'POST' + }, 'HTTP::Request' ), + '_content' => 'Can\'t connect to eutils.ncbi.nlm.nih.gov:443 + +LWP::Protocol::https::Socket: getaddrinfo: nodename nor servname provided, or not known at /System/Library/Perl/Extras/5.18/LWP/Protocol/http.pm line 51. +', + '_msg' => 'Can\'t connect to eutils.ncbi.nlm.nih.gov:443', + '_rc' => 500 + }, 'HTTP::Response' ); + +WebEnv value not found in search output - WebEnv1 diff --git a/e-utilities-lecture-notes/part1-pipe.txt b/e-utilities-lecture-notes/part1-pipe.txt new file mode 100644 index 0000000..b8af380 --- /dev/null +++ b/e-utilities-lecture-notes/part1-pipe.txt @@ -0,0 +1,3 @@ +26306366 +8097056 +2447467 diff --git a/e-utilities-lecture-notes/pubmed2.txt b/e-utilities-lecture-notes/pubmed2.txt new file mode 100644 index 0000000..fbbed8a --- /dev/null +++ b/e-utilities-lecture-notes/pubmed2.txt @@ -0,0 +1,1534 @@ + + + + + + 24102982 + + 2014 + 01 + 22 + + + 2017 + 02 + 20 + +
+ + 1742-4658 + + 280 + 23 + + 2013 + Dec + + + The FEBS journal + FEBS J. + + G-protein coupled receptor 56 promotes myoblast fusion through serum response factor- and nuclear factor of activated T-cell-mediated signalling but is not essential for muscle development in vivo. + + 6097-113 + + 10.1111/febs.12529 + + Mammalian muscle cell differentiation is a complex process of multiple steps for which many of the factors involved have not yet been defined. In a screen to identify the regulators of myogenic cell fusion, we found that the gene for G-protein coupled receptor 56 (GPR56) was transiently up-regulated during the early fusion of human myoblasts. Human mutations in the gene for GPR56 cause the disease bilateral frontoparietal polymicrogyria; however, the consequences of receptor dysfunction on muscle development have not been explored. Using knockout mice, we defined the role of GPR56 in skeletal muscle. GPR56(-/-) myoblasts have decreased fusion and smaller myotube sizes in culture. In addition, a loss of GPR56 expression in muscle cells results in decreases or delays in the expression of myogenic differentiation 1, myogenin and nuclear factor of activated T-cell (NFAT)c2. Our data suggest that these abnormalities result from decreased GPR56-mediated serum response element and NFAT signalling. Despite these changes, no overt differences in phenotype were identified in the muscle of GPR56 knockout mice, which presented only a mild but statistically significant elevation of serum creatine kinase compared to wild-type. In agreement with these findings, clinical data from 13 bilateral frontoparietal polymicrogyria patients revealed mild serum creatine kinase increase in only two patients. In summary, targeted disruption of GPR56 in mice results in myoblast abnormalities. The absence of a severe muscle phenotype in GPR56 knockout mice and human patients suggests that other factors may compensate for the lack of this G-protein coupled receptor during muscle development and that the motor delay observed in these patients is likely not a result of primary muscle abnormalities. + © 2013 FEBS. + + + + Wu + Melissa P + MP + + Department of Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA; Division of Genetics, Boston Children's Hospital, MA, USA. + + + + Doyle + Jamie R + JR + + + Barry + Brenda + B + + + Beauvais + Ariane + A + + + Rozkalne + Anete + A + + + Piao + Xianhua + X + + + Lawlor + Michael W + MW + + + Kopin + Alan S + AS + + + Walsh + Christopher A + CA + + + Gussoni + Emanuela + E + + + eng + + + 2R01NS047727 + NS + NINDS NIH HHS + United States + + + R01 NS047727 + NS + NINDS NIH HHS + United States + + + T32 GM007226 + GM + NIGMS NIH HHS + United States + + + L40 AR057721 + AR + NIAMS NIH HHS + United States + + + P30-HD1865 + HD + NICHD NIH HHS + United States + + + 1R01AR060317-01 + AR + NIAMS NIH HHS + United States + + + P30 HD018655 + HD + NICHD NIH HHS + United States + + + R01 AR060317 + AR + NIAMS NIH HHS + United States + + + K08 AR059750 + AR + NIAMS NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + + + 2013 + 10 + 08 + +
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pathology + + + Mice + + + Mice, Knockout + + + Muscle Development + physiology + + + MyoD Protein + genetics + metabolism + + + Myoblasts + cytology + metabolism + + + Myogenin + genetics + metabolism + + + NFATC Transcription Factors + antagonists & inhibitors + genetics + metabolism + + + RNA, Messenger + genetics + + + RNA, Small Interfering + genetics + + + Real-Time Polymerase Chain Reaction + + + Receptors, G-Protein-Coupled + physiology + + + Reverse Transcriptase Polymerase Chain Reaction + + + Serum Response Element + genetics + + + Signal Transduction + + + + GPR56 + dystroglycanopathies + myoblast + serum response element + skeletal muscle + +
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+ + + + 2006 + 03 + 28 + + + 2006 + 10 + 12 + + + 2006 + 11 + 01 + + + 2006 + 12 + 8 + 9 + 0 + + + 2007 + 3 + 6 + 9 + 0 + + + 2006 + 12 + 8 + 9 + 0 + + + ppublish + + 17150207 + S0012-1606(06)01341-8 + 10.1016/j.ydbio.2006.11.002 + PMC1779902 + NIHMS16058 + + +
+ +
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+ + 1742-4658 + + 280 + 23 + + 2013 + Dec + + + The FEBS journal + FEBS J. + + G-protein coupled receptor 56 promotes myoblast fusion through serum response factor- and nuclear factor of activated T-cell-mediated signalling but is not essential for muscle development in vivo. + + 6097-113 + + 10.1111/febs.12529 + + Mammalian muscle cell differentiation is a complex process of multiple steps for which many of the factors involved have not yet been defined. In a screen to identify the regulators of myogenic cell fusion, we found that the gene for G-protein coupled receptor 56 (GPR56) was transiently up-regulated during the early fusion of human myoblasts. Human mutations in the gene for GPR56 cause the disease bilateral frontoparietal polymicrogyria; however, the consequences of receptor dysfunction on muscle development have not been explored. Using knockout mice, we defined the role of GPR56 in skeletal muscle. GPR56(-/-) myoblasts have decreased fusion and smaller myotube sizes in culture. In addition, a loss of GPR56 expression in muscle cells results in decreases or delays in the expression of myogenic differentiation 1, myogenin and nuclear factor of activated T-cell (NFAT)c2. Our data suggest that these abnormalities result from decreased GPR56-mediated serum response element and NFAT signalling. Despite these changes, no overt differences in phenotype were identified in the muscle of GPR56 knockout mice, which presented only a mild but statistically significant elevation of serum creatine kinase compared to wild-type. In agreement with these findings, clinical data from 13 bilateral frontoparietal polymicrogyria patients revealed mild serum creatine kinase increase in only two patients. In summary, targeted disruption of GPR56 in mice results in myoblast abnormalities. The absence of a severe muscle phenotype in GPR56 knockout mice and human patients suggests that other factors may compensate for the lack of this G-protein coupled receptor during muscle development and that the motor delay observed in these patients is likely not a result of primary muscle abnormalities. + © 2013 FEBS. + + + + Wu + Melissa P + MP + + Department of Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA; Division of Genetics, Boston Children's Hospital, MA, USA. + + + + Doyle + Jamie R + JR + + + Barry + Brenda + B + + + Beauvais + Ariane + A + + + Rozkalne + Anete + A + + + Piao + Xianhua + X + + + Lawlor + Michael W + MW + + + Kopin + Alan S + AS + + + Walsh + Christopher A + CA + + + Gussoni + Emanuela + E + + + eng + + + 2R01NS047727 + NS + NINDS NIH HHS + United States + + + R01 NS047727 + NS + NINDS NIH HHS + United States + + + T32 GM007226 + GM + NIGMS NIH HHS + United States + + + L40 AR057721 + AR + NIAMS NIH HHS + United States + + + P30-HD1865 + HD + NICHD NIH HHS + United States + + + 1R01AR060317-01 + AR + NIAMS NIH HHS + United States + + + P30 HD018655 + HD + NICHD NIH HHS + United States + + + R01 AR060317 + AR + NIAMS NIH HHS + United States + + + K08 AR059750 + AR + NIAMS NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + + + 2013 + 10 + 08 + +
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+ + + + + 21171099 + + 2011 + 01 + 21 + + + 2016 + 11 + 22 + +
+ + 1097-4598 + + 43 + 1 + + 2011 + Jan + + + Muscle & nerve + Muscle Nerve + + Carbamylated erythropoietin does not alleviate signs of dystrophy in mdx mice. + + 88-93 + + 10.1002/mus.21785 + + Erythropoietin promotes myoblast proliferation and inhibits fibrosis and thus it could impede the pathogenesis of muscle degenerative diseases. However, its stimulation of erythropoiesis limits its use as a therapeutic agent. An erythropoietin analog, carbamylated erythropoietin (C-EPO), retains these protective actions, yet it does not interact with the erythropoietin receptor. To determine whether treatment with C-EPO alleviates the signs of muscular dystrophy in an animal model of Duchenne muscular dystrophy, we treated mdx mice with intraperitoneal injections of 50 μg/kg and 100 μg/kg C-EPO for 4 and 12 weeks, and we monitored weight, serum creatine kinase levels, and changes in muscle histology. Moderate histological improvement was observed at 4 weeks, which did not translate into a significantly decreased level of serum creatine kinase. At the doses tested, C-EPO is not an effective therapeutic for the treatment of a mouse model of Duchenne muscular dystrophy. + Copyright © 2010 Wiley Periodicals, Inc. + + + + Wu + Melissa P + MP + + Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA. + + + + Gussoni + Emanuela + E + + + eng + + + 2R01NS047727 + NS + NINDS NIH HHS + United States + + + R01 NS047727 + NS + NINDS NIH HHS + United States + + + T32 GM007226 + GM + NIGMS NIH HHS + United States + + + P50 NS040828 + NS + NINDS NIH HHS + United States + + + R01 NS047727-05A2 + NS + NINDS NIH HHS + United States + + + P50 NS040828-080004 + NS + NINDS NIH HHS + United States + + + 5P50NS040828 + NS + NINDS NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + +
+ + United States + Muscle Nerve + 7803146 + 0148-639X + + + + 0 + Neuroprotective Agents + + + 0 + carbamylated erythropoietin + + + 11096-26-7 + Erythropoietin + + + EC 2.7.3.2 + Creatine Kinase + + + IM + + + J Pediatr. 1963 Dec;63:1116-9 + 14089817 + + + J Neurol Neurosurg Psychiatry. 1964 Apr;27:96-9 + 14167093 + + + Clin Chim Acta. 1965 May;11:404-7 + 14347986 + + + Arch Phys Med Rehabil. 1964 Mar;45:117-24 + 14127953 + + + Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2046-51 + 15671158 + + + Fundam Clin Pharmacol. 2005 Aug;19(4):439-46 + 16011730 + + + J Neuroimmunol. 2006 Mar;172(1-2):27-37 + 16337691 + + + Acta Myol. 2005 Dec;24(3):230-41 + 16629058 + + + Clin Cancer Res. 2006 Apr 15;12(8):2607-12 + 16638873 + + + Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R947-56 + 16690772 + + + Mol Med. 2006 Jul-Aug;12(7-8):153-60 + 17088947 + + + J Cereb Blood Flow Metab. 2007 Mar;27(3):552-63 + 16835629 + + + Mol Ther. 2007 May;15(5):867-77 + 17387336 + + + Clin J Am Soc Nephrol. 2007 Nov;2(6):1274-82 + 17942772 + + + Crit Care. 2007;11(3):R58 + 17509156 + + + Expert Opin Investig Drugs. 2008 Aug;17(8):1175-86 + 18616414 + + + Kidney Int. 2008 Sep;74(6):695-7 + 18756292 + + + Int J Urol. 2008 Oct;15(11):1011-7 + 18759748 + + + Expert Rev Mol Med. 2009;11:e18 + 19555515 + + + Surgery. 2009 Sep;146(3):506-14 + 19715808 + + + Curr Opin Neurol. 2009 Oct;22(5):532-8 + 19745732 + + + Ann N Y Acad Sci. 2009 Sep;1175:71-9 + 19796079 + + + Brain. 2010 Apr;133(Pt 4):957-72 + 20150322 + + + Acta Neuropathol. 1986;69(1-2):91-5 + 3962599 + + + Cell. 1987 Dec 24;51(6):919-28 + 3319190 + + + Muscle Nerve. 1988 Aug;11(8):795-803 + 3173406 + + + EMBO J. 1988 Oct;7(10):3017-21 + 2903046 + + + Adv Hum Genet. 1988;17:61-98 + 3055851 + + + Genomics. 1988 Nov;3(4):337-41 + 3243547 + + + Science. 1989 Jun 30;244(4912):1578-80 + 2662404 + + + Nature. 1991 Aug 8;352(6335):536-9 + 1865908 + + + Nephron. 1993;64(1):89-94 + 8502342 + + + Biochem Biophys Res Commun. 1995 Mar 28;208(3):1060-6 + 7535525 + + + Blood. 1997 Sep 1;90(5):1867-73 + 9292519 + + + J Biol Chem. 2000 Dec 15;275(50):39754-61 + 10995753 + + + Clin Immunol. 2001 Feb;98(2):235-43 + 11161980 + + + Curr Opin Nephrol Hypertens. 2001 Sep;10(5):633-7 + 11496057 + + + Neuromuscul Disord. 2001 Sep;11(6-7):556-64 + 11525885 + + + N Engl J Med. 2002 Feb 14;346(7):469-75 + 11844847 + + + Nature. 2002 Nov 28;420(6914):418-21 + 12459784 + + + Nat Rev Drug Discov. 2003 May;2(5):379-90 + 12750741 + + + Trends Mol Med. 2003 Aug;9(8):344-50 + 12928036 + + + Med Hypotheses. 2004;63(1):73-5 + 15193351 + + + Cell Death Differ. 2004 Jul;11 Suppl 1:S37-44 + 15243580 + + + Science. 2004 Jul 9;305(5681):239-42 + 15247477 + + + Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14907-12 + 15456912 + + + Mol Cell Biol. 2004 Nov;24(21):9295-304 + 15485899 + + + Proc Natl Acad Sci U S A. 1984 Feb;81(4):1189-92 + 6583703 + + + + + Animals + + + Cell Proliferation + drug effects + + + Creatine Kinase + antagonists & inhibitors + metabolism + + + Disease Models, Animal + + + Erythropoietin + administration & dosage + analogs & derivatives + therapeutic use + + + Female + + + Injections, Intraperitoneal + + + Mice + + + Mice, Inbred C57BL + + + Mice, Inbred mdx + + + Muscle, Skeletal + drug effects + metabolism + physiopathology + + + Muscular Dystrophy, Animal + drug therapy + metabolism + physiopathology + + + Myoblasts + drug effects + metabolism + + + Neuroprotective Agents + administration & dosage + therapeutic use + + + Treatment Failure + + +
+ + + + 2010 + 12 + 21 + 6 + 0 + + + 2010 + 12 + 21 + 6 + 0 + + + 2011 + 1 + 22 + 6 + 0 + + + ppublish + + 21171099 + 10.1002/mus.21785 + PMC3057654 + NIHMS208026 + + +
+ + + + + 17150207 + + 2007 + 03 + 05 + + + 2016 + 12 + 08 + +
+ + 0012-1606 + + 301 + 1 + + 2007 + Jan + 01 + + + Developmental biology + Dev. Biol. + + C6ORF32 is upregulated during muscle cell differentiation and induces the formation of cellular filopodia. + + 70-81 + + + We have identified a gene by microarray analysis that is located on chromosome 6 (c6orf32), whose expression is increased during human fetal myoblast differentiation. The protein encoded by c6orf32 is expressed both in myogenic and non-myogenic primary cells isolated from 18-week old human fetal skeletal muscle. Immunofluorescent staining indicated that C6ORF32 localizes to the cellular cytoskeleton and filopodia, and often displays polarized expression within the cell. mRNA knockdown experiments in the C2C12 murine myoblast cell line demonstrated that cells lacking c6orf32 exhibit a myogenic differentiation defect, characterized by a decrease in the expression of myogenin and myosin heavy chain (MHC) proteins, whereas MyoD1 was unaltered. In contrast, overexpression of c6orf32 in C2C12 or HEK293 cells (a non-muscle cell line) promoted formation of long membrane protrusions (filopodia). Analysis of serial deletion mutants demonstrated that amino acids 55-113 of C6ORF32 are likely involved in filopodia formation. These results indicate that C6ORF32 is a novel protein likely to play multiple functions, including promoting myogenic cell differentiation, cytoskeletal rearrangement and filopodia formation. + + + + Yoon + Soonsang + S + + Division of Genetics and Program in Genomics, Children's Hospital Boston, Enders 554, Boston, MA 02115, USA. + + + + Molloy + Michael J + MJ + + + Wu + Melissa P + MP + + + Cowan + Douglas B + DB + + + Gussoni + Emanuela + E + + + eng + + + R01 HL088206 + HL + NHLBI NIH HHS + United States + + + R01 HL068915 + HL + NHLBI NIH HHS + United States + + + R01 NS047727 + NS + NINDS NIH HHS + United States + + + R01 HL088206-02 + HL + NHLBI NIH HHS + United States + + + P01 NS040828 + NS + NINDS NIH HHS + United States + + + 1 P01 NS40828 + NS + NINDS NIH HHS + United States + + + R01 HL068915-07 + HL + NHLBI NIH HHS + United States + + + 5 R01 NS047727 + NS + NINDS NIH HHS + United States + + + R01 HL088206-04 + HL + NHLBI NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + + + 2006 + 11 + 07 + +
+ + United States + Dev Biol + 0372762 + 0012-1606 + + + + 0 + DNA Primers + + + 0 + FAM65B protein, human + + + 0 + Proteins + + + 0 + RNA, Messenger + + + IM + + + FASEB J. 2000 Mar;14(3):461-75 + 10698961 + + + Development. 1996 Dec;122(12):3697-705 + 9012491 + + + Cell. 2000 Jul 21;102(2):189-98 + 10943839 + + + Curr Biol. 2000 Nov 16;10(22):1420-6 + 11102803 + + + Development. 2001 Nov;128(21):4229-39 + 11684659 + + + Development. 2001 Nov;128(21):4265-76 + 11684662 + + + Dev Cell. 2001 Nov;1(5):705-15 + 11709190 + + + Development. 2001 Dec;128(24):5061-73 + 11748142 + + + Nat Cell Biol. 2002 Sep;4(9):715-9 + 12198500 + + + Gene. 1997 Feb 7;185(2):153-7 + 9055809 + + + J Cell Biol. 1997 Aug 11;138(3):589-603 + 9245788 + + + Nature. 1998 Jan 1;391(6662):93-6 + 9422512 + + + Science. 1998 Jan 23;279(5350):509-14 + 9438836 + + + Biochim Biophys Acta. 1998 Mar 12;1402(1):52-60 + 9551085 + + + Science. 2005 Apr 15;308(5720):369-73 + 15831748 + + + Cell Mol Life Sci. 2005 Jul;62(14):1547-55 + 15905962 + + + Mol Cell Biol. 2005 Sep;25(17):7645-56 + 16107711 + + + Cell. 2005 Sep 9;122(5):659-67 + 16143100 + + + Semin Cell Dev Biol. 2005 Aug-Oct;16(4-5):585-95 + 16099183 + + + Mol Cell Biol. 2005 Dec;25(24):11089-101 + 16314529 + + + Genes Dev. 2006 Jul 1;20(13):1692-708 + 16818602 + + + J Cell Sci. 2006 Aug 1;119(Pt 15):3117-27 + 16835268 + + + J Cell Biol. 2006 Jul 31;174(3):403-13 + 16864654 + + + Nat Cell Biol. 2001 Oct;3(10):897-904 + 11584271 + + + J Neurobiol. 2003 Apr;55(1):31-40 + 12605457 + + + EMBO J. 2003 Mar 3;22(5):1147-57 + 12606579 + + + Int Rev Cytol. 2003;225:33-89 + 12696590 + + + Cell. 2003 May 16;113(4):483-94 + 12757709 + + + Nat Rev Genet. 2003 Jul;4(7):497-507 + 12838342 + + + Cell. 2003 Sep 19;114(6):751-62 + 14505574 + + + Curr Biol. 2003 Dec 16;13(24):R964-6 + 14680655 + + + Dev Biol. 2004 Jan 1;265(1):75-89 + 14697354 + + + Physiol Rev. 2004 Jan;84(1):209-38 + 14715915 + + + Trends Cell Biol. 2004 Aug;14(8):452-60 + 15308212 + + + Biochem J. 2004 Sep 15;382(Pt 3):1015-23 + 15239673 + + + Methods Mol Med. 2005;107:97-110 + 15492366 + + + Mech Dev. 2004 Dec;121(12):1455-68 + 15511638 + + + Cell. 1989 Feb 24;56(4):607-17 + 2537150 + + + Cell. 1989 Sep 8;58(5):823-31 + 2550138 + + + Nat Genet. 1993 May;4(1):77-81 + 8513330 + + + Neuroscience. 1993 May;54(1):167-87 + 8515841 + + + Genes Dev. 2000 Jun 15;14(12):1498-511 + 10859168 + + + Annu Rev Cell Dev Biol. 2002;18:747-83 + 12142270 + + + Nature. 2002 Dec 12;420(6916):629-35 + 12478284 + + + J Cell Sci. 1995 May;108 ( Pt 5):2077-82 + 7657725 + + + Nature. 1995 Oct 19;377(6550):652-6 + 7566181 + + + J Biol Chem. 1994 May 20;269(20):14371-4 + 7514168 + + + + + Base Sequence + + + Cell Differentiation + physiology + + + Cell Line + + + DNA Primers + + + Humans + + + Muscles + embryology + metabolism + + + Proteins + genetics + metabolism + + + RNA, Messenger + genetics + + + Up-Regulation + + +
+ + + + 2006 + 03 + 28 + + + 2006 + 10 + 12 + + + 2006 + 11 + 01 + + + 2006 + 12 + 8 + 9 + 0 + + + 2007 + 3 + 6 + 9 + 0 + + + 2006 + 12 + 8 + 9 + 0 + + + ppublish + + 17150207 + S0012-1606(06)01341-8 + 10.1016/j.ydbio.2006.11.002 + PMC1779902 + NIHMS16058 + + +
+ +
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+ + 1742-4658 + + 280 + 23 + + 2013 + Dec + + + The FEBS journal + FEBS J. + + G-protein coupled receptor 56 promotes myoblast fusion through serum response factor- and nuclear factor of activated T-cell-mediated signalling but is not essential for muscle development in vivo. + + 6097-113 + + 10.1111/febs.12529 + + Mammalian muscle cell differentiation is a complex process of multiple steps for which many of the factors involved have not yet been defined. In a screen to identify the regulators of myogenic cell fusion, we found that the gene for G-protein coupled receptor 56 (GPR56) was transiently up-regulated during the early fusion of human myoblasts. Human mutations in the gene for GPR56 cause the disease bilateral frontoparietal polymicrogyria; however, the consequences of receptor dysfunction on muscle development have not been explored. Using knockout mice, we defined the role of GPR56 in skeletal muscle. GPR56(-/-) myoblasts have decreased fusion and smaller myotube sizes in culture. In addition, a loss of GPR56 expression in muscle cells results in decreases or delays in the expression of myogenic differentiation 1, myogenin and nuclear factor of activated T-cell (NFAT)c2. Our data suggest that these abnormalities result from decreased GPR56-mediated serum response element and NFAT signalling. Despite these changes, no overt differences in phenotype were identified in the muscle of GPR56 knockout mice, which presented only a mild but statistically significant elevation of serum creatine kinase compared to wild-type. In agreement with these findings, clinical data from 13 bilateral frontoparietal polymicrogyria patients revealed mild serum creatine kinase increase in only two patients. In summary, targeted disruption of GPR56 in mice results in myoblast abnormalities. The absence of a severe muscle phenotype in GPR56 knockout mice and human patients suggests that other factors may compensate for the lack of this G-protein coupled receptor during muscle development and that the motor delay observed in these patients is likely not a result of primary muscle abnormalities. + © 2013 FEBS. + + + + Wu + Melissa P + MP + + Department of Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA; Division of Genetics, Boston Children's Hospital, MA, USA. + + + + Doyle + Jamie R + JR + + + Barry + Brenda + B + + + Beauvais + Ariane + A + + + Rozkalne + Anete + A + + + Piao + Xianhua + X + + + Lawlor + Michael W + MW + + + Kopin + Alan S + AS + + + Walsh + Christopher A + CA + + + Gussoni + Emanuela + E + + + eng + + + 2R01NS047727 + NS + NINDS NIH HHS + United States + + + R01 NS047727 + NS + NINDS NIH HHS + United States + + + T32 GM007226 + GM + NIGMS NIH HHS + United States + + + L40 AR057721 + AR + NIAMS NIH HHS + United States + + + P30-HD1865 + HD + NICHD NIH HHS + United States + + + 1R01AR060317-01 + AR + NIAMS NIH HHS + United States + + + P30 HD018655 + HD + NICHD NIH HHS + United States + + + R01 AR060317 + AR + NIAMS NIH HHS + United States + + + K08 AR059750 + AR + NIAMS NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + + + 2013 + 10 + 08 + +
+ + England + FEBS J + 101229646 + 1742-464X + + + + 0 + GPR56 protein, mouse + + + 0 + MyoD Protein + + + 0 + MyoD1 myogenic differentiation protein + + + 0 + Myogenin + + + 0 + NFATC Transcription Factors + + + 0 + RNA, Messenger + + + 0 + RNA, Small Interfering + + + 0 + Receptors, G-Protein-Coupled + + + EC 1.13.12.- + Luciferases + + + + Polymicrogyria, Bilateral Frontoparietal + + IM + + + J Biol Chem. 2001 Feb 9;276(6):4150-7 + 11050079 + + + Adv Exp Med Biol. 2010;706:49-58 + 21618825 + + + Neuropediatrics. 1990 Nov;21(4):218-21 + 2290486 + + + Brain Pathol. 2009 Oct;19(4):596-611 + 18691338 + + + FEBS Lett. 2005 Apr 25;579(11):2359-63 + 15848172 + + + Clin Chim Acta. 1965 May;11:404-7 + 14347986 + + + Dev Biol. 2001 Apr 1;232(1):115-26 + 11254352 + + + Exp Cell Res. 2010 Nov 1;316(18):3042-9 + 20471976 + + + Mol Biol Cell. 1998 Jul;9(7):1891-902 + 9658178 + + + Neuropediatrics. 1996 Apr;27(2):70-5 + 8737821 + + + Am J Pathol. 2012 Sep;181(3):961-8 + 22841819 + + + Cell. 1992 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pathology + + + Mice + + + Mice, Knockout + + + Muscle Development + physiology + + + MyoD Protein + genetics + metabolism + + + Myoblasts + cytology + metabolism + + + Myogenin + genetics + metabolism + + + NFATC Transcription Factors + antagonists & inhibitors + genetics + metabolism + + + RNA, Messenger + genetics + + + RNA, Small Interfering + genetics + + + Real-Time Polymerase Chain Reaction + + + Receptors, G-Protein-Coupled + physiology + + + Reverse Transcriptase Polymerase Chain Reaction + + + Serum Response Element + genetics + + + Signal Transduction + + + + GPR56 + dystroglycanopathies + myoblast + serum response element + skeletal muscle + +
+ + + + 2013 + 07 + 01 + + + 2013 + 08 + 24 + + + 2013 + 09 + 04 + + + 2013 + 10 + 10 + 6 + 0 + + + 2013 + 10 + 10 + 6 + 0 + + + 2014 + 1 + 23 + 6 + 0 + + + ppublish + + 24102982 + 10.1111/febs.12529 + PMC3877849 + NIHMS529672 + + +
+ + + + + 21171099 + + 2011 + 01 + 21 + + + 2016 + 11 + 22 + +
+ + 1097-4598 + + 43 + 1 + + 2011 + Jan + + + Muscle & nerve + Muscle Nerve + + Carbamylated erythropoietin does not alleviate signs of dystrophy in mdx mice. + + 88-93 + + 10.1002/mus.21785 + + Erythropoietin promotes myoblast proliferation and inhibits fibrosis and thus it could impede the pathogenesis of muscle degenerative diseases. However, its stimulation of erythropoiesis limits its use as a therapeutic agent. An erythropoietin analog, carbamylated erythropoietin (C-EPO), retains these protective actions, yet it does not interact with the erythropoietin receptor. To determine whether treatment with C-EPO alleviates the signs of muscular dystrophy in an animal model of Duchenne muscular dystrophy, we treated mdx mice with intraperitoneal injections of 50 μg/kg and 100 μg/kg C-EPO for 4 and 12 weeks, and we monitored weight, serum creatine kinase levels, and changes in muscle histology. Moderate histological improvement was observed at 4 weeks, which did not translate into a significantly decreased level of serum creatine kinase. At the doses tested, C-EPO is not an effective therapeutic for the treatment of a mouse model of Duchenne muscular dystrophy. + Copyright © 2010 Wiley Periodicals, Inc. + + + + Wu + Melissa P + MP + + Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA. + + + + Gussoni + Emanuela + E + + + eng + + + 2R01NS047727 + NS + NINDS NIH HHS + United States + + + R01 NS047727 + NS + NINDS NIH HHS + United States + + + T32 GM007226 + GM + NIGMS NIH HHS + United States + + + P50 NS040828 + NS + NINDS NIH HHS + United States + + + R01 NS047727-05A2 + NS + NINDS NIH HHS + United States + + + P50 NS040828-080004 + NS + NINDS NIH HHS + United States + + + 5P50NS040828 + NS + NINDS NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + +
+ + United States + Muscle Nerve + 7803146 + 0148-639X + + + + 0 + Neuroprotective Agents + + + 0 + carbamylated erythropoietin + + + 11096-26-7 + Erythropoietin + + + EC 2.7.3.2 + Creatine Kinase + + + IM + + + J Pediatr. 1963 Dec;63:1116-9 + 14089817 + + + J Neurol Neurosurg Psychiatry. 1964 Apr;27:96-9 + 14167093 + + + Clin Chim Acta. 1965 May;11:404-7 + 14347986 + + + Arch Phys Med Rehabil. 1964 Mar;45:117-24 + 14127953 + + + Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2046-51 + 15671158 + + + Fundam Clin Pharmacol. 2005 Aug;19(4):439-46 + 16011730 + + + J Neuroimmunol. 2006 Mar;172(1-2):27-37 + 16337691 + + + Acta Myol. 2005 Dec;24(3):230-41 + 16629058 + + + Clin Cancer Res. 2006 Apr 15;12(8):2607-12 + 16638873 + + + Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R947-56 + 16690772 + + + Mol Med. 2006 Jul-Aug;12(7-8):153-60 + 17088947 + + + J Cereb Blood Flow Metab. 2007 Mar;27(3):552-63 + 16835629 + + + Mol Ther. 2007 May;15(5):867-77 + 17387336 + + + Clin J Am Soc Nephrol. 2007 Nov;2(6):1274-82 + 17942772 + + + Crit Care. 2007;11(3):R58 + 17509156 + + + Expert Opin Investig Drugs. 2008 Aug;17(8):1175-86 + 18616414 + + + Kidney Int. 2008 Sep;74(6):695-7 + 18756292 + + + Int J Urol. 2008 Oct;15(11):1011-7 + 18759748 + + + Expert Rev Mol Med. 2009;11:e18 + 19555515 + + + Surgery. 2009 Sep;146(3):506-14 + 19715808 + + + Curr Opin Neurol. 2009 Oct;22(5):532-8 + 19745732 + + + Ann N Y Acad Sci. 2009 Sep;1175:71-9 + 19796079 + + + Brain. 2010 Apr;133(Pt 4):957-72 + 20150322 + + + Acta Neuropathol. 1986;69(1-2):91-5 + 3962599 + + + Cell. 1987 Dec 24;51(6):919-28 + 3319190 + + + Muscle Nerve. 1988 Aug;11(8):795-803 + 3173406 + + + EMBO J. 1988 Oct;7(10):3017-21 + 2903046 + + + Adv Hum Genet. 1988;17:61-98 + 3055851 + + + Genomics. 1988 Nov;3(4):337-41 + 3243547 + + + Science. 1989 Jun 30;244(4912):1578-80 + 2662404 + + + Nature. 1991 Aug 8;352(6335):536-9 + 1865908 + + + Nephron. 1993;64(1):89-94 + 8502342 + + + Biochem Biophys Res Commun. 1995 Mar 28;208(3):1060-6 + 7535525 + + + Blood. 1997 Sep 1;90(5):1867-73 + 9292519 + + + J Biol Chem. 2000 Dec 15;275(50):39754-61 + 10995753 + + + Clin Immunol. 2001 Feb;98(2):235-43 + 11161980 + + + Curr Opin Nephrol Hypertens. 2001 Sep;10(5):633-7 + 11496057 + + + Neuromuscul Disord. 2001 Sep;11(6-7):556-64 + 11525885 + + + N Engl J Med. 2002 Feb 14;346(7):469-75 + 11844847 + + + Nature. 2002 Nov 28;420(6914):418-21 + 12459784 + + + Nat Rev Drug Discov. 2003 May;2(5):379-90 + 12750741 + + + Trends Mol Med. 2003 Aug;9(8):344-50 + 12928036 + + + Med Hypotheses. 2004;63(1):73-5 + 15193351 + + + Cell Death Differ. 2004 Jul;11 Suppl 1:S37-44 + 15243580 + + + Science. 2004 Jul 9;305(5681):239-42 + 15247477 + + + Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14907-12 + 15456912 + + + Mol Cell Biol. 2004 Nov;24(21):9295-304 + 15485899 + + + Proc Natl Acad Sci U S A. 1984 Feb;81(4):1189-92 + 6583703 + + + + + Animals + + + Cell Proliferation + drug effects + + + Creatine Kinase + antagonists & inhibitors + metabolism + + + Disease Models, Animal + + + Erythropoietin + administration & dosage + analogs & derivatives + therapeutic use + + + Female + + + Injections, Intraperitoneal + + + Mice + + + Mice, Inbred C57BL + + + Mice, Inbred mdx + + + Muscle, Skeletal + drug effects + metabolism + physiopathology + + + Muscular Dystrophy, Animal + drug therapy + metabolism + physiopathology + + + Myoblasts + drug effects + metabolism + + + Neuroprotective Agents + administration & dosage + therapeutic use + + + Treatment Failure + + +
+ + + + 2010 + 12 + 21 + 6 + 0 + + + 2010 + 12 + 21 + 6 + 0 + + + 2011 + 1 + 22 + 6 + 0 + + + ppublish + + 21171099 + 10.1002/mus.21785 + PMC3057654 + NIHMS208026 + + +
+ + + + + 17150207 + + 2007 + 03 + 05 + + + 2016 + 12 + 08 + +
+ + 0012-1606 + + 301 + 1 + + 2007 + Jan + 01 + + + Developmental biology + Dev. Biol. + + C6ORF32 is upregulated during muscle cell differentiation and induces the formation of cellular filopodia. + + 70-81 + + + We have identified a gene by microarray analysis that is located on chromosome 6 (c6orf32), whose expression is increased during human fetal myoblast differentiation. The protein encoded by c6orf32 is expressed both in myogenic and non-myogenic primary cells isolated from 18-week old human fetal skeletal muscle. Immunofluorescent staining indicated that C6ORF32 localizes to the cellular cytoskeleton and filopodia, and often displays polarized expression within the cell. mRNA knockdown experiments in the C2C12 murine myoblast cell line demonstrated that cells lacking c6orf32 exhibit a myogenic differentiation defect, characterized by a decrease in the expression of myogenin and myosin heavy chain (MHC) proteins, whereas MyoD1 was unaltered. In contrast, overexpression of c6orf32 in C2C12 or HEK293 cells (a non-muscle cell line) promoted formation of long membrane protrusions (filopodia). Analysis of serial deletion mutants demonstrated that amino acids 55-113 of C6ORF32 are likely involved in filopodia formation. These results indicate that C6ORF32 is a novel protein likely to play multiple functions, including promoting myogenic cell differentiation, cytoskeletal rearrangement and filopodia formation. + + + + Yoon + Soonsang + S + + Division of Genetics and Program in Genomics, Children's Hospital Boston, Enders 554, Boston, MA 02115, USA. + + + + Molloy + Michael J + MJ + + + Wu + Melissa P + MP + + + Cowan + Douglas B + DB + + + Gussoni + Emanuela + E + + + eng + + + R01 HL088206 + HL + NHLBI NIH HHS + United States + + + R01 HL068915 + HL + NHLBI NIH HHS + United States + + + R01 NS047727 + NS + NINDS NIH HHS + United States + + + R01 HL088206-02 + HL + NHLBI NIH HHS + United States + + + P01 NS040828 + NS + NINDS NIH HHS + United States + + + 1 P01 NS40828 + NS + NINDS NIH HHS + United States + + + R01 HL068915-07 + HL + NHLBI NIH HHS + United States + + + 5 R01 NS047727 + NS + NINDS NIH HHS + United States + + + R01 HL088206-04 + HL + NHLBI NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + + + 2006 + 11 + 07 + +
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+ + + + 2006 + 03 + 28 + + + 2006 + 10 + 12 + + + 2006 + 11 + 01 + + + 2006 + 12 + 8 + 9 + 0 + + + 2007 + 3 + 6 + 9 + 0 + + + 2006 + 12 + 8 + 9 + 0 + + + ppublish + + 17150207 + S0012-1606(06)01341-8 + 10.1016/j.ydbio.2006.11.002 + PMC1779902 + NIHMS16058 + + +
+ +
\ No newline at end of file diff --git a/e-utilities-lecture-notes/zika.xml b/e-utilities-lecture-notes/zika.xml new file mode 100644 index 0000000..9056fa4 --- /dev/null +++ b/e-utilities-lecture-notes/zika.xml @@ -0,0 +1,114330 @@ + + + + + + 29507368 + + 2018 + 03 + 06 + +
+ + 2045-2322 + + 8 + 1 + + 2018 + Mar + 05 + + + Scientific reports + Sci Rep + + Efficient detection of Zika virus RNA in patients' blood from the 2016 outbreak in Campinas, Brazil. + + 4012 + + 10.1038/s41598-018-22159-2 + + Infection with Zika virus (ZIKV), a mosquito-borne flavivirus has been casually linked with increased congenital microcephaly in Brazil from 2015 through 2016. Sensitive and specific diagnosis of patients with Zika fever (ZIKF) remains critical for patient management. We developed a ZIKV NS5 qRT-PCR assay by combining primers described by Balm et al. and a new Taqman probe. The assay was evaluated and compared with another assay described by Lanciotti et al. (ZIKV 1107) using 51 blood and 42 urine samples from 54 suspected ZIKV patients. ZIKV NS5 performed better in terms of sensitivity with more samples detected as ZIKV-positive (n = 37) than ZIKV 1107 (n = 34) for urine, and ZIKV-positive (n = 29) than ZIKV 1107 (n = 26) for blood. Both assays displayed good overall agreement for urine (κappa = 0.770) and blood (κappa = 0.825) samples. Improved availability of validated diagnostic tests, such ZIKV NS5 qRT-PCR, will be critical to ensure adequate and accurate ZIKV diagnosis. + + + + Judice + Carla Cristina + CC + + Laboratory of Tropical Diseases-Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil. + + + + Tan + Jeslin J L + JJL + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. + + + + Parise + Pierina Lorencini + PL + + Laboratory of Emerging Viruses-Department of Genetics, Evolution and Bioagents, Institute of Biology, Unicamp, Brazil. + + + + Kam + Yiu-Wing + YW + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. + + + + Milanez + Guilherme Paier + GP + http://orcid.org/0000-0002-8599-1098 + + Laboratory of Emerging Viruses-Department of Genetics, Evolution and Bioagents, Institute of Biology, Unicamp, Brazil. + + + + Leite + Juliana Almeida + JA + + Laboratory of Tropical Diseases-Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil. + + + + Caserta + Leonardo Cardia + LC + + Laboratory of Animal Viruses-Department of Genetics, Evolution and Bioagents, Institute of Biology, Unicamp, Brazil. + + + + Arns + Clarice Weis + CW + + Laboratory of Animal Viruses-Department of Genetics, Evolution and Bioagents, Institute of Biology, Unicamp, Brazil. + + + + Resende + Mariangela Ribeiro + MR + + Clinical Pathology Department, School of Medical Sciences, Unicamp, Brazil. + + + + Angerami + Rodrigo + R + + Clinical Pathology Department, School of Medical Sciences, Unicamp, Brazil. + + + + Amaral + Eliana + E + + Obstetrics and Gynecology Department, School of Medical Sciences, Unicamp, Brazil. + + + + Junior + Renato Passini + RP + + Obstetrics and Gynecology Department, School of Medical Sciences, Unicamp, Brazil. + + + + Freitas + André Ricardo Ribas + ARR + + Campinas Department of Public Health Surveillance, Campinas, Brazil. + + + + Costa + Fabio Trindade Maranhão + FTM + + Laboratory of Tropical Diseases-Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil. + + + + Proenca-Modena + Jose Luiz + JL + + Laboratory of Tropical Diseases-Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil. jlmodena@unicamp.br. + + + Laboratory of Emerging Viruses-Department of Genetics, Evolution and Bioagents, Institute of Biology, Unicamp, Brazil. jlmodena@unicamp.br. + + + + Ng + Lisa F P + LFP + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. lisa_ng@immunol.a-star.edu.sg. + + + Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom. lisa_ng@immunol.a-star.edu.sg. + + + + Zika-Unicamp Network + + + eng + + Journal Article + + + 2018 + 03 + 05 + +
+ + England + Sci Rep + 101563288 + 2045-2322 + + + + Pastore + Glaucia Maria + GM + + + Mayer-Milanez + Helaine Maria Besteti Pires + HMBP + + + Ribeiro-do-Valle + Carolina C + CC + + + Calil + Roseli + R + + + Costa + Maria Laura + ML + + + Junior + João Renato Bennini + JRB + + + Lajos + Giuliane Jesus + GJ + + + Garcia + Márcia Teixeira + MT + + + Fertrin + Kleber Yotsumoto + KY + + + Moretti + Maria Luiza + ML + + + da Silva + Marcos Tadeu Nolasco + MTN + + + Coan + Ana Carolina + AC + + + Colella-Santos + Maria Francisca + MF + + + von Zuben + Andrea Paula Bruno + APB + + + Vinolo + Marco Aurélio Ramirez + MAR + + + Catharino + Rodrigo Ramos + RR + + + do Nascimento + Gabriela Mansano + GM + + + Martini + Matheus + M + + + de Moraes + Ana Paula + AP + + + Soledade + Ana Lucia Rodrigues + ALR + + + de Toledo Teixeira + Daniel Augusto + DA + + + de Morais + Évellyn Ribeiro + ÉR + + + Santos + Felipe Rebelo + FR + + + Fontana + Monique + M + + +
+ + + + 2017 + 07 + 27 + + + 2018 + 02 + 19 + + + 2018 + 3 + 7 + 6 + 0 + + + 2018 + 3 + 7 + 6 + 0 + + + 2018 + 3 + 7 + 6 + 0 + + + epublish + + 29507368 + 10.1038/s41598-018-22159-2 + 10.1038/s41598-018-22159-2 + + +
+ + + + + 29503261 + + 2018 + 03 + 09 + +
+ + 1309-0399 + + 19 + 1 + + 2018 + 03 + 01 + + + Journal of the Turkish German Gynecological Association + J Turk Ger Gynecol Assoc + + Zika virus and pregnancy in Brazil: What happened? + + 39-47 + + 10.4274/jtgga.2017.0072 + + The recent epidemic of Zika virus (ZIKV) infection in Central and South America is one of the most serious global public health emergencies since the Ebola outbreak in West Africa. In Brazil, especially in the north, northeast, and southeast parts of the country, the ZIKV outbreak is a cause of concern for pregnant women because ZIKV intrauterine infection has been found to be associated with multiple brain malformations and microcephaly. In Brazil, the number of newborns with confirmed microcephaly per year recorded during the ZIKV outbreak, has been approximately 15 times greater than previously reported. Considering that the infection is self-limiting and symptomatic, it is usually diagnosed at the time of routine prenatal scan, especially in the third trimester. In other cases, the disease is detected after childbirth through neuroimaging. This study provides an insight into the history and evolution of ZIKV in Brazil, including current knowledge concerning the transmission, diagnosis, and pathogenesis of the infection. In addition, this review describes the pre- and postnatal neuroimaging findings obtained using ultrasound, magnetic resonance imaging, and computed tomography. + + + + Pereira + Alessandra Mendelski + AM + + Department of Obstetrics and Gynecology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Monteiro + Denise Leite Maia + DLM + + Department of Obstetrics and Gynecology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Werner + Heron + H + + Department of Radiology, Clínica de Diagnóstico por Imagem, Rio de Janeiro, Brazil. + + + + Daltro + Pedro + P + + Department of Radiology, Clínica de Diagnóstico por Imagem, Rio de Janeiro, Brazil. + + + + Fazecas + Tatiana + T + + Department of Radiology, Clínica de Diagnóstico por Imagem, Rio de Janeiro, Brazil. + + + + Guedes + Bianca + B + + Department of Radiology, Clínica de Diagnóstico por Imagem, Rio de Janeiro, Brazil. + + + + Tonni + Gabriele + G + + Department of Obstetrics and Gynecology, Guastalla Civil Hospital, Reggio Emilia, Italy. + + + + Peixoto + Alberto Borges + AB + + Mário Palmério University Hospital, University of Uberaba, Uberaba, Brazil. + + + + Araujo Júnior + Edward + E + + Department of Obstetrics, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil. + + + + eng + + Journal Article + +
+ + Turkey + J Turk Ger Gynecol Assoc + 101272522 + 1309-0380 + + + + J Gen Virol. 1988 Aug;69 ( Pt 8):1913-20 + 2841406 + + + N Engl J Med. 2016 Jun 2;374(22):2195-8 + 27074370 + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + J Neurovirol. 2014 Dec;20(6):539-60 + 25287260 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + MMWR Morb Mortal Wkly Rep. 2016 Dec 02;65(47):1343-1348 + 27906905 + + + Obstet Gynecol. 2016 Apr;127(4):642-8 + 26889662 + + + Front Microbiol. 2016 Apr 19;7:496 + 27148186 + + + EBioMedicine. 2017 Mar;17 :157-162 + 28283425 + + + J Clin Virol. 2016 Nov;84:53-58 + 27721110 + + + Ultrasound Obstet Gynecol. 2016 May;47(5):657-60 + 26923098 + + + Prenat Diagn. 2016 Sep;36(9):882-7 + 27491635 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Neurology. 2009 Sep 15;73(11):887-97 + 19752457 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + BMC Pediatr. 2013 Apr 20;13:59 + 23601190 + + + Lancet. 2014 Sep 6;384(9946):857-68 + 25209487 + + + Clin Microbiol Rev. 2016 Jul;29(3):659-94 + 27281741 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + Lancet. 2016 Jun 18;387(10037):2502 + 27287830 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + Ultrasound Obstet Gynecol. 2016 Apr;47(4):530-2 + 26969966 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + BMJ. 2016 Aug 09;354:i3899 + 27509902 + + + Science. 2016 Jan 8;351(6269):110-1 + 26744386 + + + Prenat Diagn. 2016 Aug;36(8):785-9 + 27316349 + + + Lancet. 2016 Apr 9;387(10027):1531-1539 + 26948433 + + + Viral Immunol. 2003;16(3):259-78 + 14583143 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Jpn J Radiol. 2017 Mar;35(3):89-94 + 28074379 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Front Microbiol. 2017 Feb 03;8:110 + 28217114 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Ultrasound Obstet Gynecol. 2017 Jun;49(6):729-736 + 28078779 + + + Childs Nerv Syst. 2016 Jun;32(6):1057-60 + 27080092 + + + Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7852-7 + 27354515 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Sci Rep. 2016 Dec 23;6:39775 + 28008958 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Zika virus + intrauterine infection + microcephaly + ultrasound magnetic resonance imaging. + +
+ + + + 2018 + 3 + 6 + 6 + 0 + + + 2018 + 3 + 6 + 6 + 0 + + + 2018 + 3 + 6 + 6 + 1 + + + ppublish + + 29503261 + 10.4274/jtgga.2017.0072 + PMC5838777 + + +
+ + + + + 29501560 + + 2018 + 03 + 11 + +
+ + 1769-714X + + + 2018 + Mar + 06 + + + Microbes and infection + Microbes Infect. + + Zika virus: lessons learned in Brazil. + S1286-4579(18)30052-2 + 10.1016/j.micinf.2018.02.008 + + Zika virus (ZIKV) greatly impacted the international scientific and public health communities in the last two years due to its association with microcephaly and other neonatal alterations. This review will discuss lessons learned from viral pathogenesis, epidemiology and clinical findings observed during the ZIKV outbreak occurred between 2014 and 2016 in Brazil. + Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. + + + + Proenca-Modena + Jose Luiz + JL + + Laboratory of Emerging Viruses, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil. Electronic address: jlmodena@unicamp.br. + + + + Milanez + Guilherme Paier + GP + + Laboratory of Emerging Viruses, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil. + + + + Costa + Maria Laura + ML + + Obstetrics and Gynecology Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil. + + + + Judice + Carla C + CC + + Laboratory of Tropical Diseases, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil. + + + + Maranhão Costa + Fabio Trindade + FT + + Laboratory of Tropical Diseases, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil. Electronic address: costaftm@unicamp.br. + + + + eng + + Journal Article + + + 2018 + 03 + 06 + +
+ + France + Microbes Infect + 100883508 + 1286-4579 + + + Arboviruses + Brazil + Epidemics setting + Pathogenesis + Transmission + Zika virus + +
+ + + + 2017 + 12 + 13 + + + 2018 + 02 + 15 + + + 2018 + 02 + 21 + + + 2018 + 3 + 5 + 6 + 0 + + + 2018 + 3 + 5 + 6 + 0 + + + 2018 + 3 + 5 + 6 + 0 + + + aheadofprint + + 29501560 + S1286-4579(18)30052-2 + 10.1016/j.micinf.2018.02.008 + + +
+ + + + + 29500926 + + 2018 + 03 + 03 + +
+ + 2191-0308 + + 33 + 1 + + 2018 + Mar + 28 + + + Reviews on environmental health + Rev Environ Health + + Effects of climate change on the spread of zika virus: a public health threat. + + 31-42 + + 10.1515/reveh-2017-0042 + /j/reveh.2018.33.issue-1/reveh-2017-0042/reveh-2017-0042.xml + + Zika is a vector-borne viral disease transmitted to humans primarily by Aedes aegypti mosquitoes. The increased climate instability has contributed to the emergence of infections carried by mosquitoes like dengue, chikungunya and zika. While infection with the zika virus is not new, the recent epidemic of microcephaly in Brazil and other countries in South America resulting from the infection of pregnant women with the zika virus raise a number of serious public health concerns. These include the question of how climate change affects the range of zika vectors, what can we do to shorten the length of mosquito season, how and why the symptoms of zika infection have changed and what can be done to reduce the burden of human disease from this infection? Another important question that needs to be answered is what are the factors that caused the zika virus to leave the non-human primates and/or other mammals and invade the human population? + + + + Asad + Hina + H + + Institute for Health and the Environment, University at Albany, Rensselaer, NY, USA. + + + + Carpenter + David O + DO + + Institute for Health and the Environment, University at Albany, Rensselaer, NY, USA. + + + + eng + + Journal Article + +
+ + Germany + Rev Environ Health + 0425754 + 0048-7554 + + + Aedes aegypti + El Niño + climate change + dengue + global warming + microcephaly + natural disasters + urbanization + vector-borne diseases + +
+ + + + 2017 + 10 + 30 + + + 2017 + 11 + 09 + + + 2018 + 3 + 4 + 6 + 0 + + + 2018 + 3 + 4 + 6 + 0 + + + 2018 + 3 + 4 + 6 + 0 + + + ppublish + + 29500926 + 10.1515/reveh-2017-0042 + /j/reveh.2018.33.issue-1/reveh-2017-0042/reveh-2017-0042.xml + + +
+ + + + + 29494684 + + 2018 + 03 + 01 + +
+ + 1932-6203 + + 13 + 3 + + 2018 + + + PloS one + PLoS ONE + + Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition. + + e0193514 + + 10.1371/journal.pone.0193514 + + Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. + Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). + Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. + Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive management of neurogenic bladder and prompt referral so as to help mitigate CZS disease burden for patients and their families. + + + + Costa Monteiro + Lucia Maria + LM + http://orcid.org/0000-0002-7612-7249 + + Department of Pediatric Urodynamics and Dysfunctional Voiding, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Cruz + Glaura Nisya de Oliveira + GNO + + Department of Pediatric Urodynamics and Dysfunctional Voiding, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Fontes + Juliana Marin + JM + + Department of Pediatric Urodynamics and Dysfunctional Voiding, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Saad Salles + Tania Regina Dias + TRD + + Department of Pediatric Neurology, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Boechat + Marcia Cristina Bastos + MCB + + Department of Pediatric Radiology and Imagining, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Monteiro + Ana Carolina + AC + + Department of Internal Medicine, University of California Los Angeles, (U.C.L.A), Los Angeles, California, United States of America. + + + + Moreira + Maria Elizabeth Lopes + MEL + + Department of Neonatology, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + + + 2018 + 03 + 01 + +
+ + United States + PLoS One + 101285081 + 1932-6203 + +
+ + + + 2017 + 08 + 22 + + + 2018 + 02 + 13 + + + 2018 + 3 + 2 + 6 + 0 + + + 2018 + 3 + 2 + 6 + 0 + + + 2018 + 3 + 2 + 6 + 0 + + + epublish + + 29494684 + 10.1371/journal.pone.0193514 + PONE-D-17-30383 + + +
+ + + + + 29481868 + + 2018 + 03 + 11 + +
+ + 1769-714X + + + 2018 + Mar + 02 + + + Microbes and infection + Microbes Infect. + + An overview of mosquito vectors of Zika virus. + S1286-4579(18)30039-X + 10.1016/j.micinf.2018.01.006 + + The mosquito-borne arbovirus Zika virus (ZIKV, Flavivirus, Flaviviridae), has caused an outbreak impressive by its magnitude and rapid spread. First detected in Uganda in Africa in 1947, from where it spread to Asia in the 1960s, it emerged in 2007 on the Yap Island in Micronesia and hit most islands in the Pacific region in 2013. Subsequently, ZIKV was detected in the Caribbean, and Central and South America in 2015, and reached North America in 2016. Although ZIKV infections are in general asymptomatic or causing mild self-limiting illness, severe symptoms have been described including neurological disorders and microcephaly in newborns. To face such an alarming health situation, WHO has declared Zika as an emerging global health threat. This review summarizes the literature on the main vectors of ZIKV (sylvatic and urban) across all the five continents with special focus on vector competence studies. + Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved. + + + + Boyer + Sébastien + S + + Institut Pasteur of Cambodia, Unit of Medical Entomology, Phnom Penh, Cambodia. + + + + Calvez + Elodie + E + + Institut Pasteur of New Caledonia, URE Dengue and Other Arboviruses, Nouméa, New Caledonia. + + + + Chouin-Carneiro + Thais + T + + Instituto Oswaldo Cruz - Fiocruz, Laboratório de Transmissores de Hematozoários, Rio de Janeiro, Brazil. + + + + Diallo + Diawo + D + + Institut Pasteur of Dakar, Unit of Medical Entomology, Dakar, Senegal. + + + + Failloux + Anna-Bella + AB + + Institut Pasteur, URE Arboviruses and Insect Vectors, Paris, France. Electronic address: anna-bella.failloux@pasteur.fr. + + + + eng + + Journal Article + + + 2018 + 03 + 02 + +
+ + France + Microbes Infect + 100883508 + 1286-4579 + + + Aedes aegypti + Arbovirus + Mosquito vectors + Vector competence + +
+ + + + 2017 + 12 + 06 + + + 2018 + 01 + 14 + + + 2018 + 01 + 15 + + + 2018 + 2 + 27 + 6 + 0 + + + 2018 + 2 + 27 + 6 + 0 + + + 2018 + 2 + 27 + 6 + 0 + + + aheadofprint + + 29481868 + S1286-4579(18)30039-X + 10.1016/j.micinf.2018.01.006 + + +
+ + + + + 29476864 + + 2018 + 03 + 07 + +
+ + 1096-0333 + + + 2018 + Feb + 21 + + + Toxicology and applied pharmacology + Toxicol. Appl. Pharmacol. + + A systems biology approach to predictive developmental neurotoxicity of a larvicide used in the prevention of Zika virus transmission. + S0041-008X(18)30060-7 + 10.1016/j.taap.2018.02.014 + + The need to prevent developmental brain disorders has led to an increased interest in efficient neurotoxicity testing. When an epidemic of microcephaly occurred in Brazil, Zika virus infection was soon identified as the likely culprit. However, the pathogenesis appeared to be complex, and a larvicide used to control mosquitoes responsible for transmission of the virus was soon suggested as an important causative factor. Yet, it is challenging to identify relevant and efficient tests that are also in line with ethical research defined by the 3Rs rule (Replacement, Reduction and Refinement). Especially in an acute situation like the microcephaly epidemic, where little toxicity documentation is available, new and innovative alternative methods, whether in vitro or in silico, must be considered. We have developed a network-based model using an integrative systems biology approach to explore the potential developmental neurotoxicity, and we applied this method to examine the larvicide pyriproxyfen widely used in the prevention of Zika virus transmission. Our computational model covered a wide range of possible pathways providing mechanistic hypotheses between pyriproxyfen and neurological disorders via protein complexes, thus adding to the plausibility of pyriproxyfen neurotoxicity. Although providing only tentative evidence and comparisons with retinoic acid, our computational systems biology approach is rapid and inexpensive. The case study of pyriproxyfen illustrates its usefulness as an initial or screening step in the assessment of toxicity potentials of chemicals with incompletely known toxic properties. + Copyright © 2018 Elsevier Inc. All rights reserved. + + + + Audouze + Karine + K + + INSERM UMR-S 973, 75013 Paris, France; University of Paris Diderot, 75013 Paris, France. + + + + Taboureau + Olivier + O + + INSERM UMR-S 973, 75013 Paris, France; University of Paris Diderot, 75013 Paris, France. + + + + Grandjean + Philippe + P + + Harvard T.H. Chan School of Public Health, Boston, MA, USA; University of Southern Denmark, Odense, Denmark. Electronic address: pgrand@hsph.harvard.edu. + + + + eng + + Journal Article + + + 2018 + 02 + 21 + +
+ + United States + Toxicol Appl Pharmacol + 0416575 + 0041-008X + + + Computational biology + Developmental neurotoxicity + Pesticide + Predictive toxicology + Pyriproxyfen + Systems biology + Toxicity testing + +
+ + + + 2017 + 11 + 02 + + + 2018 + 02 + 09 + + + 2018 + 02 + 20 + + + 2018 + 2 + 25 + 6 + 0 + + + 2018 + 2 + 25 + 6 + 0 + + + 2018 + 2 + 25 + 6 + 0 + + + aheadofprint + + 29476864 + S0041-008X(18)30060-7 + 10.1016/j.taap.2018.02.014 + + +
+ + + + + 29470110 + + 2018 + 03 + 07 + +
+ + 1541-0048 + + 108 + 4 + + 2018 + Apr + + + American journal of public health + Am J Public Health + + Zika-Associated Microcephaly Epidemic and Birth Rate Reduction in Brazilian Cities. + + 514-516 + + 10.2105/AJPH.2017.304260 + + To estimate birth reduction potentially in response to Zika virus-associated microcephaly among the 36 largest Brazilian cities. + We analyzed the number of live births per month on the basis of information on approximately 8.2 million births from all of Brazil's state capitals and cities that had more than 10 000 annual births. + In the second half of 2016, the live birth rate was reduced by 7.78% (95% confidence interval [CI] = 6.64%, 8.89%; P < .001). This reduction was correlated with the Zika virus-associated microcephaly rate. In the cities with the highest microcephaly rate in 2015 (> 1 case per 1000 live births), the reduction in the live birth rate was 10.84% (95% CI = 8.58%, 13.04%). + The birth rate in the largest Brazilian cities during the second half of 2016 was significantly reduced, which is potentially the effect of a birth control recommendation prompted by an epidemiological alert. Public Health Implications. The effects of population-based interventions should be weighed by considering the actual risk of disease and the sociodemographic impact of strategies such as birth control. + + + + Diaz-Quijano + Fredi Alexander + FA + + Fredi Alexander Diaz-Quijano and Alexandre Dias Porto Chiavegatto Filho are with the Department of Epidemiology, School of Public Health, University of São Paulo, São Paulo, Brazil. Daniele Maria Pelissari is a PhD student in epidemiology at the Department of Epidemiology, School of Public Health, University of São Paulo. + + + + Pelissari + Daniele Maria + DM + + Fredi Alexander Diaz-Quijano and Alexandre Dias Porto Chiavegatto Filho are with the Department of Epidemiology, School of Public Health, University of São Paulo, São Paulo, Brazil. Daniele Maria Pelissari is a PhD student in epidemiology at the Department of Epidemiology, School of Public Health, University of São Paulo. + + + + Chiavegatto Filho + Alexandre Dias Porto + ADP + + Fredi Alexander Diaz-Quijano and Alexandre Dias Porto Chiavegatto Filho are with the Department of Epidemiology, School of Public Health, University of São Paulo, São Paulo, Brazil. Daniele Maria Pelissari is a PhD student in epidemiology at the Department of Epidemiology, School of Public Health, University of São Paulo. + + + + eng + + Journal Article + + + 2018 + 02 + 22 + +
+ + United States + Am J Public Health + 1254074 + 0090-0036 + +
+ + + + 2018 + 2 + 23 + 6 + 0 + + + 2018 + 2 + 23 + 6 + 0 + + + 2018 + 2 + 23 + 6 + 0 + + + ppublish + + 29470110 + 10.2105/AJPH.2017.304260 + + +
+ + + + + 29463209 + + 2018 + 02 + 27 + +
+ + 1471-2202 + + 19 + 1 + + 2018 + Feb + 20 + + + BMC neuroscience + BMC Neurosci + + Characterisation of Zika virus infection in primary human astrocytes. + + 5 + + 10.1186/s12868-018-0407-2 + + The recent Zika virus (ZIKV) outbreak has linked ZIKV with microcephaly and other central nervous system pathologies in humans. Astrocytes are among the first cells to respond to ZIKV infection in the brain and are also targets for virus infection. In this study, we investigated the interaction between ZIKV and primary human brain cortical astrocytes (HBCA). + HBCAs were highly sensitive to representatives of both Asian and African ZIKV lineages and produced high viral yields. The infection was associated with limited immune cytokine/chemokine response activation; the highest increase of expression, following infection, was seen in CXCL-10 (IP-10), interleukin-6, 8, 12, and CCL5 (RANTES). Ultrastructural changes in the ZIKV-infected HBCA were characterized by electron tomography (ET). ET reconstructions elucidated high-resolution 3D images of the proliferating and extensively rearranged endoplasmic reticulum (ER) containing viral particles and virus-induced vesicles, tightly juxtaposed to collapsed ER cisternae. + The results confirm that human astrocytes are sensitive to ZIKV infection and could be a source of proinflammatory cytokines in the ZIKV-infected brain tissue. + + + + Stefanik + Michal + M + + Department of Virology, Veterinary Research Institute, Hudcova 70, 62100, Brno, Czech Republic. + + + + Formanova + Petra + P + + Department of Virology, Veterinary Research Institute, Hudcova 70, 62100, Brno, Czech Republic. + + + + Bily + Tomas + T + + Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, 37005, Ceske Budejovice, Czech Republic. + + + Faculty of Science, University of South Bohemia, Branisovska 31, 37005, Ceske Budejovice, Czech Republic. + + + + Vancova + Marie + M + + Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, 37005, Ceske Budejovice, Czech Republic. + + + Faculty of Science, University of South Bohemia, Branisovska 31, 37005, Ceske Budejovice, Czech Republic. + + + + Eyer + Ludek + L + + Department of Virology, Veterinary Research Institute, Hudcova 70, 62100, Brno, Czech Republic. + + + Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, 37005, Ceske Budejovice, Czech Republic. + + + + Palus + Martin + M + + Department of Virology, Veterinary Research Institute, Hudcova 70, 62100, Brno, Czech Republic. + + + Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, 37005, Ceske Budejovice, Czech Republic. + + + + Salat + Jiri + J + + Department of Virology, Veterinary Research Institute, Hudcova 70, 62100, Brno, Czech Republic. + + + + Braconi + Carla Torres + CT + + Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Institute of Microbiology Sciences, University of São Paulo, São Paulo, 05508-000, Brazil. + + + + Zanotto + Paolo M de A + PMA + + Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Institute of Microbiology Sciences, University of São Paulo, São Paulo, 05508-000, Brazil. + + + + Gould + Ernest A + EA + + EHESP French School of Public Health, IRD French Institute of Research for Development, EPV UMR_D 190 Emergence des Pathologies Virales, Aix Marseille Université, Marseille, France. + + + + Ruzek + Daniel + D + http://orcid.org/0000-0003-4655-2380 + + Department of Virology, Veterinary Research Institute, Hudcova 70, 62100, Brno, Czech Republic. ruzekd@paru.cas.cz. + + + Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, 37005, Ceske Budejovice, Czech Republic. ruzekd@paru.cas.cz. + + + + eng + + + 16-20054S + Grantová Agentura České Republiky + + + + 17-02196S + Grantová Agentura České Republiky + + + + LO1218 + Ministerstvo Školství, Mládeže a Tělovýchovy + + + + LM2015062 + Ministerstvo Školství, Mládeže a Tělovýchovy + + + + FIT + European Regional Development Fund + + + + 61388963 + Development of research organization + + + + 653316 + Horizon 2020 Framework Programme + + + + TE01020118 + Technologická Agentura České Republiky + + + + + Journal Article + + + 2018 + 02 + 20 + +
+ + England + BMC Neurosci + 100966986 + 1471-2202 + + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + J Clin Virol. 2016 Oct;83:63-5 + 27598870 + + + Mayo Clin Proc. 2017 Mar;92 (3):460-466 + 28259231 + + + PLoS One. 2012;7(10):e47912 + 23112871 + + + J Neurosci. 2017 Feb 22;37(8):2161-2175 + 28123079 + + + Cell Rep. 2017 Feb 28;18(9):2113-2123 + 28249158 + + + EMBO J. 2017 Jun 14;36(12 ):1653-1668 + 28473450 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2017 Apr 22;389(10079):1595-1596 + 28593839 + + + J Med Virol. 2015 May;87(5):885-92 + 25675945 + + + Cell Host Microbe. 2009 Apr 23;5(4):365-75 + 19380115 + + + Am J Med Sci. 2017 May;353(5):466-473 + 28502333 + + + J Infect Dis. 2016 Sep 1;214(5):707-11 + 27234417 + + + Sci Rep. 2015 Jun 15;5:10745 + 26073783 + + + Lancet. 2016 Apr 2;387(10026):1481 + 26946926 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Cell Rep. 2016 Jun 14;15(11):2315-22 + 27268504 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + J Gen Virol. 2014 Nov;95(Pt 11):2411-26 + 25000960 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Cell Microbiol. 2017 Aug;19(8): + 28318141 + + + Infect Genet Evol. 2017 Apr;49:134-137 + 28095299 + + + EBioMedicine. 2016 Oct;12 :161-169 + 27688094 + + + N Engl J Med. 2016 Apr 21;374(16):1595-6 + 26958738 + + + + Astrocyte + Electron tomography + Flavivirus + Immune response + Luminex + Zika virus + +
+ + + + 2017 + 09 + 06 + + + 2018 + 02 + 16 + + + 2018 + 2 + 22 + 6 + 0 + + + 2018 + 2 + 22 + 6 + 0 + + + 2018 + 2 + 22 + 6 + 0 + + + epublish + + 29463209 + 10.1186/s12868-018-0407-2 + 10.1186/s12868-018-0407-2 + PMC5820785 + + +
+ + + + + 29452026 + + 2018 + 02 + 16 + +
+ + 1751-8431 + + + 2018 + Feb + 16 + + + Developmental neurorehabilitation + Dev Neurorehabil + + General movements and motor outcomes in two infants exposed to Zika virus: brief report. + + 1-4 + + 10.1080/17518423.2018.1437843 + + We described the general movements (GMs) in the fidgety period and the motor performance of two infants who were exposed to Zika virus (ZIKV) during distinct trimesters of gestation. + Infants were assessed at 4 and 12 months of age. Prechtl's GM assessment and the Alberta Infant Motor Scale were used. + In Case 1, the mother presented confirmed ZIKV infection in the 10th week of gestation and the infant was born full-term with brain abnormalities and microcephaly. Fidgety movements were absent at 16 weeks after term and motor development was severely impaired at 12 months of age. In Case 2, the mother presented confirmed ZIKV infection in the 34th week of gestation and the infant was born full-term with no signs of brain changes or microcephaly. Fidgety movements at 13 weeks were normal in presentation and motor outcome was typical at 12 months. + GM assessment can be useful for ZIKV-exposed infants. These findings represent the first information on GMs and long-term motor outcomes in ZIKV-exposed infants. + + + + Soares-Marangoni + Daniele de Almeida + DA + + a School of Physical Therapy , Institute of Health, Federal University of Mato Grosso do Sul, UFMS , Campo Grande , Brazil. + + + + Tedesco + Natália Matos + NM + + b Program of Post-Graduation in Health and Development , Faculty of Medicine, UFMS , Campo Grande , Brazil. + + + + Nascimento + Andressa Lagoa + AL + + b Program of Post-Graduation in Health and Development , Faculty of Medicine, UFMS , Campo Grande , Brazil. + + + + Almeida + Priscila Rimoli De + PR + + c Physical Therapy Ambulatory , Mato Grosso do Sul Regional Hospital , Campo Grande , Brazil. + + + + Santos Pereira + Caroline Neder Dos + CND + + d Pediatrics Ambulatory , Maria Aparecida Pedrossian University Hospital, UFMS , Campo Grande , Brazil. + + + + eng + + Journal Article + + + 2018 + 02 + 16 + +
+ + England + Dev Neurorehabil + 101304394 + 1751-8423 + + + Child development + Zika virus + general movements + maternal fetal infection transmission + movement disorders + +
+ + + + 2018 + 2 + 17 + 6 + 0 + + + 2018 + 2 + 17 + 6 + 0 + + + 2018 + 2 + 17 + 6 + 0 + + + aheadofprint + + 29452026 + 10.1080/17518423.2018.1437843 + + +
+ + + + + 29441490 + + 2018 + 02 + 14 + +
+ + 1538-2443 + + + 2018 + Feb + 13 + + + Journal of neurovirology + J. Neurovirol. + + Zika virus outbreak: a review of neurological complications, diagnosis, and treatment options. + 10.1007/s13365-018-0614-8 + + Zika virus (ZIKV) is an arbovirus transmitted mainly by mosquitos of Aedes species. The virus has emerged in recent years and spread throughout North and South Americas. The recent outbreak of ZIKV started in Brazil (2015) has resulted in infections surpassing a million mark. Contrary to the previous beliefs that Zika causes mildly symptomatic infections fever, headache, rash, arthralgia, and conjunctivitis, the recent outbreak associated ZIKV to serious neurological complications such as microcephaly, Guillain-Barré syndrome, and eye infections. The recent outbreak has resulted in an astonishing number of microcephaly cases in fetus and infants. Consequently, numerous studies were conducted using in vitro cell and in vivo animal models. These studies showed clear links between ZIKV infections and neurological abnormalities. Diagnosis methods based on nucleic acid and serological detection facilitated rapid and accurate identification of ZIKV infections. New transmission modalities such as sexual and transplacental transmission were uncovered. Given the seriousness of ZIKV infections, WHO declared the development of safe and effective vaccines and new antiviral drugs as an urgent global health priority. Rapid work in this direction has led to the identification of several vaccine and antiviral drug candidates. Here, we review the remarkable progress made in understanding the molecular links between ZIKV infections and neurological irregularities, new diagnosis methods, potential targets for antiviral drugs, and the current state of vaccine development. + + + + Koppolu + Veerendra + V + + Global Bioassay Development and Quality, Biopharmaceutical Development, MedImmune, Gaithersburg, MD, USA. + + + + Shantha Raju + T + T + http://orcid.org/0000-0002-6698-2508 + + Global Bioassay Development and Quality, Biopharmaceutical Development, MedImmune, Gaithersburg, MD, USA. tshantharaju@yahoo.com. + + + + eng + + Journal Article + Review + + + 2018 + 02 + 13 + +
+ + United States + J Neurovirol + 9508123 + 1355-0284 + + + Aedes mosquito + Antiviral chemotherapy + Flavivirus + Guillain-Barre syndrome + Microcephaly + Neuropathogen + Zika vaccine + Zika virus + +
+ + + + 2017 + 08 + 23 + + + 2018 + 01 + 18 + + + 2018 + 2 + 15 + 6 + 0 + + + 2018 + 2 + 15 + 6 + 0 + + + 2018 + 2 + 15 + 6 + 0 + + + aheadofprint + + 29441490 + 10.1007/s13365-018-0614-8 + 10.1007/s13365-018-0614-8 + + +
+ + + + + 29437050 + + 2018 + 02 + 13 + +
+ + 1098-4275 + + 141 + Suppl 2 + + 2018 + Feb + + + Pediatrics + Pediatrics + + Motor Abnormalities and Epilepsy in Infants and Children With Evidence of Congenital Zika Virus Infection. + + S167-S179 + + 10.1542/peds.2017-2038F + + Initial reports of congenital Zika virus (ZIKV) infection focused on microcephaly at birth with severe brain anomalies; the phenotype has broadened to include microcephaly that develops after birth and neurodevelopmental sequelae. In this narrative review, we summarize medical literature describing motor abnormalities and epilepsy in infants with evidence of congenital ZIKV infection and provide information on the impact of these conditions. Specific scenarios are used to illustrate the complex clinical course in infants with abnormalities that are consistent with congenital Zika syndrome. A search of the English-language medical literature was done to identify motor abnormalities and epilepsy in infants with evidence of congenital ZIKV infection by using Medline and PubMed, Embase, Scientific Electronic Library Online, Scopus, the OpenGrey Repository, and the Grey Literature Report in Public Health. Search terms included "Zika" only and "Zika" in combination with any of the following terms: "epilepsy," "seizure," "motor," and "cerebral palsy." Clinical features of motor abnormalities and epilepsy in these children were reviewed. Thirty-six publications were identified; 8 were selected for further review. Among infants with clinical findings that are consistent with congenital Zika syndrome, 54% had epilepsy and 100% had motor abnormalities. In these infants, impairments that are consistent with diagnoses of cerebral palsy and epilepsy occur frequently. Pyramidal and extrapyramidal motor abnormalities were notable for their early development and co-occurrence. Prompt identification of potential disabilities enables early intervention to improve the quality of life for affected children. Long-term studies of developmental outcomes and interventions in children with congenital ZIKV infection are needed. + Copyright © 2018 by the American Academy of Pediatrics. + + + + Pessoa + André + A + + Hospital Infantil Albert Sabin, Fortaleza, Brazil. + + + Department of Pediatrics and Neurology, Universidade Estadual do Ceará, Fortaleza, Brazil. + + + + van der Linden + Vanessa + V + + Association for Assistance of Disabled Children, Recife, Brazil. + + + Hospital Barāo de Lucena, Recife, Brazil. + + + + Yeargin-Allsopp + Marshalyn + M + + Centers for Disease Control and Prevention, Atlanta, Georgia; mxy1@cdc.gov. + + + + Carvalho + Maria Durce Costa Gomes + MDCG + + Osvaldo Cruz University Hospital, University of Pernambuco, Recife, Brazil. + + + + Ribeiro + Erlane Marques + EM + + Hospital Infantil Albert Sabin, Fortaleza, Brazil. + + + + Van Naarden Braun + Kim + K + + Centers for Disease Control and Prevention, Atlanta, Georgia. + + + + Durkin + Maureen S + MS + + Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin; and. + + + + Pastula + Daniel M + DM + + Departments of Neurology, Medicine (Infectious Diseases), and Epidemiology, University of Colorado, Denver, Colorado. + + + + Moore + Jazmyn T + JT + + Centers for Disease Control and Prevention, Atlanta, Georgia. + + + + Moore + Cynthia A + CA + + Centers for Disease Control and Prevention, Atlanta, Georgia. + + + + eng + + Journal Article + + + 2018 + 02 + 01 + +
+ + United States + Pediatrics + 0376422 + 0031-4005 + + POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose. +
+ + + + 2017 + 11 + 03 + + + 2018 + 2 + 14 + 6 + 0 + + + 2018 + 2 + 14 + 6 + 0 + + + 2018 + 2 + 14 + 6 + 0 + + + ppublish + + 29437050 + peds.2017-2038F + 10.1542/peds.2017-2038F + + +
+ + + + + 29432825 + + 2018 + 02 + 25 + +
+ + 1532-2742 + + + 2018 + Feb + 09 + + + The Journal of infection + J. Infect. + + Cerebrospinal fluid aspects of neonates with or without microcephaly born to mothers with gestational Zika virus clinical symptoms. + S0163-4453(18)30057-4 + 10.1016/j.jinf.2018.02.004 + + + Ramos + Clara L + CL + + Bahiana School of Medicine, Bahiana Foundation for Science Development, Salvador, 40295-050, Brazil. Electronic address: ccclr1@gmail.com. + + + + Moreno-Carvalho + Otávio A + OA + + Cerebrospinal Fluid Laboratory, José Silveira Foundation, Salvador, 40170-100, Brazil. + + + + Nascimento-Carvalho + Cristiana M + CM + + Post-graduation Program in Health Sciences and Department of Paediatrics, Federal University of Bahia School of Medicine, Salvador, 40025-010, Brazil; Brazilian Council for Scientific and Technological Development, Brazilia, Brazil. + + + + eng + + Letter + + + 2018 + 02 + 09 + +
+ + England + J Infect + 7908424 + 0163-4453 + +
+ + + + 2018 + 01 + 21 + + + 2018 + 01 + 26 + + + 2018 + 02 + 03 + + + 2018 + 2 + 13 + 6 + 0 + + + 2018 + 2 + 13 + 6 + 0 + + + 2018 + 2 + 13 + 6 + 0 + + + aheadofprint + + 29432825 + S0163-4453(18)30057-4 + 10.1016/j.jinf.2018.02.004 + + +
+ + + + + 29422006 + + 2018 + 02 + 09 + +
+ + 1996-3181 + + + 2018 + Feb + 01 + + + CNS & neurological disorders drug targets + CNS Neurol Disord Drug Targets + + Inhibition of Neurogenesis by Zika virus Infection. + 10.2174/1871527317666180202115114 + + The association between Zika virus infection and neurological disorder has raised urgent global alarm. The ongoing epidemic has triggered quick responses in the scientific community. The first case of Zika virus was reported in 2015 from Brazil and now has spread over 30 countries. Nearly four hundred cases of travel-associated Zika virus infection have also been reported in the United States. Zika virus is primarily transmitted by mosquito belongs to the genus Aedes that are widely distributed throughout the world including the Southern United States. Additionally, the virus can also be transmitted from males to females by sexual contact. The epidemiological investigations during the current outbreak found a causal link between infection in pregnant women and development of microcephaly in their unborn babies. This finding is a cause for grave concern since microcephaly is a serious neural developmental disorder that can lead to significant post-natal developmental abnormalities and disabilities. Recently, published data indicate that Zika virus infection affects the growth of fetal neural progenitor cells and cerebral neurons that results in malformation of cerebral cortex leading to microcephaly. Recently, it has been reported that Zika virus infection deregulates the signaling pathway of neuronal cell and inhibit the neurogenesis resulting into dementia. In this review we have discussed about the information about cellular and molecular mechanisms in neurodegeneration of human neuronal cells and inhibit the neurogenesis. Additionally, this information will be very helpful further not only in neuro-scientific research but also designing and development of management strategies for microcephaly and other mosquito borne disease. + Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. + + + + Ahmad + Fahim + F + + Drug Discovery Division, Southern Research, 2000, Ninth Ave, South, Birmingham, AL 35205. Birmingham. United States. + + + + Siddiqui + Amna + A + + Department of Biochemistry and Molecular Genetics, 845 19th Street South , University of Alabama, Birmingham, AL 35205 - Department of Biochemistry and Molecular Genetics Birmingham. United States. + + + + Kamal + Mohammad A + MA + + Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770; 5. Novel Global Community Educational Foundation. Australia. + + + + Sohrab + Sayed S + SS + + Special Infectious Agents Unit, King Fahd Medical Research Center King Abdulaziz University, Post Box No-80216 Jeddah -21589. Saudi Arabia. + + + + eng + + Journal Article + + + 2018 + 02 + 01 + +
+ + United Arab Emirates + CNS Neurol Disord Drug Targets + 101269155 + 1871-5273 + + + Microcephaly + Mosquitoes. + Neurodegeneration + Neuroprogenitor cells + Zika Virus + +
+ + + + 2017 + 03 + 08 + + + 2017 + 04 + 13 + + + 2017 + 05 + 01 + + + 2018 + 2 + 10 + 6 + 0 + + + 2018 + 2 + 10 + 6 + 0 + + + 2018 + 2 + 10 + 6 + 0 + + + aheadofprint + + 29422006 + CNSNDDT-EPUB-88341 + 10.2174/1871527317666180202115114 + + +
+ + + + + 29421460 + + 2018 + 02 + 08 + +
+ + 1873-5347 + + 200 + + 2018 + Jan + 31 + + + Social science & medicine (1982) + Soc Sci Med + + Media coverage of the Zika crisis in Brazil: The construction of a 'war' frame that masked social and gender inequalities. + + 137-144 + + S0277-9536(18)30023-6 + 10.1016/j.socscimed.2018.01.023 + + Between 2015 and 2016, Zika became an epidemic of global concern and the focus of intense media coverage. Using a hybrid model of frame and social representations theory, we examine how the Zika outbreak was reported in two major newspapers in Brazil: O Globo and Folha de São Paulo. The analysis of 186 articles published between December 2015 and May 2016 reveals a dominant 'war' frame supported by two sub-frames: one focused on eradicating the vector (mosquito) and another on controlling microcephaly, placing the burden of prevention on women. Scientific uncertainties about the virus and its relationship to microcephaly coupled with political uncertainties in Brazil increased the power of the war frame. This frame gave prominence and legitimacy to certain representations of disease management during the crisis, masking social and gender inequalities. We show how the cartography of the disease overlaps with that of poverty and regional inequality in Brazil to argue that addressing socio-economic aspects is essential, but normally neglected, in media communications during disease outbreaks like Zika. + Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved. + + + + Ribeiro + Barbara + B + + Manchester Institute of Innovation Research, Alliance Manchester Business School, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom. Electronic address: barbara.ribeiro@manchester.ac.uk. + + + + Hartley + Sarah + S + + The University of Exeter Business School, University of Exeter, Rennes Drive, Exeter, EX4 4PU, United Kingdom. Electronic address: sarah.hartley@exeter.ac.uk. + + + + Nerlich + Brigitte + B + + Institute for Science and Society, School of Sociology and Social Policy, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom. Electronic address: brigitte.nerlich@nottingham.ac.uk. + + + + Jaspal + Rusi + R + + School of Applied Social Sciences, Faculty of Health and Life Sciences, De Monfort University, The Gateway, Leicester, LE1 9BH, United Kingdom. Electronic address: rjaspal@dmu.ac.uk. + + + + eng + + Journal Article + + + 2018 + 01 + 31 + +
+ + England + Soc Sci Med + 8303205 + 0277-9536 + + + Brazil + Frame analysis + Gender inequality + Media + Social inequality + Social representations theory + War frame + Zika + +
+ + + + 2017 + 07 + 14 + + + 2018 + 01 + 15 + + + 2018 + 01 + 18 + + + 2018 + 2 + 9 + 6 + 0 + + + 2018 + 2 + 9 + 6 + 0 + + + 2018 + 2 + 9 + 6 + 0 + + + aheadofprint + + 29421460 + S0277-9536(18)30023-6 + 10.1016/j.socscimed.2018.01.023 + + +
+ + + + + 29412347 + + 2018 + 02 + 07 + +
+ + 2237-9622 + + 27 + 1 + + 2018 + Feb + 01 + + + Epidemiologia e servicos de saude : revista do Sistema Unico de Saude do Brasil + Epidemiol Serv Saude + + Microcephaly in Piauí, Brazil: descriptive study during the Zika virus epidemic, 2015-2016. + + e20163692 + + S2237-96222018000100300 + 10.5123/S1679-49742018000100002 + + to describe the occurrence and characteristics of microcephaly cases in Piauí, Brazil, during an epidemic of Zika virus infection in 2015-2016. + descriptive study using data of live births from January/2015 to January/2016, obtained from the Information System on Live Births (Sinasc), the Public Health Events Registry (RESP) and the active search for medical records; mothers and live births were tested for dengue, chikungunya, and Zika, besides syphilis, toxoplasmosis, rubella, cytomegalovirus, and herpes (STORCH). + of the 75 microcephaly cases, 34 were related to congenital infectious process; microcephaly prevalence was of 13.6/10 thousand live births; imaging exams confirmed that 34 live births presented calcifications, 23 had cerebral atrophies, 14 had lissencephaly, 12 had ventriculomegaly and 6 had dysgenesis; none tested positive for STORCH, dengue or chikungunya; 1 was IgM positive for Zika. + there was an outbreak of microcephaly in Piauí, possibly related to infection during pregnancy Zika virus. + + + + Ribeiro + Igor Gonçalves + IG + http://orcid.org/0000-0002-4971-9484 + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil. + + + + Andrade + Marcia Regina de + MR + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil. + + + + Silva + Janaína de Moraes + JM + + Secretaria de Estado da Saúde do Piauí, Superintendência de Atenção Integral à Saúde, Teresina, PI, Brasil. + + + + Silva + Zenira Martins + ZM + + Secretaria de Estado da Saúde do Piauí, Superintendência de Atenção Integral à Saúde, Teresina, PI, Brasil. + + + + Costa + Maria Amélia de Oliveira + MAO + + Secretaria de Estado da Saúde do Piauí, Superintendência de Atenção Integral à Saúde, Teresina, PI, Brasil. + + + + Vieira + Marcelo Adriano da Cunha E Silva + MADCES + + Secretaria de Estado da Saúde do Piauí, Instituto de Doenças Tropicais Natan Portella, Teresina, PI, Brasil. + + + + Batista + Francisca Miriane de Araújo + FMA + + Secretaria de Estado da Saúde do Piauí, Superintendência de Atenção Integral à Saúde, Teresina, PI, Brasil. + + + + Guimarães + Herlon + H + + Secretaria de Estado da Saúde do Piauí, Superintendência de Atenção Integral à Saúde, Teresina, PI, Brasil. + + + + Wada + Marcelo Yoshito + MY + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil. + + + + Saad + Eduardo + E + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil. + + + + por + eng + + Journal Article + + Microcefalia no Piauí, Brasil: estudo descritivo durante a epidemia do vírus Zika, 2015-2016. + + 2018 + 02 + 01 + +
+ + Brazil + Epidemiol Serv Saude + 101248287 + 1679-4974 + + + descrever a ocorrência e as características dos casos de microcefalia no Piauí, Brasil, durante epidemia do vírus Zika em 2015-2016. + estudo descritivo com dados dos nascidos vivos no período de janeiro/2015 a janeiro/2016, obtidos do Sistema de Informações sobre Nascidos Vivos (Sinasc), do Registro de Eventos em Saúde Pública (RESP) e de busca ativa em prontuários; mães e nascidos vivos foram testados para dengue, chikungunya e Zika, além de sífilis, toxoplasmose, rubéola, citomegalovírus e herpes (STORCH). + dos 75 casos de microcefalia, 34 foram relacionados a processo infeccioso congênito; a prevalência de microcefalia foi de 13,6/10 mil nascidos vivos; exames de imagem confirmaram que 34 nascidos vivos apresentavam calcificações, 23 atrofias cerebrais, 14 lisencefalia, 12 ventriculomegalia e 6 digenesias; nenhum apresentou resultado positivo para STORCH, dengue ou chikungunya; 1 referiu Zika IgM reagente. + houve surto de microcefalia no Piauí, possivelmente relacionado à infecção gestacional pelo vírus Zika. + + + describir la ocurrencia y las características de los casos de microcefalia en Piauí, Brasil, durante la epidemia de infección por virus Zika en 2015-2016. + Estudio descriptivo incluyendo datos del Sistema de Información de Nacidos Vivos (Sinasc) y del Registro de Eventos en Salud Pública (RESP), entre enero/2015 y enero/2016; las madres fueron testadas para dengue, chikungunya, zika y STORCH. + 75 recién nacidos (RN) presentaron microcefalias; de estos, 34 tenían microcefalia relacionada con una infección; la prevalencia de microcefalia fue de 13,6 casos/10.000 nacidos vivos; imágenes confirmaron que 34 RN presentaron calcificaciones, 23 atrofia cerebral, 14 lisencefalias, 12 ventriculomegalias y 6 disgenesias; ningún RN presentó STORCH, dengue o chikungunya, y 1 fue reactivo para Zika (IgM). + hubo un brote de microcefalia en Piauí posiblemente relacionado con infección materna previa por virus Zika. + +
+ + + + 2017 + 02 + 10 + + + 2017 + 08 + 21 + + + 2018 + 2 + 8 + 6 + 0 + + + 2018 + 2 + 8 + 6 + 0 + + + 2018 + 2 + 8 + 6 + 0 + + + epublish + + 29412347 + S2237-96222018000100300 + 10.5123/S1679-49742018000100002 + + +
+ + + + + 29406975 + + 2018 + 02 + 06 + +
+ + 1557-9824 + + 32 + 1 + + 2018 + Mar + + + Infectious disease clinics of North America + Infect. Dis. Clin. North Am. + + Zika Virus Infection in Children. + + 215-224 + + S0891-5520(17)30098-3 + 10.1016/j.idc.2017.10.003 + + Zika virus is a mosquito-borne Flavivirus responsible for symptomatic and asymptomatic infections in humans. Zika was first identified in Africa as a cause of sporadic febrile illness. Beginning in 2015, Zika virus infection was identified in Brazil and linked with several symptomatic infections. Notably, congenital infections were observed with marked neurologic abnormalities. Diagnosis relies on detection of Zika virus by real-time polymerase chain reaction or by the presence of anti-Zika antibodies. Treatment of this viral illness remains supportive; however, proactive screening and interventions are indicated in the treatment of infants with symptomatic congenital infection. + Copyright © 2017 Elsevier Inc. All rights reserved. + + + + Hendrixson + David Taylor + DT + + Department of Pediatrics, Division of Infectious Diseases, Washington University in St. Louis, St. Louis Children's Hospital, Campus Box 8116, 1 Children's Place, St Louis, MO 63110, USA. Electronic address: dthendrixson@wustl.edu. + + + + Newland + Jason G + JG + + Department of Pediatrics, Division of Infectious Diseases, Washington University in St. Louis, St. Louis Children's Hospital, Campus Box 8116, 1 Children's Place, St Louis, MO 63110, USA. + + + + eng + + Journal Article + Review + +
+ + United States + Infect Dis Clin North Am + 8804508 + 0891-5520 + + + Arthropod-borne disease + Congenital infection + Flavivirus + Microcephaly + Vertical transmission + Zika virus + +
+ + + + 2018 + 2 + 7 + 6 + 0 + + + 2018 + 2 + 7 + 6 + 0 + + + 2018 + 2 + 7 + 6 + 0 + + + ppublish + + 29406975 + S0891-5520(17)30098-3 + 10.1016/j.idc.2017.10.003 + + +
+ + + + + 29406461 + + 2018 + 02 + 28 + +
+ + 1473-656X + + 30 + 2 + + 2018 + Apr + + + Current opinion in obstetrics & gynecology + Curr. Opin. Obstet. Gynecol. + + Zika virus: a public health perspective. + + 116-122 + + 10.1097/GCO.0000000000000440 + + Zika virus' impact on pregnancy became widely known in 2015 with a dramatic increase in the number of babies born with microcephaly in Recife, Brazil. A mosquito-borne virus resulting in congenital anomalies is unique, and Zika's ability to cause neurological defects on a large scale was a grim reminder of the Rubella epidemic in the 1950s. Over the past 2 years, studies have provided insight on how Zika virus (ZIKV) infects cells and causes disease, but much remains unknown about the long-term risks of Zika exposure on infant growth and development. + The impact of ZIKV on pregnancy extends beyond microcephaly and may only first be identified in infancy. The virus has a long latency in semen and can be transmitted sexually. Transplacental passage occurs through infection of Hofbauer cells in the trophoblast. A major difficulty in management of ZIKV disease is that most infections are asymptomatic and the diagnostic methods are not ideal, making both diagnosis and ascertainment of timing of infection problematic. Several different types of vaccines are in development. Large studies are ongoing to determine the risk and total spectrum of anomalies based on the timing of infection and other environmental exposures. + This review will summarize the epidemic, what we have learned, what we hope to learn, and current recommendations for care and management. + + + + Chakhtoura + Nahida + N + + Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. + + + + Hazra + Rohan + R + + + Spong + Catherine Y + CY + + + eng + + Journal Article + +
+ + England + Curr Opin Obstet Gynecol + 9007264 + 1040-872X + +
+ + + + 2018 + 2 + 7 + 6 + 0 + + + 2018 + 2 + 7 + 6 + 0 + + + 2018 + 2 + 7 + 6 + 0 + + + ppublish + + 29406461 + 10.1097/GCO.0000000000000440 + + +
+ + + + + 29386734 + + 2018 + 02 + 04 + +
+ + 0377-1237 + + 74 + 1 + + 2018 + Jan + + + Medical journal, Armed Forces India + Med J Armed Forces India + + Zika: An enormous public health challenge for a miniscule virus. + + 61-64 + + 10.1016/j.mjafi.2016.08.010 + + Zika virus (ZIKV) infection has recently affected 4 million people across the globe. The World Health Organization has declared Zika a "Public Health Emergency of International Concern". The disease is caused by an arbovirus and transmitted byAedesmosquitoes. Zika has followed a pattern already set in by Dengue and Chikungunya viruses. The virus exists in sylvatic form with spillovers to humans. The present outbreak in Brazil started in May 2015 and spread rapidly to Latin America and the Caribbean. The rapid spread is due to availability of non-immune population. The main concern of Zika is the association with microcephaly in infants and Guillain-Barré (GB) Syndrome. During the current Zika outbreak in Brazil, incidence of microcephaly in infants has shown a 20-fold rise. Increased incidence of GB Syndrome has been noticed during the 2013 outbreak in French Polynesia, and the current outbreak. However, causality has not been proved. It is possible that the ZIKV may enter and get established in India. Surveillance against the disease needs to be scaled up. Research needs to be undertaken regarding the dynamics of Zika spread and the development of vaccines. Inter-sectoral coordination and bottom-up approach along with vector control measures under the ambit of National Vector Borne Disease Control Programme may help fight the virus. + + + + Mustafa + M S + MS + + Officer Commanding, Station Health Organisation (Large), Chennai 600032, India. + + + + Ramasethu + R + R + + Commandant, Military Hospital, Chennai 600089, India. + + + + eng + + Journal Article + Review + + + 2016 + 10 + 27 + +
+ + India + Med J Armed Forces India + 7602492 + 0377-1237 + + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + J R Soc Med. 2003 Aug;96(8):374-8 + 12893851 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Adv Parasitol. 2006;62:181-220 + 16647971 + + + Med J Armed Forces India. 2015 Jan;71(1):67-70 + 25609867 + + + J Med Virol. 2012 Sep;84(9):1501-5 + 22825831 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + PLoS Negl Trop Dis. 2014 Oct 09;8(10):e3188 + 25299181 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Aedes + Guillain–Barré Syndrome + Microcephaly + Virus + Zika + +
+ + + + 2016 + 03 + 01 + + + 2016 + 08 + 25 + + + 2019 + 01 + 01 + + + 2018 + 2 + 2 + 6 + 0 + + + 2018 + 2 + 2 + 6 + 0 + + + 2018 + 2 + 2 + 6 + 1 + + + ppublish + + 29386734 + 10.1016/j.mjafi.2016.08.010 + S0377-1237(16)30116-2 + PMC5771758 + + +
+ + + + + 29382068 + + 2018 + 01 + 31 + +
+ + 1999-4915 + + 10 + 2 + + 2018 + Jan + 27 + + + Viruses + Viruses + + Higher Cytopathic Effects of a Zika Virus Brazilian Isolate from Bahia Compared to a Canadian-Imported Thai Strain. + E53 + 10.3390/v10020053 + + Zika virus (ZIKV) is an emerging pathogen from theFlaviviridaefamily. It represents a significant threat to global health due to its neurological and fetal pathogenesis (including microcephaly and congenital malformations), and its rapid dissemination across Latin America in recent years. The virus has spread from Africa to Asia, the Pacific islands and the Americas with limited knowledge about the pathogenesis associated with infection in recent years. Herein, we compared the ability of the Canadian-imported Thai strain PLCal_ZV and the Brazilian isolate HS-2015-BA-01 from Bahia to produce infectious ZIKV particles and cytopathic effects in a cell proliferation assay. We also compared the intracellular viral RNA accumulation of the two strains by quantitative RT-PCR (reverse transcription polymerase chain reaction) analyses. Our observations show that HS-2015-BA-01 is more cytopathic than PLCal_ZV in proliferation assays in Vero, Human Embryonic Kidney HEK 293T and neuroblastoma SH-SY5Y cells. Quantitative RT-PCR shows that the level of viral RNA is higher with HS-2015-BA-01 than with PLCal_ZV in two cell lines, but similar in a neuroblastoma cell line. The two strains have 13 amino acids polymorphisms and we analyzed their predicted protein secondary structure. The increased cytopathicity and RNA accumulation of the Brazilian ZIKV isolate compared to the Thai isolate could contribute to the increased pathogenicity observed during the Brazilian epidemic. + + + + Alpuche-Lazcano + Sergio P + SP + + Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, H3T 1E2, Montréal, QC, Canada. andrew.mouland@mcgill.ca. + + + RNA Trafficking Laboratory, Lady Davis Institute for Medical Research, H3T 1E2, Montréal, QC, Canada. andrew.mouland@mcgill.ca. + + + Department of Medicine, Division of Experimental Medicine, McGill University, H4A 3J1, Montréal, QC, Canada. andrew.mouland@mcgill.ca. + + + + McCullogh + Craig R + CR + + Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, H3T 1E2, Montréal, QC, Canada. craig.mccullogh@mail.mcgill.ca. + + + Department of Microbiology and Immunology, McGill University, H3A 2B4, Montréal, QC, Canada. craig.mccullogh@mail.mcgill.ca. + + + + Del Corpo + Olivier + O + + Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, H3T 1E2, Montréal, QC, Canada. olivier.delcorpo@mail.mcgill.ca. + + + Department of Medicine, Division of Experimental Medicine, McGill University, H4A 3J1, Montréal, QC, Canada. olivier.delcorpo@mail.mcgill.ca. + + + + Rance + Elodie + E + + Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, H3T 1E2, Montréal, QC, Canada. elodie.rance@mail.mcgill.ca. + + + Department of Medicine, Division of Experimental Medicine, McGill University, H4A 3J1, Montréal, QC, Canada. elodie.rance@mail.mcgill.ca. + + + + Scarborough + Robert J + RJ + 0000-0002-7724-2441 + + Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, H3T 1E2, Montréal, QC, Canada. robert.scarborough@mail.mcgill.ca. + + + Department of Microbiology and Immunology, McGill University, H3A 2B4, Montréal, QC, Canada. robert.scarborough@mail.mcgill.ca. + + + + Mouland + Andrew J + AJ + + RNA Trafficking Laboratory, Lady Davis Institute for Medical Research, H3T 1E2, Montréal, QC, Canada. selena.sagan@mcgill.ca. + + + Department of Medicine, Division of Experimental Medicine, McGill University, H4A 3J1, Montréal, QC, Canada. selena.sagan@mcgill.ca. + + + Department of Microbiology and Immunology, McGill University, H3A 2B4, Montréal, QC, Canada. selena.sagan@mcgill.ca. + + + + Sagan + Selena M + SM + + Department of Microbiology and Immunology, McGill University, H3A 2B4, Montréal, QC, Canada. sergio.alpuche@mail.mcgill.ca. + + + Department of Biochemistry, McGill University, H3A 1A3, Montréal, QC, Canada. sergio.alpuche@mail.mcgill.ca. + + + + Teixeira + Mauro M + MM + + Departamento de Bioquimica e Imunologia do Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil. mmtex.ufmg@gmail.com. + + + + Gatignol + Anne + A + 0000-0002-4553-0836 + + Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, H3T 1E2, Montréal, QC, Canada. anne.gatignol@mcgill.ca. + + + Department of Medicine, Division of Experimental Medicine, McGill University, H4A 3J1, Montréal, QC, Canada. anne.gatignol@mcgill.ca. + + + Department of Microbiology and Immunology, McGill University, H3A 2B4, Montréal, QC, Canada. anne.gatignol@mcgill.ca. + + + + eng + + Journal Article + + + 2018 + 01 + 27 + +
+ + Switzerland + Viruses + 101509722 + 1999-4915 + + + Zika virus + cytopathicity + predicted protein structure + qRT-PCR + viral titer + + The authors declare no conflict of interest. +
+ + + + 2017 + 11 + 30 + + + 2018 + 01 + 05 + + + 2018 + 01 + 21 + + + 2018 + 2 + 1 + 6 + 0 + + + 2018 + 2 + 1 + 6 + 0 + + + 2018 + 2 + 1 + 6 + 0 + + + epublish + + 29382068 + v10020053 + 10.3390/v10020053 + + +
+ + + + + 29362686 + + 2018 + 01 + 26 + +
+ + 2157-3999 + + 9 + + 2017 + Nov + 27 + + + PLoS currents + PLoS Curr + + A Possible Link Between Pyriproxyfen and Microcephaly. + ecurrents.outbreaks.5afb0bfb8cf31d9a4baba7b19b4edbac + 10.1371/currents.outbreaks.5afb0bfb8cf31d9a4baba7b19b4edbac + + The Zika virus has been the primary suspect in the large increase in incidence of microcephaly in 2015-6 in Brazil. While evidence for Zika being the cause of some of the cases is strong, its role as the primary cause of the large number of cases in Brazil has not been confirmed. Recently, the disparity between the incidences in different geographic locations has led to questions about the virus's role. Here we consider the alternative possibility that the use of the insecticide pyriproxyfen for control of mosquito populations in Brazilian drinking water is the primary cause. Pyriproxifen is a juvenile hormone analog which has been shown to correspond in mammals to a number of fat soluble regulatory molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity and whose application during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog that was approved as an insecticide based upon tests performed in the 1970s, has metabolites that bind to the mammalian retinoid X receptor, and has been shown to cause developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via maternal exposure and activation of the retinoid X receptor in developing fetuses. Moreover, tests of pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence for developmental toxicity, actually found some evidence for such an effect, including low brain mass and arhinencephaly-incomplete formation of the anterior cerebral hemispheres-in exposed rat pups. Finally, the pyriproxyfen use in Brazil is unprecedented-it has never before been applied to a water supply on such a scale. Claims that it is not being used in Recife, the epicenter of microcephaly cases, do not distinguish the metropolitan area of Recife, where it is widely used, and the municipality, and have not been adequately confirmed. Given this combination of information about molecular mechanisms and toxicological evidence, we strongly recommend that the use of pyriproxyfen in Brazil be suspended until the potential causal link to microcephaly is investigated further. + + + + Parens + Raphael + R + + Department of Complex Systems, New England Complex Systems Institute, Cambridge, MA, USA. + + + + Nijhout + H Frederik + HF + + Biology Department, Duke University, Durham, NC, USA. + + + + Morales + Alfredo + A + + New England Complex Systems Institute. + + + + Xavier Costa + Felipe + F + + New England Complex Systems Institute, Cambridge, MA, USA. + + + + Bar-Yam + Yaneer + Y + + Department of Complex Systems, New England Complex Systems Institute, Cambridge, MA, USA. + + + + eng + + Journal Article + + + 2017 + 11 + 27 + +
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+ + + + + 29361773 + + 2018 + 02 + 13 + +
+ + 1999-4915 + + 10 + 1 + + 2018 + Jan + 22 + + + Viruses + Viruses + + Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System. + E49 + 10.3390/v10010049 + + Zika virus (ZIKV) has been defined as a teratogenic pathogen behind the increased number of cases of microcephaly in French Polynesia, Brazil, Puerto Rico, and other South American countries. Experimental studies using animal models have achieved tremendous insight into understanding the viral pathogenesis, transmission, teratogenic mechanisms, and virus-host interactions. However, the animals used in published investigations are mostly interferon (IFN)-compromised, either genetically or via antibody treatment. Herein, we studied ZIKV infection in IFN-competent mice using African (MR766) and Asian strains (PRVABC59 and SZ-WIV01). After testing four different species of mice, we found that BALB/c neonatal mice were resistant to ZIKV infection, that Kunming, ICR and C57BL/6 neonatal mice were fatally susceptible to ZIKV infection, and that the fatality of C57BL/6 neonates from 1 to 3 days old were in a viral dose-dependent manner. The size and weight of the brain were significantly reduced, and the ZIKV-infected mice showed neuronal symptoms such as hind-limb paralysis, tremor, and poor balance during walking. Pathologic and immunofluorescent experiments revealed that ZIKV infected different areas of the central nervous system (CNS) including gray matter, hippocampus, cerebral cortex, and spinal cord, but not olfactory bulb. Interestingly, ZIKV replicated in multiple organs and resulted in pathogenesis in liver and testis, implying that ZIKV infection may engender a high health risk in neonates by postnatal infection. In summary, we investigated ZIKV pathogenesis using an animal model that is not IFN-compromised. + + + + Li + Shuxuan + S + 0000-0001-6222-4323 + + State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China. lishuxuan37@163.com. + + + + Armstrong + Najealicka + N + + Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA. narmstrong@Howard.edu. + + + + Zhao + Huan + H + + State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China. zh373183889@163.com. + + + + Hou + Wangheng + W + + State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China. houwangheng@xmu.edu.cn. + + + + Liu + Jian + J + + Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USA. jl2147@njms.rutgers.edu. + + + + Chen + Chunye + C + + State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China. m13113141373@163.com. + + + + Wan + Junkai + J + + State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China. wjk927@163.com. + + + + Wang + Wei + W + + State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China. lukewang@xmu.edu.cn. + + + + Zhong + Chunlian + C + + Department of Basic Medical Sciences, Medical College of Xiamen University, Xiamen 361102, China. zhongchunlian0117@126.com. + + + + Liu + Che + C + + State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China. liuche@xmu.edu.cn. + + + + Zhu + Hua + H + + Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USA. zhuhu@njms.rutgers.edu. + + + + Xia + Ningshao + N + 0000-0003-0179-5266 + + State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China. nsxia@xmu.edu.cn. + + + + Cheng + Tong + T + + State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China. tcheng@xmu.edu.cn. + + + + Tang + Qiyi + Q + 0000-0002-6487-2356 + + Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA. qiyi.tang@howard.edu. + + + + eng + + Journal Article + + + 2018 + 01 + 22 + +
+ + Switzerland + Viruses + 101509722 + 1999-4915 + + + + Cell Host Microbe. 2016 Jun 8;19(6):882-90 + 27212660 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + J Virol. 2017 Mar 29;91(8): + 28148798 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Cell Host Microbe. 2017 Sep 13;22(3):366-376.e3 + 28910635 + + + Ann Trop Med Parasitol. 1975 Mar;69(1):49-64 + 1124969 + + + J Med Virol. 2016 Aug;88(8):1291-6 + 27124623 + + + Cell Stem Cell. 2016 Nov 3;19(5):593-598 + 27545505 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Cell. 2016 May 19;165(5):1238-1254 + 27118425 + + + Infect Immun. 2002 Jul;70(7):3521-8 + 12065491 + + + Int J Infect Dis. 2016 Mar;44:11-5 + 26854199 + + + Virol Sin. 2016 Apr;31(2):176-9 + 27105638 + + + PLoS Negl Trop Dis. 2017 Jan 9;11(1):e0005296 + 28068342 + + + Prehosp Disaster Med. 2016 Apr;31(2):119-20 + 26940218 + + + Lancet Infect Dis. 2016 Jul;16(7):e119-e126 + 27282424 + + + Cell. 2016 Dec 1;167(6):1511-1524.e10 + 27884405 + + + Trends Mol Med. 2016 Aug;22(8):639-41 + 27345865 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + BMJ. 2016 Feb 02;352:i657 + 26839247 + + + Ultrasound Obstet Gynecol. 2016 May;47(5):657-60 + 26923098 + + + Science. 2017 Nov 17;358(6365):933-936 + 28971967 + + + Am J Public Health. 2016 Apr;106(4):601-5 + 26959259 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + PLoS Pathog. 2017 Mar 9;13(3):e1006258 + 28278235 + + + Emerg Infect Dis. 2016 Jul;22(7):1185-92 + 27070380 + + + Cell Rep. 2016 Sep 20;16(12 ):3208-3218 + 27612415 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + DNA Cell Biol. 2016 Aug;35(8):367-72 + 27348136 + + + Immunology. 1986 Nov;59(3):445-50 + 2947846 + + + MMWR Morb Mortal Wkly Rep. 2017 Jun 16;66(23 ):615-621 + 28617773 + + + BMJ. 2016 Mar 01;352:i1242 + 26932976 + + + PLoS Negl Trop Dis. 2016 May 10;10 (5):e0004695 + 27163257 + + + Cell Stem Cell. 2016 Dec 1;19(6):690-702 + 27912090 + + + Exp Toxicol Pathol. 2017 Feb;69(2):63-71 + 27899230 + + + PLoS Negl Trop Dis. 2016 Apr 19;10(4):e0004682 + 27093158 + + + Emerg Infect Dis. 2016 May;22(5):933-5 + 27088323 + + + J Virol. 2016 Dec 16;91(1): + 27795432 + + + Antiviral Res. 2017 Jan;137:14-22 + 27838352 + + + Antiviral Res. 2016 Jun;130:69-80 + 26996139 + + + Lancet. 2017 Aug 26;390(10097):861-870 + 28647172 + + + Am J Trop Med Hyg. 1952 Jan;1(1):30-50 + 14903434 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + EMBO Rep. 2016 Dec;17 (12 ):1766-1775 + 27797853 + + + EBioMedicine. 2017 Nov;25:95-105 + 29107512 + + + PLoS Negl Trop Dis. 2016 May 05;10 (5):e0004658 + 27149521 + + + Antiviral Res. 2010 Aug;87(2):125-48 + 19945487 + + + PLoS Pathog. 2016 Nov 17;12 (11):e1006004 + 27855206 + + + Cell. 2016 May 19;165(5):1081-1091 + 27180225 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Nucleic Acids Res. 2016 Oct 14;44(18):8610-8620 + 27580721 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Ann Intern Med. 2016 May 17;164(10 ):689-91 + 26914810 + + + Trans R Soc Trop Med Hyg. 1956 May;50(3):238-42 + 13337908 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + + Flavivirus + Zika virus (ZIKV) + microcephaly + neonatal mouse + pathogenesis + + The authors declare no conflict of interest. +
+ + + + 2017 + 12 + 25 + + + 2018 + 01 + 17 + + + 2018 + 01 + 18 + + + 2018 + 1 + 25 + 6 + 0 + + + 2018 + 1 + 25 + 6 + 0 + + + 2018 + 1 + 25 + 6 + 0 + + + epublish + + 29361773 + v10010049 + 10.3390/v10010049 + PMC5795462 + + +
+ + + + + 29360072 + + 2018 + 01 + 23 + +
+ + 0025-7680 + + 78 + 1 + + 2018 + + + Medicina + Medicina (B Aires) + + [Dengue, zika, chikungunya and the development of vaccines]. + + 23-28 + + + Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda. ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines. + + + + Kantor + Isabel N + IN + + Comité de Redacción, Medicina (Buenos Aires), Argentina. E-mail: isabel.kantor1@gmail.com. + + + + spa + + English Abstract + Journal Article + + Dengue, zika, chikungunya y el desarrollo de vacunas. +
+ + Argentina + Medicina (B Aires) + 0204271 + 0025-7680 + + + Argentina + arbovirus + chikungunya + dengue + vaccine development + zika + +
+ + + + 2018 + 1 + 24 + 6 + 0 + + + 2018 + 1 + 24 + 6 + 0 + + + 2018 + 1 + 24 + 6 + 0 + + + ppublish + + 29360072 + + +
+ + + + + 29357841 + + 2018 + 02 + 15 + +
+ + 1471-2334 + + 18 + 1 + + 2018 + 01 + 22 + + + BMC infectious diseases + BMC Infect. Dis. + + Study on the persistence of Zika virus (ZIKV) in body fluids of patients with ZIKV infection in Brazil. + + 49 + + 10.1186/s12879-018-2965-4 + + Zika virus (ZIKV) has been identified in several body fluids of infected individuals. In most cases, it remained detected in blood from few days to 1 week after the onset of symptoms, and can persist longer in urine and in semen. ZIKV infection can have dramatic consequences such as microcephaly and Guillain-Barré syndrome. ZIKV sexual transmission has been documented. A better understanding of ZIKV presence and persistence across biologic compartments is needed to devise rational measures to prevent its transmission. + This observational cohort study will recruit non-pregnant participants aged 18 years and above with confirmed ZIKV infection [positive reverse transcriptase-polymerase chain reaction (RT-PCR) test in blood and/or urine]: symptomatic men and women in ZIKV infection acute phase, and their symptomatic or asymptomatic household/sexual infected contacts. Specimens of blood, urine, semen, vaginal secretion/menstrual blood, rectal swab, oral fluids, tears, sweat, urine and breast milk (if applicable) will be collected at pre-established intervals and tested for ZIKV RNA presence by RT-PCR, other co-infection (dengue, Chikungunya, HIV, hepatitis B and C, syphilis), antibody response (including immunoglobulins M and G), plaque reduction neutralization test (if simultaneously positive for ZIKV and dengue), and ZIKV culture and RNA sequencing. Data on socio-demographic characteristics and comorbidities will be collected in parallel. Participants will be followed up for 12 months. + This prolonged longitudinal follow-up of ZIKV infected persons with regular biologic testing and data collection will offer a unique opportunity to investigate the presence and persistence of ZIKV in various biologic compartments, their clinical and immunological correlates as well as the possibility of ZIKV reactivation/reinfection over time. This valuable information will substantially contribute to the body of knowledge on ZIKV infection and serve as a base for the development of more effective recommendation on the prevention of ZIKV transmission. + NCT03106714 . Registration Date: April, 7, 2017. + + + + Calvet + Guilherme Amaral + GA + + Acute Febrile Illnesses Laboratory, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil. guilherme.calvet@ini.fiocruz.br. + + + + Kara + Edna Oliveira + EO + + World Health Organization, Geneva, Switzerland. + + + + Giozza + Silvana Pereira + SP + + Department of STI, AIDS and Viral Hepatitis, Secretary for Health Surveillance, Ministry of Health Brazil, Brasilia, Brazil. + + + + Bôtto-Menezes + Camila Helena Aguiar + CHA + + Tropical Medicine Foundation Doctor Heitor Vieira Dourado (FMT-HVD), Manaus, Amazonas, Brazil. + + + + Gaillard + Philippe + P + + World Health Organization, Geneva, Switzerland. + + + + de Oliveira Franca + Rafael Freitas + RF + + Aggeu Magalhães Research Center, Oswaldo Cruz Foundation, Recife, Pernambuco, Brazil. + + + + de Lacerda + Marcus Vinicius Guimarães + MVG + + Tropical Medicine Foundation Doctor Heitor Vieira Dourado (FMT-HVD), Manaus, Amazonas, Brazil. + + + + da Costa Castilho + Marcia + M + + Tropical Medicine Foundation Doctor Heitor Vieira Dourado (FMT-HVD), Manaus, Amazonas, Brazil. + + + + Brasil + Patrícia + P + + Acute Febrile Illnesses Laboratory, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + de Sequeira + Patrícia Carvalho + PC + + Flavivirus Laboratory, Oswaldo Cruz Institute/Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. + + + + de Mello + Maeve Brito + MB + + Department of Communicable Diseases and Health Analysis, Pan American Health Organization/World Health Organization, Washington DC, USA. + + + + Bermudez + Ximena Pamela Diaz + XPD + + Public Health Department, University of Brasilia, Pan American Health Organization/World Health Organization, Brasilia, Brazil. + + + + Modjarrad + Kayvon + K + + Walter Reed Army Institute of Research, Silver Spring, USA. + + + + Meurant + Robyn + R + + World Health Organization, Geneva, Switzerland. + + + + Landoulsi + Sihem + S + + World Health Organization, Geneva, Switzerland. + + + + Benzaken + Adele Schwartz + AS + + Department of STI, AIDS and Viral Hepatitis, Secretary for Health Surveillance, Ministry of Health Brazil, Brasilia, Brazil. + + + Tropical Medicine Foundation Doctor Heitor Vieira Dourado (FMT-HVD), Manaus, Amazonas, Brazil. + + + + de Filippis + Ana Maria Bispo + AMB + + Flavivirus Laboratory, Oswaldo Cruz Institute/Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. + + + + Broutet + Nathalie Jeanne Nicole + NJN + + World Health Organization, Geneva, Switzerland. + + + + ZIKABRA Study Team + + + eng + + + ClinicalTrials.gov + + NCT03106714 + + + + + + Wellcome Trust + United Kingdom + + + + Journal Article + Research Support, Non-U.S. Gov't + Research Support, U.S. Gov't, Non-P.H.S. + + + 2018 + 01 + 22 + +
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+ + + + 2017 + 08 + 23 + + + 2018 + 01 + 16 + + + 2018 + 1 + 24 + 6 + 0 + + + 2018 + 1 + 24 + 6 + 0 + + + 2018 + 1 + 24 + 6 + 0 + + + epublish + + 29357841 + 10.1186/s12879-018-2965-4 + 10.1186/s12879-018-2965-4 + PMC5778641 + + +
+ + + + + 29357366 + + 2018 + 02 + 18 + +
+ + 1935-2735 + + 12 + 1 + + 2018 + Jan + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection. + + e0006154 + + 10.1371/journal.pntd.0006154 + + Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections. + + + + Paquin-Proulx + Dominic + D + http://orcid.org/0000-0003-1407-3414 + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, United States of America. + + + + Avelino-Silva + Vivian I + VI + + School of Medicine, University of São Paulo, São Paulo, Brazil. + + + Hospital Sírio Libanés, São Paulo, Brazil. + + + + Santos + Bianca A N + BAN + + School of Medicine, University of São Paulo, São Paulo, Brazil. + + + + Silveira Barsotti + Nathália + N + + School of Medicine, University of São Paulo, São Paulo, Brazil. + + + + Siroma + Fabiana + F + + Hospital Sírio Libanés, São Paulo, Brazil. + + + + Fernandes Ramos + Jessica + J + + School of Medicine, University of São Paulo, São Paulo, Brazil. + + + Hospital Sírio Libanés, São Paulo, Brazil. + + + + Coracini Tonacio + Adriana + A + + School of Medicine, University of São Paulo, São Paulo, Brazil. + + + Hospital Sírio Libanés, São Paulo, Brazil. + + + + Song + Alice + A + + School of Medicine, University of São Paulo, São Paulo, Brazil. + + + Hospital Sírio Libanés, São Paulo, Brazil. + + + + Maestri + Alvino + A + + School of Medicine, University of São Paulo, São Paulo, Brazil. + + + + Barros Cerqueira + Natalia + N + + School of Medicine, University of São Paulo, São Paulo, Brazil. + + + + Felix + Alvina Clara + AC + + Departamento de Molestias Infecciosas e Parasitarias-(LIM-52), Instituto de Medicina Tropical de São Paulo e Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. + + + + Levi + José Eduardo + JE + + Departamento de Molestias Infecciosas e Parasitarias-(LIM-52), Instituto de Medicina Tropical de São Paulo e Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. + + + + Greenspun + Benjamin C + BC + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, United States of America. + + + + de Mulder Rougvie + Miguel + M + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, United States of America. + + + + Rosenberg + Michael G + MG + + Pediatric Infectious Diseases Department, Jacobi Medical Center, Bronx, NY, United States of America. + + + + Nixon + Douglas F + DF + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, United States of America. + + + + Kallas + Esper G + EG + + School of Medicine, University of São Paulo, São Paulo, Brazil. + + + + eng + + Journal Article + + + 2018 + 01 + 22 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + + + Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5434-E5443 + 28630305 + + + J Exp Med. 2014 Jul 28;211(8):1601-10 + 25049333 + + + J Exp Med. 2013 Oct 21;210(11):2305-20 + 24101382 + + + Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10133-8 + 27543331 + + + J Clin Virol. 2012 Jan;53(1):38-42 + 22014848 + + + J Invest Dermatol. 2014 Dec;134(12 ):2898-2907 + 24945094 + + + FEMS Immunol Med Microbiol. 2000 Jun;28(2):151-5 + 10799806 + + + Elife. 2016 Apr 19;5: + 27090089 + + + PLoS Pathog. 2015 Aug 21;11(8):e1005072 + 26295709 + + + Pediatr Infect Dis J. 2017 May;36(5):500-501 + 28403053 + + + Nature. 2012 Nov 29;491(7426):717-23 + 23051753 + + + PLoS One. 2017 Apr 6;12 (4):e0175345 + 28384290 + + + Am J Trop Med Hyg. 2015 Jun;92(6):1156-62 + 25825389 + + + Nat Rev Immunol. 2011 Jul 15;11(8):532-43 + 21760609 + + + Curr Opin Immunol. 2017 Oct;48:7-14 + 28750261 + + + PLoS Negl Trop Dis. 2015 Feb 12;9(2):e0003520 + 25675375 + + + Australas J Dermatol. 2017 Aug;58(3):200-204 + 26940855 + + + Eur J Immunol. 2016 Sep;46(9):2204-10 + 27296288 + + + Nat Commun. 2016 Jun 23;7:11653 + 27337592 + + + J Immunol. 2013 Apr 1;190(7):3142-52 + 23447689 + + + J Clin Virol. 2016 Jan;74:1-3 + 26615388 + + + J Leukoc Biol. 2016 Jul;100(1):233-40 + 27034405 + + + PLoS Negl Trop Dis. 2011 Dec;5(12):e1449 + 22206036 + + + Nature. 2013 Apr 25;496(7446):504-7 + 23563266 + + + FEMS Immunol Med Microbiol. 2001 Apr;30(3):229-33 + 11335143 + + + Viruses. 2016 Nov 29;8(12 ): + 27916837 + + + Euro Surveill. 2017 Jan 19;22(3): + 28128730 + + + PLoS Negl Trop Dis. 2013 May 23;7(5):e2236 + 23717702 + + + Blood. 2013 Feb 7;121(6):951-61 + 23255555 + + + Nat Immunol. 2010 Aug;11(8):701-8 + 20581831 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Nat Commun. 2014;5:3143 + 24452018 + + + Curr Opin HIV AIDS. 2013 Mar;8(2):117-24 + 23274365 + + + Blood. 2013 Feb 14;121(7):1124-35 + 23243281 + + + Lancet. 2016 Apr 9;387(10027):1531-1539 + 26948433 + + + J Clin Virol. 2014 Nov;61(3):365-70 + 25288310 + + + J Immunol. 2009 Apr 15;182(8):4865-73 + 19342665 + + + Nature. 2003 Mar 13;422(6928):164-9 + 12634786 + + + Eur J Immunol. 2014 Jan;44(1):195-203 + 24019201 + + +
+ + + + 2017 + 07 + 25 + + + 2017 + 12 + 05 + + + 2018 + 02 + 01 + + + 2018 + 1 + 23 + 6 + 0 + + + 2018 + 1 + 23 + 6 + 0 + + + 2018 + 1 + 23 + 6 + 0 + + + epublish + + 29357366 + 10.1371/journal.pntd.0006154 + PNTD-D-17-01184 + PMC5794195 + + +
+ + + + + 29352094 + + 2018 + 02 + 14 + +
+ + 1526-632X + + 90 + 7 + + 2018 + Feb + 13 + + + Neurology + Neurology + + Auditory brainstem function in microcephaly related to Zika virus infection. + + e606-e614 + + 10.1212/WNL.0000000000004974 + + To study the effect of prenatal Zika virus (ZV) infection on brainstem function reflected in brainstem auditory evoked potentials (BAEPs). + In a cross-sectional study in 19 children (12 girls) with microcephaly related to ZV infection, aged between 12 and 62 weeks, the brainstem function was examined through BAEPs. The latencies of wave peaks I, III, and V of the left and right ears (n = 37) were standardized according to normative data, and compared between them by 2-tailedttest. The confounding variables (cephalic perimeter at the born and chronological age) were correlated with the normalized latencies using Pearson test. + All patients showed, in general, clear waveforms, with latencies within 3 SDs of the normative values. However, statistically increased latencies of waves I and III (I > III,p= 0.031) were observed, relative to wave V (p< 0.001), the latter being closer to respective normative value. The latency of wave I was observed to increase with age (r= 0.45,p= 0.005). The waves, in turn, did not depend on cephalic perimeter. + These results are consistent with the functional normality of the brainstem structure and its lack of correlation with microcephaly, suggesting that the disruption produced by the ZV infection does not act in the cell proliferation phase, but mostly in the processes of neuronal migration and differentiation in the telencephalon. + © 2018 American Academy of Neurology. + + + + Marques Abramov + Dimitri + D + + From the Laboratory of Neurobiology and Clinical Neurophysiology (D.M.A., T.S., D.d.S.e.S., I.A., V.V.L.) and Unit of Clinical Research (S.-C.G.-J., M.E.L.M.), National Institute of Women, Children and Adolescents, Health Fernandes Figueira, Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health, Rio de Janeiro, Brazil. + + + + Saad + Tania + T + + From the Laboratory of Neurobiology and Clinical Neurophysiology (D.M.A., T.S., D.d.S.e.S., I.A., V.V.L.) and Unit of Clinical Research (S.-C.G.-J., M.E.L.M.), National Institute of Women, Children and Adolescents, Health Fernandes Figueira, Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health, Rio de Janeiro, Brazil. + + + + Gomes-Junior + Saint-Clair + SC + + From the Laboratory of Neurobiology and Clinical Neurophysiology (D.M.A., T.S., D.d.S.e.S., I.A., V.V.L.) and Unit of Clinical Research (S.-C.G.-J., M.E.L.M.), National Institute of Women, Children and Adolescents, Health Fernandes Figueira, Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health, Rio de Janeiro, Brazil. + + + + de Souza E Silva + Daniel + D + + From the Laboratory of Neurobiology and Clinical Neurophysiology (D.M.A., T.S., D.d.S.e.S., I.A., V.V.L.) and Unit of Clinical Research (S.-C.G.-J., M.E.L.M.), National Institute of Women, Children and Adolescents, Health Fernandes Figueira, Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health, Rio de Janeiro, Brazil. + + + + Araújo + Izabel + I + + From the Laboratory of Neurobiology and Clinical Neurophysiology (D.M.A., T.S., D.d.S.e.S., I.A., V.V.L.) and Unit of Clinical Research (S.-C.G.-J., M.E.L.M.), National Institute of Women, Children and Adolescents, Health Fernandes Figueira, Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health, Rio de Janeiro, Brazil. + + + + Lopes Moreira + Maria Elizabeth + ME + + From the Laboratory of Neurobiology and Clinical Neurophysiology (D.M.A., T.S., D.d.S.e.S., I.A., V.V.L.) and Unit of Clinical Research (S.-C.G.-J., M.E.L.M.), National Institute of Women, Children and Adolescents, Health Fernandes Figueira, Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health, Rio de Janeiro, Brazil. + + + + Lazarev + Vladimir V + VV + + From the Laboratory of Neurobiology and Clinical Neurophysiology (D.M.A., T.S., D.d.S.e.S., I.A., V.V.L.) and Unit of Clinical Research (S.-C.G.-J., M.E.L.M.), National Institute of Women, Children and Adolescents, Health Fernandes Figueira, Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health, Rio de Janeiro, Brazil. vlad.v@iname.com. + + + + eng + + Journal Article + + + 2018 + 01 + 19 + +
+ + United States + Neurology + 0401060 + 0028-3878 + +
+ + + + 2017 + 07 + 23 + + + 2017 + 11 + 06 + + + 2018 + 1 + 21 + 6 + 0 + + + 2018 + 1 + 21 + 6 + 0 + + + 2018 + 1 + 21 + 6 + 0 + + + ppublish + + 29352094 + WNL.0000000000004974 + 10.1212/WNL.0000000000004974 + + +
+ + + + + 29346650 + + 2018 + 02 + 16 + +
+ + 1554-6578 + + 77 + 3 + + 2018 + Mar + 01 + + + Journal of neuropathology and experimental neurology + J. Neuropathol. Exp. Neurol. + + Persistence of Zika Virus After Birth: Clinical, Virological, Neuroimaging, and Neuropathological Documentation in a 5-Month Infant With Congenital Zika Syndrome. + + 193-198 + + 10.1093/jnen/nlx116 + + During the Zika epidemic in Brazil, a baby was born at term with microcephaly and arthrogryposis. The mother had Zika symptoms at 10 weeks of gestation. At 17 weeks, ultrasound showed cerebral malformation and ventriculomegaly. At 24 weeks, the amniotic fluid contained ZIKV RNA and at birth, placenta and maternal blood were also positive using RT-qPCR. At birth the baby urine contained ZIKV RNA, whereas CSF at birth and urine at 17 days did not. Seizures started at 6 days. EEG was abnormal and CT scan showed cerebral atrophy, calcifications, lissencephaly, ventriculomegaly, and cerebellar hypoplasia. Bacterial sepsis at 2 months was treated. A sudden increase in head circumference occurred at 4 months necessitating ventricle-peritoneal shunt placement. At 5 months, the infant died with sepsis due to bacterial meningitis. Neuropathological findings were as severe as some of those found in neonates who died soon after birth, including hydrocephalus, destructive lesions/calcification, gliosis, abnormal neuronal migration, dysmaturation of nerve cells, hypomyelination, loss of descending axons, and spinal motor neurons. ZIKV RNA was detected only in frozen brain tissue using RT-qPCR, but infected cells were not detected by in situ hybridization. Progressive gliosis and microgliosis in the midbrain may have contributed to aqueduct compression and subsequent hydrocephalus. The etiology of progressive disease after in utero infection is not clear and requires investigation. + © 2018 American Association of Neuropathologists, Inc. All rights reserved. + + + + Chimelli + Leila + L + + Laboratory of Neuropathology, State Institute of Brain and UFRJ. + + + + Moura Pone + Sheila + S + + Pediatric Infectious Diseases. + + + + Avvad-Portari + Elyzabeth + E + + Pathology. + + + + Farias Meira Vasconcelos + Zilton + Z + + Pathology. + + + + Araújo Zin + Andrea + A + + Clinical Research Unit. + + + + Prado Cunha + Daniela + D + + Clinical Research Unit. + + + + Raposo Thompson + Nathalia + N + + Pediatric Infectious Diseases. + + + + Lopes Moreira + Maria Elisabeth + ME + + Clinical Research Unit. + + + + Wiley + Clayton A + CA + + National Institute of Women, Children and Adolescents Health Fernandes Figueira (IFF) - Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil; and Division of Neuropathology, UPMC Presbiterian Hospital, Pittsburgh, Pennsylvania. + + + + da Silva Pone + Marcos Vinicius + MV + + Pediatric Infectious Diseases. + + + + eng + + Journal Article + +
+ + England + J Neuropathol Exp Neurol + 2985192R + 0022-3069 + + + Arthrogryposis + Calcification + Hydrocephalus + Microcephaly + Neuropathology + RT-qPCR + Zika virus + +
+ + + + 2018 + 1 + 19 + 6 + 0 + + + 2018 + 1 + 19 + 6 + 0 + + + 2018 + 1 + 19 + 6 + 0 + + + ppublish + + 29346650 + 4807504 + 10.1093/jnen/nlx116 + + +
+ + + + + 29346287 + + 2018 + 01 + 18 + +
+ + 2076-393X + + 6 + 1 + + 2018 + Jan + 18 + + + Vaccines + Vaccines (Basel) + + Development of Zika Virus Vaccines. + E7 + 10.3390/vaccines6010007 + + Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant women is associated with fetal abnormalities such as microcephaly, and infection of adults can lead to Guillain-Barré syndrome, an autoimmune disease characterized by neurological deficits. Although there are currently licensed vaccines for other flaviviruses, there remains an urgent need for preventative vaccines against ZIKV infection. Herein we describe the current efforts to accelerate the development of ZIKV vaccines using various platforms, including live attenuated virus, inactivated virus, DNA and RNA, viral vectors, and in silico-predicted immunogenic viral epitopes. Many of these approaches have leveraged lessons learned from past experience with Dengue and other flavivirus vaccines. + + + + Makhluf + Huda + H + + Department of Mathematics and Natural Sciences, National University, La Jolla, CA 92037, USA. hmakhluf@nu.edu. + + + Center for Infectious Disease, La Jolla Institute, La Jolla, CA 92037, USA. hmakhluf@nu.edu. + + + + Shresta + Sujan + S + + Center for Infectious Disease, La Jolla Institute, La Jolla, CA 92037, USA. sujan@lji.org. + + + + eng + + Journal Article + Review + + + 2018 + 01 + 18 + +
+ + Switzerland + Vaccines (Basel) + 101629355 + 2076-393X + + + Zika virus + dengue virus + vaccines + + The authors declare no conflict of interest. +
+ + + + 2017 + 11 + 23 + + + 2018 + 01 + 12 + + + 2018 + 01 + 14 + + + 2018 + 1 + 19 + 6 + 0 + + + 2018 + 1 + 19 + 6 + 0 + + + 2018 + 1 + 19 + 6 + 1 + + + epublish + + 29346287 + vaccines6010007 + 10.3390/vaccines6010007 + + +
+ + + + + 29341037 + + 2018 + 01 + 17 + +
+ + 1806-9339 + + 40 + 1 + + 2018 + Jan + + + Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia + Rev Bras Ginecol Obstet + + Reply to: Zika Virus Infection, Pregnancy and Microcephaly. + + 54-55 + + 10.1055/s-0037-1617425 + + + Duarte + Geraldo + G + + Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil. + + + + eng + + Journal Article + + Resposta para: Infecção por Vírus Zika, Gravidez e Microcefalia. + + 2018 + 01 + 16 + +
+ + Brazil + Rev Bras Ginecol Obstet + 9214757 + 0100-7203 + + Disclosure The authors report no conflicts of interest in this work. +
+ + + + 2018 + 1 + 18 + 6 + 0 + + + 2018 + 1 + 18 + 6 + 0 + + + 2018 + 1 + 18 + 6 + 0 + + + ppublish + + 29341037 + 10.1055/s-0037-1617425 + + +
+ + + + + 29329574 + + 2018 + 02 + 09 + +
+ + 1471-2458 + + 18 + 1 + + 2018 + 01 + 12 + + + BMC public health + BMC Public Health + + Microcephaly epidemic related to the Zika virus and living conditions in Recife, Northeast Brazil. + + 130 + + 10.1186/s12889-018-5039-z + + Starting in August 2015, there was an increase in the number of cases of neonatal microcephaly in Northeast Brazil. These findings were identified as being an epidemic of microcephaly related to Zika virus (ZIKV) infection. The present study aims to analyse the spatial distribution of microcephaly cases in Recife (2015-2016), which is in Northeast Brazil, and its association with the living conditions in this city. + This was an ecological study that used data from reported cases of microcephaly from the State Health Department of Pernambuco (August 2015 to July 2016). The basic spatial unit of analysis was the 94 districts of Recife. The case definition of microcephaly was: neonates with a head circumference of less than the cut-off point of -2 standard deviations below the mean value from the established Fenton growth curve. As an indicator of the living conditions of the 94 districts, the percentage of heads of households with an income of less than twice the minimum wage was calculated. The districts were classified into four homogeneous strata using the K-means clustering algorithm. We plotted the locations of each microcephaly case over a layer of living conditions. + During the study period, 347 microcephaly cases were reported, of which 142 (40.9%) fulfilled the definition of a microcephaly case. Stratification of the 94 districts resulted in the identification of four strata. The highest stratum in relation to the living conditions presented the lowest prevalence rate of microcephaly, and the overall difference between this rate and the rates of the other strata was statistically significant. The results of the Kruskal-Wallis test demonstrated that there was a strong association between a higher prevalence of microcephaly and poor living conditions. After the first 6 months of the study period, there were no microcephaly cases recorded within the population living in the richest socio-economic strata. + This study showed that those residing in areas with precarious living conditions had a higher prevalence of microcephaly compared with populations with better living conditions. + + + + Souza + Wayner Vieira de + WV + + The Aggeu Magalhães Research Center -FIOCRUZ/PE, Av. Professor Moraes Rego, s/n Cidade Universitária, Recife, Pernambuco, CEP 50.740-465, Brazil. wayner@cpqam.fiocruz.br. + + + + Albuquerque + Maria de Fátima Pessoa Militão de + MFPM + + The Aggeu Magalhães Research Center -FIOCRUZ/PE, Av. Professor Moraes Rego, s/n Cidade Universitária, Recife, Pernambuco, CEP 50.740-465, Brazil. + + + + Vazquez + Enrique + E + + Pan American Health Organization, Setor de Embaixadas Norte, Lote 19, Brasília, CEP 70800-400, Brazil. + + + + Bezerra + Luciana Caroline Albuquerque + LCA + + Pernambuco State Health Department, Rua Dona Maria Augusta Nogueira, 519, Bongi, Recife, Pernambuco, CEP 50751-530, Brazil. + + + + Mendes + Antonio da Cruz Gouveia + ADCG + + The Aggeu Magalhães Research Center -FIOCRUZ/PE, Av. Professor Moraes Rego, s/n Cidade Universitária, Recife, Pernambuco, CEP 50.740-465, Brazil. + + + + Lyra + Tereza Maciel + TM + + The Aggeu Magalhães Research Center -FIOCRUZ/PE, Av. Professor Moraes Rego, s/n Cidade Universitária, Recife, Pernambuco, CEP 50.740-465, Brazil. + + + + Araujo + Thalia Velho Barreto de + TVB + + Universidade Federal de Pernambuco, Av. Prof. Moares Rego, 1235, Cidade Universitáia, Recife, Pernambuco, CEP 50670-901, Brazil. + + + + Oliveira + André Luiz Sá de + ALS + + The Aggeu Magalhães Research Center -FIOCRUZ/PE, Av. Professor Moraes Rego, s/n Cidade Universitária, Recife, Pernambuco, CEP 50.740-465, Brazil. + + + + Braga + Maria Cynthia + MC + + The Aggeu Magalhães Research Center -FIOCRUZ/PE, Av. Professor Moraes Rego, s/n Cidade Universitária, Recife, Pernambuco, CEP 50.740-465, Brazil. + + + + Ximenes + Ricardo Arraes de Alencar + RAA + + Universidade Federal de Pernambuco, Av. Prof. Moares Rego, 1235, Cidade Universitáia, Recife, Pernambuco, CEP 50670-901, Brazil. + + + Universidade de Pernambuco, Avenida Agamenon Magalhães, S/N, Santo Amaro, Recife, Pernambuco, CEP 501100-010, Brazil. + + + + Miranda-Filho + Demócrito de Barros + DB + + Universidade de Pernambuco, Avenida Agamenon Magalhães, S/N, Santo Amaro, Recife, Pernambuco, CEP 501100-010, Brazil. + + + + Cabral Silva + Amanda Priscila de Santana + APS + + The Aggeu Magalhães Research Center -FIOCRUZ/PE, Av. Professor Moraes Rego, s/n Cidade Universitária, Recife, Pernambuco, CEP 50.740-465, Brazil. + + + + Rodrigues + Laura + L + + London School of Hygiene & Tropical Medicine, Keppel Street, London, UK. + + + + Martelli + Celina Maria Turchi + CMT + + The Aggeu Magalhães Research Center -FIOCRUZ/PE, Av. Professor Moraes Rego, s/n Cidade Universitária, Recife, Pernambuco, CEP 50.740-465, Brazil. + + + Universidade Federal de Goiás, Avenida Esperança, S/N, Campus Samambaia, Goiânia, Goiás, CEP 74690-900, Brazil. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + + + 2018 + 01 + 12 + +
+ + England + BMC Public Health + 100968562 + 1471-2458 + + + + Infect Dis Poverty. 2016 Dec 1;5(1):104 + 27903305 + + + J Gen Virol. 2016 Feb;97(2):269-73 + 26684466 + + + Cad Saude Publica. 2016;32(4):e00017216 + 27143306 + + + Acta Trop. 2016 Nov;163:54-60 + 27427218 + + + Acta Trop. 2010 Mar;113(3):234-40 + 19896921 + + + Emerg Infect Dis. 2016 Jun;22(6):1090-1093 + 27071041 + + + J Pediatr (Rio J). 1997 Mar-Apr;73(2):95-100 + 14685423 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + Lancet Infect Dis. 2016 Jul;16(7):e119-e126 + 27282424 + + + Lancet Infect Dis. 2011 Feb;11(2):131-41 + 21272793 + + + Emerg Infect Dis. 2016 Jul;22(7):1185-92 + 27070380 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Lancet. 2011 May 21;377(9779):1778-97 + 21561655 + + + Lancet. 2011 May 28;377(9780):1877-89 + 21561657 + + + An Acad Bras Cienc. 2009 Dec;81(4):655-62 + 19893891 + + + BMJ. 2015 Dec 23;351:h6983 + 26698165 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Brazil + Ecological study + Socio-economic + Zika + +
+ + + + 2017 + 02 + 07 + + + 2018 + 01 + 05 + + + 2018 + 1 + 14 + 6 + 0 + + + 2018 + 1 + 14 + 6 + 0 + + + 2018 + 1 + 14 + 6 + 0 + + + epublish + + 29329574 + 10.1186/s12889-018-5039-z + 10.1186/s12889-018-5039-z + PMC5767029 + + +
+ + + + + 29325155 + + 2018 + 03 + 08 + +
+ + 1550-9109 + + + 2018 + Jan + 06 + + + Sleep + Sleep + + Sleep findings in Brazilian children with congenital Zika syndrome. + 10.1093/sleep/zsy009 + + Zika virus infection during pregnancy may result in congenital Zika syndrome (CZS), whose characteristics are being described. + The present study aimed to investigate the sleep characteristics of 136 infants/toddlers (88 with CZS and 48 with typical development (TD), age and gender matched, 60% girls and 40% boys in both groups) using the Brief Infant Sleep Questionnaire. The ages of children in both groups ranged from 5 to 24 months (CZS 15.9 ± 0.4 vs. TD 15.8 ± 1.0 months, P= 0.90). + The results show that 34.1% of CZS and 2% of TD children were defined as poor sleepers, 15% of CZS and 2% of TD children remained awake at night for a period longer than 1 hour, and 24% of CZS and 2% of TD children slept less than 9 hours. The CZS group showed shorter total sleep time (CZS 11.24 ± 2.6 vs. TD 12.02 ± 1.9 hours, P= 0.03) and shorter nocturnal sleep duration than the TD group (CZS 8.2 ± 0.2 vs. TD 9.4 ± 0.2 hours, P= 0.0002). In contrast to the control group (P= 0.02, r= -0.34), in the CZS group, no correlation was found between age and nocturnal wakefulness. Future studies should explore these data in relation to the development and maturation of the central nervous system of these children. + Considering the well-known consequences of poor sleep quality on health in several populations, the presence of sleep disorders should be considered in CZS using multidisciplinary treatments. + © Sleep Research Society 2018. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com. + + + + Pinato + Luciana + L + + São Paulo State University - UNESP, Marilia, SP, Brazil. + + + + Ribeiro + Erlane M + EM + + Albert Sabin Children's Hospital, Fortaleza, CE, Brazil. + + + Christus University Center, Fortaleza, CE, Brazil. + + + + Leite + Rebeka F P + RFP + + Albert Sabin Children's Hospital, Fortaleza, CE, Brazil. + + + + Lopes + Thayse F + TF + + Albert Sabin Children's Hospital, Fortaleza, CE, Brazil. + + + + Pessoa + André L S + ALS + + Albert Sabin Children's Hospital, Fortaleza, CE, Brazil. + + + + Guissoni Campos + Leila M + LM + + University of Marilia - UNIMAR, Marilia, SP, Brazil. + + + + Piffer + Giovanna E + GE + + University of Marilia - UNIMAR, Marilia, SP, Brazil. + + + + Souza + Ana L D M + ALDM + + São Paulo State University - UNESP, Marilia, SP, Brazil. + + + + Giacheti + Célia M + CM + + São Paulo State University - UNESP, Marilia, SP, Brazil. + + + + eng + + Journal Article + + + 2018 + 01 + 06 + +
+ + United States + Sleep + 7809084 + 0161-8105 + + + Neurodevelopment + Zika virus + microcephaly + sleep habits + +
+ + + + 2017 + 09 + 02 + + + 2018 + 1 + 12 + 6 + 0 + + + 2018 + 1 + 13 + 6 + 0 + + + 2018 + 1 + 13 + 6 + 0 + + + aheadofprint + + 29325155 + 4791871 + 10.1093/sleep/zsy009 + + +
+ + + + + 29318332 + + 2018 + 02 + 11 + +
+ + 1433-0407 + + 89 + 2 + + 2018 + Feb + + + Der Nervenarzt + Nervenarzt + + [Zika virus infection and the nervous system]. + + 136-143 + + 10.1007/s00115-017-0472-2 + + Zika virus is an arbovirus from the family of flaviviruses, which is transmitted by the mosquito Aedes aegyptii and also by the Asian mosquito Aedes albopticus. The largest observed Zika virus epidemic is currently taking place in North and South America, in the Caribbean, southern USA and Southeast Asia. In most cases the infection is an unspecific, acute, febrile disease. Neurological manifestations consist mainly of microcephaly in newborns and Guillain-Barré syndrome but other rare manifestations have also become known in the meantime, such as meningoencephalitis and myelitis. Therefore, the Zika virus, similar to other flaviviruses, has neuropathogenic properties. In particular, the drastic increase in microcephaly cases in Brazil has induced great research activities. The virus is transmitted perinatally and can be detected in the amniotic fluid, placenta and brain tissue of the newborn. Vaccination or a causal therapy does not yet exist. The significant increase in Guillain-Barré syndrome induced by the Zika virus was observed during earlier outbreaks. In the meantime, scientifically clear connections between a Zika virus infection and these neurological manifestations have been shown. Long-term studies and animal models should be used for a better understanding of the pathomechanisms of this disease. + + + + Husstedt + I W + IW + + Klinik Maria Frieden und Medizinische Fakultät, Westfälische Wilhelms-Universität Münster, Am Krankenhaus 1, 48291, Telgte, Deutschland. husstedt@uni-muenster.de. + + + + Maschke + M + M + + Klinik für Neurologie, Krankenhaus der Barmherzigen Brüder, Trier, Deutschland. + + + + Eggers + C + C + + Krankenhaus der Barmherzigen Brüder, Linz, Österreich. + + + + Neuen-Jacob + E + E + + Institut für Neuropathologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland. + + + + Arendt + G + G + + Klinik für Neurologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland. + + + + ger + + English Abstract + Journal Article + Review + + Zika-Virus-Infektion und das Nervensystem. +
+ + Germany + Nervenarzt + 0400773 + 0028-2804 + + + + N Engl J Med. 2016 Mar 10;374(10):984-5 + 26862812 + + + Acta Trop. 2017 Feb;166:186-192 + 27876647 + + + Semin Reprod Med. 2016 Sep;34(5):273-279 + 27612158 + + + Clin Infect Dis. 2007 Nov 1;45(9):1214-20 + 17918087 + + + Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):2024-2029 + 28167751 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Neurol Clin Pract. 2016 Dec;6(6):515-522 + 28058206 + + + JAMA Ophthalmol. 2016 Feb 9;: + 26865554 + + + Neurologia. 2016 Oct 21;:null + 27776956 + + + PLoS Negl Trop Dis. 2017 Jan 9;11(1):e0005296 + 28068342 + + + Lancet. 2016 Feb 20;387(10020):719-21 + 26876373 + + + Am J Med. 2016 Oct;129(10 ):1126-30 + 27260832 + + + Lancet. 2016 Sep 10;388(10049):1089-1102 + 27427453 + + + PLoS Negl Trop Dis. 2016 Mar 02;10(3):e0004530 + 26934531 + + + Haemophilia. 2006 Mar;12 Suppl 1:3-7; discussion 26-8 + 16445811 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3 + 26796813 + + + AIDS Rev. 2016 Jan-Mar;18(1):54-5 + 27028271 + + + J Clin Virol. 2016 Jan;74:1-3 + 26615388 + + + Trop Med Int Health. 2017 May;22(5):594-603 + 28214373 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Emerg Infect Dis. 2017 Apr;23 (4):669-672 + 28084987 + + + Front Microbiol. 2017 Jan 24;8:42 + 28174559 + + + Exp Toxicol Pathol. 2017 Feb;69(2):63-71 + 27899230 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Microbiol Mol Biol Rev. 2017 Feb 8;81(1): + 28179396 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + N Engl J Med. 2017 Feb 14;:null + 28195756 + + + Acta Med Port. 2015 Nov-Dec;28(6):760-5 + 26849762 + + + Lancet. 2016 Apr 2;387(10026):1481 + 26946926 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Euro Surveill. 2016 Nov 24;21(47): + 27918261 + + + Clin Microbiol Infect. 2017 May;23 (5):296-305 + 28062314 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + BMJ. 2016 Feb 10;352:i855 + 26864344 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Theor Biol Med Model. 2016 Nov 9;13(1):20 + 27829439 + + + J Neurol Neurosurg Psychiatry. 2017 Mar;88(3):266-271 + 27799296 + + + N Engl J Med. 2016 Apr 21;374(16):1595-6 + 26958738 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Guillain-Barré syndrome + Meningoencephalitis + Microcephaly + Myelitis + Pathomechanism + +
+ + + + 2018 + 1 + 11 + 6 + 0 + + + 2018 + 1 + 11 + 6 + 0 + + + 2018 + 1 + 11 + 6 + 0 + + + ppublish + + 29318332 + 10.1007/s00115-017-0472-2 + 10.1007/s00115-017-0472-2 + + +
+ + + + + 29315224 + + 2018 + 02 + 08 + +
+ + 1660-4601 + + 15 + 1 + + 2018 + Jan + 09 + + + International journal of environmental research and public health + Int J Environ Res Public Health + + The Zika Virus Epidemic in Brazil: From Discovery to Future Implications. + E96 + 10.3390/ijerph15010096 + + The first confirmed case of Zika virus infection in the Americas was reported in Northeast Brazil in May 2015, although phylogenetic studies indicate virus introduction as early as 2013. Zika rapidly spread across Brazil and to more than 50 other countries and territories on the American continent. TheAedesaegyptimosquito is thought to be the principal vector responsible for the widespread transmission of the virus. However, sexual transmission has also been reported. The explosively emerging epidemic has had diverse impacts on population health, coinciding with cases of Guillain-Barré Syndrome and an unexpected epidemic of newborns with microcephaly and other neurological impairments. This led to Brazil declaring a national public health emergency in November 2015, followed by a similar decision by the World Health Organization three months later. While dengue virus serotypes took several decades to spread across Brazil, the Zika virus epidemic diffused within months, extending beyond the area of permanent dengue transmission, which is bound by a climatic barrier in the south and low population density areas in the north. This rapid spread was probably due to a combination of factors, including a massive susceptible population, climatic conditions conducive for the mosquito vector, alternative non-vector transmission, and a highly mobile population. The epidemic has since subsided, but many unanswered questions remain. In this article, we provide an overview of the discovery of Zika virus in Brazil, including its emergence and spread, epidemiological surveillance, vector and non-vector transmission routes, clinical complications, and socio-economic impacts. We discuss gaps in the knowledge and the challenges ahead to anticipate, prevent, and control emerging and re-emerging epidemics of arboviruses in Brazil and worldwide. + + + + Lowe + Rachel + R + 0000-0003-3939-7343 + + Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. rachel.lowe@lshtm.ac.uk. + + + Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. rachel.lowe@lshtm.ac.uk. + + + Barcelona Institute for Global Health (ISGLOBAL), Doctor Aiguader, 88, 08003 Barcelona, Spain. rachel.lowe@lshtm.ac.uk. + + + + Barcellos + Christovam + C + + Institute of Health Communication and Information, Oswaldo Cruz Foundation (Fiocruz), Avenida Brasil 4365, Rio de Janeiro 21045-900, Brazil. xris@fiocruz.br. + + + + Brasil + Patrícia + P + + Instituto Nacional de Infectologia Evandro Chagas, Oswaldo Cruz Foundation (Fiocruz), Avenida Brasil 4365, Rio de Janeiro 21045-900, Brazil. patricia.brasil@ini.fiocruz.br. + + + + Cruz + Oswaldo G + OG + + Scientific Computation Program, Oswaldo Cruz Foundation (Fiocruz), Avenida Brasil 4365, Rio de Janeiro 21045-900, Brazil. oswaldo.cruz@fiocruz.br. + + + + Honório + Nildimar Alves + NA + + Laboratório de Mosquitos Transmissores de Hematozoários, Instituto Oswaldo Cruz (Fiocruz), Avenida Brasil 4365, Rio de Janeiro 21045-900, Brazil. honorio@ioc.fiocruz.br. + + + Núcleo Operacional Sentinela de Mosquitos Vetores-Nosmove/Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21045-900, Brazil. honorio@ioc.fiocruz.br. + + + + Kuper + Hannah + H + + International Centre for Evidence in Disability, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. hannah.kuper@lshtm.ac.uk. + + + + Carvalho + Marilia Sá + MS + + Scientific Computation Program, Oswaldo Cruz Foundation (Fiocruz), Avenida Brasil 4365, Rio de Janeiro 21045-900, Brazil. marilia.carvalho@fiocruz.br. + + + + eng + + + Wellcome Trust + United Kingdom + + + + Journal Article + Review + + + 2018 + 01 + 09 + +
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+ 23275331 + + + Lancet. 2012 Sep 8;380(9845):899-907 + 22795511 + + + Proc Natl Acad Sci U S A. 2017 May 30;114(22):E4334-E4343 + 28442561 + + + Elife. 2016 Feb 24;5:null + 26910315 + + + Annu Rev Entomol. 2002;47:233-66 + 11729075 + + + Obstet Gynecol. 2017 Apr;129(4):638-642 + 28277362 + + + PLoS Negl Trop Dis. 2017 Jun 1;11(6):e0005654 + 28570693 + + + Emerg Infect Dis. 2017 Aug;23 (8):1411-1412 + 28628464 + + + Online J Public Health Inform. 2013 Jul 01;5(2):210 + 23923095 + + + Insects. 2017 Feb 10;8(1): + 28208639 + + + Emerg Microbes Infect. 2017 Aug 9;6(8):e69 + 28790458 + + + Lancet. 2015 Jul 18;386(9990):243-4 + 26194519 + + + Emerg Microbes Infect. 2017 Oct 18;6(10 ):e90 + 29044195 + + + Cad Saude Publica. 2015 Jul;31(7):1349-50 + 26248090 + + + J Med Entomol. 2009 Sep;46(5):1001-14 + 19769029 + + + + Congenital Zika Syndrome + Zika virus + epidemiology + microcephaly + socio-economic impact + surveillance + vector control + + The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results. +
+ + + + 2017 + 11 + 23 + + + 2017 + 12 + 27 + + + 2018 + 01 + 02 + + + 2018 + 1 + 10 + 6 + 0 + + + 2018 + 1 + 10 + 6 + 0 + + + 2018 + 1 + 10 + 6 + 0 + + + epublish + + 29315224 + ijerph15010096 + 10.3390/ijerph15010096 + PMC5800195 + + +
+ + + + + 29312238 + + 2018 + 01 + 11 + +
+ + 1664-302X + + 8 + + 2017 + + + Frontiers in microbiology + Front Microbiol + + Zika Virus Infects, Activates, and Crosses Brain Microvascular Endothelial Cells, without Barrier Disruption. + + 2557 + + 10.3389/fmicb.2017.02557 + + Zika virus (ZIKV) has been associated to central nervous system (CNS) harm, and virus was detected in the brain and cerebrospinal fluids of microcephaly and meningoencephalitis cases. However, the mechanism by which the virus reaches the CNS is unclear. Here, we addressed the effects of ZIKV replication in human brain microvascular endothelial cells (HBMECs), as anin vitromodel of blood brain barrier (BBB), and evaluated virus extravasation and BBB integrity in anin vivomouse experimental model. HBMECs were productively infected by African and Brazilian ZIKV strains (ZIKVMR766and ZIKVPE243), which induce increased production of type I and type III IFN, inflammatory cytokines and chemokines. Infection with ZIKVMR766promoted earlier cellular death, in comparison to ZIKVPE243, but infection with either strain did not result in enhanced endothelial permeability. Despite the maintenance of endothelial integrity, infectious virus particles crossed the monolayer by endocytosis/exocytosis-dependent replication pathway or by transcytosis. Remarkably, both viruses' strains infected IFNAR deficient mice, with high viral load being detected in the brains, without BBB disruption, which was only detected at later time points after infection. These data suggest that ZIKV infects and activates endothelial cells, and might reach the CNS through basolateral release, transcytosis or transinfection processes. These findings further improve the current knowledge regarding ZIKV dissemination pathways. + + + + Papa + Michelle P + MP + + Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Meuren + Lana M + LM + + Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Coelho + Sharton V A + SVA + + Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Lucas + Carolina G de Oliveira + CGO + + Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Mustafá + Yasmin M + YM + + Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Lemos Matassoli + Flavio + F + + Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Silveira + Paola P + PP + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Frost + Paula S + PS + + Núcleo de Neurociências da Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Pezzuto + Paula + P + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Ribeiro + Milene R + MR + + Laboratório de Pesquisas em Virologia, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, Brazil. + + + + Tanuri + Amilcar + A + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Nogueira + Mauricio L + ML + + Laboratório de Pesquisas em Virologia, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, Brazil. + + + + Campanati + Loraine + L + + Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Bozza + Marcelo T + MT + + Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Paula Neto + Heitor A + HA + + Laboratório de Alvos Moleculares, Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Pimentel-Coelho + Pedro M + PM + + Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Figueiredo + Claudia P + CP + + Núcleo de Neurociências da Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + de Aguiar + Renato S + RS + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + de Arruda + Luciana B + LB + + Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + + + 2017 + 12 + 22 + +
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+ + + + 2017 + 07 + 16 + + + 2017 + 12 + 08 + + + 2018 + 1 + 10 + 6 + 0 + + + 2018 + 1 + 10 + 6 + 0 + + + 2018 + 1 + 10 + 6 + 1 + + + epublish + + 29312238 + 10.3389/fmicb.2017.02557 + PMC5743735 + + +
+ + + + + 29311619 + + 2018 + 01 + 11 + +
+ + 2045-2322 + + 8 + 1 + + 2018 + Jan + 08 + + + Scientific reports + Sci Rep + + In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus. + + 1 + + 10.1038/s41598-017-17765-5 + + Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV. + + + + Azevedo + Raimunda S S + RSS + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + de Sousa + Jorge R + JR + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + Araujo + Marialva T F + MTF + + Departamento de Patologia, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + Martins Filho + Arnaldo J + AJ + http://orcid.org/0000-0001-9153-1234 + + Departamento de Patologia, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + de Alcantara + Bianca N + BN + + Programa de Pós-Graduação em Virologia, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + Araujo + Fernanda M C + FMC + + Laboratório Central de Saúde Pública, SES do Ceará, Fortaleza, Ceará, Brazil. + + + + Queiroz + Maria G L + MGL + + Laboratório Central de Saúde Pública, SES do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Cruz + Ana C R + ACR + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + Universidade do Estado do Pará, Belém, Pará, Brazil. + + + + Vasconcelos + Beatriz H Baldez + BHB + + Núcleo de Medicina Tropical, Universidade Federal do Pará, Belém, Pará, Brazil. + + + + Chiang + Jannifer O + JO + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + Martins + Lívia C + LC + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + Casseb + Livia M N + LMN + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + da Silva + Eliana V + EV + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + Carvalho + Valéria L + VL + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + Vasconcelos + Barbara C Baldez + BCB + + Universidade do Estado do Pará, Belém, Pará, Brazil. + + + + Rodrigues + Sueli G + SG + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + + Oliveira + Consuelo S + CS + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. + + + Universidade do Estado do Pará, Belém, Pará, Brazil. + + + + Quaresma + Juarez A S + JAS + + Universidade do Estado do Pará, Belém, Pará, Brazil. + + + Núcleo de Medicina Tropical, Universidade Federal do Pará, Belém, Pará, Brazil. + + + + Vasconcelos + Pedro F C + PFC + http://orcid.org/0000-0002-6603-5527 + + Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, Pará, Brazil. pedrovasconcelos@iec.pa.gov.br. + + + Universidade do Estado do Pará, Belém, Pará, Brazil. pedrovasconcelos@iec.pa.gov.br. + + + + eng + + Journal Article + + + 2018 + 01 + 08 + +
+ + England + Sci Rep + 101563288 + 2045-2322 + + + + Eur J Immunol. 2013 Jul;43(7):1789-98 + 23568450 + + + Acta Neuropathol. 2012 Nov;124(5):599-614 + 22825593 + + + Nat Rev Drug Discov. 2012 Oct;11(10):790-811 + 23000686 + + + J Neuroinflammation. 2014 Jun 03;11:98 + 24889886 + + + World J Biol Chem. 2014 May 26;5(2):93-105 + 24921001 + + + Viruses. 2013 Oct 22;5(10):2573-84 + 24153060 + + + Cell Stem Cell. 2016 May 5;18(5):591-6 + 27038591 + + + Immunity. 2013 Feb 21;38(2):209-23 + 23438821 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + J Inflamm (Lond). 2011 Aug 26;8(1):22 + 21871091 + + + Eur J Immunol. 2014 May;44(5):1363-74 + 24643627 + + + Front Immunol. 2014 Nov 26;5:603 + 25505468 + + + Scand J Immunol. 2015 Oct;82(4):370-9 + 26073153 + + + Annu Rev Immunol. 2009;27:485-517 + 19132915 + + + Acta Trop. 2005 May;94(2):116-27 + 15829426 + + + Inflamm Res. 2012 Apr;61(4):381-9 + 22207393 + + + PLoS One. 2012;7(8):e44153 + 22952908 + + + Immunol Rev. 2011 Sep;243(1):206-14 + 21884178 + + + Immunity. 2016 Jun 21;44(6):1455-69 + 27332734 + + + J Virol. 2015 May;89(10):5602-14 + 25762733 + + + FEMS Microbiol Lett. 2016 Sep;363(18):null + 27549304 + + + J Immunol. 2015 Feb 1;194(3):1141-53 + 25539816 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + F1000Res. 2016 Jan 26;5:null + 26918172 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + J Clin Virol. 2016 Dec;85:56-64 + 27835759 + + + Mol Neurobiol. 2016 Mar;53(2):1181-94 + 25598354 + + + Int J Mol Sci. 2010 Feb 26;11(3):789-806 + 20479986 + + + J Virol. 2012 Sep;86(17):8937-48 + 22740407 + + + Front Immunol. 2014 May 05;5:192 + 24829565 + + + Viruses. 2013 Dec 30;6(1):69-88 + 24381034 + + + Am J Trop Med Hyg. 2016 Nov 2;95(5):1169-1173 + 27573623 + + + Lancet. 2016 Apr 9;387(10027):1531-1539 + 26948433 + + + Cell Rep. 2016 Jun 14;15(11):2315-22 + 27268504 + + + J Immunol. 2014 Jan 15;192(2):683-90 + 24337378 + + + Nucleic Acids Res. 2016 Oct 14;44(18):8610-8620 + 27580721 + + + J Vis Exp. 2016 Aug 23;(114):null + 27584546 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Trends Microbiol. 2016 Aug;24(8):622-636 + 27387029 + + + J Gen Virol. 2009 Apr;90(Pt 4):818-26 + 19264621 + + + J Histochem Cytochem. 2009 Oct;57(10):973-89 + 19581627 + + + Pediatr Res. 2001 Aug;50(2):222-30 + 11477207 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + +
+ + + + 2017 + 06 + 27 + + + 2017 + 11 + 30 + + + 2018 + 1 + 10 + 6 + 0 + + + 2018 + 1 + 10 + 6 + 0 + + + 2018 + 1 + 10 + 6 + 0 + + + epublish + + 29311619 + 10.1038/s41598-017-17765-5 + 10.1038/s41598-017-17765-5 + PMC5758755 + + +
+ + + + + 29305391 + + 2018 + 02 + 13 + +
+ + 1098-4275 + + 141 + 2 + + 2018 + Feb + + + Pediatrics + Pediatrics + + Prevalence and Risk Factors for Microcephaly at Birth in Brazil in 2010. + e20170589 + 10.1542/peds.2017-0589 + + To estimate the baseline prevalence and risk factors for microcephaly at birth before the Zika virus epidemic in 2 Brazilian cities. + We used population-based data from the Brazilian Ribeirão Preto (RP) and São Luís (SL) birth cohort studies of 2010 that included hospital deliveries by resident mothers. The final sample was 7376 live births in RP and 4220 in SL. Gestational age was based on the date of the mother's last normal menstrual period or obstetric ultrasonography, if available. Microcephaly at birth was classified according to the criteria of the International Fetal and Newborn Growth Consortium for the 21st Century and the Brazilian Ministry of Health. Risk factors for microcephaly, proportionate and disproportionate microcephaly, and severe microcephaly were estimated in a hierarchized logistic regression model. + According to the International Fetal and Newborn Growth Consortium for the 21st Century definition, the prevalence of microcephaly (>2 SDs below the mean for gestational age and sex) was higher in SL (3.5%) than in RP (2.5%). The prevalence of severe microcephaly (>3 SDs below the mean) was higher in SL (0.7%) than in RP (0.5%). Low maternal schooling, living in consensual union or without a companion, maternal smoking during pregnancy, primiparity, vaginal delivery, and intrauterine growth restriction were consistently associated with microcephaly. The number of cases of microcephaly is grossly underestimated, with an underreporting rate of ∼90%. + The prevalence of severe microcephaly was much higher than expected in both cities. Our findings suggest that microcephaly was endemic in both municipalities before the circulation of the Zika virus. + Copyright © 2018 by the American Academy of Pediatrics. + + + + Silva + Antônio A + AA + + Departments of Public Health and aamouradasilva@gmail.com. + + + + Barbieri + Marco A + MA + + Departments of Puericulture and Pediatrics, and. + + + + Alves + Maria T + MT + + Departments of Public Health and. + + + + Carvalho + Carolina A + CA + + Departments of Public Health and. + + + + Batista + Rosângela F + RF + + Departments of Public Health and. + + + + Ribeiro + Marizélia R + MR + + Medicine III, Federal University of Maranhão, São Luís, Brazil; and. + + + + Lamy-Filho + Fernando + F + + Medicine III, Federal University of Maranhão, São Luís, Brazil; and. + + + + Lamy + Zeni C + ZC + + Departments of Public Health and. + + + + Cardoso + Viviane C + VC + + Departments of Puericulture and Pediatrics, and. + + + + Cavalli + Ricardo C + RC + + Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. + + + + Simões + Vanda M + VM + + Departments of Public Health and. + + + + Bettiol + Heloisa + H + + Departments of Puericulture and Pediatrics, and. + + + + eng + + Journal Article + + + 2018 + 01 + 05 + +
+ + United States + Pediatrics + 0376422 + 0031-4005 + + POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose. +
+ + + + 2017 + 10 + 09 + + + 2018 + 1 + 7 + 6 + 0 + + + 2018 + 1 + 7 + 6 + 0 + + + 2018 + 1 + 7 + 6 + 0 + + + ppublish + + 29305391 + peds.2017-0589 + 10.1542/peds.2017-0589 + + +
+ + + + + 29277550 + + 2018 + 02 + 14 + +
+ + 1873-2585 + + 28 + 2 + + 2018 + Feb + + + Annals of epidemiology + Ann Epidemiol + + Maternal Zika virus infection and newborn microcephaly-an analysis of the epidemiological evidence. + + 111-118 + + S1047-2797(17)30283-1 + 10.1016/j.annepidem.2017.11.010 + + To evaluate whether existing data and evidence support a causal link between maternal Zika virus (ZIKV) infection and newborn microcephaly. + I quantified and compared the prevalence of all and severe microcephaly in Brazil, during and before 2015-2016, to assess whether an outbreak has occurred, used time series analysis to evaluate if the presumed outbreak was linked to a previous outbreak of ZIKV infections, and quantitatively synthesized published data from observational studies testing this association. + The prevalences of microcephaly in 2015-2016 were similar or lower than background levels (prevalence ratio [PR] for all microcephaly: 0.19; 95% confidence intervals [CI]: 0.17, 0.20). Changes in the number of cases of ZIKV infections at times matching 11-18 weeks of pregnancy were not followed by changes in the number of microcephaly cases (PR for infection at 12 weeks: 1.02; 95% CI: 0.99, 1.05). In observational studies, the prevalence of microcephaly was not significantly increased in newborns of Zika-infected mothers (average PR: 1.30; 95% CI: 0.84, 2.02). + Existing evidence is insufficient to claim maternal ZIKV infection causes microcephaly. Although a public health response seems sensible, it should be consistent with existing knowledge and consider risks, potential benefits and harm, and competing priorities. + Copyright © 2017 Elsevier Inc. All rights reserved. + + + + Bautista + Leonelo E + LE + + Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin at Madison. Electronic address: lebautista@wisc.edu. + + + + eng + + Journal Article + Review + + + 2017 + 12 + 14 + +
+ + United States + Ann Epidemiol + 9100013 + 1047-2797 + + + Brazil + Disease outbreaks + Microcephaly + Time series analysis + Zika virus + +
+ + + + 2017 + 04 + 05 + + + 2017 + 10 + 16 + + + 2017 + 11 + 20 + + + 2017 + 12 + 27 + 6 + 0 + + + 2017 + 12 + 27 + 6 + 0 + + + 2017 + 12 + 27 + 6 + 0 + + + ppublish + + 29277550 + S1047-2797(17)30283-1 + 10.1016/j.annepidem.2017.11.010 + + +
+ + + + + 29276699 + + 2017 + 12 + 28 + +
+ + 2235-2988 + + 7 + + 2017 + + + Frontiers in cellular and infection microbiology + Front Cell Infect Microbiol + + Zika Virus: An Emerging Global Health Threat. + + 486 + + 10.3389/fcimb.2017.00486 + + Zika virus (ZIKV) is an emerging healthcare threat. The presence of the mosquitoAedesspecies across South and Central America in combination with complementary climates have incited an epidemic of locally transmitted cases of ZIKV infection in Brazil. As one of the most significant current public health concerns in the Americas, ZIKV epidemic has been a cause of alarm due to its known and unknown complications. At this point, there has been a clear association between ZIKV infection and severe clinical manifestations in both adults and neonates, including but not limited to neurological deficits such as Guillain-Barré syndrome (GBS) and microcephaly, respectively. The gravity of the fetal anomalies linked to ZIKV vertical transmission from the mother has prompted a discussion on whether to include ZIKV as a formal member of the TORCH [Toxoplasma gondii, other, rubella virus, cytomegalovirus (CMV), and herpes] family of pathogens known to breach placental barriers and cause congenital disease in the fetus. The mechanisms of these complex phenotypes have yet to be fully described. As such, diagnostic tools are limited and no effective modalities are available to treat ZIKV. This article will review the recent advancements in understanding the pathogenesis of ZIKV infection as well as diagnostic tests available to detect the infection. Due to the increase in incidence of ZIKV infections, there is an immediate need to develop new diagnostic tools and novel preventive as well as therapeutic modalities based on understanding the molecular mechanisms underlying the disease. + + + + Mittal + Rahul + R + + Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + Nguyen + Desiree + D + + Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + Debs + Luca H + LH + + Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + Patel + Amit P + AP + + Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + Liu + George + G + + Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + Jhaveri + Vasanti M + VM + + Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + S Kay + Sae-In + SI + + Department of Surgery, Division of Otorhinolaryngology, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States. + + + + Mittal + Jeenu + J + + Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + Bandstra + Emmalee S + ES + + Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + Younis + Ramzi T + RT + + Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States. + + + Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States. + + + Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + Chapagain + Prem + P + + Department of Physics and Biomolecular Sciences Institute, Florida International University, Miami, FL, United States. + + + + Jayaweera + Dushyantha T + DT + + Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + Liu + Xue Zhong + XZ + + Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States. + + + Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States. + + + Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States. + + + + eng + + Journal Article + Review + + + 2017 + 12 + 08 + +
+ + Switzerland + Front Cell Infect Microbiol + 101585359 + 2235-2988 + + + + Am J Reprod Immunol. 2017 Feb;77(2):null + 27885741 + + + Seizure. 2016 Dec;43:13 + 27788398 + + + Bull World Health Organ. 2016 Jun 1;94(6):406-406A + 27274588 + + + JAMA Ophthalmol. 2016 Dec 1;134(12 ):1420-1427 + 27832267 + + + Cell Host Microbe. 2016 Jun 8;19(6):882-90 + 27212660 + + + Lancet Infect Dis. 2017 Aug;17 (8):805-806 + 28741545 + + + Nature. 2016 Aug 25;536(7617):474-8 + 27355570 + + + Am J Trop Med Hyg. 2017 Oct;97(4):1070-1071 + 28722641 + + + Lancet. 2016 Mar 12;387(10023):1051 + 26944028 + + + Med Microbiol Immunol. 2016 Jun;205(3):269-73 + 26702627 + + + Virology. 2016 Jun;493:217-26 + 27060565 + + + J Med Virol. 2017 Oct 5;:null + 28980717 + + + J Infect Dev Ctries. 2016 Mar 31;10 (3):201-7 + 27031450 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Ophthalmology. 2017 Mar;124(3):407-408 + 27914834 + + + Euro Surveill. 2016;21(8):30148 + 26939607 + + + Cell Host Microbe. 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+ + + + 2017 + 08 + 24 + + + 2017 + 11 + 13 + + + 2017 + 12 + 26 + 6 + 0 + + + 2017 + 12 + 26 + 6 + 0 + + + 2017 + 12 + 26 + 6 + 0 + + + epublish + + 29276699 + 10.3389/fcimb.2017.00486 + PMC5727043 + + +
+ + + + + 29273529 + + 2018 + 03 + 09 + +
+ + 0150-9861 + + 45 + 2 + + 2018 + Mar + + + Journal of neuroradiology. Journal de neuroradiologie + J Neuroradiol + + Congenital involvement of the central nervous system by the Zika virus in a child without microcephaly - spectrum of congenital syndrome by the Zika virus. + + 152-153 + + S0150-9861(17)30347-4 + 10.1016/j.neurad.2017.11.007 + + + de Freitas Ribeiro + Bruno Niemeyer + BN + + Instituto Estadual do Cérebro Paulo Niemeyer, 156, rua do Rezende, Centro, Rio de Janeiro 20231-092, Brazil. Electronic address: bruno.niemeyer@hotmail.com. + + + + Muniz + Bernardo Carvalho + BC + + Instituto Estadual do Cérebro Paulo Niemeyer, 156, rua do Rezende, Centro, Rio de Janeiro 20231-092, Brazil. + + + + Gasparetto + Emerson Leandro + EL + + Instituto Estadual do Cérebro Paulo Niemeyer, 156, rua do Rezende, Centro, Rio de Janeiro 20231-092, Brazil. + + + + Marchiori + Edson + E + + Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + eng + + Letter + + + 2017 + 12 + 19 + +
+ + France + J Neuroradiol + 7705086 + 0150-9861 + +
+ + + + 2017 + 06 + 14 + + + 2017 + 10 + 31 + + + 2017 + 11 + 25 + + + 2017 + 12 + 24 + 6 + 0 + + + 2017 + 12 + 24 + 6 + 0 + + + 2017 + 12 + 24 + 6 + 0 + + + ppublish + + 29273529 + S0150-9861(17)30347-4 + 10.1016/j.neurad.2017.11.007 + + +
+ + + + + 29272526 + + 2017 + 12 + 22 + +
+ + 1537-6613 + + 216 + 12 + + 2017 + Dec + 19 + + + The Journal of infectious diseases + J. Infect. Dis. + + Evidence for Congenital Zika Virus Infection From Neutralizing Antibody Titers in Maternal Sera, Northeastern Brazil. + + 1501-1504 + + 10.1093/infdis/jix539 + + Reliable diagnosis of congenital Zika virus (ZIKV) infection is challenging. Here, we assessed ZIKV-specific neutralizing antibodies in 28 mothers of children with microcephaly (cases) and 122 controls from northeastern Brazil using plaque reduction neutralization tests. ZIKV-specific antibody titers were significantly higher in cases than in controls (t test, P < .0001). We identified a putative case of congenital Zika syndrome retrospectively by unusually high ZIKV-specific antibody titers. High ZIKV-specific antibody titers in cases were unrelated to prior dengue virus infection. Our data suggest a strong immunological stimulus from prolonged placental or transplacental ZIKV shedding and potential utility of maternal antibody titers to corroborate congenital ZIKV infection. + © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. + + + + Moreira-Soto + Andres + A + + Institute of Virology, University of Bonn Medical Centre, Institute of Virology, Germany. + + + Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Germany. + + + + Sarno + Manoel + M + + Hospital Universitário Professor Edgard Santos, Salvador, Brazil. + + + Maternidade Climério de Oliveira, Universidade Federal da Bahia, Salvador, Brazil. + + + + Pedroso + Celia + C + + Hospital Universitário Professor Edgard Santos, Salvador, Brazil. + + + + Netto + Eduardo Martins + EM + + Hospital Universitário Professor Edgard Santos, Salvador, Brazil. + + + + Rockstroh + Alexandra + A + + Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany. + + + + Luz + Estela + E + + Hospital Universitário Professor Edgard Santos, Salvador, Brazil. + + + + Feldmann + Marie + M + + Institute of Virology, University of Bonn Medical Centre, Institute of Virology, Germany. + + + + Fischer + Carlo + C + + Institute of Virology, University of Bonn Medical Centre, Institute of Virology, Germany. + + + + Bastos + Fernanda Anjos + FA + + Maternidade Climério de Oliveira, Universidade Federal da Bahia, Salvador, Brazil. + + + + Kümmerer + Beate M + BM + + Institute of Virology, University of Bonn Medical Centre, Institute of Virology, Germany. + + + + de Lamballerie + Xavier + X + + Aix Marseille Université, IRD French Institute of Research for Development, EHESP French 19 School of Public Health, EPV UMR_D 190 "Emergence des Pathologies Virales", Marseille, France. + + + IHU Institute hospitalo-universitaire Méditerranée Infection, AP-HM Public Hospitals of Marseille 21, Marseille, France. + + + + Drosten + Christian + C + + Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Germany. + + + German Centre for Infection Research, Germany. + + + + Ulbert + Sebastian + S + + Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany. + + + + Brites + Carlos + C + + Hospital Universitário Professor Edgard Santos, Salvador, Brazil. + + + + Drexler + Jan Felix + JF + + Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Germany. + + + German Centre for Infection Research, Germany. + + + + eng + + Journal Article + +
+ + United States + J Infect Dis + 0413675 + 0022-1899 + + + Brazil + Zika virus + microcephaly + neutralization test + parturient + +
+ + + + 2017 + 08 + 22 + + + 2017 + 10 + 04 + + + 2017 + 12 + 23 + 6 + 0 + + + 2017 + 12 + 23 + 6 + 0 + + + 2017 + 12 + 23 + 6 + 0 + + + ppublish + + 29272526 + 4386913 + 10.1093/infdis/jix539 + + +
+ + + + + 29270171 + + 2017 + 12 + 24 + +
+ + 1664-3224 + + 8 + + 2017 + + + Frontiers in immunology + Front Immunol + + Placental Histopathology and Clinical Presentation of Severe Congenital Zika Syndrome in a Human Immunodeficiency Virus-Exposed Uninfected Infant. + + 1704 + + 10.3389/fimmu.2017.01704 + + In the large Zika virus (ZIKV) epidemic that occurred in Brazil in 2015, the intrauterine fetal exposure to ZIKV was associated with a significant risk of developing microcephaly and neurological disorders in the infected infants. ZIKV-associated disease has since been reported in 24 countries in the Americas. At present, definitive evidence is lacking regarding the intrauterine co-exposure to ZIKV and other viral infections and whether the coinfection impacts the risk of acquiring either infection or disease severity. Here, we provide evidence of intrauterine exposure to both ZIKV and human immunodeficiency virus (HIV) infections, causing congenital Zika syndrome in an HIV-exposed uninfected infant. Clinical, imaging and laboratory examinations of the pregnant woman and the newborn were performed. Histopathology, ZIKV/HIV-specific immunoassays, and ultrastructural evaluation of the placenta were performed. The Zika-asymptomatic, HIV-positive pregnant woman underwent ultrasounds revealing fetal cerebral ventriculomegaly, microcephaly, and brain atrophy. Her baby girl was born small for gestational age and with the neurological sequelae of congenital Zika syndrome. The evaluation of the abnormally large term placenta revealed severe damage to the maternal decidua and chorionic villi, cells positive for ZIKV-specific antigens but not for HIV antigens, and intracellular membranous clusters of virus-like particles approximately 25 nm in diameter. The rapid progression and severity of the congenital Zika syndrome may be related to the uncontrolled HIV disease in the mother. The poor inflammatory response observed in the placenta may have reduced the inherent risk of mother-to-child transmission of HIV. + + + + Rabelo + Kíssila + K + + Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + de Souza Campos Fernandes + Regina Célia + RC + + Faculdade de Medicina de Campos, Campos dos Goytacazes, Brazil. + + + Laboratório de Biotecnologia, Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, Brazil. + + + + de Souza + Luiz José + LJ + + Faculdade de Medicina de Campos, Campos dos Goytacazes, Brazil. + + + + Louvain de Souza + Thais + T + + Faculdade de Medicina de Campos, Campos dos Goytacazes, Brazil. + + + Laboratório de Biotecnologia, Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, Brazil. + + + + Dos Santos + Flávia Barreto + FB + + Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Guerra Nunes + Priscila Conrado + PC + + Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + de Azeredo + Elzinandes Leal + EL + + Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Salomão + Natália Gedeão + NG + + Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Trindade + Gisela Freitas + GF + + Laboratório de Tecnologia Virológica, Biomanguinhos, Rio de Janeiro, Brazil. + + + + Basílio-de-Oliveira + Carlos A + CA + + Anatomia Patológica, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + de Carvalho + Jorge José + JJ + + Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Medina-Acosta + Enrique + E + + Laboratório de Biotecnologia, Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, Brazil. + + + + Paes + Marciano Viana + MV + + Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + + + 2017 + 12 + 07 + +
+ + Switzerland + Front Immunol + 101560960 + 1664-3224 + + + + Clin Neuropathol. 1997 Jul-Aug;16(4):204-8 + 9266146 + + + Arch Gynecol Obstet. 2017 Jun;295(6):1361-1368 + 28396992 + + + Am J Trop Med Hyg. 1982 Jul;31(4):830-6 + 6285749 + + + Cell Host Microbe. 2016 Aug 10;20(2):155-66 + 27443522 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Lancet. 2016 Apr 9;387(10027):1587-90 + 26952548 + + + Clin Infect Dis. 2017 Sep 15;65(6):877-883 + 28535184 + + + Trop Med Int Health. 2017 May;22(5):604-613 + 28214384 + + + DNA Repair (Amst). 2015 Nov;35:13-8 + 26408825 + + + Curr Opin Infect Dis. 2016 Jun;29(3):248-55 + 27027245 + + + J Neuroimmunol. 2017 Jul 15;308:50-64 + 28285789 + + + Mem Inst Oswaldo Cruz. 2016 May;111(5):287-93 + 27143490 + + + J Biol Chem. 2014 Mar 7;289(10):7109-20 + 24474685 + + + Arch Pathol Lab Med. 2017 Jan;141(1):68-72 + 27557413 + + + Annu Rev Microbiol. 1990;44:649-88 + 2174669 + + + Nature. 2017 Jun 15;546(7658):406-410 + 28538727 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Emerg Infect Dis. 2017 Mar;23 (3):405-414 + 27959260 + + + AIDS. 2014 Nov;28 Suppl 4:S507-14 + 25406753 + + + Cell Host Microbe. 2016 Jul 13;20(1):83-90 + 27247001 + + + BMC Bioinformatics. 2015 May 29;16:180 + 26022740 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Bull World Health Organ. 2017 Mar 1;95(3):191-198 + 28250532 + + + Clin Immunol. 2016 Mar;164:95-105 + 26826597 + + + + Zika virus + congenital Zika syndrome + histopathology + human immunodeficiency virus + microcephaly + placenta + +
+ + + + 2017 + 10 + 02 + + + 2017 + 11 + 20 + + + 2017 + 12 + 23 + 6 + 0 + + + 2017 + 12 + 23 + 6 + 0 + + + 2017 + 12 + 23 + 6 + 1 + + + epublish + + 29270171 + 10.3389/fimmu.2017.01704 + PMC5725436 + + +
+ + + + + 29267918 + + 2017 + 12 + 21 + +
+ + 1537-6613 + + 216 + suppl_10 + + 2017 + Dec + 16 + + + The Journal of infectious diseases + J. Infect. Dis. + + Zika Virus Vaccine Development. + + S957-S963 + + 10.1093/infdis/jix464 + + The emergence of Zika virus in Brazil and its association with microcephaly and Guillain-Barré syndrome led to accelerated vaccine development efforts. Based on prior flavivirus vaccine development programs, knowledge of flavivirus particle structure, definition of E dimers as the key antigenic target, and deep understanding of neutralizing mechanisms, multiple vaccine strategies have advanced to the stage of clinical evaluation with unprecedented speed. These include nucleic acid (DNA and messenger RNA), whole-inactivated virus, live-attenuated or chimeric virus, and protein or viruslike particle vaccines. Within a year from the declaration by the World Health Organization of Zika virus as a Public Health Emergency of International Concern, multiple vaccine candidates entered clinical trials, now totaling 7 products with an additional 40-plus candidate vaccines in preclinical development. The rapid progress in vaccine development demonstrates the capacity of governments, public health organizations, and the scientific community to respond to pandemic threats when sufficient prior knowledge exists, emergency funding is made available, and interagency cooperation is achieved and serves as a paradigm for preparing for future emerging infectious diseases. + Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US. + + + + Morabito + Kaitlyn M + KM + + Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. + + + + Graham + Barney S + BS + + Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. + + + + eng + + Journal Article + +
+ + United States + J Infect Dis + 0413675 + 0022-1899 + + + DNA + Zika virus + chimeric + live-attenuated + mRNA + vaccine development + whole-inactivated + +
+ + + + 2017 + 12 + 22 + 6 + 0 + + + 2017 + 12 + 22 + 6 + 0 + + + 2017 + 12 + 22 + 6 + 0 + + + ppublish + + 29267918 + 4753679 + 10.1093/infdis/jix464 + + +
+ + + + + 29253151 + + 2018 + 03 + 08 + +
+ + 1471-8391 + + 124 + 1 + + 2017 + Dec + 01 + + + British medical bulletin + Br. Med. Bull. + + Management of Zika virus in pregnancy: a review. + + 157-169 + + 10.1093/bmb/ldx038v1 + + Since 2015, an epidemic of Zika virus spread across the Americas. This coincided with an increased incidence of microcephaly reported at birth in Brazil, with subsequent evidence of a causal association. + Systemic reviews, observational studies, public health organizations. + Zika virus causes microcephaly and brain abnormalities in infants born to mothers infected during or shortly before pregnancy. Zika virus is a trigger for Guillain Barre Syndrome. Whilst mosquito bite is the main route of transmission, sexual transmission is another confirmed route. + Uncertainty remains regarding the proportion of Zika-infected pregnancies that will give rise to a significantly affected infant. + The development of a vaccine remains a priority whilst public health efforts continue to educate at risk populations on reducing transmission. + Follow-up studies of affected infants are vital to inform on prognosis and guide screening programmes of the future. + © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com + + + + Perry + Helen + H + + Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK. + + + Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St. George's University Hospitals NHS Foundation Trust, Blackshaw Road, London, SW17 0QT, UK. + + + + Khalil + Asma + A + + Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK. + + + Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St. George's University Hospitals NHS Foundation Trust, Blackshaw Road, London, SW17 0QT, UK. + + + + Aarons + Emma + E + + Rare and Imported Pathogens Laboratory, Public Health England, Manor Farm Rd, Porton Down, Salisbury SP4 0JG, UK. + + + + Russell + Katherine + K + + Emerging Infections and Zoonoses, National Infection Service, Public Health England, 61 Colindale Avenue London, NW9 5EQ, UK. + + + + O'Brien + Patrick + P + + Institute for Women's Health, University College London Hospital, 74 Huntley Street, London, WC1E 6AU UK. + + + + eng + + Journal Article + +
+ + England + Br Med Bull + 0376542 + 0007-1420 + + + Zika virus + microcephaly + pregnancy + +
+ + + + 2017 + 12 + 19 + 6 + 0 + + + 2017 + 12 + 19 + 6 + 0 + + + 2017 + 12 + 19 + 6 + 0 + + + ppublish + + 29253151 + 4743527 + 10.1093/bmb/ldx038v1 + + +
+ + + + + 29243225 + + 2018 + 03 + 06 + +
+ + 1365-2567 + + 153 + 4 + + 2018 + Apr + + + Immunology + Immunology + + Current priorities in the Zika response. + + 435-442 + + 10.1111/imm.12878 + + Zika virus (ZIKV), a single-stranded RNA virus of the Flaviviridae family, is an arbovirus (viruses transmitted by arthropods) transmitted to humans and non-human primates through the bites of infected female Aedes sp. mosquitoes. Although first isolated in 1947, it only recently emerged as a global threat, present in several countries resulting in a pandemic scenario. ZIKV infections may have severe outcomes, such as neurological impairment, and with the intrinsic ability of inducing microcephaly in fetuses of infected pregnant women, the virus has become a major public health problem. This review discusses some advances in diagnosis; vaccine development and the problems associated with their administration; the importance of the cross-reactivity with other flaviviruses in protecting or worsening the disease; the implications of the recent outbreak caused by the virus in the world; and future prospects for the complete understanding of this disease. + © 2017 John Wiley & Sons Ltd. + + + + Esposito + Danillo L A + DLA + http://orcid.org/0000-0002-2755-4471 + + Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. + + + + de Moraes + Jonathan B + JB + + Graduate Studies Programme on Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. + + + + Antônio Lopes da Fonseca + Benedito + B + http://orcid.org/0000-0003-3159-5687 + + Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. + + + + eng + + Journal Article + Review + + + 2018 + 01 + 02 + +
+ + England + Immunology + 0374672 + 0019-2805 + + + comparative immunology/evolution + vaccination + viral + zika virus and infection + +
+ + + + 2017 + 09 + 29 + + + 2017 + 11 + 06 + + + 2017 + 11 + 29 + + + 2017 + 12 + 16 + 6 + 0 + + + 2017 + 12 + 16 + 6 + 0 + + + 2017 + 12 + 16 + 6 + 0 + + + ppublish + + 29243225 + 10.1111/imm.12878 + + +
+ + + + + 29242092 + + 2018 + 02 + 27 + +
+ + 1474-4457 + + 18 + 3 + + 2018 + Mar + + + The Lancet. Infectious diseases + Lancet Infect Dis + + Zika virus and microcephaly: where do we go from here? + + 236-237 + + S1473-3099(17)30697-7 + 10.1016/S1473-3099(17)30697-7 + + + Costa + Federico + F + + Instituto da Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, Brazil; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA. + + + + Ko + Albert I + AI + + Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, Brazil; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA. Electronic address: albert.ko@yale.edu. + + + + eng + + Journal Article + + + 2017 + 12 + 11 + +
+ + United States + Lancet Infect Dis + 101130150 + 1473-3099 + +
+ + + + 2017 + 11 + 16 + + + 2017 + 11 + 16 + + + 2017 + 12 + 16 + 6 + 0 + + + 2017 + 12 + 16 + 6 + 0 + + + 2017 + 12 + 16 + 6 + 0 + + + ppublish + + 29242092 + S1473-3099(17)30697-7 + 10.1016/S1473-3099(17)30697-7 + + +
+ + + + + 29242091 + + 2018 + 02 + 27 + +
+ + 1474-4457 + + 18 + 3 + + 2018 + Mar + + + The Lancet. Infectious diseases + Lancet Infect Dis + + Association between microcephaly, Zika virus infection, and other risk factors in Brazil: final report of a case-control study. + + 328-336 + + S1473-3099(17)30727-2 + 10.1016/S1473-3099(17)30727-2 + + A Zika virus epidemic emerged in northeast Brazil in 2015 and was followed by a striking increase in congenital microcephaly cases, triggering a declaration of an international public health emergency. This is the final report of the first case-control study evaluating the potential causes of microcephaly: congenital Zika virus infection, vaccines, and larvicides. The published preliminary report suggested a strong association between microcephaly and congenital Zika virus infection. + We did a case-control study in eight public maternity hospitals in Recife, Brazil. Cases were neonates born with microcephaly, defined as a head circumference of 2 SD below the mean. Two controls without microcephaly were matched to each case by expected date of delivery and area of residence. We tested the serum of cases and controls and the CSF of cases for detection of Zika virus genomes with quantitative RT-PCR and for detection of IgM antibodies with capture-IgM ELISA. We also tested maternal serum with plaque reduction neutralisation assays for Zika and dengue viruses. We estimated matched crude and adjusted odds ratios with exact conditional logistic regression to determine the association between microcephaly and Zika virus infection. + We screened neonates born between Jan 15 and Nov 30, 2016, and prospectively recruited 91 cases and 173 controls. In 32 (35%) cases, congenital Zika virus infection was confirmed by laboratory tests and no controls had confirmed Zika virus infections. 69 (83%) of 83 cases with known birthweight were small for gestational age, compared with eight (5%) of 173 controls. The overall matched odds ratio was 73·1 (95% CI 13·0-∞) for microcephaly and Zika virus infection after adjustments. Neither vaccination during pregnancy or use of the larvicide pyriproxyfen was associated with microcephaly. Results of laboratory tests for Zika virus and brain imaging results were available for 79 (87%) cases; within these cases, ten were positive for Zika virus and had cerebral abnormalities, 13 were positive for Zika infection but had no cerebral abnormalities, and 11 were negative for Zika virus but had cerebral abnormalities. + The association between microcephaly and congenital Zika virus infection was confirmed. We provide evidence of the absence of an effect of other potential factors, such as exposure to pyriproxyfen or vaccines (tetanus, diphtheria, and acellular pertussis, measles and rubella, or measles, mumps, and rubella) during pregnancy, confirming the findings of an ecological study of pyriproxyfen in Pernambuco and previous studies on the safety of Tdap vaccine administration during pregnancy. + Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. + Copyright © 2018 Elsevier Ltd. All rights reserved. + + + + de Araújo + Thalia Velho Barreto + TVB + + Department of Social Medicine, Federal University of Pernambuco, Recife, Brazil. Electronic address: thalia@ufpe.br. + + + + Ximenes + Ricardo Arraes de Alencar + RAA + + Department of Tropical Medicine, Federal University of Pernambuco, Recife, Brazil; University of Pernambuco, Recife, Brazil. + + + + Miranda-Filho + Demócrito de Barros + DB + + University of Pernambuco, Recife, Brazil. + + + + Souza + Wayner Vieira + WV + + The Research Centre Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Montarroyos + Ulisses Ramos + UR + + University of Pernambuco, Recife, Brazil. + + + + de Melo + Ana Paula Lopes + APL + + Department of Community Health, Federal University of Pernambuco, Vitória de Santo Antão, Brazil. + + + + Valongueiro + Sandra + S + + Department of Social Medicine, Federal University of Pernambuco, Recife, Brazil. + + + + de Albuquerque + Maria de Fátima Pessoa Militão + MFPM + + The Research Centre Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Braga + Cynthia + C + + The Research Centre Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Filho + Sinval Pinto Brandão + SPB + + The Research Centre Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Cordeiro + Marli Tenório + MT + + The Research Centre Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Vazquez + Enrique + E + + Pan American Health Organization, Brasília, Brazil. + + + + Cruz + Danielle di Cavalcanti Souza + DDCS + + Instituto Materno Infantil Fernando Figueira, Recife, Brazil. + + + + Henriques + Claudio Maierovitch Pessanha + CMP + + Brazilian Ministry of Health, Brasília, Brazil. + + + + Bezerra + Luciana Caroline Albuquerque + LCA + + State Health Department of Pernambuco, Recife, Brazil. + + + + Castanha + Priscila Mayrelle da Silva + PMDS + + The Research Centre Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Dhalia + Rafael + R + + The Research Centre Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Marques-Júnior + Ernesto Torres Azevedo + ETA + + The Research Centre Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA. + + + + Martelli + Celina Maria Turchi + CMT + + The Research Centre Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Rodrigues + Laura Cunha + LC + + Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. + + + + investigators from the Microcephaly Epidemic Research Group + + + Brazilian Ministry of Health + + + Pan American Health Organization + + + Instituto de Medicina Integral Professor Fernando Figueira + + + State Health Department of Pernambuco + + + eng + + Journal Article + + + 2017 + 12 + 11 + +
+ + United States + Lancet Infect Dis + 101130150 + 1473-3099 + + + + Lancet Infect Dis. 2018 Jan 4;: + 29307514 + + + + + Dhalia + Carmen + C + + + Santos + Marcela + M + + + Cortes + Fanny + F + + + Kleber de Oliveira + Wanderson + W + + + Evelim Coelho + Giovanini + G + + + Cortez-Escalante + Juan Jose + JJ + + + Campelo de Albuquerque de Melo + Carlos Frederico + CF + + + Ramon-Pardo + Pilar + P + + + Aldighieri + Sylvain + S + + + Mendez-Rico + Jairo + J + + + Espinal + Marcos + M + + + Torres + Leuridan + L + + + Nassri Hazin + Adriano + A + + + Van der Linden + Ana + A + + + Coentro + Monica + M + + + Santiago Dimech + George + G + + + Siqueira de Assuncao + Romildo + R + + + Ismael de Carvalho + Patricia + P + + + Felix Oliveira + Valdete + V + + +
+ + + + 2017 + 04 + 26 + + + 2017 + 09 + 21 + + + 2017 + 10 + 02 + + + 2017 + 12 + 16 + 6 + 0 + + + 2017 + 12 + 16 + 6 + 0 + + + 2017 + 12 + 16 + 6 + 0 + + + ppublish + + 29242091 + S1473-3099(17)30727-2 + 10.1016/S1473-3099(17)30727-2 + + +
+ + + + + 29240727 + + 2017 + 12 + 21 + + + 2018 + 01 + 19 + +
+ + 1545-861X + + 66 + 49 + + 2017 + Dec + 15 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Health and Development at Age 19-24 Months of 19 Children Who Were Born with Microcephaly and Laboratory Evidence of Congenital Zika Virus Infection During the 2015 Zika Virus Outbreak - Brazil, 2017. + + 1347-1351 + + 10.15585/mmwr.mm6649a2 + + In November 2015, the Brazilian Ministry of Health (MOH) declared the Zika virus outbreak a public health emergency after an increase in microcephaly cases was reported in the northeast region of the country (1). During 2015-2016, 15 states in Brazil with laboratory-confirmed Zika virus transmission reported an increase in birth prevalence of microcephaly (2.8 cases per 10,000 live births), significantly exceeding prevalence in four states without confirmed transmission (0.6 per 10,000) (2). Although children with microcephaly and laboratory evidence of Zika virus infection have been described in early infancy (3), their subsequent health and development have not been well characterized, constraining planning for the care and support of these children and their families. The Brazilian MOH, the State Health Secretariat of Paraíba, and CDC collaborated on a follow-up investigation of the health and development of children in northeastern Brazil who were reported to national surveillance with microcephaly at birth. Nineteen children with microcephaly at birth and laboratory evidence of Zika virus infection were assessed through clinical evaluations, caregiver interviews, and review of medical records. At follow-up (ages 19-24 months), most of these children had severe motor impairment, seizure disorders, hearing and vision abnormalities, and sleep difficulties. Children with microcephaly and laboratory evidence of Zika virus infection have severe functional limitations and will require specialized care from clinicians and caregivers as they age. + + + + Satterfield-Nash + Ashley + A + + + Kotzky + Kim + K + + + Allen + Jacob + J + + + Bertolli + Jeanne + J + + + Moore + Cynthia A + CA + + + Pereira + Isabela Ornelas + IO + + + Pessoa + André + A + + + Melo + Flavio + F + + + Santelli + Ana Carolina Faria E Silva + ACFES + + + Boyle + Coleen A + CA + + + Peacock + Georgina + G + + + eng + + Journal Article + + + 2017 + 12 + 15 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + MMWR Morb Mortal Wkly Rep. 2017 Oct 20;66(41):1089-1099 + 29049277 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + Pediatr Neurol. 2016 Jan;54:64-69.e1 + 26552646 + + + J Clin Microbiol. 2000 May;38(5):1823-6 + 10790107 + + + JAMA Pediatr. 2017 Mar 1;171(3):288-295 + 27812690 + + + Dev Med Child Neurol. 2016 Mar;58(3):240-5 + 26306473 + + + + + Brazil + epidemiology + + + Case-Control Studies + + + Child, Preschool + + + Clinical Laboratory Techniques + + + Developmental Disabilities + epidemiology + + + Disease Outbreaks + + + Female + + + Follow-Up Studies + + + Humans + + + Infant + + + Infant, Newborn + + + Male + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Zika Virus + isolation & purification + + + Zika Virus Infection + congenital + epidemiology + + +
+ + + + 2017 + 12 + 15 + 6 + 0 + + + 2017 + 12 + 15 + 6 + 0 + + + 2017 + 12 + 22 + 6 + 0 + + + epublish + + 29240727 + 10.15585/mmwr.mm6649a2 + PMC5730218 + + +
+ + + + + 29238705 + + 2017 + 12 + 20 + +
+ + 2296-2565 + + 5 + + 2017 + + + Frontiers in public health + Front Public Health + + Can Zika Account for the Missing Babies? + + 317 + + 10.3389/fpubh.2017.00317 + + The Zika virus (ZIKV) spread rapidly in Brazil in 2015 and 2016. Rio de Janeiro was among the Brazilian cities which were hit the hardest, with more that a hundred thousand confirmed cases up to the end of 2016. Given the severity of the neurological damage caused by ZIKV on fetuses, we wondered whether it would also cause an increase in the number of miscarriages, especially very early ones. As early miscarriages are unlikely to be recorded as a health event, this effect-if it occurred-would only show up as a reduction in the number of live births. In this article, we show that there was a 15% drop in live births between September and December 2016 compared with the previous year, and that this sharp drop from epidemiological week 33 onward is strongly correlated with the number of recorded cases of Zika about 40 weeks earlier. We postulate that ZIKV is directly responsible for this drop in the birth rate. Further work is required to ascertain whether other factors such as the fear of having a microcephaly baby or the economic crisis are having a significant effect. + + + + Coelho + Flávio Codeço + FC + + Center for Mathematical Epidemiology, School of Applied Mathematics, Fundação Getúlio Vargas, Brasília, Brazil. + + + + Armstrong + Margaret + M + + Center for Mathematical Epidemiology, School of Applied Mathematics, Fundação Getúlio Vargas, Brasília, Brazil. + + + + Saraceni + Valeria + V + + Prefeitura da Cidade do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Lemos + Cristina + C + + Prefeitura da Cidade do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + + + 2017 + 11 + 29 + +
+ + Switzerland + Front Public Health + 101616579 + 2296-2565 + + + + Nat Commun. 2017 Feb 21;8:14575 + 28220786 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Am J Public Health. 2016 Apr;106(4):601-5 + 26959259 + + + N Engl J Med. 2017 Apr 20;376(16):1591-1593 + 28402236 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + N Engl J Med. 2016 Sep 8;375(10):1002-4 + 27463941 + + + J Interferon Cytokine Res. 2017 Jul;37(7):287-294 + 28402153 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + + Zika + diseases + epidemiology + infant + live birth rate + newborn + sexually transmitted diseases + +
+ + + + 2017 + 09 + 08 + + + 2017 + 11 + 13 + + + 2017 + 12 + 15 + 6 + 0 + + + 2017 + 12 + 15 + 6 + 0 + + + 2017 + 12 + 15 + 6 + 1 + + + epublish + + 29238705 + 10.3389/fpubh.2017.00317 + PMC5712541 + + +
+ + + + + 29219883 + + 2017 + 12 + 08 + +
+ + 1536-3724 + + + 2017 + Dec + 01 + + + Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine + Clin J Sport Med + + Zika Virus and the Rio Olympic Games. + 10.1097/JSM.0000000000000551 + + To evaluate the impact of Zika virus on preparation and management of the New Zealand (NZ) Olympic team. + Descriptive manuscript. + New Zealand Olympic Health team preparation and management during the Rio de Janeiro Olympic Games, 2016. + New Zealand Olympic Team members. + This manuscript describes the approaches used by the NZ Olympic Health team to the minimization of risk from Zika virus. + Although descriptive of approach forms most of the article, the results of Zika virus serology are presented. + The NZ Olympic Health team took a proactive approach to risk mitigation, including extensive education, clothing changes, mosquito spray, mosquito nets, and voluntary postexposure testing. No positive serology was observed in those tested. + The outbreak of Zika virus in Brazil, the associated complication of microcephaly, and the evolving understanding of virus transmission created significant uncertainty for NZ Olympic team members. The proactive approach taken by the health team to the mitigation of risk, combined with the anticipated low risk of arbovirus transmission over the period of the games, resulted in enhanced confidence from team members and no reports of positive serology. + + + + Hamilton + Bruce + B + + High Performance Sport NZ, Millenium Institute of Sport and Health, Mairangi Bay, Auckland, New Zealand. + + + New Zealand Olympic Committee. + + + + Exeter + Dan + D + + High Performance Sport NZ, Millenium Institute of Sport and Health, Mairangi Bay, Auckland, New Zealand. + + + Axis Sports Medicine Specialists, Auckland, New Zealand. + + + + Beable + Sarah + S + + High Performance Sport NZ, Millenium Institute of Sport and Health, Mairangi Bay, Auckland, New Zealand. + + + Axis Sports Medicine Specialists, Auckland, New Zealand. + + + + Coleman + Lynne + L + + High Performance Sport NZ, Millenium Institute of Sport and Health, Mairangi Bay, Auckland, New Zealand. + + + Apollo Medical Centre. + + + + Milne + Chris + C + + High Performance Sport NZ, Millenium Institute of Sport and Health, Mairangi Bay, Auckland, New Zealand. + + + Anglesea Sports Medicine, Hamilton, New Zealand. + + + + eng + + Journal Article + + + 2017 + 12 + 01 + +
+ + United States + Clin J Sport Med + 9103300 + 1050-642X + +
+ + + + 2017 + 12 + 9 + 6 + 0 + + + 2017 + 12 + 9 + 6 + 0 + + + 2017 + 12 + 9 + 6 + 0 + + + aheadofprint + + 29219883 + 10.1097/JSM.0000000000000551 + + +
+ + + + + 29211161 + + 2017 + 12 + 06 + +
+ + 1678-4561 + + 22 + 11 + + 2017 + Nov + + + Ciencia & saude coletiva + Cien Saude Colet + + Profile of demand and Continuous Cash Benefits (BCP) granted to children diagnosed with microcephaly in Brazil. + + 3557-3566 + + S1413-81232017021103557 + 10.1590/1413-812320172211.22182017 + + The Brazilian Federal Constitution of 1988 introduced the Continuous Cash Benefits (BCP), allowing the inclusion of people with disabilities. This is a descriptive study with aggregate municipal data about the time and geographic distribution of the incidence of microcephaly related to the Zika virus in Brazil and data of the BCP grants to children diagnosed with microcephaly. Data on the demand and BCP grants to children with microcephaly since 2009 are shown. Cases of microcephaly and/or central nervous system disorders were obtained from the Ministry of Health and totaled 2,366 confirmed cases from January 1, 2015 to December 31, 2016. The historical series of BCP granted from 2009 to 2016 was based on data from the National Institute of Social Security and showed, until 2014, a baseline with an average of 200 annual benefits for children younger than 48 months with microcephaly. In 2016, grants increased eight times, reaching 1,603 benefits granted to children of 731 municipalities spread in the 27 States. The Northeast accounted for 73% of the BCPs granted, however, this was less than 65% of the demand for incident cases. The implementation of the integrated referral system, including active search, should be strengthened to ensure access to all children entitled to BCP. + + + + Pereira + Éverton Luís + ÉL + + Departamento de Saúde Coletiva, Universidade de Brasília (UnB). Campus Universitário Darcy Ribeiro, Asa Norte. 70000000 Brasília DF Brasil. evertonpereira@unb.br. + + + + Bezerra + Josierton Cruz + JC + + Departamento de Saúde Coletiva, Universidade de Brasília (UnB). Campus Universitário Darcy Ribeiro, Asa Norte. 70000000 Brasília DF Brasil. evertonpereira@unb.br. + + + + Brant + Jonas Lotufo + JL + + Departamento de Saúde Coletiva, Universidade de Brasília (UnB). Campus Universitário Darcy Ribeiro, Asa Norte. 70000000 Brasília DF Brasil. evertonpereira@unb.br. + + + + Araújo + Wildo Navegantes de + WN + + Faculdade de Ceilândia, UnB. Brasília DF Brasil. + + + + Santos + Leonor Maria Pacheco + LMP + + Departamento de Saúde Coletiva, Universidade de Brasília (UnB). Campus Universitário Darcy Ribeiro, Asa Norte. 70000000 Brasília DF Brasil. evertonpereira@unb.br. + + + + por + eng + + Journal Article + + Perfil da demanda e dos Benefícios de Prestação Continuada (BPC) concedidos a crianças com diagnóstico de microcefalia no Brasil. +
+ + Brazil + Cien Saude Colet + 9713483 + 1413-8123 + + + A Constituição Federal de 1988 introduziu o Benefício de Prestação Continuada (BPC) possibilitando a inclusão de pessoas com deficiência. Estudo descritivo, com dados municipais agregados, da distribuição temporal e geográfica da incidência de microcefalia relacionada ao Zika vírus no Brasil e dados das concessões de BPC a crianças com diagnóstico de microcefalia. Apresentam-se dados sobre a demanda e a concessão do BPC para crianças com microcefalia desde 2009. Os casos de microcefalia e/ou alteração do sistema nervoso central foram obtidos do Ministério da Saúde e totalizaram 2.366 casos confirmados de 01/01/2015 a 31/12/2016. A série histórica da concessão de BPC de 2009 a 2016 foi elaborada a partir de dados do Instituto Nacional do Seguro Social e mostrou, até 2014, uma linha de base com a média de 200 benefícios anuais para crianças menores de 48 meses com microcefalia. Em 2016 as concessões aumentaram oito vezes atingindo 1.603 benefícios concedidos a crianças de 731 municípios, das 27 Unidades da Federação. A Região Nordeste concentrou 73% dos BPC concedidos, mas, ainda assim, isto representou menos do que 65% da demanda de casos incidentes. É preciso reforçar a implementação do sistema de referência integrado, inclusive com busca ativa, para que todas as crianças com direito ao BPC tenham acesso. + +
+ + + + 2017 + 05 + 15 + + + 2017 + 09 + 01 + + + 2017 + 12 + 7 + 6 + 0 + + + 2017 + 12 + 7 + 6 + 0 + + + 2017 + 12 + 7 + 6 + 0 + + + ppublish + + 29211161 + S1413-81232017021103557 + 10.1590/1413-812320172211.22182017 + + +
+ + + + + 29209885 + + 2017 + 12 + 06 + +
+ + 1433-0350 + + + 2017 + Dec + 05 + + + Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery + Childs Nerv Syst + + Neuroimaging findings associated with congenital Zika virus syndrome: case series at the time of first epidemic outbreak in Pernambuco State, Brazil. + 10.1007/s00381-017-3682-9 + + This study aimed to describe the prenatal and postnatal neuroimaging and clinical findings in a clinical series following congenital Zika virus syndrome during the first epidemic Zika virus (ZIKV) outbreak in the State of Pernambuco, Brazil. + We (the authors) conducted a retrospective study of a prospectively collected case series of fetuses and neonates with microcephaly born to mothers with presumed/confirmed congenital ZIKV syndrome. Prenatal ultrasound findings were reviewed to identify potential central nervous system (CNS) abnormalities. Neonates underwent postnatal neuroimaging follow up by computed tomography (CT)-scan or magnetic resonance (MR) imaging. + The prenatal and postnatal outcomes of eight fetuses/neonates born to mothers with presumed/confirmed congenital ZIKV syndrome were examined. The mean gestational age at ultrasound was 31.3 weeks. Severe microcephaly was identified in seven fetuses (87.5%), while ventriculomegaly and brain calcifications were detected in all fetuses. The mean gestational age at delivery and head circumference were 38 weeks and 30.2 cm, respectively. All cases of microcephaly but one was confirmed postnatally. Brain CT scans or MRIs were performed in seven newborns, and all had periventricular and/or parenchymal calcifications, symmetrical or asymmetrical ventriculomegaly, pachygyria, and reduced sulcation and gyration. MR imaging aided the detection of one undetected case of corpus callosum dysgenesis and was essential in documenting reduced mantel of the cerebral cortex and reduced gyration and sulcation, especially involving the parietal lobe. In addition, MR imaging was also able to display irregular interfaces with the subcortical white matter, a finding consistent with polymicrogyria, more frequently seen at the level of the frontal lobe and atrophic and thinned pons. + Severe microcephaly and CNS abnormalities may be associated with congenital ZIKV syndrome. + + + + Pires + Pedro + P + + Department of Maternal and Child, Pernambuco University (UPE), Recife, PE, Brazil. + + + + Jungmann + Patricia + P + + Department of Pathology, Pernambuco University (UPE), Recife, PE, Brazil. + + + + Galvão + Jully Moura + JM + + Department of Maternal and Child, Pernambuco University (UPE), Recife, PE, Brazil. + + + + Hazin + Adriano + A + + Department of Radiology, Instituto de Medicina Integral Professor Fernandes Figueira (IMIP), Recife, PE, Brazil. + + + + Menezes + Luiza + L + + Department of Maternal and Child, Pernambuco University (UPE), Recife, PE, Brazil. + + + + Ximenes + Ricardo + R + + Department of Tropical Medicine, Federal University of Pernambuco (UFPE), Recife, PE, Brazil. + + + + Tonni + Gabriele + G + + Department of Obstetrics and Gynecology, AUSL Reggio Emilia, Guastalla Civil Hospital, Reggio Emilia, Italy. + + + + Araujo Júnior + Edward + E + http://orcid.org/0000-0002-6145-2532 + + Department of Obstetrics, Paulista School of Medicine, Federal University of São Paulo (EPM-UNIFESP), Rua Belchior de Azevedo, 156 apto. 111 Torre Vitoria, São Paulo, SP, CEP 05089-030, Brazil. araujojred@terra.com.br. + + + + eng + + Journal Article + + + 2017 + 12 + 05 + +
+ + Germany + Childs Nerv Syst + 8503227 + 0256-7040 + + + Brain abnormalities + Computed tomography + Congenital Zika virus syndrome + Magnetic resonance imaging + Microcephaly + Ultrasound + +
+ + + + 2017 + 08 + 29 + + + 2017 + 11 + 27 + + + 2017 + 12 + 7 + 6 + 0 + + + 2017 + 12 + 7 + 6 + 0 + + + 2017 + 12 + 7 + 6 + 0 + + + aheadofprint + + 29209885 + 10.1007/s00381-017-3682-9 + 10.1007/s00381-017-3682-9 + + +
+ + + + + 29181930 + + 2018 + 03 + 01 + + + 2018 + 03 + 01 + +
+ + 0807-7096 + + 137 + 22 + + 2017 + 11 + 28 + + + Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke + Tidsskr. Nor. Laegeforen. + + + 10.4045/tidsskr.17.0655 + + + Skråning + Susanne + S + + + Lindskog + Benedikte V + BV + + + nor + + Journal Article + + The Zika outbreak in Brazil: An unequal burden. + + 2017 + 11 + 28 + +
+ + Norway + Tidsskr Nor Laegeforen + 0413423 + 0029-2001 + + IM + + + Brazil + epidemiology + + + Cost of Illness + + + Delivery of Health Care + organization & administration + + + Disease Outbreaks + economics + + + Female + + + Global Health + + + Health Services Accessibility + + + Humans + + + Infant, Newborn + + + Microcephaly + economics + virology + + + Mothers + psychology + + + One Health + + + Poverty + + + Pregnancy + + + Pregnancy Complications, Infectious + economics + epidemiology + virology + + + Social Security + + + Women's Health + + + Zika Virus + isolation & purification + + + Zika Virus Infection + congenital + economics + epidemiology + + +
+ + + + 2017 + 11 + 29 + 6 + 0 + + + 2018 + 3 + 2 + 6 + 0 + + + 2017 + 11 + 29 + 6 + 0 + + + epublish + + 29181930 + 17-0655 + 10.4045/tidsskr.17.0655 + + +
+ + + + + 29181810 + + 2018 + 01 + 19 + +
+ + 1433-0350 + + 34 + 1 + + 2018 + Jan + + + Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery + Childs Nerv Syst + + Imaging findings in congenital Zika virus infection syndrome: an update. + + 85-93 + + 10.1007/s00381-017-3637-1 + + Zika virus (ZIKV) is a neurotropic and neurotoxic RNA Flavivirus prompt to cause severe fetal brain dysmorphisms during pregnancy, a period of rapid and critical central nervous system development. A wide range of clinico-radiological findings of congenital ZIKV infections were reported in the literature, such as microcephaly, overlapping sutures, cortical migrational and corpus callosum abnormalities, intracranial calcifications, ventriculomegaly, brain stem and cerebellar malformations, spinal cord involvement, and joint contractures. ZIKV is also related to other severe neurological manifestations in grown-up individuals such as Guillain-Barré syndrome and encephalomyelitis. + Our purpose is to review the radiological central nervous system abnormalities of congenital ZIKV infection syndrome on different imaging modalities. + + + + de Souza + Andrea Silveira + AS + + D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, Rio de Janeiro, 22281-100, Brazil. + + + + de Oliveira-Szjenfeld + Patrícia Soares + PS + + Department of Diagnostic Imaging, Federal University of São Paulo, São Paulo, Brazil. + + + Foundation Institute for Education and Research in Diagnostic Imaging (FIDI), Federal University of São Paulo, São Paulo, Brazil. + + + + de Oliveira Melo + Adriana Suely + AS + + Research Institute Professor Amorim Neto (IPESQ), Campina Grande, PB, Brazil. + + + UNIFACISA, Campina Grande, PB, Brazil. + + + + de Souza + Luis Alberto Moreira + LAM + + D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, Rio de Janeiro, 22281-100, Brazil. + + + + Batista + Alba Gean Medeiros + AGM + + Research Institute Professor Amorim Neto (IPESQ), Campina Grande, PB, Brazil. + + + Hospital Pedro I, Campina Grande, PB, Brazil. + + + + Tovar-Moll + Fernanda + F + + D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, Rio de Janeiro, 22281-100, Brazil. fernanda.tovarmoll@idor.org. + + + Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. fernanda.tovarmoll@idor.org. + + + + eng + + + 440909/2016-3 + Brazilian Council for Development of Science and Technology (CNPq) + United States + + + 88887.116625/2016-01 + CAPES Foundation + United States + + + E-26/201.319/2016 + Rio de Janeiro Foundation for the Support of Science (FAPERJ) + United States + + + PNeuro + D'Or Institute for Research and Education (IDOR) + United States + + + + Journal Article + + + 2017 + 11 + 27 + +
+ + Germany + Childs Nerv Syst + 8503227 + 0256-7040 + + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + Emerg Med Clin North Am. 2016 Aug;34(3):e25-37 + 27475021 + + + Lancet. 2016 Apr 30;387(10030):1811-2 + 27103126 + + + Arch Gynecol Obstet. 2017 Jun;295(6):1361-1368 + 28396992 + + + Neuron. 2016 Dec 7;92 (5):949-958 + 27930910 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Ultrasound Obstet Gynecol. 2017 Dec;50(6):717-722 + 27644020 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Am J Obstet Gynecol. 2017 Mar;216(3):209-225 + 28126366 + + + Am J Med Genet A. 2017 Apr;173(4):841-857 + 28328129 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + Acta Neuropathol. 2017 Jun;133(6):983-999 + 28332092 + + + Jpn J Radiol. 2016 Dec;34(12 ):765-770 + 27714487 + + + Lancet. 2016 Aug 27;388(10047):898-904 + 27372395 + + + Am J Reprod Immunol. 2017 Feb;77(2):null + 28045216 + + + Brain. 2012 May;135(Pt 5):1348-69 + 22427329 + + + JAMA Neurol. 2017 May 1;74(5):610 + 28319237 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Arch Pathol Lab Med. 2017 Jan;141(1):18-25 + 27763793 + + + Prenat Diagn. 2017 Feb;37(2):207-208 + 28205302 + + + Arch Pathol Lab Med. 2017 Jan;141(1):73-81 + 27726416 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + AJNR Am J Neuroradiol. 2017 May;38(5):1045-1053 + 28364011 + + + Sci Rep. 2017 Jan 23;7:40780 + 28112162 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + JAMA Pediatr. 2017 Mar 1;171(3):288-295 + 27812690 + + + Arch Med Sci. 2016 Feb 1;12(1):10-24 + 26925114 + + + JAMA Neurol. 2016 Dec 1;73(12 ):1407-1416 + 27695855 + + + Indian J Radiol Imaging. 2014 Oct;24(4):389-400 + 25489132 + + + JAMA Ophthalmol. 2016 Aug 1;134(8):912-8 + 27228275 + + + Pediatr Radiol. 2016 Jun;46(7):1032-9 + 27090801 + + + Clin Infect Dis. 2017 May 15;64(10 ):1302-1308 + 28329257 + + + Eur J Pediatr. 2001 Nov;160(11):664-7 + 11760023 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + AJNR Am J Neuroradiol. 1999 Nov-Dec;20(10):1814-21 + 10588102 + + + AJP Rep. 2017 Apr;7(2):e68-e73 + 28413694 + + + Pathog Glob Health. 2016 Oct - Dec;110(7-8):262-268 + 27690200 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + + Arthrogryposis + Brain calcifications + Congenital malformation + Microcephaly + Ventriculomegaly + ZIKV + Zika + +
+ + + + 2017 + 10 + 09 + + + 2017 + 10 + 17 + + + 2017 + 11 + 29 + 6 + 0 + + + 2017 + 11 + 29 + 6 + 0 + + + 2017 + 11 + 29 + 6 + 0 + + + ppublish + + 29181810 + 10.1007/s00381-017-3637-1 + 10.1007/s00381-017-3637-1 + + +
+ + + + + 29167994 + + 2018 + 01 + 19 + +
+ + 1433-0350 + + 34 + 1 + + 2018 + Jan + + + Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery + Childs Nerv Syst + + Congenital Zika virus infection: a neuropathological review. + + 95-99 + + 10.1007/s00381-017-3651-3 + + A relationship between Zika virus (ZikV) infection in pregnancy and the occurrence of microcephaly was established during the Zika outbreak in Brazil (2015-2016). Neuropathological findings in congenital Zika syndrome helped to understand its pathogenetic mechanisms. + The most relevant postmortem findings in the central nervous system (CNS) of fetuses and neonates infected with ZikV early in gestation are microcephaly with ex-vacuo ventriculomegaly and large head circumference associated with obstructive hydrocephalus due to severe midbrain and aqueduct distortion. Babies with severe brain lesions are born with arthrogryposis. Histologically, there is extensive destruction of the hemispheric parenchyma, calcifications, various disturbances of neuronal migration, reactive gliosis, microglial hyperplasia and occasional perivascular cuffs of lymphocytes, also in the meninges. Hypoplastic lesions secondary to the lack of descending nerve fibers include small basis pontis, pyramids and spinal corticospinal tracts. Cerebellar hypoplasia is also common. Severe nerve motor nerve cell loss is observed in the anterior horn of the spinal cord. + A spectrum of neuropathological changes, from severe microcephaly to obstructive hydrocephalus was observed. The severity of the lesions is directly related to the gestational age, the most severe occurring when the mother is infected in the first trimester. Infection of progenitor cells at the germinal matrix was demonstrated. The lack of spinal motor neurons is responsible for fetal acynesia and consequent arthrogryposis. + + + + Chimelli + L + L + + Laboratory of Neuropathology, State Institute of Brain Paulo Niemeyer and Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. + + + + Avvad-Portari + E + E + http://orcid.org/0000-0003-2372-0898 + + Fernandes Figueira Institute-Oswaldo Cruz Foundation (Fiocruz) and State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil. bethavvad@gmail.com. + + + + eng + + Journal Article + + + 2017 + 11 + 22 + +
+ + Germany + Childs Nerv Syst + 8503227 + 0256-7040 + + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Acta Neuropathol. 2017 Jun;133(6):983-999 + 28332092 + + + Lancet. 2016 Aug 27;388(10047):898-904 + 27372395 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Emerg Infect Dis. 2017 Jul;23 (7):1164-1167 + 28459414 + + + Mem Inst Oswaldo Cruz. 2016 May;111(5):287-93 + 27143490 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Emerg Infect Dis. 2017 Jun;23 (6):982-984 + 28296632 + + + + Calcifications + Congenital Zika virus infection + Microcephaly + Migration disturbances + Neuropathology + Ventriculomegaly + +
+ + + + 2017 + 10 + 19 + + + 2017 + 10 + 27 + + + 2017 + 11 + 24 + 6 + 0 + + + 2017 + 11 + 24 + 6 + 0 + + + 2017 + 11 + 24 + 6 + 0 + + + ppublish + + 29167994 + 10.1007/s00381-017-3651-3 + 10.1007/s00381-017-3651-3 + + +
+ + + + + 29138300 + + 2017 + 12 + 19 + +
+ + 2150-7511 + + 8 + 6 + + 2017 + Nov + 14 + + + mBio + MBio + + High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks. + e01390-17 + 10.1128/mBio.01390-17 + + During 2015 to 2016, Brazil reported more Zika virus (ZIKV) cases than any other country, yet population exposure remains unknown. Serological studies of ZIKV are hampered by cross-reactive immune responses against heterologous viruses. We conducted serosurveys for ZIKV, dengue virus (DENV), and Chikungunya virus (CHIKV) in 633 individuals prospectively sampled during 2015 to 2016, including microcephaly and non-microcephaly pregnancies, HIV-infected patients, tuberculosis patients, and university staff in Salvador in northeastern Brazil using enzyme-linked immunosorbent assays (ELISAs) and plaque reduction neutralization tests. Sera sampled retrospectively during 2013 to 2015 from 277 HIV-infected patients were used to assess the spread of ZIKV over time. Individuals were georeferenced, and sociodemographic indicators were compared between ZIKV-positive and -negative areas and areas with and without microcephaly cases. Epidemiological key parameters were modeled in a Bayesian framework. ZIKV seroprevalence increased rapidly during 2015 to 2016, reaching 63.3% by 2016 (95% confidence interval [CI], 59.4 to 66.8%), comparable to the seroprevalence of DENV (75.7%; CI, 69.4 to 81.1%) and higher than that of CHIKV (7.4%; CI, 5.6 to 9.8%). Of 19 microcephaly pregnancies, 94.7% showed ZIKV IgG antibodies, compared to 69.3% of 257 non-microcephaly pregnancies (P= 0.017). Analyses of sociodemographic data revealed a higher ZIKV burden in low socioeconomic status (SES) areas. High seroprevalence, combined with case data dynamics allowed estimates of the basic reproduction numberR0of 2.1 (CI, 1.8 to 2.5) at the onset of the outbreak and an effective reproductive numberReffof <1 in subsequent years. Our data corroborate ZIKV-associated congenital disease and an association of low SES and ZIKV infection and suggest that population immunity caused cessation of the outbreak. Similar studies from other areas will be required to determine the fate of the American ZIKV outbreak.IMPORTANCEThe ongoing American Zika virus (ZIKV) outbreak involves millions of cases and has a major impact on maternal and child health. Knowledge of infection rates is crucial to project future epidemic patterns and determine the absolute risk of microcephaly upon maternal ZIKV infection during pregnancy. For unknown reasons, the vast majority of ZIKV-associated microcephaly cases are concentrated in northeastern Brazil. We analyzed different subpopulations from Salvador, a Brazilian metropolis representing one of the most affected areas during the American ZIKV outbreak. We demonstrate rapid spread of ZIKV in Salvador, Brazil, and infection rates exceeding 60%. We provide evidence for the link between ZIKV and microcephaly, report that ZIKV predominantly affects geographic areas with low socioeconomic status, and show that population immunity likely caused cessation of the outbreak. Our results enable stakeholders to identify target populations for vaccination and for trials on vaccine efficacy and allow refocusing of research efforts and intervention strategies. + Copyright © 2017 Netto et al. + + + + Netto + Eduardo Martins + EM + + Hospital Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, Brazil. + + + Instituto Brasileiro para a Investigação da Tuberculose/Fundação José Silveira (IBIT/FJS), Salvador, Brazil. + + + + Moreira-Soto + Andres + A + + Institute of Virology, University of Bonn Medical Centre, Bonn, Germany. + + + + Pedroso + Celia + C + + Hospital Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, Brazil. + + + + Höser + Christoph + C + + Institute for Hygiene and Public Health, GeoHealth Centre, WHO Collaborating Centre for Health Promoting Water Management & Risk Communication, University of Bonn, Bonn, Germany. + + + + Funk + Sebastian + S + + Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom. + + + + Kucharski + Adam J + AJ + + Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom. + + + + Rockstroh + Alexandra + A + + Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany. + + + + Kümmerer + Beate M + BM + + Institute of Virology, University of Bonn Medical Centre, Bonn, Germany. + + + German Centre for Infection Research (DZIF), Germany. + + + + Sampaio + Gilmara Souza + GS + + Hospital Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, Brazil. + + + + Luz + Estela + E + + Hospital Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, Brazil. + + + + Vaz + Sara Nunes + SN + + Hospital Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, Brazil. + + + + Dias + Juarez Pereira + JP + + Hospital Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, Brazil. + + + + Bastos + Fernanda Anjos + FA + + Maternidade Climério de Oliveira, Universidade Federal da Bahia, Salvador, Brazil. + + + + Cabral + Renata + R + + Maternidade Climério de Oliveira, Universidade Federal da Bahia, Salvador, Brazil. + + + + Kistemann + Thomas + T + + Institute for Hygiene and Public Health, GeoHealth Centre, WHO Collaborating Centre for Health Promoting Water Management & Risk Communication, University of Bonn, Bonn, Germany. + + + + Ulbert + Sebastian + S + + Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany. + + + + de Lamballerie + Xavier + X + + Aix Marseille Université, IRD French Institute of Research for Development, EHESP French 19 School of Public Health, EPV UMR_D 190 "Emergence des Pathologies Virales," Marseille, France. + + + IHU Institute hospitalo-universitaire Méditerranée Infection, APHM Public Hospitals of Marseille 21, Marseille, France. + + + + Jaenisch + Thomas + T + + German Centre for Infection Research (DZIF), Germany. + + + Section Clinical Tropical Medicine, Department for Infectious Diseases, INF 324, Heidelberg University Hospital, Heidelberg, Germany. + + + + Brady + Oliver J + OJ + + Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom. + + + + Drosten + Christian + C + + German Centre for Infection Research (DZIF), Germany. + + + Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany. + + + + Sarno + Manoel + M + + Hospital Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, Brazil. + + + Maternidade Climério de Oliveira, Universidade Federal da Bahia, Salvador, Brazil. + + + + Brites + Carlos + C + + Hospital Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, Brazil crbrites@ufba.br felix.drexler@charite.de. + + + + Drexler + Jan Felix + JF + + Institute of Virology, University of Bonn Medical Centre, Bonn, Germany crbrites@ufba.br felix.drexler@charite.de. + + + German Centre for Infection Research (DZIF), Germany. + + + Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany. + + + + eng + + Journal Article + + + 2017 + 11 + 14 + +
+ + United States + MBio + 101519231 + + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Braz J Infect Dis. 2017 Jul - Aug;21(4):481-483 + 28549857 + + + Euro Surveill. 2016 Apr 21;21(16): + 27126052 + + + BMC Med. 2015 Apr 30;13:102 + 25976325 + + + Emerg Microbes Infect. 2017 Nov 8;6(11):e99 + 29116222 + + + Nature. 2016 Jul 25;535(7613):475-6 + 27466104 + + + Science. 2016 Jul 22;353(6297):353-4 + 27417493 + + + Bull World Health Organ. 2016 Dec 1;94(12 ):880-892 + 27994281 + + + Epidemics. 2016 Dec;17 :50-55 + 27846442 + + + Acta Trop. 2010 Mar;113(3):234-40 + 19896921 + + + N Engl J Med. 2016 Jul 28;375(4):396-8 + 27331661 + + + J Clin Microbiol. 2017 Jul;55(7):2127-2136 + 28446573 + + + Science. 2016 Aug 12;353(6300):aaf8160 + 27417495 + + + Int J Epidemiol. 2009 Oct;38(5):1285-96 + 19656772 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + PLoS Negl Trop Dis. 2016 Mar 03;10(3):e0004543 + 26938868 + + + Arch Pathol Lab Med. 2017 Jan;141(1):60-67 + 27763787 + + + Am J Public Health. 2016 Apr;106(4):598-600 + 26959258 + + + Nat Microbiol. 2016 Jul 25;1(9):16126 + 27562260 + + + Blood. 2017 Jan 12;129(2):263-266 + 27827826 + + + Neurology. 2009 Sep 15;73(11):887-97 + 19752457 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + J Gen Virol. 1989 Jan;70 ( Pt 1):37-43 + 2543738 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + Nature. 2017 Jun 15;546(7658):406-410 + 28538727 + + + N Engl J Med. 2016 Oct 20;375(16):1598-1601 + 27579558 + + + Lancet. 2016 May 21;387(10033):2125-2132 + 26993883 + + + PLoS Negl Trop Dis. 2016 May 17;10 (5):e0004726 + 27186984 + + + F1000Res. 2016 Jan 19;5:null + 26918158 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + Elife. 2016 Apr 19;5:null + 27090089 + + + J Med Virol. 2017 Aug;89(8):1477-1479 + 28229481 + + + Lancet. 2016 Jul 23;388(10042):338-339 + 27477157 + + + Nature. 2017 Jun 15;546(7658):411-415 + 28538734 + + + Euro Surveill. 2016 Dec 15;21(50): + 28006649 + + + PLoS Negl Trop Dis. 2017 Jan 23;11(1):e0005334 + 28114414 + + + Ultrasound Obstet Gynecol. 2017 Jun;49(6):729-736 + 28078779 + + + Emerg Infect Dis. 2017 Jan;23 (1):91-94 + 27618573 + + + Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):8384-8389 + 28716913 + + + Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7852-7 + 27354515 + + + Lancet. 2015 Jul 18;386(9990):243-4 + 26194519 + + + PLoS Curr. 2016 Feb 01;8:null + 27330849 + + + Bull World Health Organ. 2017 Mar 1;95(3):191-198 + 28250532 + + + Emerg Infect Dis. 2017 May;23 (5):773-781 + 28418292 + + + Sci Rep. 2016 Dec 19;6:39384 + 27991555 + + + PLoS Negl Trop Dis. 2017 Jun 29;11(6):e0005698 + 28662031 + + + PLoS Negl Trop Dis. 2015 Nov 13;9(11):e0004218 + 26565964 + + + Viruses. 2015 Nov 17;7(11):5902-7 + 26593936 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Zika virus + microcephaly + risk factors + serology + socioeconomic status + +
+ + + + 2017 + 11 + 16 + 6 + 0 + + + 2017 + 11 + 16 + 6 + 0 + + + 2017 + 11 + 16 + 6 + 0 + + + epublish + + 29138300 + mBio.01390-17 + 10.1128/mBio.01390-17 + PMC5686533 + + +
+ + + + + 29133154 + + 2018 + 02 + 13 + +
+ + 1469-0691 + + + 2017 + Nov + 10 + + + Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases + Clin. Microbiol. Infect. + + Adverse birth outcomes associated with Zika virus exposure during pregnancy in São José do Rio Preto, Brazil. + S1198-743X(17)30634-1 + 10.1016/j.cmi.2017.11.004 + + We aimed to report the first 54 cases of pregnant women infected by Zika virus (ZIKV) and their virologic and clinical outcomes, as well as their newborns' outcomes, in 2016, after the emergence of ZIKV in dengue-endemic areas of São Paulo, Brazil. + This descriptive study was performed from February to October 2016 on 54 quantitative real-time PCR ZIKV-positive pregnant women identified by the public health authority of São José do Rio Preto, São Paulo, Brazil. The women were followed and had clinical and epidemiologic data collected before and after birth. Adverse outcomes in newborns were analysed and reported. Urine or blood samples from newborns were collected to identify ZIKV infection by reverse transcription PCR (RT-PCR). + A total of 216 acute Zika-suspected pregnant women were identified, and 54 had the diagnosis confirmed by RT-PCR. None of the 54 women miscarried. Among the 54 newborns, 15 exhibited adverse outcomes at birth. The highest number of ZIKV infections occurred during the second and third trimesters. No cases of microcephaly were reported, though a broad clinical spectrum of outcomes, including lenticulostriate vasculopathy, subependymal cysts, and auditory and ophthalmologic disorders, were identified. ZIKV RNA was detected in 18 of 51 newborns tested and in eight of 15 newborns with adverse outcomes. + Although other studies have associated many newborn outcomes to ZIKV infection during pregnancy, these same adverse outcomes were rare or nonexistent in this study. The clinical presentation the newborns we studied was mild compared to other reports, suggesting that there is significant heterogeneity in congenital Zika infection. + Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. + + + + Nogueira + M L + ML + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. Electronic address: mnogueira@famerp.br. + + + + Nery Júnior + N R R + NRR + + Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil. + + + + Estofolete + C F + CF + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Bernardes Terzian + A C + AC + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Guimarães + G F + GF + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Zini + N + N + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Alves da Silva + R + R + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Dutra Silva + G C + GC + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Junqueira Franco + L C + LC + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Rahal + P + P + + São Paulo State University, São José do Rio Preto, São Paulo, Brazil. + + + + Bittar + C + C + + São Paulo State University, São José do Rio Preto, São Paulo, Brazil. + + + + Carneiro + B + B + + São Paulo State University, São José do Rio Preto, São Paulo, Brazil. + + + + Vasconcelos + P F C + PFC + + Evandro Chagas Institute, Ananindeua, Pará, Brazil. + + + + Freitas Henriques + D + D + + Evandro Chagas Institute, Ananindeua, Pará, Brazil. + + + + Barbosa + D M U + DMU + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + Lopes Rombola + P + P + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + de Grande + L + L + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + Negri Reis + A F + AF + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + Palomares + S A + SA + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + Wakai Catelan + M + M + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + Cruz + L E A A + LEAA + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + Necchi + S H + SH + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + Mendonça + R C V + RCV + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + Penha Dos Santos + I N + IN + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + Alavarse Caron + S B + SB + + Health Secretariat, São José do Rio Preto, São Paulo, Brazil. + + + + Costa + F + F + + Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil; Federal University of Bahia, Salvador, Bahia, Brazil; Yale School of Public Health, New Haven, CT, USA. + + + + Bozza + F A + FA + + Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Soares de Souza + A + A + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Brandão de Mattos + C C + CC + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + de Mattos + L C + LC + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Vasilakis + N + N + + University of Texas Medical Branch (UTMB), Galveston, TX, USA. + + + + Oliani + A H + AH + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Vaz Oliani + D C M + DCM + + São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil. + + + + Ko + A I + AI + + Yale School of Public Health, New Haven, CT, USA. + + + + eng + + Journal Article + + + 2017 + 11 + 10 + +
+ + England + Clin Microbiol Infect + 9516420 + 1198-743X + + + Adverse outcome + Arbovirus + Birth + Pregnancy + Zika virus + +
+ + + + 2017 + 10 + 15 + + + 2017 + 10 + 29 + + + 2017 + 11 + 02 + + + 2017 + 11 + 15 + 6 + 0 + + + 2017 + 11 + 15 + 6 + 0 + + + 2017 + 11 + 15 + 6 + 0 + + + aheadofprint + + 29133154 + S1198-743X(17)30634-1 + 10.1016/j.cmi.2017.11.004 + + +
+ + + + + 29127595 + + 2018 + 01 + 19 + +
+ + 1433-0350 + + 34 + 1 + + 2018 + Jan + + + Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery + Childs Nerv Syst + + Neurological manifestations of congenital Zika virus infection. + + 73-78 + + 10.1007/s00381-017-3634-4 + + In 2015, it was observed a rise in the number of microcephalic newborns associated with a history of non-specific febrile sickness and rash during pregnancy in Brazil. Since then, microcephaly has emerged as a public health concern. A few months after, the causal relation between congenital microcephaly and the Zika virus was discovered. Zika virus, an arbovirus, is a new TORCH member that leads to congenital infection through vertical transmission and harms the developing brain, disrupting synaptogenesis, and causing other central nervous system lesions. + The purpose of this article is to report the congenital Zika syndrome (CZS) and to emphasize the need for follow-up of the affected children to better know the evolutionary history of this new agent and to optimize the provision of healthcare and improve the quality of life of these patients. + We review the most relevant literature about clinical manifestations and neuroimaging findings related to neurotropism of Zika virus to characterize the congenital Zika syndrome and suggest the systematization of some exams and procedures to evaluate children exposed to ZIKV with or without microcephaly, according to the author's own experience. + Vertical ZIKV infection can cause a wide spectrum of neurological manifestations that go beyond microcephaly, and even the non-microcephalic child should be followed during the first years of life, because infection may be asymptomatic or lead to neuropsicomotor delay, epilepsy, and visual abnormalities. The appropriate prospective multidisciplinary follow-up of these patients aims to understand the natural history of this new agent and to provide a better development and quality of life for them and their families. + + + + Saad + Tania + T + + Division of Pediatric Neurology, National Institute of Women, Children and Adolescents Health Fernandes Figueira/FIOCRUZ, 716 Rui Barbosa Avenue, Rio de Janeiro, 22250-020, Brazil. tsaadmd@gmail.com. + + + Estácio de Sá University, Rio de Janeiro, Brazil. tsaadmd@gmail.com. + + + + PennaeCosta + Alessandra Augusta + AA + + Division of Pediatric Neurology, National Institute of Women, Children and Adolescents Health Fernandes Figueira/FIOCRUZ, 716 Rui Barbosa Avenue, Rio de Janeiro, 22250-020, Brazil. + + + + de Góes + Fernanda Veiga + FV + + Division of Pediatric Neurology, National Institute of Women, Children and Adolescents Health Fernandes Figueira/FIOCRUZ, 716 Rui Barbosa Avenue, Rio de Janeiro, 22250-020, Brazil. + + + + de Freitas + Marcela + M + + Division of Pediatric Neurology, National Institute of Women, Children and Adolescents Health Fernandes Figueira/FIOCRUZ, 716 Rui Barbosa Avenue, Rio de Janeiro, 22250-020, Brazil. + + + + de Almeida + Julia Valeriano + JV + + Division of Pediatric Neurology, National Institute of Women, Children and Adolescents Health Fernandes Figueira/FIOCRUZ, 716 Rui Barbosa Avenue, Rio de Janeiro, 22250-020, Brazil. + + + + de Santa Ignêz + Lúcio José + LJ + + Division of Pediatric Neurology, National Institute of Women, Children and Adolescents Health Fernandes Figueira/FIOCRUZ, 716 Rui Barbosa Avenue, Rio de Janeiro, 22250-020, Brazil. + + + + Amancio + Ana Paula + AP + + Division of Pediatric Neurology, National Institute of Women, Children and Adolescents Health Fernandes Figueira/FIOCRUZ, 716 Rui Barbosa Avenue, Rio de Janeiro, 22250-020, Brazil. + + + + Alvim + Renata Joviano + RJ + + Division of Pediatric Neurology, National Institute of Women, Children and Adolescents Health Fernandes Figueira/FIOCRUZ, 716 Rui Barbosa Avenue, Rio de Janeiro, 22250-020, Brazil. + + + + Antunes Kramberger + Ludmilla Athayde + LA + + Division of Pediatric Neurology, National Institute of Women, Children and Adolescents Health Fernandes Figueira/FIOCRUZ, 716 Rui Barbosa Avenue, Rio de Janeiro, 22250-020, Brazil. + + + + eng + + Journal Article + + + 2017 + 11 + 10 + +
+ + Germany + Childs Nerv Syst + 8503227 + 0256-7040 + + + + PLoS Negl Trop Dis. 2016 Aug 25;10 (8):e0004877 + 27560129 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Acta Neuropathol. 2017 Jun;133(6):983-999 + 28332092 + + + Dev Psychobiol. 2005 Nov;47(3):230-42 + 16252291 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Neurology. 2016 Jul 5;87(1):118-9 + 27378805 + + + JAMA Pediatr. 2017 Sep 1;171(9):847-854 + 28715527 + + + N Engl J Med. 2016 Oct 20;375(16):1598-1601 + 27579558 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + JAMA Pediatr. 2017 Mar 1;171(3):288-295 + 27812690 + + + Lancet. 2016 Apr 2;387(10026):1481 + 26946926 + + + BMJ. 2016 Aug 09;354:i3899 + 27509902 + + + Emerg Infect Dis. 2016 Nov;22(11):1953-1956 + 27767931 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Arch Dis Child. 2013 Sep;98(9):707-13 + 23814088 + + + N Engl J Med. 2016 Apr 21;374(16):1595-6 + 26958738 + + + + Congenital Zika virus syndrome + Microcephaly + Neurological manifestations + Zika virus + +
+ + + + 2017 + 10 + 03 + + + 2017 + 10 + 16 + + + 2017 + 11 + 12 + 6 + 0 + + + 2017 + 11 + 12 + 6 + 0 + + + 2017 + 11 + 12 + 6 + 0 + + + ppublish + + 29127595 + 10.1007/s00381-017-3634-4 + 10.1007/s00381-017-3634-4 + + +
+ + + + + 29110197 + + 2018 + 01 + 14 + +
+ + 1433-0350 + + 34 + 1 + + 2018 + Jan + + + Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery + Childs Nerv Syst + + Zika virus infection in children: epidemiology and clinical manifestations. + + 63-71 + + 10.1007/s00381-017-3635-3 + + The purpose of this review is to comprehensively review Congenital Zika Syndrome in regard to their epidemiology and clinical manifestations. + This subject review of congenital Zika syndrome was composed after conducting a thorough review of the available literature on this topic using PubMed and other primary sources. + The first epidemic of Zika virus infection in Brazil was followed by an unexpected sharp increase in the incidence of infants born with microcephaly and the description of a new disease, the congenital Zika syndrome. This review focuses on the epidemiological and clinical aspects of Zika infection in children. We conducted a brief historical account of the virus description in 1947, the rare cases of Zika infection occurring up to 2007, and the first epidemics in the Pacific between 2007 and 2014. We also discussed the isolation of the virus in Brazil in 2015 and its spread in the Americas, the microcephaly outbreak in Brazil and its association with Zika virus, and the current epidemiological panorama. We address the known clinical spectrum of Zika virus infection in the pediatric population, including manifestations of acute infection and congenital Zika syndrome, with emphasis on cranial, ophthalmic, and orthopedic abnormalities. + While much has been learned about congenital Zika syndrome, the full spectrum of this infection is not yet known. This review is based on current, limited data about Zika vírus infection. As more information becomes available, we will have a more accurate picture of this new disease. + + + + da Silva Pone + Marcos Vinicius + MV + + Pediatric Infectious Diseases Unit, National Institute of Women, Children and Adolescents Health Fernandes Figueira (IFF)/Oswaldo Cruz Foundation (FIOCRUZ), Av. Rui Barbosa 716, Rio de Janeiro, 22250-020, Brazil. marcosvpone@gmail.com. + + + + Moura Pone + Sheila + S + + Pediatric Infectious Diseases Unit, National Institute of Women, Children and Adolescents Health Fernandes Figueira (IFF)/Oswaldo Cruz Foundation (FIOCRUZ), Av. Rui Barbosa 716, Rio de Janeiro, 22250-020, Brazil. + + + + Araujo Zin + Andrea + A + + Clinical Research Unit, National Institute of Women, Children and Adolescents Health Fernandes Figueira (IFF)/Oswaldo Cruz Foundation (FIOCRUZ), Av. Rui Barbosa 716, Rio de Janeiro, 22250-020, Brazil. + + + + Barros Mendes + Pedro Henrique + PH + + Orthopedic Unit, National Institute of Women, Children and Adolescents Health Fernandes Figueira (IFF)/Oswaldo Cruz Foundation (FIOCRUZ), Av. Rui Barbosa 716, Rio de Janeiro, 22250-020, Brazil. + + + + Senra Aibe + Mitsue + M + + Pediatric Infectious Diseases Unit, National Institute of Women, Children and Adolescents Health Fernandes Figueira (IFF)/Oswaldo Cruz Foundation (FIOCRUZ), Av. Rui Barbosa 716, Rio de Janeiro, 22250-020, Brazil. + + + + Barroso de Aguiar + Elisa + E + + Pediatric Infectious Diseases Unit, National Institute of Women, Children and Adolescents Health Fernandes Figueira (IFF)/Oswaldo Cruz Foundation (FIOCRUZ), Av. Rui Barbosa 716, Rio de Janeiro, 22250-020, Brazil. + + + + de Oliveira Gomes da Silva + Tallita + T + + Pediatric Infectious Diseases Unit, National Institute of Women, Children and Adolescents Health Fernandes Figueira (IFF)/Oswaldo Cruz Foundation (FIOCRUZ), Av. Rui Barbosa 716, Rio de Janeiro, 22250-020, Brazil. + + + + eng + + Journal Article + + + 2017 + 11 + 06 + +
+ + Germany + Childs Nerv Syst + 8503227 + 0256-7040 + + + Arthrogryposis + Congenital abnormalities + Epidemiology + Eye diseases + Signs and symptoms + Zika virus + +
+ + + + 2017 + 10 + 02 + + + 2017 + 10 + 16 + + + 2017 + 11 + 8 + 6 + 0 + + + 2017 + 11 + 8 + 6 + 0 + + + 2017 + 11 + 8 + 6 + 0 + + + ppublish + + 29110197 + 10.1007/s00381-017-3635-3 + 10.1007/s00381-017-3635-3 + + +
+ + + + + 29110196 + + 2018 + 01 + 14 + +
+ + 1433-0350 + + 34 + 1 + + 2018 + Jan + + + Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery + Childs Nerv Syst + + Challenges for molecular and serological ZIKV infection confirmation. + + 79-84 + + 10.1007/s00381-017-3641-5 + + Zika Virus (ZIKV), member of Flaviviridae family and Flavivirus genus, has recently emerged as international public health emergency after its association with neonatal microcephaly cases. Clinical diagnosis hindrance involves symptom similarities produced by other arbovirus infections, therefore laboratory confirmation is of paramount importance. + The most reliable test available is based on ZIKV RNA detection from body fluid samples. However, short viremia window periods and asymptomatic infections diminish the success rate for RT-PCR positivity. Beyond molecular detection, all serology tests in areas where other Flavivirus circulates proved to be a difficult task due to the broad range of cross-reactivity, especially with dengue pre-exposed individuals. + Altogether, lack of serological diagnostic tools brings limitations to any retrospective evaluation. Those studies are central in the context of congenital infection that could occur asymptomatically and mask prevalence and risk rates. + + + + de Vasconcelos + Zilton Farias Meira + ZFM + + Fernandes Figueira Institute, Fiocruz, Avenida Rui Barbosa 716, Flamengo, Rio de Janeiro, 22250-020, Brazil. zvasconcelos@iff.fiocruz.br. + + + + Azevedo + Renata Campos + RC + + Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Thompson + Nathália + N + + Fernandes Figueira Institute, Fiocruz, Avenida Rui Barbosa 716, Flamengo, Rio de Janeiro, 22250-020, Brazil. + + + + Gomes + Leonardo + L + + Fernandes Figueira Institute, Fiocruz, Avenida Rui Barbosa 716, Flamengo, Rio de Janeiro, 22250-020, Brazil. + + + + Guida + Letícia + L + + Fernandes Figueira Institute, Fiocruz, Avenida Rui Barbosa 716, Flamengo, Rio de Janeiro, 22250-020, Brazil. + + + + Moreira + Maria Elisabeth Lopes + MEL + + Fernandes Figueira Institute, Fiocruz, Avenida Rui Barbosa 716, Flamengo, Rio de Janeiro, 22250-020, Brazil. + + + + eng + + + NCT03255369 + National Institutes of Health + United States + + + PIP II + Fernandes Figueira Institute Research Program + United States + + + E-26/201.840/2017 + Rio de Janeiro State Research Grant + United States + + + 441098/2016-9 + Brazilian National Research Grant + United States + + + Plano Brasil sem Miséria + CAPES/FIOCRUZ + United States + + + + Journal Article + + + 2017 + 11 + 06 + +
+ + Germany + Childs Nerv Syst + 8503227 + 0256-7040 + + + Arboviruses + Microcephaly + PRNT + RT-PCR + Serology + Vertical transmission + ZIKV + +
+ + + + 2017 + 10 + 09 + + + 2017 + 10 + 17 + + + 2017 + 11 + 8 + 6 + 0 + + + 2017 + 11 + 8 + 6 + 0 + + + 2017 + 11 + 8 + 6 + 0 + + + ppublish + + 29110196 + 10.1007/s00381-017-3641-5 + 10.1007/s00381-017-3641-5 + + +
+ + + + + 29101612 + + 2018 + 01 + 19 + +
+ + 1433-0350 + + 34 + 1 + + 2018 + Jan + + + Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery + Childs Nerv Syst + + The congenital Zika virus infection: still a puzzle. + + 61-62 + + 10.1007/s00381-017-3647-z + + As a new disease, some features of the congenital Zika virus infection are not yet fully understood. The current Brazilian outbreak brought up an unexpected increase in the number of microcephaly cases as this strain is essentially neurotropic and associated with devastating effects on the developing central nervous system. + This focus session aims to discuss the several issues related to the epidemiology, diagnosis, clinical features, and treatment of the congenital Zika virus infection. + + + + Salomão + José Francisco M + JFM + + Fernandes Figueira Institute, Oswaldo Cruz Foundation (IFF-Fiocruz), Rio de Janeiro, Brazil. jfsalomao@terra.com.br. + + + + eng + + Journal Article + + + 2017 + 11 + 03 + +
+ + Germany + Childs Nerv Syst + 8503227 + 0256-7040 + + + + Childs Nerv Syst. 2018 Jan;34(1):101-106 + 29086073 + + + Virology (Auckl). 2017 May 18;8:1178122X17708993 + 28579764 + + + Acta Neuropathol. 2017 Jun;133(6):983-999 + 28332092 + + + Clin Pediatr (Phila). 2016 Jul;55(8):698-700 + 27000068 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + + Congenital Zika virus infection + Microcephaly + ZIKV outbreak + +
+ + + + 2017 + 09 + 29 + + + 2017 + 10 + 18 + + + 2017 + 11 + 5 + 6 + 0 + + + 2017 + 11 + 5 + 6 + 0 + + + 2017 + 11 + 5 + 6 + 0 + + + ppublish + + 29101612 + 10.1007/s00381-017-3647-z + 10.1007/s00381-017-3647-z + + +
+ + + + + 29093650 + + 2017 + 12 + 19 + +
+ + 1598-2629 + + 17 + 5 + + 2017 + Oct + + + Immune network + Immune Netw + + Understanding the Pathogenesis of Zika Virus Infection Using Animal Models. + + 287-297 + + 10.4110/in.2017.17.5.287 + + Zika virus (ZIKV) is a member ofFlaviviridaefamily that has emerged as a pathogen of significant public health importance. The rapid expansion of ZIKV in the South and Central America has recently gained medical attention emphasizing the capacity of ZIKV to spread to non-endemic regions. ZIKV infection during pregnancy has been demonstrated to cause microcephaly and other fetal developmental abnormalities. An increased incidence of Guillain-Barre syndrome, an immune mediated neuropathy of the peripheral nervous system, has also been reported in ZIKV-infected patients in French Polynesia and Brazil. No effective therapies currently exist for treating patients infected with ZIKV. Despite the relatively short time interval, an intensive effort by the global scientific community has resulted in development of animal models to study multiple aspects of ZIKV biology. Several animal models have been established to investigate pathogenesis of ZIKV in adults, pregnant mothers, and developing fetuses. Here we review the remarkable progress of newly developed small and large animal models for understanding ZIKV pathogenesis. + + + + Krause + Keeton K + KK + + Department of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA. + + + + Azouz + Francine + F + + Department of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA. + + + + Shin + Ok Sarah + OS + + Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Korea. + + + + Kumar + Mukesh + M + + Department of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA. + + + + eng + + + P30 GM114737 + GM + NIGMS NIH HHS + United States + + + R21 NS099838 + NS + NINDS NIH HHS + United States + + + R21 OD024896 + OD + NIH HHS + United States + + + + Journal Article + Review + + + 2017 + 10 + 19 + +
+ + Korea (South) + Immune Netw + 101137270 + 1598-2629 + + + + Cell Host Microbe. 2016 Jun 8;19(6):882-90 + 27212660 + + + N Engl J Med. 2016 Jun 2;374(22):2195-8 + 27074370 + + + Nature. 2016 Aug 25;536(7617):474-8 + 27355570 + + + Clin Infect Dis. 2016 Sep 15;63(6):805-11 + 27193747 + + + Science. 2016 Sep 9;353(6304):1129-32 + 27492477 + + + MMWR Morb Mortal Wkly Rep. 2016 Sep 30;65(38):1032-8 + 27684886 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + PLoS Negl Trop Dis. 2016 Aug 25;10 (8):e0004877 + 27560129 + + + J Virol. 2017 Mar 29;91(8): + 28148798 + + + Antiviral Res. 2009 Jun;82(3):95-102 + 19428599 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Front Microbiol. 2016 Dec 19;7:2028 + 28066354 + + + PLoS Negl Trop Dis. 2014 Feb 06;8(2):e2681 + 24516683 + + + PLoS Pathog. 2017 Feb 2;13(2):e1006164 + 28152048 + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + Placenta. 2007 Aug-Sep;28(8-9):812-5 + 17382996 + + + Cell Stem Cell. 2016 Nov 3;19(5):593-598 + 27545505 + + + Nat Rev Microbiol. 2013 Feb;11(2):115-28 + 23321534 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 Jul 22;353(6297):353-4 + 27417493 + + + Clin Infect Dis. 2017 Jan 15;64(2):211-213 + 27986688 + + + Nat Med. 2016 Dec;22(12 ):1448-1455 + 27694931 + + + Biotechnol Adv. 2017 Sep 12;:null + 28916391 + + + PLoS Negl Trop Dis. 2017 Jan 9;11(1):e0005296 + 28068342 + + + Adv Immunol. 2007;96:41-101 + 17981204 + + + Antimicrob Agents Chemother. 2002 Apr;46(4):977-81 + 11897578 + + + Cell. 2016 Dec 1;167(6):1511-1524.e10 + 27884405 + + + Nat Commun. 2017 Jun 07;8:15743 + 28589934 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + MMWR Morb Mortal Wkly Rep. 2016 Aug 05;65(30):774-9 + 27490087 + + + Lancet Infect Dis. 2017 Mar;17 (3):255 + 28244380 + + + Antiviral Res. 2013 Nov;100(2):446-54 + 24084488 + + + Bull Soc Pathol Exot Filiales. 1982 May-Jul;75(3):262-6 + 6809352 + + + Antivir Ther. 2017;22(7):613-618 + 28694390 + + + PLoS Pathog. 2017 Mar 9;13(3):e1006258 + 28278235 + + + Cell Rep. 2016 Sep 20;16(12 ):3208-3218 + 27612415 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Antiviral Res. 2017 Sep;145:82-86 + 28736077 + + + Sci Rep. 2017 Jan 18;7:40920 + 28098253 + + + Arch Virol. 2017 Sep;162(9):2847-2853 + 28597088 + + + PLoS Negl Trop Dis. 2016 Dec 20;10 (12 ):e0005262 + 27997547 + + + Nat Med. 2016 Nov;22(11):1256-1259 + 27618651 + + + Antiviral Res. 2017 Jan;137:134-140 + 27902933 + + + PLoS Negl Trop Dis. 2016 May 10;10 (5):e0004695 + 27163257 + + + Cell Rep. 2016 Dec 20;17 (12 ):3091-3098 + 28009279 + + + Int J Infect Dis. 2017 Feb;55:29-30 + 27988410 + + + Exp Toxicol Pathol. 2017 Feb;69(2):63-71 + 27899230 + + + Nat Commun. 2016 Jun 28;7:12204 + 27352279 + + + Science. 2016 Oct 14;354(6309):237-240 + 27708058 + + + PLoS Negl Trop Dis. 2016 Apr 19;10(4):e0004682 + 27093158 + + + EBioMedicine. 2016 Oct;12 :170-177 + 27693104 + + + Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):8847-8852 + 28765371 + + + Antiviral Res. 2017 Jan;137:14-22 + 27838352 + + + MMWR Morb Mortal Wkly Rep. 2016 Apr 01;65(12):323-5 + 27032078 + + + Cell. 2016 Aug 11;166(4):1016-1027 + 27475895 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + Saudi Med J. 2016 Apr;37(4):470-1 + 27508290 + + + MMWR Morb Mortal Wkly Rep. 2016 Sep 16;65(36):983-6 + 27631604 + + + PLoS Negl Trop Dis. 2016 Dec 2;10 (12 ):e0005168 + 27911897 + + + PLoS Negl Trop Dis. 2016 May 05;10 (5):e0004658 + 27149521 + + + Nature. 2016 Dec 15;540(7633):438-442 + 27798603 + + + PLoS Pathog. 2016 Nov 17;12 (11):e1006004 + 27855206 + + + Nature. 2016 Dec 15;540(7633):443-447 + 27819683 + + + Open Forum Infect Dis. 2016 Aug 30;3(4):ofw175 + 27747251 + + + Cell. 2016 May 19;165(5):1081-1091 + 27180225 + + + MBio. 2016 Jul 19;7(4):null + 27435464 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + J Hyg (Lond). 1979 Oct;83(2):213-9 + 489960 + + + Virology. 2006 Jan 5;344(1):119-30 + 16364743 + + + Cell. 2016 Aug 25;166(5):1247-1256.e4 + 27565347 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):55-8 + 26820163 + + + Virol J. 2017 Apr 11;14 (1):75 + 28399888 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + PLoS Pathog. 2017 May 25;13(5):e1006378 + 28542585 + + + Comp Med. 2008 Aug;58(4):324-40 + 18724774 + + + J Infect Dis. 2017 May 15;215(10 ):1546-1550 + 28398562 + + + J Gen Virol. 1976 Jan;30(1):123-30 + 1245842 + + + + Animal model + Etiology + Zika virus + + Conflict of Interest: The authors declared no potential conflicts of interest. +
+ + + + 2017 + 08 + 16 + + + 2017 + 10 + 06 + + + 2017 + 10 + 09 + + + 2017 + 11 + 3 + 6 + 0 + + + 2017 + 11 + 3 + 6 + 0 + + + 2017 + 11 + 3 + 6 + 1 + + + ppublish + + 29093650 + 10.4110/in.2017.17.5.287 + PMC5662778 + + +
+ + + + + 29091713 + + 2017 + 12 + 04 + + + 2017 + 12 + 19 + +
+ + 1935-2735 + + 11 + 11 + + 2017 + Nov + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + After the epidemic: Zika virus projections for Latin America and the Caribbean. + + e0006007 + + 10.1371/journal.pntd.0006007 + + Zika is one of the most challenging emergent vector-borne diseases, yet its future public health impact remains unclear. Zika was of little public health concern until recent reports of its association with congenital syndromes. By 3 August 2017 ∼217,000 Zika cases and ∼3,400 cases of associated congenital syndrome were reported in Latin America and the Caribbean. Some modelling exercises suggest that Zika virus infection could become endemic in agreement with recent declarations from the The World Health Organisation. + We produced high-resolution spatially-explicit projections of Zika cases, associated congenital syndromes and monetary costs for Latin America and the Caribbean now that the epidemic phase of the disease appears to be over. In contrast to previous studies which have adopted a modelling approach to map Zika potential, we project case numbers using a statistical approach based upon reported dengue case data as a Zika surrogate. Our results indicate that ∼12.3 (0.7-162.3) million Zika cases could be expected across Latin America and the Caribbean every year, leading to ∼64.4 (0.2-5159.3) thousand cases of Guillain-Barré syndrome and ∼4.7 (0.0-116.3) thousand cases of microcephaly. The economic burden of these neurological sequelae are estimated to be USD ∼2.3 (USD 0-159.3) billion per annum. + Zika is likely to have significant public health consequences across Latin America and the Caribbean in years to come. Our projections inform regional and federal health authorities, offering an opportunity to adapt to this public health challenge. + + + + Colón-González + Felipe J + FJ + http://orcid.org/0000-0002-9671-3405 + + School of Environmental Sciences, University of East Anglia, Norwich, Norfolk, United Kingdom. + + + + Peres + Carlos A + CA + + School of Environmental Sciences, University of East Anglia, Norwich, Norfolk, United Kingdom. + + + + Steiner São Bernardo + Christine + C + + Universidade do Estado de Mato Grosso, Rua São Pedro s/n, Cavalhada, Cáceres, Mato Grosso, Brazil. + + + + Hunter + Paul R + PR + + Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom. + + + + Lake + Iain R + IR + + School of Environmental Sciences, University of East Anglia, Norwich, Norfolk, United Kingdom. + + + + eng + + Journal Article + + + 2017 + 11 + 01 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + IM + + + PLoS Negl Trop Dis. 2016 Aug 26;10 (8):e0004968 + 27564232 + + + N Engl J Med. 2016 Sep 29;375(13):1212-6 + 27682032 + + + PLoS Negl Trop Dis. 2016 May 20;10 (5):e0004743 + 27205899 + + + PLoS Negl Trop Dis. 2013 Nov 14;7(11):e2503 + 24244765 + + + Am J Trop Med Hyg. 2004 Aug;71(2 Suppl):136-40 + 15331829 + + + Am J Trop Med Hyg. 2012 Nov;87(5):902-9 + 22987656 + + + Nature. 2012 Sep 13;489(7415):282-5 + 22951966 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Science. 2016 Jul 22;353(6297):353-4 + 27417493 + + + Nat Immunol. 2016 Aug 19;17(9):1010-2 + 27540984 + + + Travel Med Infect Dis. 2017 Jul - Aug;18:57-66 + 28487212 + + + Science. 2016 Aug 12;353(6300):aaf8160 + 27417495 + + + Euro Surveill. 2014 Oct 16;19(41):null + 25345518 + + + Am J Trop Med Hyg. 2011 May;84(5):757-63 + 21540386 + + + Am J Trop Med Hyg. 2010 Jan;82(1):128-35 + 20065008 + + + Sci Rep. 2015 Feb 16;5:8462 + 25684648 + + + PLoS Negl Trop Dis. 2013 Dec 19;7(12):e2520 + 24386496 + + + PLoS Negl Trop Dis. 2016 Dec 7;10 (12 ):e0005173 + 27926933 + + + Am J Public Health. 2016 Apr;106(4):598-600 + 26959258 + + + PLoS Negl Trop Dis. 2016 Mar 17;10(3):e0004551 + 26986468 + + + BMJ. 2016 Dec 14;355:i6716 + 27974296 + + + Nat Microbiol. 2016 Jul 25;1(9):16126 + 27562260 + + + Am J Stem Cells. 2017 Jul 25;6(2):13-22 + 28804687 + + + PLoS Negl Trop Dis. 2016 Dec 7;10 (12 ):e0005176 + 27926934 + + + Lancet. 2017 Nov 4;390(10107):2099-2109 + 28647173 + + + Nature. 2013 Apr 25;496(7446):504-7 + 23563266 + + + Am J Trop Med Hyg. 1987 Jan;36(1):143-52 + 3812879 + + + Am J Trop Med Hyg. 2005 Jun;72(6):786-91 + 15964964 + + + Proc Natl Acad Sci U S A. 2017 Jan 3;114(1):119-124 + 27994145 + + + J Microbiol. 2017 Feb;55(2):81-89 + 28120186 + + + Nature. 2016 Aug 4;536(7614):48-53 + 27338953 + + + Parasit Vectors. 2017 Jul 27;10 (1):356 + 28750651 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + Epidemiol Infect. 2009 Nov;137(11):1538-47 + 19371450 + + + PLoS Negl Trop Dis. 2015 May 07;9(5):e0003655 + 25951103 + + + N Engl J Med. 2016 Oct 20;375(16):1598-1601 + 27579558 + + + Am J Trop Med Hyg. 2012 Oct;87(4):584-93 + 23042846 + + + Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3233-8 + 24344270 + + + Proc Biol Sci. 1998 May 22;265(1399):847-54 + 9633110 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + Sci Rep. 2016 Jun 17;6:28070 + 27312324 + + + Elife. 2016 Apr 19;5:null + 27090089 + + + Euro Surveill. 2016 May 19;21(20): + 27239817 + + + Environ Health Perspect. 2001 Mar;109 Suppl 1:141-61 + 11250812 + + + Cell Rep. 2016 Aug 9;16(6):1485-1491 + 27481466 + + + Lancet. 2016 Apr 9;387(10027):1531-1539 + 26948433 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Science. 2016 Feb 5;351(6273):543-4 + 26912676 + + + Clin Microbiol Rev. 2009 Jan;22(1):13-36, Table of Contents + 19136431 + + + Trans R Soc Trop Med Hyg. 2015 May;109(5):303-12 + 25771261 + + + Nat Immunol. 2016 Sep;17 (9):1102-8 + 27339099 + + + Mem Inst Oswaldo Cruz. 2016 Sep;111(9):559-60 + 27653360 + + + MMWR Morb Mortal Wkly Rep. 2016 Jul 22;65(28):716-7 + 27442327 + + + Bioinformatics. 2001 Jun;17(6):520-5 + 11395428 + + + Lancet. 2015 Jul 18;386(9990):243-4 + 26194519 + + + Trop Med Int Health. 2010 May;15(5):619-31 + 20214764 + + + + + Aedes + virology + + + Animals + + + Caribbean Region + epidemiology + + + Disease Outbreaks + + + Endemic Diseases + + + Epidemics + + + Global Health + trends + + + Guillain-Barre Syndrome + epidemiology + virology + + + Humans + + + Latin America + epidemiology + + + Microcephaly + epidemiology + virology + + + Public Health + trends + + + World Health Organization + + + Zika Virus + isolation & purification + physiology + + + Zika Virus Infection + complications + congenital + economics + epidemiology + + +
+ + + + 2017 + 05 + 22 + + + 2017 + 10 + 03 + + + 2017 + 11 + 13 + + + 2017 + 11 + 2 + 6 + 0 + + + 2017 + 12 + 5 + 6 + 0 + + + 2017 + 11 + 2 + 6 + 0 + + + epublish + + 29091713 + 10.1371/journal.pntd.0006007 + PNTD-D-17-00777 + PMC5683651 + + +
+ + + + + 29086073 + + 2018 + 01 + 19 + +
+ + 1433-0350 + + 34 + 1 + + 2018 + Jan + + + Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery + Childs Nerv Syst + + Hydrocephalus associated to congenital Zika syndrome: does shunting improve clinical features? + + 101-106 + + 10.1007/s00381-017-3636-2 + + Congenital Zika syndrome (CZS) is a new entity with little information about its course and natural history. It is known that prenatal infection by Zika virus is associated to disrupted nervous system development, leading to typical neurological disabilities and deformities. Some children present progressive ventriculomegaly and hydrocephalus associated to aggravation of seizures and neurological impairment. The aim of this study is to evaluate the development of hydrocephalus and the impact of ventriculoperitoneal shunt insertion in the clinical condition of these children. + Data was obtained from chart review, direct interviews with patients' parents, direct neurological examination, and analysis of pre- and postoperative neuroimages. + A group of 115 patients had CZS diagnosis from November 2015 to July 2017. Among them, 21 (18.3%) patients had ventricular enlargement noted on follow-up CT scans. Six children (28.6%) underwent a ventriculoperitoneal shunt and all had some improvement after surgery concerning either waking time during the day and better interaction. Overall improvement was also noted in seizures. Spasticity decrease and more cervical control were also achieved. In two out of six cases, a slight increase in parenchymal length could be noted on the CT scans. + This series points out the possibility of hypertensive hydrocephalus development in CZS patients. Affected children may benefit from VP shunt insertion. These findings suggest a dual pathology association: fetal brain disruption and primary cortical malformation by the virus itself and hypertensive hydrocephalus. This is already seen in some cases of congenital rubella, toxoplasmosis, or cytomegalovirus-associated hydrocephalus. + + + + Jucá + Eduardo + E + + Universidade de Fortaleza (UNIFOR), Fortaleza, Ceará, Brazil. eduardojuca@gmail.com. + + + Hospital Infantil Albert Sabin, Fortaleza, Ceará, Brazil. eduardojuca@gmail.com. + + + Centro Universitário Christus, Fortaleza, Ceará, Brazil. eduardojuca@gmail.com. + + + + Pessoa + André + A + + Hospital Infantil Albert Sabin, Fortaleza, Ceará, Brazil. + + + Universidade Estadual do Ceará-UECE, Fortaleza, Brazil. + + + + Ribeiro + Erlane + E + + Hospital Infantil Albert Sabin, Fortaleza, Ceará, Brazil. + + + Centro Universitário Christus, Fortaleza, Ceará, Brazil. + + + + Menezes + Rafaela + R + + Centro Universitário Christus, Fortaleza, Ceará, Brazil. + + + + Kerbage + Saile + S + + Hospital Infantil Albert Sabin, Fortaleza, Ceará, Brazil. + + + + Lopes + Thayse + T + + Centro Universitário Christus, Fortaleza, Ceará, Brazil. + + + + Cavalcanti + Luciano Pamplona + LP + + Universidade Federal do Ceará, Fortaleza, Ceará, Brazil. + + + + eng + + Journal Article + + + 2017 + 10 + 30 + +
+ + Germany + Childs Nerv Syst + 8503227 + 0256-7040 + + + + J AAPOS. 2017 Aug;21(4):300-304.e1 + 28652051 + + + J Infect Dev Ctries. 2016 Feb 28;10 (2):116-20 + 26927450 + + + Neurol Med Chir (Tokyo). 2015 ;55(8):611-6 + 26226979 + + + MMWR Morb Mortal Wkly Rep. 2016 Dec 02;65(47):1343-1348 + 27906905 + + + Am J Med Genet A. 2017 Apr;173(4):841-857 + 28328129 + + + Neurol Clin. 2016 Nov;34(4):1049-1056 + 27719988 + + + DNA Cell Biol. 2016 Aug;35(8):367-72 + 27348136 + + + J Pediatr Neurosci. 2011 Oct;6(Suppl 1):S11-22 + 22069421 + + + Lancet. 2016 Jun 18;387(10037):2502 + 27287830 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + JAMA Pediatr. 2017 Mar 1;171(3):288-295 + 27812690 + + + AJNR Am J Neuroradiol. 1992 Mar-Apr;13(2):551-67 + 1566717 + + + Pediatr Neurol. 1985 Jan-Feb;1(1):42-7 + 2854733 + + + Neurol India. 2011 Nov-Dec;59(6):848-54 + 22234198 + + + JAMA Neurol. 2017 Jun 1;74(6):631-632 + 28418503 + + + J Venom Anim Toxins Incl Trop Dis. 2017 Mar 20;23 :15 + 28331488 + + + AJNR Am J Neuroradiol. 2003 Jan;24(1):28-32 + 12533323 + + + Childs Nerv Syst. 2016 Jun;32(6):1057-60 + 27080092 + + + Clin Infect Dis. 2015 Dec 15;61(12 ):1831-4 + 26405147 + + + Clin Perinatol. 2009 Sep;36(3):639-53 + 19732618 + + + Z Kinderchir. 1985 Dec;40 Suppl 1:10-1 + 3879067 + + + + Hydrocephalus + Microcephaly + Ventriculoperitoneal shunt + Zika virus + +
+ + + + 2017 + 10 + 09 + + + 2017 + 10 + 16 + + + 2017 + 11 + 1 + 6 + 0 + + + 2017 + 11 + 1 + 6 + 0 + + + 2017 + 11 + 1 + 6 + 0 + + + ppublish + + 29086073 + 10.1007/s00381-017-3636-2 + 10.1007/s00381-017-3636-2 + + +
+ + + + + 29067015 + + 2017 + 12 + 20 + +
+ + 1664-302X + + 8 + + 2017 + + + Frontiers in microbiology + Front Microbiol + + Serum Metabolic Alterations upon Zika Infection. + + 1954 + + 10.3389/fmicb.2017.01954 + + Zika virus (ZIKV) infection has recently emerged as a major concern worldwide due to its strong association with nervous system malformation (microcephaly) of fetuses in pregnant women infected by the virus. Signs and symptoms of ZIKV infection are often mistaken with other common viral infections. Since transmission may occur through biological fluids exchange and coitus, in addition to mosquito bite, this condition is an important infectious disease. Thus, understanding the mechanism of viral infection has become an important research focus, as well as providing potential targets for assertive clinical diagnosis and quality screening for hemoderivatives. Within this context, the present work analyzed blood plasma from 79 subjects, divided as a control group and a ZIKV-infected group. Samples underwent direct-infusion mass spectrometry and statistical analysis, where eight markers related to the pathophysiological process of ZIKV infection were elected and characterized. Among these, Angiotensin (1-7) and Angiotensin I were upregulated under infection, showing an attempt to induce autophagy of the infected cells. However, this finding is concerning about hypertensive individuals under treatment with inhibitors of the Renin-Angiotensin System (RAS), which could reduce this response against the virus and exacerbate the symptoms of the infection. Moreover, one of the most abundant glycosphingolipids in the nervous tissue, Ganglioside GM2, was also elected in the present study as an infection biomarker. Considered an important pathogen receptor at membrane's outer layer, this finding represents the importance of gangliosides for ZIKV infection and its association with brain tropism. Furthermore, a series of phosphatidylinositols were also identified as biomarkers, implying a significant role of the PI3K-AKT-mTOR Pathway in this mechanism. Finally, these pathways may also be understood as potential targets to be considered in pharmacological intervention studies on ZIKV infection management. + + + + Melo + Carlos Fernando O R + CFOR + + INNOVARE Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil. + + + + Delafiori + Jeany + J + + INNOVARE Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil. + + + + de Oliveira + Diogo N + DN + + INNOVARE Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil. + + + + Guerreiro + Tatiane M + TM + + INNOVARE Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil. + + + + Esteves + Cibele Z + CZ + + INNOVARE Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil. + + + + Lima + Estela de O + EO + + INNOVARE Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil. + + + + Pando-Robles + Victoria + V + + Unidad de Proteómica, Instituto Nacional de Salud Publica, Cuernavaca, Mexico. + + + + Catharino + Rodrigo R + RR + + INNOVARE Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil. + + + + Zika-Unicamp Network + + + eng + + Journal Article + + + 2017 + 10 + 10 + +
+ + Switzerland + Front Microbiol + 101548977 + 1664-302X + + + + Front Microbiol. 2017 Nov 29;8:2373 + 29211063 + + + PLoS Pathog. 2012;8(3):e1002584 + 22457619 + + + Cell Microbiol. 2014 Oct;16(10):1493-502 + 25131438 + + + Cell Stem Cell. 2016 Nov 3;19(5):663-671 + 27524440 + + + Med Clin North Am. 2017 Jan;101(1):129-137 + 27884224 + + + PLoS Negl Trop Dis. 2013 Aug 15;7(8):e2373 + 23967362 + + + Ann Transl Med. 2016 Nov;4(21):421 + 27942512 + + + Regul Pept. 1998 Nov 30;78(1-3):13-8 + 9879742 + + + Arch Virol. 2015 Jul;160(7):1687-92 + 25936955 + + + Clin Infect Dis. 2017 Jan 15;64(2):211-213 + 27986688 + + + Int J Biol Sci. 2016 May 25;12 (7):872-83 + 27313500 + + + Mol Cell Biol. 2005 Mar;25(5):1869-78 + 15713641 + + + Prog Lipid Res. 2016 Oct;64:123-137 + 27702593 + + + Nat Commun. 2014 May 06;5:3594 + 24800825 + + + Proc Natl Acad Sci U S A. 2011 May 31;108(22):9044-8 + 21571640 + + + Nat Protoc. 2011 Jun;6(6):743-60 + 21637195 + + + Euro Surveill. 2016 Jun 9;21(23 ): + 27311680 + + + Nat Rev Immunol. 2013 Oct;13(10):722-37 + 24064518 + + + Arch Pathol Lab Med. 2017 Jan;141(1):85-92 + 27788336 + + + Lancet Neurol. 2013 Dec;12(12):1180-8 + 24229616 + + + Clin Sci (Lond). 2013 Apr;124(7):443-56 + 23249272 + + + Nature. 2013 Apr 25;496(7446):504-7 + 23563266 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Curr Protoc Bioinformatics. 2016 Sep 07;55:14.10.1-14.10.91 + 27603023 + + + Curr Opin Nephrol Hypertens. 2011 Jan;20(1):62-8 + 21099686 + + + Clin Infect Dis. 2002 Apr 15;34(8):1150-3 + 11915007 + + + Autophagy. 2006 Jan-Mar;2(1):24-9 + 16874088 + + + PLoS One. 2011 Feb 18;6(2):e17174 + 21364758 + + + Hum Mol Genet. 2011 Mar 1;20(5):988-99 + 21159799 + + + Am J Physiol Regul Integr Comp Physiol. 2014 Jan 15;306(2):R91-101 + 24089380 + + + Hypertension. 2007 Jan;49(1):185-92 + 17116756 + + + Anal Chem. 2015 Apr 7;87(7):3585-92 + 25785304 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1154-63 + 17496209 + + + Sci Rep. 2016 Jan 27;6:19840 + 26813885 + + + BMC Med. 2016 Aug 03;14 (1):112 + 27487767 + + + BMC Infect Dis. 2013 Feb 08;13:77 + 23394216 + + + EMBO J. 2003 Sep 1;22(17):4346-55 + 12941687 + + + PLoS Med. 2008 Mar 18;5(3):e68 + 18351798 + + + Ann Clin Microbiol Antimicrob. 2016 Jul 22;15(1):42 + 27449770 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + J Clin Virol. 2016 Oct;83:66-71 + 27614319 + + + Microbiol Rev. 1983 Dec;47(4):596-620 + 6363900 + + + Lancet. 2016 Apr 9;387(10027):1531-1539 + 26948433 + + + Arch Virol. 2015 Nov;160(11):2861-5 + 26321474 + + + Parasitol Res. 2016 Nov;115(11):4107-4114 + 27412760 + + + Am J Hum Genet. 2005 May;76(5):717-28 + 15806441 + + + PLoS One. 2016 Oct 10;11(10 ):e0164377 + 27723844 + + + Brain. 2016 Jun;139(Pt 6):1622-5 + 27234059 + + + J Endocrinol. 2013 Jan 18;216(2):R1-R17 + 23092879 + + + Mass Spectrom Rev. 2014 Nov-Dec;33(6):471-500 + 24288070 + + + Eur Heart J. 2012 Aug;33(16):2088-97 + 22511654 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Zika virus + mass spectrometry + metabolomics + viromics + + + + Milanez + Guilherme P + GP + + + do Nascimento + Gabriela M + GM + + + Freitas + André R R + ARR + + + Angerami + Rodrigo + R + + + Costa + Fábio T Maranhão + FTM + + + Arns + Clarice W + CW + + + Resende + Mariangela R + MR + + + Amaral + Eliana + E + + + Junior + Renato P + RP + + + Ribeiro-do-Valle + Carolina C + CC + + + Milanez + Helaine + H + + + Moretti + Maria L + ML + + + Proenca-Modena + Jose L + JL + + + Pastore + Glaucia M + GM + + + Fertrin + Kleber Y + KY + + + Garcia + Márcia T + MT + + + Calil + Roseli + R + + + Júnior + João R B + JRB + + + Lajos + Giuliane J + GJ + + + Costa + Maria L + ML + + + da Silva + Marcos T N + MTN + + + Altemani + Albina + A + + + Coan + Ana C + AC + + + Colella-Santos + Maria F + MF + + + von Zuben + Andrea P B + APB + + + Vinolo + Marco A R + MAR + + + de Paula + Rosemeire F de O + RFO + + + Judice + Carla C + CC + + + Leite + Juliana A + JA + + + Caserta + Leonardo C + LC + + + de Moraes + Ana P + AP + + + Barnabé + Ana C S + ACS + + + da Soledade + Ana L R + ALR + + + Teixeira + Daniel A T + DAT + + + de Morais + Évellyn R + ÉR + + + Santos + Felipe R + FR + + +
+ + + + 2017 + 08 + 03 + + + 2017 + 09 + 22 + + + 2017 + 10 + 26 + 6 + 0 + + + 2017 + 10 + 27 + 6 + 0 + + + 2017 + 10 + 27 + 6 + 1 + + + epublish + + 29067015 + 10.3389/fmicb.2017.01954 + PMC5641361 + + +
+ + + + + 29058664 + + 2018 + 01 + 19 + +
+ + 1080-6059 + + 24 + 1 + + 2018 + Jan + + + Emerging infectious diseases + Emerging Infect. Dis. + + Expected Duration of Adverse Pregnancy Outcomes after Zika Epidemic. + 10.3201/eid2401.170482 + + Evidence is increasing that Zika virus-related adverse outcomes can occur throughout pregnancy. Mathematical modeling analysis using reported outcome data suggests that surveillance for these outcomes should begin as soon as an outbreak is detected and should continue for 40 weeks after the outbreak ends. + + + + Eggo + Rosalind M + RM + + + Kucharski + Adam J + AJ + + + eng + + Journal Article + + + 2018 + 01 + 17 + +
+ + United States + Emerg Infect Dis + 9508155 + 1080-6040 + + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + AJNR Am J Neuroradiol. 2017 Jul;38(7):1427-1434 + 28522665 + + + MMWR Morb Mortal Wkly Rep. 2016 Dec 02;65(47):1343-1348 + 27906905 + + + Emerg Infect Dis. 2016 May;22(5):828-32 + 27088494 + + + JAMA. 2017 Jan 3;317(1):59-68 + 27960197 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + Rev Soc Bras Med Trop. 2016 Sep-Oct;49(5):553-558 + 27812648 + + + N Engl J Med. 2017 Apr 20;376(16):1591-1593 + 28402236 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + Lancet. 2016 May 21;387(10033):2125-2132 + 26993883 + + + PLoS Negl Trop Dis. 2016 May 17;10 (5):e0004726 + 27186984 + + + PLoS Biol. 2016 Jul 28;14 (7):e1002520 + 27467271 + + + N Engl J Med. 2016 Jun 15;:null + 27305043 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Brazil + Zika virus + epidemiology + fetal development + microcephaly + miscarriage + monitoring + pregnancy + surveillance + vector-borne infections + viruses + +
+ + + + 2017 + 10 + 24 + 6 + 0 + + + 2017 + 10 + 24 + 6 + 0 + + + 2017 + 10 + 24 + 6 + 0 + + + ppublish + + 29058664 + 10.3201/eid2401.170482 + PMC5749473 + + +
+ + + + + 29048289 + + 2017 + 12 + 19 + +
+ + 1080-6059 + + 23 + 11 + + 2017 + 11 + + + Emerging infectious diseases + Emerging Infect. Dis. + + Outbreak of Zika Virus Infections, Dominica, 2016. + + 1926-1927 + + 10.3201/eid2311.171140 + + In February 2016, the World Health Organization declared the pandemic of Zika virus a public health emergency. On March 4, 2016, Dominica reported its first autochthonous Zika virus disease case; subsequently, 1,263 cases were reported. We describe the outbreak through November 2016, when the last known case was reported. + + + + Ryan + Sadie J + SJ + + + Carlson + Colin J + CJ + + + Stewart-Ibarra + Anna M + AM + + + Borbor-Cordova + Mercy J + MJ + + + Romero + Moory M + MM + + + Cox + Shelly-Ann + SA + + + Mahon + Roché + R + + + Trotman + Adrian + A + + + St Ville + Sylvester + S + + + Ahmed + Shalauddin + S + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + Research Support, U.S. Gov't, Non-P.H.S. + +
+ + United States + Emerg Infect Dis + 9508155 + 1080-6040 + + + + Emerg Infect Dis. 2015 May;21(5):909-11 + 25898214 + + + Lancet. 2016 May 21;387(10033):2070-2072 + 26993880 + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + N Engl J Med. 2016 Jun 15;:null + 27305043 + + + + Aedes + Brazil + Caribbean + Commonwealth of Dominica + Pan American Health Organization + Puerto Rico + ZIKV + Zika virus + aegypti + albopictus + autochthonous + flavivirus + microcephaly + mosquitoes + pandemic + sexual transmission + vector-borne infections + viruses + +
+ + + + 2017 + 10 + 20 + 6 + 0 + + + 2017 + 10 + 20 + 6 + 0 + + + 2017 + 10 + 20 + 6 + 0 + + + ppublish + + 29048289 + 10.3201/eid2311.171140 + PMC5652428 + + +
+ + + + + 29044149 + + 2017 + 12 + 19 + +
+ + 2045-2322 + + 7 + 1 + + 2017 + Oct + 18 + + + Scientific reports + Sci Rep + + Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification. + + 13503 + + 10.1038/s41598-017-13836-9 + + The recent outbreak of Zika virus (ZIKV) disease caused an enormous number of infections in Central and South America, and the unusual increase in the number of infants born with microcephaly associated with ZIKV infection aroused global concern. Here, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using a portable device for the detection of ZIKV. The assay specifically detected ZIKV strains of both Asian and African genotypes without cross-reactivity with other arboviruses, including Dengue and Chikungunya viruses. The assay detected viral RNA at 14.5 TCID50/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. The results of this assay were consistent with those of the reference RT-PCR test. This portable RT-LAMP assay was highly specific for ZIKV, and enable rapid diagnosis of the virus infection. Our results provide new insights into ZIKV molecular diagnostics and may improve preparedness for future outbreaks. + + + + Kurosaki + Yohei + Y + + Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan. + + + + Martins + Danyelly Bruneska Gondim + DBG + + Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Recife, 50670-901, Brazil. + + + + Kimura + Mayuko + M + + Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan. + + + + Catena + Andriu Dos Santos + ADS + + Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Recife, 50670-901, Brazil. + + + + Borba + Maria Amélia Carlos Souto Maior + MACSM + + Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Recife, 50670-901, Brazil. + + + + Mattos + Sandra da Silva + SDS + + Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Recife, 50670-901, Brazil. + + + + Abe + Haruka + H + + Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan. + + + + Yoshikawa + Rokusuke + R + + Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan. + + + + de Lima Filho + José Luiz + JL + + Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Recife, 50670-901, Brazil. + + + + Yasuda + Jiro + J + + Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan. j-yasuda@nagasaki-u.ac.jp. + + + Graduate School of Biomedical Sciences and Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Nagasaki University, Nagasaki, 852-8523, Japan. j-yasuda@nagasaki-u.ac.jp. + + + + eng + + Journal Article + + + 2017 + 10 + 18 + +
+ + England + Sci Rep + 101563288 + 2045-2322 + + + + Nucleic Acids Res. 2000 Jun 15;28(12):E63 + 10871386 + + + J Microbiol. 2015 Jan;53(1):1-5 + 25557475 + + + J Infect Dis. 2016 Oct 15;214(suppl 3):S229-S233 + 27481863 + + + PLoS Curr. 2017 Jan 25;9:null + 28239513 + + + Genome Announc. 2016 Aug 18;4(4):null + 27540058 + + + J Clin Microbiol. 2004 May;42(5):1956-61 + 15131154 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + Lancet Infect Dis. 2016 Jul;16(7):e119-e126 + 27282424 + + + J Clin Microbiol. 2016 Apr;54(4):860-7 + 26888897 + + + Medicine (Baltimore). 2016 Mar;95(12):e3201 + 27015222 + + + Anal Chem. 2016 Jul 19;88(14):7289-94 + 27306491 + + + J Virol Methods. 2016 Dec;238:86-93 + 27793644 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + Anal Chem. 2016 Dec 20;88(24):12272-12278 + 28193014 + + + J Clin Virol. 2015 Feb;63:32-5 + 25600600 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + J Clin Microbiol. 2017 Feb;55(2):535-544 + 27927917 + + + Virol J. 2013 Oct 22;10:311 + 24148652 + + + N Engl J Med. 2017 Feb 14;:null + 28195756 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + J Clin Virol. 2015 Jul;68:53-5 + 26071336 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + J Clin Virol. 2016 Apr;77:69-70 + 26921737 + + + J Med Virol. 2017 Aug;89(8):1477-1479 + 28229481 + + + Int J Infect Dis. 2017 Jan;54:121-128 + 27939768 + + + PLoS Negl Trop Dis. 2016 Feb 22;10(2):e0004472 + 26900929 + + + MMWR Morb Mortal Wkly Rep. 2016 May 13;65(18):475-8 + 27171533 + + + Clin Microbiol Infect. 2017 May;23 (5):296-305 + 28062314 + + + Transfusion. 2016 Jul;56(7):1684-8 + 27329551 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + J Clin Virol. 2016 Sep;82:1-4 + 27389909 + + + Euro Surveill. 2014 Jan 30;19(4):null + 24507467 + + + Biosens Bioelectron. 2016 Dec 15;86:420-425 + 27423039 + + +
+ + + + 2017 + 05 + 09 + + + 2017 + 10 + 02 + + + 2017 + 10 + 19 + 6 + 0 + + + 2017 + 10 + 19 + 6 + 0 + + + 2017 + 10 + 19 + 6 + 0 + + + epublish + + 29044149 + 10.1038/s41598-017-13836-9 + 10.1038/s41598-017-13836-9 + PMC5647432 + + +
+ + + + + 29030384 + + 2017 + 10 + 19 + + + 2017 + 12 + 19 + +
+ + 1756-1833 + + 359 + + 2017 + Oct + 13 + + + BMJ (Clinical research ed.) + BMJ + + Follow-up brain imaging of 37 children with congenital Zika syndrome: case series study. + + j4188 + + 10.1136/bmj.j4188 + + Objective + To compare initial brain computed tomography (CT) scans with follow-up CT scans at one year in children with congenital Zika syndrome, focusing on cerebral calcifications.Design Case series study.Setting Barão de Lucena Hospital, Pernambuco state, Brazil.Participants 37 children with probable or confirmed congenital Zika syndrome during the microcephaly outbreak in 2015 who underwent brain CT shortly after birth and at one year follow-up.Main outcome measure Differences in cerebral calcification patterns between initial and follow-up scans.Results 37 children were evaluated. All presented cerebral calcifications on the initial scan, predominantly at cortical-white matter junction. At follow-up the calcifications had diminished in number, size, or density, or a combination in 34 of the children (92%, 95% confidence interval 79% to 97%), were no longer visible in one child, and remained unchanged in two children. No child showed an increase in calcifications. The calcifications at the cortical-white matter junction which were no longer visible at follow-up occurred predominately in the parietal and occipital lobes. These imaging changes were not associated with any clear clinical improvements.Conclusion The detection of cerebral calcifications should not be considered a major criterion for late diagnosis of congenital Zika syndrome, nor should the absence of calcifications be used to exclude the diagnosis. + Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. + + + + Petribu + Natacha Calheiros de Lima + NCL + + Barão de Lucena Hospital, Recife, Brazil natachacalheiros@yahoo.com.br. + + + Faculdade Pernambucana de Saúde, Recife, Brazil. + + + + Aragao + Maria de Fatima Vasco + MFV + + Centro Diagnóstico Multimagem, Recife, Brazil. + + + Catholic University of Pernambuco, Recife, Brazil. + + + + van der Linden + Vanessa + V + + Barão de Lucena Hospital, Recife, Brazil. + + + Association for Assistance of Disabled Children, Recife, Brazil. + + + + Parizel + Paul + P + + Antwerp University Hospital, Edegem, Belgium. + + + + Jungmann + Patricia + P + + Department of Pathology, University of Pernambuco, Recife, Brazil. + + + + Araújo + Luziany + L + + Barão de Lucena Hospital, Recife, Brazil. + + + + Abath + Marília + M + + Barão de Lucena Hospital, Recife, Brazil. + + + + Fernandes + Andrezza + A + + Barão de Lucena Hospital, Recife, Brazil. + + + + Brainer-Lima + Alessandra + A + + PROCAPE, University of Pernambuco, Recife, Brazil. + + + + Holanda + Arthur + A + + Medical School, Federal University of Pernambuco, Recife, Brazil. + + + + Mello + Roberto + R + + Medical School, Federal University of Pernambuco, Recife, Brazil. + + + + Sarteschi + Camila + C + + The Research Center Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation (Fiocruz) unit, Pernambuco, Brazil. + + + + Duarte + Maria do Carmo Menezes Bezerra + MDCMB + + Esperança Hospital, Recife, Brazil. + + + The Professor Fernando Figueira Integral Medicine Institute, Recife, Brazil. + + + + eng + + Comparative Study + Journal Article + + + 2017 + 10 + 13 + +
+ + England + BMJ + 8900488 + 0959-535X + + AIM + IM + + + BMJ. 2017 Oct 16;359:j4522 + 29038290 + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + Scanning Microsc. 1995;9(4):1137-75; discussion 1175-8 + 8819895 + + + Cell Biochem Funct. 2014 Jan;32(1):77-86 + 23657822 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Acta Obstet Gynecol Scand. 2017 Sep;96(9):1039-1044 + 28646619 + + + AJNR Am J Neuroradiol. 2017 Jul;38(7):1427-1434 + 28522665 + + + MMWR Morb Mortal Wkly Rep. 2016 Dec 02;65(47):1343-1348 + 27906905 + + + Cell Microbiol. 2017 Jun;19(6):null + 28370966 + + + Nature. 2015 Jul 16;523(7560):337-41 + 26030524 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2014 Sep 6;384(9946):857-68 + 25209487 + + + Nat Med. 2016 Nov;22(11):1256-1259 + 27618651 + + + Nat Commun. 2016 Jun 28;7:12204 + 27352279 + + + J Neuroimaging. 2012 Apr;22(2):e52-63 + 22309611 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Sci Transl Med. 2012 Aug 15;4(147):147ra111 + 22896675 + + + Neuron Glia Biol. 2011 Feb;7(1):25-40 + 22377033 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + + + Brain + diagnostic imaging + pathology + virology + + + Brazil + + + Calcinosis + diagnostic imaging + virology + + + Female + + + Follow-Up Studies + + + Humans + + + Infant + + + Infant, Newborn + + + Male + + + Microcephaly + diagnostic imaging + metabolism + virology + + + Neuroimaging + methods + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnostic imaging + metabolism + virology + + + Syndrome + + + Tomography, X-Ray Computed + methods + + + White Matter + diagnostic imaging + pathology + virology + + + Zika Virus + immunology + isolation & purification + + + Zika Virus Infection + congenital + diagnosis + metabolism + virology + + + Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. +
+ + + + 2017 + 10 + 15 + 6 + 0 + + + 2017 + 10 + 17 + 6 + 0 + + + 2017 + 10 + 20 + 6 + 0 + + + epublish + + 29030384 + PMC5639438 + + +
+ + + + + 29022864 + + 2017 + 11 + 13 + + + 2017 + 11 + 13 + +
+ + 1465-2099 + + 98 + 11 + + 2017 + Nov + + + The Journal of general virology + J. Gen. Virol. + + Reverse genetic system, genetically stable reporter viruses and packaged subgenomic replicon based on a Brazilian Zika virus isolate. + + 2712-2724 + + 10.1099/jgv.0.000938 + + Zika virus (ZIKV, genus Flavivirus) has emerged as a major mosquito-transmitted human pathogen, with recent outbreaks associated with an increased incidence of neurological complications, particularly microcephaly and the Guillain-Barré syndrome. Because the virus has only very recently emerged as an important pathogen, research is being hampered by a lack of reliable molecular tools. Here we report an infectious cDNA (icDNA) clone for ZIKV isolate BeH819015 from Brazil, which was selected as representative of South American ZIKV isolated at early stages of the outbreak. icDNA clones were assembled from synthetic DNA fragments corresponding to the consensus sequence of the BeH819015 isolate. Virus rescued from the icDNA clone had properties identical to a natural ZIKV isolate from South America. Variants of the clone-derived virus, expressing nanoluciferase, enhanced green fluorescent or mCherry marker proteins in both mammalian and insect cells and being genetically stable for multiple in vitro passages, were obtained. A ZIKV subgenomic replicon, lacking a prM- and E glycoprotein encoding region and expressing a Gaussia luciferase marker, was constructed and shown to replicate both in mammalian and insect cells. In the presence of the Semliki Forest virus replicon, expressing ZIKV structural proteins, the ZIKV replicon was packaged into virus-replicon particles. Efficient reverse genetic systems, genetically stable marker viruses and packaged replicons offer significant improvements for biological studies of ZIKV infection and disease, as well as for the development of antiviral approaches. + + + + Mutso + Margit + M + + 1​Institute of Technology, University of Tartu, Tartu, Estonia. + + + 2​Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, 4222, Queensland, Australia. + + + + Saul + Sirle + S + + 1​Institute of Technology, University of Tartu, Tartu, Estonia. + + + + Rausalu + Kai + K + + 1​Institute of Technology, University of Tartu, Tartu, Estonia. + + + + Susova + Olga + O + + 3​Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, 115487, Russia. + + + + Žusinaite + Eva + E + + 1​Institute of Technology, University of Tartu, Tartu, Estonia. + + + + Mahalingam + Suresh + S + + 2​Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, 4222, Queensland, Australia. + + + + Merits + Andres + A + + 1​Institute of Technology, University of Tartu, Tartu, Estonia. + + + + eng + + Journal Article + + + 2017 + 10 + 12 + +
+ + England + J Gen Virol + 0077340 + 0022-1317 + + + + 0 + DNA, Complementary + + + EC 1.13.12.- + Luciferases + + + IM + + + Brazil + + + DNA, Complementary + genetics + isolation & purification + + + Genes, Reporter + + + Luciferases + genetics + + + Reverse Genetics + methods + + + Staining and Labeling + methods + + + Zika Virus + genetics + isolation & purification + + + + Zika virus + flavivirus + infectious cDNA + replicon + reporter protein + reverse genetics + +
+ + + + 2017 + 10 + 13 + 6 + 0 + + + 2017 + 11 + 14 + 6 + 0 + + + 2017 + 10 + 13 + 6 + 0 + + + ppublish + + 29022864 + 10.1099/jgv.0.000938 + + +
+ + + + + 29020159 + + 2018 + 03 + 08 + +
+ + 1537-6591 + + 65 + 11 + + 2017 + Nov + 13 + + + Clinical infectious diseases : an official publication of the Infectious Diseases Society of America + Clin. Infect. Dis. + + Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests. + + 1829-1836 + + 10.1093/cid/cix672 + + The explosive spread of Zika virus (ZIKV) and associated microcephaly present an urgent need for sensitive and specific serodiagnostic tests, particularly for pregnant women in dengue virus (DENV)-endemic regions. Recent reports of enhanced ZIKV replication by dengue-immune sera have raised concerns about the role of previous DENV infection on the risk and severity of microcephaly and other ZIKV complications. + Enzyme-linked immunosorbent assays (ELISAs) based on ZIKV and DENV nonstructural protein 1 (NS1) were established to test acute, convalescent phase, and post-convalescent phase serum/plasma samples from reverse-transcription polymerase chain reaction-confirmed cases including 20 primary ZIKV, 25 ZIKV with previous DENV, 58 secondary DENV, and 16 primary DENV1 infections. + ZIKV-NS1 immunoglobulin M (IgM) and immunoglobulin G (IgG) ELISAs combined can detect ZIKV infection with a sensitivity of 95% and specificity of 66.7%. The ZIKV-NS1 IgG cross-reactivity by samples from secondary DENV infection cases ranged from 66.7% to 28.1% (within 1 month to 1-2 years post-illness, respectively). Addition of DENV1-NS1 IgG ELISA can distinguish primary ZIKV infection; the ratio of absorbance of ZIKV-NS1 to DENV1-NS1 IgG ELISA can distinguish ZIKV with previous DENV and secondary DENV infections with a sensitivity of 87.5% and specificity of 81.3%. These findings were supported by analysis of sequential samples. + An algorithm for ZIKV serodiagnosis based on 3 simple ELISAs is proposed to distinguish primary ZIKV, ZIKV with previous DENV, and secondary DENV infections; this could be applied to serodiagnosis for ZIKV, serosurveillance, and monitoring ZIKV infection during pregnancy to understand the epidemiology, pathogenesis, and complications of ZIKV in dengue-endemic regions. + © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. + + + + Tsai + Wen-Yang + WY + + Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu. + + + + Youn + Han Ha + HH + + Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu. + + + + Brites + Carlos + C + + Laboratory of Infection Research, School of Medicine, Federal University of Bahia, Salvador, Brazil. + + + + Tsai + Jih-Jin + JJ + + Divison of Infectious Diseases. + + + Department of Internal Medicine and Tropical Medicine Center, Kaohsiung Medical University Hospital. + + + Department of Medicine, College of Medicine. + + + Center for Dengue Fever Control and Research, Kaohsiung Medical University, Taiwan. + + + + Tyson + Jasmine + J + + Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu. + + + + Pedroso + Celia + C + + Laboratory of Infection Research, School of Medicine, Federal University of Bahia, Salvador, Brazil. + + + + Drexler + Jan Felix + JF + + University of Bonn Medical Centre, Institute of Virology. + + + German Centre for Infection Research, Bonn-Cologne, Germany. + + + + Stone + Mars + M + + Blood Systems Research Institute. + + + + Simmons + Graham + G + + Blood Systems Research Institute. + + + University of California, San Francisco. + + + + Busch + Michael P + MP + + Blood Systems Research Institute. + + + University of California, San Francisco. + + + + Lanteri + Marion + M + + Blood Systems Research Institute. + + + University of California, San Francisco. + + + + Stramer + Susan L + SL + + American Red Cross Scientific Support Office, Gaithersburg, Maryland. + + + + Balmaseda + Angel + A + + National Virology Laboratory, National Center for Diagnosis and Reference, Ministry of Health, Managua, Nicaragua. + + + + Harris + Eva + E + + Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley. + + + + Wang + Wei-Kung + WK + + Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu. + + + + eng + + + R01 AI110769 + AI + NIAID NIH HHS + United States + + + + Journal Article + +
+ + United States + Clin Infect Dis + 9203213 + 1058-4838 + + + Zika virus + cross-reactivity + dengue virus + non-structural protein 1 + serological test + +
+ + + + 2017 + 04 + 21 + + + 2017 + 07 + 27 + + + 2017 + 10 + 12 + 6 + 0 + + + 2017 + 10 + 12 + 6 + 0 + + + 2017 + 10 + 12 + 6 + 0 + + + ppublish + + 29020159 + 4056010 + 10.1093/cid/cix672 + + +
+ + + + + 29019762 + + 2017 + 11 + 14 + +
+ + 1527-1323 + + 37 + 6 + + 2017 + Oct + + + Radiographics : a review publication of the Radiological Society of North America, Inc + Radiographics + + Central Nervous System Effects of Intrauterine Zika Virus Infection: A Pictorial Review. + + 1840-1850 + + 10.1148/rg.2017170023 + + Relatively few agents have been associated with congenital infections involving the brain. One such agent is the Zika virus, which has caused several outbreaks worldwide and has spread in the Americas since 2015. The Zika virus is an arbovirus transmitted by infected female mosquito vectors, such as the Aedes aegypti mosquito. This virus has been commonly associated with congenital infections of the central nervous system and has greatly increased the rates of microcephaly. Ultrasonography (US) remains the method of choice for fetal evaluation of congenital Zika virus infection. For improved assessment of the extent of the lesions, US should be complemented by magnetic resonance (MR) imaging. Postnatal computed tomography and MR imaging can also unveil additional findings of central nervous system involvement, such as microcephaly with malformation of cortical development, ventriculomegaly, and multifocal calcifications in the cortical-subcortical junction, along with associated cortical atrophy. The calcifications may be punctate, dystrophic, linear, or coarse and may follow a predominantly bandlike distribution. A small anterior fontanelle with prematurely closed sutures is also observed with Zika virus infection. In this review, the prenatal and postnatal neurologic imaging findings of congenital Zika virus infection are covered. Radiologists must be aware of this challenging entity and have knowledge of the various patterns that may be depicted with each imaging modality and the main differential diagnosis of the disease. As in other neurologic infections, serial imaging is able to help demonstrate the progression of the findings.©RSNA, 2017. + + + + Ribeiro + Bianca Guedes + BG + + From the Department of Radiology, Centro Médico Barrashopping, Clínica de Diagnóstico por Imagem (CDPI/DASA), Av das Américas 4666, Sala 325, 3° Piso, Barra da Tijuca, Rio de Janeiro 22640-902, Brazil (B.G.R., H.W., F.P.P.L.L., L.C.H.d.C., T.M.F., P.A.N.D., R.A.N.); Hospital Municipal Jesus, Rio de Janeiro, Brazil (B.G.R., T.M.F.); Americas Medical City, Rio de Janeiro, Brazil (B.G.R., L.C.H.d.C., R.A.N.); Instituto Fernandes Figueira-FIOCRUZ, Rio de Janeiro, Brazil (P.A.N.D.); and Department of Radiology, Universidade Federal do Rio Janeiro-UFRJ, Rio de Janeiro, Brazil (F.P.P.L.L.). + + + + Werner + Heron + H + + From the Department of Radiology, Centro Médico Barrashopping, Clínica de Diagnóstico por Imagem (CDPI/DASA), Av das Américas 4666, Sala 325, 3° Piso, Barra da Tijuca, Rio de Janeiro 22640-902, Brazil (B.G.R., H.W., F.P.P.L.L., L.C.H.d.C., T.M.F., P.A.N.D., R.A.N.); Hospital Municipal Jesus, Rio de Janeiro, Brazil (B.G.R., T.M.F.); Americas Medical City, Rio de Janeiro, Brazil (B.G.R., L.C.H.d.C., R.A.N.); Instituto Fernandes Figueira-FIOCRUZ, Rio de Janeiro, Brazil (P.A.N.D.); and Department of Radiology, Universidade Federal do Rio Janeiro-UFRJ, Rio de Janeiro, Brazil (F.P.P.L.L.). + + + + Lopes + Flávia P P L + FPPL + + From the Department of Radiology, Centro Médico Barrashopping, Clínica de Diagnóstico por Imagem (CDPI/DASA), Av das Américas 4666, Sala 325, 3° Piso, Barra da Tijuca, Rio de Janeiro 22640-902, Brazil (B.G.R., H.W., F.P.P.L.L., L.C.H.d.C., T.M.F., P.A.N.D., R.A.N.); Hospital Municipal Jesus, Rio de Janeiro, Brazil (B.G.R., T.M.F.); Americas Medical City, Rio de Janeiro, Brazil (B.G.R., L.C.H.d.C., R.A.N.); Instituto Fernandes Figueira-FIOCRUZ, Rio de Janeiro, Brazil (P.A.N.D.); and Department of Radiology, Universidade Federal do Rio Janeiro-UFRJ, Rio de Janeiro, Brazil (F.P.P.L.L.). + + + + Hygino da Cruz + L Celso + LC + Jr + + From the Department of Radiology, Centro Médico Barrashopping, Clínica de Diagnóstico por Imagem (CDPI/DASA), Av das Américas 4666, Sala 325, 3° Piso, Barra da Tijuca, Rio de Janeiro 22640-902, Brazil (B.G.R., H.W., F.P.P.L.L., L.C.H.d.C., T.M.F., P.A.N.D., R.A.N.); Hospital Municipal Jesus, Rio de Janeiro, Brazil (B.G.R., T.M.F.); Americas Medical City, Rio de Janeiro, Brazil (B.G.R., L.C.H.d.C., R.A.N.); Instituto Fernandes Figueira-FIOCRUZ, Rio de Janeiro, Brazil (P.A.N.D.); and Department of Radiology, Universidade Federal do Rio Janeiro-UFRJ, Rio de Janeiro, Brazil (F.P.P.L.L.). + + + + Fazecas + Tatiana M + TM + + From the Department of Radiology, Centro Médico Barrashopping, Clínica de Diagnóstico por Imagem (CDPI/DASA), Av das Américas 4666, Sala 325, 3° Piso, Barra da Tijuca, Rio de Janeiro 22640-902, Brazil (B.G.R., H.W., F.P.P.L.L., L.C.H.d.C., T.M.F., P.A.N.D., R.A.N.); Hospital Municipal Jesus, Rio de Janeiro, Brazil (B.G.R., T.M.F.); Americas Medical City, Rio de Janeiro, Brazil (B.G.R., L.C.H.d.C., R.A.N.); Instituto Fernandes Figueira-FIOCRUZ, Rio de Janeiro, Brazil (P.A.N.D.); and Department of Radiology, Universidade Federal do Rio Janeiro-UFRJ, Rio de Janeiro, Brazil (F.P.P.L.L.). + + + + Daltro + Pedro A N + PAN + + From the Department of Radiology, Centro Médico Barrashopping, Clínica de Diagnóstico por Imagem (CDPI/DASA), Av das Américas 4666, Sala 325, 3° Piso, Barra da Tijuca, Rio de Janeiro 22640-902, Brazil (B.G.R., H.W., F.P.P.L.L., L.C.H.d.C., T.M.F., P.A.N.D., R.A.N.); Hospital Municipal Jesus, Rio de Janeiro, Brazil (B.G.R., T.M.F.); Americas Medical City, Rio de Janeiro, Brazil (B.G.R., L.C.H.d.C., R.A.N.); Instituto Fernandes Figueira-FIOCRUZ, Rio de Janeiro, Brazil (P.A.N.D.); and Department of Radiology, Universidade Federal do Rio Janeiro-UFRJ, Rio de Janeiro, Brazil (F.P.P.L.L.). + + + + Nogueira + Renata A + RA + + From the Department of Radiology, Centro Médico Barrashopping, Clínica de Diagnóstico por Imagem (CDPI/DASA), Av das Américas 4666, Sala 325, 3° Piso, Barra da Tijuca, Rio de Janeiro 22640-902, Brazil (B.G.R., H.W., F.P.P.L.L., L.C.H.d.C., T.M.F., P.A.N.D., R.A.N.); Hospital Municipal Jesus, Rio de Janeiro, Brazil (B.G.R., T.M.F.); Americas Medical City, Rio de Janeiro, Brazil (B.G.R., L.C.H.d.C., R.A.N.); Instituto Fernandes Figueira-FIOCRUZ, Rio de Janeiro, Brazil (P.A.N.D.); and Department of Radiology, Universidade Federal do Rio Janeiro-UFRJ, Rio de Janeiro, Brazil (F.P.P.L.L.). + + + + eng + + Journal Article + +
+ + United States + Radiographics + 8302501 + 0271-5333 + + + + Radiographics. 2017 Oct;37(6):1850-1853 + 29019746 + + +
+ + + + 2017 + 10 + 12 + 6 + 0 + + + 2017 + 10 + 12 + 6 + 0 + + + 2017 + 10 + 12 + 6 + 0 + + + ppublish + + 29019762 + 10.1148/rg.2017170023 + + +
+ + + + + 28959858 + + 2017 + 09 + 29 + +
+ + 1000-3061 + + 33 + 1 + + 2017 + Jan + 25 + + + Sheng wu gong cheng xue bao = Chinese journal of biotechnology + Sheng Wu Gong Cheng Xue Bao + + [Progress in Zika virus and its vaccines]. + + 1-15 + + 10.13345/j.cjb.160361 + + Like Yellow fever virus, Dengue virus, Japanese encephalitis virus and West Nile virus, Zika virus is also a mosquito-borne flavivirus. Since it was isolated in 1947, there has been little concern over Zika virus due to its limited distribution and mild symptoms. In recent years, especially since 2015, Zika virus has become a global concern because of its outbreak in Brazil and associated microcephaly. Vaccines against Zika virus, regarded as the effective measures to control Zika fever epidemic, are being developed in nearly thirty institutions worldwide. In this paper, biology, epidemiology and clinical features of Zika virus were reviewed along with current research and development of different types of Zika vaccines. In addition, several other flavivirus vaccines approved or in clinical trials were briefly introduced, to provide valuable reference for Zika vaccines researchers. + + + + Tian + Deqiao + D + + Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China. + + + + Chen + Wei + W + + Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China. + + + + chi + + English Abstract + Journal Article + +
+ + China + Sheng Wu Gong Cheng Xue Bao + 9426463 + 1000-3061 + + + 寨卡病毒与黄热病毒、登革热病毒、日本脑炎病毒、西尼罗病毒等都属于蚊媒传播的黄病毒属病毒。寨卡病毒分离于1947 年,但由于分布区域有限,所致寨卡热症状较轻,很长一段时间并没有引起太多的关注。最近一些年,特别是2015 年后,巴西的寨卡疫情暴发及其与新生儿小头畸形的关联,引起了全球越来越多的关注。疫苗是应对寨卡疫情的重要手段,目前全球有30 余个机构在进行寨卡病毒疫苗的研发。本文综述了寨卡病毒的生物学、流行病学、临床特征以及当前不同类型寨卡病毒疫苗研发现状,同时对其他几种黄病毒属病毒批准和临床阶段疫苗情况进行了概述,以为相关研究人员提供参考。. + + + Dengue virus + Japanese encephalitis virus + Yellow fever virus + Zika virus + vaccines + +
+ + + + 2017 + 9 + 30 + 6 + 0 + + + 2017 + 9 + 30 + 6 + 0 + + + 2017 + 9 + 30 + 6 + 0 + + + ppublish + + 28959858 + 10.13345/j.cjb.160361 + + +
+ + + + + 28954927 + + 2018 + 01 + 19 + +
+ + 1946-6242 + + 9 + 409 + + 2017 + Sep + 27 + + + Science translational medicine + Sci Transl Med + + Rapid antigen tests for dengue virus serotypes and Zika virus in patient serum. + eaan1589 + 10.1126/scitranslmed.aan1589 + + The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1-4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-μl serum sample, the sensitivity and specificity values of the DENV1-4 tests and the pan-DENV test, which detects all four dengue serotypes, ranged from 0.76 to 1.00. Sensitivity/specificity for the ZIKV rapid test was 0.81/0.86, respectively, using a 150-μl serum input. Serum ZIKV NS1 protein concentrations were about 10-fold lower than corresponding DENV NS1 concentrations in infected patients; moreover, ZIKV NS1 protein was not detected in polymerase chain reaction-positive patient urine samples. Our rapid immunochromatography approach and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses. + Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. + + + + Bosch + Irene + I + http://orcid.org/0000-0003-1352-5888 + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. + + + + de Puig + Helena + H + http://orcid.org/0000-0002-5368-6996 + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + + Hiley + Megan + M + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + + Carré-Camps + Marc + M + http://orcid.org/0000-0002-1863-367X + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, Spain. + + + + Perdomo-Celis + Federico + F + http://orcid.org/0000-0003-0119-8306 + + Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Colombia. + + + + Narváez + Carlos F + CF + + Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Colombia. + + + + Salgado + Doris M + DM + + Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Colombia. + + + + Senthoor + Dewahar + D + http://orcid.org/0000-0002-2820-4107 + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + + O'Grady + Madeline + M + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + + Phillips + Elizabeth + E + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + + Durbin + Ann + A + http://orcid.org/0000-0002-7348-5243 + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + Program in Virology, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA. + + + + Fandos + Diana + D + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, Spain. + + + + Miyazaki + Hikaru + H + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + + Yen + Chun-Wan + CW + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + + Gélvez-Ramírez + Margarita + M + http://orcid.org/0000-0002-4851-1753 + + Universidad Industrial de Santander and AEDES Program (Alianza para el desarrollo de estrategias que disminuyan el impacto de enfermedades transmitidas por Aedes como resultado del estudio de sus endemias y epidemias), Bucaramanga, Santander, Colombia. + + + + Warke + Rajas V + RV + + HiMedia Laboratories Pvt. Ltd., Mumbai, India. + + + + Ribeiro + Lucas S + LS + http://orcid.org/0000-0001-8876-3827 + + Immunopharmacology Group, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, Brazil. + + + + Teixeira + Mauro M + MM + http://orcid.org/0000-0002-6944-3008 + + Immunopharmacology Group, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, Brazil. + + + + Almeida + Roque P + RP + http://orcid.org/0000-0003-2988-8165 + + Departamento de Medicina Interna e Patologia, Hospital Universitário/Empresa Brasileira de Serviços Hospitalares (EBSERH), Universidade Federal de Sergipe, Aracaju, Brazil. + + + + Muñóz-Medina + José E + JE + http://orcid.org/0000-0002-1289-4457 + + Laboratorio Central de Epidemiología, Instituto Mexicano del Seguro Social, Avenida Jacarandas S/N, Esquina Circuito Interior, Colonia La Raza Del Azcapotzalco, Código Postal 02990 México D.F., México. + + + + Ludert + Juan E + JE + + Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México, México. + + + + Nogueira + Mauricio L + ML + + Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, Brazil. + + + + Colombo + Tatiana E + TE + + Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, Brazil. + + + + Terzian + Ana C B + ACB + + Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, Brazil. + + + + Bozza + Patricia T + PT + http://orcid.org/0000-0001-8349-9529 + + Immunopharmacology Laboratory, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. + + + + Calheiros + Andrea S + AS + + Immunopharmacology Laboratory, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. + + + + Vieira + Yasmine R + YR + + National Institute of Infectious Disease Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil. + + + + Barbosa-Lima + Giselle + G + + National Institute of Infectious Disease Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil. + + + + Vizzoni + Alexandre + A + + National Institute of Infectious Disease Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil. + + + + Cerbino-Neto + José + J + + National Institute of Infectious Disease Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil. + + + + Bozza + Fernando A + FA + + National Institute of Infectious Disease Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil. + + + D'Or Institute of Research and Education (IDOR), Rio de Janeiro, Brazil. + + + + Souza + Thiago M L + TML + + Immunopharmacology Laboratory, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. + + + National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), FIOCRUZ, Rio de Janeiro, Brazil. + + + + Trugilho + Monique R O + MRO + http://orcid.org/0000-0001-9240-9978 + + Toxinology Laboratory and Center for Technological Development in Health (CDTS), FIOCRUZ, Rio de Janeiro, Brazil. + + + + de Filippis + Ana M B + AMB + + Flavivirus Laboratory, FIOCRUZ, Rio de Janeiro, Brazil. + + + + de Sequeira + Patricia C + PC + http://orcid.org/0000-0003-4415-3837 + + Flavivirus Laboratory, FIOCRUZ, Rio de Janeiro, Brazil. + + + + Marques + Ernesto T A + ETA + http://orcid.org/0000-0003-3826-9358 + + Aggeu Magalhães Research Center, FIOCRUZ, Pernambuco, Recife, Brazil. + + + Department of Infectious Disease and Microbiology, University of Pittsburgh, Pittsburgh, PA 15213, USA. + + + + Magalhaes + Tereza + T + + Aggeu Magalhães Research Center, FIOCRUZ, Pernambuco, Recife, Brazil. + + + Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. + + + + Díaz + Francisco J + FJ + http://orcid.org/0000-0003-3352-3652 + + Immunovirology Group, School of Medicine, University of Antioquia, Medellín, Colombia. + + + + Restrepo + Berta N + BN + + Instituto Colombiano de Medicina Tropical (ICMT), Universidad CES, Sabaneta, Antioquia, Colombia. + + + + Marín + Katerine + K + + Instituto Colombiano de Medicina Tropical (ICMT), Universidad CES, Sabaneta, Antioquia, Colombia. + + + + Mattar + Salim + S + http://orcid.org/0000-0003-0526-4630 + + Universidad de Córdoba, Montería, Córdoba, Colombia. + + + + Olson + Daniel + D + + Division of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA. + + + + Asturias + Edwin J + EJ + + Division of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA. + + + + Lucera + Mark + M + + Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA. + + + + Singla + Mohit + M + + Department of Paediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. + + + + Medigeshi + Guruprasad R + GR + http://orcid.org/0000-0001-5333-9743 + + Translational Health Science and Technology Institute, Faridabad, India. + + + + de Bosch + Norma + N + + Universidad Central de Venezuela, Caracas, Venezuela. + + + + Tam + Justina + J + http://orcid.org/0000-0003-0183-8326 + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + Winchester Engineering Analytical Center (WEAC), Winchester, MA 01890, USA. + + + + Gómez-Márquez + Jose + J + http://orcid.org/0000-0002-7100-5592 + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. + + + + Clavet + Charles + C + + Winchester Engineering Analytical Center (WEAC), Winchester, MA 01890, USA. + + + + Villar + Luis + L + http://orcid.org/0000-0002-3873-0901 + + Universidad Industrial de Santander and AEDES Program (Alianza para el desarrollo de estrategias que disminuyan el impacto de enfermedades transmitidas por Aedes como resultado del estudio de sus endemias y epidemias), Bucaramanga, Santander, Colombia. + + + + Hamad-Schifferli + Kimberly + K + http://orcid.org/0000-0002-4839-3179 + + Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. kim.hamad@umb.edu lgehrke@mit.edu. + + + Department of Engineering, University of Massachusetts Boston, Boston, MA 02125, USA. + + + + Gehrke + Lee + L + http://orcid.org/0000-0002-9387-8212 + + Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. kim.hamad@umb.edu lgehrke@mit.edu. + + + Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. + + + + eng + + + IA/S(I)/14/1/501291 + Wellcome Trust-DBT India Alliance + India + + + + Journal Article + +
+ + United States + Sci Transl Med + 101505086 + 1946-6234 + +
+ + + + 2017 + 03 + 14 + + + 2017 + 06 + 02 + + + 2017 + 09 + 08 + + + 2017 + 9 + 29 + 6 + 0 + + + 2017 + 9 + 29 + 6 + 0 + + + 2017 + 9 + 29 + 6 + 0 + + + ppublish + + 28954927 + 9/409/eaan1589 + 10.1126/scitranslmed.aan1589 + + +
+ + + + + 28954064 + + 2017 + 11 + 20 + + + 2017 + 11 + 28 + +
+ + 1678-9849 + + 50 + 4 + + 2017 Jul-Aug + + + Revista da Sociedade Brasileira de Medicina Tropical + Rev. Soc. Bras. Med. Trop. + + The role of Brazilian National Health Information Systems in assessing the impact of Zika virus outbreak. + + 450-457 + + S0037-86822017000400450 + 10.1590/0037-8682-0506-2016 + + The Zika virus (ZIKV) epidemic has become a public health emergency following its association with severe neurological complications. We aim to discuss how the Brazilian National Health Information Systems can help to assess the impact of the ZIKV epidemic on health outcomes potentially related to ZIKV. Health outcomes potentially related to ZIKV infection were described based on a literature review of published studies on ZIKV infection outcomes and on recent protocols developed and published by the Brazilian Ministry of Health for different stages of the life cycle. These outcomes were correlated with the International Classification of Diseases 10th Revision (ICD-10) classification system, as this is the diagnostic classification registered in the Health Information System. A suggested list of 50 clinical manifestations, dispersed into 4 ICD chapters, and their information sources was created to help monitor the ZIKV epidemics and trends. Correlation of these selected ICD-10 codes and the HIS, as well as, a review of the potentialities and limitations of health information systems were performed. The potential of the Health Information System and its underutilization by stakeholders and researchers have been a barrier in diagnosing and reporting ZIKV infection and its complications. The ZIKV outbreak is still a challenge for health practice and the Brazilian Health Information System. + + + + Pavão + Ana Luiza Braz + ALB + + Laboratório de Informação em Saúde, Instituto de Informação e Comunicação Científica e Tecnológica em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil. + + + + Barcellos + Christovam + C + + Laboratório de Informação em Saúde, Instituto de Informação e Comunicação Científica e Tecnológica em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil. + + + + Pedroso + Marcel + M + + Laboratório de Informação em Saúde, Instituto de Informação e Comunicação Científica e Tecnológica em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil. + + + + Boccolini + Cristiano + C + + Laboratório de Informação em Saúde, Instituto de Informação e Comunicação Científica e Tecnológica em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil. + + + + Romero + Dália + D + + Laboratório de Informação em Saúde, Instituto de Informação e Comunicação Científica e Tecnológica em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil. + + + + eng + + Journal Article + +
+ + Brazil + Rev Soc Bras Med Trop + 7507456 + 0037-8682 + + IM + + + Brazil + epidemiology + + + Disease Outbreaks + + + Health Information Systems + standards + statistics & numerical data + + + Humans + + + Microcephaly + epidemiology + virology + + + Zika Virus Infection + complications + epidemiology + + +
+ + + + 2016 + 12 + 05 + + + 2017 + 06 + 02 + + + 2017 + 9 + 28 + 6 + 0 + + + 2017 + 9 + 28 + 6 + 0 + + + 2017 + 11 + 29 + 6 + 0 + + + ppublish + + 28954064 + S0037-86822017000400450 + 10.1590/0037-8682-0506-2016 + + +
+ + + + + 28942698 + + 2017 + 10 + 26 + +
+ + 1476-4954 + + + 2017 + Oct + 11 + + + The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians + J. Matern. Fetal. Neonatal. Med. + + Neuroimaging findings using transfontanellar ultrasound in newborns with microcephaly: a possible association with congenital Zika virus infection. + + 1-9 + + 10.1080/14767058.2017.1384459 + + The objective of this study is to determine the main neuroimaging findings of microcephalic newborns with possible Zika virus (ZIKV) intrauterine infection using transfontanellar cranial ultrasound. + We performed a retrospective study to describe the main neuroimaging findings in newborns with microcephaly and possible association with congenital ZIKV infection. Microcephaly was defined in the postnatal period using transfontanellar cranial examination which was performed using both two- (2D) and three-dimensional (3D) ultrasound. + One hundred and fifty newborns with microcephaly were identified during the study period. The mean ± (standard deviation - SD) of cephalic perimeter was 28.5 ± 4.2 cm (range, 25-38 cm). Transfontanellar neuroimaging patterns detected cerebral calcifications, neuronal migrational abnormalities, dysgenesis of the corpus callosum, and cerebellar atrophy in 34.9%, 31.1%, 26%, and 16.2%, respectively. Hydrocephalus was seen in 28% of overall newborns. A history of maculopapular rash was present in almost half of the mothers (46.1%). + Neuroimaging patterns by means of transfontanellar ultrasound are accurate and diagnostic investigations of brain pathology in newborns affected by microcephaly and possible intrauterine ZIKV infection. + + + + Ximenes + Ana Sofia França Cruz + ASFC + + a Department of Radiology , Pernambuco University (UPE) , Recife , Brazil. + + + + Pires + Pedro + P + + b Department of Maternal and Child , Pernambuco University (UPE) , Recife , Brazil. + + + + Werner + Heron + H + + c Department of Radiology , Clínica de Diagnóstico por Imagem (CDPI) , Rio de Janeiro , Brazil. + + + + Jungmann + Patricia Mello + PM + + d Department of Pathology , Pernambuco University (UPE) , Recife , Brazil. + + + + Rolim Filho + Epitácio Leite + EL + + e Department of Surgery , Federal University of Pernambuco (UFPE) , Recife , Brazil. + + + + Andrade + Etiene Pedrosa + EP + + f Radiology Unit , Getúlio Vargas Hospital , Recife , Brazil. + + + + Lemos + Roberto Souza + RS + + f Radiology Unit , Getúlio Vargas Hospital , Recife , Brazil. + + + + Peixoto + Alberto Borges + AB + + g Mário Palmério University Hospital, University of Uberaba (UNIUBE) , Uberaba , Brazil. + + + + Zare Mehrjardi + Mohammad + M + http://orcid.org/0000-0001-5793-5323 + + h Department of Radiology, Shohada Tajrish Hospital, School of Medicine , Shahid Beheshti University of Medical Sciences , Tehran , Iran. + + + i Section of Pediatric Imaging, Division of Clinical Research , Climax Radiology Education Foundation , Tehran , Iran. + + + + Tonni + Gabriele + G + + j Department of Obstetrics and Gynecology , Guastalla Civil Hospital, AUSL Reggio Emilia , Italy. + + + + Araujo Júnior + Edward + E + http://orcid.org/0000-0002-6145-2532 + + k Department of Obstetrics, Paulista School of Medicine , Federal University of São Paulo (EPM-UNIFESP) , São Paulo , Brazil. + + + + eng + + Journal Article + + + 2017 + 10 + 11 + +
+ + England + J Matern Fetal Neonatal Med + 101136916 + 1476-4954 + + + Congenital Zika virus infection + microcephaly + newborns + transfontanelle cranial ultrasound + +
+ + + + 2017 + 9 + 26 + 6 + 0 + + + 2017 + 9 + 26 + 6 + 0 + + + 2017 + 9 + 26 + 6 + 0 + + + aheadofprint + + 28942698 + 10.1080/14767058.2017.1384459 + + +
+ + + + + 28932235 + + 2017 + 09 + 24 + +
+ + 1678-9199 + + 23 + + 2017 + + + The journal of venomous animals and toxins including tropical diseases + J Venom Anim Toxins Incl Trop Dis + + Zika virus congenital syndrome: experimental models and clinical aspects. + + 41 + + 10.1186/s40409-017-0131-x + + Viral infections have long been the cause of severe diseases to humans, increasing morbidity and mortality rates worldwide, either in rich or poor countries. Yellow fever virus, H1N1 virus, HIV, dengue virus, hepatitis B and C are well known threats to human health, being responsible for many million deaths annually, associated to a huge economic and social cost. In this context, a recently introduced flavivirus in South America, called Zika virus (ZIKV), led the WHO to declare in February 1st 2016 a warning on Public Health Emergency of International Concern (PHEIC). ZIKV is an arbovirus of theFlaviviridaefamily firstly isolated from sentinelsRhesussp. monkeys at the Ziika forest in Uganda, Africa, in 1947. Lately, the virus has well adapted to the worldwide spreadAedes aegyptimosquito, the vector for DENV, CHIKV, YFV and many others. At first, it was not considered a threat to human health, but everything changed when a skyrocketing number of babies born with microcephaly and adults with Guillain-Barré syndrome were reported, mainly in northeastern Brazil. It is now well established that the virus is responsible for the so called congenital Zika syndrome (CZS), whose most dramatic features are microcephaly, arthrogryposis and ocular damage. Thus, in this review, we provide a brief discussion of these main clinical aspects of the CZS, correlating them with the experimental animal models described so far. + + + + Polonio + Carolina Manganeli + CM + + Neuroimmune Interactions Laboratory, Immunology Department - ICB IV, University of São Paulo (USP), Av. Prof. Lineu Prestes, 1730, Cidade Universitária, São Paulo, SP CEP 05508-900 Brazil. + 0000 0004 1937 0722 + grid.11899.38 + + + + de Freitas + Carla Longo + CL + + Neuroimmune Interactions Laboratory, Immunology Department - ICB IV, University of São Paulo (USP), Av. Prof. Lineu Prestes, 1730, Cidade Universitária, São Paulo, SP CEP 05508-900 Brazil. + 0000 0004 1937 0722 + grid.11899.38 + + + + Zanluqui + Nagela Ghabdan + NG + + Neuroimmune Interactions Laboratory, Immunology Department - ICB IV, University of São Paulo (USP), Av. Prof. Lineu Prestes, 1730, Cidade Universitária, São Paulo, SP CEP 05508-900 Brazil. + 0000 0004 1937 0722 + grid.11899.38 + + + + Peron + Jean Pierre Schatzmann + JPS + + Neuroimmune Interactions Laboratory, Immunology Department - ICB IV, University of São Paulo (USP), Av. Prof. Lineu Prestes, 1730, Cidade Universitária, São Paulo, SP CEP 05508-900 Brazil. + 0000 0004 1937 0722 + grid.11899.38 + + + + eng + + Journal Article + Review + + + 2017 + 09 + 15 + +
+ + England + J Venom Anim Toxins Incl Trop Dis + 101201501 + 1678-9180 + + + + Euro Surveill. 2016 Jun 16;21(24): + 27336620 + + + Cell Host Microbe. 2016 Jun 8;19(6):882-90 + 27212660 + + + Nature. 2016 Aug 25;536(7617):474-8 + 27355570 + + + Science. 2016 Sep 9;353(6304):1129-32 + 27492477 + + + BMJ. 2016 Jun 17;353:i3416 + 27317419 + + + Arch Pathol Lab Med. 2017 Jan;141(1):26-32 + 27636525 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Cell Stem Cell. 2016 Nov 3;19(5):663-671 + 27524440 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Neurology. 2006 Aug 22;67(4):597-601 + 16924011 + + + Cell Stem Cell. 2016 May 5;18(5):591-6 + 27038591 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + ISRN Obstet Gynecol. 2012;2012:264918 + 23050160 + + + Hum Mol Genet. 2010 Apr 1;19(7):1165-73 + 20045868 + + + Emerg Infect Dis. 2014 Aug;20(8):1412-4 + 25062427 + + + N Engl J Med. 2016 Jul 28;375(4):394-6 + 27332784 + + + N Engl J Med. 2016 Nov 10;375(19):1907-1909 + 27681699 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Euro Surveill. 2014 Oct 16;19(41):null + 25345518 + + + Lancet. 2016 Apr 9;387(10027):1587-90 + 26952548 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + Lancet. 2016 Aug 27;388(10047):898-904 + 27372395 + + + Trans R Soc Trop Med Hyg. 1977;71(3):254-60 + 407675 + + + Clin Infect Dis. 2016 Dec 15;63(12 ):1622-1625 + 27601223 + + + Cell Rep. 2016 Sep 20;16(12 ):3208-3218 + 27612415 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Ophthalmic Surg Lasers Imaging Retina. 2016 Oct 1;47(10 ):952-955 + 27759862 + + + J Bone Joint Surg Am. 2009 Jul;91 Suppl 4:40-6 + 19571066 + + + Ann Clin Microbiol Antimicrob. 2016 Sep 29;15(1):57 + 27686610 + + + Arch Pathol Lab Med. 2017 Jan;141(1):68-72 + 27557413 + + + Lancet. 2016 Jun 18;387(10037):2502 + 27287830 + + + Arch Pathol Lab Med. 2017 Jan;141(1):73-81 + 27726416 + + + Arch Neurol. 2008 Aug;65(8):1083-90 + 18695058 + + + Arq Bras Oftalmol. 2016 Feb;79(1):63 + 26840174 + + + Lancet. 2016 May 21;387(10033):2125-2132 + 26993883 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Emerg Infect Dis. 2017 Mar;23 (3):405-414 + 27959260 + + + Nature. 2017 May 25;545(7655):482-486 + 28514450 + + + Eur J Med Genet. 2014 Aug;57(8):464-72 + 24704792 + + + Am J Public Health. 2016 Apr;106(4):606-12 + 26959260 + + + Arch Med Sci. 2016 Feb 1;12(1):10-24 + 26925114 + + + Trans R Soc Trop Med Hyg. 1977;71(4):300-3 + 413216 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + JAMA Neurol. 2016 Dec 1;73(12 ):1407-1416 + 27695855 + + + Cell. 2016 May 19;165(5):1081-1091 + 27180225 + + + BMJ. 2016 Aug 09;354:i3899 + 27509902 + + + Oman J Ophthalmol. 2013 May;6(2):77-82 + 24082663 + + + Retin Cases Brief Rep. 2017 Jan 02;:null + 28060137 + + + JAMA Ophthalmol. 2016 Aug 1;134(8):912-8 + 27228275 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Lancet. 2016 Apr 9;387(10027):1531-1539 + 26948433 + + + Pediatr Neurol. 1993 Sep-Oct;9(5):343-8 + 8292208 + + + J Pediatr Orthop B. 1997 Jul;6(3):159-66 + 9260643 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + J Paediatr Child Health. 1994 Oct;30(5):450-2 + 7833087 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Arthrogryposis + Congenital infection + Experimental models + Ocular abnormality + Zika virus + +
+ + + + 2017 + 03 + 10 + + + 2017 + 09 + 01 + + + 2017 + 9 + 22 + 6 + 0 + + + 2017 + 9 + 22 + 6 + 0 + + + 2017 + 9 + 22 + 6 + 1 + + + epublish + + 28932235 + 10.1186/s40409-017-0131-x + 131 + PMC5602956 + + +
+ + + + + 28929534 + + 2017 + 11 + 20 + +
+ + 1099-1654 + + 27 + 6 + + 2017 + Nov + + + Reviews in medical virology + Rev. Med. Virol. + + Emerging arboviruses in Rio Grande do Sul, Brazil: Chikungunya and Zika outbreaks, 2014-2016. + 10.1002/rmv.1943 + + The recent emergence of arboviruses such as Chikungunya virus (CHIKV) and Zika virus (ZIKV) in Brazil has posed a threat to human health and to the country's economy. Outbreaks occur mainly in tropical areas; however, increasing number of cases have been observed in Rio Grande do Sul (RS), the Southernmost state; therefore, surveillance of these arboviruses is essential for public health measures. + In this study, we analyzed 1276 samples from patients with clinically suspected arboviral diseases between 2014 and 2016. Demographic and clinical data were collected and described; cases of microcephaly associated with congenital infection were analyzed. + Results show that CHIKV and ZIKV entered RS in 2014 and 2015, respectively, with imported cases confirmed. Autochthonous infections occurred in 2016 for both viruses, with a total of 5 autochthonous cases for CHIKV and 44 for ZIKV. Most patients were older than 21 years; the main symptoms were fever, arthralgia, myalgia, and headache; rash, conjunctivitis, and pruritus were also reported in ZIKV cases. Three cases of congenital Zika syndrome were confirmed in our study, while another 20 cases of microcephaly associated with congenital infection were confirmed (10 positive for syphilis, 6 for toxoplasmosis and 4 for cytomegalovirus). + Considering co-circulation of different arbovirus in RS, including Dengue virus, CHIKV, and ZIKV, and the presence of Aedes aegypti and Aedes albopictus in the area, surveillance of patients infected by these viruses contributes to the control and prevention of such diseases. Practical difficulties in diagnosing these infections are discussed. + Copyright © 2017 John Wiley & Sons, Ltd. + + + + Gregianini + Tatiana Schäffer + TS + + Laboratório Central de Saúde Pública do Estado do Rio Grande do Sul, IPB-LACEN/RS, Secretaria de Saúde do Estado do Rio Grande do Sul - SES/RS, Porto Alegre, RS, Brazil. + + + + Ranieri + Tani + T + + Centro Estadual de Vigilância em Saúde - CEVS, Secretaria de Saúde do Estado do Rio Grande do Sul - SES/RS, Rio Grande do Sul, Porto Alegre, RS, Brazil. + + + + Favreto + Cátia + C + + Centro Estadual de Vigilância em Saúde - CEVS, Secretaria de Saúde do Estado do Rio Grande do Sul - SES/RS, Rio Grande do Sul, Porto Alegre, RS, Brazil. + + + + Nunes + Zenaida Marion Alves + ZMA + + Laboratório Central de Saúde Pública do Estado do Rio Grande do Sul, IPB-LACEN/RS, Secretaria de Saúde do Estado do Rio Grande do Sul - SES/RS, Porto Alegre, RS, Brazil. + + + + Tumioto Giannini + Gabriela Luchiari + GL + + Laboratório Central de Saúde Pública do Estado do Rio Grande do Sul, IPB-LACEN/RS, Secretaria de Saúde do Estado do Rio Grande do Sul - SES/RS, Porto Alegre, RS, Brazil. + + + + Sanberg + Nara Druck + ND + + Laboratório Central de Saúde Pública do Estado do Rio Grande do Sul, IPB-LACEN/RS, Secretaria de Saúde do Estado do Rio Grande do Sul - SES/RS, Porto Alegre, RS, Brazil. + + + + da Rosa + Marilda Tereza Mar + MTM + + Laboratório Central de Saúde Pública do Estado do Rio Grande do Sul, IPB-LACEN/RS, Secretaria de Saúde do Estado do Rio Grande do Sul - SES/RS, Porto Alegre, RS, Brazil. + + + + da Veiga + Ana Beatriz Gorini + ABG + http://orcid.org/0000-0003-1462-5506 + + Laboratório de Biologia Molecular, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, RS, Brazil. + + + + eng + + Journal Article + Review + + + 2017 + 09 + 20 + +
+ + England + Rev Med Virol + 9112448 + 1052-9276 + + + Chikungunya virus-CHIKV + Zika virus-ZIKV + arboviral diseases + congenital Zika syndrome + microcephaly + +
+ + + + 2017 + 07 + 03 + + + 2017 + 08 + 11 + + + 2017 + 08 + 15 + + + 2017 + 9 + 21 + 6 + 0 + + + 2017 + 9 + 21 + 6 + 0 + + + 2017 + 9 + 21 + 6 + 0 + + + ppublish + + 28929534 + 10.1002/rmv.1943 + + +
+ + + + + 28916391 + + 2018 + 01 + 19 + +
+ + 1873-1899 + + 36 + 1 + + 2018 Jan - Feb + + + Biotechnology advances + Biotechnol. Adv. + + Zika virus structural biology and progress in vaccine development. + + 47-53 + + S0734-9750(17)30115-5 + 10.1016/j.biotechadv.2017.09.004 + + The growing number of zika virus (ZIKV) infections plus a 20-fold increase in neonatal microcephaly in newborns in Brazil have raised alarms in many countries regarding the threat to pregnant women. Instances of microcephaly and central nervous system malformations continue to increase in ZIKV outbreak regions. ZIKV is a small enveloped positive-strand RNA virus belonging to the Flavivirus genus of the Flaviviridae family. High-resolution ZIKV structures recently identified by cryo-electron microscopy indicate that the overall ZIKV structure is similar to those of other flaviviruses. With its compact surface, ZIKV is more thermally stable than the dengue virus (DENV). ZIKV E proteins have a characteristic "herringbone" structure with a single glycosylation site. The ZIKV E protein, the major protein involved in receptor binding and fusion, is formed as a head-to-tail dimer on the surfaces of viral particles. The E monomer consists of three distinct domains: DI, DII, and DIII. The finger-like DII contains a fusion loop (FL) that is inserted into the host cell endosomal membrane during pH-dependent conformational changes that drive fusion. Quaternary E:E dimer epitopes located at the interaction site of prM and E dimers can be further divided into two dimer epitopes. To date, more than 50 ZIKV vaccine candidates are now in various stages of research and development. Candidate ZIKV vaccines that are currently in phase I/II clinical trials include inactivated whole viruses, recombinant measles viral vector-based vaccines, DNA and mRNA vaccines, and a mosquito salivary peptide vaccine. Stabilized forms of ZIKV E:E dimer proteins have been successfully obtained either by introducing additional inter-subunit disulfide bond(s) in DII or via the direct assembly of E:E dimer proteins by immobilization with monomeric E proteins. The VLP-based approach is another alternative method for presenting native E:E dimer antigens among the vaccine components. Several forms of ZIKV VLPs have been reported featuring the co-expression of the prM-E, prM-E-NS1, C-prM-E, and NS2B/NS3 viral genes in human cells. To minimize the effect of the cross-reactive ADE-facilitating antibodies between ZIKV and DENV, several novel mutations have been reported either in or near the FL of DII or DIII to dampen the production of cross-reactive antibodies. Future ZIKV vaccine design efforts should be focused on eliciting improved neutralizing antibodies with a reduced level of cross-reactivity to confer sterilizing immunity. + Copyright © 2017 Elsevier Inc. All rights reserved. + + + + Lin + Hsiao-Han + HH + + Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan. + + + + Yip + Bak-Sau + BS + + Department of Neurology, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan. + + + + Huang + Li-Min + LM + + Department of Pediatrics, National Taiwan University, Children's Hospital, Hsinchu, Taiwan. + + + + Wu + Suh-Chin + SC + + Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan; Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan. Electronic address: scwu@mx.nthu.edu.tw. + + + + eng + + Journal Article + Review + + + 2017 + 09 + 12 + +
+ + England + Biotechnol Adv + 8403708 + 0734-9750 + + + Cross reactivity + Structure biology + Vaccine + Zika virus + +
+ + + + 2017 + 01 + 24 + + + 2017 + 09 + 06 + + + 2017 + 09 + 08 + + + 2017 + 9 + 17 + 6 + 0 + + + 2017 + 9 + 17 + 6 + 0 + + + 2017 + 9 + 17 + 6 + 0 + + + ppublish + + 28916391 + S0734-9750(17)30115-5 + 10.1016/j.biotechadv.2017.09.004 + + +
+ + + + + 28893652 + + 2017 + 12 + 06 + +
+ + 1872-7492 + + + 2017 + Sep + 08 + + + Virus research + Virus Res. + + A new threat to human reproduction system posed by Zika virus (ZIKV): From clinical investigations to experimental studies. + S0168-1702(17)30668-8 + 10.1016/j.virusres.2017.09.005 + + Zika virus (ZIKV) was first isolated in 1947 from a rhesus monkey in the Zika forest of Uganda. ZIKV has since been silently circulating in a number of equatorial countries for over 50 years. The largest outbreak in humans occurred in Brazil in 2015-2016. Unlike its flavivirus relatives, sexual and post-transfusion transmissions of ZIKV have been reported. In addition, fetal infection can result in microcephaly and congenital Zikv syndrome has been reported in neonates. Moreover, ZIKV RNA can persist for at least 6 months in semen and 11 weeks in vaginal secretions after the infection, suggesting potential tropism for the male and female genital tracts. Accordingly, it is important to determine whether genital ZIKV infection could have deleterious effects on the male and female reproductive systems. + Copyright © 2017. Published by Elsevier B.V. + + + + Li + Xiangdong + X + + Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China. Electronic address: xiangdongli@cau.edu.cn. + + + + Ma + Wenqiang + W + + Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China. + + + + Wong + Gary + G + + CAS Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. + + + + Ma + Shuoqian + S + + Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China. + + + + Li + Shihua + S + + CAS Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. + + + + Bi + Yuhai + Y + + CAS Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. + + + + Gao + George F + GF + + CAS Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; Chinese Center for Disease Control and Prevention (China CDC), Beijing, China. Electronic address: gaof@im.ac.cn. + + + + eng + + Journal Article + Review + + + 2017 + 09 + 08 + +
+ + Netherlands + Virus Res + 8410979 + 0168-1702 + + + Animal models + Reproductive system + Zika virus + +
+ + + + 2017 + 09 + 05 + + + 2017 + 09 + 07 + + + 2017 + 9 + 13 + 6 + 0 + + + 2017 + 9 + 13 + 6 + 0 + + + 2017 + 9 + 13 + 6 + 0 + + + aheadofprint + + 28893652 + S0168-1702(17)30668-8 + 10.1016/j.virusres.2017.09.005 + + +
+ + + + + 28887877 + + 2018 + 03 + 02 + +
+ + 2050-084X + + 6 + + 2017 + Sep + 09 + + + eLife + Elife + + Epidemiological and ecological determinants of Zika virus transmission in an urban setting. + 10.7554/eLife.29820 + e29820 + + The Zika virus has emerged as a global public health concern. Its rapid geographic expansion is attributed to the success ofAedesmosquito vectors, but local epidemiological drivers are still poorly understood. Feira de Santana played a pivotal role in the Chikungunya epidemic in Brazil and was one of the first urban centres to report Zika infections. Using a climate-driven transmission model and notified Zika case data, we show that a low observation rate and high vectorial capacity translated into a significant attack rate during the 2015 outbreak, with a subsequent decline in 2016 and fade-out in 2017 due to herd-immunity. We find a potential Zika-related, low risk for microcephaly per pregnancy, but with significant public health impact given high attack rates. The balance between the loss of herd-immunity and viral re-importation will dictate future transmission potential of Zika in this urban setting. + + + + Lourenço + José + J + http://orcid.org/0000-0002-9318-2581 + + Department of Zoology, University of Oxford, Oxford, United Kingdom. + + + + Maia de Lima + Maricelia + M + + Laboratory of Haematology, Genetics and Computational Biology, FIOCRUZ, SalvadorBahia, Brazil. + + + + Faria + Nuno Rodrigues + NR + http://orcid.org/0000-0001-8839-2798 + + Department of Zoology, University of Oxford, Oxford, United Kingdom. + + + + Walker + Andrew + A + + Department of Zoology, University of Oxford, Oxford, United Kingdom. + + + + Kraemer + Moritz Ug + MU + http://orcid.org/0000-0001-8838-7147 + + Department of Zoology, University of Oxford, Oxford, United Kingdom. + + + + Villabona-Arenas + Christian Julian + CJ + http://orcid.org/0000-0001-9928-3968 + + Institut de Recherche pour le Développement, UMI 233, INSERM U1175 and Institut de Biologie Computationnelle, LIRMM, Université de Montpellier, Montpellier, France. + + + + Lambert + Ben + B + + Department of Zoology, University of Oxford, Oxford, United Kingdom. + + + + Marques de Cerqueira + Erenilde + E + + Centre of PostGraduation in Collective Health, Department of Health, Universidade Estadual de Feira de Santana, Feira de SantanaBahia, Brazil. + + + + Pybus + Oliver G + OG + + Department of Zoology, University of Oxford, Oxford, United Kingdom. + + + + Alcantara + Luiz Cj + LC + + Laboratory of Haematology, Genetics and Computational Biology, FIOCRUZ, SalvadorBahia, Brazil. + + + + Recker + Mario + M + http://orcid.org/0000-0001-9489-1315 + + Centre for Mathematics and the Environment, University of Exeter, Penryn, United Kingdom. + + + + eng + + + Wellcome Trust + United Kingdom + + + 268904 + European Research Council + International + + + T32 HD040128 + HD + NICHD NIH HHS + United States + + + + Journal Article + + + 2017 + 09 + 09 + +
+ + England + Elife + 101579614 + 2050-084X + + + + PLoS Negl Trop Dis. 2016 Aug 26;10 (8):e0004968 + 27564232 + + + PLoS Negl Trop Dis. 2012;6(11):e1908 + 23209852 + + + Bull World Health Organ. 1970;43(2):319-25 + 5312528 + + + J Theor Biol. 1981 Feb 21;88(4):719-31 + 6790878 + + + Lancet. 2016 Jun 18;387(10037):2501 + 27287833 + + + N Engl J Med. 2016 Mar 10;374(10):984-5 + 26862812 + + + Int J Environ Res Public Health. 2013 Apr 26;10(5):1698-719 + 23624579 + + + Epidemiol Infect. 2009 Aug;137(8):1188-202 + 19192322 + + + BMC Med. 2015 Apr 30;13:102 + 25976325 + + + PLoS Comput Biol. 2013 Oct;9(10):e1003308 + 24204241 + + + Am J Trop Med Hyg. 1995 Nov;53(5):489-506 + 7485707 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Elife. 2016 Apr 19;5: + 27090089 + + + Science. 2016 Jul 22;353(6297):353-4 + 27417493 + + + J Am Mosq Control Assoc. 2008 Mar;24(1):11-5 + 18437808 + + + Lancet Infect Dis. 2016 Nov;16(11):1237-1245 + 27593584 + + + Int J Infect Dis. 2016 Apr;45:95-7 + 26923081 + + + JAMA. 2017 Jan 3;317(1):59-68 + 27960197 + + + PLoS Negl Trop Dis. 2014 Aug 21;8(8):e3083 + 25144749 + + + Reprod Toxicol. 2006 May;21(4):390-8 + 16580940 + + + Lancet Infect Dis. 2017 Mar;17 (3):330-338 + 28017559 + + + PLoS Negl Trop Dis. 2013 Aug 01;7(8):e2348 + 23936579 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + Sci Rep. 2017 Jul 19;7(1):5829 + 28724972 + + + Emerg Infect Dis. 2016 Feb;22(2):336-9 + 26812472 + + + PLoS Negl Trop Dis. 2016 Dec 7;10 (12 ):e0005173 + 27926933 + + + PLoS One. 2011 May 03;6(5):e18860 + 21559329 + + + Bull World Health Organ. 2016 Nov 1;94(11):841-849 + 27821887 + + + Nat Microbiol. 2016 Jul 25;1(9):16126 + 27562260 + + + J Chem Phys. 2009 Mar 7;130(9):094104 + 19275393 + + + Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13422-7 + 23882078 + + + Glob Health Action. 2014 Dec 08;7:23119 + 25511884 + + + Bull Math Biol. 2006 Nov;68(8):1945-74 + 16832731 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11802-7 + 16868086 + + + Parasit Vectors. 2013 Dec 12;6:351 + 24330720 + + + Proc Natl Acad Sci U S A. 2017 Jan 3;114(1):119-124 + 27994145 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + PLoS Negl Trop Dis. 2012;6(8):e1792 + 22953014 + + + Acta Trop. 2011 Jul;119(1):38-43 + 21549680 + + + Proc Natl Acad Sci U S A. 2011 May 3;108(18):7460-5 + 21502510 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + Nature. 2017 Jun 15;546(7658):406-410 + 28538727 + + + Proc Natl Acad Sci U S A. 2015 Oct 20;112(42):13069-74 + 26438851 + + + Lancet. 2016 May 21;387(10033):2125-2132 + 26993883 + + + PLoS Negl Trop Dis. 2016 May 17;10 (5):e0004726 + 27186984 + + + Genome Med. 2016 Sep 29;8(1):97 + 27683027 + + + Lancet. 2017 Aug 26;390(10097):861-870 + 28647172 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + Sci Rep. 2016 Jun 17;6:28070 + 27312324 + + + Elife. 2016 Nov 29;5:null + 27897973 + + + PLoS Negl Trop Dis. 2016 May 05;10 (5):e0004658 + 27149521 + + + Elife. 2015 Jun 30;4:e08347 + 26126267 + + + Am J Trop Med Hyg. 2004 Apr;70(4):346-50 + 15100445 + + + Lancet Infect Dis. 2016 Oct;16(10 ):1100-1102 + 27676337 + + + J Infect Dis. 2016 Feb 15;213(4):604-10 + 26410592 + + + J Med Entomol. 1995 Jan;32(1):27-33 + 7869339 + + + PLoS Negl Trop Dis. 2011 Sep;5(9):e1322 + 21980544 + + + PLoS Curr. 2016 May 31;8:null + 27366586 + + + J Med Entomol. 2001 Sep;38(5):646-56 + 11580037 + + + Nature. 2016 Feb 4;530(7588):13-4 + 26842033 + + + J Hyg (Lond). 1979 Oct;83(2):213-9 + 489960 + + + PLoS Negl Trop Dis. 2016 May 05;10 (5):e0004702 + 27149628 + + + PLoS Negl Trop Dis. 2014 Feb 13;8(2):e2669 + 24551251 + + + Bull World Health Organ. 2016 Nov 1;94(11):835-840 + 27821886 + + + Aust N Z J Obstet Gynaecol. 2016 Feb;56(1):9-18 + 26391432 + + + Trans R Soc Trop Med Hyg. 2015 May;109(5):303-12 + 25771261 + + + Glob Health Action. 2014 Dec;7(1):23119 + 28672611 + + + PLoS One. 2012;7(11):e49085 + 23139836 + + + Proc Natl Acad Sci U S A. 2017 May 30;114(22):E4334-E4343 + 28442561 + + + Vector Borne Zoonotic Dis. 2004 Spring;4(1):33-42 + 15018771 + + + Epidemics. 2017 Dec;21:48-55 + 28688996 + + + Mem Inst Oswaldo Cruz. 2002 Apr;97(3):415-20 + 12048575 + + + Emerg Infect Dis. 2016 Oct;22(10 ):1788-92 + 27448188 + + + PLoS Curr. 2016 Feb 01;8:null + 27330849 + + + Bull World Health Organ. 2017 Mar 1;95(3):191-198 + 28250532 + + + Am J Trop Med Hyg. 1986 Nov;35(6):1263-79 + 3789275 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Zika + epidemiology + global health + herd-immunity + infectious disease + mathematical model + microbiology + virus + +
+ + + + 2017 + 06 + 21 + + + 2017 + 09 + 04 + + + 2017 + 9 + 10 + 6 + 0 + + + 2017 + 9 + 10 + 6 + 0 + + + 2017 + 9 + 10 + 6 + 0 + + + epublish + + 28887877 + 10.7554/eLife.29820 + PMC5638629 + + +
+ + + + + 28878777 + + 2017 + 09 + 10 + +
+ + 1664-3224 + + 8 + + 2017 + + + Frontiers in immunology + Front Immunol + + Zika Virus Promotes Neuronal Cell Death in a Non-Cell Autonomous Manner by Triggering the Release of Neurotoxic Factors. + + 1016 + + 10.3389/fimmu.2017.01016 + + Zika virus (ZIKV) has recently caused a worldwide outbreak of infections associated with severe neurological complications, including microcephaly in infants born from infected mothers. ZIKV exhibits high neurotropism and promotes neuroinflammation and neuronal cell death. We have recently demonstrated thatN-methyl-d-aspartate receptor (NMDAR) blockade by memantine prevents ZIKV-induced neuronal cell death. Here, we show that ZIKV induces apoptosis in a non-cell autonomous manner, triggering cell death of uninfected neurons by releasing cytotoxic factors. Neuronal cultures infected with ZIKV exhibit increased levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and glutamate. Moreover, infected neurons exhibit increased expression of GluN2B and augmented intracellular Ca2+concentration. Blockade of GluN2B-containing NMDAR by ifenprodil normalizes Ca2+levels and rescues neuronal cell death. Notably, TNF-α and IL-1β blockade decreases ZIKV-induced Ca2+flux through GluN2B-containing NMDARs and reduces neuronal cell death, indicating that these cytokines might contribute to NMDAR sensitization and neurotoxicity. In addition, ZIKV-infected cultures treated with ifenprodil exhibits increased activation of the neuroprotective pathway including extracellular signal-regulated kinase and cAMP response element-binding protein, which may underlie ifenprodil-mediated neuroprotection. Together, our data shed some light on the neurotoxic mechanisms triggered by ZIKV and begin to elucidate how GluN2B-containing NMDAR blockade can prevent neurotoxicity. + + + + Olmo + Isabella G + IG + + Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + Carvalho + Toniana G + TG + + Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + Costa + Vivian V + VV + + Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + Alves-Silva + Juliana + J + + Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + Ferrari + Carolina Z + CZ + + Department of Pharmacology, ICB, UFMG, Belo Horizonte, Brazil. + + + + Izidoro-Toledo + Tatiane C + TC + + Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + da Silva + Juliana F + JF + + Institute of Education and Research Santa Casa, Belo Horizonte, Brazil. + + + + Teixeira + Antonio L + AL + + Neuropsychiatry Program, Department of Psychiatry and Behavioral Science, UT Health, Houston, TX, United States. + + + + Souza + Danielle G + DG + + Department of Microbiology, ICB, UFMG, Belo Horizonte, Brazil. + + + + Marques + Joao T + JT + + Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + Teixeira + Mauro M + MM + + Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + Vieira + Luciene B + LB + + Department of Pharmacology, ICB, UFMG, Belo Horizonte, Brazil. + + + + Ribeiro + Fabiola M + FM + + Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + eng + + Journal Article + + + 2017 + 08 + 23 + +
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+ + + + + 28878742 + + 2017 + 09 + 10 + +
+ + 1664-302X + + 8 + + 2017 + + + Frontiers in microbiology + Front Microbiol + + Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic? + + 1554 + + 10.3389/fmicb.2017.01554 + + Zika is a viral disease transmitted mainly by mosquitoes of the genusAedes.In recent years, it has expanded geographically, changing from an endemic mosquito-borne disease across equatorial Asia and Africa, to an epidemic disease causing large outbreaks in several areas of the world. With the recent Zika virus (ZIKV) outbreaks in the Americas, the disease has become a focus of attention of public health agencies and of the international research community, especially due to an association with neurological disorders in adults and to the severe neurological and ophthalmological abnormalities found in fetuses and newborns of mothers exposed to ZIKV during pregnancy. A large number of studies have been published in the last 3 years, revealing the structure of the virus, how it is transmitted and how it affects human cells. Many different animal models have been developed, which recapitulate several features of ZIKV disease and its neurological consequences. Moreover, several vaccine candidates are now in active preclinical development, and three of them have already entered phase I clinical trials. Likewise, many different compounds targeting viral and cellular components are being tested inin vitroand in experimental animal models. This review aims to discuss the current state of this rapidly growing literature from a multidisciplinary perspective, as well as to present an overview of the public health response to Zika and of the perspectives for the prevention and treatment of this disease. + + + + Saiz + Juan-Carlos + JC + + Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y AlimentariaMadrid, Spain. + + + + Martín-Acebes + Miguel A + MA + + Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y AlimentariaMadrid, Spain. + + + + Bueno-Marí + Rubén + R + + Departamento de Investigación y Desarrollo (I+D), Laboratorios LokímicaValencia, Spain. + + + + Salomón + Oscar D + OD + + Instituto Nacional de Medicina TropicalPuerto Iguazú, Argentina. + + + + Villamil-Jiménez + Luis C + LC + + Grupo de Epidemiología y Salud Pública, Universidad de La SalleBogota, Colombia. + + + + Heukelbach + Jorg + J + + Department of Community Health, School of Medicine, Federal University of CearáFortaleza, Brazil. + + + College of Public Health, Medical and Veterinary Sciences, Division of Tropical Health and Medicine, James Cook University, TownsvilleQLD, Australia. + + + + Alencar + Carlos H + CH + + Department of Community Health, School of Medicine, Federal University of CearáFortaleza, Brazil. + + + + Armstrong + Paul K + PK + + Communicable Disease Control Directorate, Western Australia Department of Health, PerthWA, Australia. + + + + Ortiga-Carvalho + Tania M + TM + + Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de JaneiroRio de Janeiro, Brazil. + + + + Mendez-Otero + Rosalia + R + + Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de JaneiroRio de Janeiro, Brazil. + + + + Rosado-de-Castro + Paulo H + PH + + Instituto de Ciências Biomédicas, Universidade Federal do Rio de JaneiroRio de Janeiro, Brazil. + + + Instituto D'Or de Pesquisa e EnsinoRio de Janeiro, Brazil. + + + + Pimentel-Coelho + Pedro M + PM + + Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de JaneiroRio de Janeiro, Brazil. + + + + eng + + Journal Article + Review + + + 2017 + 08 + 22 + +
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+ + 1756-0500 + + 10 + 1 + + 2017 + Sep + 06 + + + BMC research notes + BMC Res Notes + + Association between suspected Zika virus disease during pregnancy and giving birth to a newborn with congenital microcephaly: a matched case-control study. + + 457 + + 10.1186/s13104-017-2796-1 + + In early 2015, an outbreak of an acute exanthematous illness with dengue-like symptoms occurred in northeastern Brazil. By the end of the same year, an unexpected increase in the number of cases of microcephaly was observed in the region. The microcephaly outbreak cause was unknown and rumors pointing to various potential causes arose. Since we were unaware at the time if this scenario would attract the interest of the broader scientific community, due to the neglected regions associated and as often happens with many others health conditions related to infectious diseases in Latin America. This coupled with the fact that diagnostic testing for Zika virus was not available, prompted us to design a study that could demonstrate the correlation between the development of an exanthematous illness with Zika-like symptoms during pregnancy and the delivery of a newborn with congenital microcephaly. + Mothers who experienced symptoms associated with the Zika virus during pregnancy had 10 times higher odds of delivering newborns with congenital microcephaly when compared with mothers who did not exhibit Zika-like symptoms. Thus, the acute exanthematous illness outbreak could be associated with the congenital microcephaly outbreak. We could not distinguish which virus caused the acute exanthematous illness in the study subjects (Zika, dengue or chikungunya), but these results could help to reduce the misquided speculation in regards to the cause of the microcephaly and could have expedited public health policies intended for controlling the mosquito vector. In addition to the lower head circumference, microcephalic neonates also had lower thoracic circumference, lower height and lower weight compared to non-microcephalic babies suggesting intrauterine growth restriction. Additionally, we found borderline association between mothers classified as homemakers and, who had past dengue infections with microcephaly. Prior contraction of dengue virus seems to play a role in the risk for the condition reflecting the domestication of the Aedes Aegypti and the enhancement of the Zika virus infection by dengue antibodies, respectively. The limitations of this study are: (a) participants recall bias, (b) absence of laboratory test results for Zika virus and other arboviruses and (c) incomplete test results for other pathogens that could lead to microcephaly. The study protocol was registered at ClinicalTrial.gov under the identifier NCT02741882. Registered on April 13th, 2016. + + + + Santa Rita + Ticiane Henriques + TH + + Sabin Laboratory, SAAN Quadra 03, Lotes 165 e 245, Federal District, Brasília, Brazil. + + + University of Brasília, Federal District, Brasilia, Brazil. + + + + Barra + Renata Barcelos + RB + + Secretaria do Estado da Saúde, Federal District, Brasília, Brazil. + + + + Peixoto + Gisele Pasquali + GP + + Secretaria do Estado da Saúde, Federal District, Brasília, Brazil. + + + + Mesquita + Pedro Goes + PG + + Sabin Laboratory, SAAN Quadra 03, Lotes 165 e 245, Federal District, Brasília, Brazil. + + + + Barra + Gustavo Barcelos + GB + + Sabin Laboratory, SAAN Quadra 03, Lotes 165 e 245, Federal District, Brasília, Brazil. gbbarra@gmail.com. + + + University of Brasília, Federal District, Brasilia, Brazil. gbbarra@gmail.com. + + + + eng + + + ClinicalTrials.gov + + NCT02741882 + + + + + Journal Article + + + 2017 + 09 + 06 + +
+ + England + BMC Res Notes + 101462768 + 1756-0500 + + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + MMWR Morb Mortal Wkly Rep. 2016 Jun 03;65(21):543-6 + 27254248 + + + Lancet. 2016 Feb 20;387(10020):719-21 + 26876373 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + Medicine (Baltimore). 2016 Mar;95(12):e3201 + 27015222 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + N Engl J Med. 2017 Feb 14;:null + 28195756 + + + JAMA Pediatr. 2017 Mar 1;171(3):288-295 + 27812690 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Emerg Infect Dis. 2017 Apr;23 (4):569-573 + 28322690 + + + J Epidemiol Community Health. 1990 Sep;44(3):179-86 + 2273353 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Emerg Infect Dis. 2015 Dec;21(12):2274-6 + 26584464 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Case–control study + Microcephaly + Zika virus + +
+ + + + 2017 + 04 + 03 + + + 2017 + 08 + 31 + + + 2017 + 9 + 8 + 6 + 0 + + + 2017 + 9 + 8 + 6 + 0 + + + 2017 + 9 + 8 + 6 + 0 + + + epublish + + 28877754 + 10.1186/s13104-017-2796-1 + 10.1186/s13104-017-2796-1 + PMC5588708 + + +
+ + + + + 28844634 + + 2018 + 01 + 05 + +
+ + 1474-4457 + + 18 + 1 + + 2018 + Jan + + + The Lancet. Infectious diseases + Lancet Infect Dis + + Infectious causes of microcephaly: epidemiology, pathogenesis, diagnosis, and management. + + e1-e13 + + S1473-3099(17)30398-5 + 10.1016/S1473-3099(17)30398-5 + + Microcephaly is an important sign of neurological malformation and a predictor of future disability. The 2015-16 outbreak of Zika virus and congenital Zika infection brought the world's attention to links between Zika infection and microcephaly. However, Zika virus is only one of the infectious causes of microcephaly and, although the contexts in which they occur vary greatly, all are of concern. In this Review, we summarise important aspects of major congenital infections that can cause microcephaly, and describe the epidemiology, transmission, clinical features, pathogenesis, management, and long-term consequences of these infections. We include infections that cause substantial impairment: cytomegalovirus, herpes simplex virus, rubella virus, Toxoplasma gondii, and Zika virus. We highlight potential issues with classification of microcephaly and show how some infants affected by congenital infection might be missed or incorrectly diagnosed. Although Zika virus has brought the attention of the world to the problem of microcephaly, prevention of all infectious causes of microcephaly and appropriately managing its consequences remain important global public health priorities. + Copyright © 2018 Elsevier Ltd. All rights reserved. + + + + Devakumar + Delan + D + + Institute for Global Health, University College London, London, UK. Electronic address: d.devakumar@ucl.ac.uk. + + + + Bamford + Alasdair + A + + Infectious Diseases Department, Great Ormond Street Hospital, London, UK; Great Ormond Street Institute of Child Health, University College London, London, UK. + + + + Ferreira + Marcelo U + MU + + Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil. + + + + Broad + Jonathan + J + + Department of Paediatrics, University of Oxford, Oxford, UK. + + + + Rosch + Richard E + RE + + Great Ormond Street Institute of Child Health, University College London, London, UK. + + + + Groce + Nora + N + + Leonard Cheshire Disability and Inclusive Development Centre, University College London, London, UK. + + + + Breuer + Judith + J + + Division of Infection and Immunity, University College London, London, UK. + + + + Cardoso + Marly A + MA + + Department of Nutrition, School of Public Health, University of São Paulo, São Paulo, Brazil. + + + + Copp + Andrew J + AJ + + Great Ormond Street Institute of Child Health, University College London, London, UK. + + + + Alexandre + Paula + P + + Great Ormond Street Institute of Child Health, University College London, London, UK. + + + + Rodrigues + Laura C + LC + + Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. + + + + Abubakar + Ibrahim + I + + Institute for Global Health, University College London, London, UK. + + + + eng + + Journal Article + Review + + + 2017 + 08 + 30 + +
+ + United States + Lancet Infect Dis + 101130150 + 1473-3099 + +
+ + + + 2016 + 11 + 01 + + + 2017 + 06 + 02 + + + 2017 + 06 + 15 + + + 2017 + 8 + 29 + 6 + 0 + + + 2017 + 8 + 29 + 6 + 0 + + + 2017 + 8 + 29 + 6 + 0 + + + ppublish + + 28844634 + S1473-3099(17)30398-5 + 10.1016/S1473-3099(17)30398-5 + + +
+ + + + + 28837029 + + 2017 + 08 + 31 + +
+ + 1518-0557 + + 21 + 3 + + 2017 + 09 + 01 + + + JBRA assisted reproduction + JBRA Assist Reprod + + Zika Virus Outbreak - Should assisted reproduction patients avoid pregnancy? + + 208-211 + + 10.5935/1518-0557.20170040 + + To discuss the requirement from the National Health Surveillance Agency (ANVISA), for assisted reproduction treatment patients to undergo laboratory tests for ZIKV detection, and if the public health authorities and government leaders' recommendations to women simply avoid pregnancy is prudent. + This study was performed in a university-affiliated in vitro fertilization center in Brazil. We present a critical discussion on the risk of microcephaly due to ZIKV infection and the prevalence of other harmful pathogens to vulnerable pregnant women and infants. We assessed, 954 patients undergoing intracytoplasmic sperm injection cycles (ICSI), between April and November of 2016, concerning the results of ZIKV test, according to different regions in Brazil. + Patients undergoing ICSI cycles were split into groups, according to their region of origin: 28 (3.0%) were from the North, 27 (2.8%) were from the Northeast, 40 (4.2%) were from the Midwest, 830 (87.2%) were from the Southeast, and 29 (3.0%) were from the South. Concerning the diagnosis, 112 samples had a positive or inconclusive result for ZIKV, by chromatography immunoassay. These samples were re-analyzed by ELISA and no result was positive. All positive results were from the Southeast region and none from the Northeast or Midwest regions, which are considered endemic regions. + ZIKV test before the onset of assisted reproduction treatments does not rule out the risk of the infection during pregnancy. In addition, although ZIKV infection risk is extremely high, the microcephaly risk due to ZIKV is not higher than the risk of miscarriage and birth defects due to other recognized pathogens. + + + + Borges + Edson + E + Jr + + Fertility - Medical Group, São Paulo, SP - Brazil. + + + Instituto Sapientiae - Centro de Estudos e Pesquisa em Reprodução Humana Assistida, São Paulo, SP - Brazil. + + + + Braga + Daniela Paes de Almeida Ferreira + DPAF + + Fertility - Medical Group, São Paulo, SP - Brazil. + + + Disciplina de Urologia, Área de Reprodução Humana, Departamento de Cirurgia, Universidade Federal de São Paulo - UNIFESP. + + + + Zanetti + Bianca Ferrarini + BF + + Fertility - Medical Group, São Paulo, SP - Brazil. + + + + Setti + Amanda Souza + AS + + Instituto Sapientiae - Centro de Estudos e Pesquisa em Reprodução Humana Assistida, São Paulo, SP - Brazil. + + + + Provenza + Rodrigo Rosa + RR + + Fertility - Medical Group, São Paulo, SP - Brazil. + + + + Iaconelli + Assumpto + A + Jr + + Fertility - Medical Group, São Paulo, SP - Brazil. + + + + eng + + Journal Article + + + 2017 + 09 + 01 + +
+ + Brazil + JBRA Assist Reprod + 101684552 + 1517-5693 + + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + Sex Transm Infect. 2008 Apr;84(2):117-21 + 17901085 + + + Science. 2016 Aug 12;353(6300):aaf8160 + 27417495 + + + Lancet. 2016 Feb 20;387(10020):719-21 + 26876373 + + + JAMA. 1999 Mar 24-31;281(12):1099-105 + 10188660 + + + J Pediatr. 2001 Aug;139(2):210-4 + 11487745 + + + J Epidemiol Community Health. 1986 Sep;40(3):205-9 + 3021888 + + + Lancet. 2016 Aug 13;388(10045):717-27 + 26948435 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Sex Transm Dis. 2008 May;35(5):507-11 + 18356772 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + Sex Transm Infect. 2006 Dec;82 Suppl 5:v26-8 + 17118954 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Trop Med Int Health. 2014 Aug;19(8):943-57 + 24815954 + + + Lancet. 2016 Jan 16;387(10015):227-8 + 26775124 + + + Vaccine. 2015 May 15;33(21):2406-13 + 25839105 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Obstet Gynecol. 2005 Oct;106(4):845-56 + 16199646 + + + Arch Gynecol Obstet. 2012 May;285(5):1271-85 + 22350326 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + N Engl J Med. 2014 Jun 5;370(23):2211-8 + 24897084 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):55-8 + 26820163 + + + Microbiol Spectr. 2016 Aug;4(4):null + 27726776 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Zika virus + birth defects + microcephaly + miscarriage + pregnancy + +
+ + + + 2017 + 8 + 25 + 6 + 0 + + + 2017 + 8 + 25 + 6 + 0 + + + 2017 + 8 + 25 + 6 + 0 + + + epublish + + 28837029 + 10.5935/1518-0557.20170040 + PMC5574642 + + +
+ + + + + 28835931 + + 2017 + 08 + 29 + +
+ + 2469-2964 + + 2 + 2 + + 2017 + + + Pathogens & immunity + Pathog Immun + + T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus. + + 274-292 + + 10.20411/pai.v2i2.188 + + The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or otherflavivirusesendemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection. + We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNγ ELISPOT. + Three peptides induced IFNγ production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects. + We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE. + + + + Paquin-Proulx + Dominic + D + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, D.C. + + + + Leal + Fabio E + FE + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, D.C. + + + + Terrassani Silveira + Cassia G + CG + + Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, SP, Brazil. + + + + Maestri + Alvino + A + + Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, SP, Brazil. + + + + Brockmeyer + Claudia + C + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, D.C. + + + + Kitchen + Shannon M + SM + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, D.C. + + + + Cabido + Vinicius D + VD + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, D.C. + + + + Kallas + Esper G + EG + + Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, SP, Brazil. + + + + Nixon + Douglas F + DF + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, D.C. + + + + eng + + + P30 AI117970 + AI + NIAID NIH HHS + United States + + + + Journal Article + + + 2017 + 06 + 30 + +
+ + United States + Pathog Immun + 101683909 + 2469-2964 + + + + Nucleic Acids Res. 2013 Jul;41(Web Server issue):W597-600 + 23671338 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + N Engl J Med. 2015 Sep 24;373(13):1195-206 + 26214039 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + JAMA. 2017 Jan 3;317(1):59-68 + 27960197 + + + Sci Transl Med. 2016 Mar 16;8(330):330ra36 + 27089205 + + + Nucleic Acids Res. 2015 Jul 1;43(W1):W580-4 + 25845596 + + + J Infect Dis. 2015 Dec 1;212(11):1743-51 + 25980035 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + MMWR Morb Mortal Wkly Rep. 2016 Dec 16;65(49):1409-1413 + 27977645 + + + Rev Bras Hematol Hemoter. 2012;34(1):25-30 + 23049380 + + + Nat Med. 2016 Nov;22(11):1256-1259 + 27618651 + + + BMC Bioinformatics. 2007 Oct 31;8:424 + 17973982 + + + PLoS Comput Biol. 2008 Apr 04;4(4):e1000048 + 18389056 + + + Clin Transl Immunology. 2016 Dec 16;5(12 ):e117 + 28090318 + + + Nat Med. 2003 Jul;9(7):921-7 + 12808447 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + J Immunol. 2010 Jun 1;184(11):6320-6 + 20439913 + + + Lancet. 2016 May 21;387(10033):2125-2132 + 26993883 + + + Int J Immunogenet. 2015 Feb;42(1):19-25 + 25418108 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + J Infect Dis. 2017 Mar 1;215(5):781-785 + 28039355 + + + Emerg Infect Dis. 2017 Apr;23 (4):569-573 + 28322690 + + + Cell. 2016 Aug 25;166(5):1247-1256.e4 + 27565347 + + + Nat Immunol. 2016 Sep;17 (9):1102-8 + 27339099 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + BMC Bioinformatics. 2010 Nov 22;11:568 + 21092157 + + + Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7852-7 + 27354515 + + + Immunology. 2017 Feb;150(2):146-154 + 27763656 + + + J Virol. 2017 Feb 14;91(5): + 27974563 + + + Nat Microbiol. 2017 Mar 13;2:17036 + 28288094 + + + Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12 + 25348405 + + + + CD4 + ELISPOT + IFNγ + T cell + antibody dependent enhancement + dengue virus + zika virus + + POTENTIAL CONFLICTS OF INTEREST The authors declare that no competing interests exist. +
+ + + + 2017 + 8 + 25 + 6 + 0 + + + 2017 + 8 + 25 + 6 + 0 + + + 2017 + 8 + 25 + 6 + 1 + + + ppublish + + 28835931 + 10.20411/pai.v2i2.188 + PMC5565216 + NIHMS889896 + + + +
+ + + + + 28825520 + + 2017 + 09 + 18 + + + 2017 + 09 + 18 + +
+ + 1544-0591 + + 96 + 10 + + 2017 + Sep + + + Journal of dental research + J. Dent. Res. + + Postnatal Identification of Zika Virus Peptides from Saliva. + + 1078-1084 + + 10.1177/0022034517723325 + + We explored the potential to diagnose Zika virus (ZIKV) infection by analyzing peptides in saliva during a convalescent phase of infection, long after resolution of acute disease. A 25-y-old woman clinically diagnosed with Zika fever in the first trimester was enrolled with her dizygotic twins for a 3-mo postnatal sample of saliva (9-mo after maternal infection). The female baby (A) had microcephaly while the male baby (B) was born healthy. Peptidomic analysis was completed by mass spectrometry (MS/MS), and ZIKV peptides were identified using the National Institutes of Health Zika Virus Resource database, then aligned and mapped to the ZIKV polyprotein to determine proteome coverage and phylogenetic studies. A total of 423 (mother), 607 (baby A), and 183 (baby B) unique ZIKV peptides were identified in saliva by MS/MS, providing a coverage of 67%, 84%, and 45%, respectively, of the entire ZIKV polyprotein (>3,400 amino acids). All peptides were aligned to other flaviviruses that are circulating in Brazil (dengue and yellow fever) to discard false-positive matches. Nine peptides identified were highly conserved to dengue virus. Alignment of a contiguous peptide sequence for mother/babies with the 74 ZIKV sequences suggested that the virus may have entered the oral cavity through the salivary glands, leading to an infection that persists into the postnatal period (vertical transmission). Furthermore, we identified 9 sequence variations that were unique to the baby with microcephaly (not found in the mother or the twin). This sequence information could provide a template for future neuropathogenic studies. A much larger sample size is required to determine whether sequence variation in the envelope protein significantly associates with microcephaly. Finally, from a public health perspective, it will be important to determine whether viral replication is still taking place after birth and whether the virus can be transmitted through salivary contact. + + + + Zuanazzi + D + D + + 1 Schulich Dentistry and Department of Biochemistry, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada. + + + + Arts + E J + EJ + + 2 Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada. + + + + Jorge + P K + PK + + 1 Schulich Dentistry and Department of Biochemistry, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada. + + + 3 Department of Pediatric Dentistry, Bauru Dental School, University of São Paulo Bauru, São Paulo, Brazil. + + + + Mulyar + Y + Y + + 1 Schulich Dentistry and Department of Biochemistry, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada. + + + + Gibson + R + R + + 2 Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada. + + + + Xiao + Y + Y + + 1 Schulich Dentistry and Department of Biochemistry, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada. + + + + Bringel Dos Santos + M + M + + 3 Department of Pediatric Dentistry, Bauru Dental School, University of São Paulo Bauru, São Paulo, Brazil. + + + + Machado + Maria Aparecida A M + MAAM + + 3 Department of Pediatric Dentistry, Bauru Dental School, University of São Paulo Bauru, São Paulo, Brazil. + + + + Siqueira + W L + WL + + 1 Schulich Dentistry and Department of Biochemistry, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada. + + + + eng + + Case Reports + Journal Article + +
+ + United States + J Dent Res + 0354343 + 0022-0345 + + + + 0 + Peptides + + + D + IM + + + Adult + + + Brazil + + + Female + + + Humans + + + Infant + + + Male + + + Mass Spectrometry + + + Microcephaly + virology + + + Peptides + analysis + + + Pregnancy + + + Proteomics + + + Saliva + virology + + + Twins, Dizygotic + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + + + + diagnosis + mass spectrometry + microcephaly + proteins + proteomics + viral markers + +
+ + + + 2017 + 8 + 22 + 6 + 0 + + + 2017 + 8 + 22 + 6 + 0 + + + 2017 + 9 + 19 + 6 + 0 + + + ppublish + + 28825520 + 10.1177/0022034517723325 + + +
+ + + + + 28818572 + + 2017 + 10 + 24 + +
+ + 1872-9096 + + 146 + + 2017 + Oct + + + Antiviral research + Antiviral Res. + + Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice. + + 1-11 + + S0166-3542(17)30197-3 + 10.1016/j.antiviral.2017.08.007 + + Zika fever, a mosquito-borne infectious disease caused by Zika virus (ZIKV), is an epidemic disease for which no effective therapy has been established. The recent outbreaks of ZIKV in Brazil and French Polynesia have been linked to a considerable increase in the incidence of fetal microcephaly and other diseases such as Guillain-Barre syndrome. Because there is currently no specific therapy or vaccine, the early exploitation of a method to prevent expansion of ZIKV is a high priority. To validate commonly used antiviral drugs, we evaluated the effect of ribavirin, a drug used to treat hepatitis C with interferon-β (IFN-β), on ZIKV replication. In mammalian cells, we observed an inhibitory effect of ribavirin on ZIKV replication and ZIKV-induced cell death without cytotoxic effect. Furthermore, we found that STAT1-deficient mice, which lack type I IFN signaling, were highly sensitive to ZIKV infection and exhibited lethal outcome. Ribavirin abrogated viremia in ZIKV-infected STAT-1-deficient mice. These data suggest that the inhibition of viral RNA-dependent RNA polymerases may be effective for treatment of ZIKV infection. Our data provide a new insight into the mechanisms for inhibition of ZIKV replication and prevention of Zika fever. + Copyright © 2017 Elsevier B.V. All rights reserved. + + + + Kamiyama + Naganori + N + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. Electronic address: kamiyama@oita-u.ac.jp. + + + + Soma + Ryusuke + R + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Hidano + Shinya + S + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Watanabe + Kei + K + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Umekita + Hiroshi + H + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Fukuda + Chiaki + C + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Noguchi + Kaori + K + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Gendo + Yoshiko + Y + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Ozaki + Takashi + T + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Sonoda + Akira + A + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Sachi + Nozomi + N + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Runtuwene + Lucky Ronald + LR + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Miura + Yumako + Y + + Department of Neurology, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Matsubara + Etsuro + E + + Department of Neurology, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Tajima + Shigeru + S + + Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan. + + + + Takasaki + Tomohiko + T + + Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan. + + + + Eshita + Yuki + Y + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. + + + + Kobayashi + Takashi + T + + Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, Japan. Electronic address: takashik@oita-u.ac.jp. + + + + eng + + Journal Article + + + 2017 + 08 + 14 + +
+ + Netherlands + Antiviral Res + 8109699 + 0166-3542 + + + Ribavirin + STAT1-deficient mice + Zika virus + +
+ + + + 2017 + 03 + 17 + + + 2017 + 06 + 27 + + + 2017 + 08 + 13 + + + 2017 + 8 + 19 + 6 + 0 + + + 2017 + 8 + 19 + 6 + 0 + + + 2017 + 8 + 19 + 6 + 0 + + + ppublish + + 28818572 + S0166-3542(17)30197-3 + 10.1016/j.antiviral.2017.08.007 + + +
+ + + + + 28790458 + + 2018 + 01 + 19 + + + 2018 + 01 + 19 + +
+ + 2222-1751 + + 6 + 8 + + 2017 + Aug + 09 + + + Emerging microbes & infections + Emerg Microbes Infect + + Zika virus replication in the mosquito Culex quinquefasciatus in Brazil. + + e69 + + 10.1038/emi.2017.59 + + Zika virus (ZIKV) is a flavivirus that has recently been associated with an increased incidence of neonatal microcephaly and other neurological disorders. The virus is primarily transmitted by mosquito bite, although other routes of infection have been implicated in some cases. The Aedes aegypti mosquito is considered to be the main vector to humans worldwide; however, there is evidence that other mosquito species, including Culex quinquefasciatus, transmit the virus. To test the potential of Cx. quinquefasciatus to transmit ZIKV, we experimentally compared the vector competence of laboratory-reared Ae. aegypti and Cx. quinquefasciatus. Interestingly, we were able to detect the presence of ZIKV in the midgut, salivary glands and saliva of artificially fed Cx. quinquefasciatus. In addition, we collected ZIKV-infected Cx. quinquefasciatus from urban areas with high microcephaly incidence in Recife, Brazil. Corroborating our experimental data from artificially fed mosquitoes, ZIKV was isolated from field-caught Cx. quinquefasciatus, and its genome was partially sequenced. Collectively, these findings indicate that there may be a wider range of ZIKV vectors than anticipated. + + + + Guedes + Duschinka Rd + DR + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Paiva + Marcelo Hs + MH + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + Núcleo de Ciências da Vida, Centro Acadêmico do Agreste, Universidade Federal de Pernambuco, Caruaru 55002-970, Brazil. + + + + Donato + Mariana Ma + MM + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Barbosa + Priscilla P + PP + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Krokovsky + Larissa + L + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Rocha + Sura W Dos S + SWDS + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Saraiva + Karina LA + K + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Crespo + Mônica M + MM + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Rezende + Tatiana Mt + TM + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Wallau + Gabriel L + GL + http://orcid.org/0000-0002-1419-5713 + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Barbosa + Rosângela Mr + RM + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Oliveira + Cláudia Mf + CM + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Melo-Santos + Maria Av + MA + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Pena + Lindomar + L + http://orcid.org/0000-0003-1134-5699 + + Laboratório de Virologia e Terapia Experimental, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50670-420, Brazil. + + + + Cordeiro + Marli T + MT + + Laboratório de Virologia e Terapia Experimental, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50670-420, Brazil. + + + + Franca + Rafael F de O + RFO + + Laboratório de Virologia e Terapia Experimental, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50670-420, Brazil. + + + + Oliveira + André Ls de + AL + + Núcleo de Estatística e Geoprocessamento, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50670-420, Brazil. + + + + Peixoto + Christina A + CA + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + Leal + Walter S + WS + + Department of Molecular and Cellular Biology, University of California-Davis, Davis, CA 95616, USA. + + + + Ayres + Constância Fj + CF + + Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife 50760-420, Brazil. + + + + eng + + + R01 AI095514 + AI + NIAID NIH HHS + United States + + + R21 AI128931 + AI + NIAID NIH HHS + United States + + + + Journal Article + + + 2017 + 08 + 09 + +
+ + United States + Emerg Microbes Infect + 101594885 + 2222-1751 + + IM + + + Emerg Infect Dis. 2001 Jul-Aug;7(4):626-30 + 11585523 + + + Appl Environ Microbiol. 2009 Feb;75(4):1044-9 + 19098223 + + + PLoS Negl Trop Dis. 2016 Sep 06;10 (9):e0004993 + 27598421 + + + Lancet. 2016 Apr 30;387(10030):1811-2 + 27103126 + + + J Virol. 2016 Oct 28;90(22):10145-10159 + 27581979 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Am J Trop Med Hyg. 1998 May;58(5):578-86 + 9598444 + + + Nat Methods. 2012 Mar 04;9(4):357-9 + 22388286 + + + Mem Inst Oswaldo Cruz. 1995 Jan-Feb;90(1):115-9 + 8524072 + + + Euro Surveill. 2016 Sep 1;21(35): + 27605159 + + + PLoS One. 2014 Oct 13;9(10):e109442 + 25310102 + + + Emerg Microbes Infect. 2016 Sep 07;5(9):e102 + 27599470 + + + J Med Entomol. 2005 May;42(3):429-44 + 15962797 + + + Am J Trop Med Hyg. 1987 Nov;37(3 Suppl):69S-76S + 2891312 + + + PLoS Negl Trop Dis. 2016 Apr 20;10(4):e0004641 + 27096156 + + + PLoS Negl Trop Dis. 2016 Mar 03;10(3):e0004543 + 26938868 + + + BMC Microbiol. 2007 Jan 30;7:9 + 17263893 + + + Bioinformatics. 2014 Aug 1;30(15):2114-20 + 24695404 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + PLoS Negl Trop Dis. 2012;6(8):e1792 + 22953014 + + + Mem Inst Oswaldo Cruz. 2016 Oct;111(10 ):655-658 + 27706382 + + + Trans R Soc Trop Med Hyg. 1956 Sep;50(5):442-8 + 13380987 + + + Vector Borne Zoonotic Dis. 2015 Jul;15(7):397-403 + 26186511 + + + J Autoimmun. 2016 Apr;68:1-13 + 26925496 + + + Euro Surveill. 2016 Sep 1;21(35): + 27605056 + + + Genome Med. 2016 Sep 29;8(1):97 + 27683027 + + + Sci Rep. 2016 Apr 27;6:24885 + 27117953 + + + Emerg Microbes Infect. 2016 Mar 16;5:e22 + 26980239 + + + Tissue Cell. 2015 Oct;47(5):515-25 + 26250484 + + + PLoS Negl Trop Dis. 2016 Sep 21;10(9):e0005024 + 27654962 + + + Cell Host Microbe. 2016 Jun 8;19(6):771-4 + 27156023 + + + Nature. 2016 Mar 10;531(7593):173 + 26961650 + + + Am J Trop Med Hyg. 1998 Apr;58(4):519-24 + 9574802 + + + Vector Borne Zoonotic Dis. 2012 Jul;12(7):605-8 + 22276651 + + + Pest Manag Sci. 2013 Dec;69(12):1307-14 + 23576326 + + + PLoS Negl Trop Dis. 2016 Sep 19;10 (9):e0004959 + 27643685 + + + PLoS Negl Trop Dis. 2016 Oct 5;10 (10 ):e0005048 + 27706161 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Emerg Infect Dis. 2016 Oct;22(10):1857-9 + 27434194 + + + PLoS Negl Trop Dis. 2016 Oct 26;10 (10 ):e0005101 + 27783679 + + + Southeast Asian J Trop Med Public Health. 1989 Dec;20(4):611-21 + 2576966 + + + Lancet Infect Dis. 2016 Mar;16(3):278-9 + 26852727 + + + Vector Borne Zoonotic Dis. 2016 Oct;16(10 ):673-6 + 27556838 + + + Am J Trop Med Hyg. 2007 Jan;76(1):118-28 + 17255239 + + + BJOG. 2016 Jul;123(8):1265-1269 + 27150580 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + BMC Evol Biol. 2009 Jul 09;9:160 + 19589156 + + + Trans R Soc Trop Med Hyg. 1956 May;50(3):238-42 + 13337908 + + + BMC Infect Dis. 2015 Nov 02;15:492 + 26527535 + + + F1000Res. 2016 Oct 20;5:2546 + 27853521 + + + Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11255-9 + 20534559 + + + Proteomics. 2016 Oct;16(19):2582-2586 + 27343150 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Aedes + virology + + + Animals + + + Brazil + epidemiology + + + Culex + virology + + + Genome, Viral + + + Humans + + + Microcephaly + epidemiology + + + Mosquito Vectors + physiology + virology + + + Saliva + virology + + + Salivary Glands + virology + + + Sequence Analysis, DNA + + + Virus Replication + + + Zika Virus + genetics + isolation & purification + physiology + + + Zika Virus Infection + epidemiology + transmission + virology + + +
+ + + + 2016 + 11 + 14 + + + 2017 + 05 + 15 + + + 2017 + 06 + 04 + + + 2017 + 8 + 10 + 6 + 0 + + + 2017 + 8 + 10 + 6 + 0 + + + 2018 + 1 + 20 + 6 + 0 + + + epublish + + 28790458 + emi201759 + 10.1038/emi.2017.59 + PMC5583667 + + +
+ + + + + 28783051 + + 2017 + 09 + 06 + +
+ + 1422-0067 + + 18 + 8 + + 2017 + Aug + 05 + + + International journal of molecular sciences + Int J Mol Sci + + Microcephaly Prevalence in Infants Born to Zika Virus-Infected Women: A Systematic Review and Meta-Analysis. + E1714 + 10.3390/ijms18081714 + + Zika virus is an emergent flavivirus transmitted byAedesgenus mosquitoes that recently reached the Americas and was soon implicated in an increase of microcephaly incidence. The objective of the present study is to systematically review the published data and perform a meta-analysis to estimate the prevalence of microcephaly in babies born to Zika virus-infected women during pregnancy. We searched PubMed and Cochrane databases, included cohort studies, and excluded case reports and case series publications. We extracted sample sizes and the number of microcephaly cases from eight studies, which permitted a calculation of prevalence rates that are pooled in a random-effects model meta-analysis. We estimated the prevalence of microcephaly of 2.3% (95% CI = 1.0-5.3%) among all pregnancies. Limitations include mixed samples of women infected at different pregnancy times, since it is known that infection at the first trimester is associated with higher risk to congenital anomalies. The estimates are deceptively low, given the devastating impact the infection causes over children and their families. We hope our study contributes to public health knowledge to fight Zika virus epidemics to protect mothers and their newborns. + + + + Coelho + Antonio Victor Campos + AVC + + Department of Genetics, Federal University of Pernambuco, Avenida da Engenharia, Cidade Universitária, Recife 50740-600, Brazil. avccbio@gmail.com. + + + + Crovella + Sergio + S + + Institute for Maternal and Child Health, Scientific Institute for Research, Hospitalization and Care (IRCCS) Burlo Garofolo, 34137 Trieste, Italy. crovella@burlo.trieste.it. + + + Department of Developmental and Reproductive Sciences, Genetic Unit, University of Trieste, 34127 Trieste, Italy. crovella@burlo.trieste.it. + + + + eng + + Journal Article + Review + + + 2017 + 08 + 05 + +
+ + Switzerland + Int J Mol Sci + 101092791 + 1422-0067 + + + + Am J Obstet Gynecol. 2017 Mar;216(3):292.e1-292.e8 + 28153665 + + + Cad Saude Publica. 2016 Jul 21;32(7): + 27462846 + + + Ann Ist Super Sanita. 1993;29(1):57-67 + 8129273 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + JAMA. 2017 Jan 3;317(1):59-68 + 27960197 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + MMWR Morb Mortal Wkly Rep. 2016 Aug 05;65(30):774-9 + 27490087 + + + Emerg Infect Dis. 2016 Jul;22(7):1185-92 + 27070380 + + + JAMA Pediatr. 2016 Oct 1;170(10 ):940-945 + 27544075 + + + PLoS Med. 2017 Jan 3;14 (1):e1002203 + 28045901 + + + Rev Soc Bras Med Trop. 2016 Sep-Oct;49(5):553-558 + 27812648 + + + MMWR Morb Mortal Wkly Rep. 2017 Mar 03;66(8):219-222 + 28253231 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + Lancet. 2016 May 21;387(10033):2125-2132 + 26993883 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + J Natl Cancer Inst. 1959 Apr;22(4):719-48 + 13655060 + + + JAMA Neurol. 2016 Dec 1;73(12 ):1407-1416 + 27695855 + + + Contemp Clin Trials. 2007 Feb;28(2):105-14 + 16807131 + + + MMWR Morb Mortal Wkly Rep. 2017 Apr 07;66(13):366-373 + 28384133 + + + Pediatr Infect Dis J. 2017 May;36(5):528-530 + 28403061 + + + Emerg Infect Dis. 2016 Aug;22(8):1438-44 + 27144515 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Proc Natl Acad Sci U S A. 2017 May 30;114(22):E4334-E4343 + 28442561 + + + BMJ. 2016 Sep 13;354:i4721 + 27623840 + + + Ultrasound Obstet Gynecol. 2017 Jun;49(6):729-736 + 28078779 + + + Bull World Health Organ. 2017 Mar 1;95(3):191-198 + 28250532 + + + N Engl J Med. 2016 Jun 15;:null + 27305043 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):211-4 + 26938703 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + arbovirus + congenital Zika virus syndrome + emergent diseases + flavivirus + microcephaly + + The authors declare no conflict of interest. +
+ + + + 2017 + 06 + 13 + + + 2017 + 07 + 31 + + + 2017 + 08 + 03 + + + 2017 + 8 + 8 + 6 + 0 + + + 2017 + 8 + 8 + 6 + 0 + + + 2017 + 8 + 8 + 6 + 0 + + + epublish + + 28783051 + ijms18081714 + 10.3390/ijms18081714 + PMC5578104 + + +
+ + + + + 28780216 + + 2017 + 12 + 03 + +
+ + 1701-2163 + + 39 + 12 + + 2017 + Dec + + + Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC + J Obstet Gynaecol Can + + Neuroimaging Findings of Congenital Toxoplasmosis, Cytomegalovirus, and Zika Virus Infections: A Comparison of Three Cases. + + 1150-1155 + + S1701-2163(17)30317-1 + 10.1016/j.jogc.2017.05.013 + + Toxoplasmosis, cytomegalovirus (CMV), and Zika virus (ZIKV) are among the common infectious agents that may infect the fetuses vertically. Clinical presentations of these congenital infections overlap significantly, and it is usually impossible to determine the causative agent clinically. The objective was the comparison of neuroimaging findings in three fetuses who underwent intrauterine infection by toxoplasmosis, CMV, and ZIKV. + Three confirmed cases of congenital toxoplasmosis, CMV, and ZIKV infections were included in the study over 7 months prospectively. Prenatal ultrasound, fetal brain MRI, and postnatal neuroimaging (CT or MRI) were performed on all of the included cases and interpreted by an expert radiologist. + The mean GA at the time of prenatal imaging was 34.5 ± 3.5 weeks. The main neuroimaging findings in congenital toxoplasmosis were randomly distributed brain calcifications and ventricular dilatation on ultrasounds (US), as well as white matter signal change on fetal brain MRI. The main neuroimaging findings of congenital CMV infection included microcephaly, ventriculomegaly, and periventricular calcifications on US, as well as pachygyria revealed by fetal MRI. The case of congenital ZIKV infection showed microcephaly, ventriculomegaly, and periventricular calcifications on ultrasound, as well as brain atrophy and brain surface smoothness on fetal MRI. + Although the neuroimaging findings in congenital infections are not pathognomonic, in combination with the patient history may be suggestive of one of the infectious agents, which will guide the management strategy. + Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved. + + + + Werner + Heron + H + + Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, Brazil. + + + + Daltro + Pedro + P + + Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, Brazil. + + + + Fazecas + Tatiana + T + + Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, Brazil. + + + + Zare Mehrjardi + Mohammad + M + + Department of Radiology, Shohada Tajrish Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Section of Neuroimaging, Division of Clinical Research, Climax Radiology Education Foundation, Tehran, Iran. + + + + Araujo Júnior + Edward + E + + Department of Obstetrics, Paulista School of Medicine, Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil. Electronic address: araujojred@terra.com.br. + + + + eng + + Journal Article + + + 2017 + 08 + 02 + +
+ + Netherlands + J Obstet Gynaecol Can + 101126664 + 1701-2163 + + + Toxoplasmosis + Zika virus + cytomegalovirus + magnetic resonance imaging + ultrasound + +
+ + + + 2017 + 03 + 22 + + + 2017 + 05 + 08 + + + 2017 + 05 + 10 + + + 2017 + 8 + 7 + 6 + 0 + + + 2017 + 8 + 7 + 6 + 0 + + + 2017 + 8 + 7 + 6 + 0 + + + ppublish + + 28780216 + S1701-2163(17)30317-1 + 10.1016/j.jogc.2017.05.013 + + +
+ + + + + 28767975 + + 2017 + 10 + 04 + + + 2017 + 10 + 04 + +
+ + 1678-8060 + + 112 + 8 + + 2017 + Jun + 26 + + + Memorias do Instituto Oswaldo Cruz + Mem. Inst. Oswaldo Cruz + + Culex quinquefasciatus from areas with the highest incidence of microcephaly associated with Zika virus infections in the Northeast Region of Brazil are refractory to the virus. + + 577-579 + + S0074-02762017000800577 + 10.1590/0074-02760170145 + + Zika virus (ZIKV) is widely distributed in Brazil and the Northeast Region (NE) is the most affected zone, showing the highest incidence of microcephaly associated with ZIKV congenital infections worldwide. We report attempts to infect three populations of Culex quinquefasciatus from severely affected sites in the NE and Southeast Region (SE) of Brazil with three strains of ZIKV isolated from these localities. An Aedes aegypti population from the SE was used as a positive control. All tested Cx. quinquefasciatus populations were refractory to the ZIKV isolates. For these reasons, we believe Cx. quinquefasciatus should not be considered a potential vector of ZIKV in Brazil. + + + + Fernandes + Rosilainy Surubi + RS + + Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Mosquitos Transmissores de Hematozoários, Rio de Janeiro, RJ, Brasil. + + + + Campos + Stéphanie Silva + SS + + Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Mosquitos Transmissores de Hematozoários, Rio de Janeiro, RJ, Brasil. + + + + Ribeiro + Paulino Siqueira + PS + + Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Mosquitos Transmissores de Hematozoários, Rio de Janeiro, RJ, Brasil. + + + + Raphael + Lidiane Ms + LM + + Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular de Flavivírus, Rio de Janeiro, RJ, Brasil. + + + + Bonaldo + Myrna C + MC + + Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular de Flavivírus, Rio de Janeiro, RJ, Brasil. + + + + Lourenço-de-Oliveira + Ricardo + R + + Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Mosquitos Transmissores de Hematozoários, Rio de Janeiro, RJ, Brasil. + + + + eng + + + U01 AI115595 + AI + NIAID NIH HHS + United States + + + + Journal Article + + + 2017 + 06 + 26 + +
+ + Brazil + Mem Inst Oswaldo Cruz + 7502619 + 0074-0276 + + IM + + + Mem Inst Oswaldo Cruz. 2017 May;112(5):319-327 + 28443985 + + + Emerg Infect Dis. 2017 Jul;23 (7):1085-1091 + 28430562 + + + PLoS Negl Trop Dis. 2016 Sep 06;10 (9):e0004993 + 27598421 + + + PLoS Negl Trop Dis. 2016 Jun 24;10 (6):e0004816 + 27341420 + + + Int J Environ Res Public Health. 2013 Jan 11;10(1):249-77 + 23343982 + + + Euro Surveill. 2016 Sep 1;21(35): + 27605159 + + + Emerg Microbes Infect. 2016 Sep 07;5(9):e102 + 27599470 + + + Emerg Infect Dis. 2017 Mar;23 (3):559-560 + 28005002 + + + Mem Inst Oswaldo Cruz. 2016 Oct;111(10 ):655-658 + 27706382 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + PLoS Negl Trop Dis. 2016 Sep 19;10 (9):e0004959 + 27643685 + + + PLoS Negl Trop Dis. 2016 Oct 5;10 (10 ):e0005048 + 27706161 + + + PLoS Negl Trop Dis. 2016 Oct 26;10 (10 ):e0005101 + 27783679 + + + Trends Parasitol. 2011 Mar;27(3):111-4 + 21215699 + + + + + Animals + + + Brazil + epidemiology + + + Culex + virology + + + Incidence + + + Microcephaly + epidemiology + virology + + + Mosquito Vectors + virology + + + Saliva + virology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + transmission + + +
+ + + + 2017 + 04 + 13 + + + 2017 + 05 + 15 + + + 2017 + 8 + 3 + 6 + 0 + + + 2017 + 8 + 3 + 6 + 0 + + + 2017 + 10 + 5 + 6 + 0 + + + epublish + + 28767975 + S0074-02762017005007101 + 10.1590/0074-02760170145 + PMC5530542 + + +
+ + + + + 28755567 + + 2017 + 12 + 05 + +
+ + 1934-8800 + + 49 + + 2017 + Nov + + + Infant behavior & development + Infant Behav Dev + + Microcephaly and Zika virus: Neuroradiological aspects, clinical findings and a proposed framework for early evaluation of child development. + + 70-82 + + S0163-6383(16)30134-5 + 10.1016/j.infbeh.2017.07.002 + + As the recent outbreak of microcephaly cases caused by Zika virus has been declared a global health emergency, providing assessment guidelines for multidisciplinary teams providing early developmental screening and stimulation to infants with microcephaly is much needed. Thus, the aim of this manuscript is to provide an overview on what is known about neuroradiological aspects and clinical findings in infants with microcephaly caused by Zika virus and to propose a framework for early evaluation of child development. + The keywords "Zika virus" and "microcephaly" were searched in PubMed database for articles published from incept to May 2017. These texts were reviewed, and the ones addressing neuroradiological and clinical findings in infants were selected. Recommendations for early assessment were made based on the International Classification of Functionality Disability and Health (ICF) model. + The database search yielded 599 publications and 36 were selected. The studies detected microcephaly with diffuse brain malformations and calcifications, ventriculomegaly, optic nerve hypoplasia, macular atrophy, cataracts, impaired visual and hearing function, arthrogryposis, spasticity, hyperreflexia, irritability, tremors, and seizures, but very little is known about early development. Early assessments were described based on the ICF domains (Body Function and Structures, Activities and Participation and Contextual factors). + Studies published showed abnormal brain, optic, neurologic and orthopedic findings, but very little is known about other aspects of functioning in infants with microcephaly caused by Zika virus. The biopsychosocial model based on the ICF paradigm provides an adequate framework to describe the condition of the infant with microcephaly receiving rehabilitative efforts to minimize disability. Efforts towards early identification of developmental delays should be taken within the first six months of life. + Copyright © 2017 Elsevier Inc. All rights reserved. + + + + Cicuto Ferreira Rocha + Nelci Adriana + NA + + Department of Physical Therapy, Child Development Analysis Laboratory (LADI), Federal University of São Carlos (UFSCar), Rodovia Washington Luis, km 235, São Carlos, SP, 13565-905, Brazil. Electronic address: acicuto@gmail.com. + + + + de Campos + Ana Carolina + AC + + Department of Physical Therapy, Child Development Analysis Laboratory (LADI), Federal University of São Carlos (UFSCar), Rodovia Washington Luis, km 235, São Carlos, SP, 13565-905, Brazil. + + + + Cicuto Ferreira Rocha + Fellipe + F + + Medical School, Pontifical Catholic University of Campinas (PUC-Campinas), Av. John Boyd Dunlop, s/n - Jardim Ipaussurama, Campinas, SP, 13060-904, Brazil. + + + + Pereira Dos Santos Silva + Fernanda + F + + Department of Physical Therapy, Child Development Analysis Laboratory (LADI), Federal University of São Carlos (UFSCar), Rodovia Washington Luis, km 235, São Carlos, SP, 13565-905, Brazil. + + + + eng + + Journal Article + + + 2017 + 07 + 26 + +
+ + United States + Infant Behav Dev + 7806016 + 0163-6383 + + + Early development + Infant + International Classification of Functionality Disability and Health + Microcephaly + Zika virus + +
+ + + + 2016 + 09 + 01 + + + 2017 + 05 + 30 + + + 2017 + 07 + 14 + + + 2017 + 7 + 30 + 6 + 0 + + + 2017 + 7 + 30 + 6 + 0 + + + 2017 + 7 + 30 + 6 + 0 + + + ppublish + + 28755567 + S0163-6383(16)30134-5 + 10.1016/j.infbeh.2017.07.002 + + +
+ + + + + 28728607 + + 2017 + 07 + 23 + +
+ + 1756-3305 + + 10 + 1 + + 2017 + Jul + 20 + + + Parasites & vectors + Parasit Vectors + + Zika virus transmission to mouse ear by mosquito bite: a laboratory model that replicates the natural transmission process. + + 346 + + 10.1186/s13071-017-2286-2 + + Zika disease has transformed into a serious global health problem due to the rapid spread of the arbovirus and alarming severity including congenital complications, microcephaly and Guillain-Barré syndrome. Zika virus (ZIKV) is primarily transmitted to humans through the bite of an infective mosquito, with Aedes aegypti being the main vector. + We successfully developed a ZIKV experimental transmission model by single infectious Ae. aegypti bite to a laboratory mouse using circulating Brazilian strains of both arbovirus and vector. Mosquitoes were orally infected and single Ae. aegypti were allowed to feed on mouse ears 14 days post-infection. Additionally, salivary gland (SG) homogenates from infected mosquitoes were intrathoracically inoculated into naïve Ae. aegypti. Mosquito and mouse tissue samples were cultured in C6/36 cells and processed by quantitative real-time PCR. + A total of 26 Ae. aegypti were allowed to feed individually on mouse ears. Of these, 17 mosquitoes fed, all to full engorgement. The transmission rate of ZIKV by bite from these engorged mosquitoes to mouse ears was 100%. The amount of virus inoculated into the ears by bites ranged from 2 × 102-2.1 × 1010ZIKV cDNA copies and was positively correlated with ZIKV cDNA quantified from SGs dissected from mosquitoes post-feeding. Replicating ZIKV was confirmed in macerated SGs (2.45 × 107cDNA copies), mouse ear tissue (1.15 × 103cDNA copies, and mosquitoes 14 days post-intrathoracic inoculation (1.49 × 107cDNA copies) by cytopathic effect in C6/36 cell culture and qPCR. + Our model illustrates successful transmission of ZIKV by an infectious mosquito bite to a live vertebrate host. This approach offers a comprehensive tool for evaluating the development of infection in and transmission from mosquitoes, and the vertebrate-ZIKV interaction and progression of infection following a natural transmission process. + + + + Secundino + Nagila Francinete Costa + NFC + + Laboratory of Medical Entomology, René Rachou Research Centre - FIOCRUZ-MG, Belo Horizonte, Minas Gerais, Brazil. nagila@cpqrr.fiocruz.br. + + + + Chaves + Barbara Aparecida + BA + + Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil. + + + + Orfano + Alessandra Silva + AS + + Laboratory of Medical Entomology, René Rachou Research Centre - FIOCRUZ-MG, Belo Horizonte, Minas Gerais, Brazil. + + + + Silveira + Karine Renata Dias + KRD + + Laboratory of Medical Entomology, René Rachou Research Centre - FIOCRUZ-MG, Belo Horizonte, Minas Gerais, Brazil. + + + + Rodrigues + Nilton Barnabe + NB + + Laboratory of Medical Entomology, René Rachou Research Centre - FIOCRUZ-MG, Belo Horizonte, Minas Gerais, Brazil. + + + + Campolina + Thais Bonifácio + TB + + Laboratory of Medical Entomology, René Rachou Research Centre - FIOCRUZ-MG, Belo Horizonte, Minas Gerais, Brazil. + + + + Nacif-Pimenta + Rafael + R + + Laboratory of Medical Entomology, René Rachou Research Centre - FIOCRUZ-MG, Belo Horizonte, Minas Gerais, Brazil. + + + + Villegas + Luiz Eduardo Martinez + LEM + + Laboratory of Medical Entomology, René Rachou Research Centre - FIOCRUZ-MG, Belo Horizonte, Minas Gerais, Brazil. + + + + Silva + Breno Melo + BM + + Department of Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil. + + + + Lacerda + Marcus Vinícius Guimarães + MVG + + Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil. + + + Leonidas e Maria Deane Research Centre - FIOCRUZ, Manaus, Amazonas, Brazil. + + + + Norris + Douglas Eric + DE + + Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. + + + + Pimenta + Paulo Filemon Paolucci + PFP + + Laboratory of Medical Entomology, René Rachou Research Centre - FIOCRUZ-MG, Belo Horizonte, Minas Gerais, Brazil. + + + + eng + + Journal Article + + + 2017 + 07 + 20 + +
+ + England + Parasit Vectors + 101462774 + 1756-3305 + + + + Infect Genet Evol. 2014 Dec;28:691-703 + 25117872 + + + PLoS Pathog. 2007 Sep 14;3(9):1262-70 + 17941708 + + + J Neuroimmune Pharmacol. 2017 Apr 25;:null + 28444557 + + + Science. 2008 Aug 15;321(5891):970-4 + 18703742 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + J Hyg (Lond). 1956 Jun;54(2):192-200 + 13346079 + + + Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10125-30 + 18626016 + + + Parasit Vectors. 2012 Jan 19;5:20 + 22260275 + + + Science. 2016 Aug 12;353(6300):aaf8160 + 27417495 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Immunity. 2016 Jun 21;44(6):1455-69 + 27332734 + + + Genome Announc. 2016 Mar 03;4(2):null + 26941134 + + + Trans R Soc Trop Med Hyg. 2004 Jan;98(1):43-54 + 14702837 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Mem Inst Oswaldo Cruz. 2016 Oct;111(10 ):655-658 + 27706382 + + + Nat Commun. 2016 Jun 28;7:12204 + 27352279 + + + Science. 2000 Nov 17;290(5495):1351-4 + 11082061 + + + Cell Host Microbe. 2016 Jun 8;19(6):771-4 + 27156023 + + + PLoS Negl Trop Dis. 2016 May 05;10 (5):e0004658 + 27149521 + + + PLoS Negl Trop Dis. 2016 May 05;10 (5):e0004702 + 27149628 + + + Virology. 2017 Jul;507:75-81 + 28431281 + + + J Vis Exp. 2016 Aug 23;(114):null + 27584546 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Parasit Vectors. 2014 Jul 11;7:320 + 25015526 + + + Trans R Soc Trop Med Hyg. 1956 May;50(3):238-42 + 13337908 + + + PLoS Pathog. 2009 Jun;5(6):e1000484 + 19543375 + + + + Aedes aegypti + Laboratory model + Transmission + Zika virus + +
+ + + + 2017 + 05 + 26 + + + 2017 + 07 + 12 + + + 2017 + 7 + 22 + 6 + 0 + + + 2017 + 7 + 22 + 6 + 0 + + + 2017 + 7 + 22 + 6 + 0 + + + epublish + + 28728607 + 10.1186/s13071-017-2286-2 + 10.1186/s13071-017-2286-2 + PMC5520231 + + +
+ + + + + 28727526 + + 2017 + 08 + 22 + + + 2017 + 08 + 22 + +
+ + 1541-0048 + + 107 + 9 + + 2017 + Sep + + + American journal of public health + Am J Public Health + + Zika and Reproductive Rights in Brazil: Challenge to the Right to Health. + + 1376-1380 + + 10.2105/AJPH.2017.303924 + + The Zika virus epidemic rapidly spread across Brazil and Latin America, gaining international attention because of the causal relationship between Zika and birth defects. The high number of cases in Brazil has been attributed to a failure of the state to contain the epidemic and protect the affected people, especially women. Therefore, the public health crisis created by Zika exposed a stark conflict between Brazil's constitutional right to health and the long-standing violation of reproductive rights in the country. Although health is considered to be a right of all in Brazil, women struggle with barriers to reproductive services and lack of access to safe and legal abortions. In response to the epidemic, women's rights advocates have filed a lawsuit with Brazil's supreme court that requires the decriminalization of abortion upon the diagnosis of Zika virus. However, the selective decriminalization of abortion may lead to negative social consequences and further stigmatization of people with disabilities. A solution to the reproductive health crisis in Brazil must reconcile women's right to choose and the rights of people with disabilities. + + + + Valente + Pablo K + PK + + At the time of writing, Pablo K. Valente was a graduate student in the Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, NY. + + + + eng + + Journal Article + + + 2017 + 07 + 20 + +
+ + United States + Am J Public Health + 1254074 + 0090-0036 + + AIM + IM + + + Cad Saude Publica. 2016 Jun 3;32(5): + 27276695 + + + + + Abortion, Legal + + + Brazil + epidemiology + + + Developing Countries + + + Female + + + Healthcare Disparities + + + Humans + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Reproductive Health + legislation & jurisprudence + + + Reproductive Rights + legislation & jurisprudence + + + Women's Rights + legislation & jurisprudence + + + Zika Virus Infection + epidemiology + + +
+ + + + 2017 + 7 + 21 + 6 + 0 + + + 2017 + 8 + 23 + 6 + 0 + + + 2017 + 7 + 21 + 6 + 0 + + + ppublish + + 28727526 + 10.2105/AJPH.2017.303924 + + +
+ + + + + 28719330 + + 2017 + 07 + 31 + + + 2017 + 09 + 26 + +
+ + 1476-1645 + + 97 + 1 + + 2017 + Jul + + + The American journal of tropical medicine and hygiene + Am. J. Trop. Med. Hyg. + + Case Report: Microcephaly in Twins due to the Zika Virus. + + 151-154 + + 10.4269/ajtmh.16-1021 + + Recent studies have demonstrated an association between congenital Zika virus (ZIKV) infection and microcephaly; however, to date, there have been no reports on the consequences of ZIKV infection on fetuses in twin pregnancies. Herein, we reported on the first case of a monochorionic diamniotic (MCDA) twin pregnancy having ZIKV-related microcephaly. Our findings suggested that, in an MCDA twin pregnancy, the ZIKV may cause infection in both fetuses, resulting in severe abnormalities in the central nervous system due to neural cell destruction and the disruption of the normal development processes of the brain. This case report and other similar twin cases may help to understand the pathogenesis and to confirm the etiology of ZIKV as a teratogenic microorganism. + + + + Santos + Victor S + VS + + Federal University of Sergipe, Aracaju, Brazil. + + + + Oliveira + Sheila J G + SJG + + Federal University of Sergipe, Aracaju, Brazil. + + + + Gurgel + Ricardo Q + RQ + + Federal University of Sergipe, Aracaju, Brazil. + + + + Lima + Dorothy R R + DRR + + Federal University of Sergipe, Aracaju, Brazil. + + + + Dos Santos + Cliomar A + CA + + Central Public Health Laboratory, Aracaju, Brazil. + + + + Martins-Filho + Paulo R S + PRS + + Federal University of Sergipe, Aracaju, Brazil. + + + + eng + + Case Reports + Journal Article + +
+ + United States + Am J Trop Med Hyg + 0370507 + 0002-9637 + + AIM + IM + + + J Am Acad Audiol. 2000 May;11(5):283-90 + 10821506 + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Lancet. 2017 Jan 7;389(10064):125-126 + 27939402 + + + Pediatrics. 2003 Aug;112(2):e153-7 + 12897321 + + + MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65(33):870-878 + 27559830 + + + Dtsch Arztebl Int. 2011 Mar;108(12):197-204 + 21505601 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + MMWR Morb Mortal Wkly Rep. 2016 Sep 02;65(34):917-9 + 27585248 + + + Radiographics. 2013 Jan-Feb;33(1):47-59 + 23322826 + + + BJOG. 2006 Mar;113(3):295-300 + 16487201 + + + BMC Pediatr. 2013 Apr 20;13:59 + 23601190 + + + Mem Inst Oswaldo Cruz. 2016 May;111(5):287-93 + 27143490 + + + Prog Brain Res. 2006;151:1-42 + 16221584 + + + Hum Pathol. 2004 May;35(5):536-45 + 15138926 + + + Am J Reprod Immunol. 2017 Feb;77(2): + 27966815 + + + Emerg Infect Dis. 2017 Mar;23 (3):405-414 + 27959260 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + JCI Insight. 2016 Aug 18;1(13):null + 27595140 + + + BMC Pediatr. 2013 Jan 02;13:1 + 23281628 + + + JAMA Ophthalmol. 2016 Aug 1;134(8):912-8 + 27228275 + + + J Matern Fetal Neonatal Med. 2016 Nov;29(21):3439-44 + 26689083 + + + Cell Host Microbe. 2016 Jul 13;20(1):83-90 + 27247001 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Trends Hear. 2014 Jul 29;18:null + 25080364 + + + Arch Pathol Lab Med. 2017 Jan;141(1):43-48 + 27681334 + + + + + Adolescent + + + Diseases in Twins + virology + + + Exotropia + congenital + etiology + pathology + + + Female + + + Humans + + + Infant, Newborn + + + Microcephaly + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + virology + + + Zika Virus Infection + complications + congenital + + +
+ + + + 2018 + 07 + 12 + + + 2017 + 7 + 19 + 6 + 0 + + + 2017 + 7 + 19 + 6 + 0 + + + 2017 + 8 + 2 + 6 + 0 + + + ppublish + + 28719330 + 10.4269/ajtmh.16-1021 + PMC5508915 + + +
+ + + + + 28715527 + + 2017 + 09 + 26 + + + 2018 + 01 + 16 + +
+ + 2168-6211 + + 171 + 9 + + 2017 + Sep + 01 + + + JAMA pediatrics + JAMA Pediatr + + Screening Criteria for Ophthalmic Manifestations of Congenital Zika Virus Infection. + + 847-854 + + 10.1001/jamapediatrics.2017.1474 + + Current guidelines recommend screening eye examinations for infants with microcephaly or laboratory-confirmed Zika virus infection but not for all infants potentially exposed to Zika virus in utero. + To evaluate eye findings in a cohort of infants whose mothers had polymerase chain reaction-confirmed Zika virus infection during pregnancy. + In this descriptive case series performed from January 2 through October 30, 2016, infants were examined from birth to 1 year of age by a multidisciplinary medical team, including a pediatric ophthalmologist, from Fernandes Figueira Institute, a Ministry of Health referral center for high-risk pregnancies and infectious diseases in children in Rio de Janeiro, Brazil. + Mother-infant pairs from Rio de Janeiro, Brazil, who presented with suspected Zika virus infection during pregnancy were referred to our institution and had serum, urine, amniotic fluid, or placenta samples tested by real-time polymerase chain reaction for Zika virus. + Description of eye findings, presence of microcephaly or other central nervous system abnormalities, and timing of infection in infants with confirmed Zika virus during pregnancy. Eye abnormalities were correlated with central nervous system findings, microcephaly, and the timing of maternal infection. + Of the 112 with polymerase chain reaction-confirmed Zika virus infection in maternal specimens, 24 infants (21.4%) examined had eye abnormalities (median age at first eye examination, 31 days; range, 0-305 days). Ten infants (41.7%) with eye abnormalities did not have microcephaly, and 8 (33.3%) did not have any central nervous system findings. Fourteen infants with eye abnormalities (58.3%) were born to women infected in the first trimester, 8 (33.3%) in the second trimester, and 2 (8.3%) in the third trimester. Optic nerve and retinal abnormalities were the most frequent findings. Eye abnormalities were statistically associated with microcephaly (odds ratio [OR], 19.1; 95% CI, 6.0-61.0), other central nervous system abnormalities (OR, 4.3; 95% CI, 1.6-11.2), arthrogryposis (OR, 29.0; 95% CI, 3.3-255.8), and maternal trimester of infection (first trimester OR, 5.1; 95% CI, 1.9-13.2; second trimester OR, 0.5; 95% CI, 0.2-1.2; and third trimester OR, 0.3; 95% CI, 0.1-1.2). + Eye abnormalities may be the only initial finding in congenital Zika virus infection. All infants with potential maternal Zika virus exposure at any time during pregnancy should undergo screening eye examinations regardless of the presence or absence of central nervous system abnormalities. + + + + Zin + Andrea A + AA + + Departamento de Pesquisa Clinica, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Tsui + Irena + I + + Department of Ophthalmology, University of California, Los Angeles. + + + + Rossetto + Julia + J + + Departamento de Pesquisa Clinica, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + Departamento de Oftalmologia, Federal University of São Paulo, São Paulo, Brazil. + + + + Vasconcelos + Zilton + Z + + Departamento de Pesquisa Clinica, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Adachi + Kristina + K + + Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles. + + + + Valderramos + Stephanie + S + + Obstetrics, Gynecology, and Reproductive Sciences Department, University of California, San Francisco. + + + + Halai + Umme-Aiman + UA + + Department of Ophthalmology, University of California, Los Angeles. + + + + Pone + Marcos Vinicius da Silva + MVDS + + Departamento de Doenças Infecciosas, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Pone + Sheila Moura + SM + + Departamento de Doenças Infecciosas, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Silveira Filho + Joel Carlos Barros + JCB + + Departamento de Oftalmologia, Universidade Unigranrio, Rio de Janeiro, Brazil. + + + + Aibe + Mitsue S + MS + + Departamento de Doenças Infecciosas, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + da Costa + Ana Carolina C + ACC + + Departamento de Pesquisa Clinica, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Zin + Olivia A + OA + + Departamento de Oftalmologia, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil. + + + + Belfort + Rubens + R + Jr + + Departamento de Oftalmologia, Federal University of São Paulo, São Paulo, Brazil. + + + + Brasil + Patricia + P + + Laboratório de Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Nielsen-Saines + Karin + K + + Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles. + + + + Moreira + Maria Elisabeth Lopes + MEL + + Departamento de Pesquisa Clinica, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + eng + + + R21 AI129534 + AI + NIAID NIH HHS + United States + + + R21 EY028318 + EY + NEI NIH HHS + United States + + + + Journal Article + +
+ + United States + JAMA Pediatr + 101589544 + 2168-6203 + + AIM + IM + + + Semin Fetal Neonatal Med. 2015 Oct;20(5):335-45 + 26092301 + + + Ophthalmology. 2017 Mar;124(3):407-408 + 27914834 + + + MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65(33):870-878 + 27559830 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + JAMA Ophthalmol. 2016 Feb 9;: + 26865554 + + + MMWR Morb Mortal Wkly Rep. 2016 Dec 02;65(47):1343-1348 + 27906905 + + + Ophthalmology. 2016 Aug;123(8):1788-94 + 27236271 + + + JAMA Ophthalmol. 2016 Oct 1;134(10 ):1200-1201 + 27490307 + + + N Engl J Med. 2016 Dec 29;375(26):2611-2613 + 27959695 + + + Jpn J Radiol. 2016 Dec;34(12 ):765-770 + 27714487 + + + JAMA Ophthalmol. 2016 Aug 1;134(8):946 + 27253205 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Lancet. 2016 Jun 18;387(10037):2502 + 27287830 + + + JAMA Ophthalmol. 2016 Nov 1;134(11):1219-1220 + 27685812 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + JAMA Ophthalmol. 2016 Aug 1;134(8):945 + 27254835 + + + J Diabetes Sci Technol. 2015 Dec 29;10 (2):301-7 + 26719134 + + + JAMA Pediatr. 2017 Mar 1;171(3):288-295 + 27812690 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Retin Cases Brief Rep. 2017 Jan 02;:null + 28060137 + + + JAMA Ophthalmol. 2016 Aug 1;134(8):912-8 + 27228275 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Telemed J E Health. 2017 Jan;23 (1):41-48 + 27310867 + + + + + Brazil + + + Cohort Studies + + + Eye Abnormalities + diagnosis + epidemiology + etiology + + + Female + + + Humans + + + Infant + + + Infant, Newborn + + + Mass Screening + methods + + + Polymerase Chain Reaction + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Prospective Studies + + + Zika Virus + + + Zika Virus Infection + complications + diagnosis + + +
+ + + + 2018 + 09 + 05 + + + 2017 + 7 + 18 + 6 + 0 + + + 2017 + 9 + 28 + 6 + 0 + + + 2017 + 7 + 18 + 6 + 0 + + + ppublish + + 28715527 + 2636587 + 10.1001/jamapediatrics.2017.1474 + PMC5710409 + + +
+ + + + + 28708997 + + 2017 + 08 + 01 + + + 2018 + 01 + 27 + +
+ + 1097-4172 + + 170 + 2 + + 2017 + Jul + 13 + + + Cell + Cell + + Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease. + + 273-283.e12 + + S0092-8674(17)30759-6 + 10.1016/j.cell.2017.06.040 + + The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted. + Copyright © 2017 Elsevier Inc. All rights reserved. + + + + Richner + Justin M + JM + + Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. + + + + Jagger + Brett W + BW + + Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. + + + + Shan + Chao + C + + Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA. + + + + Fontes + Camila R + CR + + Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA. + + + + Dowd + Kimberly A + KA + + Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, Bethesda, MD USA. + + + + Cao + Bin + B + + Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA. + + + + Himansu + Sunny + S + + Valera LLC, a Moderna Venture, 500 Technology Square, Cambridge, MA, USA. + + + + Caine + Elizabeth A + EA + + Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. + + + + Nunes + Bruno T D + BTD + + Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Medeiros + Daniele B A + DBA + + Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Muruato + Antonio E + AE + + Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. + + + + Foreman + Bryant M + BM + + Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, Bethesda, MD USA. + + + + Luo + Huanle + H + + Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. + + + + Wang + Tian + T + + Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA. + + + + Barrett + Alan D + AD + + Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA. + + + + Weaver + Scott C + SC + + Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA. + + + + Vasconcelos + Pedro F C + PFC + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil; Department of Pathology, Pará State University, Belém, Brazil. + + + + Rossi + Shannan L + SL + + Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA. + + + + Ciaramella + Giuseppe + G + + Valera LLC, a Moderna Venture, 500 Technology Square, Cambridge, MA, USA. + + + + Mysorekar + Indira U + IU + + Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. + + + + Pierson + Theodore C + TC + + Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, Bethesda, MD USA. Electronic address: piersontc@niaid.nih.gov. + + + + Shi + Pei-Yong + PY + + Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: peshi@utmb.edu. + + + + Diamond + Michael S + MS + + Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: diamond@wusm.wustl.edu. + + + + eng + + + R01 AI073755 + AI + NIAID NIH HHS + United States + + + U54 HD087011 + HD + NICHD NIH HHS + United States + + + P01 AI106695 + AI + NIAID NIH HHS + United States + + + T32 AI007172 + AI + NIAID NIH HHS + United States + + + R24 AI120942 + AI + NIAID NIH HHS + United States + + + R01 AI104972 + AI + NIAID NIH HHS + United States + + + R01 HD091218 + HD + NICHD NIH HHS + United States + + + + Journal Article + +
+ + United States + Cell + 0413066 + 0092-8674 + + + + 0 + Antibodies, Neutralizing + + + 0 + Antibodies, Viral + + + 0 + Lipids + + + 0 + NS1 protein, zika virus + + + 0 + RNA, Messenger + + + 0 + Vaccines, Subunit + + + 0 + Viral Nonstructural Proteins + + + 0 + Viral Vaccines + + + IM + + + Nature. 2016 Aug 25;536(7617):474-8 + 27355570 + + + Science. 2016 Sep 9;353(6304):1129-32 + 27492477 + + + Curr Protoc Microbiol. 2013 Nov 05;31:15D.3.1-15D.3.18 + 24510289 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Methods Mol Biol. 2017;1499:109-121 + 27987145 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + MBio. 2015 Nov 03;6(6):e01559-15 + 26530385 + + + J Virol. 2002 Jun;76(12):5847-56 + 12021317 + + + Nat Rev Microbiol. 2016 Jan;14 (1):45-54 + 26639777 + + + Sci Adv. 2017 Feb 22;3(2):e1602899 + 28261663 + + + Birth Defects Res B Dev Reprod Toxicol. 2009 Aug;86(4):328-44 + 19626656 + + + EBioMedicine. 2017 Mar;17 :157-162 + 28283425 + + + Cell Rep. 2016 Aug 9;16(6):1485-91 + 27481466 + + + Cell. 2017 Mar 9;168(6):1114-1125.e10 + 28222903 + + + Cell. 2016 Dec 1;167(6):1511-1524.e10 + 27884405 + + + J Gen Virol. 1998 Nov;79 ( Pt 11):2631-9 + 9820138 + + + J Immunol. 2009 Mar 1;182(5):2583-9 + 19234152 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + Virology. 1996 Aug 1;222(1):159-68 + 8806496 + + + Mol Cell. 2001 Mar;7(3):593-602 + 11463384 + + + Vaccine. 2011 Dec 6;29(52):9702-10 + 21945257 + + + J Exp Med. 2016 Dec 12;213(13):2913-2929 + 27852793 + + + Lancet Infect Dis. 2016 Oct;16(10):1106-7 + 27676340 + + + Nat Struct Mol Biol. 2017 Feb;24(2):184-186 + 28067914 + + + J Virol. 2016 Apr 29;90(10 ):4864-75 + 26962217 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + EBioMedicine. 2017 Mar;17 :145-156 + 28196656 + + + Nat Med. 2017 Jun;23 (6):763-767 + 28394328 + + + Semin Reprod Med. 2016 Sep;34(5):299-304 + 27607566 + + + Antiviral Res. 2013 May;98(2):192-208 + 23523765 + + + J Interferon Cytokine Res. 2006 Nov;26(11):804-19 + 17115899 + + + Science. 2016 Oct 14;354(6309):237-240 + 27708058 + + + Trends Immunol. 2013 Oct;34(10):487-94 + 24012144 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + Microbiol Mol Biol Rev. 2017 Feb 8;81(1): + 28179396 + + + Emerg Infect Dis. 2017 Jan;23 (1):99-101 + 27748649 + + + Vaccine. 2010 Jan 22;28(4):1075-83 + 19896447 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Nature. 2016 Dec 15;540(7633):438-442 + 27798603 + + + Nature. 2016 Dec 15;540(7633):443-447 + 27819683 + + + Cell Host Microbe. 2016 Jun 8;19(6):891-900 + 27198478 + + + Lancet. 2016 Apr 9;387(10027):1531-1539 + 26948433 + + + Virology. 2011 May 10;413(2):253-64 + 21429549 + + + Cell. 2016 Aug 25;166(5):1247-1256.e4 + 27565347 + + + RNA Biol. 2012 Nov;9(11):1319-30 + 23064118 + + + Nature. 2017 Mar 9;543(7644):248-251 + 28151488 + + + Cell. 2016 Aug 11;166(4):1016-27 + 27475895 + + + Cell. 2002 Mar 8;108(5):717-25 + 11893341 + + + + + Aedes + virology + + + Animals + + + Antibodies, Neutralizing + blood + + + Antibodies, Viral + blood + + + Blood Cells + virology + + + Embryo, Mammalian + virology + + + Female + + + Fetus + virology + + + Humans + + + Lipids + administration & dosage + + + Male + + + Mice + + + Mice, Inbred C57BL + + + Mutation + + + RNA, Messenger + genetics + immunology + + + Specific Pathogen-Free Organisms + + + Vaccines, Subunit + administration & dosage + immunology + + + Viral Nonstructural Proteins + genetics + immunology + + + Viral Vaccines + administration & dosage + immunology + + + Zika Virus + physiology + + + Zika Virus Infection + immunology + prevention & control + virology + + + + Vaccine + antibody + fetus + flavivirus + immunity + microcephaly + pregnancy + transmission + +
+ + + + 2017 + 04 + 05 + + + 2017 + 06 + 19 + + + 2017 + 06 + 26 + + + 2018 + 07 + 13 + + + 2017 + 7 + 15 + 6 + 0 + + + 2017 + 7 + 15 + 6 + 0 + + + 2017 + 8 + 2 + 6 + 0 + + + ppublish + + 28708997 + S0092-8674(17)30759-6 + 10.1016/j.cell.2017.06.040 + PMC5546158 + NIHMS888886 + + +
+ + + + + 28655548 + + 2017 + 12 + 28 + +
+ + 1872-7492 + + + 2017 + Jun + 26 + + + Virus research + Virus Res. + + Recent advances in understanding the adaptive immune response to Zika virus and the effect of previous flavivirus exposure. + S0168-1702(17)30462-8 + 10.1016/j.virusres.2017.06.019 + + Zika virus (ZIKV) caused explosive epidemics across the Americas, starting in Brazil in 2015, and has been associated with severe manifestations such as microcephaly in babies born to infected mothers and Guillain-Barré syndrome in adults. As the underlying mechanisms of pathogenesis remain largely unknown, diverse investigations have focused on a potential role for flavivirus cross-reactive antibodies in enhancing ZIKV infection. Antibody-dependent enhancement is especially concerning due to structural similarities between ZIKV and other flaviviruses, especially dengue virus (DENV), that co-circulate in areas affected by ZIKV. Conversely, investigating cross-neutralizing antibodies is important for understanding protection among flaviviruses, including ZIKV. In this review, we discuss the latest findings regarding ZIKV-induced adaptive immunity, such as monoclonal and polyclonal antibody responses, structural immunology, and T cell-mediated responses. Much progress has been made in a short amount of time, but many questions remain. Fully understanding the specificity, magnitude, and kinetics of B cell/antibody and T cell responses in ZIKV-infected individuals with or without prior exposure to flaviviruses is of great relevance for diagnostics and vaccine development. + Copyright © 2017 Elsevier B.V. All rights reserved. + + + + Andrade + Daniela V + DV + + Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, United States. + + + + Harris + Eva + E + + Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, United States. Electronic address: eharris@berkeley.edu. + + + + eng + + + P01 AI106695 + AI + NIAID NIH HHS + United States + + + + Journal Article + Review + + + 2017 + 06 + 26 + +
+ + Netherlands + Virus Res + 8410979 + 0168-1702 + + + + Science. 2016 Sep 9;353(6304):1129-32 + 27492477 + + + EMBO Mol Med. 2014 Mar;6(3):358-71 + 24421336 + + + J Virol. 2014 Oct;88(19):11383-94 + 25056881 + + + Cell Host Microbe. 2016 Aug 10;20(2):155-66 + 27443522 + + + Cytobios. 1987;49(196):49-55 + 3028713 + + + Int Arch Allergy Immunol. 1996 Apr;109(4):318-26 + 8634515 + + + Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16922-7 + 20837518 + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + Nat Struct Mol Biol. 2013 Jan;20(1):105-10 + 23241927 + + + Nat Rev Microbiol. 2013 Feb;11(2):115-28 + 23321534 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 Aug 19;353(6301):823-6 + 27417494 + + + Science. 1988 Jan 29;239(4839):476-81 + 3277268 + + + Adv Virus Res. 2003;60:421-67 + 14689700 + + + Nat Immunol. 2015 Feb;16(2):170-177 + 25501631 + + + Trans R Soc Trop Med Hyg. 1964 Jul;58:335-8 + 14175744 + + + Proc Natl Acad Sci U S A. 2013 May 28;110(22):E2046-53 + 23580623 + + + Neurology. 2016 Oct 11;87(15):1623-1624 + 27466468 + + + Cell. 2017 May 4;169(4):597-609.e11 + 28475892 + + + Adv Virus Res. 2003;59:141-75 + 14696329 + + + Cell Stem Cell. 2016 Aug 4;19(2):258-265 + 27162029 + + + Am J Trop Med Hyg. 2016 Nov 2;95(5):1157-1160 + 27645785 + + + Cell Host Microbe. 2016 May 11;19(5):696-704 + 27158114 + + + PLoS Pathog. 2017 Mar 9;13(3):e1006258 + 28278235 + + + J Infect Dis. 2016 Oct 1;214(7):1117-24 + 27443615 + + + Cell Rep. 2016 Sep 6;16(10 ):2576-2592 + 27568284 + + + J Immunol. 2011 Jul 1;187(1):424-33 + 21642539 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Structure. 2004 Sep;12(9):1607-18 + 15341726 + + + Nature. 2016 Apr 19;533(7603):425-8 + 27093288 + + + J Immunol. 2010 Jun 15;184(12):7281-7 + 20483770 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Arch Virol. 2013 Jul;158(7):1445-59 + 23471635 + + + Proc Natl Acad Sci U S A. 2012 May 8;109(19):7439-44 + 22499787 + + + Cell Host Microbe. 2017 Jan 11;21(1):35-46 + 28081442 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + EMBO J. 2016 Oct 17;35(20):2170-2178 + 27578809 + + + Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6986-91 + 12759475 + + + Am J Trop Med Hyg. 1952 Jan;1(1):30-50 + 14903434 + + + Emerg Infect Dis. 2017 Mar;23 (3):405-414 + 27959260 + + + Nature. 2015 Apr 2;520(7545):109-13 + 25581790 + + + Nat Struct Mol Biol. 2016 May;23 (5):456-8 + 27088990 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + Yale J Biol Med. 1970 Apr;42(5):311-28 + 5419206 + + + Nat Commun. 2017 Mar 16;8:14722 + 28300075 + + + Nature. 2016 Dec 15;540(7633):443-447 + 27819683 + + + Science. 2016 Apr 22;352(6284):467-70 + 27033547 + + + MBio. 2016 Jul 19;7(4):null + 27435464 + + + Viruses. 2015 Aug 13;7(8):4640-56 + 26287232 + + + Euro Surveill. 2016;21(10 ):30159 + 26987769 + + + J Virol. 2012 Feb;86(4):2337-46 + 22156523 + + + N Engl J Med. 2016 Sep 8;375(10):1002-4 + 27463941 + + + Emerg Infect Dis. 2016 Dec;22(12 ):2228-2230 + 27617352 + + + Lancet Infect Dis. 2016 Oct;16(10 ):1106-1107 + 27676340 + + + Nat Immunol. 2016 Sep;17 (9):1102-8 + 27339099 + + + Science. 2017 Apr 14;356(6334):175-180 + 28360135 + + + J Virol. 2006 Dec;80(23):11467-74 + 16987985 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Cell Host Microbe. 2010 Sep 16;8(3):271-83 + 20833378 + + + Emerg Infect Dis. 2017 May;23 (5):773-781 + 28418292 + + + PLoS Negl Trop Dis. 2017 May 15;11(5):e0005554 + 28505154 + + + MBio. 2015 Oct 13;6(5):e01461-15 + 26463165 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Antibody-dependent enhancement + Cross-reactivity + Dengue virus + Envelope protein + Flaviviruses + Immunity + Memory B cells + Monoclonal antibody + Neutralizing antibodies + Polyclonal antibody response + Structural immunology + T cells + Zika virus + +
+ + + + 2017 + 06 + 07 + + + 2017 + 06 + 22 + + + 2017 + 06 + 23 + + + 2018 + 12 + 26 + + + 2017 + 6 + 29 + 6 + 0 + + + 2017 + 6 + 29 + 6 + 0 + + + 2017 + 6 + 29 + 6 + 0 + + + aheadofprint + + 28655548 + S0168-1702(17)30462-8 + 10.1016/j.virusres.2017.06.019 + PMC5743770 + NIHMS897444 + + +
+ + + + + 28647173 + + 2017 + 11 + 08 + +
+ + 1474-547X + + 390 + 10107 + + 2017 + Nov + 04 + + + Lancet (London, England) + Lancet + + An update on Zika virus infection. + + 2099-2109 + + S0140-6736(17)31450-2 + 10.1016/S0140-6736(17)31450-2 + + The epidemic history of Zika virus began in 2007, with its emergence in Yap Island in the western Pacific, followed in 2013-14 by a larger epidemic in French Polynesia, south Pacific, where the first severe complications and non-vector-borne transmission of the virus were reported. Zika virus emerged in Brazil in 2015 and was declared a national public health emergency after local researchers and physicians reported an increase in microcephaly cases. In 2016, WHO declared the recent cluster of microcephaly cases and other neurological disorders reported in Brazil a global public health emergency. Similar clusters of microcephaly cases were also observed retrospectively in French Polynesia in 2014. In 2015-16, Zika virus continued its spread to cause outbreaks in the Americas and the Pacific, and the first outbreaks were reported in continental USA, Africa, and southeast Asia. Non-vector-borne transmission was confirmed and Zika virus was established as a cause of severe neurological complications in fetuses, neonates, and adults. This Review focuses on important updates and gaps in the knowledge of Zika virus as of early 2017. + Copyright © 2017 Elsevier Ltd. All rights reserved. + + + + Baud + David + D + + Materno-fetal and Obstetrics Research Unit, Obstetric Service, Department "Femme-Mère-Enfant", University Hospital, Lausanne, Switzerland. Electronic address: david.baud@chuv.ch. + + + + Gubler + Duane J + DJ + + Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore. + + + + Schaub + Bruno + B + + Centre Pluridisciplinaire de Diagnostic Prénatal de Martinique, Service de Gynécologie Obstétrique, Maison de la Femme de la Mère et de l'Enfant, Fort de France, Martinique, France; Registre des Malformations des Antilles (REMALAN), Maison de la Femme de la Mère et de l'Enfant, Centre Hospitalier Universitaire de Martinique, Fort de France, Martinique, France. + + + + Lanteri + Marion C + MC + + Blood Systems Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA; Cerus Corporation, Concord, CA, USA. + + + + Musso + Didier + D + + Unit of Emerging Infectious Diseases, Institut Louis Malardé, Tahiti, French Polynesia. + + + + eng + + Journal Article + Review + + + 2017 + 06 + 21 + +
+ + England + Lancet + 2985213R + 0140-6736 + +
+ + + + 2017 + 03 + 08 + + + 2017 + 04 + 04 + + + 2017 + 04 + 06 + + + 2017 + 6 + 26 + 6 + 0 + + + 2017 + 6 + 26 + 6 + 0 + + + 2017 + 6 + 26 + 6 + 0 + + + ppublish + + 28647173 + S0140-6736(17)31450-2 + 10.1016/S0140-6736(17)31450-2 + + +
+ +
+ + + + + 28647172 + + 2017 + 08 + 29 + +
+ + 1474-547X + + 390 + 10097 + + 2017 + Aug + 26 + + + Lancet (London, England) + Lancet + + Infection-related microcephaly after the 2015 and 2016 Zika virus outbreaks in Brazil: a surveillance-based analysis. + + 861-870 + + S0140-6736(17)31368-5 + 10.1016/S0140-6736(17)31368-5 + + On Nov 11, 2015, the Brazilian Ministry of Health declared a Public Health Emergency of National Concern in response to an increased number of microcephaly cases, possibly related to previous Zika virus outbreaks. We describe the course of the dual epidemics of the Zika virus infection during pregnancy and microcephaly in Brazil up to Nov 12, 2016, the first anniversary of this declaration. + We used secondary data for Zika virus and microcephaly cases obtained through the Brazilian Ministry of Health's surveillance systems from Jan 1, 2015, to Nov 12, 2016. We deemed possible Zika virus infections during pregnancy as all suspected cases of Zika virus disease and all initially suspected, but later discarded, cases of dengue and chikungunya fever. We defined confirmed infection-related microcephaly in liveborn infants as the presence of a head circumference of at least 2 SDs below the mean for their age and sex, accompanied by diagnostic imaging consistent with an infectious cause, or laboratory, clinical, or epidemiological results positive for Zika virus or STORCH (infectious agents known to cause congenital infection, mainly syphilis, toxoplasmosis, cytomegalovirus, and herpes simplex virus). We excluded cases of congenital anomalies or death without microcephaly. We analyse the spatial clustering of these diseases in Brazil to obtain the kernel density estimation. + Two distinct waves of possible Zika virus infection extended across all Brazilian regions in 2015 and 2016. 1 673 272 notified cases were reported, of which 41 473 (2·5%) were in pregnant women. During this period, 1950 cases of infection-related microcephaly were confirmed. Most cases (1373 [70·4%]) occurred in the northeast region after the first wave of Zika virus infection, with peak monthly occurrence estimated at 49·9 cases per 10 000 livebirths. After a major, well documented second wave of Zika virus infection in all regions of Brazil from September, 2015, to September, 2016, occurrence of microcephaly was much lower than that following the first wave of Zika virus infection, reaching epidemic levels in all but the south of Brazil, with estimated monthly peaks varying from 3·2 cases to 15 cases per 10 000 livebirths. + The distribution of infection-related microcephaly after Zika virus outbreaks has varied across time and Brazilian regions. Reasons for these apparent differences remain to be elucidated. + None. + Copyright © 2017 Elsevier Ltd. All rights reserved. + + + + de Oliveira + Wanderson Kleber + WK + + Secretariat of Health Surveillance, Brazilian Ministry of Health, Brasília, Brazil; Postgraduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: wkoliveira@gmail.com. + + + + de França + Giovanny Vinícius Araújo + GVA + + Secretariat of Health Surveillance, Brazilian Ministry of Health, Brasília, Brazil. + + + + Carmo + Eduardo Hage + EH + + Secretariat of Health Surveillance, Brazilian Ministry of Health, Brasília, Brazil. + + + + Duncan + Bruce Bartholow + BB + + Postgraduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. + + + + de Souza Kuchenbecker + Ricardo + R + + Postgraduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. + + + + Schmidt + Maria Inês + MI + + Postgraduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. + + + + eng + + Journal Article + + + 2017 + 06 + 21 + +
+ + England + Lancet + 2985213R + 0140-6736 + +
+ + + + 2016 + 11 + 18 + + + 2017 + 02 + 24 + + + 2017 + 03 + 13 + + + 2017 + 6 + 26 + 6 + 0 + + + 2017 + 6 + 26 + 6 + 0 + + + 2017 + 6 + 26 + 6 + 0 + + + ppublish + + 28647172 + S0140-6736(17)31368-5 + 10.1016/S0140-6736(17)31368-5 + + +
+ + + + + 28646619 + + 2017 + 08 + 21 + + + 2017 + 08 + 21 + +
+ + 1600-0412 + + 96 + 9 + + 2017 + Sep + + + Acta obstetricia et gynecologica Scandinavica + Acta Obstet Gynecol Scand + + Early insights into Zika's microcephaly physiopathology from the epicenter of the outbreak: teratogenic apoptosis in the central nervous system. + + 1039-1044 + + 10.1111/aogs.13184 + + Fetal infection by the Zika virus has been implicated in the exceptional rise in the number of microcephalic newborns recorded by the end of 2015 in Brazil. The mechanism by which this teratogenic effect is produced in the developing brain has not been fully established. Very early in the outbreak, we addressed this question by evaluating available initial data from a gestational and postnatal clinical investigation in the Brazilian state of Pernambuco. The present study was undertaken to test the hypothesis that the subtractive dysmorphic brain malformations observed in Zika-related microcephaly are primarily due to the massive induction of apoptosis of neuroprogenitor cells. We designed a physiopathological algorithm based on the examination of the following medical findings: epidemiological data, ultrasound images, computed tomography scans, placental tissue, cerebral fluid analysis, eye fundoscopy, neurological examination and necroscopy findings. + © 2017 Nordic Federation of Societies of Obstetrics and Gynecology. + + + + Jungmann + Patricia + P + + Department of Pathology, Pernambuco University, Recife, Brazil. + + + + Pires + Pedro + P + + Department of Maternal and Child Care, Pernambuco University, Recife, Brazil. + + + + Araujo Júnior + Edward + E + http://orcid.org/0000-0002-6145-2532 + + Department of Obstetrics, Paulista School of Medicine, Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil. + + + + eng + + Journal Article + +
+ + United States + Acta Obstet Gynecol Scand + 0370343 + 0001-6349 + + + + 0 + Teratogens + + + IM + + + Apoptosis + + + Brazil + epidemiology + + + Central Nervous System + pathology + virology + + + Disease Outbreaks + + + Female + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + physiopathology + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Teratogens + toxicity + + + Zika Virus + pathogenicity + + + Zika Virus Infection + + + + Intrauterine infection + Zika virus + apoptosis + microcephaly + ultrasound + +
+ + + + 2017 + 03 + 31 + + + 2017 + 06 + 14 + + + 2017 + 6 + 25 + 6 + 0 + + + 2017 + 8 + 22 + 6 + 0 + + + 2017 + 6 + 25 + 6 + 0 + + + ppublish + + 28646619 + 10.1111/aogs.13184 + + +
+ + + + + 28610628 + + 2017 + 09 + 25 + + + 2018 + 01 + 20 + +
+ + 1471-2334 + + 17 + 1 + + 2017 + 06 + 13 + + + BMC infectious diseases + BMC Infect. Dis. + + Case report: microcephaly associated with Zika virus infection, Colombia. + + 423 + + 10.1186/s12879-017-2522-6 + + Recently there has been a large outbreak of Zika virus infections in Colombia, South America. The epidemic began in September 2015 and continued to April 2017, for the total number of Zika cases reported of 107,870. For those confirmed Zika cases, there were nearly 20,000 (18.5%) suspected to be pregnant women, resulting in 157 confirmed cases of microcephaly in newborns reported by their health government agency. There is a clear under-estimation of the total number of cases and in addition no prior publications have been published to demonstrate the clinical aspects of the Zika infection in Colombia. We characterized one Zika presentation to be able to compare and contrast with other cases of Zika infection already reported in the literature. + In this case report, we demonstrate congenital microcephaly at week 19 of gestation in a 34-year-old mother who showed symptoms compatible with Zika virus infection from Sincelejo, State of Sucre, in the Colombian Caribbean. Zika virus RNA was detected in the placenta using real-time reverse transcriptase polymerase chain reaction (RT-PCR). At week 25, the fetus weigh estimate was 770 g, had a cephalic perimeter of 20.2 cm (5th percentile), ventriculomegaly on the right side and dilatation of the fourth ventricle. At week 32, the microcephaly was confirmed with a cephalic perimeter of 22 cm, dilatation of the posterior atrium to 13 mm, an abnormally small cerebellum (29 mm), and an augmented cisterna magna. At birth (39 weeks by cesarean section), the head circumference was 27.5 cm, and computerized axial tomography (Siemens Corp, 32-slides) confirmed microcephaly with calcifications. + We report a first case of maternal Zika virus infection associated with fetal microcephaly in Colombia and confirmed similar presentation to those observed previous in Brazil, 2015-2016. + + + + Mattar + Salim + S + 0000-0003-0526-4630 + + Universidad de Cordoba, Instituto de Investigaciones Biologicas del Tropico, Monteria, Colombia. mattarsalim@hotmail.com. + + + Clinic Salud Social, Sincelejo, Colombia. mattarsalim@hotmail.com. + + + + Ojeda + Carolina + C + + Clinic Salud Social, Sincelejo, Colombia. + + + + Arboleda + Janna + J + + Clinic Salud Social, Sincelejo, Colombia. + + + + Arrieta + German + G + + Universidad de Cordoba, Instituto de Investigaciones Biologicas del Tropico, Monteria, Colombia. + + + Clinic Salud Social, Sincelejo, Colombia. + + + CECAR, Corporacion Universitaria del Caribe, Public health group, Sincelejo, Colombia. + + + + Bosch + Irene + I + + MIT, Cambridge, MA, USA. + + + + Botia + Ingrid + I + + Clinic Salud Social, Sincelejo, Colombia. + + + + Alvis-Guzman + Nelson + N + + Universidad de Cartagena, Health Economics group, Cartagena, Colombia. + + + + Perez-Yepes + Carlos + C + + Clinica IMAT, Monteria, Colombia. + + + + Gerhke + Lee + L + + MIT, Cambridge, MA, USA. + + + + Montero + German + G + + Clinic Salud Social, Sincelejo, Colombia. + + + + eng + + Case Reports + Journal Article + + + 2017 + 06 + 13 + +
+ + England + BMC Infect Dis + 100968551 + 1471-2334 + + + Cerebellar Hypoplasia + + IM + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + Am J Obstet Gynecol. 2017 Mar;216(3):209-225 + 28126366 + + + MMWR Morb Mortal Wkly Rep. 2016 Sep 02;65(34):917-9 + 27585248 + + + MMWR Morb Mortal Wkly Rep. 2016 Dec 16;65(49):1409-1413 + 27977645 + + + Obstet Gynecol. 2016 Oct;128(4):724-30 + 27479770 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + N Engl J Med. 2016 Jun 15;:null + 27305043 + + + Braz J Infect Dis. 2016 May-Jun;20(3):227-8 + 27215946 + + + + + Brazil + + + Cerebellum + abnormalities + virology + + + Colombia + + + Developmental Disabilities + virology + + + Female + + + Humans + + + Hydrocephalus + virology + + + Infant, Newborn + + + Microcephaly + virology + + + Nervous System Malformations + virology + + + Placenta + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + virology + + + Zika Virus + pathogenicity + + + Zika Virus Infection + etiology + + + + Central nervous system vascular malformations + Colombia + Microcephaly + Pediatrics + Zika + +
+ + + + 2017 + 01 + 24 + + + 2017 + 06 + 05 + + + 2017 + 6 + 15 + 6 + 0 + + + 2017 + 6 + 15 + 6 + 0 + + + 2017 + 9 + 26 + 6 + 0 + + + epublish + + 28610628 + 10.1186/s12879-017-2522-6 + 10.1186/s12879-017-2522-6 + PMC5470308 + + +
+ + + + + 28604336 + + 2017 + 11 + 11 + +
+ + 1080-6059 + + 23 + 8 + + 2017 + 08 + + + Emerging infectious diseases + Emerging Infect. Dis. + + Characteristics of Dysphagia in Infants with Microcephaly Caused by Congenital Zika Virus Infection, Brazil, 2015. + + 1253-1259 + + 10.3201/eid2308.170354 + + We summarize the characteristics of dysphagia in 9 infants in Brazil with microcephaly caused by congenital Zika virus infection. The Schedule for Oral Motor Assessment, fiberoptic endoscopic evaluation of swallowing, and the videofluoroscopic swallowing study were used as noninstrumental and instrumental assessments. All infants had a degree of neurologic damage and showed abnormalities in the oral phase. Of the 9 infants, 8 lacked oral and upper respiratory tract sensitivity, leading to delays in initiation of the pharyngeal phase of swallowing. Those delays, combined with marked oral dysfunction, increased the risk for aspiration of food, particularly liquid foods. Dysphagia resulting from congenital Zika virus syndrome microcephaly can develop in infants >3 months of age and is severe. + + + + Leal + Mariana C + MC + + + van der Linden + Vanessa + V + + + Bezerra + Thiago P + TP + + + de Valois + Luciana + L + + + Borges + Adriana C G + ACG + + + Antunes + Margarida M C + MMC + + + Brandt + Kátia G + KG + + + Moura + Catharina X + CX + + + Rodrigues + Laura C + LC + + + Ximenes + Coeli R + CR + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + + + 2017 + 08 + 15 + +
+ + United States + Emerg Infect Dis + 9508155 + 1080-6040 + + + + Lancet. 2016 Apr 30;387(10030):1811-2 + 27103126 + + + Dysphagia. 2000 Winter;15(1):39-44 + 10594257 + + + Laryngoscope. 2007 Oct;117(10):1723-7 + 17906496 + + + MMWR Morb Mortal Wkly Rep. 2016 Dec 02;65(47):1343-1348 + 27906905 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + J Child Neurol. 2014 May;29(5):646-53 + 24022110 + + + Lancet. 2016 Aug 27;388(10047):898-904 + 27372395 + + + Dev Med Child Neurol. 2008 Aug;50(8):625-30 + 18754902 + + + J Child Neurol. 2012 Jun;27(6):708-12 + 22019841 + + + Lancet. 2014 Sep 6;384(9946):857-68 + 25209487 + + + Dysphagia. 1996 Spring;11(2):93-8 + 8721066 + + + Dev Disabil Res Rev. 2008;14(2):118-27 + 18646015 + + + Dysphagia. 1993 Fall;8(4):359-67 + 8269732 + + + Dev Med Child Neurol. 1995 Jun;37(6):528-43 + 7789662 + + + BMJ. 2016 Aug 09;354:i3899 + 27509902 + + + J Pediatr Rehabil Med. 2013 Jan 1;6(4):239-42 + 24705659 + + + Arch Dis Child Educ Pract Ed. 2012 Dec;97(6):222-9 + 22293504 + + + Dev Disabil Res Rev. 2008;14(2):77-86 + 18646019 + + + Dysphagia. 1988;2(4):216-9 + 3251697 + + + J Am Diet Assoc. 2002 Mar;102(3):361-73 + 11902369 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + Dysphagia. 2010 Sep;25(3):250-7 + 19730940 + + + Dev Med Child Neurol. 2012 Sep;54(9):784-95 + 22582745 + + + + Brazil + Zika virus infection + aspiration risk + congenital Zika syndrome + congenital infection + dysphagia + esophageal phase + infants + microcephaly + neurologic disease + oral motor dysfunction + oral phase + pharyngeal phase + swallowing + vector-borne infections + viruses + +
+ + + + 2017 + 6 + 13 + 6 + 0 + + + 2017 + 6 + 13 + 6 + 0 + + + 2017 + 6 + 13 + 6 + 0 + + + ppublish + + 28604336 + 10.3201/eid2308.170354 + PMC5547788 + + +
+ + + + + 28601976 + + 2017 + 06 + 11 + +
+ + 1559-1182 + + + 2017 + Jun + 11 + + + Molecular neurobiology + Mol. Neurobiol. + + Zika Virus as an Emerging Neuropathogen: Mechanisms of Neurovirulence and Neuro-Immune Interactions. + 10.1007/s12035-017-0635-y + + Zika virus (ZIKV) is an emerging arbovirus of the genus Flaviviridae, which causes a febrile illness and has spread from across the Pacific to the Americas in a short timeframe. Convincing evidence has implicated the ZIKV to incident cases of neonatal microcephaly and a set of neurodevelopmental abnormalities referred to as the congenital Zika virus syndrome. In addition, emerging data points to an association with the ZIKV and the development of the so-called Guillain-Barre syndrome, an acute autoimmune polyneuropathy. Accumulating knowledge suggests that neurovirulent strains of the ZIKV have evolved from less pathogenic lineages of the virus. Nevertheless, mechanisms of neurovirulence and host-pathogen neuro-immune interactions remain incompletely elucidated. This review provides a critical discussion of genetic and structural alterations in the ZIKV which could have contributed to the emergence of neurovirulent strains. In addition, a mechanistic framework of neuro-immune mechanisms related to the emergence of neuropathology after ZIKV infection is discussed. Recent advances in knowledge point to avenues for the development of a putative vaccine as well as novel therapeutic strategies. Nevertheless, there are unique unmet challenges that need to be addressed in this regard. Finally, a research agenda is proposed. + + + + Morris + Gerwyn + G + + Tir Na Nog, Bryn Road seaside 87, Llanelli, Wales, SA15 2LW, UK. + + + + Barichello + Tatiana + T + + Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil. + + + Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. + + + Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA. + + + + Stubbs + Brendon + B + + Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK. + + + Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK. + + + Faculty of Health, Social Care and Education, Anglia Ruskin University, Bishop Hall Lane, Chelmsford, CM1 1SQ, UK. + + + + Köhler + Cristiano A + CA + + Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. + + + + Carvalho + André F + AF + + Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. + + + + Maes + Michael + M + http://orcid.org/0000-0002-2012-871X + + IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, 3220, Australia. dr.michaelmaes@hotmail.com. + + + Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Parana, Brazil. dr.michaelmaes@hotmail.com. + + + Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. dr.michaelmaes@hotmail.com. + + + Revitalis, Waalre, The Netherlands. dr.michaelmaes@hotmail.com. + + + Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria. dr.michaelmaes@hotmail.com. + + + + eng + + Journal Article + Review + + + 2017 + 06 + 11 + +
+ + United States + Mol Neurobiol + 8900963 + 0893-7648 + + + Autoimmunity + Cytokines + Guillain-Barre syndrome + Microcephaly + Neurodevelopment + Neurology + Perinatal infection + Psychiatry + Zika virus + +
+ + + + 2017 + 01 + 05 + + + 2017 + 05 + 23 + + + 2017 + 6 + 12 + 6 + 0 + + + 2017 + 6 + 12 + 6 + 0 + + + 2017 + 6 + 12 + 6 + 0 + + + aheadofprint + + 28601976 + 10.1007/s12035-017-0635-y + 10.1007/s12035-017-0635-y + + +
+ + + + + 28579764 + + 2017 + 08 + 16 + +
+ + 1178-122X + + 8 + + 2017 + + + Virology : research and treatment + Virology (Auckl) + + Is Zika Virus an Emerging TORCH Agent? An Invited Commentary. + + 1178122X17708993 + + 10.1177/1178122X17708993 + + Zika virus (ZIKV) is a mosquito-borne arbovirus from the familyFlaviviridae, which had caused some epidemics since its discovery in 1947 without any significant impacts on public health. In 2015, however, a 20-fold increase in congenital microcephaly cases in northeastern Brazil was attributed to prenatally acquired ZIKV infection. Traditionally, TORCH agents have 4 common characteristics including causing a mild illness in infected mother, vertical transmission to fetus, developing several anomalies in the affected fetus, and in some instances, maternal therapy may not ameliorate fetal prognosis. Prenatal ZIKV infection has shown the aforementioned characteristics during the recent epidemics in South America and the Caribbean region; therefore, it should be considered as an emerging TORCH agent that may seriously threaten public health. Fetal ultrasound can be used as a safe, inexpensive, and easy-to-access imaging modality for detecting suspicious cases of congenital Zika syndrome in utero and suggesting confirmatory diagnostic examinations to these patients. + + + + Mehrjardi + Mohammad Zare + MZ + + Department of Radiology, Shohada Tajrish Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. + + + Section of Fetal Imaging, Division of Clinical Research, Climax Radiology Education Foundation, Tehran, Iran. + + + + eng + + Journal Article + + + 2017 + 05 + 18 + +
+ + United States + Virology (Auckl) + 101515268 + 1178-122X + + + + Sci Rep. 2016 Oct 19;6:35296 + 27759009 + + + Jpn J Radiol. 2017 Jan;35(1):41-42 + 27830429 + + + Lancet. 2016 Apr 9;387(10027):1587-90 + 26952548 + + + Jpn J Radiol. 2016 Dec;34(12 ):765-770 + 27714487 + + + J Clin Virol. 2016 Nov;84:53-58 + 27721110 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Jpn J Radiol. 2017 Feb;35(2):87-88 + 28074378 + + + Arch Pathol Lab Med. 2017 Jan;141(1):18-25 + 27763793 + + + Curr Infect Dis Rep. 2017 Jan;19(1):4 + 28220392 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + Am J Med Genet A. 2013 Nov;161A(11):2726-33 + 24124000 + + + JAMA Pediatr. 2017 Mar 1;171(3):288-295 + 27812690 + + + Clin Pediatr (Phila). 2016 Jul;55(8):698-700 + 27000068 + + + Nat Rev Microbiol. 2016 Nov;14 (11):707-715 + 27573577 + + + Am J Med Genet. 1984 Feb;17(2):509-21 + 6702901 + + + JCI Insight. 2016 Aug 18;1(13):null + 27595140 + + + Cell Host Microbe. 2016 Jul 13;20(1):83-90 + 27247001 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + Jpn J Radiol. 2017 Mar;35(3):89-94 + 28074379 + + + Curr Womens Health Rep. 2002 Aug;2(4):253-8 + 12150751 + + + Arch Pathol Lab Med. 2017 Jan;141(1):43-48 + 27681334 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + + TORCH + ZIKV + Zika virus + congenital Zika syndrome + microcephaly + pathogenesis + + DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. +
+ + + + 2017 + 02 + 09 + + + 2017 + 04 + 06 + + + 2017 + 6 + 6 + 6 + 0 + + + 2017 + 6 + 6 + 6 + 0 + + + 2017 + 6 + 6 + 6 + 1 + + + epublish + + 28579764 + 10.1177/1178122X17708993 + 10.1177_1178122x17708993 + PMC5439991 + + +
+ + + + + 28575919 + + 2017 + 08 + 09 + +
+ + 1806-9339 + + 39 + 5 + + 2017 + 05 + + + Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia + Rev Bras Ginecol Obstet + + Zika Virus Infection in Pregnant Women and Microcephaly. + + 235-248 + + 10.1055/s-0037-1603450 + + From the discovery of the Zika virus (ZIKV) in 1947 in Uganda (Africa), until its arrival in South America, it was not known that it would affect human reproductive life so severely. Today, damage to the central nervous system is known to be multiple, and microcephaly is considered the tip of the iceberg. Microcephaly actually represents the epilogue of this infection's devastating process on the central nervous system of embryos and fetuses. As a result of central nervous system aggression by the ZIKV, this infection brings the possibility of arthrogryposis, dysphagia, deafness and visual impairment. All of these changes of varying severity directly or indirectly compromise the future life of these children, and are already considered a congenital syndrome linked to the ZIKV. Diagnosis is one of the main difficulties in the approach of this infection. Considering the clinical part, it has manifestations common to infections by the dengue virus and the chikungunya fever, varying only in subjective intensities. The most frequent clinical variables are rash, febrile state, non-purulent conjunctivitis and arthralgia, among others. In terms of laboratory resources, there are also limitations to the subsidiary diagnosis. Molecular biology tests are based on polymerase chain reaction (PCR) with reverse transcriptase (RT) action, since the ZIKV is a ribonucleic acid (RNA) virus. The RT-PCR shows serum or plasma positivity for a short period of time, no more than five days after the onset of the signs and symptoms. The ZIKV urine test is positive for a longer period, up to 14 days. There are still no reliable techniques for the serological diagnosis of this infection. If there are no complications (meningoencephalitis or Guillain-Barré syndrome), further examination is unnecessary to assess systemic impairment. However, evidence is needed to rule out other infections that also cause rashes, such as dengue, chikungunya, syphilis, toxoplasmosis, cytomegalovirus, rubella, and herpes. There is no specific antiviral therapy against ZIKV, and the therapeutic approach to infected pregnant women is limited to the use of antipyretics and analgesics. Anti-inflammatory drugs should be avoided until the diagnosis of dengue is discarded. There is no need to modify the schedule of prenatal visits for pregnant women infected by ZIKV, but it is necessary to guarantee three ultrasound examinations during pregnancy for low-risk pregnancies, and monthly for pregnant women with confirmed ZIKV infection. Vaginal delivery and natural breastfeeding are advised. + Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil. + + + + Duarte + Geraldo + G + + Universidade de São Paulo, Ribeirão Preto, SP, Brazil. + + + + Moron + Antonio Fernandes + AF + + Universidade Federal de São Paulo, São Paulo, SP, Brazil. + + + + Timerman + Artur + A + + Hospital Professor Edmundo Vasconcelos, São Paulo, SP, Brazil. + + + + Fernandes + César Eduardo + CE + + Faculdade de Medicina do ABC, Santo André, SP, Brazil. + + + + Mariani Neto + Corintio + C + + Hospital Maternidade Leonor Mendes de Barros, São Paulo, SP, Brazil. + + + + Almeida Filho + Gutemberg Leão de + GL + + Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. + + + + Werner Junior + Heron + H + + Alta Excelência Diagnóstica, Rio de Janeiro, RJ, Brazil. + + + + Espírito Santo + Hilka Flavia Barra do + HFBD + + Universidade Federal do Amazonas, Manaus, AM, Brazil. + + + + Steibel + João Alfredo Piffero + JAP + + Pontifícia Universidade Católica, Porto Alegre, RS, Brazil. + + + + Bortoletti Filho + João + J + + Universidade Federal de São Paulo, São Paulo, SP, Brazil. + + + + Andrade + Juvenal Barreto Borriello de + JBB + + Consultório Médico Juvenal Barreto Borriello de Andrade, São Paulo, SP, Brazil. + + + + Burlá + Marcelo + M + + Clínica Marcelo Burlá, Rio de Janeiro, RJ Brazil. + + + + Silva de Sá + Marcos Felipe + MF + + Universidade de São Paulo, Ribeirão Preto, SP, Brazil. + + + + Busso + Newton Eduardo + NE + + Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brazil. + + + + Giraldo + Paulo César + PC + + Universidade Estadual de Campinas, Campinas, SP, Brazil. + + + + Moreira de Sá + Renato Augusto + RA + + Universidade Federal Fluminense, Niterói, RJ, Brazil. + + + + Passini Junior + Renato + R + + Universidade Estadual de Campinas, Campinas, SP, Brazil. + + + + Mattar + Rosiane + R + + Universidade Federal de São Paulo, São Paulo, SP, Brazil. + + + + Francisco + Rossana Pulcineli Vieira + RPV + + Universidade de São Paulo, São Paulo, SP, Brazil. + + + + eng + + Journal Article + + Infecção do vírus Zika em gestantes e microcefalia. + + 2017 + 06 + 02 + +
+ + Brazil + Rev Bras Ginecol Obstet + 9214757 + 0100-7203 + + + Desde a descoberta do vírus Zika (VZIK) em 1947 em Uganda, na África, até sua chegada na América do Sul, não se tinha notícia de que ele seria capaz de comprometer a vida reprodutiva em humanos de forma tão severa. Hoje, sabe-se que os danos sobre o sistema nervoso central são múltiplos, e a microcefalia é considerada a ponta do iceberg, visto que na realidade ela representa o epílogo de um processo devastador desta infecção sobre o sistema nervoso central do embrião e do feto. Em decorrência da agressão do sistema nervoso central pelo VZIK, esta infecção pode provocar artrogripose, disfagia, surdez e comprometimento visual. Todas estas alterações, de gravidade variável, direta ou indiretamente comprometem a vida futura dessas crianças, já sendo considerada uma síndrome congênita ligada ao VZIK. Uma das principais dificuldades na abordagem dessa infecção é relativa ao diagnóstico. Considerando a parte clínica, observa-se que ela apresenta manifestações comuns às infecções pelos vírus da dengue e da febre chikungunya, variando apenas em suas intensidades subjetivas. As variáveis clínicas mais frequentes são o exantema, febrícula, conjuntivite não purulenta e artralgia. No tocante aos recursos laboratoriais, também existem limitações ao diagnóstico subsidiário. As provas de biologia molecular se fundamentam na reação em cadeia da polimerase (RCP) com ação da transcriptase reversa (TT), visto que o VZIK é um vírus ácido ribonucleico (ARN). A TR-RCP apresenta positividade sérica ou plasmática por um período curto de tempo, não ultrapassando cinco dias após início dos sinais e sintomas. Esta pesquisa do VZIK na urina fica positiva por período mais prolongado, chegando a 14 dias. Ainda não existem técnicas seguras para diagnóstico sorológico dessa infecção. Não havendo complicações (meningoencefalite ou síndrome de Guillain-Barré), dificilmente são necessários mais exames complementares para avaliar o comprometimento sistêmico. No entanto, são necessárias provas para descartar as outras infecções que causam exantema, como dengue, chikungunya, sífilis, toxoplasmose, citomegalovírus, rubéola e herpes. Sabe-se que não existe terapia antiviral específica contra o VZIK, e a abordagem terapêutica de gestantes portadoras da infecção limita-se ao uso de antitérmicos e analgésicos. Orienta-se evitar anti-inflamatórios até que o diagnóstico de dengue seja descartado. Sobre a condução do pré-natal, não há necessidade de modificar o cronograma de consultas pré-natais para gestantes que foram infectadas pelo VZIK, mas é necessária a garantia de três exames ecográficos durante a gravidez para gestantes de baixo risco, e mensais para a gestante com infecção confirmada pelo VZIK. A via de parto é vaginal, e está liberado o aleitamento natural. + + Disclosure The authors report no conflicts of interest in this work. +
+ + + + 2017 + 6 + 3 + 6 + 0 + + + 2017 + 6 + 3 + 6 + 0 + + + 2017 + 6 + 3 + 6 + 0 + + + ppublish + + 28575919 + 10.1055/s-0037-1603450 + + +
+ + + + + 28572454 + + 2018 + 01 + 11 + + + 2018 + 02 + 07 + +
+ + 1095-9203 + + 357 + 6346 + + 2017 + 07 + 07 + + + Science (New York, N.Y.) + Science + + Neurodevelopmental protein Musashi-1 interacts with the Zika genome and promotes viral replication. + + 83-88 + + 10.1126/science.aam9243 + + A recent outbreak of Zika virus in Brazil has led to a simultaneous increase in reports of neonatal microcephaly. Zika targets cerebral neural precursors, a cell population essential for cortical development, but the cause of this neurotropism remains obscure. Here we report that the neural RNA-binding protein Musashi-1 (MSI1) interacts with the Zika genome and enables viral replication. Zika infection disrupts the binding of MSI1 to its endogenous targets, thereby deregulating expression of factors implicated in neural stem cell function. We further show that MSI1 is highly expressed in neural progenitors of the human embryonic brain and is mutated in individuals with autosomal recessive primary microcephaly. Selective MSI1 expression in neural precursors could therefore explain the exceptional vulnerability of these cells to Zika infection. + Copyright © 2017, American Association for the Advancement of Science. + + + + Chavali + Pavithra L + PL + 0000-0002-7525-5230 + + Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. + + + + Stojic + Lovorka + L + 0000-0001-6691-3396 + + Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. + + + + Meredith + Luke W + LW + + Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. + + + + Joseph + Nimesh + N + 0000-0002-9204-9164 + + Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. + + + + Nahorski + Michael S + MS + + Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. + + + + Sanford + Thomas J + TJ + 0000-0002-5091-1457 + + Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. + + + + Sweeney + Trevor R + TR + 0000-0003-4016-7326 + + Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. + + + + Krishna + Ben A + BA + 0000-0003-0919-2961 + + Department of Medicine, University of Cambridge, Hills Road, Cambridge CB2 2QQ, UK. + + + + Hosmillo + Myra + M + 0000-0002-3514-7681 + + Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. + + + + Firth + Andrew E + AE + 0000-0002-7986-9520 + + Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. + + + + Bayliss + Richard + R + 0000-0003-0604-2773 + + Faculty of Biological Sciences, Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. + + + + Marcelis + Carlo L + CL + 0000-0001-7095-4641 + + Department of Human Genetics, Radboud University Medical Centre, Nijmegen, Netherlands. + + + + Lindsay + Susan + S + 0000-0003-2980-4582 + + Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK. + + + + Goodfellow + Ian + I + + Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. + + + + Woods + C Geoffrey + CG + 0000-0002-8077-2101 + + Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. + + + + Gergely + Fanni + F + 0000-0002-2441-8095 + + Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. fanni.gergely@cruk.cam.ac.uk. + + + + eng + + + Wellcome Trust + United Kingdom + + + Medical Research Council + United Kingdom + + + + Journal Article + Research Support, Non-U.S. Gov't + + + 2017 + 06 + 01 + +
+ + United States + Science + 0404511 + 0036-8075 + + + + 0 + MSI1 protein, human + + + 0 + Nerve Tissue Proteins + + + 0 + RNA-Binding Proteins + + + IM + + + Science. 2017 Jul 7;357(6346):33-34 + 28684491 + + + EMBO J. 2006 Jul 12;25(13):3167-78 + 16794580 + + + Philos Trans R Soc Lond B Biol Sci. 2014 Sep 5;369(1650):null + 25047622 + + + Nature. 2015 Oct 1;526(7571):68-74 + 26432245 + + + Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15194-9 + 12407178 + + + PLoS Negl Trop Dis. 2016 Aug 25;10 (8):e0004877 + 27560129 + + + Nature. 2013 Jan 10;493(7431):216-20 + 23201682 + + + Nucleic Acids Res. 2015 Jan;43(Database issue):D726-36 + 25348401 + + + Am J Hum Genet. 2006 May;78(5):889-96 + 16642444 + + + J Vis Exp. 2014 May 17;(87):null + 24893926 + + + Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):2024-2029 + 28167751 + + + J Virol. 2017 Jan 18;91(3): + 27852856 + + + Cell Stem Cell. 2016 Nov 3;19(5):593-598 + 27545505 + + + N Engl J Med. 2012 Jan 19;366(3):243-9 + 22168587 + + + Am J Hum Genet. 2002 Jul;71(1):136-42 + 12046007 + + + Nature. 2014 Apr 10;508(7495):199-206 + 24695229 + + + Methods Mol Biol. 2016;1402:11-17 + 26721479 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Cell. 2016 Dec 1;167(6):1511-1524.e10 + 27884405 + + + EBioMedicine. 2016 Aug;10 :71-6 + 27453325 + + + Nat Commun. 2016 Feb 02;7:10406 + 26832224 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + J Neurosci. 2001 Oct 15;21(20):8091-107 + 11588182 + + + Cell Stem Cell. 2016 Aug 4;19(2):258-265 + 27162029 + + + Braz J Med Biol Res. 2016;49(5):e5420 + 27143174 + + + Genes Dev. 2016 Oct 1;30(19):2158-2172 + 27737959 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Mol Cell Biol. 2001 Jun;21(12):3888-900 + 11359897 + + + Science. 1987 Jun 19;236(4808):1567-70 + 2884728 + + + Wiley Interdiscip Rev Dev Biol. 2013 Jul;2(4):461-78 + 24014418 + + + Mol Cell Neurosci. 2006 Jan;31(1):85-96 + 16214366 + + + Am J Hum Genet. 2004 Aug;75(2):261-6 + 15199523 + + + Reproduction. 2013 Oct 01;146(5):R151-62 + 23884862 + + + PLoS Pathog. 2015 Jan 30;11(1):e1004604 + 25635835 + + + J Cell Biol. 2008 May 19;181(4):639-53 + 18490513 + + + Cell. 2016 Nov 3;167(4):1079-1087.e5 + 27814505 + + + Lancet. 2016 May 21;387(10033):2125-2132 + 26993883 + + + Hum Mol Genet. 2013 Dec 20;22(25):5199-214 + 23918663 + + + Methods Mol Biol. 2007;396:185-206 + 18025694 + + + RNA Biol. 2011 Mar-Apr;8(2):305-15 + 21505273 + + + Cell Stem Cell. 2016 May 5;18(5):559-60 + 27152436 + + + J Med Genet. 2004 Aug;41(8):e101 + 15286161 + + + Stem Cells. 2015 Dec;33(12 ):3621-34 + 26303183 + + + Annu Rev Cell Dev Biol. 2015;31:249-67 + 26566113 + + + Dev Biol. 1996 Jun 15;176(2):230-42 + 8660864 + + + PLoS Negl Trop Dis. 2016 Oct 5;10 (10 ):e0005048 + 27706161 + + + J Mol Biol. 1999 Mar 26;287(2):315-30 + 10080895 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Am J Pathol. 2016 Sep;186(9):2271-8 + 27470713 + + + Nat Med. 2016 Oct;22(10 ):1101-1107 + 27571349 + + + J Med Genet. 1993 Sep;30(9):798-9 + 8411082 + + + Mol Cell Biol. 2015 Sep 1;35(17):2965-78 + 26100017 + + + Dev Neurosci. 2000;22(1-2):139-53 + 10657706 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + J Mol Biol. 1993 Dec 5;234(3):779-815 + 8254673 + + + Exp Eye Res. 2009 Mar;88(3):347-55 + 18662689 + + + + + Animals + + + Brain + abnormalities + metabolism + virology + + + Cercopithecus aethiops + + + Child + + + Female + + + Genome, Viral + + + HEK293 Cells + + + Humans + + + Male + + + Microcephaly + genetics + metabolism + virology + + + Mutation + + + Nerve Tissue Proteins + metabolism + + + Neural Stem Cells + metabolism + physiology + virology + + + RNA-Binding Proteins + metabolism + + + Vero Cells + + + Virus Replication + + + Zika Virus + genetics + physiology + + + Zika Virus Infection + virology + + +
+ + + + 2017 + 02 + 08 + + + 2017 + 05 + 16 + + + 2017 + 6 + 3 + 6 + 0 + + + 2018 + 1 + 13 + 6 + 0 + + + 2017 + 6 + 3 + 6 + 0 + + + ppublish + + 28572454 + science.aam9243 + 10.1126/science.aam9243 + PMC5798584 + EMS75691 + + +
+ + + + + 28541340 + + 2017 + 09 + 14 + + + 2017 + 09 + 14 + +
+ + 1476-4687 + + 545 + 7655 + + 2017 + 05 + 24 + + + Nature + Nature + + Drop in cases of Zika threatens large-scale trials. + + 396-397 + + 10.1038/545396a + + + Butler + Declan + D + + + eng + + News + +
+ + England + Nature + 0410462 + 0028-0836 + + + + 0 + Viral Vaccines + + + IM + + + Biomedical Research + trends + + + Brazil + epidemiology + + + Clinical Trials as Topic + + + Disease Outbreaks + + + Female + + + Humans + + + Incidence + + + International Cooperation + + + Microcephaly + epidemiology + virology + + + Multicenter Studies as Topic + + + Patient Selection + + + Pregnancy + + + Sample Size + + + Viral Vaccines + immunology + + + Zika Virus + immunology + isolation & purification + pathogenicity + + + Zika Virus Infection + congenital + epidemiology + immunology + transmission + + +
+ + + + 2017 + 5 + 26 + 6 + 0 + + + 2017 + 5 + 26 + 6 + 0 + + + 2017 + 9 + 15 + 6 + 0 + + + ppublish + + 28541340 + 545396a + 10.1038/545396a + + +
+ + + + + 28538727 + + 2017 + 10 + 06 + + + 2017 + 12 + 15 + +
+ + 1476-4687 + + 546 + 7658 + + 2017 + 06 + 15 + + + Nature + Nature + + Establishment and cryptic transmission of Zika virus in Brazil and the Americas. + + 406-410 + + 10.1038/nature22401 + + Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus. + + + + Faria + N R + NR + + Department of Zoology, University of Oxford, Oxford OX1 3SY, UK. + + + Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil. + + + + Quick + J + J + + Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK. + + + + Claro + I M + IM + + Department of Infectious Disease, School of Medicine &Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil. + + + + Thézé + J + J + + Department of Zoology, University of Oxford, Oxford OX1 3SY, UK. + + + + de Jesus + J G + JG + + Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil. + + + + Giovanetti + M + M + + Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil. + + + University of Rome Tor Vergata, Rome, Italy. + + + + Kraemer + M U G + MUG + + Department of Zoology, University of Oxford, Oxford OX1 3SY, UK. + + + Harvard Medical School, Boston, Massachusetts, USA. + + + Boston Children's Hospital, Boston, Massachusetts, USA. + + + + Hill + S C + SC + + Department of Zoology, University of Oxford, Oxford OX1 3SY, UK. + + + + Black + A + A + + Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. + + + Department of Epidemiology, University of Washington, Seattle, Washington, USA. + + + + da Costa + A C + AC + + Department of Infectious Disease, School of Medicine &Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil. + + + + Franco + L C + LC + + Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil. + + + + Silva + S P + SP + + Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil. + + + + Wu + C-H + CH + + Department of Statistics, University of Oxford, Oxford OX1 3LB, UK. + + + + Raghwani + J + J + + Department of Zoology, University of Oxford, Oxford OX1 3SY, UK. + + + + Cauchemez + S + S + + Mathematical Modelling of Infectious Diseases and Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, France. + + + Centre National de la Recherche Scientifique, URA3012, Paris, France. + + + + du Plessis + L + L + + Department of Zoology, University of Oxford, Oxford OX1 3SY, UK. + + + + Verotti + M P + MP + + Coordenação dos Laboratórios de Saúde (CGLAB/DEVIT/SVS), Ministry of Health, Brasília, Brazil. + + + + de Oliveira + W K + WK + + Coordenação Geral de Vigilância e Resposta às Emergências em Saúde Pública (CGVR/DEVIT), Ministry of Health, Brasília, Brazil. + + + Center of Data and Knowledge Integration for Health (CIDACS), Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil. + + + + Carmo + E H + EH + + Departamento de Vigilância das Doenças Transmissíveis, Ministry of Health, Brasilia, Brazil. + + + + Coelho + G E + GE + + Coordenação Geral dos Programas de Controle e Prevenção da Malária e das Doenças Transmitidas pelo Aedes, Ministry of Health, Brasília, Brazil. + + + Pan American Health Organization (PAHO), Buenos Aires, Argentina. + + + + Santelli + A C F S + ACFS + + Coordenação Geral dos Programas de Controle e Prevenção da Malária e das Doenças Transmitidas pelo Aedes, Ministry of Health, Brasília, Brazil. + + + Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil. + + + + Vinhal + L C + LC + + Coordenação Geral dos Programas de Controle e Prevenção da Malária e das Doenças Transmitidas pelo Aedes, Ministry of Health, Brasília, Brazil. + + + + Henriques + C M + CM + + Departamento de Vigilância das Doenças Transmissíveis, Ministry of Health, Brasilia, Brazil. + + + + Simpson + J T + JT + + Ontario Institute for Cancer Research, Toronto, Ontario, Canada. + + + + Loose + M + M + + University of Nottingham, Nottingham, UK. + + + + Andersen + K G + KG + + Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA. + + + + Grubaugh + N D + ND + + Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA. + + + + Somasekar + S + S + + Departments of Laboratory Medicine and Medicine &Infectious Diseases, University of California, San Francisco, California, USA. + + + + Chiu + C Y + CY + + Departments of Laboratory Medicine and Medicine &Infectious Diseases, University of California, San Francisco, California, USA. + + + + Muñoz-Medina + J E + JE + + División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico. + + + + Gonzalez-Bonilla + C R + CR + + División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico. + + + + Arias + C F + CF + + Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico. + + + + Lewis-Ximenez + L L + LL + + Instituto Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil. + + + + Baylis + S A + SA + + Paul-Ehrlich-Institut, Langen, Germany. + + + + Chieppe + A O + AO + + Laboratório Central de Saúde Pública Noel Nutels, Rio de Janeiro, Brazil. + + + + Aguiar + S F + SF + + Laboratório Central de Saúde Pública Noel Nutels, Rio de Janeiro, Brazil. + + + + Fernandes + C A + CA + + Laboratório Central de Saúde Pública Noel Nutels, Rio de Janeiro, Brazil. + + + + Lemos + P S + PS + + Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil. + + + + Nascimento + B L S + BLS + + Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil. + + + + Monteiro + H A O + HAO + + Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil. + + + + Siqueira + I C + IC + + Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil. + + + + de Queiroz + M G + MG + + Laboratório Central de Saúde Pública do Estado do Rio Grande do Norte, Natal, Brazil. + + + + de Souza + T R + TR + + Laboratório Central de Saúde Pública do Estado do Rio Grande do Norte, Natal, Brazil. + + + Universidade Potiguar do Rio Grande do Norte, Natal, Brazil. + + + + Bezerra + J F + JF + + Laboratório Central de Saúde Pública do Estado do Rio Grande do Norte, Natal, Brazil. + + + Faculdade Natalense de Ensino e Cultura, Rio Grande do Norte, Natal, Brazil. + + + + Lemos + M R + MR + + Laboratório Central de Saúde Pública do Estado da Paraíba, João Pessoa, Brazil. + + + + Pereira + G F + GF + + Laboratório Central de Saúde Pública do Estado da Paraíba, João Pessoa, Brazil. + + + + Loudal + D + D + + Laboratório Central de Saúde Pública do Estado da Paraíba, João Pessoa, Brazil. + + + + Moura + L C + LC + + Laboratório Central de Saúde Pública do Estado da Paraíba, João Pessoa, Brazil. + + + + Dhalia + R + R + + Fundação Oswaldo Cruz (FIOCRUZ), Recife, Pernambuco, Brazil. + + + + França + R F + RF + + Fundação Oswaldo Cruz (FIOCRUZ), Recife, Pernambuco, Brazil. + + + + Magalhães + T + T + + Fundação Oswaldo Cruz (FIOCRUZ), Recife, Pernambuco, Brazil. + + + Department of Microbiology, Immunology &Pathology, Colorado State University, Fort Collins, Colorado 80523, USA. + + + + Marques + E T + ET + Jr + + Fundação Oswaldo Cruz (FIOCRUZ), Recife, Pernambuco, Brazil. + + + + Jaenisch + T + T + + Section Clinical Tropical Medicine, Department for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany. + + + + Wallau + G L + GL + + Fundação Oswaldo Cruz (FIOCRUZ), Recife, Pernambuco, Brazil. + + + + de Lima + M C + MC + + Laboratório Central de Saúde Pública do Estado de Alagoas, Maceió, Brazil. + + + + Nascimento + V + V + + Laboratório Central de Saúde Pública do Estado de Alagoas, Maceió, Brazil. + + + + de Cerqueira + E M + EM + + Laboratório Central de Saúde Pública do Estado de Alagoas, Maceió, Brazil. + + + + de Lima + M M + MM + + Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil. + + + + Mascarenhas + D L + DL + + Secretaria de Saúde de Feira de Santana, Feira de Santana, Bahia, Brazil. + + + + Neto + J P Moura + JPM + + Universidade Federal do Amazonas, Manaus, Brazil. + + + + Levin + A S + AS + + Department of Infectious Disease, School of Medicine &Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil. + + + + Tozetto-Mendoza + T R + TR + + Department of Infectious Disease, School of Medicine &Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil. + + + + Fonseca + S N + SN + + Hospital São Francisco, Ribeirão Preto, Brazil. + + + + Mendes-Correa + M C + MC + + Department of Infectious Disease, School of Medicine &Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil. + + + + Milagres + F P + FP + + Universidade Federal do Tocantins, Palmas, Brazil. + + + + Segurado + A + A + + Department of Infectious Disease, School of Medicine &Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil. + + + + Holmes + E C + EC + + University of Sydney, Sydney, Australia. + + + + Rambaut + A + A + + Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK. + + + Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA. + + + + Bedford + T + T + + Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. + + + + Nunes + M R T + MRT + + Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil. + + + Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555, USA. + + + + Sabino + E C + EC + + Department of Infectious Disease, School of Medicine &Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil. + + + + Alcantara + L C J + LCJ + + Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil. + + + + Loman + N J + NJ + + Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK. + + + + Pybus + O G + OG + + Department of Zoology, University of Oxford, Oxford OX1 3SY, UK. + + + Metabiota, San Francisco, California 94104, USA. + + + + eng + + + R35 GM119774 + GM + NIGMS NIH HHS + United States + + + MC_PC_15100/ZK/16-078 + Wellcome Trust + United Kingdom + + + 101237/Z/13/Z + Wellcome Trust + United Kingdom + + + Wellcome Trust + United Kingdom + + + R01 HL105704 + HL + NHLBI NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + + + 2017 + 05 + 24 + +
+ + England + Nature + 0410462 + 0028-0836 + + IM + + + Nature. 2017 Jun 15;546(7658):355-357 + 28538722 + + + Infect Genet Evol. 2016 Jul;41:142-145 + 27071531 + + + Mol Biol Evol. 2009 Apr;26(4):801-14 + 19131426 + + + Am J Epidemiol. 2013 Nov 1;178(9):1505-12 + 24043437 + + + BMC Infect Dis. 2011 Jun 09;11:166 + 21658238 + + + Science. 2016 Dec 2;354(6316):1088-1089 + 27934714 + + + Science. 2016 Jul 22;353(6297):353-4 + 27417493 + + + Cell. 2015 Jun 18;161(7):1516-26 + 26091036 + + + Lancet Infect Dis. 2016 Nov;16(11):1237-1245 + 27593584 + + + Philos Trans R Soc Lond B Biol Sci. 2008 Dec 27;363(1512):3985-95 + 18852111 + + + Bull World Health Organ. 2016 Dec 1;94(12 ):880-892 + 27994281 + + + Virus Evol. 2015 May 26;1(1):vev003 + 27774277 + + + Mol Biol Evol. 2006 Jan;23(1):7-9 + 16177232 + + + Science. 2016 Aug 12;353(6300):aaf8160 + 27417495 + + + PLoS Comput Biol. 2014 Apr 10;10(4):e1003537 + 24722319 + + + J Mol Evol. 1985;22(2):160-74 + 3934395 + + + Bull World Health Organ. 2016 Nov 1;94(11):841-849 + 27821887 + + + Nat Microbiol. 2016 Jul 25;1(9):16126 + 27562260 + + + Nature. 2017 Jun 15;546(7658):401-405 + 28538723 + + + Mol Biol Evol. 2012 Aug;29(8):1969-73 + 22367748 + + + Genetics. 2006 Apr;172(4):2665-81 + 16489234 + + + Curr Biol. 2011 Aug 9;21(15):1251-8 + 21737280 + + + Vector Borne Zoonotic Dis. 2016 May;16(5):295-301 + 26991057 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Emerg Microbes Infect. 2016 Oct 26;5(10 ):e111 + 27780969 + + + N Engl J Med. 2017 Apr 13;376(15):1397-1399 + 28273000 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Proc Natl Acad Sci U S A. 2017 Jan 3;114(1):119-124 + 27994145 + + + J Virol. 2003 Oct;77(20):11296-8 + 14512579 + + + Bioinformatics. 2005 Mar 1;21(5):676-9 + 15509596 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + Elife. 2015 Jun 30;4:e08347 + 26126267 + + + Lancet. 2016 Jan 23;387(10016):335-336 + 26777915 + + + Genome Announc. 2016 Sep 01;4(5):null + 27587826 + + + PLoS Negl Trop Dis. 2011 Sep;5(9):e1322 + 21980544 + + + Mol Biol Evol. 2013 Feb;30(2):239-43 + 23090976 + + + Nature. 2016 Feb 11;530(7589):228-232 + 26840485 + + + EBioMedicine. 2016 Jul;9:250-256 + 27344225 + + + Nature. 2016 Oct 12;538(7624):193-200 + 27734858 + + + Nature. 2017 Jun 15;546(7658):411-415 + 28538734 + + + Bull World Health Organ. 2016 Sep 1;94(9):675-686C + 27708473 + + + MBio. 2016 Oct 11;7(5):null + 27729507 + + + PLoS Genet. 2015 Aug 12;11(8):e1005421 + 26267488 + + + PLoS Comput Biol. 2009 Sep;5(9):e1000520 + 19779555 + + + Virus Evol. 2016 Apr 09;2(1):vew007 + 27774300 + + + Emerg Infect Dis. 2016 Oct;22(10):1788-92 + 27448188 + + + PLoS One. 2014 Mar 06;9(3):e89783 + 24603439 + + + Bioinformatics. 2015 Aug 1;31(15):2577-9 + 25819675 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Mol Biol Evol. 2006 Feb;23(2):254-67 + 16221896 + + + Syst Biol. 2010 May;59(3):307-21 + 20525638 + + + Nat Methods. 2012 Jul 30;9(8):772 + 22847109 + + + N Engl J Med. 2016 Jun 15;:null + 27305043 + + + Mol Biol Evol. 2005 May;22(5):1208-22 + 15703242 + + + Genetics. 2000 Oct;156(2):879-91 + 11014833 + + + Nat Protoc. 2017 Jun;12 (6):1261-1276 + 28538739 + + + + + Americas + epidemiology + + + Basic Reproduction Number + + + Brazil + epidemiology + + + Genetic Variation + + + Genome, Viral + genetics + + + Humans + + + Microcephaly + epidemiology + virology + + + Molecular Epidemiology + + + Phylogeography + + + Spatio-Temporal Analysis + + + Zika Virus + genetics + isolation & purification + + + Zika Virus Infection + epidemiology + transmission + virology + + +
+ + + + 2017 + 02 + 08 + + + 2017 + 05 + 02 + + + 2017 + 5 + 26 + 6 + 0 + + + 2017 + 10 + 7 + 6 + 0 + + + 2017 + 5 + 25 + 6 + 0 + + + ppublish + + 28538727 + nature22401 + 10.1038/nature22401 + PMC5722632 + NIHMS922795 + + +
+ + + + + 28534929 + + 2017 + 10 + 05 + +
+ + 1415-4757 + + 40 + 2 + + 2017 Apr-Jun + + + Genetics and molecular biology + Genet. Mol. Biol. + + Teratogens: a public health issue - a Brazilian overview. + + 387-397 + + S1415-47572017000300387 + 10.1590/1678-4685-GMB-2016-0179 + + Congenital anomalies are already the second cause of infant mortality in Brazil, as in many other middle-income countries in Latin America. Birth defects are a result of both genetic and environmental factors, but a multifactorial etiology has been more frequently observed. Here, we address the environmental causes of birth defects - or teratogens - as a public health issue and present their mechanisms of action, categories and their respective maternal-fetal deleterious effects. We also present a survey from 2008 to 2013 of Brazilian cases involving congenital anomalies (annual average of 20,205), fetal deaths (annual average of 1,530), infant hospitalizations (annual average of 82,452), number of deaths of hospitalized infants (annual average of 2,175), and the average cost of hospitalizations (annual cost of $7,758). Moreover, we report on Brazilian cases of teratogenesis due to the recent Zika virus infection, and to the use of misoprostol, thalidomide, alcohol and illicit drugs. Special attention has been given to the Zika virus infection, now proven to be responsible for the microcephaly outbreak in Brazil, with 8,039 cases under investigation (from October 2015 to June 2016). From those cases, 1,616 were confirmed and 324 deaths occurred due to microcephaly complications or alterations on the central nervous system. Congenital anomalies impact life quality and raise costs in specialized care, justifying the classification of teratogens as a public health issue. + + + + Mazzu-Nascimento + Thiago + T + + Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil. + + + Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP, Brazil. + + + + Melo + Débora Gusmão + DG + + Departamento de Medicina, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP, Brazil. + + + + Morbioli + Giorgio Gianini + GG + + Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil. + + + Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP, Brazil. + + + School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA. + + + + Carrilho + Emanuel + E + + Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil. + + + Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP, Brazil. + + + + Vianna + Fernanda Sales Luiz + FSL + + Sistema Nacional de Informação sobre Agentes Teratogênicos (SIAT), Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. + + + Programa de Pós-Graduação em Genética e Biologia Molecular, Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. + + + + Silva + André Anjos da + AA + + Sistema Nacional de Informação sobre Agentes Teratogênicos (SIAT), Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. + + + UNIVATES University, Lajeado, RS, Brazil. + + + + Schuler-Faccini + Lavinia + L + + Sistema Nacional de Informação sobre Agentes Teratogênicos (SIAT), Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. + + + Programa de Pós-Graduação em Genética e Biologia Molecular, Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. + + + + eng + + Journal Article + + + 2017 + 05 + 22 + +
+ + Brazil + Genet Mol Biol + 100883590 + 1415-4757 + + + + Ann Clin Lab Sci. 2010 Spring;40(2):99-114 + 20421621 + + + N Engl J Med. 2016 Jun 2;374(22):2195-8 + 27074370 + + + Obstet Gynecol. 1988 Aug;72(2):147-51 + 3393357 + + + J Community Genet. 2014 Jul;5(3):269-82 + 24081606 + + + Development. 2012 Mar;139(5):829-41 + 22318624 + + + Eur J Clin Pharmacol. 1995;48(3-4):177-8 + 7589037 + + + Toxicol Sci. 2011 Jul;122(1):1-6 + 21507989 + + + Mol Genet Genomic Med. 2014 Jul;2(4):280-91 + 25077170 + + + Reprod Toxicol. 1999 Mar-Apr;13(2):147-51 + 10213522 + + + Reprod Toxicol. 2006 Nov;22(4):666-71 + 16750609 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + J Public Health (Oxf). 2005 Jun;27(2):215-21 + 15820994 + + + Reprod Toxicol. 2015 Jun;53:63-7 + 25828060 + + + J Child Neurol. 2002 Feb;17(2):117-22 + 11952071 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + N Engl J Med. 2004 Apr 8;350(15):1579-82 + 15071140 + + + Am J Med Genet. 2002 Oct 15;112(3):297-303 + 12357474 + + + Clin Infect Dis. 2000 Oct;31(4):920-6 + 11049771 + + + Teratology. 1996 Dec;54(6):273-7 + 9098920 + + + Birth Defects Res A Clin Mol Teratol. 2015 Mar;103(3):178-85 + 25371388 + + + Curr Probl Pediatr. 1979 Dec;10(2):1-42 + 535420 + + + Res Dev Disabil. 2012 Jul-Aug;33(4):1147-56 + 22502840 + + + Reprod Toxicol. 2012 Sep;34(2):180-5 + 22610102 + + + Lancet. 1998 May 30;351(9116):1624-7 + 9620717 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Pediatr Neonatol. 2015 Feb;56(1):25-30 + 25267275 + + + Mutat Res. 1997 Dec 12;396(1-2):65-78 + 9434860 + + + Neurology. 2009 Sep 15;73(11):887-97 + 19752457 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + FEBS Lett. 2006 Oct 9;580(23):5442-9 + 16876788 + + + Hum Reprod Update. 2010 Jul-Aug;16(4):378-94 + 20061329 + + + Birth Defects Res C Embryo Today. 2006 Dec;78(4):293-307 + 17315243 + + + Dev Med Child Neurol. 2013 Mar;55(3):271-7 + 23241019 + + + J Pediatr. 1982 Nov;101(5):810-5 + 7131168 + + + Obstet Gynecol. 1995 Jan;85(1):141-9 + 7800312 + + + Cad Saude Publica. 2008 Jun;24(6):1447-53 + 18545770 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + PLoS One. 2011;6(7):e21735 + 21754997 + + + Reprod Toxicol. 2012 Sep;34(2):186-91 + 22659091 + + + Int J Gynaecol Obstet. 2015 Dec;131(3):219-25 + 26433469 + + + Cad Saude Publica. 2005 Jul-Aug;21(4):1055-64 + 16021243 + + + Neurotoxicol Teratol. 2003 Mar-Apr;25(2):131-282 + 12748001 + + + Birth Defects Res B Dev Reprod Toxicol. 2005 Oct;74(5):392-8 + 16193500 + + + Integr Cancer Ther. 2004 Dec;3(4):294-300 + 15523100 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Obstet Gynecol Clin North Am. 2014 Jun;41(2):229-39 + 24845487 + + + Exp Physiol. 2008 Jan;93(1):27-42 + 18165431 + + + Am J Med Genet. 2000 Dec 11;95(4):302-6 + 11186881 + + + Am J Clin Nutr. 2000 May;71(5 Suppl):1295S-303S + 10799405 + + + Genet Mol Biol. 2012 Dec;35(4 (suppl)):960-5 + 23412828 + + + J Epidemiol Community Health. 2003 May;57(5):344-6 + 12700217 + + + Birth Defects Res A Clin Mol Teratol. 2010 Dec;88(12):1008-16 + 20878909 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Birth Defects Res A Clin Mol Teratol. 2007 Sep;79(9):671-2 + 17676592 + + + Rev Soc Bras Med Trop. 2008 May-Jun;41(3):309-12 + 18719816 + + + Rev Obstet Gynecol. 2009 Summer;2(3):159-68 + 19826573 + + + Teratology. 1994 Aug;50(2):97-8 + 7801306 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Hum Reprod Update. 1996 Jan-Feb;2(1):43-55 + 9079402 + + + Clin Dermatol. 1999 Jul-Aug;17(4):469-78 + 10497734 + + + Fed Regist. 2014 Dec 4;79(233):72063-103 + 25509060 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + J Allergy Clin Immunol. 1999 Feb;103(2 Pt 2):S337-42 + 9949334 + + + Int J Gynaecol Obstet. 1998 Dec;63 Suppl 1:S131-9 + 10075223 + + + J Pediatr. 1963 Oct;63:650-9 + 14074423 + + + Cien Saude Colet. 2014 Mar;19(3):853-63 + 24714899 + + + Am J Med Genet C Semin Med Genet. 2014 Jun;166C(2):124-39 + 24816482 + + + Rev Saude Publica. 2007 Jun;41(3):396-403 + 17515993 + + + Teratology. 2002;66 Suppl 1:S3-6 + 12239736 + + + Drug Alcohol Depend. 1987 Jan;19(1):51-70 + 3545731 + + +
+ + + + 2016 + 07 + 01 + + + 2016 + 10 + 07 + + + 2017 + 5 + 24 + 6 + 0 + + + 2017 + 5 + 24 + 6 + 1 + + + 2017 + 5 + 24 + 6 + 0 + + + ppublish + + 28534929 + S1415-47572017005014103 + 10.1590/1678-4685-GMB-2016-0179 + PMC5488458 + + +
+ + + + + 28522665 + + 2017 + 07 + 13 + +
+ + 1936-959X + + 38 + 7 + + 2017 + Jul + + + AJNR. American journal of neuroradiology + AJNR Am J Neuroradiol + + Nonmicrocephalic Infants with Congenital Zika Syndrome Suspected Only after Neuroimaging Evaluation Compared with Those with Microcephaly at Birth and Postnatally: How Large Is the Zika Virus "Iceberg"? + + 1427-1434 + + 10.3174/ajnr.A5216 + + Although microcephaly is the most prominent feature of congenital Zika syndrome, a spectrum with less severe cases is starting to be recognized. Our aim was to review neuroimaging of infants to detect cases without microcephaly and compare them with those with microcephaly. + We retrospectively evaluated all neuroimaging (MR imaging/CT) of infants 1 year of age or younger. Patients with congenital Zika syndrome were divided into those with microcephaly at birth, postnatal microcephaly, and without microcephaly. Neuroimaging was compared among groups. + Among 77 infants, 24.6% had congenital Zika syndrome (11.7% microcephaly at birth, 9.1% postnatal microcephaly, 3.9% without microcephaly). The postnatal microcephaly and without microcephaly groups showed statistically similar imaging findings. The microcephaly at birth compared with the group without microcephaly showed statistically significant differences for the following: reduced brain volume, calcifications outside the cortico-subcortical junctions, corpus callosum abnormalities, moderate-to-severe ventriculomegaly, an enlarged extra-axial space, an enlarged cisterna magna (all absent in those without microcephaly), and polymicrogyria (the only malformation present without microcephaly). There was a trend toward pachygyria (absent in groups without microcephaly). The group with microcephaly at birth compared with the group with postnatal microcephaly showed significant differences for simplified gyral pattern, calcifications outside the cortico-subcortical junctions, corpus callosum abnormalities, moderate-to-severe ventriculomegaly, and an enlarged extra-axial space. + In microcephaly at birth, except for polymicrogyria, all patients showed abnormalities described in the literature. In postnatal microcephaly, the only abnormalities not seen were a simplified gyral pattern and calcifications outside the cortico-subcortical junction. Infants with normocephaly presented with asymmetric frontal polymicrogyria, calcifications in the cortico-subcortical junction, mild ventriculomegaly, and delayed myelination. + © 2017 by American Journal of Neuroradiology. + + + + Aragao + M F V V + MFVV + http://orcid.org/0000-0002-2341-1422 + + From the Centro Diagnostico Multimagem (M.F.V.V.A.), Recife, Brazil fatima.vascoaragao@gmail.com. + + + + Holanda + A C + AC + http://orcid.org/0000-0002-4127-2366 + + Federal University of Pernambuco (A.C.H.), Recife, Brazil. + + + + Brainer-Lima + A M + AM + http://orcid.org/0000-0003-0096-4101 + + Pronto-Socorro Cardiológico de Pernambuco (Procape) (A.M.B.-L., M.M.V.), University of Pernambuco, Recife, Brazil. + + + + Petribu + N C L + NCL + http://orcid.org/0000-0002-4418-9429 + + Barão de Lucena Hospital (N.C.L.P.), Recife, Brazil. + + + + Castillo + M + M + http://orcid.org/0000-0003-2960-1064 + + Department of Radiology (M.C.), University of North Carolina, Chapel Hill, North Carolina. + + + + van der Linden + V + V + http://orcid.org/0000-0003-1641-9386 + + Association for Assistance of Disabled Children (V.v.d.L.), Recife, Brazil. + + + + Serpa + S C + SC + http://orcid.org/0000-0003-2007-6216 + + Clínica de Apoio Ocupacional (S.C.S.), Jaboatão dos Guararapes, Brazil. + + + + Tenório + A G + AG + http://orcid.org/0000-0003-4765-2527 + + Dom Malan Hospital (A.G.T.), Petrolina, Brazil. + + + + Travassos + P T C + PTC + http://orcid.org/0000-0002-1014-4169 + + Laboratório Fernando Travassos (P.T.C.T.), Recife, Brazil. + + + + Cordeiro + M T + MT + http://orcid.org/0000-0001-8196-807X + + Centro de Pesquisas Aggeu Magalhães (M.T.C., C.S.), Fiocruz, Recife, Brazil. + + + + Sarteschi + C + C + http://orcid.org/0000-0001-8536-0598 + + Centro de Pesquisas Aggeu Magalhães (M.T.C., C.S.), Fiocruz, Recife, Brazil. + + + + Valenca + M M + MM + http://orcid.org/0000-0003-0678-3782 + + Pronto-Socorro Cardiológico de Pernambuco (Procape) (A.M.B.-L., M.M.V.), University of Pernambuco, Recife, Brazil. + + + + Costello + A + A + http://orcid.org/0000-0002-0460-4245 + + Department of Maternal, Child, and Adolescent Health (A.C.), World Health Organization, Geneva, Switzerland. + + + + eng + + Journal Article + + + 2017 + 05 + 18 + +
+ + United States + AJNR Am J Neuroradiol + 8003708 + 0195-6108 + +
+ + + + 2017 + 02 + 11 + + + 2017 + 03 + 06 + + + 2017 + 5 + 20 + 6 + 0 + + + 2017 + 5 + 20 + 6 + 0 + + + 2017 + 5 + 20 + 6 + 0 + + + ppublish + + 28522665 + ajnr.A5216 + 10.3174/ajnr.A5216 + + +
+ + + + + 28502333 + + 2017 + 06 + 15 + + + 2018 + 02 + 22 + +
+ + 1538-2990 + + 353 + 5 + + 2017 + 05 + + + The American journal of the medical sciences + Am. J. Med. Sci. + + Zika Virus: Epidemiology, Pathogenesis and Human Disease. + + 466-473 + + S0002-9629(16)30696-6 + 10.1016/j.amjms.2016.12.018 + + The Zika virus is a positive sense, single-stranded RNA arbovirus in the Flaviviridae family, genus Flavivirus. This virus was initially isolated in Africa and is transmitted to nonhuman primates and humans by mosquitoes. Initial reports describe sporadic mild viral infection with fever, arthralgia, myalgia and conjunctivitis in Africa and Asia. However, its geographic distribution has significantly increased, and it has caused large outbreaks in the Yap Islands in 2007, in French Polynesia in 2013 and in Brazil in 2015. Multiple cases of Guillain-Barre´ syndrome occurred in French Polynesia and Columbia during outbreaks, and infections in pregnant women in Brazil have been associated with microcephaly and fetal loss. The viremic phase in humans is short, and diagnosis usually depends on positive immunoglobulin M titers with serum neutralization tests for confirmation. Treatment is directed at symptoms; there are no antiviral drugs available. Transmission can also occur through sexual contact with infected men and through blood transfusion. Prevention is important in women and includes limiting travel to endemic areas when possible, control of mosquito populations and condom use when appropriate. The Centers for Disease Control and Prevention is actively involved in tracking these infections and providing up-to-date information. + Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. + + + + Nugent + Elizabeth K + EK + + University of Texas Health Sciences Center at Houston, Houston, Texas. + + + + Nugent + Anne K + AK + + University of Kansas Medical Center, Kansas City, Kansas. + + + + Nugent + Rebecca + R + + Carnegie-Mellon University, Pittsburgh, Pennsylvania. + + + + Nugent + Kenneth + K + + Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas. Electronic address: kenneth.nugent@ttuhsc.edu. + + + + eng + + Journal Article + Review + + + 2016 + 12 + 30 + +
+ + United States + Am J Med Sci + 0370506 + 0002-9629 + + AIM + IM + + + Animals + + + Culicidae + + + Female + + + Guillain-Barre Syndrome + epidemiology + virology + + + Insect Control + + + Pregnancy + + + Pregnancy Complications + epidemiology + virology + + + Public Health + + + United States + epidemiology + + + Zika Virus + physiology + + + Zika Virus Infection + complications + diagnosis + epidemiology + virology + + + + Arbovirus + Fetal microcephaly + Guillain-Barre´ syndrome + Mosquitoes + Zika virus + +
+ + + + 2016 + 08 + 01 + + + 2016 + 10 + 31 + + + 2016 + 12 + 28 + + + 2017 + 5 + 16 + 6 + 0 + + + 2017 + 5 + 16 + 6 + 0 + + + 2017 + 6 + 16 + 6 + 0 + + + ppublish + + 28502333 + S0002-9629(16)30696-6 + 10.1016/j.amjms.2016.12.018 + + +
+ + + + + 28493351 + + 2017 + 10 + 02 + +
+ + 1440-1789 + + 37 + 5 + + 2017 + Oct + + + Neuropathology : official journal of the Japanese Society of Neuropathology + Neuropathology + + Human Zika and West Nile virus neurological infections: What is the difference? + + 393-397 + + 10.1111/neup.12385 + + The recent epidemic of West Nile Virus (WNV) infection in the United States was associated with severe neurological disease in immunocompromised hosts, while the emergence of Zika virus infection in the Americas has been notable for an association with increased microcephaly in the fetuses of infected mothers. Rare autopsies of WNV infected humans have shown multiple organ involvement with a clear neurotropism. We have recently had the opportunity to examine the distribution of Zika virus in autopsies of newborns from infected pregnancies. While both viruses infect multiple organs, Zika appears to cause neurological disease in the fetus through two different mechanisms. Infection during the first trimester showed the potential to infect neural progenitor cells causing severe developmental abnormalities, while infection later in gestation was associated with meningeal infection and destructive ischemic lesions of the brain. Both viruses infect kidney tubules but Zika shares a prominent hepatotropism characteristic of other flaviviruses (e.g., Dengue). Limited transplacental Zika infection would be consistent with restriction to primary maternal infections with high viremia. In the absence of a vaccine, restriction of travel by immunosuppressed and pregnant non-immune individuals to endemic regions seems prudent. + © 2017 Japanese Society of Neuropathology. + + + + Wiley + Clayton A + CA + http://orcid.org/0000-0002-2697-7691 + + University of Pittsburgh School of Medicine, Department of Pathology, Pittsburgh, Pennsylvania, USA. + + + + Chimelli + Leila + L + http://orcid.org/0000-0001-6059-0872 + + Laboratory of Neuropathology, State Institute of Brain Paulo Niemeyer, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + Review + + + 2017 + 05 + 11 + +
+ + Australia + Neuropathology + 9606526 + 0919-6544 + +
+ + + + 2017 + 03 + 22 + + + 2017 + 03 + 23 + + + 2017 + 5 + 12 + 6 + 0 + + + 2017 + 5 + 12 + 6 + 0 + + + 2017 + 5 + 12 + 6 + 0 + + + ppublish + + 28493351 + 10.1111/neup.12385 + + +
+ + + + + 28492766 + + 2017 + 05 + 11 + +
+ + 2237-9622 + + 26 + 2 + + 2017 Apr-Jun + + + Epidemiologia e servicos de saude : revista do Sistema Unico de Saude do Brasil + Epidemiol Serv Saude + + Clinical-epidemiological description of live births with microcephaly in the state of Sergipe, Brazil, 2015. + + 245-254 + + S2237-96222017000200245 + 10.5123/S1679-49742017000200002 + + to describe the clinical and epidemiological characteristics of microcephaly cases in live births in Sergipe, Brazil, and to calculate the prevalence in its municipalities. + this is a descriptive study on live births from September 1st to November 30th, 2015, with data from medical records and interviews with mothers. + 83 cases of microcephaly were confirmed, with three deaths; prevalence in the 26 municipalities with confirmed cases ranged from 18 to 185/10,000 live births; the median of head circumference was 31 cm (range: 22.5-33.0); agenesis of corpus callosum (26/43), lissencephaly (12/43), absence of midline (10/43) and ventriculomegaly (8/43) were observed in the transfontanellar ultrasound; 40 mothers reported rash in pregnancy, 23 in the first trimester, with pruritus, arthralgia and headache; seven were positive for infections potentially causing malformations. + there was a high occurrence of cases of microcephaly, and reports of signs and symptoms compatible with Zika virus infection during pregnancy. + + + + Cabral + Cibelle Mendes + CM + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Nóbrega + Martha Elizabeth Brasil da + MEBD + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Leite + Priscila Leal E + PLE + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Souza + Mércia Simone Feitosa de + MSF + + Secretaria de Estado da Saúde de Sergipe, Diretoria de Vigilância em Saúde, Aracaju-SE, Brasil. + + + + Teixeira + Daniela Cabral Pizzi + DCP + + Secretaria de Estado da Saúde de Sergipe, Diretoria de Vigilância em Saúde, Aracaju-SE, Brasil. + + + + Cavalcante + Taíse Ferreira + TF + + Secretaria Municipal de Saúde de Aracaju, Diretoria de Vigilância em Saúde, Aracaju-SE, Brasil. + + + + Lima + Raulinna Gomes de Souza + RGS + + Secretaria Municipal de Saúde de Aracaju, Diretoria de Vigilância em Saúde, Aracaju-SE, Brasil. + + + + Tavares + Lúcia Maria Sayde de Azevedo + LMSA + + Ministério da Saúde, Departamento Nacional de Auditoria do Sistema Único de Saúde, Aracaju-SE, Brasil. + + + + Souza + Priscila Bochi de + PB + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Saad + Eduardo + E + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + por + eng + + Journal Article + + Descrição clínico-epidemiológica dos nascidos vivos com microcefalia no estado de Sergipe, 2015. +
+ + Brazil + Epidemiol Serv Saude + 101248287 + 1679-4974 + +
+ + + + 2016 + 09 + 30 + + + 2016 + 11 + 29 + + + 2017 + 5 + 12 + 6 + 0 + + + 2017 + 5 + 12 + 6 + 0 + + + 2017 + 5 + 12 + 6 + 0 + + + ppublish + + 28492766 + S2237-96222017000200245 + 10.5123/S1679-49742017000200002 + + +
+ + + + + 28459414 + + 2017 + 11 + 09 + +
+ + 1080-6059 + + 23 + 7 + + 2017 + 07 + + + Emerging infectious diseases + Emerging Infect. Dis. + + Postmortem Findings for 7 Neonates with Congenital Zika Virus Infection. + + 1164-1167 + + 10.3201/eid2307.162019 + + Postmortem examination of 7 neonates with congenital Zika virus infection in Brazil revealed microcephaly, ventriculomegaly, dystrophic calcifications, and severe cortical neuronal depletion in all and arthrogryposis in 6. Other findings were leptomeningeal and brain parenchymal inflammation and pulmonary hypoplasia and lymphocytic infiltration in liver and lungs. Findings confirmed virus neurotropism and multiple organ infection. + + + + Sousa + Anastácio Q + AQ + + + Cavalcante + Diane I M + DIM + + + Franco + Luciano M + LM + + + Araújo + Fernanda M C + FMC + + + Sousa + Emília T + ET + + + Valença-Junior + José Telmo + JT + + + Rolim + Dionne B + DB + + + Melo + Maria E L + MEL + + + Sindeaux + Pedro D T + PDT + + + Araújo + Marialva T F + MTF + + + Pearson + Richard D + RD + + + Wilson + Mary E + ME + + + Pompeu + Margarida M L + MML + + + eng + + Journal Article + + + 2017 + 07 + 15 + +
+ + United States + Emerg Infect Dis + 9508155 + 1080-6040 + + + + Euro Surveill. 2016 Jun 16;21(24): + 27336620 + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + Arch Dis Child. 1981 Aug;56(8):601-5 + 7271300 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Lancet. 2016 Aug 27;388(10047):898-904 + 27372395 + + + PLoS Negl Trop Dis. 2010 Jul 06;4(7):e738 + 20625558 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Arch Med Sci. 2016 Feb 1;12(1):10-24 + 26925114 + + + J Virol Methods. 2011 Oct;177(1):128-31 + 21798288 + + + Hum Pathol. 2014 Jun;45(6):1221-33 + 24767772 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + + Brazil + Zika virus + autopsy + congenital + microcephaly + neonates + postmortem + viruses + +
+ + + + 2017 + 5 + 2 + 6 + 0 + + + 2017 + 5 + 2 + 6 + 0 + + + 2017 + 5 + 2 + 6 + 0 + + + ppublish + + 28459414 + 10.3201/eid2307.162019 + PMC5512501 + + +
+ + + + + 28450178 + + 2017 + 08 + 28 + +
+ + 1528-3933 + + 21 + 4 + + 2017 + Aug + + + Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus + J AAPOS + + Visual impairment in children with congenital Zika syndrome. + + 295-299.e2 + + S1091-8531(17)30311-7 + 10.1016/j.jaapos.2017.04.003 + + To describe the visual impairment associated with ocular and neurological abnormalities in a cohort of children with congenital Zika syndrome (CZS). + This cross-sectional study included infants with microcephaly born in Pernambuco, Brazil, from May to December 2015. Immunoglobulin M antibody capture enzyme-linked immunosorbent assay for the Zika virus on the cerebrospinal fluid samples was positive for all infants. Clinical evaluation consisted of comprehensive ophthalmologic examination including visual acuity, visual function assessment, visual developmental milestone, neurologic examination, and neuroimaging. + A total of 32 infants (18 males [56%]) were included. Mean age at examination was 5.7 ± 0.9 months (range, 4-7 months). Visual function and visual developmental milestone could not be tested in 1 child (3%). Visual impairment was detected in 32 infants (100%). Retinal and/or optic nerve findings were observed in 14 patients (44%). There was no statistical difference between the patients with ocular findings and those without (P = 0.180). All patients (100%) demonstrated neurological and neuroimaging abnormalities; 3 (9%) presented with late-onset of microcephaly. + Children with CZS demonstrated visual impairment regardless of retina and/or optic nerve abnormalities. This finding suggests that cortical/cerebral visual impairment may be the most common cause of blindness identified in children with CZS. + Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved. + + + + Ventura + Liana O + LO + + Altino Ventura Foundation (FAV), Recife, PE, Brazil; Department of Ophthalmology, HOPE Eye Hospital, Recife, PE, Brazil. + + + + Ventura + Camila V + CV + + Altino Ventura Foundation (FAV), Recife, PE, Brazil; Department of Ophthalmology, HOPE Eye Hospital, Recife, PE, Brazil; Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida. + + + + Lawrence + Linda + L + + Private Ophthalmology practice, Salina, Kansas. Electronic address: lmlawrencemd@gmail.com. + + + + van der Linden + Vanessa + V + + Department of Pediatric Neurology, Disabled Children's Assistance Association (AACD), Recife, PE, Brazil. + + + + van der Linden + Ana + A + + Department of Pediatric Neurology, Materno Infantil Institute of Pernambuco (IMIP Hospital), Recife, PE, Brazil. + + + + Gois + Adriana L + AL + + Altino Ventura Foundation (FAV), Recife, PE, Brazil; Department of Ophthalmology, HOPE Eye Hospital, Recife, PE, Brazil. + + + + Cavalcanti + Milena M + MM + + Altino Ventura Foundation (FAV), Recife, PE, Brazil; Department of Pediatric Neurology, Disabled Children's Assistance Association (AACD), Recife, PE, Brazil. + + + + Barros + Eveline A + EA + + Altino Ventura Foundation (FAV), Recife, PE, Brazil; Department of Ophthalmology, HOPE Eye Hospital, Recife, PE, Brazil. + + + + Dias + Natalia C + NC + + Altino Ventura Foundation (FAV), Recife, PE, Brazil. + + + + Berrocal + Audina M + AM + + Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida. + + + + Miller + Marilyn T + MT + + Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, Illinois. + + + + eng + + Journal Article + + + 2017 + 04 + 24 + +
+ + United States + J AAPOS + 9710011 + 1091-8531 + +
+ + + + 2016 + 11 + 25 + + + 2017 + 03 + 22 + + + 2017 + 4 + 30 + 6 + 0 + + + 2017 + 4 + 30 + 6 + 0 + + + 2017 + 4 + 29 + 6 + 0 + + + ppublish + + 28450178 + S1091-8531(17)30311-7 + 10.1016/j.jaapos.2017.04.003 + + +
+ + + + + 28443985 + + 2017 + 08 + 24 + + + 2017 + 08 + 24 + +
+ + 1678-8060 + + 112 + 5 + + 2017 + May + + + Memorias do Instituto Oswaldo Cruz + Mem. Inst. Oswaldo Cruz + + Zika puzzle in Brazil: peculiar conditions of viral introduction and dissemination - A Review. + + 319-327 + + S0074-02762017000500319 + 10.1590/0074-02760160510 + + This article discusses the peculiar conditions that favoured the unexpected introduction of Zika virus into the poorest northeastern region of Brazil in 2015, its speed of transmission to other Brazilian states, other Latin American countries and other regions, and the severity of related neurological disorders in newborns and adults. Contrasting with evidence that Zika had so far caused only mild cases in humans in the last six decades, the epidemiological scenario of this outbreak in Brazil indicates dramatic health effects: in 2015, an increase of 20-fold in notified cases of microcephaly and/or central nervous system (CNS) alterations suggestive of Zika congenital infection, followed by an exponential increase in 2016, with 2366 cumulative cases confirmed in the country by the end of December 2016. A significant increase in Guillain-Barré syndrome in adults has also been reported. Factors involved in viral dissemination, neural pathogenesis and routes of transmission in Brazil are examined, such as the role of social and environmental factors and the controversies involved in the hypothesis of antibody-dependent enhancement, to explain the incidence of congenital Zika syndrome in Brazil. Responses to the Zika outbreak and the development of new products are also discussed. + + + + Possas + Cristina + C + + Fundação Oswaldo Cruz-Fiocruz, Bio-Manguinhos, Assessoria Científica Sênior, Rio de Janeiro, RJ, Brasil. + + + + Brasil + Patricia + P + + Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica em Doenças Febris Agudas, Rio de Janeiro, RJ, Brasil. + + + + Marzochi + Mauro Ca + MC + + Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses, Rio de Janeiro, RJ, Brasil. + + + + Tanuri + Amilcar + A + + Universidade Federal do Rio de Janeiro, Instituto de Biologia, Departamento de Genética, Rio de Janeiro, RJ, Brasil. + + + + Martins + Reinaldo M + RM + + Fundação Oswaldo Cruz-Fiocruz, Bio-Manguinhos, Assessoria Científica Sênior, Rio de Janeiro, RJ, Brasil. + + + + Marques + Ernesto Ta + ET + + Fundação Oswaldo Cruz-Fiocruz, Centro de Pesquisas Aggeu Magalhães, Departamento de Virologia, Recife, PE, Brasil. + + + University of Pittsburgh, Center for Vaccine Research, Pittsburgh, PA, United States. + + + + Bonaldo + Myrna C + MC + + Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular de Flavivírus, Rio de Janeiro, RJ, Brasil. + + + + Ferreira + Antonio Gp + AG + + Fundação Oswaldo Cruz-Fiocruz, Bio-Manguinhos, Departamento de Reativos para Diagnóstico, Rio de Janeiro, RJ, Brasil. + + + + Lourenço-de-Oliveira + Ricardo + R + + Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Mosquitos Transmissores de Hematozoários, Rio de Janeiro, RJ, Brasil. + + + + Nogueira + Rita Maria R + RMR + + Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Flavivírus, Rio de Janeiro, RJ, Brasil. + + + + Sequeira + Patricia C + PC + + Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Flavivírus, Rio de Janeiro, RJ, Brasil. + + + + Marzochi + Keyla Bf + KB + + Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses, Rio de Janeiro, RJ, Brasil. + + + + Homma + Akira + A + + Fundação Oswaldo Cruz-Fiocruz, Bio-Manguinhos, Assessoria Científica Sênior, Rio de Janeiro, RJ, Brasil. + + + + eng + + Journal Article + Review + + + 2017 + 04 + 06 + +
+ + Brazil + Mem Inst Oswaldo Cruz + 7502619 + 0074-0276 + + IM + + + N Engl J Med. 2016 Jun 2;374(22):2195-8 + 27074370 + + + Int J Infect Dis. 2016 Oct;51:128-132 + 27664930 + + + Lancet. 2016 Apr 2;387(10026):1482 + 27115821 + + + Nature. 2016 Aug 25;536(7617):474-8 + 27355570 + + + PLoS Negl Trop Dis. 2016 Apr 12;10(4):e0004636 + 27070912 + + + PLoS Negl Trop Dis. 2016 Jun 24;10 (6):e0004816 + 27341420 + + + Lancet. 2016 Apr 30;387(10030):1811-2 + 27103126 + + + Semin Reprod Med. 2016 Sep;34(5):273-279 + 27612158 + + + Hum Vaccin Immunother. 2014;10(5):1256-65 + 24553128 + + + J Clin Virol. 2016 Oct;83:63-5 + 27598870 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + MMWR Morb Mortal Wkly Rep. 2016 Apr 15;65(14):372-4 + 27078057 + + + MMWR Morb Mortal Wkly Rep. 2016 May 27;65(20):514-9 + 27248295 + + + Emerg Infect Dis. 2016 May;22(5):828-32 + 27088494 + + + Obstet Gynecol. 2016 Apr;127(4):642-8 + 26889662 + + + Lancet Infect Dis. 2016 Apr;16(4):405 + 26949027 + + + Lancet Infect Dis. 2016 Aug;16(8):894-5 + 27477981 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + PLoS Negl Trop Dis. 2016 Mar 03;10(3):e0004543 + 26938868 + + + F1000Res. 2016 Feb 09;5:150 + 27134728 + + + Cell Host Microbe. 2016 May 11;19(5):561-5 + 27091703 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Sci Rep. 2017 Jan 18;7:40920 + 28098253 + + + Mem Inst Oswaldo Cruz. 2016 Oct;111(10 ):655-658 + 27706382 + + + Clin Transl Immunology. 2016 Dec 16;5(12 ):e117 + 28090318 + + + Nature. 2016 Aug 4;536(7614):48-53 + 27338953 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + J Infect Dis. 2016 Sep 1;214(5):707-11 + 27234417 + + + PLoS Negl Trop Dis. 2016 Sep 21;10(9):e0005024 + 27654962 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Braz J Infect Dis. 2016 May-Jun;20(3):282-9 + 27102780 + + + Science. 2016 Apr 22;352(6284):467-70 + 27033547 + + + Epidemiol Health. 2016 May 31;38:e2016023 + 27283140 + + + Lancet Infect Dis. 2016 Mar;16(3):278-9 + 26852727 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Nat Immunol. 2016 Sep;17 (9):1102-8 + 27339099 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7852-7 + 27354515 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Immunology. 2017 Feb;150(2):146-154 + 27763656 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + PLoS Negl Trop Dis. 2016 Sep 06;10(9):e0004993 + 27598421 + + + Euro Surveill. 2016 Aug 11;21(32): + 27541989 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + + + Brazil + epidemiology + + + Dengue + epidemiology + immunology + + + Disease Notification + + + Disease Outbreaks + + + Female + + + Humans + + + Incidence + + + Infant, Newborn + + + Microcephaly + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Spatial Analysis + + + Zika Virus Infection + complications + immunology + transmission + + +
+ + + + 2016 + 11 + 24 + + + 2017 + 02 + 20 + + + 2017 + 4 + 27 + 6 + 0 + + + 2017 + 4 + 27 + 6 + 0 + + + 2017 + 8 + 25 + 6 + 0 + + + ppublish + + 28443985 + S0074-02762017005006103 + 10.1590/0074-02760160510 + PMC5398166 + + +
+ + + + + 28442607 + + 2018 + 01 + 08 + + + 2018 + 02 + 22 + +
+ + 2150-7511 + + 8 + 2 + + 2017 + 04 + 25 + + + mBio + MBio + + N +-Methyl-d-Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection. + e00350-17 + 10.1128/mBio.00350-17 + + Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated byN-methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover,in vivoexperiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP) induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration.IMPORTANCEZika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage bothin vitroandin vivoThese results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment. + Copyright © 2017 Costa et al. + + + + Costa + Vivian V + VV + + Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + Host-Interaction Microorganism Lab, Department of Microbiology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. + + + + Del Sarto + Juliana L + JL + + Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + + Rocha + Rebeca F + RF + + Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + + Silva + Flavia R + FR + + Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + + Doria + Juliana G + JG + + Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + + Olmo + Isabella G + IG + + Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + + Marques + Rafael E + RE + + Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + + Queiroz-Junior + Celso M + CM + + Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. + + + + Foureaux + Giselle + G + + Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. + + + + Araújo + Julia Maria S + JMS + + Host-Interaction Microorganism Lab, Department of Microbiology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. + + + + Cramer + Allysson + A + + Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + Immunoregulation of Infectious Disease Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + + Real + Ana Luíza C V + ALCV + + Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + + Ribeiro + Lucas S + LS + + Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + Host-Interaction Microorganism Lab, Department of Microbiology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. + + + + Sardi + Silvia I + SI + + Virology Lab, Department of Virology, Universidade Federal da Bahia (UFBA), Salvador, Bahia, Brazil. + + + + Ferreira + Anderson J + AJ + + Cardiac Biology Lab, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. + + + + Machado + Fabiana S + FS + + Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + Immunoregulation of Infectious Disease Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + + de Oliveira + Antônio C + AC + + Neuropharmacology Lab, Department of Pharmacology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. + + + + Teixeira + Antônio L + AL + + Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical Houston, University of Texas Health Science Center at Houston, Houston, Texas, USA. + + + + Nakaya + Helder I + HI + + Metabolomics Applied to Health Lab, Department of Clinical Analyses and Toxicology, School of Pharmaceutical Science, Universidade de Sao Paulo (USP), Sao Paulo, Brazil. + + + + Souza + Danielle G + DG + + Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. + + + Host-Interaction Microorganism Lab, Department of Microbiology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. + + + + Ribeiro + Fabiola M + FM + + Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil fmribeiro@icb.ufmg.br mmtex.ufmg@gmail.com. + + + + Teixeira + Mauro M + MM + + Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil fmribeiro@icb.ufmg.br mmtex.ufmg@gmail.com. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + + + 2017 + 04 + 25 + +
+ + United States + MBio + 101519231 + + + + 0 + Neuroprotective Agents + + + 0 + Receptors, N-Methyl-D-Aspartate + + + IM + + + Lancet. 2016 Apr 2;387(10026):1482 + 27115821 + + + Trends Neurosci. 1990 Jul;13(7):286-9 + 1695405 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Med Microbiol Immunol. 2016 Jun;205(3):269-73 + 26702627 + + + J Neurochem. 2000 Oct;75(4):1590-9 + 10987840 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + J Neurol. 2007 Mar;254(3):351-8 + 17345042 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Cell Rep. 2016 Sep 20;16(12):3208-18 + 27612415 + + + Trends Neurosci. 1996 Jul;19(7):267-71 + 8799968 + + + Int J Infect Dis. 2016 Mar;44:11-5 + 26854199 + + + FASEB J. 2008 Dec;22(12):4258-71 + 18711223 + + + N Engl J Med. 2016 Jul 28;375(4):394-6 + 27332784 + + + CNS Neurol Disord Drug Targets. 2013 Sep;12(6):773-84 + 24047523 + + + Eur J Pharmacol. 1990 Aug 21;185(1):19-24 + 2226632 + + + Invest Ophthalmol Vis Sci. 2013 Jun 21;54(6):4296-306 + 23702784 + + + Front Biosci (Elite Ed). 2014 Jun 01;6:341-59 + 24896210 + + + Nat Rev Drug Discov. 2006 Feb;5(2):160-70 + 16424917 + + + J Cereb Blood Flow Metab. 2017 Mar;37(3):980-993 + 27170698 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + BMJ. 2016 Feb 02;352:i657 + 26839247 + + + J Pharmacol Exp Ther. 2004 Nov;311(2):677-82 + 15192085 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Am J Pathol. 2013 Jun;182(6):1950-61 + 23567637 + + + Cell Host Microbe. 2016 Aug 10;20(2):259-70 + 27476412 + + + Neurology. 1992 Jul;42(7):1403-5 + 1620355 + + + AIDS Res Hum Retroviruses. 1991 Jan;7(1):89-95 + 1707644 + + + PLoS Negl Trop Dis. 2011 Dec;5(12):e1449 + 22206036 + + + Hum Mol Genet. 2010 Apr 15;19(R1):R12-20 + 20413653 + + + Trends Genet. 2004 Mar;20(3):146-54 + 15036808 + + + Annu Rev Biochem. 1984;53:749-90 + 6206782 + + + PLoS Negl Trop Dis. 2016 May 10;10 (5):e0004695 + 27163257 + + + J Neurosci. 1992 Nov;12(11):4427-36 + 1432103 + + + Neuroscience. 1998 Oct;86(4):1121-32 + 9697119 + + + J Physiol. 1997 Feb 15;499 ( Pt 1):27-46 + 9061638 + + + J Autoimmun. 2016 Apr;68:1-13 + 26925496 + + + PLoS Negl Trop Dis. 2016 Apr 19;10(4):e0004682 + 27093158 + + + J Neurosci. 2004 Aug 11;24(32):7194-8 + 15306653 + + + Neuropsychiatr Dis Treat. 2016 Jul 14;12:1747-60 + 27478378 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Curr Opin Virol. 2016 Jun;18:76-81 + 27179929 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):154-8 + 26890470 + + + J Immunol Methods. 1990 Aug 7;131(2):165-72 + 2391427 + + + Brain Res. 2005 Feb 21;1035(1):24-31 + 15713273 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Curr Opin Pharmacol. 2006 Feb;6(1):61-7 + 16368266 + + + Trends Pharmacol Sci. 1995 Oct;16(10):356-9 + 7491714 + + + Eur J Pharmacol. 1992 Jul 1;226(3):209-14 + 1426020 + + + Nat Rev Neurosci. 2013 Jun;14(6):383-400 + 23686171 + + + Med Microbiol Immunol. 2014 Aug;203(4):231-50 + 24723052 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Nucleic Acids Res. 2016 Oct 14;44(18):8610-8620 + 27580721 + + + J Neurosci. 2010 Aug 18;30(33):11246-50 + 20720132 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Stroke. 2014 Jul;45(7):2093-100 + 24938836 + + + Cell Res. 2016 Jun;26(6):645-54 + 27174054 + + + Annu Rev Pharmacol Toxicol. 1997;37:205-37 + 9131252 + + + CNS Neurosci Ther. 2013 Aug;19(8):549-55 + 23593992 + + + J Clin Invest. 2003 Feb;111(3):299-302 + 12569151 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + PLoS Negl Trop Dis. 2012;6(5):e1663 + 22666512 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + J Neuroinflammation. 2011 Mar 09;8:23 + 21388530 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Animals + + + Disease Models, Animal + + + Mice + + + Neurodegenerative Diseases + drug therapy + pathology + + + Neuroprotective Agents + administration & dosage + + + Receptors, N-Methyl-D-Aspartate + antagonists & inhibitors + + + Treatment Outcome + + + Zika Virus + growth & development + + + Zika Virus Infection + complications + pathology + + + + NMDA receptor + Zika virus + intraocular pressure + memantine + microgliosis + mouse model + neuronal death + +
+ + + + 2017 + 4 + 27 + 6 + 0 + + + 2017 + 4 + 27 + 6 + 0 + + + 2018 + 1 + 9 + 6 + 0 + + + epublish + + 28442607 + mBio.00350-17 + 10.1128/mBio.00350-17 + PMC5405231 + + +
+ + + + + 28442561 + + 2017 + 12 + 12 + +
+ + 1091-6490 + + 114 + 22 + + 2017 + May + 30 + + + Proceedings of the National Academy of Sciences of the United States of America + Proc. Natl. Acad. Sci. U.S.A. + + Spread of Zika virus in the Americas. + + E4334-E4343 + + 10.1073/pnas.1620161114 + + We use a data-driven global stochastic epidemic model to analyze the spread of the Zika virus (ZIKV) in the Americas. The model has high spatial and temporal resolution and integrates real-world demographic, human mobility, socioeconomic, temperature, and vector density data. We estimate that the first introduction of ZIKV to Brazil likely occurred between August 2013 and April 2014 (90% credible interval). We provide simulated epidemic profiles of incident ZIKV infections for several countries in the Americas through February 2017. The ZIKV epidemic is characterized by slow growth and high spatial and seasonal heterogeneity, attributable to the dynamics of the mosquito vector and to the characteristics and mobility of the human populations. We project the expected timing and number of pregnancies infected with ZIKV during the first trimester and provide estimates of microcephaly cases assuming different levels of risk as reported in empirical retrospective studies. Our approach represents a modeling effort aimed at understanding the potential magnitude and timing of the ZIKV epidemic and it can be potentially used as a template for the analysis of future mosquito-borne epidemics. + + + + Zhang + Qian + Q + + Laboratory for the Modeling of Biological and Socio-technical Systems, Northeastern University, Boston, MA 02115. + + + + Sun + Kaiyuan + K + + Laboratory for the Modeling of Biological and Socio-technical Systems, Northeastern University, Boston, MA 02115. + + + + Chinazzi + Matteo + M + + Laboratory for the Modeling of Biological and Socio-technical Systems, Northeastern University, Boston, MA 02115. + + + + Pastore Y Piontti + Ana + A + + Laboratory for the Modeling of Biological and Socio-technical Systems, Northeastern University, Boston, MA 02115. + + + + Dean + Natalie E + NE + + Department of Biostatistics, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32611. + + + + Rojas + Diana Patricia + DP + + Department of Epidemiology, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32611. + + + + Merler + Stefano + S + + Bruno Kessler Foundation, 38123 Trento, Italy. + + + + Mistry + Dina + D + + Laboratory for the Modeling of Biological and Socio-technical Systems, Northeastern University, Boston, MA 02115. + + + + Poletti + Piero + P + + Dondena Centre for Research on Social Dynamics and Public Policy, Universitá Commerciale L. Bocconi, 20136 Milan, Italy. + + + + Rossi + Luca + L + + Institute for Scientific Interchange Foundation, 10126 Turin, Italy. + + + + Bray + Margaret + M + + Laboratory for the Modeling of Biological and Socio-technical Systems, Northeastern University, Boston, MA 02115. + + + + Halloran + M Elizabeth + ME + + Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109. + + + Department of Biostatistics, University of Washington, Seattle, WA 98195. + + + + Longini + Ira M + IM + Jr + + Department of Biostatistics, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32611. + + + + Vespignani + Alessandro + A + + Laboratory for the Modeling of Biological and Socio-technical Systems, Northeastern University, Boston, MA 02115; a.vespignani@northeastern.edu. + + + Institute for Scientific Interchange Foundation, 10126 Turin, Italy. + + + + eng + + + U54 GM111274 + GM + NIGMS NIH HHS + United States + + + + Journal Article + + + 2017 + 04 + 25 + +
+ + United States + Proc Natl Acad Sci U S A + 7505876 + 0027-8424 + + + + N Engl J Med. 2016 Jun 2;374(22):2195-8 + 27074370 + + + Euro Surveill. 2014 Oct 23;19(42):null + 25358040 + + + Sci Data. 2015 Jul 07;2:150035 + 26175912 + + + PLoS Med. 2016 Oct 25;13(10 ):e1002157 + 27780196 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + PLoS Negl Trop Dis. 2014 Feb 06;8(2):e2681 + 24516683 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + Nature. 2016 Jul 25;535(7613):475-6 + 27466104 + + + BMC Med. 2012 Dec 13;10:165 + 23237460 + + + Science. 2016 Jul 22;353(6297):353-4 + 27417493 + + + PLoS Negl Trop Dis. 2016 Apr 25;10(4):e0004687 + 27111294 + + + Science. 2016 Aug 12;353(6300):aaf8160 + 27417495 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + Lancet. 2016 Jan 23;387(10016):335-6 + 26777915 + + + PLoS Negl Trop Dis. 2016 Mar 03;10(3):e0004543 + 26938868 + + + J Clin Virol. 2016 Nov;84:53-58 + 27721110 + + + Nat Microbiol. 2016 Jul 25;1(9):16126 + 27562260 + + + Arch Gesamte Virusforsch. 1973;43(4):315-9 + 4799154 + + + Emerg Infect Dis. 2016 Jul;22(7):1185-92 + 27070380 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + J Comput Sci. 2010 Aug 1;1(3):132-145 + 21415939 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Lancet Infect Dis. 2016 Oct;16(10):1100-2 + 27676337 + + + Euro Surveill. 2016 Jul 14;21(28): + 27452806 + + + Nat Microbiol. 2016 Aug 26;1(9):16157 + 27562269 + + + Proc Natl Acad Sci U S A. 2011 May 3;108(18):7460-5 + 21502510 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + PLoS Negl Trop Dis. 2016 May 17;10 (5):e0004726 + 27186984 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3510-7 + 16473945 + + + Sci Rep. 2016 Jun 17;6:28070 + 27312324 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + BMC Med. 2016 Aug 03;14 (1):112 + 27487767 + + + Elife. 2016 Apr 19;5:null + 27090089 + + + PLoS One. 2014 Aug 11;9(8):e104915 + 25111394 + + + PLoS One. 2008 Aug 26;3(8):e3066 + 18725980 + + + BMC Med. 2009 Sep 10;7:45 + 19744314 + + + PLoS Curr. 2016 May 31;8:null + 27366586 + + + Clin Infect Dis. 2016 Jul 1;63(1):141-2 + 27048746 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Emerg Infect Dis. 2015 Dec;21(12):2274-6 + 26584464 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Emerg Infect Dis. 2017 Jan;23 (1):91-94 + 27618573 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Lancet. 2016 May 21;387(10033):2070-2 + 26993880 + + + N Engl J Med. 2016 Jun 15;:null + 27305043 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Zika virus + computational epidemiology + metapopulation network model + vector-borne diseases + + The authors declare no conflict of interest. +
+ + + + 2017 + 4 + 27 + 6 + 0 + + + 2017 + 4 + 27 + 6 + 0 + + + 2017 + 4 + 27 + 6 + 0 + + + ppublish + + 28442561 + 1620161114 + 10.1073/pnas.1620161114 + PMC5465916 + + +
+ + + + + 28442104 + + 2018 + 02 + 19 + +
+ + 2352-4146 + + 10 + 3 + + 2017 + Mar + + + Asian Pacific journal of tropical medicine + Asian Pac J Trop Med + + Zika virus infection and its emerging trends in Southeast Asia. + + 211-219 + + S1995-7645(16)30601-0 + 10.1016/j.apjtm.2017.03.002 + + Zika virus is a mosquito-borne flavivirus that represents a public health emergency at the ongoing epidemic. Previously, this rare virus was limited to sporadic cases in Africa and Asia until its emergence in Brazil, South America in 2015, where it rapidly spread throughout the world. Recently, a high number of cases were reported in Singapore and other Southeast Asia countries. A combination of factors explains the current Zika virus outbreak although it is highly likely that the changes in the climate and high frequency of travelling contribute to the spread of Aedes vector carrying the Zika virus mainly to the tropical climate countries such as the Southeast Asia. The Zika virus is known to cause mild clinical symptoms similar to those of dengue and chikungunya and transmitted by different species of Aedes mosquitoes. However, neurological complications such as Guillain-Barré syndrome in adults, and congenital anomalies, including microcephaly in babies born to infected mothers, raised a serious concern. Currently, there is no specific antiviral treatment or vaccine available for Zika virus infection. Therefore, international public health response is primarily focused on preventing infection, particularly in pregnant women, and on providing up-to-date recommendations to reduce the risk of non-vector transmission of Zika virus. + Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved. + + + + Salehuddin + Ahmad Ruzain + AR + + Discipline of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia. Electronic address: ruz_arbs@yahoo.com. + + + + Haslan + Haszianaliza + H + + Discipline of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia. + + + + Mamikutty + Norshalizah + N + + Discipline of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia. + + + + Zaidun + Nurul Hannim + NH + + Discipline of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia. + + + + Azmi + Mohamad Fairuz + MF + + Discipline of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia. + + + + Senin + Mohamad Mu'izuddin + MM + + Discipline of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia; Klinik Dr. Muiz, Selangor, Malaysia. + + + + Syed Ahmad Fuad + Syed Baharom + SB + + Discipline of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia. + + + + Thent + Zar Chi + ZC + + Discipline of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia. + + + + eng + + Journal Article + Review + + + 2017 + 03 + 10 + +
+ + India + Asian Pac J Trop Med + 101533720 + 1995-7645 + + + Emerging infection + Microcephaly + Neurological complication + Zika virus + +
+ + + + 2016 + 12 + 16 + + + 2017 + 01 + 17 + + + 2017 + 02 + 18 + + + 2017 + 4 + 27 + 6 + 0 + + + 2017 + 4 + 27 + 6 + 0 + + + 2017 + 4 + 27 + 6 + 0 + + + ppublish + + 28442104 + S1995-7645(16)30601-0 + 10.1016/j.apjtm.2017.03.002 + + +
+ + + + + 28429099 + + 2017 + 10 + 23 + + + 2017 + 10 + 23 + +
+ + 1435-1102 + + 20 + 3 + + 2017 + 06 + + + Archives of women's mental health + Arch Womens Ment Health + + Anxiety, depression, and quality of life in mothers of newborns with microcephaly and presumed congenital Zika virus infection: a follow-up study during the first year after birth. + + 473-475 + + 10.1007/s00737-017-0724-y + + + Dos Santos Oliveira + Sheila Jaqueline Gomes + SJG + + Postgraduate Program in Health Sciences, Federal University of Sergipe, Aracaju, Brazil. + + + Tiradentes University, Aracaju, Brazil. + + + + Dos Reis + Caroline Lima + CL + + Tiradentes University, Aracaju, Brazil. + + + + Cipolotti + Rosana + R + + Postgraduate Program in Health Sciences, Federal University of Sergipe, Aracaju, Brazil. + + + Department of Medicine, Federal University of Sergipe, Aracaju, Brazil. + + + + Gurgel + Ricardo Queiroz + RQ + + Postgraduate Program in Health Sciences, Federal University of Sergipe, Aracaju, Brazil. + + + Department of Medicine, Federal University of Sergipe, Aracaju, Brazil. + + + + Santos + Victor Santana + VS + + Postgraduate Program in Health Sciences, Federal University of Sergipe, Aracaju, Brazil. + + + Tiradentes University, Aracaju, Brazil. + + + + Martins-Filho + Paulo Ricardo Saquete + PRS + 0000-0001-8779-0727 + + Postgraduate Program in Health Sciences, Federal University of Sergipe, Aracaju, Brazil. martins-filho@ufs.br. + + + Investigative Pathology Laboratory, Federal University of Sergipe, Aracaju, Brazil. martins-filho@ufs.br. + + + Universidade Federal de Sergipe, Hospital Universitário, Laboratório de Patologia Investigativa, Rua Cláudio Batista, s/n. Bairro Sanatório, Aracaju, Sergipe, 49060-100, Brazil. martins-filho@ufs.br. + + + + eng + + Letter + + + 2017 + 04 + 21 + +
+ + Austria + Arch Womens Ment Health + 9815663 + 1434-1816 + + IM + + + Anxiety + diagnosis + psychology + + + Depression + diagnosis + psychology + + + Female + + + Follow-Up Studies + + + Humans + + + Infant, Newborn + + + Microcephaly + diagnosis + + + Mothers + psychology + + + Postpartum Period + + + Pregnancy + + + Quality of Life + + + Zika Virus Infection + congenital + + +
+ + + + 2017 + 01 + 13 + + + 2017 + 04 + 10 + + + 2017 + 4 + 22 + 6 + 0 + + + 2017 + 10 + 24 + 6 + 0 + + + 2017 + 4 + 22 + 6 + 0 + + + ppublish + + 28429099 + 10.1007/s00737-017-0724-y + 10.1007/s00737-017-0724-y + + +
+ + + + + 28426680 + + 2017 + 09 + 07 + + + 2017 + 09 + 07 + +
+ + 1932-6203 + + 12 + 4 + + 2017 + + + PloS one + PLoS ONE + + Echocardiographic findings in infants with presumed congenital Zika syndrome: Retrospective case series study. + + e0175065 + + 10.1371/journal.pone.0175065 + + To report the echocardiographic evaluation of 103 infants with presumed congenital Zika syndrome. + An observational retrospective study was performed at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil. 103 infants with presumed congenital Zika syndrome. All infants had microcephaly and head computed tomography findings compatible with congenital Zika syndrome. Zika IgM antibody was detected in cerebrospinal fluid samples of 23 infants. In 80 infants, the test was not performed because it was not available at that time. All infants had negative serology for HIV, syphilis, rubella, cytomegalovirus and toxoplasmosis. A complete transthoracic two-dimensional, M-mode, continuous wave and pulsed wave Doppler and color Doppler echocardiographic (PHILIPS HD11XE or HD15) examination was performed on all infants. + 14/103 (13.5%) echocardiograms were compatible with congenital heart disease: 5 with an ostium secundum atrial septal defect, 8 had a hemodynamically insignificant small apical muscular ventricular septal defect and one infant with dyspnea had a large membranous ventricular septal defect. The echocardiograms considered normal included 45 infants with a persistent foramen ovale and 16 with a minimum patent ductus arteriosus. + Preliminarily this study suggests that congenital Zika syndrome may be associated with an increase prevalence of congenital heart disease. However the types of defects noted were septal defects, a proportion of which would not be hemodynamically significant. + + + + Cavalcanti + Danielle Di + DD + + Department of Pediatrics, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil. + + + + Alves + Lucas V + LV + http://orcid.org/0000-0002-9170-0808 + + Department of Pediatrics, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil. + + + + Furtado + Geraldo J + GJ + + Department of Pediatrics, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil. + + + + Santos + Cleusa C + CC + + Department of Pediatric Cardiology, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil. + + + + Feitosa + Fabiana G + FG + + Department of Pediatric Cardiology, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil. + + + + Ribeiro + Maria C + MC + + Department of Pediatric Cardiology, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil. + + + + Menge + Paulo + P + + Department of Pediatric Cardiology, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil. + + + + Lira + Izabelle M + IM + + Department of Pediatric Cardiology, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil. + + + + Alves + Joao G + JG + + Department of Pediatric Cardiology, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil. + + + + eng + + Journal Article + + + 2017 + 04 + 20 + +
+ + United States + PLoS One + 101285081 + 1932-6203 + + IM + + + Bull World Health Organ. 2016 Jun 1;94(6):406-406A + 27274588 + + + Int J Cardiol. 2016 Oct 15;221:859 + 27434361 + + + Cases J. 2009 May 27;2:7147 + 19829922 + + + Circulation. 1971 Mar;43(3):323-32 + 5102136 + + + Am J Public Health. 2016 Apr;106(4):598-600 + 26959258 + + + BMC Pediatr. 2013 Apr 20;13:59 + 23601190 + + + Acta Paediatr. 2011 Aug;100(8):e55-60 + 21362039 + + + Am J Cardiol. 1999 Jun 1;83(11):1552-5 + 10363870 + + + J Paediatr Child Health. 2012 Dec;48(12 ):1082-5 + 22621644 + + + J Pediatr. 1957 Jul;51(1):12-7 + 13439480 + + + Clin Infect Dis. 2013 Sep;57(6):812-9 + 23784923 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Pediatrics. 2006 Oct;118(4):1560-5 + 17015547 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):55-8 + 26820163 + + + Proc (Bayl Univ Med Cent). 2015 Oct;28(4):516-20 + 26424961 + + + + + Electrocardiography + + + Humans + + + Infant + + + Retrospective Studies + + + Zika Virus Infection + congenital + diagnostic imaging + physiopathology + + +
+ + + + 2016 + 09 + 19 + + + 2017 + 03 + 20 + + + 2017 + 4 + 21 + 6 + 0 + + + 2017 + 4 + 21 + 6 + 0 + + + 2017 + 9 + 8 + 6 + 0 + + + epublish + + 28426680 + 10.1371/journal.pone.0175065 + PONE-D-16-37549 + PMC5398518 + + +
+ + + + + 28418539 + + 2017 + 07 + 19 + + + 2017 + 07 + 19 + +
+ + 2168-6173 + + 135 + 5 + + 2017 + May + 01 + + + JAMA ophthalmology + JAMA Ophthalmol + + Ophthalmic Manifestations of Congenital Zika Syndrome in Colombia and Venezuela. + + 440-445 + + 10.1001/jamaophthalmol.2017.0561 + + The ocular manifestations and sequelae of Zika virus infection are not well known. Recently, the World Health Organization changed the declaration of Zika as a public health emergency and designated the viral outbreak and related microcephaly clusters as a long-term program of work. This change indicates the urgent need to evaluate and document ophthalmic manifestations in patients for timely management of this disease. In addition, confirmation whether the public health problem in Brazil extends to other regions in South America is needed. + To report the ocular manifestations of congenital Zika syndrome with microcephaly in Colombia and Venezuela. + This prospective case series included 43 patients from 2 ophthalmic centers in Colombia and Venezuela who underwent evaluation from October 1, 2015, through June 30, 2016, and were clinically diagnosed with congenital Zika syndrome. Twenty patients were Hispanic; 13, African; 8, white; and 2, Native American. + Ophthalmic and systemic evaluations and serologic testing were performed on all infants. Patients underwent external ocular examination and dilated ophthalmoscopy. Serologic testing ruled out toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus. + Ophthalmic manifestations of congenital Zika syndrome. + Of the 43 patients included in this series (28 female and 15 male), the mean (SD) age at examination was 2.1 (1.5) months. The mothers of all the children had no ophthalmic findings and did not report ocular symptoms during pregnancy. All patients had bilateral ophthalmic manifestations. Optic nerve findings included hypoplasia with the double-ring sign, pallor, and increased cup-disc ratio in 5 patients (11.6%). Macular abnormalities included mild to severe pigment mottling in 27 patients (63%) and lacunar maculopathy in 3 (6.9%). Chorioretinal scarring was present in 3 patients (7%). Eleven patients (26%) had a combination of lesions in the posterior pole. Five patients (12%) were diagnosed with congenital glaucoma, characterized by the clinical triad of epiphora, photophobia, and blepharospasm; increased intraocular pressure; corneal clouding at birth; and buphthalmos. These data reveal that 12% (95% CI, 5%-24%) of cases of congenital Zika with microcephaly had anterior segment abnormalities and 88% (95% CI, 76%-94%) had important macular and optic nerve abnormalities. The visual sequelae of these ophthalmic manifestations remain unknown. + Congenital Zika syndrome in the current study had severe ocular abnormalities, and all patients had bilateral involvement. Ocular findings were focal macular pigment mottling, chorioretinal atrophy with a predilection for the macular area, congenital glaucoma and optical nerve hypoplasia, and optic disc abnormalities. Ophthalmic examination is recommended in patients with congenital Zika syndrome. + + + + Yepez + Juan B + JB + + Department of Vitreoretinal Surgery, Clínica de Ojos, Maracaibo, Venezuela2Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. + + + + Murati + Felipe A + FA + + Department of Vitreoretinal Surgery, Clínica de Ojos, Maracaibo, Venezuela. + + + + Pettito + Michele + M + + Department of Glaucoma, Clínica de Ojos, Maracaibo, Venezuela. + + + + Peñaranda + Carlos F + CF + + Clínica Oftalmológica Peñaranda, Cúcuta, Colombia. + + + + de Yepez + Jazmin + J + + Department of Pediatric Ophthalmology, Clínica de Ojos, Maracaibo, Venezuela. + + + + Maestre + Gladys + G + + Division of Neurosciences, Department of Biomedical Sciences, University of Texas Rio Grande Valley School of Medicine, Brownsville. + + + + Arevalo + J Fernando + JF + + Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland8Johns Hopkins Zika Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. + + + + Johns Hopkins Zika Center + + + eng + + Journal Article + Multicenter Study + +
+ + United States + JAMA Ophthalmol + 101589539 + 2168-6165 + + AIM + IM + + + Lancet. 2016 Apr 2;387(10026):1482 + 27115821 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Ophthalmology. 2017 Mar;124(3):407-408 + 27914834 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + JAMA Ophthalmol. 2016 Feb 9;: + 26865554 + + + Ophthalmology. 2016 Aug;123(8):1788-94 + 27236271 + + + JAMA. 2016 Mar 1;315(9):865-6 + 26818622 + + + Am J Ophthalmol. 2003 Oct;136(4):733-5 + 14516816 + + + BMJ. 2016 Feb 02;352:i657 + 26839247 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Br J Ophthalmol. 1993 Jun;77(6):358-63 + 8318483 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + Lancet. 2016 Jun 18;387(10037):2502 + 27287830 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + JAMA. 2013 Nov 27;310(20):2191-4 + 24141714 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + N Engl J Med. 2016 Jun 15;:null + 27305043 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Colombia + epidemiology + + + Eye Abnormalities + diagnosis + epidemiology + etiology + + + Female + + + Humans + + + Incidence + + + Infant + + + Male + + + Ophthalmoscopy + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Prospective Studies + + + Syndrome + + + Venezuela + epidemiology + + + Zika Virus + + + Zika Virus Infection + complications + congenital + + +
+ + + + 2018 + 05 + 11 + + + 2017 + 4 + 19 + 6 + 0 + + + 2017 + 7 + 20 + 6 + 0 + + + 2017 + 4 + 19 + 6 + 0 + + + ppublish + + 28418539 + 2617257 + 10.1001/jamaophthalmol.2017.0561 + PMC5470423 + + +
+ + + + + 28409618 + + 2017 + 04 + 25 + + + 2017 + 04 + 25 + +
+ + 1532-0650 + + 95 + 8 + + 2017 + Apr + 15 + + + American family physician + Am Fam Physician + + Zika Virus: Common Questions and Answers. + + 507-513 + + + Since local mosquito-borne transmission of Zika virus was first reported in Brazil in early 2015, the virus has spread rapidly, with active transmission reported in at least 61 countries and territories worldwide, including the United States. Zika virus infection during pregnancy is a cause of microcephaly and other severe brain anomalies. The virus is transmitted primarily through the bite of an infected Aedes mosquito, but other routes of transmission include sexual, mother-to-fetus during pregnancy, mother-to-infant at delivery, laboratory exposure, and, possibly, transfusion of blood products. Most persons with Zika virus infection are asymptomatic or have only mild symptoms; hospitalizations and deaths are rare. When symptoms are present, maculopapular rash, fever, arthralgia, and conjunctivitis are most common. Zika virus testing is recommended for persons with possible exposure (those who have traveled to or live in an area with active transmission, or persons who had sex without a condom with a person with possible exposure) if they have symptoms consistent with Zika virus disease. Testing is also recommended for pregnant women with possible exposure, regardless of whether symptoms are present. Treatment is supportive, and no vaccine is currently available. The primary methods of prevention include avoiding bites of infected Aedes mosquitoes and reducing the risk of sexual transmission. Pregnant women should not travel to areas with active Zika virus transmission, and men and women who are planning to conceive in the near future should consider avoiding nonessential travel to these areas. Condoms can reduce the risk of sexual transmission. + + + + Igbinosa + Irogue I + II + + Centers for Disease Control and Prevention, Atlanta, GA, USA. + + + + Rabe + Ingrid B + IB + + Centers for Disease Control and Prevention, Atlanta, GA, USA. + + + + Oduyebo + Titilope + T + + Centers for Disease Control and Prevention, Atlanta, GA, USA. + + + + Rasmussen + Sonja A + SA + + Centers for Disease Control and Prevention, Atlanta, GA, USA. + + + + eng + + Journal Article + +
+ + United States + Am Fam Physician + 1272646 + 0002-838X + + AIM + IM + + + Aedes + + + Animals + + + Condoms + utilization + + + Education, Medical, Continuing + + + Exanthema + virology + + + Female + + + Fever + virology + + + Guidelines as Topic + + + Humans + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + prevention & control + virology + + + Risk Factors + + + Travel + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + diagnosis + prevention & control + transmission + + +
+ + + + 2017 + 4 + 15 + 6 + 0 + + + 2017 + 4 + 15 + 6 + 0 + + + 2017 + 4 + 26 + 6 + 0 + + + ppublish + + 28409618 + d13231 + + +
+ + + + + 28403061 + + 2017 + 04 + 20 + + + 2017 + 04 + 20 + +
+ + 1532-0987 + + 36 + 5 + + 2017 + May + + + The Pediatric infectious disease journal + Pediatr. Infect. Dis. J. + + Microcephaly Case Fatality Rate Associated with Zika Virus Infection in Brazil: Current Estimates. + + 528-530 + + 10.1097/INF.0000000000001486 + + Considering the currently confirmed cases of microcephaly and related deaths associated with Zika virus in Brazil, the estimated case fatality rate is 8.3% (95% confidence interval: 7.2-9.6). However, a third of the reported cases remain under investigation. If the confirmation rates of cases and deaths are the same in the future, the estimated case fatality rate will be as high as 10.5% (95% confidence interval: 9.5-11.7). + + + + Cunha + Antonio José Ledo Alves da + AJ + + From the *Departamento de Pediatria da Faculdade de Medicina da Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Puericultura e Pediatria Martagão Gesteira (IPPMG), Rio de Janeiro, Brazil; †Departamento de Pediatria, Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Brazil; and ‡Departamento de Medicina Preventiva, Instituto de Estudos em Saúde Coletiva (IESC) da Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. + + + + de Magalhães-Barbosa + Maria Clara + MC + + + Lima-Setta + Fernanda + F + + + Medronho + Roberto de Andrade + RA + + + Prata-Barbosa + Arnaldo + A + + + eng + + Journal Article + +
+ + United States + Pediatr Infect Dis J + 8701858 + 0891-3668 + + IM + + + Adult + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Fetus + + + Humans + + + Infant + + + Infant, Newborn + + + Microcephaly + epidemiology + etiology + mortality + virology + + + Perinatal Mortality + trends + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + epidemiology + mortality + virology + + + Survival Analysis + + + Zika Virus + pathogenicity + physiology + + + Zika Virus Infection + complications + epidemiology + mortality + virology + + +
+ + + + 2017 + 4 + 14 + 6 + 0 + + + 2017 + 4 + 14 + 6 + 0 + + + 2017 + 4 + 21 + 6 + 0 + + + ppublish + + 28403061 + 10.1097/INF.0000000000001486 + 00006454-201705000-00027 + + +
+ + + + + 28403053 + + 2017 + 04 + 20 + + + 2017 + 04 + 20 + +
+ + 1532-0987 + + 36 + 5 + + 2017 + May + + + The Pediatric infectious disease journal + Pediatr. Infect. Dis. J. + + Zika Virus Infection Associated With Congenital Birth Defects in a HIV-infected Pregnant Woman. + + 500-501 + + 10.1097/INF.0000000000001482 + + We describe a case of Zika virus infection acquired during the first trimester in a HIV-infected pregnant woman that led to multiple fetal malformations and fetal demise in Rio de Janeiro, Brazil. + + + + João + Esaú Custódio + EC + + From the *Infectious Diseases Department, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil; †Instituto Nacional de Infectologia Evandro Chagas - Fiocruz, Rio de Janeiro, Brazil; and ‡Hospital Maternidade Maria Amelia Buarque de Hollanda, Rio de Janeiro, Brazil. + + + + Gouvea + Maria Isabel Fragoso da Silveira + MI + + + Teixeira + Maria de Lourdes Benamor + ML + + + Mendes-Silva + Wallace + W + + + Esteves + Juliana Silva + JS + + + Santos + Edwiges Motta + EM + + + Ledesma + Leandro Augusto + LA + + + Gomes + Ana Paula + AP + + + Cruz + Maria Letícia + ML + + + eng + + Case Reports + Journal Article + +
+ + United States + Pediatr Infect Dis J + 8701858 + 0891-3668 + + IM + + + Arthrogryposis + diagnostic imaging + pathology + virology + + + Brazil + + + Edema + diagnostic imaging + pathology + + + Female + + + Fetal Death + + + Fetus + diagnostic imaging + pathology + virology + + + HIV + pathogenicity + physiology + + + HIV Infections + diagnostic imaging + pathology + virology + + + Humans + + + Microcephaly + diagnostic imaging + pathology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnostic imaging + pathology + virology + + + Pregnancy Trimester, First + + + Zika Virus + pathogenicity + physiology + + + Zika Virus Infection + diagnostic imaging + pathology + virology + + +
+ + + + 2017 + 4 + 14 + 6 + 0 + + + 2017 + 4 + 14 + 6 + 0 + + + 2017 + 4 + 21 + 6 + 0 + + + ppublish + + 28403053 + 10.1097/INF.0000000000001482 + 00006454-201705000-00013 + + +
+ + + + + 28402236 + + 2017 + 05 + 09 + + + 2017 + 10 + 25 + +
+ + 1533-4406 + + 376 + 16 + + 2017 + 04 + 20 + + + The New England journal of medicine + N. Engl. J. Med. + + Zika Virus Infection and Associated Neurologic Disorders in Brazil. + + 1591-1593 + + 10.1056/NEJMc1608612 + + + de Oliveira + Wanderson K + WK + + Ministry of Health, Brasilia, Brazil. + + + + Carmo + Eduardo H + EH + + Ministry of Health, Brasilia, Brazil. + + + + Henriques + Claudio M + CM + + Oswaldo Cruz Foundation, Brasilia, Brazil. + + + + Coelho + Giovanini + G + + Ministry of Health, Brasilia, Brazil. + + + + Vazquez + Enrique + E + + Pan American Health Organization, Brasilia, Brazil. + + + + Cortez-Escalante + Juan + J + + Pan American Health Organization, Brasilia, Brazil. + + + + Molina + Joaquin + J + + Pan American Health Organization, Brasilia, Brazil. + + + + Aldighieri + Sylvain + S + + Pan American Health Organization, Washington, DC. + + + + Espinal + Marcos A + MA + + Pan American Health Organization, Washington, DC. + + + + Dye + Christopher + C + + World Health Organization, Geneva, Switzerland dyec@who.int. + + + + eng + + + 001 + World Health Organization + International + + + + Letter + Research Support, Non-U.S. Gov't + + + 2017 + 03 + 29 + +
+ + United States + N Engl J Med + 0255562 + 0028-4793 + + AIM + IM + + + Science. 2016 Jul 22;353(6297):353-4 + 27417493 + + + Emerg Infect Dis. 2010 Mar;16(3):418-25 + 20202416 + + + Rev Soc Bras Med Trop. 2016 Sep-Oct;49(5):553-558 + 27812648 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + + + Brazil + epidemiology + + + Epidemics + + + Female + + + Guillain-Barre Syndrome + epidemiology + etiology + + + Humans + + + Incidence + + + Microcephaly + epidemiology + etiology + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Zika Virus + + + Zika Virus Infection + complications + epidemiology + + +
+ + + + 2017 + 4 + 13 + 6 + 0 + + + 2017 + 5 + 10 + 6 + 0 + + + 2017 + 4 + 13 + 6 + 0 + + + ppublish + + 28402236 + 10.1056/NEJMc1608612 + PMC5544116 + EMS73289 + + +
+ + + + + 28394328 + + 2017 + 08 + 29 + + + 2017 + 08 + 29 + +
+ + 1546-170X + + 23 + 6 + + 2017 + Jun + + + Nature medicine + Nat. Med. + + A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models. + + 763-767 + + 10.1038/nm.4322 + + Zika virus (ZIKV) infection of pregnant women can cause a wide range of congenital abnormalities, including microcephaly, in the infant, a condition now collectively known as congenital ZIKV syndrome. A vaccine to prevent or significantly attenuate viremia in pregnant women who are residents of or travelers to epidemic or endemic regions is needed to avert congenital ZIKV syndrome, and might also help to suppress epidemic transmission. Here we report on a live-attenuated vaccine candidate that contains a 10-nucleotide deletion in the 3' untranslated region of the ZIKV genome (10-del ZIKV). The 10-del ZIKV is highly attenuated, immunogenic, and protective in type 1 interferon receptor-deficient A129 mice. Crucially, a single dose of 10-del ZIKV induced sterilizing immunity with a saturated neutralizing antibody titer, which no longer increased after challenge with an epidemic ZIKV, and completely prevented viremia. The immunized mice also developed a robust T cell response. Intracranial inoculation of 1-d-old immunocompetent CD-1 mice with 1 × 104infectious focus units (IFU) of 10-del ZIKV caused no mortality, whereas infections with 10 IFU of wild-type ZIKV were lethal. Mechanistically, the attenuated virulence of 10-del ZIKV may be due to decreased viral RNA synthesis and increased sensitivity to type-1-interferon inhibition. The attenuated 10-del ZIKV was incapable of infecting mosquitoes after oral feeding of spiked-blood meals, representing an additional safety feature. Collectively, the safety and efficacy results suggest that further development of this promising, live-attenuated ZIKV vaccine candidate is warranted. + + + + Shan + Chao + C + + Department of Biochemistry &Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA. + + + + Muruato + Antonio E + AE + + Institute for Human Infections &Immunity, University of Texas Medical Branch, Galveston, Texas, USA. + + + Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas, USA. + + + + Nunes + Bruno T D + BTD + + Department of Biochemistry &Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA. + + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Luo + Huanle + H + + Department of Microbiology &Immunology, University of Texas Medical Branch, Galveston, Texas, USA. + + + + Xie + Xuping + X + + Department of Biochemistry &Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA. + + + + Medeiros + Daniele B A + DBA + + Department of Biochemistry &Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA. + + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Wakamiya + Maki + M + + Department of Biochemistry &Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA. + + + + Tesh + Robert B + RB + + Institute for Human Infections &Immunity, University of Texas Medical Branch, Galveston, Texas, USA. + + + Department of Pathology and Center for Biodefense &Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA. + + + + Barrett + Alan D + AD + + Institute for Human Infections &Immunity, University of Texas Medical Branch, Galveston, Texas, USA. + + + Department of Pathology and Center for Biodefense &Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA. + + + Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA. + + + + Wang + Tian + T + + Department of Microbiology &Immunology, University of Texas Medical Branch, Galveston, Texas, USA. + + + Department of Pathology and Center for Biodefense &Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA. + + + Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA. + + + + Weaver + Scott C + SC + + Institute for Human Infections &Immunity, University of Texas Medical Branch, Galveston, Texas, USA. + + + Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas, USA. + + + Department of Microbiology &Immunology, University of Texas Medical Branch, Galveston, Texas, USA. + + + Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA. + + + Sealy Center for Structural Biology &Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas, USA. + + + + Vasconcelos + Pedro F C + PFC + http://orcid.org/0000-0002-6603-5527 + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + Department of Pathology, Pará State University, Belém, Brazil. + + + + Rossi + Shannan L + SL + + Institute for Human Infections &Immunity, University of Texas Medical Branch, Galveston, Texas, USA. + + + Department of Pathology and Center for Biodefense &Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA. + + + + Shi + Pei-Yong + PY + + Department of Biochemistry &Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA. + + + Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA. + + + Sealy Center for Structural Biology &Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas, USA. + + + Department of Phamarcology &Toxicology, University of Texas Medical Branch, Galveston, Texas, USA. + + + + eng + + Journal Article + + + 2017 + 04 + 10 + +
+ + United States + Nat Med + 9502015 + 1078-8956 + + + + 0 + 3' Untranslated Regions + + + 0 + Antibodies, Neutralizing + + + 0 + Interferon Type I + + + 0 + RNA, Viral + + + 0 + Receptors, Interferon + + + 0 + Vaccines, Attenuated + + + IM + + + Bull World Health Organ. 2016 Jun 1;94(6):406-406A + 27274588 + + + J Virol. 2004 Jan;78(2):1032-8 + 14694136 + + + Nature. 2016 Aug 25;536(7617):474-8 + 27355570 + + + Science. 2016 Sep 9;353(6304):1129-32 + 27492477 + + + World Health Organ Tech Rep Ser. 1987;747:1-29 + 3107222 + + + Expert Rev Vaccines. 2016;15(4):509-17 + 26559731 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Cell Host Microbe. 2008 Dec 11;4(6):579-91 + 19064258 + + + J Virol. 2002 Jun;76(12):5847-56 + 12021317 + + + J Gen Virol. 1986 Apr;67 ( Pt 4):631-7 + 3958694 + + + J Virol. 2003 Sep;77(18):10004-14 + 12941911 + + + Cell. 2017 Mar 9;168(6):1114-1125.e10 + 28222903 + + + Proc Natl Acad Sci U S A. 2013 May 28;110(22):E2046-53 + 23580623 + + + Cell. 2016 Dec 1;167(6):1511-1524.e10 + 27884405 + + + MBio. 2017 Feb 7;8(1):null + 28174309 + + + J Infect Dis. 2016 Nov 1;214(9):1349-1356 + 27436433 + + + ACS Infect Dis. 2016 Mar 11;2(3):170-2 + 27623030 + + + Mem Inst Oswaldo Cruz. 2016 Oct;111(10 ):655-658 + 27706382 + + + Science. 2015 Oct 9;350(6257):217-21 + 26138103 + + + EBioMedicine. 2016 Oct;12 :156-160 + 27658737 + + + Science. 2016 Oct 14;354(6309):237-240 + 27708058 + + + Biol Reprod. 2014 Jan 16;90(1):8 + 24174576 + + + Antiviral Res. 2016 Jun;130:69-80 + 26996139 + + + J Virol. 1998 Sep;72(9):7270-9 + 9696822 + + + J Gen Virol. 2016 Oct;97(10 ):2575-2591 + 27498826 + + + Nature. 2016 Dec 15;540(7633):438-442 + 27798603 + + + Antiviral Res. 2010 May;86(2):163-71 + 20153777 + + + Science. 2016 Dec 2;354(6316):1148-1152 + 27934765 + + + J Virol. 1999 Nov;73(11):9247-55 + 10516033 + + + Infect Genet Evol. 2016 Sep;43:43-9 + 27156653 + + + Cell Host Microbe. 2016 Jun 8;19(6):891-900 + 27198478 + + + J Virol. 2015 Jan 15;89(2):1298-313 + 25392211 + + + J Immunol. 2009 Apr 15;182(8):4865-73 + 19342665 + + + Nature. 2017 Mar 9;543(7644):248-251 + 28151488 + + + + + 3' Untranslated Regions + genetics + + + Aedes + + + Animals + + + Antibodies, Neutralizing + drug effects + immunology + + + Cercopithecus aethiops + + + Fluorescent Antibody Technique + + + Immunogenicity, Vaccine + + + Interferon Type I + drug effects + immunology + + + Mice + + + Mice, Knockout + + + Mosquito Vectors + virology + + + Mutation + + + RNA, Viral + drug effects + metabolism + + + Real-Time Polymerase Chain Reaction + + + Receptors, Interferon + genetics + + + Vaccines, Attenuated + pharmacology + + + Vero Cells + + + Virus Replication + drug effects + + + Zika Virus + drug effects + genetics + immunology + + + Zika Virus Infection + prevention & control + + +
+ + + + 2016 + 12 + 06 + + + 2017 + 03 + 09 + + + 2017 + 4 + 11 + 6 + 0 + + + 2017 + 8 + 30 + 6 + 0 + + + 2017 + 4 + 11 + 6 + 0 + + + ppublish + + 28394328 + nm.4322 + 10.1038/nm.4322 + + +
+ + + + + 28383800 + + 2017 + 10 + 10 + + + 2017 + 11 + 29 + +
+ + 1759-7692 + + 6 + 4 + + 2017 + 07 + + + Wiley interdisciplinary reviews. Developmental biology + Wiley Interdiscip Rev Dev Biol + + Potential mechanisms of Zika-linked microcephaly. + 10.1002/wdev.273 + + A recent outbreak of Zika virus (ZIKV) in Brazil is associated with microcephaly in infants born of infected mothers. As this pandemic spreads, rapid scientific investigation is shedding new light on how prenatal infection with ZIKV causes microcephaly. In this analysis we provide an overview of both microcephaly and ZIKV, explore the connection between prenatal ZIKV infection and microcephaly, and highlight recent insights into how prenatal ZIKV infection depletes the pool of neural progenitors in the developing brain. WIREs Dev Biol 2017, 6:e273. doi: 10.1002/wdev.273 For further resources related to this article, please visit the WIREs website. + © 2017 The Authors. WIREs Developmental Biology published by Wiley Periodicals, Inc. + + + + Merfeld + Emily + E + + Biology Department, Reed College, Portland, OR, USA. + + + + Ben-Avi + Lily + L + + Biology Department, Reed College, Portland, OR, USA. + + + + Kennon + Mason + M + + Biology Department, Reed College, Portland, OR, USA. + + + + Cerveny + Kara L + KL + 0000-0003-0667-827X + + Biology Department, Reed College, Portland, OR, USA. + + + + eng + + Journal Article + Review + + + 2017 + 04 + 06 + +
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+ + + + 2016 + 08 + 16 + + + 2017 + 02 + 20 + + + 2017 + 02 + 23 + + + 2017 + 4 + 7 + 6 + 0 + + + 2017 + 10 + 11 + 6 + 0 + + + 2017 + 4 + 7 + 6 + 0 + + + ppublish + + 28383800 + 10.1002/wdev.273 + PMC5516183 + + +
+ + + + + 28370966 + + 2018 + 01 + 12 + + + 2018 + 01 + 12 + +
+ + 1462-5822 + + 19 + 6 + + 2017 + Jun + + + Cellular microbiology + Cell. Microbiol. + + Zika infection and the development of neurological defects. + 10.1111/cmi.12744 + + Starting with the outbreak in Brazil, Zika virus (ZIKV) infection has been correlated with severe syndromes such as congenital Zika syndrome and Guillain-Barré syndrome. Here, we review the status of Zika virus pathogenesis in the central nervous system (CNS). One of the main concerns about ZIKV exposure during pregnancy is abnormal brain development, which results in microcephaly in newborns. Recent advances in in vitro research show that ZIKV can infect and obliterate cells from the CNS, such as progenitors, neurons, and glial cells. Neural progenitor cells seem to be the main target of the virus, with infection leading to less cell migration, neurogenesis impairment, cell death and, consequently, microcephaly in newborns. The downsizing of the brain can be directly associated with defective development of the cortical layer. In addition, in vivo investigations in mice reveal that ZIKV can cross the placenta and migrate to fetuses, but with a significant neurotropism, which results in brain damage for the pups. Another finding shows that hydrocephaly is an additional consequence of ZIKV infection, being detected during embryonic and fetal development in mouse, as well as after birth in humans. In spite of the advances in ZIKV research in the last year, the mechanisms underlying ZIKV infection in the CNS require further investigation particularly as there are currently no treatments or vaccines against ZIKV infection. + © 2017 John Wiley & Sons Ltd. + + + + Russo + Fabiele Baldino + FB + http://orcid.org/0000-0002-4076-1846 + + Department of Surgery, University of São Paulo, São Paulo, Brazil. + + + Department of Microbiology, University of São Paulo, São Paulo, Brazil. + + + + Jungmann + Patricia + P + + Department of Pathology, University of Pernambuco, Recife, Pernambuco, Brazil. + + + + Beltrão-Braga + Patricia Cristina Baleeiro + PCB + http://orcid.org/0000-0003-0004-1091 + + Department of Surgery, University of São Paulo, São Paulo, Brazil. + + + Department of Microbiology, University of São Paulo, São Paulo, Brazil. + + + Department of Obstetrics, School of Arts Sciences and Humanities, São Paulo, Brazil. + + + + eng + + Journal Article + Review + + + 2017 + 05 + 03 + +
+ + England + Cell Microbiol + 100883691 + 1462-5814 + + IM + + + Animals + + + Brain + embryology + virology + + + Cell Movement + physiology + + + Female + + + Humans + + + Hydrocephalus + virology + + + Mice + + + Microcephaly + virology + + + Neural Stem Cells + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Zika Virus + pathogenicity + + + Zika Virus Infection + pathology + virology + + + + ZIKV + Zika + brain damage + congenital Zika syndrome + flaviviruses + microcephaly + +
+ + + + 2016 + 12 + 31 + + + 2017 + 03 + 12 + + + 2017 + 03 + 28 + + + 2017 + 4 + 4 + 6 + 0 + + + 2018 + 1 + 13 + 6 + 0 + + + 2017 + 4 + 4 + 6 + 0 + + + ppublish + + 28370966 + 10.1111/cmi.12744 + + +
+ + + + + 28362944 + + 2017 + 12 + 22 + + + 2018 + 03 + 08 + +
+ + 1537-6591 + + 64 + 7 + + 2017 + Apr + 01 + + + Clinical infectious diseases : an official publication of the Infectious Diseases Society of America + Clin. Infect. Dis. + + Zika Virus Infects Human Fetal Brain Microglia and Induces Inflammation. + + 914-920 + + 10.1093/cid/ciw878 + + The unprecedented reemergence of Zika virus (ZIKV) has startled the world with reports of increased microcephaly in Brazil. ZIKV can infect human neural progenitors and impair brain growth. However, direct evidence of ZIKV infection in human fetal brain tissues remains elusive. + Investigations were performed with brain cell preparations obtained from 9 donors. Virus infectivity was assessed by detection of virus antigen by flow cytometry together with various hematopoietic cell surface markers. Virus replication was determined by viral RNA quantification. Cytokine levels in supernatant obtained from virus-infected fetal brain cells were measured simultaneously in microbead-based immunoassays. + We also show that ZIKV infection was particularly evident in hematopoietic cells with microglia, the brain-resident macrophage population being one of the main targets. Infection induces high levels of proinflammatory immune mediators such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and monocyte chemotactic protein 1 (MCP-1). + Our results highlight an important role for microglia and neuroinflammation during congenital ZIKV pathogenesis. + © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. + + + + Lum + Fok-Moon + FM + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). + + + + Low + Donovan K S + DK + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). + + + + Fan + Yiping + Y + + Department of Reproductive Medicine and. + + + + Tan + Jeslin J L + JJ + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). + + + + Lee + Bernett + B + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). + + + + Chan + Jerry K Y + JK + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). + + + Department of Reproductive Medicine and. + + + KK Research Centre, KK Women's and Children's Hospital, and. + + + Cancer and Stem Cell Program, Duke-NUS Medical School, Singapore; and. + + + + Rénia + Laurent + L + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). + + + + Ginhoux + Florent + F + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). + + + + Ng + Lisa F P + LF + + Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR). + + + Institute of Infection and Global Health, University of Liverpool, United Kingdom. + + + + eng + + Journal Article + +
+ + United States + Clin Infect Dis + 9203213 + 1058-4838 + + + + 0 + Cytokines + + + IM + + + Animals + + + Brain + pathology + virology + + + Cell Line + + + Cells, Cultured + + + Cercopithecus aethiops + + + Cytokines + metabolism + + + Encephalitis, Viral + immunology + metabolism + pathology + virology + + + Fetus + + + Humans + + + Macrophages + immunology + metabolism + virology + + + Microcephaly + etiology + + + Microglia + metabolism + virology + + + Monocytes + immunology + metabolism + virology + + + Vero Cells + + + Viral Load + + + Zika Virus + + + Zika Virus Infection + immunology + metabolism + pathology + virology + + + + Zika virus + inflammation + microglia. + +
+ + + + 2016 + 10 + 12 + + + 2017 + 01 + 04 + + + 2017 + 4 + 1 + 6 + 0 + + + 2017 + 4 + 1 + 6 + 0 + + + 2017 + 12 + 23 + 6 + 0 + + + ppublish + + 28362944 + 3041121 + 10.1093/cid/ciw878 + + +
+ + + + + 28358795 + + 2017 + 04 + 03 + + + 2018 + 01 + 19 + +
+ + 1545-861X + + 66 + 12 + + 2017 + Mar + 31 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Zika Virus Transmission - Region of the Americas, May 15, 2015-December 15, 2016. + + 329-334 + + 10.15585/mmwr.mm6612a4 + + Zika virus, a mosquito-borne flavivirus that can cause rash with fever, emerged in the Region of the Americas on Easter Island, Chile, in 2014 and in northeast Brazil in 2015 (1). In response, in May 2015, the Pan American Health Organization (PAHO), which serves as the Regional Office of the Americas for the World Health Organization (WHO), issued recommendations to enhance surveillance for Zika virus. Subsequently, Brazilian investigators reported Guillain-Barré syndrome (GBS), which had been previously recognized among some patients with Zika virus disease, and identified an association between Zika virus infection during pregnancy and congenital microcephaly (2). On February 1, 2016, WHO declared Zika virus-related microcephaly clusters and other neurologic disorders a Public Health Emergency of International Concern.* In March 2016, PAHO developed case definitions and surveillance guidance for Zika virus disease and associated complications (3). Analysis of reports submitted to PAHO by countries in the region or published in national epidemiologic bulletins revealed that Zika virus transmission had extended to 48 countries and territories in the Region of the Americas by late 2016. Reported Zika virus disease cases peaked at different times in different areas during 2016. Because of ongoing transmission and the risk for recurrence of large outbreaks, response efforts, including surveillance for Zika virus disease and its complications, and vector control and other prevention activities, need to be maintained. + + + + Ikejezie + Juniorcaius + J + + + Shapiro + Craig N + CN + + + Kim + Jisoo + J + + + Chiu + Monica + M + + + Almiron + Maria + M + + + Ugarte + Ciro + C + + + Espinal + Marcos A + MA + + + Aldighieri + Sylvain + S + + + eng + + Journal Article + + + 2017 + 03 + 31 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + J Infect Dev Ctries. 2016 Feb 28;10 (2):116-20 + 26927450 + + + Science. 2016 Aug 12;353(6300):aaf8160 + 27417495 + + + MMWR Morb Mortal Wkly Rep. 2016 Dec 16;65(49):1409-1413 + 27977645 + + + N Engl J Med. 2016 Oct 20;375(16):1598-1601 + 27579558 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + + + Americas + epidemiology + + + Disease Outbreaks + prevention & control + + + Humans + + + Population Surveillance + + + Public Health Practice + + + Time Factors + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + prevention & control + transmission + + +
+ + + + 2017 + 3 + 31 + 6 + 0 + + + 2017 + 3 + 31 + 6 + 0 + + + 2017 + 4 + 4 + 6 + 0 + + + epublish + + 28358795 + 10.15585/mmwr.mm6612a4 + PMC5657956 + + +
+ + + + + 28357366 + + 2017 + 08 + 16 + +
+ + 2311-2638 + + 3 + 7 + + 2016 + Jun + 27 + + + Microbial cell (Graz, Austria) + Microb Cell + + Inhibition of Zika virus byWolbachiainAedes aegypti. + + 293-295 + + 10.15698/mic2016.07.513 + + Through association with cases of microcephaly in 2015, Zika virus (ZIKV) has transitioned from a relatively unknown mosquito-transmitted pathogen to a global health emergency, emphasizing the need to improve existing mosquito control programs to prevent future disease outbreaks. The response to Zika must involve a paradigm shift from traditional to novel methods of mosquito control, and according to the World Health Organization should incorporate the release of mosquitoes infected with the bacterial endosymbiontWolbachiapipientis. In our recent paper [Dutra, HLCet al., Cell Host & Microbe 2016] we investigated the potential ofWolbachiainfections inAedes aegyptito restrict infection and transmission of Zika virus recently isolated in Brazil.Wolbachiais now well known for its ability to block or reduce infection with a variety of pathogens in different mosquito species including the dengue (DENV), yellow fever, and chikungunya viruses, and malaria-causingPlasmodium, and consequently has great potential to control mosquito-transmitted diseases across the globe. Our results demonstrated that thewMelWolbachiastrain in BrazilianAe. aegyptiis a strong inhibitor of ZIKV infection, and furthermore appears to prevent transmission of infectious viral particles in mosquito saliva, which highlights the bacterium's suitability for more widespread use in Zika control. + + + + Caragata + Eric Pearce + EP + + Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Centro de Pesquisas René Rachou - Fiocruz, Belo Horizonte, MG, Brazil. + + + + Dutra + Heverton Leandro Carneiro + HL + + Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Centro de Pesquisas René Rachou - Fiocruz, Belo Horizonte, MG, Brazil. + + + + Moreira + Luciano Andrade + LA + + Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Centro de Pesquisas René Rachou - Fiocruz, Belo Horizonte, MG, Brazil. + + + + eng + + Journal Article + Comment + + + 2016 + 06 + 27 + +
+ + Austria + Microb Cell + 101632887 + 2311-2638 + + + + Cell Host Microbe. 2016 Jun 8;19(6):771-4 + 27156023 + + + + Aedes aegypti + Wolbachia + Zika virus + mosquito-transmitted disease + + Conflict of interest: The authors declare that no competing interests exist. +
+ + + + 2017 + 3 + 31 + 6 + 0 + + + 2017 + 3 + 31 + 6 + 0 + + + 2017 + 3 + 31 + 6 + 1 + + + epublish + + 28357366 + 10.15698/mic2016.07.513 + MIC0176E170 + PMC5354594 + + +
+ + + + + 28357156 + + 2017 + 04 + 03 + +
+ + 2157-3999 + + 9 + + 2017 + Feb + 22 + + + PLoS currents + PLoS Curr + + Does Zika Virus Cause Microcephaly - Applying the Bradford Hill Viewpoints. + ecurrents.outbreaks.2fced6e886074f6db162a00d4940133b + 10.1371/currents.outbreaks.2fced6e886074f6db162a00d4940133b + + Zika virus has been documented since 1952, but been associated with mild, self-limiting disease. Zika virus is classified as an arbovirus from a family of Flaviviridae and primarily spread by Aedes Aegypti mosquitos. However, in a large outbreak in Brazil in 2015, Zika virus has been associated with microcephaly. + In this review we applied the Bradford-Hill viewpoints  to investigate the association between Zika virus and microcephaly. We examined historical studies, available data and also compared historical rates of microcephaly prior to the Zika virus outbreak. The available evidence was reviewed against the Bradford Hill viewpoints. + All  the nine criteria were met to varying degrees: strength of association, consistency of the association, specificity, temporality, plausibility, coherence, experimental evidence, biological gradient and analogy. Conclusion: Using the Bradford Hill Viewpoints as an evaluation framework for causation is highly suggestive that the association between Zika virus and microcephaly is causal. Further studies using animal models on the viewpoints which were not as strongly fulfilled would be helpful. + + + + Awadh + Asma + A + + University Of New South Wales University Of New South Wales. + + + + Chughtai + Abrar Ahmad + AA + + University of New South Wales. + + + + Dyda + Amalie + A + + School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW, Australia. + + + + Sheikh + Mohamud + M + + Faculty of Medicine The University of New South Wales. + + + + Heslop + David J + DJ + + + MacIntyre + Chandini Raina + CR + + School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW, Australia. + + + + eng + + Journal Article + + + 2017 + 02 + 22 + +
+ + United States + PLoS Curr + 101515638 + 2157-3999 + + + + Clin Perinatol. 2005 Sep;32(3):523-59 + 16085019 + + + Rev Med Virol. 2012 Mar;22(2):69-87 + 22086854 + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + J Neuropathol Exp Neurol. 2015 Mar;74(3):250-60 + 25668565 + + + Lancet. 2016 Apr 30;387(10030):1811-2 + 27103126 + + + Emerg Themes Epidemiol. 2005 Nov 03;2:11 + 16269083 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Lancet. 2008 Feb 9;371(9611):500-9 + 18262042 + + + Acta Med Port. 2015 Nov-Dec;28(6):679-80 + 26849748 + + + Adv Virus Res. 2014;89:201-75 + 24751197 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + EMBO Mol Med. 2016 Mar 31;8(4):305-7 + 26976611 + + + Lancet. 2016 Mar 12;387(10023):1051-2 + 26944027 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + J Long Term Eff Med Implants. 2005;15(3):319-28 + 16022642 + + + Bull World Health Organ. 2005 Oct;83(10):792-5 + 16283057 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Lancet. 2016 Apr 2;387(10026):1481 + 26946926 + + + Euro Surveill. 2016;21(13):null + 27063794 + + + Science. 2016 Apr 22;352(6284):467-70 + 27033547 + + + Cell Host Microbe. 2009 Apr 23;5(4):318-28 + 19380111 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + +
+ + + + 2017 + 3 + 31 + 6 + 0 + + + 2017 + 3 + 31 + 6 + 0 + + + 2017 + 3 + 31 + 6 + 0 + + + epublish + + 28357156 + 10.1371/currents.outbreaks.2fced6e886074f6db162a00d4940133b + PMC5346029 + + +
+ + + + + 28343414 + + 2017 + 06 + 22 + + + 2017 + 06 + 22 + +
+ + 1476-8321 + + 32 + 7 + + 2017 + Jul + + + Psychology & health + Psychol Health + + Zika virus and pregnant women: A psychological approach. + + 798-809 + + 10.1080/08870446.2017.1307369 + + Zika virus presents risk of physical harm to pregnant women, but the fear of infection is also affecting women around the world. There is a gap in the research on Zika virus in the areas involving the impact on the psychosocial well-being of pregnant women. Therefore, this study is aimed at the investigation of the psychosocial adjustment of pregnant women to the risks of Zika virus infection during pregnancy. We investigated 14 pregnant women who were classified in three different groups: six in the first trimester, five in the second trimester and three in the third trimester, aged from 28 to 40 years (33.43 ± 3.76 years). Content analysis was used to interpret data. Our results show that the psychosocial adjustment of participants was significantly negative and included five aspects: (1) negative feelings, (2) changes in family planning, (3) adopting new customs (avoiding places of risk, use of specific clothes and use of repellent), (4) changed attitudes regarding body image and (5) feeling of external demand regarding prevention. The fear of Zika virus infection and all its associated risks have a negative biopsychosocial impact on the pregnant women in this study. + + + + Filgueiras Meireles + Juliana Fernandes + JF + + a Psychology Post-Graduation Program , Federal University of Juiz de Fora , Juiz de Fora , Brazil. + + + + Neves + Clara Mockdece + CM + + a Psychology Post-Graduation Program , Federal University of Juiz de Fora , Juiz de Fora , Brazil. + + + + Morgado + Fabiane Frota da Rocha + FFDR + + b Faculty of Physical Education , Rural Federal University of Rio de Janeiro , Rio de Janeiro , Brazil. + + + + Caputo Ferreira + Maria Elisa + ME + + a Psychology Post-Graduation Program , Federal University of Juiz de Fora , Juiz de Fora , Brazil. + + + + eng + + Journal Article + + + 2017 + 03 + 27 + +
+ + England + Psychol Health + 8807983 + 0887-0446 + + IM + + + Adult + + + Brazil + + + Emotional Adjustment + + + Emotions + + + Fear + + + Female + + + Focus Groups + + + Humans + + + Pregnancy + + + Pregnancy Complications, Infectious + psychology + + + Pregnant Women + psychology + + + Qualitative Research + + + Risk + + + Zika Virus Infection + psychology + + + + Zika virus + fetus + microcephaly + pregnancy + transmission + wellbeing + +
+ + + + 2017 + 3 + 28 + 6 + 0 + + + 2017 + 6 + 24 + 6 + 0 + + + 2017 + 3 + 28 + 6 + 0 + + + ppublish + + 28343414 + 10.1080/08870446.2017.1307369 + + +
+ + + + + 28342826 + + 2017 + 10 + 24 + + + 2017 + 10 + 24 + +
+ + 1873-0442 + + 16 + + 2017 Mar - Apr + + + Travel medicine and infectious disease + Travel Med Infect Dis + + New trends of the microcephaly and Zika virus outbreak in Brazil, July 2016-December 2016. + + 52-57 + + S1477-8939(17)30040-6 + 10.1016/j.tmaid.2017.03.009 + + + Magalhães-Barbosa + Maria Clara de + MC + + Instituto D'Or de Pesquisa e Ensino (IDOR), Departamento de Pediatria, Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, Rio de Janeiro, 22281-100, Brazil. Electronic address: mariaclaramb@globo.com. + + + + Prata-Barbosa + Arnaldo + A + + Instituto D'Or de Pesquisa e Ensino (IDOR), Departamento de Pediatria, Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, Rio de Janeiro, 22281-100, Brazil; Faculdade de Medicina da Universidade Federal do Rio de Janeiro, Departamento de Pediatria, Cidade Universitária, Rua Bruno Lobo, nº 50, Rio de Janeiro, 21941-612, Brazil. Electronic address: arnaldoprata@globo.com. + + + + Robaina + Jaqueline Rodrigues + JR + + Instituto D'Or de Pesquisa e Ensino (IDOR), Departamento de Pediatria, Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, Rio de Janeiro, 22281-100, Brazil. Electronic address: jaque.robaina@gmail.com. + + + + Raymundo + Carlos Eduardo + CE + + Instituto D'Or de Pesquisa e Ensino (IDOR), Departamento de Pediatria, Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, Rio de Janeiro, 22281-100, Brazil. Electronic address: caducer@gmail.com. + + + + Lima-Setta + Fernanda + F + + Instituto D'Or de Pesquisa e Ensino (IDOR), Departamento de Pediatria, Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, Rio de Janeiro, 22281-100, Brazil. Electronic address: felimasetta@gmail.com. + + + + Cunha + Antonio José Ledo Alves da + AJLAD + + Faculdade de Medicina da Universidade Federal do Rio de Janeiro, Departamento de Pediatria, Rua Bruno Lobo, nº 50, Cidade Universitária, Rio de Janeiro, 21941-612, Brazil. Electronic address: acunha@hucff.ufrj.br. + + + + eng + + Letter + + + 2017 + 03 + 22 + +
+ + Netherlands + Travel Med Infect Dis + 101230758 + 1477-8939 + + IM + + + Brazil + epidemiology + + + Disease Outbreaks + statistics & numerical data + + + Female + + + Humans + + + Incidence + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Zika Virus + + + Zika Virus Infection + epidemiology + virology + + +
+ + + + 2017 + 03 + 08 + + + 2017 + 03 + 19 + + + 2017 + 03 + 21 + + + 2017 + 3 + 28 + 6 + 0 + + + 2017 + 10 + 25 + 6 + 0 + + + 2017 + 3 + 27 + 6 + 0 + + + ppublish + + 28342826 + S1477-8939(17)30040-6 + 10.1016/j.tmaid.2017.03.009 + + +
+ + + + + 28340908 + + 2017 + 06 + 15 + + + 2017 + 06 + 15 + +
+ + 1545-1534 + + 27 + 4 + + 2016 + Dec + + + Wilderness & environmental medicine + Wilderness Environ Med + + Preparing the United States for Zika Virus: Pre-emptive Vector Control and Personal Protection. + + 450-457 + + S1080-6032(16)30184-3 + 10.1016/j.wem.2016.07.006 + + Discovered in 1947 in a monkey in the Zika forest of Uganda, Zika virus was dismissed as a cause of a mild illness that was confined to Africa and Southeast Asia and transmitted by Aedes mosquitoes. In 2007, Zika virus appeared outside of its endemic borders in an outbreak on the South Pacific Island of Yap. In 2013, Zika virus was associated with a major neurological complication, Guillain-Barré syndrome, in a larger outbreak in the French Polynesian Islands. From the South Pacific, Zika invaded Brazil in 2015 and caused another severe neurological complication, fetal microcephaly. The mosquito-borne transmission of Zika virus can be propagated by sexual transmission and, possibly, by blood transfusions, close personal contacts, and organ transplants, like other flaviviruses. Since these combined mechanisms of infectious disease transmission could result in catastrophic incidences of severe neurological diseases in adults and children, the public should know what to expect from Zika virus, how to prevent infection, and what the most likely failures in preventive measures will be. With federal research funding stalled, a Zika vaccine is far away. The only national strategies to prepare the United States for Zika virus invasion now are effective vector control measures and personal protection from mosquito bites. In addition to a basic knowledge of Aedes mosquito vectors and their biting behaviors, an understanding of simple household vector control measures, and the selection of the best chemical and physical mosquito repellents will be required to repel the Zika threat. + Copyright © 2016 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved. + + + + Diaz + James H + JH + + Program in Environmental and Occupational Health Sciences, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA. Electronic address: jdiaz@lsuhsc.edu. + + + + eng + + Editorial + + + 2016 + 10 + 27 + +
+ + United States + Wilderness Environ Med + 9505185 + 1080-6032 + + IM + + + Aedes + physiology + virology + + + Animals + + + Brazil + epidemiology + + + Female + + + Humans + + + Insect Bites and Stings + prevention & control + + + Male + + + Mosquito Control + methods + + + Mosquito Vectors + virology + + + United States + epidemiology + + + Zika Virus + pathogenicity + + + Zika Virus Infection + epidemiology + prevention & control + transmission + + + + Aedes aegypti + Aedes albopictus + Zika virus + arboviruses + mosquito-borne infectious diseases + +
+ + + + 2016 + 05 + 17 + + + 2016 + 07 + 26 + + + 2016 + 07 + 29 + + + 2017 + 3 + 26 + 6 + 0 + + + 2017 + 3 + 28 + 6 + 0 + + + 2017 + 6 + 16 + 6 + 0 + + + ppublish + + 28340908 + S1080-6032(16)30184-3 + 10.1016/j.wem.2016.07.006 + + +
+ + + + + 28339472 + + 2017 + 06 + 19 + + + 2017 + 06 + 19 + +
+ + 1935-2735 + + 11 + 3 + + 2017 + Mar + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + Vector status of Aedes species determines geographical risk of autochthonous Zika virus establishment. + + e0005487 + + 10.1371/journal.pntd.0005487 + + The 2015-16 Zika virus pandemic originating in Latin America led to predictions of a catastrophic global spread of the disease. Since the current outbreak began in Brazil in May 2015 local transmission of Zika has been reported in over 60 countries and territories, with over 750 thousand confirmed and suspected cases. As a result of its range expansion attention has focused on possible modes of transmission, of which the arthropod vector-based disease spread cycle involving Aedes species is believed to be the most important. Additional causes of concern are the emerging new links between Zika disease and Guillain-Barre Syndrome (GBS), and a once rare congenital disease, microcephaly. + Like dengue and chikungunya, the geographic establishment of Zika is thought to be limited by the occurrence of its principal vector mosquito species, Ae. aegypti and, possibly, Ae. albopictus. While Ae. albopictus populations are more widely established than those of Ae. aegypti, the relative competence of these species as a Zika vector is unknown. The analysis reported here presents a global risk model that considers the role of each vector species independently, and quantifies the potential spreading risk of Zika into new regions. Six scenarios are evaluated which vary in the weight assigned to Ae. albopictus as a possible spreading vector. The scenarios are bounded by the extreme assumptions that spread is driven by air travel and Ae. aegypti presence alone and spread driven equally by both species. For each scenario destination cities at highest risk of Zika outbreaks are prioritized, as are source cities in affected regions. Finally, intercontinental air travel routes that pose the highest risk for Zika spread are also ranked. The results are compared between scenarios. + Results from the analysis reveal that if Ae. aegypti is the only competent Zika vector, then risk is geographically limited; in North America mainly to Florida and Texas. However, if Ae. albopictus proves to be a competent vector of Zika, which does not yet appear to be the case, then there is risk of local establishment in all American regions including Canada and Chile, much of Western Europe, Australia, New Zealand, as well as South and East Asia, with a substantial increase in risk to Asia due to the more recent local establishment of Zika in Singapore. + + + + Gardner + Lauren + L + + School of Civil and Environmental Engineering, University of New South Wales (UNSW) Sydney, Sydney, NSW, Australia. + + + + Chen + Nan + N + + School of Civil and Environmental Engineering, University of New South Wales (UNSW) Sydney, Sydney, NSW, Australia. + + + + Sarkar + Sahotra + S + + Department of Integrative Biology and Department of Philosophy, University of Texas at Austin, Austin, Texas, United States of America. + + + + eng + + Journal Article + + + 2017 + 03 + 24 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + IM + + + Euro Surveill. 2014 Jan 30;19(4):null + 24507466 + + + PLoS Negl Trop Dis. 2014 Feb 06;8(2):e2681 + 24516683 + + + Cell Stem Cell. 2016 May 5;18(5):591-6 + 27038591 + + + PLoS Negl Trop Dis. 2010 Jan 19;4(1):e585 + 20098495 + + + PLoS One. 2007 Nov 14;2(11):e1168 + 18000540 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + Med Clin North Am. 2008 Nov;92(6):1377-90, x + 19061757 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + PLoS One. 2007 Sep 05;2(9):e824 + 17786196 + + + Lancet Infect Dis. 2016 Nov;16(11):1237-1245 + 27593584 + + + Emerg Infect Dis. 2014 Aug;20(8):1412-4 + 25062427 + + + PLoS Negl Trop Dis. 2016 Aug 09;10(8):e0004901 + 27505002 + + + Lancet. 2016 Jan 23;387(10016):335-6 + 26777915 + + + PLoS Negl Trop Dis. 2013 Aug 01;7(8):e2348 + 23936579 + + + PLoS Negl Trop Dis. 2016 Mar 03;10(3):e0004543 + 26938868 + + + PLoS Pathog. 2007 Dec;3(12):e201 + 18069894 + + + J Infect Dis. 2016 Nov 1;214(9):1349-1356 + 27436433 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + PeerJ. 2016 Apr 05;4:e1904 + 27069825 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + PLoS Negl Trop Dis. 2012;6(8):e1792 + 22953014 + + + PLoS Negl Trop Dis. 2010 Oct 05;4(10):null + 20957148 + + + Emerg Infect Dis. 2016 May;22(5):933-5 + 27088323 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + PLoS One. 2013 Aug 29;8(8):e72129 + 24009672 + + + PLoS Curr. 2016 Mar 16;8:null + 27066299 + + + J Clin Virol. 2015 Jul;68:53-5 + 26071336 + + + Elife. 2015 Jun 30;4:e08347 + 26126267 + + + J Trop Med. 2012;2012:103679 + 22523497 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + Am J Trop Med Hyg. 2001 May-Jun;64(5-6):310-6 + 11463123 + + + Trans R Soc Trop Med Hyg. 1977;71(4):300-3 + 413216 + + + Elife. 2016 Apr 19;5:null + 27090089 + + + Euro Surveill. 2016;21(13):null + 27063794 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Emerg Infect Dis. 2016 Oct;22(10):1857-9 + 27434194 + + + Lancet Infect Dis. 2016 Mar;16(3):278-9 + 26852727 + + + J Hyg (Lond). 1979 Oct;83(2):213-9 + 489960 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):55-8 + 26820163 + + + Trans R Soc Trop Med Hyg. 1983;77(4):442-5 + 6314612 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Philos Trans R Soc Lond B Biol Sci. 2015 Apr 5;370(1665):null + 25688023 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + J Wildl Dis. 2003 Jan;39(1):73-83 + 12685070 + + + Lancet Infect Dis. 2016 May;16(5):522-3 + 26997578 + + + Trans R Soc Trop Med Hyg. 1956 May;50(3):238-42 + 13337908 + + + BMC Infect Dis. 2015 Nov 02;15:492 + 26527535 + + + Euro Surveill. 2014 Jan 30;19(4):null + 24507467 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Aedes + growth & development + + + Animals + + + Global Health + + + Mosquito Vectors + growth & development + + + Risk Assessment + + + Zika Virus Infection + epidemiology + transmission + + +
+ + + + 2016 + 04 + 22 + + + 2017 + 03 + 13 + + + 2017 + 04 + 05 + + + 2017 + 3 + 25 + 6 + 0 + + + 2017 + 6 + 20 + 6 + 0 + + + 2017 + 3 + 25 + 6 + 0 + + + epublish + + 28339472 + 10.1371/journal.pntd.0005487 + PNTD-D-16-00730 + PMC5381944 + + +
+ + + + + 28335029 + + 2017 + 03 + 23 + +
+ + 1465-3664 + + + 2017 + Mar + 10 + + + Journal of tropical pediatrics + J. Trop. Pediatr. + + The Challenge of Assessing Microcephaly in the Context of the Zika Virus Epidemic. + 10.1093/tropej/fmx015 + + The present article examines the impact of the current limitations of the microcephaly definition in the context of the Zika virus outbreak. It highlights its dependence on the method used for determining gestational age and other anthropometric parameters, and includes original results of prevalence of microcephaly in four countries from two different continents (Mozambique, Brazil, Guatemala and Colombia). Alternative definitions of microcephaly are proposed to allow the identification of true cases of microcephaly in a more accurate manner. + © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. + + + + Quintó + Llorenç + L + + ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain. + + + CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. + + + + García-Basteiro + Alberto L + AL + + ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain. + + + Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique. + + + Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam, The Netherlands. + + + + Bardají + Azucena + A + + ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain. + + + CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. + + + Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique. + + + + González + Raquel + R + + ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain. + + + CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. + + + Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique. + + + + Padilla + Norma + N + + Centro de Estudios en Salud, Universidad del Valle da Guatemala (CES-UVG), Guatemala, Guatemala. + + + + Martinez-Espinosa + Flor E + FE + + Gerência de Malária, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil. + + + Instituto Leônidas e Maria Deane, FIOCRUZ, Amazônia, Brazil. + + + + Arévalo-Herrera + Myriam + M + + Centro Internacional de Vacunas (CIV)/Facultad de Salud, Universidad del Valle, Cali, Colombia. + + + + Macete + Eusébio + E + + Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique. + + + National Directare of Health, Ministry of Health, Maputo, Mozambique. + + + + Menéndez + Clara + C + + ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain. + + + CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. + + + Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique. + + + + eng + + Journal Article + + + 2017 + 03 + 10 + +
+ + England + J Trop Pediatr + 8010948 + 0142-6338 + +
+ + + + 2017 + 3 + 24 + 6 + 0 + + + 2017 + 3 + 24 + 6 + 0 + + + 2017 + 3 + 24 + 6 + 0 + + + aheadofprint + + 28335029 + 3065358 + 10.1093/tropej/fmx015 + + +
+ + + + + 28332092 + + 2017 + 12 + 06 + + + 2017 + 12 + 06 + +
+ + 1432-0533 + + 133 + 6 + + 2017 + Jun + + + Acta neuropathologica + Acta Neuropathol. + + The spectrum of neuropathological changes associated with congenital Zika virus infection. + + 983-999 + + 10.1007/s00401-017-1699-5 + + A major concern associated with ZIKV infection is the increased incidence of microcephaly with frequent calcifications in infants born from infected mothers. To date, postmortem analysis of the central nervous system (CNS) in congenital infection is limited to individual reports or small series. We report a comprehensive neuropathological study in ten newborn babies infected with ZIKV during pregnancy, including the spinal cords and dorsal root ganglia (DRG), and also muscle, pituitaries, eye, systemic organs, and placentas. Using in situ hybridization (ISH) and electron microscopy, we investigated the role of direct viral infection in the pathogenesis of the lesions. Nine women had Zika symptoms between the 4th and 18th and one in the 28th gestational week. Two babies were born at 32, one at 34 and 36 weeks each and six at term. The cephalic perimeter was reduced in four, and normal or enlarged in six patients, although the brain weights were lower than expected. All had arthrogryposis, except the patient infected at 28 weeks gestation. We defined three patterns of CNS lesions, with different patterns of destructive, calcification, hypoplasia, and migration disturbances. Ventriculomegaly was severe in the first pattern due to midbrain damage with aqueduct stenosis/distortion. The second pattern had small brains and mild/moderate (ex-vacuo) ventriculomegaly. The third pattern, a well-formed brain with mild calcification, coincided with late infection. The absence of descending fibres resulted in hypoplastic basis pontis, pyramids, and cortico-spinal tracts. Spinal motor cell loss explained the intrauterine akinesia, arthrogryposis, and neurogenic muscle atrophy. DRG, dorsal nerve roots, and columns were normal. Lympho-histiocytic inflammation was mild. ISH showed meningeal, germinal matrix, and neocortical infection, consistent with neural progenitors death leading to proliferation and migration disorders. A secondary ischemic process may explain the destructive lesions. In conclusion, we characterized the destructive and malformative consequences of ZIKV in the nervous system, as reflected in the topography and severity of lesions, anatomic localization of the virus, and timing of infection during gestation. Our findings indicate a developmental vulnerability of the immature CNS, and shed light on possible mechanisms of brain injury of this newly recognized public health threat. + + + + Chimelli + Leila + L + + Laboratory of Neuropathology, State Institute of Brain Paulo Niemeyer and Federal University of Rio de Janeiro (UFRJ), Rua do Resende 156, Rio de Janeiro, RJ, CEP 20231-092, Brazil. chimelli@hucff.ufrj.br. + + + + Melo + Adriana S O + ASO + + Research Institute Prof. Amorim Neto, Rua Duque de Caxias, 330, Prata, Campina Grande, PB, CEP 58400506, Brazil. + + + Health Secretary Campina Grande, Rua Duque de Caxias, 330, Prata, Campina Grande, PB, CEP 58400506, Brazil. + + + + Avvad-Portari + Elyzabeth + E + + Fernandes Figueira Institute-FioCruz, Avenida Rui Barbosa, 716, Flamengo, Rio De Janeiro, RJ, CEP 22250-020, Brazil. + + + + Wiley + Clayton A + CA + + Division of Neuropathology, UPMC Presbiterian Hospital, S701 Scaife Hall 200 Lothrop Street, Pittsburgh, PA,  15213, USA. + + + + Camacho + Aline H S + AHS + + Laboratory of Neuropathology, State Institute of Brain Paulo Niemeyer and Federal University of Rio de Janeiro (UFRJ), Rua do Resende 156, Rio de Janeiro, RJ, CEP 20231-092, Brazil. + + + + Lopes + Vania S + VS + + Department of Pathology, Antonio Pedro University Hospital, Fluminense Federal University, Rua Marques de Paraná, 303, Centro, Niterói, RJ, CEP 24033-900, Brazil. + + + + Machado + Heloisa N + HN + + Fernandes Figueira Institute-FioCruz, Avenida Rui Barbosa, 716, Flamengo, Rio De Janeiro, RJ, CEP 22250-020, Brazil. + + + + Andrade + Cecilia V + CV + + Fernandes Figueira Institute-FioCruz, Avenida Rui Barbosa, 716, Flamengo, Rio De Janeiro, RJ, CEP 22250-020, Brazil. + + + + Dock + Dione C A + DCA + + Fernandes Figueira Institute-FioCruz, Avenida Rui Barbosa, 716, Flamengo, Rio De Janeiro, RJ, CEP 22250-020, Brazil. + + + + Moreira + Maria Elisabeth + ME + + Fernandes Figueira Institute-FioCruz, Avenida Rui Barbosa, 716, Flamengo, Rio De Janeiro, RJ, CEP 22250-020, Brazil. + + + + Tovar-Moll + Fernanda + F + + D'Or Institute for Research and Education (IDOR) and UFRJ, Rua Diniz Cordeiro, 30, Botafogo, Rio De Janeiro, RJ, CEP 22281-100, Brazil. + + + + Oliveira-Szejnfeld + Patricia S + PS + + Fetal Medicine Research, Foundation Institute for Education and Research in Diagnostic Imaging (FIDI), Rua Napoleão de Barros, 800, Vila Clementino, São Paulo, SP, CEP 04024-002, Brazil. + + + + Carvalho + Angela C G + ACG + + Department of Pathology, Antonio Pedro University Hospital, Fluminense Federal University, Rua Marques de Paraná, 303, Centro, Niterói, RJ, CEP 24033-900, Brazil. + + + + Ugarte + Odile N + ON + + Department of Pathology, Antonio Pedro University Hospital, Fluminense Federal University, Rua Marques de Paraná, 303, Centro, Niterói, RJ, CEP 24033-900, Brazil. + + + + Batista + Alba G M + AGM + + Health Secretary Campina Grande, Rua Duque de Caxias, 330, Prata, Campina Grande, PB, CEP 58400506, Brazil. + + + + Amorim + Melania M R + MMR + + Research Institute Prof. Amorim Neto, Rua Duque de Caxias, 330, Prata, Campina Grande, PB, CEP 58400506, Brazil. + + + + Melo + Fabiana O + FO + + Research Institute Prof. Amorim Neto, Rua Duque de Caxias, 330, Prata, Campina Grande, PB, CEP 58400506, Brazil. + + + + Ferreira + Thales A + TA + + Research Institute Prof. Amorim Neto, Rua Duque de Caxias, 330, Prata, Campina Grande, PB, CEP 58400506, Brazil. + + + + Marinho + Jacqueline R L + JRL + + Health Secretary Campina Grande, Rua Duque de Caxias, 330, Prata, Campina Grande, PB, CEP 58400506, Brazil. + + + + Azevedo + Girlene S + GS + + Research Institute Prof. Amorim Neto, Rua Duque de Caxias, 330, Prata, Campina Grande, PB, CEP 58400506, Brazil. + + + + Leal + Jeime I B F + JIBF + + Health Secretary Campina Grande, Rua Duque de Caxias, 330, Prata, Campina Grande, PB, CEP 58400506, Brazil. + + + + da Costa + Rodrigo F Madeiro + RFM + + D'Or Institute for Research and Education (IDOR) and UFRJ, Rua Diniz Cordeiro, 30, Botafogo, Rio De Janeiro, RJ, CEP 22281-100, Brazil. + + + + Rehen + Stevens + S + + D'Or Institute for Research and Education (IDOR) and UFRJ, Rua Diniz Cordeiro, 30, Botafogo, Rio De Janeiro, RJ, CEP 22281-100, Brazil. + + + + Arruda + Monica B + MB + + Laboratory of Medical Virology, Departamento de Genética, Instituto de Biologia, CCS, Bloco A, sala 121, UFRJ, Rio De Janeiro, RJ, CEP 21941-902, Brazil. + + + + Brindeiro + Rodrigo M + RM + + Laboratory of Medical Virology, Departamento de Genética, Instituto de Biologia, CCS, Bloco A, sala 121, UFRJ, Rio De Janeiro, RJ, CEP 21941-902, Brazil. + + + + Delvechio + Rodrigo + R + + Laboratory of Medical Virology, Departamento de Genética, Instituto de Biologia, CCS, Bloco A, sala 121, UFRJ, Rio De Janeiro, RJ, CEP 21941-902, Brazil. + + + + Aguiar + Renato S + RS + + Laboratory of Medical Virology, Departamento de Genética, Instituto de Biologia, CCS, Bloco A, sala 121, UFRJ, Rio De Janeiro, RJ, CEP 21941-902, Brazil. + + + + Tanuri + Amilcar + A + + Laboratory of Medical Virology, Departamento de Genética, Instituto de Biologia, CCS, Bloco A, sala 121, UFRJ, Rio De Janeiro, RJ, CEP 21941-902, Brazil. + + + + eng + + Journal Article + + + 2017 + 03 + 22 + +
+ + Germany + Acta Neuropathol + 0412041 + 0001-6322 + + IM + + + Adolescent + + + Adult + + + Brain + diagnostic imaging + pathology + + + Eye + diagnostic imaging + pathology + + + Female + + + Humans + + + Infant, Newborn + + + Male + + + Microcephaly + diagnostic imaging + etiology + pathology + + + Muscle, Skeletal + pathology + + + Pituitary Gland + diagnostic imaging + pathology + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Spinal Cord + diagnostic imaging + pathology + + + Young Adult + + + Zika Virus Infection + complications + congenital + diagnostic imaging + pathology + + + + Calcification + Congenital ZIKV infection + In situ hybridization + Microcephaly + Neuropathology + Zika virus + +
+ + + + 2016 + 12 + 03 + + + 2017 + 03 + 15 + + + 2017 + 03 + 15 + + + 2017 + 3 + 24 + 6 + 0 + + + 2017 + 12 + 7 + 6 + 0 + + + 2017 + 3 + 24 + 6 + 0 + + + ppublish + + 28332092 + 10.1007/s00401-017-1699-5 + 10.1007/s00401-017-1699-5 + + +
+ + + + + 28329257 + + 2018 + 01 + 23 + + + 2018 + 01 + 23 + +
+ + 1537-6591 + + 64 + 10 + + 2017 + May + 15 + + + Clinical infectious diseases : an official publication of the Infectious Diseases Society of America + Clin. Infect. Dis. + + Lessons Learned at the Epicenter of Brazil's Congenital Zika Epidemic: Evidence From 87 Confirmed Cases. + + 1302-1308 + + 10.1093/cid/cix166 + + Congenital Zika virus infection has stimulated great international concern. A prospective case series of 87 infants with laboratory-confirmed congenital Zika syndrome (CZS) at the epicenter of the Brazilian Zika epidemic in Pernambuco state is presented. Mothers were interviewed for symptoms of possible Zika virus (ZIKV) infection during pregnancy, and fetal ultrasounds were obtained. Infant cerebrospinal fluid (CSF) samples were tested for ZIKV-specific antibodies, and sera were screened for other congenital infections. Neuroimaging and ophthalmologic evaluations were also performed. Sixty-six mothers (76%) reported symptoms of ZIKV infection during gestation. Fetal ultrasounds were available from 90% of the mothers, and all demonstrated brain structural abnormalities. All of the CSF samples tested positive for ZIKV immunoglobulin M. The majority of infants (89%) were term; the mean birth weight was 2577 ± 260 g, and the mean head circumference was 28.1 ± 1.8 cm. Severe microcephaly, defined as head circumference 3 SD below the mean for sex and gestational age, was found in 72 (82%) infants. All infants had an abnormal neurological exam, and 18 (20.7%) had arthrogryposis. The main abnormalities detected in computed tomography scans were calcifications (99%), followed by ventricular enlargement (94%), cortical hypogyration (81%), and less commonly, cerebellar hypoplasia (52%). Unilateral diaphragm paralysis was identified in 3 infants. Maternal young age, term infant, small for gestational age, and the presence of ophthalmologic abnormalities were significantly associated with a smaller head circumference Z score. Our findings, based on laboratory-confirmed ZIKV infection, add valuable evidence for the understanding of CZS. + © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. + + + + Meneses + Jucille do Amaral + JDA + + Division of Neonatology, Professor Fernando Figueira Integral Medicine Institute. + + + + Ishigami + Ana Catarina + AC + + Division of Neonatology, Professor Fernando Figueira Integral Medicine Institute. + + + + de Mello + Luisa Medeiros + LM + + Division of Neonatology, Professor Fernando Figueira Integral Medicine Institute. + + + + de Albuquerque + Luciano Lira + LL + + Division of Neonatology, Professor Fernando Figueira Integral Medicine Institute. + + + + de Brito + Carlos Alexandre Antunes + CAA + + Department of Clinical Medicine, Federal University of Pernambuco, Recife, Brazil. + + + + Cordeiro + Marli Tenório + MT + + Department of Virology, Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, and. + + + + Pena + Lindomar José + LJ + + Department of Virology, Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, and. + + + + eng + + Journal Article + Observational Study + +
+ + United States + Clin Infect Dis + 9203213 + 1058-4838 + + + + 0 + Antibodies, Viral + + + 0 + Immunoglobulin M + + + + Cerebellar Hypoplasia + + IM + + + Antibodies, Viral + blood + cerebrospinal fluid + + + Arthrogryposis + epidemiology + virology + + + Brain + abnormalities + virology + + + Brazil + epidemiology + + + Cerebellum + abnormalities + diagnostic imaging + virology + + + Developmental Disabilities + diagnostic imaging + epidemiology + virology + + + Epidemics + statistics & numerical data + + + Female + + + Fetal Diseases + epidemiology + virology + + + Gestational Age + + + Humans + + + Immunoglobulin M + blood + cerebrospinal fluid + + + Infant + + + Microcephaly + diagnostic imaging + epidemiology + virology + + + Mothers + + + Nervous System Malformations + diagnostic imaging + epidemiology + virology + + + Neuroimaging + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Prospective Studies + + + Respiratory Paralysis + diagnostic imaging + epidemiology + virology + + + Ultrasonography + + + Zika Virus + immunology + isolation & purification + + + Zika Virus Infection + congenital + epidemiology + virology + + + + Zika virus + congenital Zika syndrome (CZS) + diaphragm paralysis + immunoglobulin M. + microcephaly + +
+ + + + 2016 + 12 + 06 + + + 2017 + 02 + 21 + + + 2017 + 3 + 23 + 6 + 0 + + + 2018 + 1 + 24 + 6 + 0 + + + 2017 + 3 + 23 + 6 + 0 + + + ppublish + + 28329257 + 3051955 + 10.1093/cid/cix166 + + +
+ + + + + 28328129 + + 2017 + 10 + 30 + + + 2017 + 10 + 30 + +
+ + 1552-4833 + + 173 + 4 + + 2017 + Apr + + + American journal of medical genetics. Part A + Am. J. Med. Genet. A + + The phenotypic spectrum of congenital Zika syndrome. + + 841-857 + + 10.1002/ajmg.a.38170 + + In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV. + © 2017 Wiley Periodicals, Inc. + + + + Del Campo + Miguel + M + + Division of Dysmorphology and Teratology, Department of Pediatrics, UCSD, San Diego, California. + + + + Feitosa + Ian M L + IM + + Departamento de Genetica, Universidade Federal de Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. + + + Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife, Brazil. + + + + Ribeiro + Erlane M + EM + + Hospital Infantil Albert Sabin, Fortaleza, Ceara, Brazil. + + + + Horovitz + Dafne D G + DD + + Instituto Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Pessoa + André L S + AL + + Hospital Infantil Albert Sabin, Fortaleza, Ceara, Brazil. + + + + França + Giovanny V A + GV + + Secretariat of Health Surveillance, Ministry of Health, Brasilia, Brazil. + + + + García-Alix + Alfredo + A + + Institut de Recerca Pediàtrica Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain. + + + + Doriqui + Maria J R + MJ + + Hospital Infantil Dr. Juvêncio Mattos, São Luiz, Brazil. + + + + Wanderley + Hector Y C + HY + + Secretaria de Estado da Saúde do Espírito Santo, Vitória, Brazil. + + + + Sanseverino + Maria V T + MV + + SIAT-Brazilian Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. + + + + Neri + João I C F + JI + + Universidade Potiguar, Natal, Brazil. + + + + Pina-Neto + João M + JM + + Faculdade de Medicina de Ribeirao Preto, Departamento de Genetica, Universidade de Sao Paolo, Ribeirao Preto, Brazil. + + + + Santos + Emerson S + ES + + Universidade Federal de Sergipe, Lagarto, Brazil. + + + + Verçosa + Islane + I + + Centro de Aperfeiçoamento Visual Ver a Esperança Renascer/CAVIVER, Fortaleza, Brazil. + + + + Cernach + Mirlene C S P + MC + + Departamento de Genetica Medica, Universidade Federal de Sao Paolo (UNIFESP), Sao Paolo, Brazil. + + + + Medeiros + Paula F V + PF + + Universidade Federal de Campina Grande, Campina Grande, Paraiba, Brazil. + + + + Kerbage + Saile C + SC + + Hospital Infantil Albert Sabin, Fortaleza, Ceara, Brazil. + + + + Silva + André A + AA + + Departamento de Genetica, Universidade Federal de Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. + + + SIAT-Brazilian Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. + + + UNIVATES University, Porto Alegre, Rio Grande do Sul, Brazil. + + + + van der Linden + Vanessa + V + + Associação de Assistência à Criança Deficiente/AACD, Recife, Brazil. + + + + Martelli + Celina M T + CM + + Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brazil. + + + + Cordeiro + Marli T + MT + + Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brazil. + + + + Dhalia + Rafael + R + + Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brazil. + + + + Vianna + Fernanda S L + FS + + Departamento de Genetica, Universidade Federal de Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. + + + SIAT-Brazilian Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. + + + + Victora + Cesar G + CG + + Graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil. + + + + Cavalcanti + Denise P + DP + + Departamento de Genetica Medica, Universidade de Campinas UNICAMP, Campinas, Brazil. + + + + Schuler-Faccini + Lavinia + L + + Departamento de Genetica, Universidade Federal de Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. + + + Universidade Potiguar, Natal, Brazil. + + + + Zika Embryopathy Task Force-Brazilian Society of Medical Genetics ZETF-SBGM + + + eng + + Journal Article + +
+ + United States + Am J Med Genet A + 101235741 + 1552-4825 + + + + 0 + Antibodies, Viral + + + 0 + Immunoglobulin G + + + IM + + + Antibodies, Viral + cerebrospinal fluid + + + Brain + abnormalities + virology + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Fetal Diseases + diagnostic imaging + epidemiology + pathology + + + Fetus + + + Humans + + + Immunoglobulin G + cerebrospinal fluid + + + Infant + + + Microcephaly + complications + diagnostic imaging + epidemiology + pathology + + + Neuroimaging + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + epidemiology + pathology + + + Syndrome + + + Zika Virus + growth & development + immunology + pathogenicity + + + Zika Virus Infection + complications + diagnostic imaging + epidemiology + pathology + + + + Zika virus + congenital Zika infection + congenital Zika sequence + congenital Zika syndrome + disruption + disruptive sequence + dysmorphology + fetal brain disruption sequence + teratogen + teratology + +
+ + + + 2016 + 12 + 20 + + + 2017 + 01 + 13 + + + 2017 + 01 + 19 + + + 2017 + 3 + 23 + 6 + 0 + + + 2017 + 3 + 23 + 6 + 0 + + + 2017 + 10 + 31 + 6 + 0 + + + ppublish + + 28328129 + 10.1002/ajmg.a.38170 + + +
+ + + + + 28319244 + + 2017 + 05 + 08 + +
+ + 2168-6157 + + 74 + 5 + + 2017 + May + 01 + + + JAMA neurology + JAMA Neurol + + Congenital Zika Virus Infection: Beyond Neonatal Microcephaly-Reply. + + 610-611 + + 10.1001/jamaneurol.2017.0051 + + + Melo + Adriana Suely de Oliveira + ASO + + Instituto de Pesquisa Professor Amorim Neto (IPESQ), Campina Grande, Paraiba, Brazil2Instituto de Saude Elpidio de Almeida, Campina Grande, Paraiba, Brazil3Faculdade de Ciencias Medicas de Campina Grande, Campina Grande, Paraiba, Brazil4Hospital Municipal Pedro I, Campina Grande, Paraiba, Brazil. + + + + Chimelli + Leila + L + + Laboratorio de Neuropatologia do Instituto Estadual do Cerebro Paulo Niemeyer, Rio de Janeiro, Brazil. + + + + Tanuri + Amilcar + A + + Departamento de Genetica, Instituto de Biologia, Universidade, Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + +
+ + United States + JAMA Neurol + 101589536 + 2168-6149 + +
+ + + + 2017 + 3 + 21 + 6 + 0 + + + 2017 + 3 + 21 + 6 + 0 + + + 2017 + 3 + 21 + 6 + 0 + + + ppublish + + 28319244 + 2612475 + 10.1001/jamaneurol.2017.0051 + + +
+ + + + + 28319237 + + 2017 + 05 + 08 + +
+ + 2168-6157 + + 74 + 5 + + 2017 + May + 01 + + + JAMA neurology + JAMA Neurol + + Congenital Zika Virus Infection: Beyond Neonatal Microcephaly. + + 610 + + 10.1001/jamaneurol.2017.0048 + + + Leyser + Marcio + M + + Antônio Pedro University Hospital, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil. + + + + Nascimento + Osvaldo J M + OJM + + Antônio Pedro University Hospital, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + +
+ + United States + JAMA Neurol + 101589536 + 2168-6149 + +
+ + + + 2017 + 3 + 21 + 6 + 0 + + + 2017 + 3 + 21 + 6 + 0 + + + 2017 + 3 + 21 + 6 + 0 + + + ppublish + + 28319237 + 2612474 + 10.1001/jamaneurol.2017.0048 + + +
+ + + + + 28302630 + + 2017 + 09 + 05 + + + 2018 + 01 + 23 + +
+ + 1468-2044 + + 102 + 8 + + 2017 + 08 + + + Archives of disease in childhood + Arch. Dis. Child. + + Prevalence of microcephaly in eight south-eastern and midwestern Brazilian neonatal intensive care units: 2011-2015. + + 728-734 + + 10.1136/archdischild-2016-311541 + + To describe the prevalence of microcephaly in infants admitted to the neonatal intensive care units (NICUs) in eight private hospitals in south-eastern and midwestern Brazil, from 2011 to 2015. + Observational, cross-sectional study in a cohort of neonates. + Eight private NICUs situated in the cities of Rio de Janeiro (RJ), São Paulo (SP) and Federal District of Brasilia (FDB). + Neonates up to 7 days of age and >23 weeks of gestational age. + Primary outcomes were the annual prevalence of microcephaly and severe microcephaly, both overall and in subgroups according to gestational age, type of microcephaly (proportional or disproportional) and the NICU's location in RJ, SP or FDB. + In this cohort of 8275 neonates admitted to eight private NICUs, the overall prevalence of microcephaly was 5.6% (95% CI 5.1% to 6.1%) and severe microcephaly, 1.5% (95% CI 1.2% to 1.7%). There was no annual variation in these overall estimates (p=0.48 and p=0.99, respectively), nor in the studied subgroups. Microcephaly prevalence was higher in extremely premature and term newborns (7.7% and 7.2%; p<0.001, respectively). Disproportional microcephaly was much more common than proportional microcephaly (prevalence 5.0% vs 0.6%; p<0.001). + The prevalence of microcephaly showed little variation from 2011 to 2015 in these south-eastern and midwestern Brazilian NICUs, suggesting that the impact of the Zika epidemic in neonates that occurred mainly in the north-eastern region in 2015 did not yet affect the infants of those regions during the studied period. These prevalence results can serve as a reference for comparisons with any future Zika outbreaks in the same or similar populations from these regions. + Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. + + + + de Magalhães-Barbosa + Maria Clara + MC + + Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Prata-Barbosa + Arnaldo + A + + Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Rio de Janeiro, Brazil. + + + Instituto de Puericultura e Pediatria Martagão Gesteira-Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Robaina + Jaqueline Rodrigues + JR + + Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Raymundo + Carlos Eduardo + CE + + Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Lima-Setta + Fernanda + F + + Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Rio de Janeiro, Brazil. + + + Instituto Fernandes Figueira da Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Antonio José Ledo Alves da Cunha + + Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + Multicenter Study + Observational Study + + + 2017 + 03 + 16 + +
+ + England + Arch Dis Child + 0372434 + 0003-9888 + + AIM + IM + + + Brazil + epidemiology + + + Cross-Sectional Studies + + + Female + + + Gestational Age + + + Humans + + + Infant, Newborn + + + Intensive Care Units, Neonatal + + + Male + + + Microcephaly + epidemiology + + + Premature Birth + epidemiology + + + Prevalence + + + Term Birth + physiology + + + Zika Virus Infection + epidemiology + + + + Infants + Microcephaly + Neonatal Intensive Care Units + Prevalence + + Competing interests: None declared. +
+ + + + 2016 + 06 + 30 + + + 2017 + 02 + 05 + + + 2017 + 02 + 10 + + + 2017 + 3 + 18 + 6 + 0 + + + 2017 + 9 + 7 + 6 + 0 + + + 2017 + 3 + 18 + 6 + 0 + + + ppublish + + 28302630 + archdischild-2016-311541 + 10.1136/archdischild-2016-311541 + + +
+ + + + + 28270583 + + 2017 + 07 + 11 + + + 2018 + 02 + 22 + +
+ + 2150-7511 + + 8 + 2 + + 2017 + 03 + 07 + + + mBio + MBio + + A Reverse Genetics Platform That Spans the Zika Virus Family Tree. + e02014-16 + 10.1128/mBio.02014-16 + + Zika virus (ZIKV), a mosquito-borne flavivirus discovered in 1947, has only recently caused large outbreaks and emerged as a significant human pathogen. In 2015, ZIKV was detected in Brazil, and the resulting epidemic has spread throughout the Western Hemisphere. Severe complications from ZIKV infection include neurological disorders such as Guillain-Barré syndrome in adults and a variety of fetal abnormalities, including microcephaly, blindness, placental insufficiency, and fetal demise. There is an urgent need for tools and reagents to study the pathogenesis of epidemic ZIKV and for testing vaccines and antivirals. Using a reverse genetics platform, we generated six ZIKV infectious clones and derivative viruses representing diverse temporal and geographic origins. These include three versions of MR766, the prototype 1947 strain (with and without a glycosylation site in the envelope protein), and H/PF/2013, a 2013 human isolate from French Polynesia representative of the virus introduced to Brazil. In the course of synthesizing a clone of a circulating Brazilian strain, phylogenetic studies identified two distinct ZIKV clades in Brazil. We reconstructed viable clones of strains SPH2015 and BeH819015, representing ancestral members of each clade. We assessed recombinant virus replication, binding to monoclonal antibodies, and virulence in mice. This panel of molecular clones and recombinant virus isolates will enable targeted studies of viral determinants of pathogenesis, adaptation, and evolution, as well as the rational attenuation of contemporary outbreak strains to facilitate the design of vaccines and therapeutics.IMPORTANCEViral emergence is a poorly understood process as evidenced by the sudden emergence of Zika virus in Latin America and the Caribbean. Malleable reagents that both predate and span an expanding epidemic are key to understanding the virologic determinants that regulate pathogenesis and transmission. We have generated representative cDNA molecular clones and recombinant viruses that span the known ZIKV family tree, including early Brazilian isolates. Recombinant viruses replicated efficiently in cell culture and were pathogenic in immunodeficient mice, providing a genetic platform for rational vaccine and therapeutic design. + Copyright © 2017 Widman et al. + + + + Widman + Douglas G + DG + + Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Young + Ellen + E + + Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Yount + Boyd L + BL + + Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Plante + Kenneth S + KS + + Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Gallichotte + Emily N + EN + + Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Carbaugh + Derek L + DL + + Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Peck + Kayla M + KM + 0000-0001-7745-6995 + + Department of Biology, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Plante + Jessica + J + + Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Swanstrom + Jesica + J + + Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Heise + Mark T + MT + + Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. + + + Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Lazear + Helen M + HM + + Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + Baric + Ralph S + RS + + Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA rbaric@email.unc.edu. + + + Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. + + + + eng + + + U19 AI109761 + AI + NIAID NIH HHS + United States + + + T32 AI007151 + AI + NIAID NIH HHS + United States + + + U19 AI107810 + AI + NIAID NIH HHS + United States + + + U19 AI100625 + AI + NIAID NIH HHS + United States + + + R01 AI107731 + AI + NIAID NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + + + 2017 + 03 + 07 + +
+ + United States + MBio + 101519231 + + IM + + + N Engl J Med. 2016 Jun 2;374(22):2195-8 + 27074370 + + + Lancet. 2016 Apr 2;387(10026):1482 + 27115821 + + + PLoS Negl Trop Dis. 2016 Apr 12;10(4):e0004636 + 27070912 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + J Virol. 1994 Jul;68(7):4580-8 + 8207832 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + J Gen Virol. 2004 Dec;85(Pt 12):3637-45 + 15557236 + + + Curr Protoc Microbiol. 2013 Nov 05;31:15D.3.1-15D.3.18 + 24510289 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12995-3000 + 14569023 + + + MMWR Morb Mortal Wkly Rep. 2016 Jun 03;65(21):543-6 + 27254248 + + + Nature. 2006 Jan 19;439(7074):344-8 + 16327776 + + + Arch Virol. 2016 Mar;161(3):665-8 + 26611910 + + + Nucleic Acids Res. 2012 Jul;40(Web Server issue):W569-72 + 22695796 + + + Cell Host Microbe. 2016 May 11;19(5):561-5 + 27091703 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + Biotechniques. 1991 Apr;10(4):484, 486 + 1651093 + + + Genome Announc. 2016 Mar 03;4(2):null + 26941134 + + + J Virol. 2005 Jul;79(13):8339-47 + 15956579 + + + PLoS Negl Trop Dis. 2012;6(2):e1486 + 22389731 + + + J Clin Virol. 2016 Jan;74:1-3 + 26615388 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Nucleic Acids Res. 2002 Jul 15;30(14):3059-66 + 12136088 + + + Genome Announc. 2014 Jun 05;2(3):null + 24903869 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Nature. 2016 Apr 19;533(7603):425-8 + 27093288 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + New Biol. 1989 Dec;1(3):285-96 + 2487295 + + + mSphere. 2016 Sep 28;1(5):null + 27704051 + + + J Virol. 2016 Apr 29;90(10 ):5090-7 + 26962223 + + + Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16157-62 + 24043791 + + + Bioinformatics. 2014 May 1;30(9):1312-3 + 24451623 + + + Lancet. 2016 Mar 12;387(10023):1051-2 + 26944027 + + + MBio. 2016 Aug 23;7(4):null + 27555311 + + + Emerg Infect Dis. 2016 May;22(5):933-5 + 27088323 + + + J Virol. 2016 Dec 16;91(1): + 27795432 + + + Emerg Microbes Infect. 2016 Mar 16;5:e22 + 26980239 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + J Virol. 2011 Mar;85(6):2927-41 + 21228244 + + + Virology. 2006 Mar 30;347(1):175-82 + 16406457 + + + Euro Surveill. 2016;21(9):30154 + 26967758 + + + MBio. 2016 Jul 19;7(4):null + 27435464 + + + Cell Host Microbe. 2016 Jun 8;19(6):891-900 + 27198478 + + + Cell. 2016 Aug 25;166(5):1247-1256.e4 + 27565347 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + J Virol. 2000 Apr;74(7):3011-9 + 10708415 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Nat Methods. 2012 Jul 30;9(8):772 + 22847109 + + + MBio. 2015 Oct 13;6(5):e01461-15 + 26463165 + + + Elife. 2016 Mar 15;5:e13974 + 26978794 + + + Virology. 2016 Oct;497:157-62 + 27471954 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Humans + + + Molecular Biology + methods + + + Reverse Genetics + methods + + + Virology + methods + + + Zika Virus + genetics + immunology + pathogenicity + physiology + + +
+ + + + 2017 + 3 + 9 + 6 + 0 + + + 2017 + 3 + 9 + 6 + 0 + + + 2017 + 7 + 14 + 6 + 0 + + + epublish + + 28270583 + mBio.02014-16 + 10.1128/mBio.02014-16 + PMC5340872 + + +
+ + + + + 28259231 + + 2017 + 06 + 09 + + + 2017 + 06 + 09 + +
+ + 1942-5546 + + 92 + 3 + + 2017 + Mar + + + Mayo Clinic proceedings + Mayo Clin. Proc. + + Zika Virus Meningoencephalitis in an Immunocompromised Patient. + + 460-466 + + S0025-6196(17)30027-7 + 10.1016/j.mayocp.2016.12.019 + + The World Health Organization considers the Zika virus (ZIKV) outbreak in the Americas a global public health emergency. The neurologic complications due to ZIKV infection comprise microcephaly, meningoencephalitis, and Guillain-Barré syndrome. We describe a fatal case of an adult patient receiving an immunosuppressive regimen following heart transplant. The patient was admitted with acute neurologic impairment and experienced progressive hemodynamic instability and mental deterioration that finally culminated in death. At autopsy, a pseudotumoral form of ZIKV meningoencephalitis was confirmed. Zika virus infection was documented by reverse trancriptase-polymerase chain reaction, immunohistochemistry, and immunofluorescence and electron microscopy of the brain parenchyma and cerebral spinal fluid. The sequencing of the viral genome in this patient confirmed a Brazilian ZIKV strain. In this case, central nervous system involvement and ZIKV propagation to other organs in a disseminated pattern is quite similar to that observed in other fatal Flaviviridae viral infections. + Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved. + + + + Schwartzmann + Pedro V + PV + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. Electronic address: pedrovs@usp.br. + + + + Ramalho + Leandra N Z + LN + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. + + + + Neder + Luciano + L + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. + + + + Vilar + Fernando C + FC + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. + + + + Ayub-Ferreira + Sílvia M + SM + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. + + + + Romeiro + Marília F + MF + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. + + + + Takayanagui + Osvaldo M + OM + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. + + + + Dos Santos + Antonio C + AC + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. + + + + Schmidt + André + A + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. + + + + Figueiredo + Luiz T M + LT + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. + + + + Arena + Ross + R + + Department of Physical Therapy, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL. + + + + Simões + Marcus V + MV + + Cardiology Centre, Internal Medicine Department, Medical School of Ribeirão Preto, University of São Paulo, Brazil. + + + + eng + + Case Reports + Journal Article + +
+ + England + Mayo Clin Proc + 0405543 + 0025-6196 + + + + 0 + Immunosuppressive Agents + + + AIM + IM + + + Acute Disease + + + Adult + + + Cerebrospinal Fluid + virology + + + Fatal Outcome + + + Fluorescent Antibody Technique + methods + + + Genome, Viral + + + Heart Transplantation + adverse effects + + + Humans + + + Immunocompromised Host + + + Immunohistochemistry + + + Immunosuppressive Agents + adverse effects + therapeutic use + + + Magnetic Resonance Imaging + + + Male + + + Meningoencephalitis + diagnostic imaging + immunology + virology + + + Neuroimaging + + + Parenchymal Tissue + virology + + + Reverse Transcriptase Polymerase Chain Reaction + + + Zika Virus + genetics + isolation & purification + + + Zika Virus Infection + complications + diagnosis + immunology + + +
+ + + + 2016 + 07 + 06 + + + 2016 + 11 + 02 + + + 2016 + 12 + 22 + + + 2017 + 3 + 6 + 6 + 0 + + + 2017 + 3 + 6 + 6 + 0 + + + 2017 + 6 + 10 + 6 + 0 + + + ppublish + + 28259231 + S0025-6196(17)30027-7 + 10.1016/j.mayocp.2016.12.019 + + +
+ + + + + 28250906 + + 2017 + 08 + 16 + +
+ + 2008-7802 + + 8 + + 2017 + + + International journal of preventive medicine + Int J Prev Med + + Zika Virus Diseases - The New Face of an Ancient Enemy as Global Public Health Emergency (2016): Brief Review and Recent Updates. + + 6 + + 10.4103/2008-7802.199641 + + Zika virus (ZIKV) disease is caused by a virus transmitted byAedesmosquito. It presents as flu-like symptoms lasting for 5-7 days and shows potential association with neurological and autoimmune complications such as congenital microcephaly and adult paralysis disorder, Guillain-Barré syndrome. Treatment measures are conservative as the disease is self-limiting. ZIKV earlier affected several tropical regions of Africa and Asia from 1951 to 2006. Subsequently, it moved out from these regions to land as outbreaks in Yap Island, French Polynesia, South America, and most recently in Brazil. The WHO declared it as an international public health emergency in 2016 and an extraordinary event with recommendations for improving communications, tightening vigil on ZIKV infections, and improving mosquito control measures. The authors in this article aim to briefly discuss ZIKV infection, its epidemiology, clinical manifestations, management, and prevention. + + + + Passi + Deepak + D + + Department of Oral and Maxillofacial Surgery, ESIC Dental College and Hospital, New Delhi, India. + + + + Sharma + Sarang + S + + Department of Conservative Dentistry and Endodontics, ESIC Dental College and Hospital, New Delhi, India. + + + + Dutta + Shubha Ranjan + SR + + Department of Oral and Maxillofacial Surgery, MB Kedia Dental College, Birgunj, Nepal. + + + + Ahmed + Musharib + M + + Department of Pedodontics, Inderprastha Dental College and Hospital, Sahibabad, Ghaziabad, Uttar Pradesh, India. + + + + eng + + Journal Article + Review + + + 2017 + 02 + 07 + +
+ + Iran + Int J Prev Med + 101535380 + 2008-7802 + + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Arch Virol. 2016 Mar;161(3):665-8 + 26611910 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Euro Surveill. 2014 Oct 16;19(41):null + 25345518 + + + Am J Reprod Immunol. 2015 Mar;73(3):199-213 + 25582523 + + + Trans R Soc Trop Med Hyg. 1977;71(3):254-60 + 407675 + + + Nucleic Acids Res. 2011 Jan;39(Database issue):D576-82 + 20947564 + + + Arch Gesamte Virusforsch. 1973;43(4):315-9 + 4799154 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Transfusion. 2016 Jan;56(1):33-40 + 26283013 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Bull World Health Organ. 2016 Sep 1;94(9):675-686C + 27708473 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):55-8 + 26820163 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Aedes + Guillain–Barré syndrome + Zika virus + arbovirus + congenital microcephaly + + There are no conflicts of interest. +
+ + + + 2016 + 07 + 23 + + + 2016 + 12 + 16 + + + 2017 + 3 + 3 + 6 + 0 + + + 2017 + 3 + 3 + 6 + 0 + + + 2017 + 3 + 3 + 6 + 1 + + + epublish + + 28250906 + 10.4103/2008-7802.199641 + IJPVM-8-6 + PMC5320867 + + +
+ + + + + 28250532 + + 2017 + 09 + 25 + + + 2017 + 09 + 25 + +
+ + 1564-0604 + + 95 + 3 + + 2017 + Mar + 01 + + + Bulletin of the World Health Organization + Bull. World Health Organ. + + Risk of microcephaly after Zika virus infection in Brazil, 2015 to 2016. + + 191-198 + + 10.2471/BLT.16.178608 + + To estimate the risk of microcephaly in babies born to women infected by the Zika virus during pregnancy in Brazil in an epidemic between 2015 and 2016. + We obtained data on the number of notified and confirmed microcephaly cases in each Brazilian state between November 2015 and October 2016 from the health ministry. For Pernambuco State, one of the hardest hit, weekly data were available from August 2015 to October 2016 for different definitions of microcephaly. The absolute risk of microcephaly was calculated using the average number of live births reported in each state in the corresponding time period between 2012 and 2014 and assuming two infection rates: 10% and 50%. The relative risk was estimated using the reported background frequency of microcephaly in Brazil of 1.98 per 10 000 live births. + The estimated absolute risk of a notified microcephaly case varied from 0.03 to 17.1% according to geographical area, the definition of microcephaly used and the infection rate. Assuming a 50% infection rate, there was an 18-127 fold higher probability of microcephaly in children born to mothers with infection during pregnancy compared with children born to mothers without infection during pregnancy in Pernambuco State. For a 10% infection rate, the probability was 88-635 folds higher. + A large variation in the estimated risk of microcephaly was found in Brazil. Research is needed into possible effect modifiers, reliable measures of Zika virus infection and clear endpoints for congenital malformations. + + + + Jaenisch + Thomas + T + + Section of Clinical Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 324, Heidelberg, 69120, Germany . + + + + Rosenberger + Kerstin Daniela + KD + + Section of Clinical Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 324, Heidelberg, 69120, Germany . + + + + Brito + Carlos + C + + Department of Internal Medicine, Federal University of Pernambuco, Recife, Brazil . + + + + Brady + Oliver + O + + Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, England . + + + + Brasil + Patrícia + P + + Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil . + + + + Marques + Ernesto Ta + ET + + Virology and Experimental Therapeutics Laboratory, Aggeu Magalhães Research Center, Recife, Brazil . + + + + eng + + Journal Article + +
+ + Switzerland + Bull World Health Organ + 7507052 + 0042-9686 + + IM + + + PLoS Negl Trop Dis. 2016 Apr 12;10(4):e0004636 + 27070912 + + + Clin Infect Dis. 2016 Sep 15;63(6):805-11 + 27193747 + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Science. 1997 Jan 3;275(5296):65-7 + 8974392 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Acta Med Port. 2015 Nov-Dec;28(6):679-80 + 26849748 + + + Lancet. 2016 Feb 20;387(10020):719-21 + 26876373 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Lancet. 2016 Mar 12;387(10023):1051-2 + 26944027 + + + Lancet. 2016 Mar 5;387(10022):919-21 + 26921913 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + BMJ. 2016 Jan 21;352:i383 + 26796917 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant, Newborn + + + Male + + + Microcephaly + etiology + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Residence Characteristics + + + Risk Assessment + + + Zika Virus Infection + complications + + + + Estimer le risque de microcéphalie chez les enfants nés de femmes infectées par le virus Zika durant la grossesse lors de l'épidémie survenue au Brésil entre 2015 et 2016. + Nous avons obtenu du ministère de la Santé des données sur le nombre de cas de microcéphalie signalés et confirmés dans chaque État brésilien entre novembre 2015 et octobre 2016. Dans l'État de Pernambuco, l'un des plus durement touchés, des données hebdomadaires étaient disponibles d'août 2015 à octobre 2016 pour différentes définitions de la microcéphalie. Le risque absolu de microcéphalie a été calculé à partir du nombre moyen de naissances vivantes déclaré dans chaque État pendant la même durée entre 2012 et 2014 et en prenant deux taux d'infection: 10% et 50%. Le risque relatif a été estimé à partir de la fréquence habituelle de microcéphalie déclarée au Brésil, qui était de 1,98 pour 10 000 naissances vivantes. + L’estimation du risque absolu de signalement de microcéphalie allait de 0,03 à 17,1% suivant la zone géographique, la définition de la microcéphalie employée et le taux d'infection. En prenant un taux d'infection de 50%, dans l'État de Pernambuco, la probabilité de microcéphalie chez les enfants nés de mères infectées par le virus Zika pendant la grossesse était 18 à 127 fois supérieure à celle des enfants nés de mères non touchées par le virus pendant la grossesse. Avec un taux d'infection de 10%, cette probabilité était 88 à 635 fois supérieure. + De gros écarts ont été observés au niveau de l'estimation du risque de microcéphalie au Brésil. Il est nécessaire de mener des recherches sur les éventuels facteurs modifiants, d'avoir des mesures fiables de l'infection à virus Zika et de définir clairement des critères d'évaluation des malformations congénitales. + + + Estimar el riesgo de microcefalia en bebés nacidos de mujeres infectadas por el virus de Zika durante el embarazo en Brasil en una epidemia desatada entre 2015 y 2016. + Se obtuvieron datos del Ministerio de Salud sobre el número de casos de microcefalia notificados y confirmados en todos los estados de Brasil entre noviembre de 2015 y octubre de 2016. En el estado de Pernambuco, uno de los más afectados, se disponía de datos semanales desde agosto de 2015 hasta octubre de 2016 para diferentes definiciones de microcefalia. Se calculó el riesgo absoluto de microcefalia utilizando la cifra media de nacidos vivos registrados en todos los estados en el periodo de tiempo correspondiente entre 2012 y 2014 y asumiendo dos tasas de infección: 10% y 50%. El riesgo relativo se estimó utilizando la frecuencia de fondo de microcefalia registrada en Brasil de 1,98 por cada 10 000 nacidos vivos. + El riesgo absoluto estimado de una microcefalia notificada varió del 0,03% al 17,1% según la zona geográfica, la definición de microcefalia utilizada y la tasa de infección. Asumiendo una tasa de infección del 50%, hubo una probabilidad de microcefalia de 18 a 127 veces mayor en los niños nacidos de madres infectadas por el virus de Zika durante el embarazo, en comparación con los nacidos de madres no infectadas por el virus de Zika durante el embarazo en el estado de Pernambuco. Con una tasa de infección del 10%, la probabilidad fue de 88 a 635 veces mayor. + En Brasil, se descubrió una gran variación en cuanto al riesgo estimado de microcefalia. Es necesario realizar una investigación sobre posibles modificadores de efectos, medidas fiables para el contagio del virus de Zika y resultados claros para malformaciones congénitas. + + + تقدير خطر وقوع الصعل (صغر الرأس) للرضع المولودين لنساء قد أُصبن بعدوى فيروس زيكا خلال فترة الحمل في البرازيل في سياق الانتشار الوبائي الذي حدث في الفترة بين عامي 2015 و2016. + حصلنا على بيانات عن عدد حالات الإخطار بوقوع الصعل والحالات المؤكدة لوقوعه في دولة البرازيل في الفترة بين تشرين الثاني/نوفمبر 2015 وتشرين الأول/أكتوبر 2016، وذلك من خلال وزارة الصحة. وبالنظر إلى ولاية بيرنامبوكو، التي تمثل واحدة من أكثر المناطق المنكوبة بالمرض، كانت البيانات متاحةً أسبوعيًا في الفترة من أغسطس/آب 2015 حتى أكتوبر/تشرين الأول 2016 فيما يتعلق بتعريفات مختلفة للصعل. وتم احتساب الاختطار المطلق للإصابة بالصعل باستخدام متوسط عدد المواليد الأحياء الذين تم الإبلاغ بهم في كل ولاية في الفترة الزمنية المناظرة بين عامي 2012 و2014 مع افتراض معدلين للإصابة بالعدوى: 10‏% و50‏%. وتم تقدير الاختطار النسبي باستخدام المعدل السابق لتكرار الإصابة بالصعل والذي تم الإبلاغ به في البرازيل حيث بلغ 1.98 من كل 10 آلاف مولود من المواليد الأحياء. + تباين الاختطار النسبي المقدَّر فيما يتعلق بحالات الإصابة بالصعل التي تم الإخطار بها حيث تراوح بين 0.03 و‏17.1‏%، وتوقف ذلك على المنطقة الجغرافية والتعريف المستخدم للصعل ومعدل الإصابة بالعدوى. وبافتراض وصول معدل الإصابة إلى ‏50%، ارتفع احتمال الإصابة بالصعل لدى الأطفال المولودين لأمهات مصابات بعدوى فيروس زيكا بمقدار 18 – 127 مرة أثناء فترة الحمل في بيرنامبوكو. أما بالنظر إلى معدل الإصابة بالعدوى البالغ 10‏%، فقد ارتفع هذا الاحتمال بمقدار 88 – 635 مرة. + تم التوصل إلى وجود تباين كبير في الخطر الذي تم تقديره فيما يتعلق بالإصابة بالصعل في البرازيل. ويحتاج الأمر إلى إجراء البحث العلمي بشأن العوامل المحتملة لتغيير التأثير، وما يمكن الاعتماد عليه من الإجراءات الواجب اتخاذها حيال عدوى فيروس زيكا ونقاط نهاية واضحة للتشوهات الولادية. + + + 旨在估测 2015 至 2016 年流行病蔓延期间孕期感染寨卡病毒女性所生婴儿的小头症患病风险。. + 我们从卫生部获取了 2015 年 11 月至 2016 年 10 月期间巴西各州通报及确认的小头症病例的数据。 从伯南布哥州,患病重灾区之一,可获取其 2015 年 8 月至 2016 年 10 月期间具有不同定义的小头症的周数据。 小头症绝对患病风险的计算采用各州在 2012 年至 2014 年相应时间段内呈报的活产婴儿的平均数量,并假设两个感染率为: 10% 和 50%。 相对风险采用巴西每 10,000 个活产婴儿中 1.98 例小头症患儿这一报道背景频率进行估测。. + 根据地理区域、所采用的小头症定义以及感染率的不同,所呈报小头症的估测绝对患病风险也有所不同,其变化范围为 0.03 至 17.1%。 在伯南布哥州,假设感染率为 50%,相较于未在孕期感染寨卡病毒的母亲所生的婴儿,孕期感染寨卡病毒母亲所生婴儿的小头症患病可能性高出前者 18-127 倍。 若感染率为 10%,该可能性则高出前者 88-635 倍。. + 经发现,在巴西,估测的小头症患病风险有较大差异。 仍需对寨卡病毒感染及先天性畸形确切终结点的可能影响效应及可靠措施进行研究。. + + + Оценить риск микроцефалии у младенцев, рожденных от женщин, которые заразились вирусом Зика во время беременности в Бразилии в период эпидемии между 2015 и 2016 годами. + Министерство здравоохранения предоставило данные о количестве зарегистрированных и подтвержденных случаев микроцефалии в каждом штате Бразилии в период с ноября 2015 года по октябрь 2016 года. По штату Пернамбуку, который был одним из наиболее пострадавших штатов, были доступны еженедельные данные для различных определений микроцефалии в период с августа 2015 года по октябрь 2016 года. Абсолютный риск микроцефалии рассчитали с помощью среднего количества живорожденных младенцев, зарегистрированных в каждом штате в соответствующий период времени между 2012 и 2014 годами, принимая во внимание два уровня заболеваемости: 10 и 50%. Для оценки относительного риска использовалась зарегистрированная фоновая частота микроцефалии в Бразилии, составлявшая 1,98 на 10 000 живорожденных младенцев. + Полученный абсолютный риск зарегистрированного случая микроцефалии колебался от 0,03 до 17,1%, в зависимости от географического района, используемого определения микроцефалии и уровня заболеваемости. При предположительном уровне заболеваемости, равном 50%, вероятность развития микроцефалии у детей, рожденных от матерей с вирусной инфекцией Зика во время беременности, по сравнению с детьми, рожденными от матерей без вирусной инфекции Зика во время беременности, была в 18–127 раз выше в штате Пернамбуку. Для 10-процентного уровня заболеваемости вероятность была в 88–635 раз выше. + В Бразилии был обнаружен большой разброс в оценке риска развития микроцефалии. Необходимы дальнейшие исследования возможных модификаторов эффекта, надежных показателей вирусной инфекции Зика и четких конечных критериев оценки для врожденных пороков развития. + +
+ + + + 2017 + 3 + 3 + 6 + 0 + + + 2017 + 3 + 3 + 6 + 0 + + + 2017 + 9 + 26 + 6 + 0 + + + ppublish + + 28250532 + 10.2471/BLT.16.178608 + BLT.16.178608 + PMC5328112 + + +
+ + + + + 28239566 + + 2017 + 08 + 16 + +
+ + 2220-3249 + + 6 + 1 + + 2017 + Feb + 12 + + + World journal of virology + World J Virol + + Biological and historical overview of Zika virus. + + 1-8 + + 10.5501/wjv.v6.i1.1 + + The recent outbreak of the Zika virus attracts worldwide attention probably because the most recently affected country (Brazil) will host the 2016 Olympic Game. Zika virus infected cases are now spreading to many other countries and its infection might be linked to some severe medical sequelae. Since its first isolation from the infected monkey in 1947 in Uganda, only a few studies had been taken until recent outbreak. According to the history of referenced publications, there is a 19-year gap from 1989 to 2007. This might be because only mild diseases were diagnosed from Zika virus infected populations. Obviously, the recent reports that Zika virus infection is probably associated with microcephaly of the neonates makes us reevaluate the medical significance of the viral pathogen. It can be transmitted sexually or by mosquito biting. Sexual transmission of the Zika virus distinguishes it from other members of the Genus Flavivirus. Detailed information of the Zika virus is needed through a thorough investigation covering basic, epidemical, subclinical and clinical studies. Here, we reviewed the published information of Zika virus. + + + + Armstrong + Najealicka + N + + Najealicka Armstrong, Wangheng Hou, Qiyi Tang, Deparment of Microbiology, Howard University, College of Medicine, Washington, DC 20059, United States. + + + + Hou + Wangheng + W + + Najealicka Armstrong, Wangheng Hou, Qiyi Tang, Deparment of Microbiology, Howard University, College of Medicine, Washington, DC 20059, United States. + + + + Tang + Qiyi + Q + + Najealicka Armstrong, Wangheng Hou, Qiyi Tang, Deparment of Microbiology, Howard University, College of Medicine, Washington, DC 20059, United States. + + + + eng + + + G12 MD007597 + MD + NIMHD NIH HHS + United States + + + SC1 AI112785 + AI + NIAID NIH HHS + United States + + + + Journal Article + Review + +
+ + United States + World J Virol + 101608353 + 2220-3249 + + + + Euro Surveill. 2014 Jan 30;19(4):null + 24507466 + + + Infection. 2016 Dec;44(6):797-802 + 27209175 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Arch Virol. 2007;152(4):687-96 + 17195954 + + + Vector Borne Zoonotic Dis. 2014 Dec;14(12):862-5 + 25514122 + + + J Gen Virol. 2006 Nov;87(Pt 11):3279-83 + 17030861 + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Ann Trop Med Parasitol. 1975 Mar;69(1):49-64 + 1124969 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + J Virol. 1987 Nov;61(11):3641-4 + 2959795 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + Emerg Infect Dis. 2015 Feb;21(2):381-2 + 25625687 + + + Microbes Infect. 2016 May;18(5):295-301 + 26993028 + + + Front Microbiol. 2016 Apr 19;7:496 + 27148186 + + + Prehosp Disaster Med. 2016 Apr;31(2):119-20 + 26940218 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):63-7 + 26820387 + + + Traffic. 2005 Nov;6(11):967-77 + 16190978 + + + Emerg Infect Dis. 2016 May;22(5):927-9 + 27089253 + + + Virus Genes. 2014 Dec;49(3):490-2 + 25260554 + + + Bull Soc Pathol Exot Filiales. 1982 May-Jul;75(3):262-6 + 6809352 + + + Ultrasound Obstet Gynecol. 2016 May;47(5):657-60 + 26923098 + + + Ann Intern Med. 2016 May 17;164(10):689-91 + 26914810 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + IDCases. 2016 Apr 07;4:46-9 + 27134823 + + + Genome Announc. 2014 Jun 05;2(3):null + 24903869 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Ann Trop Med Parasitol. 1983 Apr;77(2):131-7 + 6309104 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + East Afr Med J. 2010 Jun;87(6):262-8 + 23057269 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + BMJ. 2016 Mar 01;352:i1242 + 26932976 + + + Emerg Infect Dis. 2012 Feb;18(2):349-51 + 22305269 + + + Antiviral Res. 2013 May;98(2):192-208 + 23523765 + + + Trans R Soc Trop Med Hyg. 1956 Sep;50(5):442-8 + 13380987 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + J Virol. 2014 Mar;88(6):3379-91 + 24390334 + + + Lancet. 2016 Mar 5;387(10022):919-21 + 26921913 + + + Protein Cell. 2016 Jun;7(6):461-4 + 27209301 + + + Cell Host Microbe. 2014 Sep 10;16(3):314-27 + 25211074 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + Emerg Microbes Infect. 2016 Mar 16;5:e22 + 26980239 + + + J Virol. 2003 Jun;77(12):7143-9 + 12768036 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + PLoS Curr. 2016 Apr 15;8:null + 27158557 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + J Virol. 1991 Oct;65(10):5579-83 + 1716695 + + + Antiviral Res. 2010 Aug;87(2):125-48 + 19945487 + + + Science. 2008 Mar 28;319(5871):1830-4 + 18369147 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Lancet. 2016 Jan 16;387(10015):227-8 + 26775124 + + + Euro Surveill. 2015 Jun 11;20(23):null + 26084316 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + J Hyg (Lond). 1979 Oct;83(2):213-9 + 489960 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + J Biol Chem. 2011 Jun 24;286(25):22147-59 + 21511946 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + J Wildl Dis. 2003 Jan;39(1):73-83 + 12685070 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + J Virol. 2008 May;82(10):4731-41 + 18337583 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Lancet. 2015 Jul 18;386(9990):243-4 + 26194519 + + + Trans R Soc Trop Med Hyg. 1956 May;50(3):238-42 + 13337908 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Congenital infection + Flavivirus + Microcephaly + Outbreak + Zika virus + + Conflict-of-interest statement: The authors declare that they have no conflict of interest. +
+ + + + 2016 + 05 + 10 + + + 2016 + 06 + 20 + + + 2016 + 08 + 11 + + + 2017 + 2 + 28 + 6 + 0 + + + 2017 + 2 + 28 + 6 + 0 + + + 2017 + 2 + 28 + 6 + 1 + + + ppublish + + 28239566 + 10.5501/wjv.v6.i1.1 + PMC5303855 + + +
+ + + + + 28231241 + + 2017 + 07 + 12 + + + 2017 + 07 + 13 + +
+ + 1935-2735 + + 11 + 2 + + 2017 + Feb + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study. + + e0005363 + + 10.1371/journal.pntd.0005363 + + The teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model. Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection. The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains, providing a better analogy to the human condition than approaches involving immunodeficient, genetically modified animals, or direct ZIKV injection into the brain. When injected via the jugular vein into the blood of pregnant females harboring conceptuses from early gastrulation to organogenesis stages, akin to the human second and fifth week of pregnancy, ZIKV infects maternal tissues, placentas and embryos/fetuses. Early exposure to ZIKV at developmental day 5 (second week in humans) produced complex manifestations of anterior and posterior dysraphia and hydrocephalus, as well as severe malformations and delayed development in 10.5 days post-coitum (dpc) embryos. Exposure to the virus at 7.5-9.5 dpc induces intra-amniotic hemorrhage, widespread edema, and vascular rarefaction, often prominent in the cephalic region. At these stages, most affected embryos/fetuses displayed gross malformations and/or intrauterine growth restriction (IUGR), rather than isolated microcephaly. Disrupted conceptuses failed to achieve normal developmental landmarks and died in utero. Importantly, this is the only model so far to display dysraphia and hydrocephalus, the harbinger of microcephaly in humans, as well as arthrogryposis, a set of abnormal joint postures observed in the human setting. Late exposure to ZIKV at 12.5 dpc failed to produce noticeable malformations. We have thus characterized a developmental window of opportunity for ZIKV-induced teratogenesis encompassing early gastrulation, neurulation and early organogenesis stages. This should not, however, be interpreted as evidence for any safe developmental windows for ZIKV exposure. Late developmental abnormalities correlated with damage to the placenta, particularly to the labyrinthine layer, suggesting that circulatory changes are integral to the altered phenotypes. + + + + Xavier-Neto + Jose + J + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Carvalho + Murilo + M + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Pascoalino + Bruno Dos Santos + BD + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Cardoso + Alisson Campos + AC + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Costa + Ângela Maria Sousa + ÂM + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Pereira + Ana Helena Macedo + AH + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Santos + Luana Nunes + LN + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. + + + + Saito + Ângela + Â + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Marques + Rafael Elias + RE + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Smetana + Juliana Helena Costa + JH + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Consonni + Silvio Roberto + SR + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Bandeira + Carla + C + + Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. + + + + Costa + Vivian Vasconcelos + VV + + Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Belo Horizonte, MG, Brazil. + + + + Bajgelman + Marcio Chaim + MC + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Oliveira + Paulo Sérgio Lopes de + PS + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Cordeiro + Marli Tenorio + MT + + CPqAM-Fiocruz. Federal University of Pernambuco, Av. Professor Moraes Rego s/n, Cidade Universitária, Recife, PE, Brazil. + + + + Gonzales Gil + Laura Helena Vega + LH + + CPqAM-Fiocruz. Federal University of Pernambuco, Av. Professor Moraes Rego s/n, Cidade Universitária, Recife, PE, Brazil. + + + + Pauletti + Bianca Alves + BA + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Granato + Daniela Campos + DC + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Paes Leme + Adriana Franco + AF + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Freitas-Junior + Lucio + L + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Holanda de Freitas + Carolina Borsoi Moraes + CB + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + Teixeira + Mauro Martins + MM + + Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Belo Horizonte, MG, Brazil. + + + + Bevilacqua + Estela + E + + Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. + + + + Franchini + Kleber + K + + Brazilian Biosciences National Laboratory, LNBio, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, SP, Brazil. + + + + eng + + Journal Article + + + 2017 + 02 + 23 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + + + 0 + Teratogens + + + IM + + + Lancet. 2016 Apr 2;387(10026):1482 + 27115821 + + + Int J Dev Biol. 2014;58(2-4):281-9 + 25023694 + + + Am J Trop Med Hyg. 2006 Jan;74(1):132-41 + 16407358 + + + Arch Pathol Lab Med. 2017 Jan;141(1):26-32 + 27636525 + + + Placenta. 2014 Feb;35 Suppl:S51-6 + 24215782 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Arq Neuropsiquiatr. 2016 Mar;74(3):253-5 + 27050856 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Dev Cell. 2013 Nov 25;27(4):373-86 + 24286824 + + + Virol J. 2010 Aug 19;7:194 + 20723234 + + + Pediatr Neurosci. 1989;15(1):1-12 + 2699756 + + + Curr Protoc Microbiol. 2012 Nov;Chapter 15:Unit 15D.2. + 23184594 + + + Development. 2016 Nov 15;143(22):4127-4136 + 27729407 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + J Immunol. 2000 Feb 15;164(4):2120-30 + 10657666 + + + Obstet Gynecol. 2012 Dec;120(6):1345-53 + 23168759 + + + Placenta. 2010 Feb;31(2):126-33 + 20022372 + + + Neurology. 2009 Sep 15;73(11):887-97 + 19752457 + + + Nature. 2016 Apr 19;533(7603):425-8 + 27093288 + + + Antiviral Res. 2014 Oct;110:20-30 + 25046486 + + + Arch Pathol Lab Med. 2017 Jan;141(1):18-25 + 27763793 + + + PLoS Negl Trop Dis. 2016 May 05;10(5):e0004658 + 27149521 + + + PLoS Negl Trop Dis. 2016 Apr 19;10(4):e0004682 + 27093158 + + + Clin Perinatol. 2003 Sep;30(3):531-9 + 14533894 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Curr Protoc Immunol. 2007 May;Chapter 15:Unit 15.1 + 18432984 + + + Mol Genet Metab. 2003 Sep-Oct;80(1-2):36-53 + 14567956 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + Curr Opin Virol. 2016 Jun;18:76-81 + 27179929 + + + J Immunol. 1999 Jun 15;162(12):7501-9 + 10358205 + + + Nat Rev Microbiol. 2016 Nov;14 (11):707-715 + 27573577 + + + Virology. 2006 Mar 30;347(1):175-82 + 16406457 + + + Development. 1993 Aug;118(4):1255-66 + 8269852 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Cell. 2016 Aug 25;166(5):1247-1256.e4 + 27565347 + + + Cerebellum. 2002 Jan-Mar;1(1):57-68 + 12879974 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + Cell Res. 2016 Jun;26(6):645-54 + 27174054 + + + Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7852-7 + 27354515 + + + Am J Physiol. 1996 Oct;271(4 Pt 2):H1407-15 + 8897934 + + + Arch Pathol Lab Med. 2017 Jan;141(1):43-48 + 27681334 + + + PLoS One. 2014 Nov 20;9(11):e110620 + 25412181 + + + Lab Anim (NY). 2008 Jan;37(1):26-32 + 18094699 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + + + Animals + + + Arthrogryposis + embryology + immunology + pathology + virology + + + Disease Models, Animal + + + Female + + + Humans + + + Hydrocephalus + embryology + immunology + pathology + virology + + + Male + + + Mice + + + Mice, Inbred C57BL + + + Placenta + abnormalities + immunology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + immunology + pathology + virology + + + Teratogens + analysis + + + Zika Virus + physiology + + + Zika Virus Infection + embryology + immunology + pathology + virology + + +
+ + + + 2016 + 09 + 12 + + + 2017 + 01 + 27 + + + 2017 + 2 + 24 + 6 + 0 + + + 2017 + 2 + 24 + 6 + 0 + + + 2017 + 7 + 14 + 6 + 0 + + + epublish + + 28231241 + 10.1371/journal.pntd.0005363 + PNTD-D-16-01623 + PMC5322881 + + +
+ + + + + 28217114 + + 2017 + 08 + 16 + +
+ + 1664-302X + + 8 + + 2017 + + + Frontiers in microbiology + Front Microbiol + + Zika Virus: Transmission, Detection, Control, and Prevention. + + 110 + + 10.3389/fmicb.2017.00110 + + Zika virus (ZIKV) is a mosquito-borneFlavivirusdiscovered in Uganda in the 1940s. To date, three major ZIKV outbreaks have been reported. ZIKV infections have known to be primarily asymptomatic while causing mild illness in a few cases. However, the recent emergence and spread of ZIKV in the Americas has resulted in the declaration of "Public Health Emergency of International Concern" due to the potential association between the infection and prenatal microcephaly or other brain anomalies. In Brazil, a 20-fold increase in prenatal microcephaly cases and 19% increase in Guillain-Barré Syndrome (GBS) cases were reported in 2015, as compared to the preceding year. The probable deleterious effects of ZIKV infection prompt the urgent development of diagnostics and therapeutics. To this end, the existing evidences supporting the increasingly common prenatal microcephaly and GBS association and the current known ZIKV transmission dynamics, modes of detection (molecular and serology-based), and current control strategies are summarized in this review. This review also emphasizes the importance of understanding ZIKV transmission in order to design a sensitive yet cost and time-efficient detection technique. Development of an efficient detection technique would subsequently allow for better surveillance and control of ZIKV infection. Currently, limited literature is available on the pathogenesis of ZIKV, hence, focusing on the modes of ZIKV transmission could potentially contribute to the understanding of the disease spectrum and formulation of targeted treatment and control. + + + + Sharma + Anshika + A + + School of Science, Monash University Selangor, Malaysia. + + + + Lal + Sunil K + SK + + School of Science, Monash University Selangor, Malaysia. + + + + eng + + Journal Article + Review + + + 2017 + 02 + 03 + +
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+ + + + 2016 + 09 + 28 + + + 2017 + 01 + 16 + + + 2017 + 2 + 21 + 6 + 0 + + + 2017 + 2 + 22 + 6 + 0 + + + 2017 + 2 + 22 + 6 + 1 + + + epublish + + 28217114 + 10.3389/fmicb.2017.00110 + PMC5290000 + + +
+ + + + + 28207688 + + 2017 + 03 + 17 + + + 2018 + 01 + 19 + +
+ + 1545-861X + + 66 + 6 + + 2017 + Feb + 17 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Transmission of Zika Virus - Haiti, October 12, 2015-September 10, 2016. + + 172-176 + + 10.15585/mmwr.mm6606a4 + + Zika virus disease is caused by infection with a flavivirus with broad geographic distribution and is most frequently transmitted by the bite of an infected mosquito. The disease was first identified in the World Health Organization's Region of the Americas in 2015 and was followed by a surge in reported cases of congenital microcephaly in Brazil; Zika virus disease rapidly spread to the rest of the region and the Caribbean (1), including Haiti. Infection with the virus is associated with adverse fetal outcomes (1) and rare neurologic complications in adults. The magnitude of public health issues associated with Zika virus led the World Health Organization to declare the Zika virus outbreak a Public Health Emergency of International Concern on February 1, 2016 (2). Because many persons with mild Zika virus disease are asymptomatic and might not seek care, it is difficult to estimate the actual incidence of Zika virus infection. During October 12, 2015-September 10, 2016, the Haitian Ministry of Public Health and Population (Ministère de la Santé Publique et de la Population [MSPP]) detected 3,036 suspected cases of Zika virus infection in the general population, 22 suspected cases of Zika virus disease among pregnant women, 13 suspected cases of Guillain-Barré syndrome (GBS), and 29 suspected cases of Zika-associated congenital microcephaly. Nineteen (0.6%) patients with suspected Zika virus disease, residing in Ouest (10 patients), Artibonite (six), and Centre (three) administrative departments,* have been confirmed by laboratory testing, including two among pregnant women and 17 in the general population. Ongoing laboratory-enhanced surveillance to monitor Zika virus disease in Haiti is important to understanding the outbreak and ensuring effective response activities. + + + + Journel + Ito + I + + + Andrécy + Lesly L + LL + + + Metellus + Dudley + D + + + Pierre + Jean S + JS + + + Faublas + Rose Murka + RM + + + Juin + Stanley + S + + + Dismer + Amber M + AM + + + Fitter + David L + DL + + + Neptune + Daniel + D + + + Laraque + Marie José + MJ + + + Corvil + Salomon + S + + + Pierre + Manise + M + + + Buteau + Josiane + J + + + Lafontant + Donald + D + + + Patel + Roopal + R + + + Lemoine + Jean Frantz + JF + + + Lowrance + David W + DW + + + Charles + Macarthur + M + + + Boncy + Jacques + J + + + Adrien + Paul + P + + + eng + + Journal Article + + + 2017 + 02 + 17 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Nat Microbiol. 2016 Jul 25;1(9):16126 + 27562260 + + + + + Adolescent + + + Adult + + + Child + + + Child, Preschool + + + Disease Outbreaks + + + Female + + + Guillain-Barre Syndrome + epidemiology + + + Haiti + epidemiology + + + Humans + + + Incidence + + + Infant + + + Infant, Newborn + + + Microcephaly + epidemiology + + + Middle Aged + + + Population Surveillance + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Public Health Practice + + + Young Adult + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + transmission + + +
+ + + + 2017 + 2 + 17 + 6 + 0 + + + 2017 + 2 + 17 + 6 + 0 + + + 2017 + 3 + 18 + 6 + 0 + + + epublish + + 28207688 + 10.15585/mmwr.mm6606a4 + PMC5657860 + + +
+ + + + + 28207337 + + 2017 + 06 + 15 + + + 2017 + 06 + 15 + +
+ + 1541-0048 + + 107 + 4 + + 2017 + Apr + + + American journal of public health + Am J Public Health + + Engaging Human Rights in the Response to the Evolving Zika Virus Epidemic. + + 525-531 + + 10.2105/AJPH.2017.303658 + + In late 2015, an increase in the number of infants born with microcephaly in poor communities in northeast Brazil prompted investigation of antenatal Zika infection as the cause. Zika now circulates in 69 countries, and has affected pregnancies of women in 29 countries. Public health officials, policymakers, and international organizations are considering interventions to address health consequences of the Zika epidemic. To date, public health responses have focused on mosquito vector eradication, sexual and reproductive health services, knowledge and technology including diagnostic test and vaccine development, and health system preparedness. We summarize responses to date and apply human rights and related principles including nondiscrimination, participation, the legal and policy context, and accountability to identify shortcomings and to offer suggestions for more equitable, effective, and sustainable Zika responses. + + + + Rasanathan + Jennifer J K + JJ + + Jennifer J. K. Rasanathan is with the Public Health Program, Open Society Foundations, New York, NY. Sarah MacCarthy is with Rand Corporation, Santa Monica, CA. Debora Diniz is with the Faculty of Law, University of Brasília, Brasília DF, Brazil. Els Torreele is with Access to Medicines and Innovation, Public Health Program, Open Society Foundations. Sofia Gruskin is with the Keck School of Medicine, Gould School of Law, and Program on Global Health and Human Rights, Institute for Global Health, University of Southern California, Los Angeles. + + + + MacCarthy + Sarah + S + + Jennifer J. K. Rasanathan is with the Public Health Program, Open Society Foundations, New York, NY. Sarah MacCarthy is with Rand Corporation, Santa Monica, CA. Debora Diniz is with the Faculty of Law, University of Brasília, Brasília DF, Brazil. Els Torreele is with Access to Medicines and Innovation, Public Health Program, Open Society Foundations. Sofia Gruskin is with the Keck School of Medicine, Gould School of Law, and Program on Global Health and Human Rights, Institute for Global Health, University of Southern California, Los Angeles. + + + + Diniz + Debora + D + + Jennifer J. K. Rasanathan is with the Public Health Program, Open Society Foundations, New York, NY. Sarah MacCarthy is with Rand Corporation, Santa Monica, CA. Debora Diniz is with the Faculty of Law, University of Brasília, Brasília DF, Brazil. Els Torreele is with Access to Medicines and Innovation, Public Health Program, Open Society Foundations. Sofia Gruskin is with the Keck School of Medicine, Gould School of Law, and Program on Global Health and Human Rights, Institute for Global Health, University of Southern California, Los Angeles. + + + + Torreele + Els + E + + Jennifer J. K. Rasanathan is with the Public Health Program, Open Society Foundations, New York, NY. Sarah MacCarthy is with Rand Corporation, Santa Monica, CA. Debora Diniz is with the Faculty of Law, University of Brasília, Brasília DF, Brazil. Els Torreele is with Access to Medicines and Innovation, Public Health Program, Open Society Foundations. Sofia Gruskin is with the Keck School of Medicine, Gould School of Law, and Program on Global Health and Human Rights, Institute for Global Health, University of Southern California, Los Angeles. + + + + Gruskin + Sofia + S + + Jennifer J. K. Rasanathan is with the Public Health Program, Open Society Foundations, New York, NY. Sarah MacCarthy is with Rand Corporation, Santa Monica, CA. Debora Diniz is with the Faculty of Law, University of Brasília, Brasília DF, Brazil. Els Torreele is with Access to Medicines and Innovation, Public Health Program, Open Society Foundations. Sofia Gruskin is with the Keck School of Medicine, Gould School of Law, and Program on Global Health and Human Rights, Institute for Global Health, University of Southern California, Los Angeles. + + + + eng + + Journal Article + + + 2017 + 02 + 16 + +
+ + United States + Am J Public Health + 1254074 + 0090-0036 + + AIM + IM + + + Adult + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Global Health + + + Human Rights + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Zika Virus Infection + epidemiology + therapy + + +
+ + + + 2017 + 2 + 17 + 6 + 0 + + + 2017 + 6 + 16 + 6 + 0 + + + 2017 + 2 + 17 + 6 + 0 + + + ppublish + + 28207337 + 10.2105/AJPH.2017.303658 + + +
+ + + + + 28205302 + + 2017 + 10 + 26 + + + 2017 + 10 + 30 + +
+ + 1097-0223 + + 37 + 2 + + 2017 + 02 + + + Prenatal diagnosis + Prenat. Diagn. + + Response to "Associated ultrasonographic findings in fetuses with microcephaly because of suspected Zika virus (ZIKV) infection during pregnancy". + + 207-208 + + 10.1002/pd.4985 + + + Carvalho + Francisco Herlânio Costa + FH + + Department of Maternal and Child Health, School of Medicine, Federal University of Ceará (UFC), Fortaleza, CE, Brazil. + + + + eng + + Letter + Comment + +
+ + England + Prenat Diagn + 8106540 + 0197-3851 + + IM + + + Prenat Diagn. 2017 Feb;37(2):206 + 28205300 + + + + + Female + + + Fetus + + + Humans + + + Microcephaly + virology + + + Pregnancy + + + Zika Virus + + + Zika Virus Infection + + +
+ + + + 2016 + 11 + 27 + + + 2016 + 12 + 11 + + + 2017 + 2 + 17 + 6 + 0 + + + 2017 + 2 + 17 + 6 + 0 + + + 2017 + 10 + 27 + 6 + 0 + + + ppublish + + 28205302 + 10.1002/pd.4985 + + +
+ + + + + 28190239 + + 2018 + 02 + 22 + +
+ + 1559-1182 + + 55 + 2 + + 2018 + Feb + + + Molecular neurobiology + Mol. Neurobiol. + + Evaluation of Possible Consequences of Zika Virus Infection in the Developing Nervous System. + + 1620-1629 + + 10.1007/s12035-017-0442-5 + + The Zika virus (ZIKV) outbreak that occurred in the northeast of Brazil in 2015 led to alarming numbers of babies born with microcephaly in this region. Since then, several studies have evaluated the relationship between ZIKV infection and development of the malformation although the specific mechanistic interaction between ZIKV and human physiological processes that ultimately manifest as microcephaly remains debated. Importantly, most current studies did not consider the specificities of the biology and life cycle of ZIKV. As a consequence, specificities of the infection on the developing central nervous system (CNS) were frequently disregarded. In order to begin to address this important gap in our knowledge, we have collated and critically reviewed the existing evidence in this area to identify any emerging consensus on this topic and thereafter describe possible mechanisms by which ZIKV infection could interfere with specific processes of CNS development, such as neuronal proliferation, and the complex interactions of immature neurons with radial glial cells. With this, we were able to present the current knowledge on this important topic in the neurobiology field. + + + + Walter + Lais Takata + LT + + Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil. + + + + Higa + Guilherme Shigueto Vilar + GSV + + Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil. + + + Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil. + + + + Ikebara + Juliane Midori + JM + + Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil. + + + + Vedovello + Danila + D + + Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil. + + + + Salvador + Felipe Scassi + FS + + Laboratório de Virologia, Instituto de Medicina Tropical da Universidade de São Paulo, São Paulo, SP, Brazil. + + + + Takada + Silvia Honda + SH + + Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil. + + + + Kinjo + Erika Reime + ER + + Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil. + + + + Whalley + Benjamin J + BJ + + School of Chemistry, Food and Nutritional Sciences, and Pharmacy, University of Reading, Whiteknights, Berkshire, Reading, UK. + + + + Sperança + Márcia Aparecida + MA + + Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil. + + + + Kihara + Alexandre Hiroaki + AH + + Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, SP, Brazil. alexandrekihara@gmail.com. + + + Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil. alexandrekihara@gmail.com. + + + + eng + + + 2015/04495-0 + Fundação de Amparo à Pesquisa do Estado de São Paulo + + + + 2014/15018-5 + Fundação de Amparo à Pesquisa do Estado de São Paulo + + + + 2014/16711-6 + Fundação de Amparo à Pesquisa do Estado de São Paulo + + + + 2012/03583-4 + Fundação de Amparo à Pesquisa do Estado de São Paulo + + + + 2014/04568-4 + Fundação de Amparo à Pesquisa do Estado de São Paulo + + + + 308608/2014-3 + Conselho Nacional de Desenvolvimento Científico e Tecnológico + + + + + Journal Article + Review + + + 2017 + 02 + 11 + +
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+ Mem Inst Oswaldo Cruz. 2016 May;111(5):287-93 + 27143490 + + + Nat Cell Biol. 2011 Feb;13(2):132-41 + 21258367 + + + Nat Rev Drug Discov. 2008 Dec;7(12 ):1013-30 + 19043451 + + + Nat Rev Drug Discov. 2016 Jul 29;15(8):521-2 + 27469223 + + + Virology. 2016 Sep;496:215-218 + 27344138 + + + J Clin Invest. 2005 Oct;115(10 ):2656-64 + 16200199 + + + Pediatrics. 2000 Aug;106(2 Pt 1):235-43 + 10920145 + + + Trends Neurosci. 2008 May;31(5):243-50 + 18403031 + + + Curr Biol. 2001 Sep 4;11(17):1364-8 + 11553331 + + + Front Microbiol. 2014 Jun 03;5:266 + 24917859 + + + Annu Rev Microbiol. 1990;44:649-88 + 2174669 + + + Nature. 2016 Aug 4;536(7614):48-53 + 27338953 + + + Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11836-41 + 22753484 + + + PLoS Negl Trop Dis. 2016 Apr 19;10(4):e0004682 + 27093158 + + + Viruses. 2014 Nov 24;6(11):4703-30 + 25421894 + + + Philos Trans R Soc Lond B Biol Sci. 2014 Feb 03;369(1638):20130094 + 24493742 + + + Virology. 1998 Jun 5;245(2):203-15 + 9636360 + + + Front 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+ 23263672 + + + Cell Rep. 2016 Jun 14;15(11):2315-22 + 27268504 + + + Virology. 2009 Mar 1;385(1):47-57 + 19068261 + + + J Neuropathol Exp Neurol. 2003 Mar;62(3):304-14 + 12638734 + + + Nat Immunol. 2016 Sep;17 (9):1102-8 + 27339099 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + J Neurosci. 1997 May 1;17(9):3096-111 + 9096144 + + + J Virol. 2010 Feb;84(3):1641-7 + 19906906 + + + BJOG. 2016 Jul;123(8):1265-1269 + 27150580 + + + Cell Res. 2016 Jun;26(6):645-54 + 27174054 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Oncogene. 2008 Oct 27;27(50):6434-51 + 18955971 + + + Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7852-7 + 27354515 + + + J Cell Biol. 2001 Jul 9;154(1):217-30 + 11449002 + + + Neuroscience. 2015 Aug 27;302:2-22 + 26117714 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Novartis Found Symp. 2006;277:23-39; discussion 40, 71-3, 251-3 + 17319152 + + + Annu Rev Immunol. 2011;29:587-619 + 21219187 + + + Nat Rev Microbiol. 2005 Jan;3(1):13-22 + 15608696 + + + Nat Rev Mol Cell Biol. 2007 Sep;8(9):741-52 + 17717517 + + + J Virol. 2014 Feb;88(4):1897-913 + 24284321 + + + Virol J. 2006 Apr 07;3:26 + 16603059 + + + Nat Rev Immunol. 2011 May;11(5):318-29 + 21508982 + + + Virology. 2003 Aug 1;312(2):458-69 + 12919750 + + + Mediators Inflamm. 2016;2016:8562805 + 27313404 + + + Cell Res. 2014 Jan;24(1):24-41 + 24366339 + + + + Disease + Infection + Microcephaly + Neurodevelopment + Virulence + +
+ + + + 2016 + 11 + 01 + + + 2017 + 02 + 03 + + + 2017 + 2 + 13 + 6 + 0 + + + 2017 + 2 + 13 + 6 + 0 + + + 2017 + 2 + 13 + 6 + 0 + + + ppublish + + 28190239 + 10.1007/s12035-017-0442-5 + 10.1007/s12035-017-0442-5 + + +
+ + + + + 28189347 + + 2017 + 09 + 26 + + + 2017 + 09 + 26 + +
+ + 1773-0597 + + 40 + 2 + + 2017 + Feb + + + Journal francais d'ophtalmologie + J Fr Ophtalmol + + [Ocular manifestations of Zika virus: What we do and do not know]. + + 138-145 + + S0181-5512(17)30025-6 + 10.1016/j.jfo.2017.01.002 + + Zika virus (ZIKV) disease outbreak, which was declared by the end of 2015 in Brazil, has become the largest one to date. Being reported in the Americas and in certain islands of the Pacific, it has the potential to spread worldwide. Although ZIKV infections are mostly self-limiting and/or asymptomatic in the healthy adult, they are responsible for devastating congenital neurologic malformations ZIKV (mainly microcephaly) when contracted during the first months of pregnancy. Ocular manifestations during the acute adult infection include conjunctivitis and more rarely ocular inflammation. Congenital infection is associated with chorioretinal atrophy pigment mottling of the retina retinal vasculature abnormalities and optic nerve atrophy. Therefore, complete ophthalmological evaluation is recommended for suspected congenital infections. + Copyright © 2017 Elsevier Masson SAS. All rights reserved. + + + + Benzekri + R + R + + Service d'ophtalmologie, hôpital de Bicêtre, Assistance publique-Hôpitaux de Paris, DHU vision et handicap, université Paris-Sud, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France. + + + + Belfort + R + R + Jr + + Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of São Paulo and Vision Institute, São Paulo, Brésil. + + + + Ventura + C V + CV + + Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of São Paulo and Vision Institute, São Paulo, Brésil; Altino Ventura Foundation, Recife, Brésil; Department of Ophthalmology, Pernambuco's Eye Hospital (HOPE), Recife, Brésil. + + + + de Paula Freitas + B + B + + Department of Ophthalmology, Hospital Geral Roberto Santos, Salvador, Brésil. + + + + Maia + M + M + + Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of São Paulo and Vision Institute, São Paulo, Brésil. + + + + Leite + M + M + + Service d'ophtalmologie, hôpital de Bicêtre, Assistance publique-Hôpitaux de Paris, DHU vision et handicap, université Paris-Sud, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France. + + + + Labetoulle + M + M + + Service d'ophtalmologie, hôpital de Bicêtre, Assistance publique-Hôpitaux de Paris, DHU vision et handicap, université Paris-Sud, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; UMR 1184, Immunologie des infections virales et maladies auto-immunes, commissariat à l'énergie atomique et aux énergies alternatives, Fontenay-aux-Roses, France. + + + + Rousseau + A + A + + Service d'ophtalmologie, hôpital de Bicêtre, Assistance publique-Hôpitaux de Paris, DHU vision et handicap, université Paris-Sud, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; UMR 1184, Immunologie des infections virales et maladies auto-immunes, commissariat à l'énergie atomique et aux énergies alternatives, Fontenay-aux-Roses, France. Electronic address: antoine.rousseau@aphp.fr. + + + + fre + + Journal Article + Review + + Manifestations oculaires du virus Zika : où en sommes-nous ? + + 2017 + 02 + 09 + +
+ + France + J Fr Ophtalmol + 7804128 + 0181-5512 + + IM + + + Brazil + epidemiology + + + Disease Outbreaks + + + Epidemics + + + Eye Infections, Viral + congenital + diagnosis + epidemiology + therapy + + + Female + + + Humans + + + Infant, Newborn + + + Infant, Newborn, Diseases + diagnosis + epidemiology + therapy + + + Infectious Disease Transmission, Vertical + statistics & numerical data + + + Neonatal Screening + methods + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + epidemiology + therapy + + + Zika Virus Infection + congenital + diagnosis + epidemiology + therapy + + + + Conjonctivite + Conjunctivitis + Epidemics + Maculopathie + Maculopathy + Microcephaly + Microcéphalie + Uveitis + Uvéite + Virus + Zika + Épidémie + +
+ + + + 2016 + 12 + 08 + + + 2017 + 01 + 12 + + + 2017 + 2 + 13 + 6 + 0 + + + 2017 + 9 + 28 + 6 + 0 + + + 2017 + 2 + 13 + 6 + 0 + + + ppublish + + 28189347 + S0181-5512(17)30025-6 + 10.1016/j.jfo.2017.01.002 + + +
+ + + + + 28185126 + + 2018 + 02 + 22 + +
+ + 1559-1182 + + 55 + 2 + + 2018 + Feb + + + Molecular neurobiology + Mol. Neurobiol. + + ZIKA Virus and Neuroscience: the Need for a Translational Collaboration. + + 1551-1555 + + 10.1007/s12035-017-0429-2 + + Zika virus (ZIKV) has become a major challenge for scientists and health agencies. ZIKV's involvement with human fetal microcephaly and Guillain-Barré syndrome and its transmission through Aedes africanus and Aedes aegypti mosquitos highlighted the epidemiological and neurological risks associated to ZIKV infection. In 2013, ZIKV arrives in Brazil but the first outbreak in the country was reported in 2015. Here, we used the Web of Science as a search tool for comparing the evolution of world and Brazilian scientific research on dengue virus (DENV)-also present in mosquito-, ZIKV and microcephaly. The association between ZIKV and microcephaly was only evidenced in 2015. Interestingly, Brazil and the USA are the responsible for most of these reports. Furthermore, the level of double-counted articles indicates a high degree of international collaborative effort in studying ZIKV and microcephaly. The ZIKV research clearly requires multidisciplinary expertise including epidemiologic, clinical, virological, and neurochemical backgrounds. This letter intends to emphasize the need of multidisciplinary studies and put forward some as yet unanswered questions in attempting to contribute to the understanding of this multifaceted health problem. In line with this, we recently constituted a collaborative and multidisciplinary taskforce encompassing eight Brazilian scientific institutions of excellence, The ZIKV translational research taskforce. This taskforce comprises a vast international network of collaborators and welcomes additional collaborators. We intend to advance fast in terms of mechanisms, which can potentially contribute to treat or halt ZIKV spreading around the world. + + + + Schuler-Faccini + Lavínia + L + + Department of Genetics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. + + + + Roehe + Paulo + P + + Microbiology, Immunobiology and Parasitology, Laboratory of Virology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. + + + + Zimmer + Eduardo R + ER + + Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, 2600 Ramiro Barcelos St, Santana, Porto Alegre, RS, 90035003, Brazil. + + + Brain Institute (BraIns) of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. + + + + Quincozes-Santos + André + A + + Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, 2600 Ramiro Barcelos St, Santana, Porto Alegre, RS, 90035003, Brazil. + + + + de Assis + Adriano M + AM + + Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, 2600 Ramiro Barcelos St, Santana, Porto Alegre, RS, 90035003, Brazil. + + + + Lima + Elizabeth Obino Cirne + EOC + + Embryology and Cell Differentiation Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. + + + + Guimarães + Jorge Almeida + JA + + Hospital de Clínicas de Porto Alegre and Laboratory of Biochemical Pharmacology, Centre of Biotechnology, UFRGS, Porto Alegre, Brazil. + + + + Victora + Cesar + C + + International Center for Equity in Health, Post-Graduation Program in Epidemiology, Federal University of Pelotas, Rua Marechal Deodoro, Pelotas, Brazil. + + + + Neto + Vivaldo Moura + VM + + Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Souza + Diogo O + DO + + Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, 2600 Ramiro Barcelos St, Santana, Porto Alegre, RS, 90035003, Brazil. diogo@ufrgs.br. + + + + eng + + + 440763/2016-9 + Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR) + + + + + Journal Article + + + 2017 + 02 + 09 + +
+ + United States + Mol Neurobiol + 8900963 + 0893-7648 + + + + Lancet. 2016 Apr 2;387(10026):1482 + 27115821 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Cell Stem Cell. 2016 May 5;18(5):591-6 + 27038591 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + Nat Immunol. 2015 Feb;16(2):170-177 + 25501631 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + PLoS Negl Trop Dis. 2007 Nov 07;1(2):e114 + 18060077 + + + Development. 2014 Jun;141(12):2494-505 + 24917504 + + + Nature. 2016 Aug 4;536(7614):48-53 + 27338953 + + + J Infect Dev Ctries. 2016 Jun 30;10 (6):563-6 + 27367003 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Science. 2016 Apr 15;352(6283):345-349 + 27013429 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Lancet. 2016 Jun 25;387(10038):2599-600 + 27353815 + + + Trends Cell Biol. 2016 Aug;26(8):587-97 + 27004698 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Emerg Infect Dis. 2015 Dec;21(12):2274-6 + 26584464 + + + Nat Immunol. 2016 Sep;17 (9):1102-8 + 27339099 + + + Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7852-7 + 27354515 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + + Brazil + Microcephaly + Translational research + ZIKV + +
+ + + + 2016 + 11 + 22 + + + 2017 + 01 + 27 + + + 2017 + 2 + 12 + 6 + 0 + + + 2017 + 2 + 12 + 6 + 0 + + + 2017 + 2 + 11 + 6 + 0 + + + ppublish + + 28185126 + 10.1007/s12035-017-0429-2 + 10.1007/s12035-017-0429-2 + + +
+ + + + + 28182667 + + 2017 + 06 + 23 + + + 2017 + 06 + 23 + +
+ + 1935-2735 + + 11 + 2 + + 2017 + Feb + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + Environmental and Social Change Drive the Explosive Emergence of Zika Virus in the Americas. + + e0005135 + + 10.1371/journal.pntd.0005135 + + Since Zika virus (ZIKV) was detected in Brazil in 2015, it has spread explosively across the Americas and has been linked to increased incidence of microcephaly and Guillain-Barré syndrome (GBS). In one year, it has infected over 500,000 people (suspected and confirmed cases) in 40 countries and territories in the Americas. Along with recent epidemics of dengue (DENV) and chikungunya virus (CHIKV), which are also transmitted by Aedes aegypti and Ae. albopictus mosquitoes, the emergence of ZIKV suggests an ongoing intensification of environmental and social factors that have given rise to a new regime of arbovirus transmission. Here, we review hypotheses and preliminary evidence for the environmental and social changes that have fueled the ZIKV epidemic. Potential drivers include climate variation, land use change, poverty, and human movement. Beyond the direct impact of microcephaly and GBS, the ZIKV epidemic will likely have social ramifications for women's health and economic consequences for tourism and beyond. + + + + Ali + Sofia + S + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Gugliemini + Olivia + O + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Harber + Serena + S + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Harrison + Alexandra + A + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Houle + Lauren + L + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Ivory + Javarcia + J + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Kersten + Sierra + S + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Khan + Rebia + R + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Kim + Jenny + J + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + LeBoa + Chris + C + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Nez-Whitfield + Emery + E + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + O'Marr + Jamieson + J + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Rothenberg + Emma + E + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Segnitz + R Max + RM + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Sila + Stephanie + S + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Verwillow + Anna + A + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Vogt + Miranda + M + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Yang + Adrienne + A + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + Mordecai + Erin A + EA + http://orcid.org/0000-0002-4402-5547 + + Department of Biology, Stanford University, Stanford, California, United States of America. + + + + eng + + Journal Article + Review + + + 2017 + 02 + 09 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + IM + + + Emerg Infect Dis. 2007 Jan;13(1):1-5 + 17370508 + + + J Cult Divers. 2011 Winter;18(4):114-9 + 22288207 + + + PLoS Negl Trop Dis. 2014 Feb 06;8(2):e2681 + 24516683 + + + Trop Med Int Health. 2015 Jan;20(1):77-88 + 25328988 + + + Insects. 2015 Jun 11;6(2):576-94 + 26463204 + + + PLoS Negl Trop Dis. 2015 Jul 02;9(7):e0003864 + 26135160 + + + Proc Biol Sci. 2015 Jan 7;282(1798):20142124 + 25392474 + + + Lancet. 2002 Sep 14;360(9336):830-4 + 12243917 + + + Lancet. 2016 Feb 20;387(10020):745 + 26850984 + + + Novartis Found Symp. 2006;277:3-16; discussion 16-22, 71-3, 251-3 + 17319151 + + + Lancet. 2016 Jan 23;387(10016):335-6 + 26777915 + + + PLoS Negl Trop Dis. 2013 Aug 01;7(8):e2348 + 23936579 + + + PLoS Negl Trop Dis. 2016 Mar 03;10(3):e0004543 + 26938868 + + + J Med Entomol. 2013 May;50(3):467-78 + 23802440 + + + N Engl J Med. 1947 Jun 26;236(26):978-88 + 20248435 + + + Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):11887-92 + 26351662 + + + Trans R Soc Trop Med Hyg. 1982;76(4):552-62 + 6304948 + + + Am J Trop Med Hyg. 2007 May;76(5):820-6 + 17488898 + + + Nature. 2013 Apr 25;496(7446):504-7 + 23563266 + + + PLoS Negl Trop Dis. 2012;6(8):e1792 + 22953014 + + + Clin Transl Immunology. 2016 Dec 16;5(12 ):e117 + 28090318 + + + Emerg Infect Dis. 2014 Aug;20(8):1394-5 + 25061832 + + + Trends Microbiol. 2002 Feb;10(2):100-3 + 11827812 + + + Clin Microbiol Rev. 1998 Jul;11(3):480-96 + 9665979 + + + Epidemiol Infect. 2016 Jul;144(9):1904-6 + 27040593 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Lancet. 2005 Mar 12-18;365(9463):989-96 + 15767002 + + + Stud Fam Plann. 2014 Sep;45(3):301-14 + 25207494 + + + Bull World Health Organ. 1970;43(4):539-52 + 5313066 + + + Am J Trop Med Hyg. 2001 May-Jun;64(5-6):310-6 + 11463123 + + + Science. 2009 Dec 4;326(5958):1362-7 + 19965751 + + + Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):994-9 + 23277539 + + + Euro Surveill. 2016 Apr 14;21(15): + 27104366 + + + Lancet. 2015 Jan 3;385(9962):29-35 + 25458732 + + + PLoS Negl Trop Dis. 2016 Dec 15;10 (12 ):e0005055 + 27977671 + + + Trans R Soc Trop Med Hyg. 1977;71(6):512-7 + 605465 + + + Bull World Health Organ. 2016 Sep 1;94(9):675-686C + 27708473 + + + Emerg Infect Dis. 2015 Apr;21(4):557-61 + 25816211 + + + MMWR Morb Mortal Wkly Rep. 2016 Jul 22;65(28):711-5 + 27442184 + + + Trans R Soc Trop Med Hyg. 1983;77(4):442-5 + 6314612 + + + Rev Soc Bras Med Trop. 2016 Feb;49(1):4-10 + 26689277 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Lancet. 2015 Jul 18;386(9990):243-4 + 26194519 + + + PLoS One. 2013 Nov 12;8(11):e78263 + 24324542 + + + Annu Rev Entomol. 2014;59:205-24 + 24160434 + + + PLoS One. 2015 Jul 15;10(7):e0132645 + 26177451 + + + Parasitol Res. 2016 May;115(5):1747-54 + 26932263 + + + + + Americas + epidemiology + + + Climate + + + Disease Reservoirs + + + Environmental Exposure + + + Epidemics + + + Humans + + + Mosquito Vectors + growth & development + + + Social Change + + + Zika Virus Infection + epidemiology + + + The authors have declared that no competing interests exist. +
+ + + + 2017 + 2 + 10 + 6 + 0 + + + 2017 + 2 + 10 + 6 + 0 + + + 2017 + 6 + 24 + 6 + 0 + + + epublish + + 28182667 + 10.1371/journal.pntd.0005135 + PNTD-D-16-01379 + PMC5300271 + + +
+ + + + + 28153056 + + 2017 + 05 + 04 + + + 2017 + 12 + 22 + +
+ + 1742-4755 + + 14 + 1 + + 2017 + Feb + 02 + + + Reproductive health + Reprod Health + + Study protocol on establishment of sentinel sites network for contraceptive and abortion trends, needs and utilization of services in Zika virus affected countries. + + 19 + + 10.1186/s12978-017-0282-9 + + ZIKV(Zika Virus) during pregnancy can result in many adverse events such as fetal deaths or newborns with congenital abnormalities including microcephaly and other neural irregularities. Due to these harmful outcomes of pregnancy associated with the Zika virus, we can expect to see a change in the type and scale of demand for family planning and safe abortion services in areas affected by the Zika virus. The monitoring and reporting capacities of the local health clinics in these areas could benefit from the introduction of infrastructural improvements necessary to establish a sentinel site network. Through these sites, the WHO will collect data on the situation from local health professionals to get real time information from the population group and act accordingly to mitigate the consequences of the Zika virus outbreak in a localized and culturally appropriate way. The objectives are to establish a sentinel sites surveillance network for reporting on uptake and utilization of contraception and safe abortion care services; to strengthen monitoring, and data quality assurance in the selected sentinel surveillance sites; and finally to assess the contraception and safe abortion care service utilization trends in the affected sites on a regular basis. + The proposal includes a set of objectives and actions that enable the creation of a set of criteria for the selection of the sentinel sites, as well the implementation of monitoring and reporting systems that will be used in data collection. + The data collected will be used to better understand the changing demand for family planning and safe abortion needs. This will ultimately be used to inform local health workers and policy makers as to how best to track the continued Zika virus outbreak and mitigate the consequences. The learning from establishment of surveillance sentinel sites will help to strengthen health systems at regional and subregional levels that are more adaptable and capable of providing reproductive healthcare services and of responding to future emergencies. + + + + Ali + Moazzam + M + + Department of Reproductive Health and Research, World Health Organization, Avenue Appia 20, Geneva 27, CH-1211, Switzerland. alimoa@who.int. + + + + Miller + Kelsey + K + + Department of Reproductive Health and Research, World Health Organization, Avenue Appia 20, Geneva 27, CH-1211, Switzerland. + + + + Folz + Rachel + R + + Department of Reproductive Health and Research, World Health Organization, Avenue Appia 20, Geneva 27, CH-1211, Switzerland. + + + + Johnson + Brooke Ronald + BR + Jr + + Department of Reproductive Health and Research, World Health Organization, Avenue Appia 20, Geneva 27, CH-1211, Switzerland. + + + + Kiarie + James + J + + Department of Reproductive Health and Research, World Health Organization, Avenue Appia 20, Geneva 27, CH-1211, Switzerland. + + + + eng + + Journal Article + + + 2017 + 02 + 02 + +
+ + England + Reprod Health + 101224380 + 1742-4755 + + IM + + + Bull World Health Organ. 2016 Jun 1;94(6):406-406A + 27274588 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Lancet Glob Health. 2015 Mar;3(3):e130 + 25618242 + + + N Engl J Med. 2016 Jul 28;375(4):396-8 + 27331661 + + + Int J Equity Health. 2014 Jan 31;13:10 + 24479581 + + + Bull World Health Organ. 2007 Dec;85(12 ):904-5 + 18278243 + + + Bull World Health Organ. 2016 Sep 1;94(9):705-708 + 27708476 + + + Bull World Health Organ. 2012 Dec 1;90(12):895-904 + 23284195 + + + J Infect Dis. 2005 Sep 1;192 Suppl 1:S127-32 + 16088796 + + + Lancet. 2016 Feb 27;387(10021):843 + 26880123 + + + Lancet Glob Health. 2016 Jul;4(7):e427 + 27339992 + + + Reprod Health. 2017 Dec 19;14 (1):177 + 29258544 + + + + + Abortion, Induced + methods + trends + + + Brazil + + + Colombia + + + Contraception + methods + trends + utilization + + + Female + + + Health Services Accessibility + + + Health Services Needs and Demand + + + Honduras + + + Humans + + + Patient Acceptance of Health Care + + + Pregnancy + + + Sentinel Surveillance + + + Sex Education + + + Zika Virus + + + Zika Virus Infection + epidemiology + prevention & control + + + + Contraception demand + Family planning + Safe abortion + Sentinel Sites + Zika virus + +
+ + + + 2016 + 12 + 13 + + + 2017 + 01 + 07 + + + 2017 + 2 + 4 + 6 + 0 + + + 2017 + 2 + 6 + 6 + 0 + + + 2017 + 5 + 5 + 6 + 0 + + + epublish + + 28153056 + 10.1186/s12978-017-0282-9 + 10.1186/s12978-017-0282-9 + PMC5289038 + + +
+ + + + + 28134669 + + 2018 + 01 + 03 + + + 2018 + 01 + 03 + +
+ + 1473-656X + + 29 + 2 + + 2017 + Apr + + + Current opinion in obstetrics & gynecology + Curr. Opin. Obstet. Gynecol. + + Prenatal imaging findings in fetal Zika virus infection. + + 95-105 + + 10.1097/GCO.0000000000000345 + + The aim of this review is to report the most recent observations concerning intrauterine Zika virus (ZIKV) infection and associated neuroimaging. + ZIKV outbreak in Brazil in 2015 was associated with an impressive registration of cases of congenital microcephaly in women with symptoms suggestive of ZIKV infection. Clinical and laboratory testing for ZIKV and hypothetic etiopathogenetic mechanisms are described. Diagnostic tests on blood, urine and amniotic fluid should be performed in all mothers with symptoms suggestive of intrauterine ZIKV infection. ZIKV causes multiple teratogenic malformations, mainly affecting the developing brain. + Neuroimaging investigation contributes to the prenatal detection of microcephaly and other brain abnormalities in cases of intrauterine ZIKV infection. Neuroimaging is based antenatally on two-dimensional and three-dimensional ultrasound and fetal MRI, whereas computed tomography scan is performed postnatally. Although neuropathology associated with intrauterine ZIKV infection is characterized by nonspecific findings of brain disorder, reduced cortical gyration and white-matter hypomyelination or dysmyelination and cerebellar hypoplasia have been consistently observed in the majority of fetuses and newborns. Prenatal or postnatal genetic workup should be carried out to exclude cases of primary microcephaly. Follow-up should rely upon MRI and computed tomography scan as well as neuropediatrician to better define developmental outcome in survivors. + + + + Araujo Júnior + Edward + E + + aDepartment of Obstetrics, Paulista School of Medicine, Federal University of São Paulo (EPM-UNIFESP), São Paulo, São Paulo bDepartment of Maternal and Child, Federal University of Ceará (UFC), Fortaleza, Ceará, Brazil cDepartment of Obstetrics and Gynecology, Guastalla Civil Hospital, AUSL, Reggio Emilia, Italy dDepartment of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Carvalho + Francisco H C + FH + + + Tonni + Gabriele + G + + + Werner + Heron + H + + + eng + + Journal Article + Review + +
+ + England + Curr Opin Obstet Gynecol + 9007264 + 1040-872X + + IM + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Humans + + + Microcephaly + physiopathology + virology + + + Neuroimaging + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnostic imaging + physiopathology + virology + + + Pregnant Women + + + Prenatal Care + + + Zika Virus Infection + complications + diagnostic imaging + physiopathology + + +
+ + + + 2017 + 1 + 31 + 6 + 0 + + + 2018 + 1 + 4 + 6 + 0 + + + 2017 + 1 + 31 + 6 + 0 + + + ppublish + + 28134669 + 10.1097/GCO.0000000000000345 + + +
+ + + + + 28126366 + + 2017 + 06 + 07 + + + 2018 + 01 + 10 + +
+ + 1097-6868 + + 216 + 3 + + 2017 + 03 + + + American journal of obstetrics and gynecology + Am. J. Obstet. Gynecol. + + Testing for Zika virus infection in pregnancy: key concepts to deal with an emerging epidemic. + + 209-225 + + S0002-9378(17)30127-8 + 10.1016/j.ajog.2017.01.020 + + Zika virus is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Following epidemics in Micronesia and French Polynesia during the past decade, more recent Zika virus infection outbreaks were first reported in South America as early as May 2013 and spread to now 50 countries throughout the Americas. Although no other flavivirus has previously been known to cause major fetal malformations following perinatal infection, reports of a causal link between Zika virus and microcephaly, brain and ocular malformations, and fetal loss emerged from hard-hit regions of Brazil by October 2015. Among the minority of infected women with symptoms, clinical manifestations of Zika virus infection may include fever, headache, arthralgia, myalgia, and maculopapular rash; however, only 1 of every 4-5 people who are infected have any symptoms. Thus, clinical symptom reporting is an ineffective screening tool for the relative risk assessment of Zika virus infection in the majority of patients. As previously occurred with other largely asymptomatic viral infections posing perinatal transmission risk (such as HIV or cytomegalovirus), we must develop and implement rapid, sensitive, and specific screening and diagnostic testing for both viral detection and estimation of timing of exposure. Unfortunately, despite an unprecedented surge in attempts to rapidly advance perinatal clinical testing for a previously obscure arbovirus, there are several ongoing hindrances to molecular- and sonographic-based screening and diagnosis of congenital Zika virus infection. These include the following: (1) difficulty in estimating the timing of exposure for women living in endemic areas and thus limited interpretability of immunoglobulin M serologies; (2) cross-reaction of immunoglobulin serologies with other endemic flaviruses, such as dengue; (3) persistent viremia and viruria in pregnancy weeks to months after primary exposure; and (4) fetal brain malformations and anomalies preceding the sonographic detection of microcephaly. In this commentary, we discuss screening and diagnostic considerations that are grounded not only in the realities of current obstetrical practice in a largely global population but also in basic immunology and virology. We review recent epidemiological data pertaining to the risk of congenital Zika virus malformations based on trimester of exposure and consider side by side with emerging data demonstrating replication of Zika virus in placental and fetal tissue throughout gestation. We discuss limitations to ultrasound based strategies that rely largely or solely on the detection of microcephaly and provide alternative neurosonographic approaches for the detection of malformations that may precede or occur independent of a small head circumference. This expert review provides information that is of value for the following: (1) obstetrician, maternal-fetal medicine specialist, midwife, patient, and family in cases of suspected Zika virus infection; (2) review of the methodology for laboratory testing to explore the presence of the virus and the immune response; (3) ultrasound-based assessment of the fetus suspected to be exposed to Zika virus with particular emphasis on the central nervous system; and (4) identification of areas ready for development. + Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved. + + + + Eppes + Catherine + C + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. + + + + Rac + Martha + M + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. + + + + Dunn + James + J + + Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX; Department of Pathology and Immunology, Texas Children's Hospital, Houston, TX. + + + + Versalovic + James + J + + Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX; National School for Tropical Medicine, Baylor College of Medicine, Houston, TX; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Department of Pathology and Immunology, Texas Children's Hospital, Houston, TX; Department of Pediatrics, Texas Children's Hospital, Houston, TX. + + + + Murray + Kristy O + KO + + National School for Tropical Medicine, Baylor College of Medicine, Houston, TX; Department of Pediatrics, Texas Children's Hospital, Houston, TX. + + + + Suter + Melissa A + MA + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. + + + + Sanz Cortes + Magda + M + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. + + + + Espinoza + Jimmy + J + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. + + + + Seferovic + Maxim D + MD + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. + + + + Lee + Wesley + W + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. + + + + Hotez + Peter + P + + National School for Tropical Medicine, Baylor College of Medicine, Houston, TX; Department of Pediatrics, Texas Children's Hospital, Houston, TX. + + + + Mastrobattista + Joan + J + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. + + + + Clark + Steven L + SL + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. + + + + Belfort + Michael A + MA + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; National School for Tropical Medicine, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. + + + + Aagaard + Kjersti M + KM + + Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX; National School for Tropical Medicine, Baylor College of Medicine, Houston, TX; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Children's Hospital, Houston, TX. Electronic address: aagaardt@bcm.edu. + + + + eng + + + K99 HD075858 + HD + NICHD NIH HHS + United States + + + + Journal Article + Review + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + + + 2017 + 01 + 23 + +
+ + United States + Am J Obstet Gynecol + 0370476 + 0002-9378 + + AIM + IM + + + Communicable Diseases, Emerging + congenital + diagnosis + epidemiology + + + Epidemics + + + Female + + + Humans + + + Microcephaly + diagnosis + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + epidemiology + + + Prenatal Diagnosis + methods + + + Zika Virus Infection + congenital + diagnosis + epidemiology + + + + Centers for Disease Control and Prevention recommendations + Dengue virus + Food and Drug Administration regulations + Zika virus + Zika virus in pregnancy + amniotic fluid analysis + counseling of the patient at risk + epidemiology + fetal magnetic resonance imaging + flaviviridae family + head circumference + immunoglobulin M serology + microcephaly + neurosonography + perinatal viral infection + plaque reduction neutralization test + reverse transcriptase–polymerase chain reaction + transplacental transmission of viruses + viral culture + viral detection with polymerase chain reaction + viral detection with real-time reverse transcriptase–polymerase chain reaction + +
+ + + + 2016 + 12 + 18 + + + 2017 + 01 + 05 + + + 2017 + 01 + 17 + + + 2017 + 1 + 28 + 6 + 0 + + + 2017 + 6 + 8 + 6 + 0 + + + 2017 + 1 + 28 + 6 + 0 + + + ppublish + + 28126366 + S0002-9378(17)30127-8 + 10.1016/j.ajog.2017.01.020 + + +
+ + + + + 28112162 + + 2017 + 02 + 20 + +
+ + 2045-2322 + + 7 + + 2017 + Jan + 23 + + + Scientific reports + Sci Rep + + Zika virus disrupts molecular fingerprinting of human neurospheres. + + 40780 + + 10.1038/srep40780 + + Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it. + + + + Garcez + Patricia P + PP + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Nascimento + Juliana Minardi + JM + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + Institute of Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil. + + + + de Vasconcelos + Janaina Mota + JM + + Center for Technological Innovation, Evandro Chagas Institute, Belém, Brazil. + + + + Madeiro da Costa + Rodrigo + R + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + + Delvecchio + Rodrigo + R + + Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Trindade + Pablo + P + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + + Loiola + Erick Correia + EC + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + + Higa + Luiza M + LM + + Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Cassoli + Juliana S + JS + + Institute of Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil. + + + + Vitória + Gabriela + G + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + + Sequeira + Patricia C + PC + + Institute Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. + + + + Sochacki + Jaroslaw + J + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + + Aguiar + Renato S + RS + + Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Fuzii + Hellen Thais + HT + + Federal University of Pará, Belém, Brazil. + + + + de Filippis + Ana M Bispo + AM + + Institute Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. + + + + da Silva Gonçalves Vianez Júnior + João Lídio + JL + + Center for Technological Innovation, Evandro Chagas Institute, Belém, Brazil. + + + + Tanuri + Amilcar + A + + Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Martins-de-Souza + Daniel + D + + Institute of Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil. + + + + Rehen + Stevens K + SK + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + + + 2017 + 01 + 23 + +
+ + England + Sci Rep + 101563288 + 2045-2322 + + + + Cell Metab. 2012 Sep 5;16(3):311-21 + 22958918 + + + Mol Biol Evol. 2013 Apr;30(4):772-80 + 23329690 + + + Cell Stem Cell. 2016 May 5;18(5):591-6 + 27038591 + + + Bioinformatics. 2012 Jun 15;28(12):1647-9 + 22543367 + + + Cell. 2016 May 19;165(5):1238-54 + 27118425 + + + Cell Stem Cell. 2016 Nov 3;19(5):593-598 + 27545505 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + PLoS Pathog. 2014 Jun 26;10(6):e1004199 + 24968230 + + + Genome Biol. 2013 Apr 25;14(4):R36 + 23618408 + + + Nucleic Acids Res. 2009 Jan;37(Database issue):D412-6 + 18940858 + + + Nat Methods. 2014 Feb;11(2):167-70 + 24336358 + + + Nucleic Acids Res. 2009 Oct;37(19):e131 + 19706733 + + + Dev Dyn. 2007 May;236(5):1347-57 + 17393485 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Nucleic Acids Res. 2009 Jan;37(1):1-13 + 19033363 + + + Nat Biotechnol. 2010 May;28(5):511-5 + 20436464 + + + Stem Cells Transl Med. 2013 Nov;2(11):862-70 + 24113065 + + + Mol Biol Evol. 2013 Dec;30(12):2725-9 + 24132122 + + + Emerg Infect Dis. 2007 May;13(5):764-7 + 17553261 + + + Cell Stem Cell. 2016 Aug 4;19(2):258-65 + 27162029 + + + PLoS One. 2013 Jun 24;8(6):e67437 + 23826300 + + + Toxicol In Vitro. 2015 Oct;29(7):1369-76 + 26004619 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Adv Virol. 2011;2011:514681 + 22312344 + + + J Viral Hepat. 2003 Jul;10(4):241-8 + 12823589 + + + Wiley Interdiscip Rev Dev Biol. 2013 Jul;2(4):461-78 + 24014418 + + + J Virol. 2010 Jul;84(13):6810-24 + 20392846 + + + Nature. 2013 Sep 19;501(7467):373-9 + 23995685 + + + Bioinformatics. 2014 May 1;30(9):1312-3 + 24451623 + + + Cytometry A. 2007 Mar;71(3):125-31 + 17252584 + + + FASEB J. 2008 Aug;22(8):3001-9 + 18445785 + + + Nat Neurosci. 2016 May;19(5):690-6 + 27019013 + + + J Virol. 2011 Jul;85(14):6882-92 + 21543503 + + + Nat Rev Microbiol. 2016 Nov;14 (11):707-715 + 27573577 + + + Semin Immunol. 2007 Feb;19(1):33-40 + 17336545 + + + Cell Stem Cell. 2016 May 5;18(5):559-60 + 27152436 + + + Nat Protoc. 2012 Mar 01;7(3):562-78 + 22383036 + + + PLoS Pathog. 2014 Sep 04;10(9):e1004319 + 25188232 + + + FEBS Lett. 2013 Jul 11;587(14):2150-7 + 23714367 + + + Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13517-22 + 19628699 + + + Nucleic Acids Res. 2016 Oct 14;44(18):8610-8620 + 27580721 + + + Nat Protoc. 2009;4(1):44-57 + 19131956 + + + Cell Transplant. 2012;21(7):1547-59 + 21975034 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + Cell Res. 2016 Jun;26(6):645-54 + 27174054 + + + Bioinformatics. 2002 Mar;18(3):502-4 + 11934758 + + + J Immunol. 2013 Mar 1;190(5):2217-28 + 23365087 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Nat Methods. 2012 Jul 30;9(8):772 + 22847109 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + J Virol. 2009 Sep;83(18):9329-38 + 19587044 + + + RNA Biol. 2011 Nov-Dec;8(6):1173-86 + 21957497 + + + Nucleic Acids Res. 2013 Jun;41(11):5626-38 + 23599003 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + +
+ + + + 2016 + 08 + 01 + + + 2016 + 12 + 09 + + + 2017 + 1 + 24 + 6 + 0 + + + 2017 + 1 + 24 + 6 + 0 + + + 2017 + 1 + 24 + 6 + 0 + + + epublish + + 28112162 + srep40780 + 10.1038/srep40780 + PMC5256095 + + +
+ + + + + 28108286 + + 2017 + 10 + 10 + + + 2017 + 11 + 30 + +
+ + 1090-2104 + + 492 + 4 + + 2017 + 10 + 28 + + + Biochemical and biophysical research communications + Biochem. Biophys. Res. Commun. + + The impact of Zika virus in the brain. + + 603-607 + + S0006-291X(17)30108-0 + 10.1016/j.bbrc.2017.01.074 + + The recent outbreak of ZIKV in Brazil called the attention of the world because the effects of viral infection in the brain under development in fetuses. Consequences of vertical infection comprise brain malformation, especially microcephaly, eye and musculoskeletal abnormalities, among others. In adults, outcomes of infection include meningoencephalitis and Guillain-Barré Syndrome. Recent data specific suggest that neural progenitor cells are the main targets of ZIKV infection, causing massive cellular death and impairment in the neurogenesis process. Here we review the fetal and adult brain damage after ZIKV exposure, exploring models to study the mechanisms underlying the pathways related to microcephaly and cell death. + Copyright © 2017 Elsevier Inc. All rights reserved. + + + + Russo + Fabiele Baldino + FB + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo, 05508-270, Brazil. + + + + Beltrão-Braga + Patricia Cristina Baleeiro + PCB + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo, 05508-270, Brazil; School of Arts Sciences and Humanities, Department of Obstetrics, São Paulo, SP, 03828-000, Brazil. Electronic address: patriciacbbbraga@usp.br. + + + + eng + + Journal Article + Review + Research Support, Non-U.S. Gov't + + + 2017 + 01 + 17 + +
+ + United States + Biochem Biophys Res Commun + 0372516 + 0006-291X + + IM + + + Animals + + + Apoptosis + + + Brain + pathology + virology + + + Encephalitis, Viral + pathology + virology + + + Female + + + Humans + + + Neural Stem Cells + pathology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + pathology + virology + + + Zika Virus + physiology + + + Zika Virus Infection + pathology + virology + + + + Brain damage + Flavivirus + Microcephaly + Neuroprogenitor cells + ZIKV + Zika + +
+ + + + 2016 + 12 + 09 + + + 2017 + 01 + 16 + + + 2017 + 1 + 22 + 6 + 0 + + + 2017 + 10 + 11 + 6 + 0 + + + 2017 + 1 + 22 + 6 + 0 + + + ppublish + + 28108286 + S0006-291X(17)30108-0 + 10.1016/j.bbrc.2017.01.074 + + +
+ + + + + 28102136 + + 2017 + 02 + 23 + + + 2017 + 02 + 23 + +
+ + 1474-547X + + 389 + 10065 + + 2017 + 01 + 14 + + + Lancet (London, England) + Lancet + + Zika rash and increased risk of congenital brain abnormalities - Authors' reply. + + 152 + + S0140-6736(17)30015-6 + 10.1016/S0140-6736(17)30015-6 + + + Victora + Cesar G + CG + + Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil. Electronic address: cvictora@equidade.org. + + + + Castro + Marcia C + MC + + Harvard T H Chan School of Public Health, Boston, MA, USA. + + + + França + Giovanny V A + GV + + Secretariat of Health Surveillance, Ministry of Health, Brasilia, Brazil. + + + + Schuler-Faccini + Lavinia + L + + Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil. + + + + Barros + Fernando C + FC + + Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil; Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil. + + + + eng + + Letter + Comment + + + 2017 + 01 + 13 + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Lancet. 2017 Jan 14;389(10065):151-152 + 28102133 + + + + + Brain + + + Exanthema + + + Humans + + + Microcephaly + + + Pregnancy Complications, Infectious + + + Risk + + + Zika Virus + + + Zika Virus Infection + + +
+ + + + 2016 + 09 + 23 + + + 2016 + 10 + 10 + + + 2017 + 1 + 20 + 6 + 0 + + + 2017 + 1 + 20 + 6 + 0 + + + 2017 + 2 + 24 + 6 + 0 + + + ppublish + + 28102136 + S0140-6736(17)30015-6 + 10.1016/S0140-6736(17)30015-6 + + +
+ + + + + 28099714 + + 2017 + 05 + 16 + + + 2017 + 07 + 21 + +
+ + 1879-3479 + + 136 + 1 + + 2017 + Jan + + + International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics + Int J Gynaecol Obstet + + Zika virus infection in Brazil and human rights obligations. + + 105-110 + + 10.1002/ijgo.12018 + + The February 2016 WHO declaration that congenital Zika virus syndrome constitutes a Public Health Emergency of International Concern reacted to the outbreak of the syndrome in Brazil. Public health emergencies can justify a spectrum of human rights responses, but in Brazil, the emergency exposed prevailing inequities in the national healthcare system. The government's urging to contain the syndrome, which is associated with microcephaly among newborns, is confounded by lack of reproductive health services. Women with low incomes in particular have little access to such health services. The emergency also illuminates the harm of restrictive abortion legislation, and the potential violation of human rights regarding women's health and under the UN Conventions on the Rights of the Child and on the Rights of Persons with Disabilities. Suggestions have been proposed by which the government can remedy the widespread healthcare inequities among the national population that are instructive for other countries where congenital Zika virus syndrome is prevalent. + © 2016 International Federation of Gynecology and Obstetrics. + + + + Diniz + Debora + D + + Faculty of Law, University of Brasilia, Brasilia, Brazil. + + + + Gumieri + Sinara + S + + Anis Institute of Bioethics, Brasilia, Brazil. + + + + Bevilacqua + Beatriz Galli + BG + + Ipas, Rio de Janeiro, Brazil. + + + + Cook + Rebecca J + RJ + + Faculty of Law, Faculty of Medicine and Joint Centre for Bioethics, University of Toronto, Toronto, ON, Canada. + + + + Dickens + Bernard M + BM + + Faculty of Law, Faculty of Medicine and Joint Centre for Bioethics, University of Toronto, Toronto, ON, Canada. + + + + eng + + Journal Article + + + 2016 + 11 + 03 + +
+ + United States + Int J Gynaecol Obstet + 0210174 + 0020-7292 + + IM + + + Brazil + epidemiology + + + Developing Countries + + + Female + + + Health Promotion + + + Healthcare Disparities + + + Human Rights + legislation & jurisprudence + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Poverty + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Public Health + + + Zika Virus Infection + epidemiology + + + + Children's rights + Congenital Zika virus syndrome + Disability rights + Human rights + Public health + Women's rights + Zika infection + +
+ + + + 2017 + 1 + 19 + 6 + 0 + + + 2017 + 1 + 19 + 6 + 0 + + + 2017 + 5 + 17 + 6 + 0 + + + ppublish + + 28099714 + 10.1002/ijgo.12018 + + +
+ + + + + 28077143 + + 2017 + 10 + 27 + + + 2017 + 10 + 27 + +
+ + 1755-8794 + + 10 + 1 + + 2017 + Jan + 11 + + + BMC medical genomics + BMC Med Genomics + + Pregnant women carrying microcephaly foetuses and Zika virus contain potentially pathogenic microbes and parasites in their amniotic fluid. + + 5 + + 10.1186/s12920-016-0242-1 + + Microcephaly has become a major public health problem in Brazil. The total number of newborns with microcephaly was reported to be >4000 in June 2016. Studies suggest that Zika Virus is a major cause of new microcephaly cases in Brazil. Inside the uterus, the foetus is surrounded by the Amniotic Fluid, a proximal fluid that contains foetal and maternal cells as well as microorganisms and where Zika Virus was already found. + A previous study reported the presence of the Zika Virus in the amniotic fluid (collected in the 28th gestational week) of two pregnant women carrying microcephaly foetuses in Brazil. The virus was detected by means of real-time PCR and metatranscriptomic analysis. We compared the microbiome of these two cases with metatranscriptomic sequences from 16 pregnant women collected at various times in their pregnancies CONCLUSION: Several strains of bacteria (e.g., Streptococcus and Propionibacterium) found in Amniotic Fluid may be involved in neurological diseases. When the foetus is infected by the Zika Virus, due to neurological damage, they do not move inside the uterus, thus changing the Amniotic Fluid environment, potentially leading to secondary problems. Zika infection could also lead to an immunodeficient state, making bacterial colonization of the foetuses easier. An altered microbial composition during pregnancy may also result in harmful secondary metabolite production from certain microbes that further impair foetal brain development. However, these observations of potentially harmful microbial species are correlations and thus cannot be assumed to be causative agents of (microcephaly) disease. In our study, microbial and parasitic diversity of the Amniotic Fluid was lower in patients infected by ZIKV, compared to that of Prenatal and Preterm controls. The present study was a first attempt to shed light on the microbial and parasitic diversity associated with ZIKV-infected pregnant women bearing microcephaly foetuses, and the presence of diverse microbial and parasite communities in the Amniotic Fluid suggests a poor health status of both the pregnant women and the foetuses they carry. + + + + Tschoeke + Diogo Antonio + DA + + Instituto de Biologia, CCS, Laboratório de Microbiologia, Anexo ao Bloco A, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, 21941-902, Brazil. + + + Laboratório de Sistemas Avançados de Gestão de Produção-SAGE-COPPE, Centro de Gestão Tecnológica-CT2, UFRJ, Rio de Janeiro, RJ, Brazil. + + + Núcleo em Ecologia e Desenvolvimento Sócio-Ambiental de Macaé (NUPEM), Universidade Federal do Rio de Janeiro, Macaé, RJ, Brazil. + + + + de Oliveira + Louisi Souza + LS + + Instituto de Biologia, CCS, Laboratório de Microbiologia, Anexo ao Bloco A, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, 21941-902, Brazil. + + + + Leomil + Luciana + L + + Instituto de Biologia, CCS, Laboratório de Microbiologia, Anexo ao Bloco A, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, 21941-902, Brazil. + + + + Tanuri + Amilcar + A + + Instituto de Biologia, CCS, Laboratório de Virologia Molecular, Bloco A, Ilha do Fundão, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. + + + + Thompson + Fabiano Lopes + FL + + Instituto de Biologia, CCS, Laboratório de Microbiologia, Anexo ao Bloco A, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, 21941-902, Brazil. fabianothompson1@gmail.com. + + + Laboratório de Sistemas Avançados de Gestão de Produção-SAGE-COPPE, Centro de Gestão Tecnológica-CT2, UFRJ, Rio de Janeiro, RJ, Brazil. fabianothompson1@gmail.com. + + + + eng + + Case Reports + Journal Article + + + 2017 + 01 + 11 + +
+ + England + BMC Med Genomics + 101319628 + 1755-8794 + + IM + + + Genome Res. 2011 Sep;21(9):1552-60 + 21690186 + + + Bioinformatics. 2014 Mar 1;30(5):614-20 + 24142950 + + + PLoS One. 2011 Mar 09;6(3):e17288 + 21408061 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Lancet Infect Dis. 2015 Oct;15(10):1226-35 + 26364132 + + + ISME J. 2009 Aug;3(8):944-54 + 19369970 + + + J Infect Dis. 2008 Feb 1;197(3):435-8 + 18199029 + + + BMC Med Genomics. 2015 Oct 22;8:67 + 26493725 + + + Front Immunol. 2014 Nov 27;5:595 + 25505898 + + + Curr HIV/AIDS Rep. 2012 Mar;9(1):44-51 + 22193889 + + + Nat Rev Genet. 2012 Mar 13;13(4):260-70 + 22411464 + + + PLoS Negl Trop Dis. 2008 Apr 30;2(4):e217 + 18446236 + + + PLoS One. 2008 Aug 26;3(8):e3056 + 18725970 + + + PLoS Biol. 2013;11(8):e1001631 + 23976878 + + + Pediatr Res. 2015 Jan;77(1-2):189-95 + 25310759 + + + Infect Dis Obstet Gynecol. 2010;2010:737425 + 21197076 + + + Dev Med Child Neurol. 2014 Aug;56(8):732-41 + 24617602 + + + Genome Biol. 2014;15(11):510 + 25413302 + + + Semin Fetal Neonatal Med. 2012 Feb;17(1):2-11 + 22137615 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Mucosal Immunol. 2014 Jul;7(4):983-94 + 24399150 + + + + + Amniotic Fluid + microbiology + parasitology + + + Female + + + Humans + + + Microcephaly + microbiology + parasitology + virology + + + Pregnancy + + + Zika Virus + physiology + + + + Metatranscriptomics + Microbiome + Microchepaly + Zika Virus + +
+ + + + 2016 + 06 + 22 + + + 2016 + 12 + 27 + + + 2017 + 1 + 13 + 6 + 0 + + + 2017 + 1 + 13 + 6 + 0 + + + 2017 + 10 + 28 + 6 + 0 + + + epublish + + 28077143 + 10.1186/s12920-016-0242-1 + 10.1186/s12920-016-0242-1 + PMC5225515 + + +
+ + + + + 28076569 + + 2017 + 09 + 18 + + + 2017 + 09 + 18 + +
+ + 1678-2925 + + 79 + 6 + + 2016 Nov-Dec + + + Arquivos brasileiros de oftalmologia + Arq Bras Oftalmol + + Optical coherence tomography of macular atrophy associated with microcephaly and presumed intrauterine Zika virus infection. + + 400-401 + + S0004-27492016000600400 + 10.5935/0004-2749.20160112 + + This case report describes the retinal optical coherence tomography (OCT) findings in a microcephalic infant with macular atrophy presumably caused by intrauterine Zika virus infection. OCT demonstrated atrophy of the outer retinal layers and choriocapillaris, including the outer nuclear layer and ellipsoid zone, associated with retinal pigment epithelium hyper-reflectivity and increased OCT penetration into deeper layers of the choroid and sclera. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with the Zika virus. It is becoming increasingly difficult to ignore the upsurge in congenital microcephaly observed in Brazil. Recently, ocular findings in infants with microcephaly associated with intrauterine Zika virus infection have been described. This is the first report of OCT imaging of macular atrophy in a child with presumed Zika virus infection-associated microcephaly. + + + + Campos + Adriana Gondim de Moura + AG + + Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil. + + + + Lira + Rodrigo Pessoa Cavalcanti + RP + + Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil. + + + + Arantes + Tiago Eugenio Faria E + TE + + Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. + + + + eng + + Case Reports + +
+ + Brazil + Arq Bras Oftalmol + 0400645 + 0004-2749 + + IM + + + Atrophy + + + Eye Infections, Viral + diagnostic imaging + + + Female + + + Humans + + + Infant, Newborn + + + Macula Lutea + diagnostic imaging + pathology + + + Male + + + Microcephaly + virology + + + Retinal Diseases + diagnostic imaging + virology + + + Tomography, Optical Coherence + + + Zika Virus Infection + complications + + +
+ + + + 2016 + 03 + 29 + + + 2016 + 06 + 09 + + + 2017 + 1 + 12 + 6 + 0 + + + 2017 + 1 + 12 + 6 + 0 + + + 2017 + 9 + 19 + 6 + 0 + + + ppublish + + 28076569 + S0004-27492016000600400 + 10.5935/0004-2749.20160112 + + +
+ + + + + 28074379 + + 2017 + 08 + 29 + + + 2017 + 11 + 04 + +
+ + 1867-108X + + 35 + 3 + + 2017 + Mar + + + Japanese journal of radiology + Jpn J Radiol + + Neuroimaging findings of congenital Zika virus infection: a pictorial essay. + + 89-94 + + 10.1007/s11604-016-0609-4 + + Zika virus (ZIKV) is a mosquito-borne arbovirus from the Flaviviridae family. It had caused several epidemics since its discovery in 1947, but there was no significant attention to this virus until the recent outbreak in Brazil in 2015. The main concern is the causal relationship between prenatal ZIKV infection and congenital microcephaly, which has been confirmed recently. Moreover, ZIKV may cause other central nervous system abnormalities such as brain parenchymal atrophy with secondary ventriculomegaly, intracranial calcification, malformations of cortical development (such as polymicrogyria, and lissencephaly-pachygyria), agenesis/hypoplasia of the corpus callosum, cerebellar and brainstem hypoplasia, sensorineural hearing-loss, and ocular abnormalities as well as arthrogryposis in the infected fetuses. Postnatal (acquired) ZIKV infection usually has an asymptomatic or mildly symptomatic course, while prenatal (congenital) ZIKV infection has a more severe course and may cause severe brain anomalies that are described as congenital Zika syndrome. In this pictorial essay, we aim to illustrate the prenatal and postnatal neuroimaging findings that may be seen in fetuses and neonates with congenital Zika syndrome, and will discuss possible radiological differential diagnoses. A detailed knowledge of these findings is paramount for an early correct diagnosis, prognosis determination, and counseling of the affected children and families. + + + + Zare Mehrjardi + Mohammad + M + http://orcid.org/0000-0001-5793-5323 + + Department of Radiology, Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. zare@sbmu.ac.ir. + + + + Poretti + Andrea + A + + Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. + + + + Huisman + Thierry A G M + TA + + Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. + + + + Werner + Heron + H + + Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, RJ, Brazil. + + + + Keshavarz + Elham + E + + Department of Radiology, Mahdieh Women's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. + + + + Araujo Júnior + Edward + E + + Department of Obstetrics, Paulista School of Medicine, Federal University of São Paulo (EPM-UNIFESP), São Paulo, SP, Brazil. + + + + eng + + Journal Article + + + 2017 + 01 + 10 + +
+ + Japan + Jpn J Radiol + 101490689 + 1867-1071 + + IM + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + MMWR Morb Mortal Wkly Rep. 2016 Dec 02;65(47):1343-1348 + 27906905 + + + Jpn J Radiol. 2017 Jan;35(1):41-42 + 27830429 + + + Jpn J Radiol. 2016 Dec;34(12 ):765-770 + 27714487 + + + Ultrasound Obstet Gynecol. 2016 May;47(5):657-60 + 26923098 + + + Prenat Diagn. 2016 Sep;36(9):882-7 + 27491635 + + + Am J Med Genet A. 2013 Nov;161A(11):2726-33 + 24124000 + + + JAMA Pediatr. 2017 Mar 1;171(3):288-295 + 27812690 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Pediatr Radiol. 2016 Jun;46(7):1032-9 + 27090801 + + + Prenat Diagn. 2016 Aug;36(8):785-9 + 27316349 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + AJNR Am J Neuroradiol. 2016 Aug 4;:null + 27492074 + + + + + Humans + + + Microcephaly + diagnostic imaging + virology + + + Neuroimaging + methods + + + Zika Virus + isolation & purification + + + Zika Virus Infection + congenital + diagnostic imaging + + + + Congenital + Microcephaly + Neuroimaging + Radiology + Zika virus (ZIKV) + +
+ + + + 2016 + 11 + 25 + + + 2016 + 12 + 27 + + + 2017 + 1 + 12 + 6 + 0 + + + 2017 + 8 + 30 + 6 + 0 + + + 2017 + 1 + 12 + 6 + 0 + + + ppublish + + 28074379 + 10.1007/s11604-016-0609-4 + 10.1007/s11604-016-0609-4 + + +
+ + + + + 28073577 + + 2018 + 01 + 16 + + + 2018 + 01 + 16 + +
+ + 1989-7286 + + 92 + 2 + + 2017 + Feb + + + Archivos de la Sociedad Espanola de Oftalmologia + Arch Soc Esp Oftalmol + + Zika virus. A teratogenic agent for the eyes. + + 51-53 + + S0365-6691(16)30239-8 + 10.1016/j.oftal.2016.11.010 + + + Pinazo-Durán + M D + MD + + Unidad de Investigación Oftalmológica Santiago Grisolía (FISABIO). Unidad de Oftalmobiología Celular y Molecular, Departamento de Cirugía, Facultad de Medicina y Odontología, Universidad de Valencia, Valencia, España; Nodo de Valencia 12/0034/0008, Red Temática de Investigación Cooperativa del Instituto de Salud Carlos III (OFTARED). Electronic address: pinazoduran@yahoo.es. + + + + Silva + E D + ED + + IBILI, Facultad de Medicina, Universidad de Coimbra, Coimbra, Portugal; Departamento de Oftalmología, Centro Hospitalario Lisboa Norte (CHLN), Lisboa, Portugal; Centro Quirúrgico de Coimbra, Coimbra, Portugal. + + + + eng + spa + + Journal Article + + El virus del Zika. Un agente teratogénico ocular. + + 2017 + 01 + 07 + +
+ + Spain + Arch Soc Esp Oftalmol + 1304603 + 0365-6691 + + IM + + + Abnormalities, Multiple + etiology + + + Brazil + epidemiology + + + Communicable Diseases, Emerging + + + Disease Outbreaks + + + Eye Abnormalities + etiology + + + Female + + + Global Health + + + Humans + + + Infant, Newborn + + + Infectious Disease Transmission, Vertical + + + Macula Lutea + pathology + + + Male + + + Microcephaly + etiology + + + Neonatal Screening + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Tears + virology + + + Zika Virus + isolation & purification + pathogenicity + + + Zika Virus Infection + complications + congenital + epidemiology + transmission + + +
+ + + + 2016 + 11 + 19 + + + 2016 + 11 + 21 + + + 2017 + 1 + 12 + 6 + 0 + + + 2018 + 1 + 18 + 6 + 0 + + + 2017 + 1 + 12 + 6 + 0 + + + ppublish + + 28073577 + S0365-6691(16)30239-8 + 10.1016/j.oftal.2016.11.010 + + +
+ + + + + 28045216 + + 2017 + 12 + 26 + + + 2017 + 12 + 26 + +
+ + 1600-0897 + + 77 + 2 + + 2017 + Feb + + + American journal of reproductive immunology (New York, N.Y. : 1989) + Am. J. Reprod. Immunol. + + Zika virus and pregnancy: An overview. + 10.1111/aji.12616 + + In May 2015, the first episodes of Zika virus infection of the Latin America were confirmed in Brazil, where currently 196 976 cases were reported. The main route of transmission occurs by Aedes mosquitoes, and the most common symptoms are maculopapular rash, fever, conjunctivitis, polyarthralgia, and periarticular edema. However, the infection is asymptomatic in 80% of the cases. The congenital infection is characterized when the transmission to the fetus occurs during pregnancy, but the mechanisms of how the virus infects the placenta remain unclear. Anatomopathological findings were described in first- and third-trimester human placentas; however, the major affected tissue of the baby is the neural. Several clinical situations were listed in these fetuses, such as neurological, ophthalmological, auditory, and articular alterations. The World Health Organization proposed a new congenital syndrome caused by Zika virus. The virus has an important neurotropism and the main manifestation observed in the syndrome is microcephaly, which is usually severe and associated with other neurological injuries. The appearance of sudden rash in pregnant women determines immediate investigation through RT-PCR and serological analysis. Moreover, the prevention consists in using repellents and avoiding endemic areas, considering that the vaccine is still under development. + © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. + + + + de Carvalho + Newton Sérgio + NS + http://orcid.org/0000-0001-7561-4566 + + Department of Gynecology and Obstetrics, Infectious Diseases in Gynecology and Obstetrics Sector, Clinics Hospital, Federal University of Parana, Curitiba, PR, Brazil. + + + + de Carvalho + Beatriz Freitas + BF + + Pontifical Catholic University of Parana, Curitiba, PR, Brazil. + + + + Dóris + Bruna + B + + Pontifical Catholic University of Parana, Curitiba, PR, Brazil. + + + + Silverio Biscaia + Evellyn + E + + Pontifical Catholic University of Parana, Curitiba, PR, Brazil. + + + + Arias Fugaça + Cyllian + C + + Pontifical Catholic University of Parana, Curitiba, PR, Brazil. + + + + de Noronha + Lúcia + L + + Pontifical Catholic University of Parana, Curitiba, PR, Brazil. + + + + eng + + Journal Article + Review + + + 2017 + 01 + 03 + +
+ + Denmark + Am J Reprod Immunol + 8912860 + 1046-7408 + + IM + + + Animals + + + Asymptomatic Diseases + + + Brazil + epidemiology + + + Female + + + Humans + + + Microcephaly + epidemiology + + + Nervous System + pathology + virology + + + Nervous System Malformations + epidemiology + + + Placenta + immunology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Viral Tropism + + + World Health Organization + + + Zika Virus + physiology + + + Zika Virus Infection + epidemiology + + + + Zika virus + congenital malformations + microcephaly + obstetrician + pregnancy + +
+ + + + 2016 + 10 + 30 + + + 2016 + 11 + 10 + + + 2017 + 1 + 4 + 6 + 0 + + + 2017 + 12 + 27 + 6 + 0 + + + 2017 + 1 + 4 + 6 + 0 + + + ppublish + + 28045216 + 10.1111/aji.12616 + + +
+ + + + + 28035106 + + 2017 + 04 + 14 + + + 2017 + 04 + 14 + +
+ + 0972-9062 + + 53 + 4 + + 2016 Oct-Dec + + + Journal of vector borne diseases + J Vector Borne Dis + + Zika virus infection: Past and present of another emerging vector-borne disease. + + 305-311 + + + Zika virus infection is an emerging mosquito-borne disease, first identified in Uganda in 1947. It is caused by the Zika arbovirus, and transmitted by the bites of infected mosquitoes of the genus Aedes. For almost half a century, the Zika virus was reported as the causative agent of sporadic human infections. In 2007, the Zika virus emerged outside Asia and Africa causing an epidemic on the Island of Yap in Micronesia. The manifestation of the newly acquired human infection varies from asymptomatic to self-limiting acute febrile illness with symptoms and clinical features similar to those caused by the Dengue virus ('Dengue-like syndrome'). The real-time PCR and serological methods have been successfully applied for the diagnosis of the disease. The treatment is symptomatic, since there is no specific antiviral treatment or a vaccine. During the recent outbreaks in French Polynesia and Brazil, incidents of Guillain-Barrι syndrome and microcephaly were associated with Zika virus infection, giving rise to fears of further global spread of the virus. Prevention and vector control strategies have to be urgently implemented by national health authorities in order to contain future outbreaks in vulnerable populations. This review summarizes the existing information on Zika virus characteristics, pathogenesis and epidemiology, the available methods for the diagnosis of Zika virus infection and recent approaches for prevention and control. + + + + Sakkas + Hercules + H + + Microbiology Department, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece. + + + + Economou + Vangelis + V + + Laboratory of Hygiene of Foods of Animal Origin, Faculty of Veterinary Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece. + + + + Papadopoulou + Chrissanthy + C + + Microbiology Department, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece. + + + + eng + + Journal Article + Review + +
+ + India + J Vector Borne Dis + 101212761 + 0972-9062 + + IM + + + Communicable Diseases, Emerging + complications + diagnosis + epidemiology + pathology + + + Disease Transmission, Infectious + prevention & control + + + Global Health + + + Guillain-Barre Syndrome + epidemiology + etiology + + + Humans + + + Microcephaly + epidemiology + etiology + + + Mosquito Control + methods + + + Mosquito Vectors + growth & development + + + Zika Virus Infection + complications + diagnosis + epidemiology + pathology + + +
+ + + + 2016 + 12 + 31 + 6 + 0 + + + 2016 + 12 + 31 + 6 + 0 + + + 2017 + 4 + 15 + 6 + 0 + + + ppublish + + 28035106 + JVectorBorneDis_2016_53_4_305_197260 + + +
+ + + + + 28032327 + + 2017 + 11 + 03 + + + 2017 + 11 + 03 + +
+ + 0065-2598 + + 972 + + 2017 + + + Advances in experimental medicine and biology + Adv. Exp. Med. Biol. + + Emerging Zika Virus Infection: A Rapidly Evolving Situation. + + 61-86 + + 10.1007/5584_2016_187 + + Zika virus is a mosquito-borne flavivirus, firstly identified in Uganda and responsible for sporadic human cases in Africa and Asia until recently, when large outbreak occurred in Pacific Ocean and the Americas. Since the main vectors during its spread outside of Africa have been Ae. albopictus and Ae. aegypti mosquitoes, which are widely distributed all over the world, there is urgent need for a coordinated response for prevention and spread of ZIKV epidemics.Despite clinical manifestation of Zika virus infection are usually mild and self limiting, there are reports suggesting, during the recent epidemic, an association of ZIKV infection with severe consequences, including fetal/newborn microcephaly, due to vertical in utero transmission, autoimmune-neurological presentations including cranial nerve dysfunction, and Guillain-Barré Syndrome in adults. The primary mode of transmission of Zika virus between humans is through the bite of an infected female mosquito of the Aedes genus, but also sexual and blood transfusion transmission may occur. Moreover, a case of non-sexual spread from one person to another has been described, indicating that we still have more to learn about Zika transmission.Biological basis for pathogenetic effects are under investigation. Laboratory diagnosis is challenging since, so far, there are no "gold standard" diagnostic tools, and the low and short viremia in the acute phase, and together with the high cross-reactivity among the members of flavivirus genus are the most challenging aspects to be overcome. + + + + Bordi + Licia + L + + Laboratory of virology, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Via Portuense 292, 00149, Rome, Italy. + + + + Avsic-Zupanc + Tatjana + T + + Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. + + + + Lalle + Eleonora + E + + Laboratory of virology, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Via Portuense 292, 00149, Rome, Italy. + + + + Vairo + Francesco + F + + Emerging and Reemerging Infectious Disease Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy. + + + + Capobianchi + Maria Rosaria + MR + + Laboratory of virology, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Via Portuense 292, 00149, Rome, Italy. maria.capobianchi@inmi.it. + + + + da Costa Vasconcelos + Pedro Fernando + PF + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará, Brazil. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + +
+ + United States + Adv Exp Med Biol + 0121103 + 0065-2598 + + IM + + + Adv Exp Med Biol. 2017;972:141 + 28255910 + + + + + Animals + + + Central Nervous System Infections + pathology + virology + + + Communicable Diseases, Emerging + virology + + + Disease Outbreaks + + + Disease Reservoirs + + + Global Health + trends + + + Humans + + + Infectious Disease Transmission, Vertical + + + Insect Vectors + + + Microcephaly + virology + + + Phylogeny + + + Sexually Transmitted Diseases, Viral + + + Zika Virus + genetics + + + Zika Virus Infection + epidemiology + pathology + transmission + virology + + + + Clinical Manifestation + Diagnosis + Pathogenetic Effects + Phylogenesis + Spread + Transmission + Zika Virus + +
+ + + + 2016 + 12 + 30 + 6 + 0 + + + 2017 + 11 + 4 + 6 + 0 + + + 2016 + 12 + 30 + 6 + 0 + + + ppublish + + 28032327 + 10.1007/5584_2016_187 + + +
+ + + + + 28017252 + + 2017 + 05 + 30 + + + 2017 + 08 + 17 + +
+ + 1878-5883 + + 372 + + 2017 + Jan + 15 + + + Journal of the neurological sciences + J. Neurol. Sci. + + Microcephaly and arthrogryposis multiplex congenita: The full-blown CNS spectrum in newborns with ZIKV infection. + + 73-74 + + S0022-510X(16)30732-8 + 10.1016/j.jns.2016.11.030 + + The recent alarming statements concerning the newborn ZIKV-induced microcephaly epidemics in the Northeast of Brazil, released by the Brazilian Ministry of Health, as well as important international health agencies, such as the World Health Organization and the Pan American Health Organization, raised many "why and how" questions so far, that will hopefully be scientifically answered, as more researches in that regard come up in the long term. In this paper, we describe another potentially ZIKV-induced central nervous system and musculoskeletal disorder that has accompanied microcephaly in these children: atrhogryposis multiplex congenita. The goal is to bring up some hypotheses for possible underlying molecular mechanisms based on published data taken from animal models, such as ovine and cattle, which once infected by other types of arboviroses and viruses that also belong to the Flaviviridae family, presented, too, with the full-blown CNS spectrum of malformations at birth. + Copyright © 2016 Elsevier B.V. All rights reserved. + + + + Leyser + Marcio + M + + Federal Fluminense University, Antônio Pedro University Hospital, 24033-900, Niterói, Rio de Janeiro, Brazil. Electronic address: marcioley@icloud.com. + + + + Fernandes + Alexandre + A + + Federal Fluminense University, Antônio Pedro University Hospital, 24033-900, Niterói, Rio de Janeiro, Brazil. + + + + Passos + Pamela + P + + Federal Fluminense University, Antônio Pedro University Hospital, 24033-900, Niterói, Rio de Janeiro, Brazil. + + + + Pupe + Camila + C + + Federal Fluminense University, Antônio Pedro University Hospital, 24033-900, Niterói, Rio de Janeiro, Brazil. + + + + Matta + Andre Pc + AP + + Federal Fluminense University, Antônio Pedro University Hospital, 24033-900, Niterói, Rio de Janeiro, Brazil. + + + + Vasconcelos + Marcio Moacyr + MM + + Federal Fluminense University, Antônio Pedro University Hospital, 24033-900, Niterói, Rio de Janeiro, Brazil. + + + + Nascimento + Osvaldo Jm + OJ + + Federal Fluminense University, Antônio Pedro University Hospital, 24033-900, Niterói, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + + + 2016 + 11 + 16 + +
+ + Netherlands + J Neurol Sci + 0375403 + 0022-510X + + IM + + + Arthrogryposis + etiology + virology + + + Central Nervous System + pathology + virology + + + Female + + + Humans + + + Infant, Newborn + + + Male + + + Microcephaly + etiology + virology + + + Zika Virus Infection + complications + pathology + + +
+ + + + 2016 + 11 + 09 + + + 2016 + 11 + 13 + + + 2016 + 12 + 27 + 6 + 0 + + + 2016 + 12 + 27 + 6 + 0 + + + 2017 + 5 + 31 + 6 + 0 + + + ppublish + + 28017252 + S0022-510X(16)30732-8 + 10.1016/j.jns.2016.11.030 + + +
+ + + + + 28008958 + + 2017 + 02 + 20 + +
+ + 2045-2322 + + 6 + + 2016 + Dec + 23 + + + Scientific reports + Sci Rep + + Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells. + + 39775 + + 10.1038/srep39775 + + Zika virus (ZIKV) infection has been associated with severe complications both in the developing and adult nervous system. To investigate the deleterious effects of ZIKV infection, we used human neural progenitor cells (NPC), derived from induced pluripotent stem cells (iPSC). We found that NPC are highly susceptible to ZIKV and the infection results in cell death. ZIKV infection led to a marked reduction in cell proliferation, ultrastructural alterations and induction of autophagy. Induction of apoptosis of Sox2+cells was demonstrated by activation of caspases 3/7, 8 and 9, and by ultrastructural and flow cytometry analyses. ZIKV-induced death of Sox2+cells was prevented by incubation with the pan-caspase inhibitor, Z-VAD-FMK. By confocal microscopy analysis we found an increased number of cells with supernumerary centrosomes. Live imaging showed a significant increase in mitosis abnormalities, including multipolar spindle, chromosome laggards, micronuclei and death of progeny after cell division. FISH analysis for chromosomes 12 and 17 showed increased frequency of aneuploidy, such as monosomy, trisomy and polyploidy. Our study reinforces the link between ZIKV and abnormalities in the developing human brain, including microcephaly. + + + + Souza + Bruno S F + BS + + Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil. + + + Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil. + + + + Sampaio + Gabriela L A + GL + + Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil. + + + + Pereira + Ciro S + CS + + Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil. + + + + Campos + Gubio S + GS + + Laboratory of Virology, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil. + + + + Sardi + Silvia I + SI + + Laboratory of Virology, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil. + + + + Freitas + Luiz A R + LA + + Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil. + + + Department of Pathology, Federal University of Bahia Salvador, Bahia, 40110-100, Brazil. + + + + Figueira + Claudio P + CP + + Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil. + + + + Paredes + Bruno D + BD + + Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil. + + + + Nonaka + Carolina K V + CK + + Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil. + + + Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil. + + + + Azevedo + Carine M + CM + + Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil. + + + Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil. + + + + Rocha + Vinicius P C + VP + + Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil. + + + Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil. + + + + Bandeira + Antonio C + AC + + Hospital Couto Maia, Salvador, Bahia, 40425-060, Brazil. + + + + Mendez-Otero + Rosalia + R + + Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil. + + + + Dos Santos + Ricardo Ribeiro + RR + + Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil. + + + + Soares + Milena B P + MB + + Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil. + + + Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, 41253-190, Brazil. + + + + eng + + Journal Article + + + 2016 + 12 + 23 + +
+ + England + Sci Rep + 101563288 + 2045-2322 + + + + Curr Top Microbiol Immunol. 2005;285:139-73 + 15609503 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Annu Rev Neurosci. 2009;32:149-84 + 19555289 + + + Cell Stem Cell. 2016 Nov 3;19(5):663-671 + 27524440 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Trends Genet. 2009 Nov;25(11):501-10 + 19850369 + + + Nat Methods. 2011 May;8(5):409-12 + 21460823 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Cell Stem Cell. 2016 Nov 3;19(5):593-598 + 27545505 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Nat Protoc. 2008;3(6):1101-8 + 18546601 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet Infect Dis. 2016 Feb;16(2):156-7 + 26723756 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Microbes Infect. 2016 Mar;18(3):169-71 + 26774331 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Rev Med Virol. 2009 Nov;19(6):359-78 + 19750559 + + + Nature. 2013 Sep 19;501(7467):373-9 + 23995685 + + + J Neurosci. 2007 Apr 4;27(14):3734-42 + 17409237 + + + Nature. 2009 Jul 9;460(7252):278-82 + 19506557 + + + Lancet. 2016 Mar 12;387(10023):1051-2 + 26944027 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + Emerg Microbes Infect. 2016 Mar 16;5:e22 + 26980239 + + + Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15672-7 + 26644564 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + Nat Cell Biol. 2013 Jul;15(7):731-40 + 23666084 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):55-8 + 26820163 + + + Cell. 2007 Nov 30;131(5):861-72 + 18035408 + + + BMB Rep. 2013 Aug;46(8):383-90 + 23977985 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + PLoS One. 2009;4(4):e5046 + 19352491 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + +
+ + + + 2016 + 09 + 09 + + + 2016 + 11 + 28 + + + 2016 + 12 + 24 + 6 + 0 + + + 2016 + 12 + 23 + 6 + 0 + + + 2016 + 12 + 23 + 6 + 0 + + + epublish + + 28008958 + srep39775 + 10.1038/srep39775 + PMC5180086 + + +
+ + + + + 28002820 + + 2017 + 10 + 10 + + + 2017 + 10 + 10 + +
+ + 1423-0003 + + 63 + 3 + + 2017 + + + Gerontology + Gerontology + + Zika Virus Infection in the Elderly: Possible Relationship with Guillain-Barré Syndrome. + + 210-215 + + 10.1159/000453579 + + The Zika virus (ZIKV) outbreak in French Polynesia, in 2013, and in Brazil, in 2015, was correlated with neurological complications, which comprised, among others, congenital microcephaly and Guillain-Barré syndrome (GBS), which includes a group of acute autoimmune neuropathies generally reported after respiratory or gastrointestinal infectious diseases. Despite being relatively rare, the incidence rate of GBS rises with age, which makes GBS more frequent in the elderly, in whom it is also a more severe disease with slower recovery than in younger patients. Different forms of GBS have been described having diagnostic confirmation of a previous infection with the ZIKV virus. Although we do not have enough evidence that elderly people are a particularly susceptible population to developing GBS following ZIKV infection, this is plausible. We should consider this possibility, particularly taking into account that aging subjects are more susceptible to infections. In this context, a deeper understanding of how the immune system in the elderly functions in relation to ZIKV infection is necessary, as well as an understanding of what kind of alterations of the nervous system such an infection triggers in the elderly, beyond GBS. This will be relevant for better therapeutic interventions and for designing vaccine candidates that can be applied in an aging population, particularly those prone to develop ZIKV-induced autoimmunity. + © 2016 S. Karger AG, Basel. + + + + Savino + Wilson + W + + Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. + + + + Messias + Carolina V + CV + + + Mendes-da-Cruz + Daniella A + DA + + + Passos + Pamela + P + + + Ferreira + Ana Carolina A F + AC + + + Nascimento + Osvaldo J + OJ + + + eng + + Journal Article + Review + + + 2016 + 12 + 22 + +
+ + Switzerland + Gerontology + 7601655 + 0304-324X + + IM + + + Aged + + + Aging + immunology + + + Autoimmunity + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Guillain-Barre Syndrome + epidemiology + etiology + immunology + + + Humans + + + Male + + + Polynesia + epidemiology + + + Zika Virus + pathogenicity + + + Zika Virus Infection + complications + epidemiology + immunology + + +
+ + + + 2016 + 08 + 21 + + + 2016 + 11 + 18 + + + 2016 + 12 + 22 + 6 + 0 + + + 2017 + 10 + 11 + 6 + 0 + + + 2016 + 12 + 22 + 6 + 0 + + + ppublish + + 28002820 + 000453579 + 10.1159/000453579 + + +
+ + + + + 27998595 + + 2017 + 08 + 07 + +
+ + 1474-4457 + + 16 + 12 + + 2016 + Dec + + + The Lancet. Infectious diseases + Lancet Infect Dis + + Zika virus and microcephaly - Authors' reply. + + 1332 + + S1473-3099(16)30457-1 + 10.1016/S1473-3099(16)30457-1 + + + de Araújo + Thália V B + TVB + + Department of Social Medicine, Federal University of Pernambuco, Recife, Brazil; Department of Community Health, Federal University of Pernambuco, Vitória de Santo Antão, Brazil. Electronic address: thalia@ufpe.br. + + + + Martelli + Celina T + CT + + Department of Community Health, Federal University of Goiás, Goiânia, Brazil. + + + + de Souza + Wayner V + WV + + The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Rodrigues + Laura C + LC + + Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. + + + + eng + + Letter + + + 2016 + 11 + 15 + +
+ + United States + Lancet Infect Dis + 101130150 + 1473-3099 + +
+ + + + 2016 + 10 + 18 + + + 2016 + 10 + 20 + + + 2016 + 12 + 22 + 6 + 0 + + + 2016 + 12 + 22 + 6 + 0 + + + 2016 + 12 + 22 + 6 + 0 + + + ppublish + + 27998595 + S1473-3099(16)30457-1 + 10.1016/S1473-3099(16)30457-1 + + +
+ + + + + 27982355 + + 2017 + 04 + 05 + + + 2017 + 04 + 05 + +
+ + 1678-9946 + + 58 + + 2016 + Dec + 08 + + + Revista do Instituto de Medicina Tropical de Sao Paulo + Rev. Inst. Med. Trop. Sao Paulo + + DETECTION OF HUMAN ANTI-ZIKA VIRUS IgG BY ELISA USING AN ANTIGEN FROM in vitro INFECTED VERO CELLS: PRELIMINARY RESULTS. + + 89 + + S0036-46652016005000270 + 10.1590/S1678-9946201658089 + + Zika virus (ZKV) infection is a huge public health problem in Brazil because of the increased incidence of microcephaly in neonates from infected mothers. Detection of specific IgG antibodies in maternal serum samples constitutes an important approach for diagnosing ZKV infection and evaluating its relationship with neonatal microcephaly. However, as there is no serological test produced in Brazil to detect IgM and IgG antibodies against ZKV, we sought to examine specific IgG in serum samples from patients or suspected mothers to detect previous infection and to test for specificity with regard to flaviviral infections occurring in the same area. Brazilian Zika virus native antigens were obtained from infected Vero cell layers or free virions in the culture medium and then used in ELISA. We tested sera from eight ZKV RNA-diagnosed infected patients (ZKVR), seven neonates with microcephaly and their mothers after delivery (MM), 140 dengue virus IgM-positive (DM) and IgG (DG)-positive patients, and 100 yellow fever (YF)-vaccinated patients. According to the ELISA, ZKVR samples were mostly positive (7/8), and all the MM serum samples were positive for ZKV IgG (7/7). In contrast, cross-reactions for dengue or yellow fever-vaccinated patients were observed, including DM (48/95), DG (10/45) or YF (3/100) serum samples; however, these cross-reactions exhibited low antigen avidity so that 6 M urea largely removed this cross-reactivity, with only a few cross-reacting samples remaining (8/140). ELISA based on extracted virions was much more specific, with all ZKVR (8/8) and MM sera being positive for ZKV IgG (7/7) and only borderline cross-reactivity found for DM (6/95), DG (3/45) or YF (4/100)-vaccinated serum samples. This technique (ELISA) can identify specific IgG in ZKV-infected patients and may be helpful in diagnosing congenital infetions after maternal RNA virus clearance or in epidemiological studies. + + + + Sumita + Laura Masami + LM + + Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, Laboratório de Virologia, São Paulo, SP, Brasil. + + + + Rodrigues + Jaqueline Polizeli + JP + + Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, Laboratório de Protozoologia, São Paulo, SP, Brasil. + + + + Ferreira + Noely Evangelista + NE + + Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, Laboratório de Virologia, São Paulo, SP, Brasil. + + + + Felix + Alvina Clara + AC + + Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, Laboratório de Virologia, São Paulo, SP, Brasil. + + + + Souza + Nathalia Caroline Santiago + NC + + Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, Laboratório de Virologia, São Paulo, SP, Brasil. + + + + Machado + Clarisse Martins + CM + + Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, Laboratório de Virologia, São Paulo, SP, Brasil. + + + + Júnior + Heitor Franco de Andrade + HF + + Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, Laboratório de Protozoologia, São Paulo, SP, Brasil. + + + + eng + + Comparative Study + Journal Article + + + 2016 + 12 + 08 + +
+ + Brazil + Rev Inst Med Trop Sao Paulo + 7507484 + 0036-4665 + + + + 0 + Antibodies, Viral + + + 0 + Antigens, Viral + + + 0 + Epitopes + + + 0 + Immunoglobulin G + + + 0 + Immunoglobulin M + + + IM + + + Clin Vaccine Immunol. 2014 Oct;21(10):1377-84 + 25165026 + + + Lancet. 2016 Apr 30;387(10030):1811-2 + 27103126 + + + J Med Virol. 1997 Jul;52(3):275-9 + 9210036 + + + Am J Reprod Immunol. 2013 Apr;69(4):346-58 + 23432802 + + + Am J Reprod Immunol. 2014 Aug;72(2):107-16 + 24995526 + + + J Clin Virol. 2006 Mar;35(3):285-91 + 16310405 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Clin Perinatol. 2015 Mar;42(1):77-103, viii + 25677998 + + + Int J Environ Res Public Health. 2013 Nov 12;10(11):6049-83 + 24225644 + + + Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 + 388439 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Childs Nerv Syst. 2003 Aug;19(7-8):429-32 + 12811485 + + + Clin Microbiol Infect. 2006 Jun;12(6):504-12 + 16700697 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Rev Inst Med Trop Sao Paulo. 1994 Jul-Aug;36(4):373-6 + 7732269 + + + Diagn Microbiol Infect Dis. 2016 Jan;84(1):22-33 + 26458281 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + N Engl J Med. 1988 Feb 4;318(5):271-5 + 3336419 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Swiss Med Wkly. 2016 Feb 09;146:w14296 + 26859285 + + + + + Animals + + + Antibodies, Viral + blood + immunology + + + Antibody Specificity + + + Antigens, Viral + immunology + + + Cercopithecus aethiops + + + Enzyme-Linked Immunosorbent Assay + + + Epitopes + + + Humans + + + Immunoglobulin G + blood + immunology + + + Immunoglobulin M + blood + immunology + + + Vero Cells + + + Zika Virus + immunology + ultrastructure + + + Zika Virus Infection + diagnosis + + +
+ + + + 2016 + 06 + 20 + + + 2016 + 09 + 22 + + + 2016 + 12 + 17 + 6 + 0 + + + 2016 + 12 + 17 + 6 + 0 + + + 2017 + 4 + 6 + 6 + 0 + + + epublish + + 27982355 + S0036-46652016005000270 + 10.1590/S1678-9946201658089 + PMC5147719 + + +
+ + + + + 27977881 + + 2017 + 06 + 14 + + + 2017 + 06 + 14 + +
+ + 1531-8249 + + 81 + 1 + + 2017 + Jan + + + Annals of neurology + Ann. Neurol. + + Immune activation in amniotic fluid from Zika virus-associated microcephaly. + + 152-156 + + 10.1002/ana.24839 + + Recent advances in the understanding of neuropathogenesis associated with Zika virus (ZIKV) infection has led to descriptions of neonatal microcephaly cases. However, none of these reports have evaluated the humoral response during ZIKV infection. We report here polyfunctional immune activation associated with increased interferon-gamma-inducible protein 10, interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), monocyte chemoattractive protein 1 (MCP-1), and granulocyte colony-stimulating factor (G-CSF) levels in the amniotic fluid of ZIKV-positive pregnant women with neonatal microcephaly. These cytokines have been associated not only with neuronal damage, but also with differentiation and proliferation of neural progenitor cells. Our results suggested that the immune activation caused by ZIKV infection in the uterine environment could also interfere with fetal development. ANN NEUROL 2017;81:152-156. + © 2016 American Neurological Association. + + + + Ornelas + Alice M M + AM + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Pezzuto + Paula + P + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Silveira + Paola P + PP + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Melo + Fabiana O + FO + + Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil. + + + + Ferreira + Thales A + TA + + Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil. + + + + Oliveira-Szejnfeld + Patricia S + PS + + Fundação Instituto de Ensino e Pesquisa em Diagnóstico por Imagem (FIDI), Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo, São Paulo, Brazil. + + + + Leal + Jeime I + JI + + Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil. + + + + Amorim + Melania M R + MM + + Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil. + + + + Hamilton + Stuart + S + + Virology Research, POWH & UNSW Research Laboratories, Prince of Wales Hospital, Randwick, NSW, Australia. + + + + Rawlinson + William D + WD + + Virology Research, POWH & UNSW Research Laboratories, Prince of Wales Hospital, Randwick, NSW, Australia. + + + + Cardoso + Cynthia C + CC + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Nixon + Douglas F + DF + + Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC. + + + + Tanuri + Amilcar + A + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Melo + Adriana S + AS + + Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil. + + + + Aguiar + Renato S + RS + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + +
+ + United States + Ann Neurol + 7707449 + 0364-5134 + + + + 0 + CCL2 protein, human + + + 0 + CXCL10 protein, human + + + 0 + Chemokine CCL2 + + + 0 + Chemokine CXCL10 + + + 0 + Inflammation Mediators + + + 0 + Interleukin-6 + + + 0 + Interleukin-8 + + + 0 + Vascular Endothelial Growth Factor A + + + 143011-72-7 + Granulocyte Colony-Stimulating Factor + + + IM + + + Adolescent + + + Adult + + + Amniotic Fluid + immunology + metabolism + + + Case-Control Studies + + + Chemokine CCL2 + metabolism + + + Chemokine CXCL10 + metabolism + + + Female + + + Granulocyte Colony-Stimulating Factor + metabolism + + + Humans + + + Inflammation Mediators + metabolism + + + Interleukin-6 + metabolism + + + Interleukin-8 + metabolism + + + Microcephaly + etiology + immunology + metabolism + pathology + + + Neural Stem Cells + cytology + immunology + metabolism + + + Pregnancy + + + Vascular Endothelial Growth Factor A + metabolism + + + Young Adult + + + Zika Virus Infection + complications + immunology + metabolism + pathology + + +
+ + + + 2016 + 07 + 06 + + + 2016 + 12 + 02 + + + 2016 + 12 + 03 + + + 2016 + 12 + 16 + 6 + 0 + + + 2017 + 6 + 15 + 6 + 0 + + + 2016 + 12 + 16 + 6 + 0 + + + ppublish + + 27977881 + 10.1002/ana.24839 + + +
+ + + + + 27966802 + + 2017 + 12 + 26 + + + 2017 + 12 + 26 + +
+ + 1600-0897 + + 77 + 2 + + 2017 + Feb + + + American journal of reproductive immunology (New York, N.Y. : 1989) + Am. J. Reprod. Immunol. + + Zika virus: A new threat to human reproduction. + 10.1111/aji.12614 + + Zika virus (ZIKV) was first isolated in 1947 in a rhesus monkey from the Zika forest of Uganda. Until 2007, only 14 human cases were reported. The first large human outbreak occurred in 2007 (Yap Island, Federated States of Micronesia, Pacific) followed by French Polynesia in 2013 and Brazil in 2015. The virus is mainly transmitted through Aedes mosquito bites, but sexual and post-transfusion transmissions have been reported. Symptoms include low-grade fever, maculopapular rash, conjunctivitis, myalgia, arthralgia, and asthenia. During the recent outbreaks in French Polynesia and Brazil, ZIKV infection has been associated with two major complications: microcephaly and Guillain-Barré syndrome. Since fetal infection includes other birth defects, congenital Zika syndrome has been used to define in utero infection. The majority of sexual transmission occurred from a symptomatic male to a female, but female-to-male and male-to-male transmission have been reported. Asymptomatic male-to-female transmission has also been described. Importantly, ZIKV RNA can persist at least 6 months in semen. The male urogenital tract may therefore act as a reservoir for the virus. ZIKV RNA was detected in a cervical swab of a patient 3 days after presenting the classic symptoms suggesting a potential tropism for the female genital tract. Long-lasting presence of ZIKV RNA might not indicate that the individual is infectious but makes recommendation for couples potentially exposed to the virus and willing to conceive difficult. It will also be important to determine whether genital ZIKV infection might have a deleterious effect on male and female fertility. + © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. + + + + Baud + David + D + + Materno-Fetal and Obstetrics Research Unit, Department "Femme-Mere-Enfant", Lausanne University Hospital, Lausanne, Switzerland. + + + + Musso + Didier + D + + Unit of Emerging Infectious Diseases, Institut Louis Malardé, Tahiti, French Polynesia. + + + + Vouga + Manon + M + + Materno-Fetal and Obstetrics Research Unit, Department "Femme-Mere-Enfant", Lausanne University Hospital, Lausanne, Switzerland. + + + + Alves + Marco P + MP + + Institute of Virology and Immunology, Mittelhäusern, Switzerland. + + + Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. + + + + Vulliemoz + Nicolas + N + + Reproductive Medicine Unit, Department "Femme-Mere-Enfant", Lausanne University Hospital, Lausanne, Switzerland. + + + + eng + + Journal Article + Review + + + 2016 + 12 + 14 + +
+ + Denmark + Am J Reprod Immunol + 8912860 + 1046-7408 + + IM + + + Aedes + virology + + + Animals + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Guillain-Barre Syndrome + epidemiology + + + Humans + + + Infant, Newborn + + + Infant, Newborn, Diseases + epidemiology + + + Infertility, Female + virology + + + Microcephaly + epidemiology + + + Polynesia + epidemiology + + + Reproduction + + + Zika Virus + immunology + + + Zika Virus Infection + epidemiology + immunology + + + + Zika + congenital infection + microcephaly + semen + sexual transmission + +
+ + + + 2016 + 10 + 25 + + + 2016 + 11 + 07 + + + 2016 + 12 + 15 + 6 + 0 + + + 2017 + 12 + 27 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + ppublish + + 27966802 + 10.1111/aji.12614 + + +
+ + + + + 27955630 + + 2017 + 05 + 16 + + + 2017 + 05 + 16 + +
+ + 1471-2334 + + 16 + 1 + + 2016 + Dec + 12 + + + BMC infectious diseases + BMC Infect. Dis. + + Estimation of Zika virus prevalence by appearance of microcephaly. + + 754 + + + There currently is a severe Zika Virus (ZIKV) epidemic in Brazil and other South American countries. Due to international travel, this poses severe public health risk of ZIKV importation to other countries. We estimate the prevalence of ZIKV in an import region by the time a microcephaly case is detected, since microcephaly is presently the most significant indication of ZIKV presence. + We establish a mathematical model to describe ZIKV spread from a source region to an import region. This model incorporates both vector transmission (between humans and mosquitoes) and sexual transmission (from males to females). We take account of population structure through a contact network for sexually active individuals. Parameter values of our model are either taken from the literature or estimated from travel data. + This model gives us the probability distribution of time until detection of the first microcephaly case. Based on current field observations, our results also indicate that the percentage of infected pregnant women that results in fetal abnormalities is more likely to be on the smaller end of the 1%-30% spectrum that is currently hypothesized. Our model predicts that for import regions with at least 250,000 people, on average 1,000-12,000 will have been infected by the time of the first detection of microcephaly, and on average 200-1,500 will be infectious at this time. Larger population sizes do not significantly change our predictions. + By the first detection of a microcephaly case, a sizable fraction of the population will have been infected by ZIKV. It is thus clear that adequate surveillance, isolation, and quarantine are needed in susceptible import regions to stop the dissemination of a Zika epidemic. + + + + Saad-Roy + C M + CM + + Department of Mathematics and Statistics, University of Victoria, Victoria, BC, V8W 2Y2, Canada. + + + + van den Driessche + P + P + + Department of Mathematics and Statistics, University of Victoria, Victoria, BC, V8W 2Y2, Canada. + + + + Ma + Junling + J + http://orcid.org/0000-0002-0197-2317 + + Department of Mathematics and Statistics, University of Victoria, Victoria, BC, V8W 2Y2, Canada. junlingm@uvic.ca. + + + + eng + + Journal Article + + + 2016 + 12 + 12 + +
+ + England + BMC Infect Dis + 100968551 + 1471-2334 + + IM + + + Lancet. 2009 Aug 8;374(9688):451-8 + 19643469 + + + N Engl J Med. 2016 Jun 2;374(22):2195-8 + 27074370 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Am J Trop Med Hyg. 2016 Jul 6;95(1):15-8 + 26903610 + + + Epidemics. 2016 Dec;17 :50-55 + 27846442 + + + J Theor Biol. 2014 Sep 7;356:174-91 + 24801860 + + + MMWR Morb Mortal Wkly Rep. 2016 Apr 01;65(12):315-22 + 27031943 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + J R Soc Interface. 2013 Feb 13;10(81):20120921 + 23407571 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Emerg Infect Dis. 2016 May;22(5):940 + 27088817 + + + Sci Rep. 2016 Jun 17;6:28070 + 27312324 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + CMAJ. 2016 Mar 15;188(5):367 + 26858352 + + + Science. 2009 Jan 2;323(5910):141-4 + 19119237 + + + BMJ. 2016 Feb 04;352:i720 + 26848011 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Female + + + Humans + + + Male + + + Microcephaly + diagnosis + etiology + + + Models, Theoretical + + + Pregnancy + + + Prevalence + + + Sexually Transmitted Diseases + diagnosis + virology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + epidemiology + transmission + virology + + + + Contact network + Mathematical model + Microcephaly + Sexual transmission + Vector transmission + Zika prevalence + +
+ + + + 2016 + 09 + 01 + + + 2016 + 11 + 29 + + + 2016 + 12 + 14 + 6 + 0 + + + 2016 + 12 + 14 + 6 + 0 + + + 2017 + 5 + 17 + 6 + 0 + + + epublish + + 27955630 + 10.1186/s12879-016-2076-z + 10.1186/s12879-016-2076-z + PMC5153823 + + +
+ + + + + 27934901 + + 2017 + 02 + 20 + +
+ + 2045-2322 + + 6 + + 2016 + Dec + 09 + + + Scientific reports + Sci Rep + + Towards peptide vaccines against Zika virus: Immunoinformatics combined with molecular dynamics simulations to predict antigenic epitopes of Zika viral proteins. + + 37313 + + 10.1038/srep37313 + + The recent outbreak of Zika virus (ZIKV) infection in Brazil has developed to a global health concern due to its likely association with birth defects (primary microcephaly) and neurological complications. Consequently, there is an urgent need to develop a vaccine to prevent or a medicine to treat the infection. In this study, immunoinformatics approach was employed to predict antigenic epitopes of Zika viral proteins to aid in development of a peptide vaccine against ZIKV. Both linear and conformational B-cell epitopes as well as cytotoxic T-lymphocyte (CTL) epitopes were predicted for ZIKV Envelope (E), NS3 and NS5 proteins. We further investigated the binding interactions of altogether 15 antigenic CTL epitopes with three class I major histocompatibility complex (MHC I) proteins after docking the peptides to the binding groove of the MHC I proteins. The stability of the resulting peptide-MHC I complexes was further studied by molecular dynamics simulations. The simulation results highlight the limits of rigid-body docking methods. Some of the antigenic epitopes predicted and analyzed in this work might present a preliminary set of peptides for future vaccine development against ZIKV. + + + + Usman Mirza + Muhammad + M + + Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Pakistan. + + + + Rafique + Shazia + S + + Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan. + + + + Ali + Amjad + A + + Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan. + + + + Munir + Mobeen + M + + Division of Science and Technology, University of Education Lahore, Pakistan. + + + + Ikram + Nazia + N + + Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Pakistan. + + + + Manan + Abdul + A + + Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Pakistan. + + + + Salo-Ahen + Outi M H + OM + + Structural Bioinformatics Laboratory, Faculty of Science and Engineering, Biochemistry, Åbo Akademi University, Turku, Finland. + + + Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Pharmacy, Åbo Akademi University, Turku, Finland. + + + + Idrees + Muhammad + M + + Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan. + + + Vice Chancellor Hazara University, Mansehra, Pakistan. + + + + eng + + Journal Article + + + 2016 + 12 + 09 + +
+ + England + Sci Rep + 101563288 + 2045-2322 + + + + Infect Genet Evol. 2016 Nov;45:187-197 + 27590716 + + + Curr Protein Pept Sci. 2009 Jun;10(3):286-96 + 19519456 + + + Asian Pac J Trop Med. 2016 Sep;9(9):844-50 + 27633296 + + + J Virol. 1985 Sep;55(3):836-9 + 2991600 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Nucleic Acids Res. 2016 Jul 8;44(W1):W449-54 + 27131374 + + + Biochemistry. 1986 Sep 23;25(19):5425-32 + 2430611 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Methods. 1996 Jun;9(3):465-72 + 8812702 + + + Biophys J. 2014 Jul 1;107(1):134-45 + 24988348 + + + J Mol Graph. 1990 Mar;8(1):52-6, 29 + 2268628 + + + Expert Rev Clin Immunol. 2005 May;1(1):145-57 + 20477662 + + + Drug Discov Today. 2007 May;12(9-10):389-95 + 17467575 + + + J Immunol. 2015 Nov 1;195(9):4503-13 + 26416272 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Microb Biotechnol. 2012 Mar;5(2):149-55 + 21880117 + + + Curr Opin Microbiol. 2000 Oct;3(5):445-50 + 11050440 + + + Mol Immunol. 2008 Aug;45(14):3714-22 + 18639935 + + + Viruses. 2015 Mar 27;7(4):1558-77 + 25826188 + + + Lancet Infect Dis. 2016 Apr;16(4):405 + 26949027 + + + J Virol. 2000 Sep;74(17):8140-50 + 10933725 + + + BMC Bioinformatics. 2008 Dec 02;9:514 + 19055730 + + + EMBO J. 1986 Feb;5(2):409-13 + 2423325 + + + Proteins. 2007 Oct 1;69(1):139-59 + 17598144 + + + Open Biol. 2013 Jan 08;3(1):120139 + 23303307 + + + Expert Rev Vaccines. 2004 Feb;3(1):59-76 + 14761244 + + + Bioinformatics. 2005 Apr 1;21(7):1028-36 + 15546935 + + + J Comput Chem. 2004 Oct;25(13):1605-12 + 15264254 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Methods Enzymol. 1997;277:396-404 + 9379925 + + + Proc Natl Acad Sci U S A. 1987 Dec;84(23):8568-72 + 2446325 + + + Adv Virus Res. 2003;59:23-61 + 14696326 + + + BMC Bioinformatics. 2007 Oct 31;8:424 + 17973982 + + + Proteins. 2003 Jul 1;52(1):107-12 + 12784375 + + + FEBS Lett. 1990 Dec 10;276(1-2):172-4 + 1702393 + + + Vaccines (Basel). 2015 Mar 24;3(2):203-20 + 26343185 + + + Rev Med Virol. 2009 Mar;19(2):77-96 + 19101924 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + Antiviral Res. 2008 Oct;80(1):23-35 + 18611413 + + + Emerg Infect Dis. 2015 May;21(5):911-3 + 25898277 + + + Nature. 1986 Aug 21-27;322(6081):747-8 + 2427953 + + + Immunology. 2016 Dec;149(4):386-399 + 27485738 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Proc IEEE Comput Soc Bioinform Conf. 2003;2:17-26 + 16826643 + + + PLoS One. 2015 Aug 13;10(8):e0135421 + 26270965 + + + BMC Res Notes. 2015 Nov 27;8:729 + 26613722 + + + Viral Immunol. 2016 Sep;29(7):436-43 + 27438351 + + + Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W229-32 + 18424796 + + + Antiviral Res. 2008 Oct;80(1):11-22 + 18585795 + + + Proteins. 2007 Nov 1;69(2):394-408 + 17600832 + + + Methods Mol Biol. 2014;1137:1-15 + 24573470 + + + Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W244-8 + 15980461 + + + Immunity. 2005 Jul;23(1):29-40 + 16039577 + + + Genome Med. 2015 Nov 20;7:119 + 26589500 + + + J Immunol. 2002 Mar 1;168(5):2371-82 + 11859128 + + + Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 + 9254694 + + + Rev Inst Med Trop Sao Paulo. 2011 Jul-Aug;53(4):223-5 + 21915467 + + +
+ + + + 2016 + 07 + 22 + + + 2016 + 10 + 27 + + + 2016 + 12 + 10 + 6 + 0 + + + 2016 + 12 + 10 + 6 + 0 + + + 2016 + 12 + 10 + 6 + 0 + + + epublish + + 27934901 + srep37313 + 10.1038/srep37313 + PMC5146661 + + +
+ + + + + 27932442 + + 2018 + 02 + 22 + + + 2018 + 02 + 22 + +
+ + 1460-2350 + + 32 + 1 + + 2017 + Jan + + + Human reproduction (Oxford, England) + Hum. Reprod. + + Contraceptive sales in the setting of the Zika virus epidemic. + + 88-93 + + + Has there been any influence of the Zika virus (ZIKV) outbreak on the sales of contraceptive methods in Brazil? + Contraceptive sales in the 24 months of evaluation showed little variation and no significant change has been observed since the ZIKV outbreak. + Transmission of ZIKV is primarily by Aedes aegypti mosquitoes; however, sexual transmission has also been described. The association of several birth defects and the ZIKV infection during pregnancy has been established, and it was estimated in Bahia, Brazil that the infection rate could range from 10% to 80%. The World Health Organisation (WHO) declared the cluster of microcephaly cases and other neurological disorders a health emergency on 1 February 2016. The Brazilian government also made recommendations for women who were planning to become pregnant and who reside in ZIKV-affected areas to reconsider or postpone pregnancy. + The objective of this study was to assess the sales of contraceptive methods in Brazil, tracking it from before and through the ZIKV outbreak. We obtained information from all pharmaceutical companies based in Brazil and from the manufacturers of long-acting reversible contraceptives (LARCs), including the copper-intrauterine device (IUD), the levonorgestrel-releasing intrauterine system (LNG-IUS) and implants, about contraceptives sales in the public and private sectors between September 2014 and August 2016. + We analyzed the data for: (i) oral contraceptives, i.e. combined oral contraceptives (COC) and progestin-only pills (POP), and vaginal and transdermal contraceptives, (ii) injectable contraceptives, i.e. once-a-month and depot-medroxyprogesterone acetate, (iii) LARCs and (iv) emergency contraceptive (EC) pills. + Monthly sales of COC, POP, patches and vaginal rings represent the major sales segment of the market, i.e. 12.7-13.8 million cycles/units per month (90%). The second largest group of sales was injectables, representing 0.8-1.5 million ampoules per month (9.5%). Following this, are LARC methods with sales of 37 000-41 000 devices per month (0.5%). It is important to note that although the peak months of sales were different for each group of contraceptives, there were no significant differences overall between the months of observation. The EC pill sales were between 1.0 million and 1.3 million of pills per month. + Although the use of contraceptive methods was already high and no change was noted, the ZIKV outbreak may have changed the pregnancy intentions of Brazilian women. Consequently, the number of women planning pregnancy may be lower than that recorded. The contraceptive sales figures did not include condoms. Since condoms might not only prevent pregnancies, but also sexual transmission of ZIKV, this lack of information is a limitation. + The results from this assessment showed that the sales of contraceptives presented little variation during the ZIKV outbreak in Brazil. Furthermore, it is possible that access to LARC methods was limited. Although we did not investigate the reason for low LARC uptake, we suspect that it is due to lack of availability of LARC in the public sector, the high cost of the methods and the incomplete insurance coverage on contraception for women. Projections estimate millions of additional cases of ZIKV transmission. Thus, a coordinated response is needed to ensure access to a wide range of contraceptive methods for women during the ZIKV outbreak. In conclusion, this assessment of contraceptive sales in Brazil identifies challenges in contraceptive access, especially for LARC methods, and represents an alternative source of data to help us understand the trends in demand for contraception in ZIKV-affected areas. + This study received partial financial support from Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP) award # 2015/20504-9 and from an anonymous donor. The funding sources did not play a role in the study design, in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the article for publication. The authors declare no conflict of interest associated with this study. + N/A. + © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. + + + + Bahamondes + Luis + L + + Family Planning Clinic, Department of Obstetrics and Gynaecology, University of Campinas (UNICAMP) Medical School, Caixa Postal 6181, 13084-971 Campinas, SP, Brazil bahamond@caism.unicamp.br. + + + + Ali + Moazzam + M + + Department of Reproductive Health and Research, World Health Organisation, Avenue Appia 20, 1211 Genève 27, Switzerland. + + + + Monteiro + Ilza + I + + Family Planning Clinic, Department of Obstetrics and Gynaecology, University of Campinas (UNICAMP) Medical School, Caixa Postal 6181, 13084-971 Campinas, SP, Brazil. + + + + Fernandes + Arlete + A + + Family Planning Clinic, Department of Obstetrics and Gynaecology, University of Campinas (UNICAMP) Medical School, Caixa Postal 6181, 13084-971 Campinas, SP, Brazil. + + + + eng + + Journal Article + + + 2016 + 12 + 07 + +
+ + England + Hum Reprod + 8701199 + 0268-1161 + + + + 0 + Contraceptive Agents + + + IM + + + N Engl J Med. 2016 Jun 2;374(22):2195-8 + 27074370 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 25;65(11):286-9 + 27023833 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + Int J Womens Health. 2014 Jul 16;6:663-70 + 25075201 + + + N Engl J Med. 2014 Oct 2;371(14):1316-23 + 25271604 + + + N Engl J Med. 2016 Jul 28;375(4):396-8 + 27331661 + + + Hum Reprod. 2014 Oct 10;29(10):2163-70 + 25085802 + + + Obstet Gynecol. 2012 Dec;120(6):1291-7 + 23168752 + + + MMWR Morb Mortal Wkly Rep. 2016 Jul 25;65(29):745-7 + 27466758 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Natl Health Stat Report. 2015 Nov 10;(86):1-14 + 26556545 + + + J Pediatr Adolesc Gynecol. 2010 Jun;23(3):142-5 + 19822446 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + MMWR Morb Mortal Wkly Rep. 2016 Jul 22;65(28):716-7 + 27442327 + + + + + Adult + + + Brazil + + + Commerce + + + Contraception + economics + + + Contraceptive Agents + economics + + + Female + + + Humans + + + Pregnancy + + + Zika Virus + + + Zika Virus Infection + + + + Brazil + Zika virus + contraception + long-acting contraceptive methods + unintended pregnancies + +
+ + + + 2016 + 08 + 19 + + + 2016 + 10 + 31 + + + 2016 + 11 + 09 + + + 2016 + 12 + 10 + 6 + 0 + + + 2018 + 2 + 23 + 6 + 0 + + + 2016 + 12 + 10 + 6 + 0 + + + ppublish + + 27932442 + dew310 + 10.1093/humrep/dew310 + PMC5165082 + + +
+ + + + + 27923950 + + 2017 + 05 + 22 + + + 2017 + 05 + 22 + +
+ + 1537-6613 + + 214 + 12 + + 2016 + Dec + 15 + + + The Journal of infectious diseases + J. Infect. Dis. + + Results of a Zika Virus (ZIKV) Immunoglobulin M-Specific Diagnostic Assay Are Highly Correlated With Detection of Neutralizing Anti-ZIKV Antibodies in Neonates With Congenital Disease. + + 1897-1904 + + +  Usually, immunoglobulin M (IgM) serologic analysis is not sufficiently specific to confirm Zika virus (ZIKV) infection. However, since IgM does not cross the placenta, it may be a good marker of infection in neonates. +  We tested blood from 42 mothers and neonates with microcephaly and collected cerebrospinal fluid (CSF) specimens from 30 neonates. Molecular assays were performed for detection of ZIKV, dengue virus, and chikungunya virus; IgM enzyme-linked immunosorbent assays and plaque-reduction neutralization tests (PRNTs) were performed to detect ZIKV and dengue virus. No control neonates without microcephaly were evaluated. +  Among neonates, all 42 tested positive for ZIKV IgM: 38 of 42 serum specimens (90.5%) were positive, whereas 30 of 30 CSF specimens (100%) were positive. ZIKV IgM-specific ELISA ratios, calculated as the mean optical density (OD) of the test sample when reacted on viral antigen divided by the mean OD of the negative control when reacted with viral antigen, were higher in CSF specimens (median, 14.9 [range, 9.3-16.4]) than in serum (median, 8.9 [range, 2.1-20.6]; P = .0003). All ZIKV IgM-positive results among the neonates were confirmed by the detection of neutralizing antibodies. Mother/neonate pairs with primary ZIKV infection had neutralizing antibodies to ZIKV only, and mother/neonate pairs with ZIKV virus infection secondary to infection with another flavivirus had high titers of neutralizing antibodies to ZIKV. Among secondary infections, median titers in serum were 2072 (range, 232-12 980) for mothers and 2730 (range, 398-12 980) for neonates (P < .0001), and the median titer in CSF was 93 (range, 40-578) among neonates (P < .0001). +  Among neonates, detection of ZIKV IgM in serum is confirmatory of congenital ZIKV infection, and detection of ZIKV IgM in CSF is confirmatory of neurologic infection. Therefore, we recommend testing for ZIKV IgM in neonates suspected of having congenital ZIKV infection and performance of PRNTs in equivocal cases. + © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com. + + + + Cordeiro + Marli T + MT + + Department of Virology, Aggeu Magalhães Research Center, Fundação Oswaldo Cruz. + + + + Brito + Carlos A A + CA + + Department of Clinical Medicine, Federal University of Pernambuco. + + + + Pena + Lindomar J + LJ + + Department of Virology, Aggeu Magalhães Research Center, Fundação Oswaldo Cruz. + + + + Castanha + Priscila M S + PM + + Department of Virology, Aggeu Magalhães Research Center, Fundação Oswaldo Cruz. + + + + Gil + Laura H V G + LH + + Department of Virology, Aggeu Magalhães Research Center, Fundação Oswaldo Cruz. + + + + Lopes + Kennya G S + KG + + Department of Virology, Aggeu Magalhães Research Center, Fundação Oswaldo Cruz. + + + + Dhalia + Rafael + R + + Department of Virology, Aggeu Magalhães Research Center, Fundação Oswaldo Cruz. + + + + Meneses + Jucille A + JA + + Department of Pediatrics, Instituto de Medicina Integral Professor Fernando Figueira. + + + + Ishigami + Ana C + AC + + Department of Pediatrics, Instituto de Medicina Integral Professor Fernando Figueira. + + + + Mello + Luisa M + LM + + Department of Pediatrics, Instituto de Medicina Integral Professor Fernando Figueira. + + + + Alencar + Liciana X E + LX + + Central Public Health Laboratory, Secretaria de Saúde do Estado de Pernambuco, Recife, Brazil. + + + + Guarines + Klarissa M + KM + + Central Public Health Laboratory, Secretaria de Saúde do Estado de Pernambuco, Recife, Brazil. + + + + Rodrigues + Laura C + LC + + Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, United Kingdom. + + + + Marques + Ernesto T A + ET + + Department of Virology, Aggeu Magalhães Research Center, Fundação Oswaldo Cruz. + + + Center for Vaccine Research. + + + Department of Infectious Disease and Microbiology, University of Pittsburgh, Pennsylvania. + + + + eng + + Evaluation Studies + Journal Article + + + 2016 + 10 + 05 + +
+ + United States + J Infect Dis + 0413675 + 0022-1899 + + + + 0 + Antibodies, Neutralizing + + + 0 + Antibodies, Viral + + + 0 + Immunoglobulin M + + + AIM + IM + + + Adolescent + + + Adult + + + Antibodies, Neutralizing + blood + cerebrospinal fluid + + + Antibodies, Viral + blood + cerebrospinal fluid + + + Blood + immunology + + + Cerebrospinal Fluid + immunology + + + Enzyme-Linked Immunosorbent Assay + + + Female + + + Humans + + + Immunoglobulin M + blood + + + Infant, Newborn + + + Male + + + Neutralization Tests + + + Sensitivity and Specificity + + + Viral Plaque Assay + + + Young Adult + + + Zika Virus + immunology + + + Zika Virus Infection + congenital + diagnosis + + + + ZIKV antibodies + Zika virus + anti-ZIKV IgM + congenital Zika + microcephaly + +
+ + + + 2016 + 06 + 13 + + + 2016 + 10 + 03 + + + 2016 + 12 + 8 + 6 + 0 + + + 2016 + 12 + 8 + 6 + 0 + + + 2017 + 5 + 23 + 6 + 0 + + + ppublish + + 27923950 + jiw477 + 10.1093/infdis/jiw477 + + +
+ + + + + 27923187 + + 2017 + 05 + 31 + + + 2017 + 10 + 16 + +
+ + 1872-8952 + + 128 + 1 + + 2017 + Jan + + + Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology + Clin Neurophysiol + + Sleep EEG patterns in infants with congenital Zika virus syndrome. + + 204-214 + + S1388-2457(16)30648-4 + 10.1016/j.clinph.2016.11.004 + + To describe sleep EEG patterns of neonates, and infants with microcephaly due to congenital Zika virus (ZikV) syndrome. + A descriptive case series of EEGs performed in a cohort of neonates with microcephaly monitored from October 2015 to February 2016 at a University Hospital in Northeast Brazil. Infants were investigated following an established protocol that includes EEG, neuroimaging studies, PCR and specific antibodies for ZikV detection. + EEGs (n=37) from 37 infants were reviewed. Age at investigation varied from 1 to 5months (mean=2.6). Diffuse low voltage (n=7), background asymmetry (n=6) and modified hypsarrhythmia with or without burst-suppression (n=11), were the main background abnormalities identified. Interictal EEG abnormalities were identified in 23 recordings (62%) and localized as focal frontal (n=8) or occipital (n=2) spikes/sharp, multifocal spikes/sharp waves (n=13). Electrographic seizures without clinical manifestation were identified in 4 recordings and characterized as focal pseudo rhythmic pattern. Further findings were focal high amplitude slow waves that were registered in the frontal (n=3) or occipital (n=1) regions. + Different types of EEG abnormalities were encountered with a predominance of interictal epileptogenic activity and hypsarrhythmia. + Sleep EEGs in congenital Zika virus syndrome are consistently abnormal even in infants who have not yet developed epilepsy. + Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. + + + + Carvalho + Maria Durce Costa Gomes + MD + + UPE (University of Pernambuco), Recife, Brazil. + + + + Miranda-Filho + Demócrito de Barros + DB + + UPE (University of Pernambuco), Recife, Brazil. + + + + van der Linden + Vanessa + V + + Associação de Assistência à Criança Deficiente (AACD), Recife, Brazil. + + + + Sobral + Paula Fabiana + PF + + UPE (University of Pernambuco), Recife, Brazil. + + + + Ramos + Regina Coeli Ferreira + RC + + UPE (University of Pernambuco), Recife, Brazil. + + + + Rocha + Maria Ângela Wanderley + + + UPE (University of Pernambuco), Recife, Brazil. + + + + Cordeiro + Marli Tenório + MT + + Department of Virology, Aggeu Magalhães Research Center, Fiocruz-PE, Brazil. + + + + de Alencar + Sarah Pinheiro + SP + + UPE (University of Pernambuco), Recife, Brazil. + + + + Nunes + Magda Lahorgue + ML + + School of Medicine - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) and Brain Institute of Rio Grande do Sul (BraIns), Porto Alegre, Brazil. Electronic address: nunes@pucrs.br. + + + + eng + + Journal Article + + + 2016 + 11 + 14 + +
+ + Netherlands + Clin Neurophysiol + 100883319 + 1388-2457 + + IM + + + Clin Neurophysiol. 2017 Feb;128(2):289 + 28042993 + + + + + Cohort Studies + + + Electroencephalography + methods + + + Female + + + Humans + + + Infant + + + Male + + + Microcephaly + diagnosis + etiology + physiopathology + + + Sleep + physiology + + + Sleep Wake Disorders + diagnosis + physiopathology + + + Zika Virus + + + Zika Virus Infection + complications + diagnosis + physiopathology + + + + EEG + Microcephaly + Newborns + Zika virus + +
+ + + + 2016 + 08 + 14 + + + 2016 + 11 + 01 + + + 2016 + 11 + 04 + + + 2016 + 12 + 7 + 6 + 0 + + + 2017 + 6 + 1 + 6 + 0 + + + 2016 + 12 + 7 + 6 + 0 + + + ppublish + + 27923187 + S1388-2457(16)30648-4 + 10.1016/j.clinph.2016.11.004 + + +
+ + + + + 27919154 + + 2018 + 01 + 23 + + + 2018 + 01 + 23 + +
+ + 1120-9763 + + 40 + 6 + + 2016 Nov-Dec + + + Epidemiologia e prevenzione + Epidemiol Prev + + [Many doubts about the relationship between cases of microcephaly and Zika virus in Brazil]. + + 466-471 + + + During the last few years, Zika virus rapidly spread across Central and South America and in the last months has spread also across Southern States of USA. As the epidemic began in Brazil, an increase of microcephaly cases was registered, causing concern and inducing the World Health Organization to raise an alarm. Certainly, the Zika virus, as many other viruses, has the capacity to induce severe cerebral lesions in foetuses of women infected during the first months of pregnancy. Moreover, more than 80% of cases of craniostenosys that verisimilarly took place in Brazil from September 2015 up to now were registered in few states of North- Eastern Brazil, where peaks of this malformation were registered several years before the appearance of Zika virus. In addition, in none of the 60 Countries where Zika virus is epidemiologically active an increase of the incidence of microcephaly has been reported. This paper intends to analyse some doubts concerning the link between Zika virus and the epidemic of craniostenosys. + + + + Ronchetti + Roberto + R + + Facoltà di medicina e chirurgia 1, Università "Sapienza" Roma. roberto.ronchetti@uniroma1.it. + + + Presidente sezione laziale, Associazione "Medici per l'ambiente - ISDE Italia", Roma. + + + + Bianco + Pietro Massimiliano + PM + + Institute for Environmental Protection and Research (ISPRA), Roma. + + + + ita + + Journal Article + + I molti dubbi sul rapporto tra casi di microcefalia e infezione da virus Zika in Brasile. +
+ + Italy + Epidemiol Prev + 8902507 + 1120-9763 + + IM + + + Brazil + epidemiology + + + Female + + + Humans + + + Incidence + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + prevention & control + virology + + + Retrospective Studies + + + Zika Virus Infection + complications + epidemiology + prevention & control + + +
+ + + + 2016 + 12 + 7 + 6 + 0 + + + 2016 + 12 + 7 + 6 + 0 + + + 2018 + 1 + 24 + 6 + 0 + + + ppublish + + 27919154 + 10.19191/EP16.6.P466.128 + 3607 + + +
+ + + + + 27916837 + + 2017 + 09 + 13 + + + 2017 + 12 + 12 + +
+ + 1999-4915 + + 8 + 12 + + 2016 + 11 + 29 + + + Viruses + Viruses + + Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models. + E322 + + Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres. + + + + Delvecchio + Rodrigo + R + + Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. digodelvecchio@gmail.com. + + + + Higa + Luiza M + LM + + Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. luizahiga@gmail.com. + + + + Pezzuto + Paula + P + + Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. paulapezzuto81@gmail.com. + + + + Valadão + Ana Luiza + AL + + Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. analuvaladao@gmail.com. + + + + Garcez + Patrícia P + PP + + Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. ppgarcez@gmail.com. + + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro 22281-100, Brazil. ppgarcez@gmail.com. + + + + Monteiro + Fábio L + FL + + Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. fabiolimonte@gmail.com. + + + + Loiola + Erick C + EC + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro 22281-100, Brazil. erickloiola@lance-ufrj.org. + + + + Dias + André A + AA + + Department of Immunology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. aadias2005@yahoo.com.br. + + + + Silva + Fábio J M + FJ + + Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. fabiojms@icb.ufrj.br. + + + + Aliota + Matthew T + MT + + Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. mtaliota@wisc.edu. + + + + Caine + Elizabeth A + EA + + Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. eacaine@wisc.edu. + + + + Osorio + Jorge E + JE + + Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. jorge.osorio@wisc.edu. + + + + Bellio + Maria + M + + Department of Immunology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. mariabellioufrj@gmail.com. + + + + O'Connor + David H + DH + + Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA. dhoconno@wisc.edu. + + + + Rehen + Stevens + S + + Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. srehen@lance-ufrj.org. + + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro 22281-100, Brazil. srehen@lance-ufrj.org. + + + + de Aguiar + Renato Santana + RS + + Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. santanarnt@gmail.com. + + + + Savarino + Andrea + A + + Istituto Superiore di Sanità, Deptartment of Infectious Diseases, 299 Viale Regina Elena, 00161 Rome, Italy. ansavari@yahoo.com. + + + + Campanati + Loraine + L + + Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. lcampanati@gmail.com. + + + + Tanuri + Amilcar + A + + Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. atanuri@biologia.ufrj.br. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 11 + 29 + +
+ + Switzerland + Viruses + 101509722 + 1999-4915 + + + + 0 + Antiviral Agents + + + 886U3H6UFF + Chloroquine + + + IM + + + N Engl J Med. 2016 Jun 2;374(22):2195-8 + 27074370 + + + Antimicrob Agents Chemother. 2009 Aug;53(8):3416-21 + 19506054 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + J Virol. 1998 Jan;72(1):783-8 + 9420287 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Virol J. 2006 May 29;3:39 + 16729896 + + + PLoS One. 2013;8(4):e60579 + 23577127 + + + PLoS One. 2012;7(6):e39565 + 22761827 + + + J Virol. 2001 Feb;75(3):1236-51 + 11152497 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Cell. 2016 May 19;165(5):1238-54 + 27118425 + + + MMWR Morb Mortal Wkly Rep. 2016 Apr 15;65(14):372-4 + 27078057 + + + Microb Pathog. 2001 Jan;30(1):19-28 + 11162182 + + + PLoS Negl Trop Dis. 2010 Aug 10;4(8):e785 + 20706626 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Antiviral Res. 2014 Jun;106:125-34 + 24680954 + + + Br J Clin Pharmacol. 2008 May;65(5):674-9 + 18279478 + + + ScientificWorldJournal. 2013;2013:282734 + 23431254 + + + Viruses. 2011 Feb;3(2):160-71 + 22049308 + + + Cell Host Microbe. 2016 May 11;19(5):705-12 + 27066743 + + + AIDS Res Hum Retroviruses. 1990 Apr;6(4):481-9 + 1692728 + + + Cell Res. 2013 Feb;23(2):300-2 + 23208422 + + + J Rheumatol. 1988 Apr;15(4):607-10 + 3397970 + + + Stem Cells Transl Med. 2013 Nov;2(11):862-70 + 24113065 + + + Mem Inst Oswaldo Cruz. 2013 Aug;108(5):596-9 + 23903975 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Cell Host Microbe. 2016 Aug 10;20(2):259-70 + 27476412 + + + Retrovirology. 2015 Jun 18;12:51 + 26084487 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Wiley Interdiscip Rev Dev Biol. 2013 Jul;2(4):461-78 + 24014418 + + + Br Med J (Clin Res Ed). 1985 May 18;290(6480):1466-7 + 3922534 + + + Trans R Soc Trop Med Hyg. 1956 Sep;50(5):442-8 + 13380987 + + + Am J Med. 1983 Jul 18;75(1A):40-5 + 6869410 + + + Viruses. 2014 Jul 18;6(7):2796-825 + 25046180 + + + J Med Microbiol. 2000 Apr;49(4):313-8 + 10755624 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + J Virol. 2012 Dec;86(24):13407-22 + 23015720 + + + J Virol. 2002 Dec;76(24):12866-76 + 12438612 + + + JAMA Neurol. 2016 Dec 1;73(12 ):1407-1416 + 27695855 + + + PLoS Negl Trop Dis. 2016 Oct 5;10 (10 ):e0005048 + 27706161 + + + N Engl J Med. 1994 Nov 3;331(18):1173-80 + 7935654 + + + J Med Virol. 2016 Dec;88(12 ):2170-2178 + 27183377 + + + Cell Transplant. 2012;21(7):1547-59 + 21975034 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Ther Drug Monit. 1989;11(4):369-79 + 2662478 + + + Lancet Infect Dis. 2003 Nov;3(11):722-7 + 14592603 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + N Engl J Med. 2016 Apr 21;374(16):1595-6 + 26958738 + + + Am J Perinatol. 1991 May;8(3):174-8 + 2029276 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Animals + + + Antiviral Agents + pharmacology + + + Cell Line + + + Cercopithecus aethiops + + + Chloroquine + pharmacology + + + Endocytosis + drug effects + + + Humans + + + Mice + + + Zika Virus + drug effects + physiology + + + Zika Virus Infection + virology + + + + Zika virus + antiviral + chloroquine + microcephaly + neural stem cell + + The authors declare no conflict of interest. +
+ + + + 2016 + 10 + 16 + + + 2016 + 11 + 16 + + + 2016 + 11 + 18 + + + 2016 + 12 + 6 + 6 + 0 + + + 2016 + 12 + 6 + 6 + 0 + + + 2017 + 9 + 14 + 6 + 0 + + + epublish + + 27916837 + v8120322 + 10.3390/v8120322 + PMC5192383 + + +
+ + + + + 27909576 + + 2017 + 09 + 05 + +
+ + 2046-1402 + + 5 + + 2016 + + + F1000Research + F1000Res + + Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library. + + 2523 + + + Background +The recent epidemics of Zika virus (ZIKV) implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the Guillain-Barré syndrome in otherwise healthy patients. Recent findings showed that anti-Dengue antibodies are capable of amplifying ZIKV infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. This scenario becomes potentially catastrophic when the global burden of Dengue and the advent of the newly approved anti-Dengue vaccines in the near future are taken into account. Thus, antiviral chemotherapy should be pursued as a priority strategy to control the spread of the virus and prevent the complications associated with Zika.MethodsHere we describe a fast and reliable cell-based, high-content screening assay for discovery of anti-ZIKV compounds. This methodology has been used to screen the National Institute of Health Clinical Collection compound library, a small collection of FDA-approved drugs.Results and conclusionFrom 725 FDA-approved compounds triaged, 29 (4%) were found to have anti-Zika virus activity, of which 22 had confirmed (76% of confirmation) by dose-response curves. Five candidates presented selective activity against ZIKV infection and replication in a human cell line. These hits have abroad spectrum of chemotypes and therapeutic uses, offering valuable opportunities for selection of leads for antiviral drug discovery. + + + + Pascoalino + Bruno S + BS + + Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas-SP, 10000, Brazil; Present Address: Instituto Butantan, São Paulo-SP, 1500, Brazil. + + + + Courtemanche + Gilles + G + + BIOASTER, Paris, 75015, France. + + + + Cordeiro + Marli T + MT + + Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz -Fiocruz, Recife/PE, Brazil. + + + + Gil + Laura H V G + LH + + Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz -Fiocruz, Recife/PE, Brazil. + + + + Freitas-Junior + Lucio + L + + Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas-SP, 10000, Brazil; Present Address: Instituto Butantan, São Paulo-SP, 1500, Brazil. + + + + eng + + Journal Article + + + 2016 + 10 + 14 + +
+ + England + F1000Res + 101594320 + 2046-1402 + + + + PLoS Negl Trop Dis. 2013;7(2):e2073 + 23437413 + + + Nat Rev Drug Discov. 2013 Jun;12(6):447-64 + 23722347 + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + BJOG. 2004 Sep;111(9):940-3 + 15327608 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + J Neurochem. 2007 Mar;100(5):1265-77 + 17286627 + + + J Gen Virol. 1978 Sep;40(3):531-44 + 690610 + + + J Biomol Screen. 1999;4(2):67-73 + 10838414 + + + Antiviral Res. 2003 Mar;58(1):73-9 + 12719009 + + + Nat Commun. 2016 May 12;7:11320 + 27177310 + + + Curr Protoc Microbiol. 2012 Nov;Chapter 15:Unit 15D.2. + 23184594 + + + N Engl J Med. 2015 Jan 8;372(2):113-23 + 25365753 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Cell Host Microbe. 2016 Aug 10;20(2):259-70 + 27476412 + + + PLoS One. 2014 Feb 21;9(2):e87412 + 24586275 + + + Virology. 2009 Jun 20;389(1-2):8-19 + 19419745 + + + Clin Infect Dis. 2016 Feb 15;62(4):468-476 + 26565005 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + Ann N Y Acad Sci. 1977 Mar 4;284:410-7 + 280143 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + Assay Drug Dev Technol. 2010 Oct;8(5):553-70 + 20973722 + + + J Virol. 2013 Sep;87(17):9411-9 + 23824813 + + + Reprod Toxicol. 2014 Dec;50:134-7 + 25450422 + + + Lancet. 2014 Oct 11;384(9951):1358-65 + 25018116 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + J Virol. 2004 Nov;78(21):12062-5 + 15479847 + + + Nat Immunol. 2016 Sep;17 (9):1102-8 + 27339099 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Curr Protoc Mol Biol. 2008 Jul;Chapter 11:Unit 11.10 + 18633992 + + + Antimicrob Agents Chemother. 2005 Nov;49(11):4508-14 + 16251289 + + + Nat Med. 2016 Oct;22(10 ):1101-1107 + 27571349 + + + Hepatology. 2006 Jul;44(1):117-25 + 16799963 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + Nat Rev Cancer. 2003 May;3(5):330-8 + 12724731 + + + PLoS Negl Trop Dis. 2013 Oct 31;7(10):e2471 + 24205414 + + + F1000Res. 2016 Oct 14;5:2523 + 27909576 + + + Bioorg Med Chem. 2008 Apr 15;16(8):4401-18 + 18329276 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + + FDA-approved drugs + High content screening drug discovery + Zika + + No competing interests were disclosed. +
+ + + + 2016 + 10 + 06 + + + 2016 + 12 + 3 + 6 + 0 + + + 2016 + 12 + 3 + 6 + 0 + + + 2016 + 12 + 3 + 6 + 1 + + + epublish + + 27909576 + 10.12688/f1000research.9648.1 + PMC5112578 + + +
+ + + + + 27906905 + + 2017 + 01 + 17 + + + 2017 + 01 + 17 + +
+ + 1545-861X + + 65 + 47 + + 2016 + Dec + 02 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Description of 13 Infants Born During October 2015-January 2016 With Congenital Zika Virus Infection Without Microcephaly at Birth - Brazil. + + 1343-1348 + + 10.15585/mmwr.mm6547e2 + + Congenital Zika virus infection can cause microcephaly and severe brain abnormalities (1). Congenital Zika syndrome comprises a spectrum of clinical features (2); however, as is the case with most newly recognized teratogens, the earliest documented clinical presentation is expected to be the most severe. Initial descriptions of the effects of in utero Zika virus infection centered prominently on the finding of congenital microcephaly (3). To assess the possibility of clinical presentations that do not include congenital microcephaly, a retrospective assessment of 13 infants from the Brazilian states of Pernambuco and Ceará with normal head size at birth and laboratory evidence of congenital Zika virus infection was conducted. All infants had brain abnormalities on neuroimaging consistent with congenital Zika syndrome, including decreased brain volume, ventriculomegaly, subcortical calcifications, and cortical malformations. The earliest evaluation occurred on the second day of life. Among all infants, head growth was documented to have decelerated as early as 5 months of age, and 11 infants had microcephaly. These findings provide evidence that among infants with prenatal exposure to Zika virus, the absence of microcephaly at birth does not exclude congenital Zika virus infection or the presence of Zika-related brain and other abnormalities. These findings support the recommendation for comprehensive medical and developmental follow-up of infants exposed to Zika virus prenatally. Early neuroimaging might identify brain abnormalities related to congenital Zika infection even among infants with a normal head circumference (4). + + + + van der Linden + Vanessa + V + + + Pessoa + André + A + + + Dobyns + William + W + + + Barkovich + A James + AJ + + + Júnior + Hélio van der Linden + HV + + + Filho + Epitacio Leite Rolim + EL + + + Ribeiro + Erlane Marques + EM + + + Leal + Mariana de Carvalho + MC + + + Coimbra + Pablo Picasso de Araújo + PP + + + Aragão + Maria de Fátima Viana Vasco + MF + + + Verçosa + Islane + I + + + Ventura + Camila + C + + + Ramos + Regina Coeli + RC + + + Cruz + Danielle Di Cavalcanti Sousa + DD + + + Cordeiro + Marli Tenório + MT + + + Mota + Vivian Maria Ribeiro + VM + + + Dott + Mary + M + + + Hillard + Christina + C + + + Moore + Cynthia A + CA + + + eng + + Case Reports + Journal Article + + + 2016 + 12 + 02 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant + + + Infant, Newborn + + + Male + + + Microcephaly + epidemiology + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Retrospective Studies + + + Zika Virus + isolation & purification + + + Zika Virus Infection + congenital + diagnosis + + +
+ + + + 2016 + 12 + 2 + 6 + 0 + + + 2016 + 12 + 3 + 6 + 0 + + + 2017 + 1 + 18 + 6 + 0 + + + epublish + + 27906905 + 10.15585/mmwr.mm6547e2 + + +
+ + + + + 27902502 + + 2017 + 07 + 10 + + + 2018 + 01 + 03 + +
+ + 1526-7598 + + 124 + 1 + + 2017 + 01 + + + Anesthesia and analgesia + Anesth. Analg. + + Zika Virus and Patient Blood Management. + + 282-289 + + + Sporadic Zika virus infections had only occurred in Africa and Asia until an outbreak in Micronesia (Oceania) in 2007. In 2013 to 2014, several outer Pacific Islands reported local outbreaks. Soon thereafter, the virus was likely introduced in Brazil from competing athletes from French Polynesia and other countries that participated in a competition there. Transmission is thought to have occurred through mosquito bites and spread to the immunologically naive population. Being also a flavivirus, the Zika virus is transmitted by the Aedes mosquito that is endemic in South and Central America that is also the vector of West Nile virus, dengue, and chikungunya. In less than a year, physicians in Brazil reported a many-fold increase in the number of babies born with microcephaly. Despite initial skepticism regarding the causal association of the Zika virus epidemic and birth defects, extensive basic and clinical research evidence has now confirmed this relationship. In the United States, more than 4000 travel-associated infections have been reported by the middle of 2016 to the Centers for Disease Control and Prevention. Furthermore, many local mosquito-borne infections have occurred in Puerto Rico and Florida. Considering that the virus causes a viremia in which 80% of infected individuals have no symptoms, the potential for transfusion transmission from an asymptomatic blood donor is high if utilizing donor screening alone without testing. Platelet units have been shown to infect 2 patients via transfusion in Brazil. Although there was an investigational nucleic acid test available for testing donors, not all blood centers were initially required to participate. Subsequently, the US Food and Drug Administration issued a guidance in August 2016 that recommended universal nucleic acid testing for the Zika virus on blood donors.In this report, we review the potentially devastating effects of Zika virus infection during pregnancy and its implication in cases of Guillain-Barre syndrome in adults. Furthermore, we urge hospital-based clinicians and transfusion medicine specialists to implement perisurgical patient blood management strategies to avoid blood component transfusions with their potential risks of emerging pathogens, illustrated here by the Zika virus. Ultimately, this current global threat, as described by the World Health Organization, will inevitably be followed by future outbreaks of other bloodborne pathogens; the principles and practices of perioperative patient blood management will reduce the risks from not only known, but also unknown risks of blood transfusion for our patients. + + + + Goodnough + Lawrence T + LT + + From Departments of *Pathology and †Medicine, Stanford University, Stanford, California; and ‡Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama. + + + + Marques + Marisa B + MB + + + eng + + Journal Article + Review + +
+ + United States + Anesth Analg + 1310650 + 0003-2999 + + AIM + IM + + + Blood Donors + + + Blood Loss, Surgical + prevention & control + + + Blood Transfusion + methods + + + Communicable Diseases, Emerging + blood + diagnosis + prevention & control + transmission + + + Disease Outbreaks + prevention & control + + + Donor Selection + + + Female + + + Guillain-Barre Syndrome + blood + prevention & control + virology + + + Humans + + + Infection Control + methods + + + Male + + + Patient Safety + + + Pregnancy + + + Pregnancy Complications, Infectious + blood + diagnosis + prevention & control + virology + + + Risk Assessment + + + Risk Factors + + + Transfusion Reaction + + + Travel + + + Zika Virus + isolation & purification + + + Zika Virus Infection + blood + diagnosis + prevention & control + transmission + + +
+ + + + 2016 + 12 + 3 + 6 + 0 + + + 2017 + 7 + 14 + 6 + 0 + + + 2016 + 12 + 1 + 6 + 0 + + + ppublish + + 27902502 + 10.1213/ANE.0000000000001770 + + +
+ + + + + 27901259 + + 2017 + 06 + 27 + + + 2017 + 08 + 17 + +
+ + 1678-4227 + + 74 + 11 + + 2016 + Nov + + + Arquivos de neuro-psiquiatria + Arq Neuropsiquiatr + + Neurological manifestations of Chikungunya and Zika infections. + + 937-943 + + S0004-282X2016001100937 + 10.1590/0004-282X20160138 + + The epidemics of Chikungunya virus (CHIKV) and Zika virus (ZIKV) infections have been considered the most important epidemiological occurrences in the Americas. The clinical picture of CHIKV infection is characterized by high fever, exanthema, myalgia, headaches, and arthralgia. Besides the typical clinical picture of CHIKV, atypical manifestations of neurological complications have been reported: meningo-encephalitis, meningoencephalo-myeloradiculitis, myeloradiculitis, myelitis, myeloneuropathy, Guillain-Barré syndrome and others. The diagnosis is based on clinical, epidemiological, and laboratory criteria. The most common symptoms of ZIKV infection are skin rash (mostly maculopapular), fever, arthralgia, myalgia, headache, and conjunctivitis. Some epidemics that have recently occurred in French Polynesia and Brazil, reported the most severe conditions, with involvement of the nervous system (Guillain-Barré syndrome, transverse myelitis, microcephaly and meningitis). The treatment for ZIKV and CHIKV infections are symptomatic and the management for neurological complications depends on the type of affliction. Intravenous immunoglobulin, plasmapheresis, and corticosteroid pulse therapy are options. + + + + Pinheiro + Talys J + TJ + + Hospital dos Servidores do Estado, Serviço de Neurologia, Rio de Janeiro RJ, Brasil. + + + + Guimarães + Luis F + LF + + Hospital dos Servidores do Estado, Serviço de Neurologia, Rio de Janeiro RJ, Brasil. + + + + Silva + Marcus Tulius T + MT + + Laboratório de Pesquisa Clínica em Doenças Neuroinfecciosas, Instituto Nacional de Doenças Infecciosas Evandro Chagas/ Fundação Oswaldo Cruz, RJ, Brasil. + + + + Soares + Cristiane N + CN + + Hospital dos Servidores do Estado, Serviço de Neurologia, Rio de Janeiro RJ, Brasil. + + + + eng + + Journal Article + Review + +
+ + Brazil + Arq Neuropsiquiatr + 0125444 + 0004-282X + + IM + + + Chikungunya Fever + complications + epidemiology + physiopathology + + + Disease Outbreaks + statistics & numerical data + + + Global Health + + + Guillain-Barre Syndrome + virology + + + Humans + + + Nervous System Diseases + epidemiology + physiopathology + virology + + + Zika Virus Infection + complications + epidemiology + physiopathology + + +
+ + + + 2016 + 07 + 08 + + + 2016 + 07 + 26 + + + 2016 + 12 + 1 + 6 + 0 + + + 2016 + 12 + 3 + 6 + 0 + + + 2017 + 6 + 28 + 6 + 0 + + + ppublish + + 27901259 + S0004-282X2016001100937 + 10.1590/0004-282X20160138 + + +
+ + + + + 27899230 + + 2017 + 03 + 10 + + + 2017 + 03 + 10 + +
+ + 1618-1433 + + 69 + 2 + + 2017 + Feb + + + Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie + Exp. Toxicol. Pathol. + + Experimental Zika virus infection induces spinal cord injury and encephalitis in newborn Swiss mice. + + 63-71 + + S0940-2993(16)30330-X + 10.1016/j.etp.2016.11.004 + + A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America, with neurological symptons including meningoencephalitis and Guillain-Barré syndrome in adults, besides an apparent increased incidence of microcephaly in infants born to infected mothers. It is becoming a necessity to have a trustworthy animal model to better understand ZIKV infection. In this study we used newborn white Swiss mice as a model to investigate the ZIKV strain recently isolated in Brazil. ZIKV was inoculated via intracerebral and subcutaneous routes and analysed through gross histopathology and immunohistochemistry. Here we demonstrated first that the intracerebral group (ICG) displayed severe cerebral lesions, with neuronal death, presence of apoptotic bodies, white matter degeneration and neutrophil perivascular cuffing. In the subcutaneous group (SCG), we observed moderate cerebral lesions, morphologically similar to that found in ICG and additional myelopathy, with architectural loss, marked by neuronal death and apoptotic bodies. Interestingly, we found an intense astrogliosis in brain of both groups, with increased immunoexpression of GFAP (glial fibrillary acidic protein) and presence of hypertrophic astrocytes. The spinal cord of subcutaneous group (SCG) exhibited reduction of astrocytes, but those positive for GFAP were hypertrophic and presented prolonged cellular processes. Finally significant lesions in the central nervous system (CNS) were present in newborn mice inoculated by both routes, but SCG method led to an important neurological manifestations (including myelopathy), during a longer period of time and appears for us to be a better model for ZIKV infection. + Copyright © 2016 Elsevier GmbH. All rights reserved. + + + + Fernandes + Natália C C A + NC + + Instituto Adolfo Lutz (IAL), Centro de Patologia, Brasil, Av. Dr. Arnaldo, 351-7°, Andar, Sala 706, Pacaembú, São Paulo, SP, 01246-000, Brazil. Electronic address: nccafernandes@yahoo.com.br. + + + + Nogueira + Juliana S + JS + + Instituto Adolfo Lutz (IAL), Centro de Virologia, Brasil, Av. Dr. Arnaldo, 355, Prédio da Virologia, Subsolo, Pacaembú, São Paulo, SP, 01246-000, Brazil. + + + + Réssio + Rodrigo A + RA + + Instituto Adolfo Lutz (IAL), Centro de Patologia, Brasil, Av. Dr. Arnaldo, 351-7°, Andar, Sala 706, Pacaembú, São Paulo, SP, 01246-000, Brazil. + + + + Cirqueira + Cinthya S + CS + + Instituto Adolfo Lutz (IAL), Centro de Patologia, Brasil, Av. Dr. Arnaldo, 351-7°, Andar, Sala 706, Pacaembú, São Paulo, SP, 01246-000, Brazil. + + + + Kimura + Lidia M + LM + + Instituto Adolfo Lutz (IAL), Centro de Patologia, Brasil, Av. Dr. Arnaldo, 351-7°, Andar, Sala 706, Pacaembú, São Paulo, SP, 01246-000, Brazil. + + + + Fernandes + Karolina R + KR + + Instituto Adolfo Lutz (IAL), Centro de Patologia, Brasil, Av. Dr. Arnaldo, 351-7°, Andar, Sala 706, Pacaembú, São Paulo, SP, 01246-000, Brazil. + + + + Cunha + Mariana S + MS + + Instituto Adolfo Lutz (IAL), Centro de Virologia, Brasil, Av. Dr. Arnaldo, 355, Prédio da Virologia, Subsolo, Pacaembú, São Paulo, SP, 01246-000, Brazil. + + + + Souza + Renato P + RP + + Instituto Adolfo Lutz (IAL), Centro de Virologia, Brasil, Av. Dr. Arnaldo, 355, Prédio da Virologia, Subsolo, Pacaembú, São Paulo, SP, 01246-000, Brazil. + + + + Guerra + Juliana M + JM + + Instituto Adolfo Lutz (IAL), Centro de Patologia, Brasil, Av. Dr. Arnaldo, 351-7°, Andar, Sala 706, Pacaembú, São Paulo, SP, 01246-000, Brazil. + + + + eng + + Journal Article + + + 2016 + 11 + 26 + +
+ + Germany + Exp Toxicol Pathol + 9208920 + 0940-2993 + + IM + + + Animals + + + Animals, Newborn + + + Brain + pathology + + + Disease Models, Animal + + + Encephalitis + pathology + virology + + + Female + + + Male + + + Mice + + + Myelitis + pathology + virology + + + Spinal Cord + pathology + + + Zika Virus Infection + pathology + + + + Brain + Encephalopathy + Flavivirus + Mouse + Myelitis + Pathology + +
+ + + + 2016 + 05 + 24 + + + 2016 + 11 + 02 + + + 2016 + 11 + 21 + + + 2016 + 12 + 3 + 6 + 0 + + + 2017 + 3 + 11 + 6 + 0 + + + 2016 + 12 + 1 + 6 + 0 + + + ppublish + + 27899230 + S0940-2993(16)30330-X + 10.1016/j.etp.2016.11.004 + + +
+ + + + + 27892990 + + 2017 + 07 + 05 + + + 2017 + 07 + 05 + +
+ + 2168-619X + + 143 + 1 + + 2017 + Jan + 01 + + + JAMA otolaryngology-- head & neck surgery + JAMA Otolaryngol Head Neck Surg + + Zika Virus-What the Otolaryngologist Should Know: A Review. + + 81-84 + + 10.1001/jamaoto.2016.3427 + + Initially discovered in 1947, Zika virus infection received little notoriety as a tropical disease until 2015 when an outbreak of microcephaly cases was reported in Brazil. Zika is a single-stranded RNA arbovirus of the Flaviviridae family. The primary source of infection in humans stems from Aedes aegypti mosquito bites but can also occur through sexual, blood, and perinatal transmission. With expectations that 3 to 4 million people across the Americas will be infected over the next year, the World Health Organization has declared this event a Public Health Emergency of International Concern. + Although acute Zika virus infection is typically mild and self-limited, researchers have demonstrated serious neurologic complications associated with it such as microcephaly and Guillain-Barre syndrome. Otolaryngologists should be aware of head and neck manifestations which include conjunctivitis, retro-orbital pain, cephalgia, and odynophagia. The Centers for Disease Control and Prevention have developed specific molecular and serologic testing protocols and algorithms for follow-up care of suspected cases. Currently, the mainstay of management is conservative care while researchers attempt to develop a vaccine. Strategies to contain the Zika virus include vector control, travel restriction for women who are pregnant or trying to become pregnant, and avoidance of mosquito bites in endemic regions of the world. + The future outlook regarding the current Zika virus outbreak in the Americas remains uncertain. What is certain is our need to promptly and efficiently address research gaps in our understanding of clinical outcomes from infection and environmental factors that influence emergence meanwhile improving diagnostic, therapeutic, and preventive measures against the disease. + + + + Arnaoutakis + Demetri + D + + Department of Otolaryngology-Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas. + + + + Padhya + Tapan + T + + Department of Otolaryngology-Head and Neck Surgery, University of South Florida College of Medicine, Tampa. + + + + eng + + Journal Article + Review + +
+ + United States + JAMA Otolaryngol Head Neck Surg + 101589542 + 2168-6181 + + AIM + IM + + + Clinical Competence + + + Communicable Disease Control + organization & administration + + + Disease Outbreaks + prevention & control + + + Female + + + Global Health + + + Humans + + + Incidence + + + Male + + + Needs Assessment + + + Otolaryngologists + education + + + Pregnancy + + + Risk Assessment + + + Travel + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + prevention & control + + +
+ + + + 2016 + 11 + 29 + 6 + 0 + + + 2017 + 7 + 6 + 6 + 0 + + + 2016 + 11 + 29 + 6 + 0 + + + ppublish + + 27892990 + 2585379 + 10.1001/jamaoto.2016.3427 + + +
+ + + + + 27878100 + + 2017 + 08 + 16 + +
+ + 2220-3249 + + 5 + 4 + + 2016 + Nov + 12 + + + World journal of virology + World J Virol + + Neurological manifestations of Zika virus infection. + + 135-143 + + + Zika virus (ZIKV) is a flavivirus (Flaviviridaefamily) transmitted mainly byAedesmosquitoes. The virus was restricted to the African continent until its spread to south-east Asia in the 1980's, the Micronesia in 2007, the French Polynesia in 2013 and, more recently in the Americas in 2015, where, up to date, the World Health Organization (WHO) has estimated about 3-4 million total cases of ZIKV infection. During outbreaks in the French Polynesia and Brazil in 2013 and 2015, respectively, national health authorities reported potential neurological complications of ZIKV disease, chiefly an upsurge in Guillain-Barré syndrome, which coincided with ZIKV outbreaks. On the other hand, the emergence of ZIKV in Brazil has been associated with a striking increase in the number of reported cases of microcephaly in fetus and newborns, twenty times higher than in that reported in previous years. While investigations are currently assessing whether there is an actual association between neurological complications and ZIKV infections, the evidence was enough worrisome for WHO to declare a public health emergency of international concern. Here we present an updated review addressing what is currently known about the possible association between ZIKV infection and the development of severe neurological disorders. + + + + Blázquez + Ana-Belén + AB + + Ana-Belén Blázquez, Juan-Carlos Saiz, Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, 28040 Madrid, Spain. + + + + Saiz + Juan-Carlos + JC + + Ana-Belén Blázquez, Juan-Carlos Saiz, Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, 28040 Madrid, Spain. + + + + eng + + Review + Journal Article + +
+ + United States + World J Virol + 101608353 + 2220-3249 + + + + Virus Res. 2010 Aug;151(2):240-3 + 20438776 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Lancet. 2016 Mar 12;387(10023):1051 + 26944028 + + + PLoS Negl Trop Dis. 2016 Mar 18;10(3):e0004589 + 26991663 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + J Gen Virol. 2004 Dec;85(Pt 12):3637-45 + 15557236 + + + Arch Virol. 2007;152(4):687-96 + 17195954 + + + Cell. 2015 Aug 13;162(4):738-50 + 26276630 + + + Vector Borne Zoonotic Dis. 2014 Dec;14(12):862-5 + 25514122 + + + Cytobios. 1987;49(196):49-55 + 3028713 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + Sci Transl Med. 2016 Mar 16;8(330):330ed2 + 27089202 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Front Microbiol. 2016 Apr 19;7:496 + 27148186 + + + Lancet Infect Dis. 2016 Apr;16(4):405 + 26949027 + + + Euro Surveill. 2014 Oct 16;19(41):null + 25345518 + + + Lancet. 2016 Apr 9;387(10027):1587-90 + 26952548 + + + Neurology. 2013 Apr 30;80(18):1650-4 + 23576619 + + + PLoS Negl Trop Dis. 2016 Mar 02;10(3):e0004530 + 26934531 + + + Hepatology. 2013 Jan;57(1):46-58 + 22911572 + + + N Engl J Med. 2012 Jun 14;366(24):2294-304 + 22694000 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3 + 26796813 + + + Rev Neurol. 2014 Jan 1;58(1):4-10 + 24343535 + + + Trans R Soc Trop Med Hyg. 1958 May;52(3):263-8 + 13556872 + + + Lancet. 2016 Aug 13;388(10045):717-27 + 26948435 + + + Virology. 1987 Aug;159(2):237-43 + 2441520 + + + Neurol India. 2015 Jul-Aug;63(4):497-516 + 26238884 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Genome Announc. 2014 Jun 05;2(3):null + 24903869 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Lancet. 2016 Apr 9;387(10027):1486-8 + 26948432 + + + Nature. 2016 Apr 19;533(7603):425-8 + 27093288 + + + J Virol. 2016 Apr 29;90(10 ):4864-75 + 26962217 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + J Pediatr (Rio J). 2016 Mar-Apr;92 (2):103-5 + 27036749 + + + J Clin Virol. 2016 Apr;77:29-31 + 26895226 + + + J Virol. 2007 Jul;81(13):7136-48 + 17459925 + + + EMBO Mol Med. 2016 Mar 31;8(4):305-7 + 26976611 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Lancet. 2016 Mar 12;387(10023):1051-2 + 26944027 + + + J Virol. 2006 Dec;80(23):11418-31 + 16928749 + + + Emerg Infect Dis. 2016 May;22(5):940 + 27088817 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + J Gen Virol. 2006 Mar;87(Pt 3):613-22 + 16476982 + + + Antiviral Res. 2016 Jun;130:69-80 + 26996139 + + + MMWR Morb Mortal Wkly Rep. 2016 Apr 01;65(12):323-5 + 27032078 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Virol J. 2013 Oct 22;10:311 + 24148652 + + + PLoS Pathog. 2015 Nov 12;11(11):e1005277 + 26562291 + + + J Clin Virol. 2015 Jul;68:53-5 + 26071336 + + + Elife. 2015 Jun 30;4:e08347 + 26126267 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + Am J Trop Med Hyg. 2001 May-Jun;64(5-6):310-6 + 11463123 + + + Dev Med Child Neurol. 2014 Aug;56(8):732-41 + 24617602 + + + Science. 2016 Apr 22;352(6284):467-70 + 27033547 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Viruses. 2012 Mar;4(3):397-413 + 22590678 + + + Emerg Infect Dis. 2011 Sep;17(9):1779-80 + 21888828 + + + Neurology. 2004 Jul 27;63(2):206-7 + 15277609 + + + Euro Surveill. 2016;21(8):null + 26939607 + + + Clin Infect Dis. 2013 Aug;57(3):415-7 + 23575200 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Nature. 2016 Mar 10;531(7593):153 + 26961637 + + + Virology. 1995 Jan 10;206(1):49-56 + 7530394 + + + World J Virol. 2012 Apr 12;1(2):51-70 + 24175211 + + + Nature. 2010 Nov 18;468(7322):452-6 + 21085181 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Lancet. 2016 May 21;387(10033):2070-2 + 26993880 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Lancet Infect Dis. 2016 Feb;16(2):157 + 26867462 + + + Neurology. 2007 Nov 27;69(22):2105-7 + 18040016 + + + BMJ. 2016 Feb 04;352:i720 + 26848011 + + + J Pediatr. 2013 Nov;163(5):1514-6 + 23916226 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Flavivirus + Guillain-Barré syndrome + Microcephaly + Transmission routes + Zika virus + + Conflict-of-interest statement: The authors report no conflict of interest. +
+ + + + 2016 + 04 + 08 + + + 2016 + 06 + 29 + + + 2016 + 08 + 11 + + + 2016 + 11 + 24 + 6 + 0 + + + 2016 + 11 + 24 + 6 + 0 + + + 2016 + 11 + 24 + 6 + 1 + + + ppublish + + 27878100 + 10.5501/wjv.v5.i4.135 + PMC5105046 + + +
+ + + + + 27869982 + + 2016 + 11 + 23 + +
+ + 2237-9622 + + 25 + 4 + + 2016 Oct-Dec + + + Epidemiologia e servicos de saude : revista do Sistema Unico de Saude do Brasil + Epidemiol Serv Saude + + Characteristics of the first cases of microcephaly possibly related to Zika virus reported in the Metropolitan Region of Recife, Pernambuco State, Brazil. + + 691-700 + + S2237-96222016000400691 + 10.5123/S1679-49742016000400003 + + to describe the first cases of microcephaly possibly related to Zika virus in live born babies reported in the Metropolitan Region of Recife, Pernambuco State, Brazil. + this was a descriptive case series study (cases reported between August 1st and October 31st 2015), using medical record data and data from a questionnaire answered by the mothers of the babies. + 40 microcephaly cases were confirmed, distributed in eight municipalities within the Metropolitan Region, with Recife itself having the highest concentration of cases (n=12); median head circumference was 29 cm, median chest girth was 31 cm and median weight was 2,628 grams; 21/25 cases had brain calcification, ventriculomegaly or lissencephaly; 27 of the 40 mothers reported rash during pregnancy, 20 in the first trimester and 7 in the second trimester, as well as itching, headache, myalgia and absence of fever. + the majority of the cases bore the characteristics of congenital infection; the clinical condition of the majority of mothers suggested Zika virus infection during pregnancy. + + + + Vargas + Alexander + A + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Saad + Eduardo + E + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Dimech + George Santiago + GS + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Santos + Roselene Hans + RH + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Sivini + Maria Auxiliadora Vieira Caldas + MA + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Albuquerque + Luciana Carolina + LC + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Lima + Patricia Michelly Santos + PM + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Barreto + Idalacy de Carvalho + IC + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Andrade + Michelly Evangelista de + ME + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Estima + Nathalie Mendes + NM + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Carvalho + Patrícia Ismael de + PI + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Azevedo + Rayane Souza de Andrade + RS + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Vasconcelos + Rita de Cássia de Oliveira + RC + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Assunção + Romildo Siqueira + RS + + Secretaria Estadual de Saúde de Pernambuco, Recife-PE, Brasil. + + + + Frutuoso + Lívia Carla Vinhal + LC + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Carmo + Greice Madeleine Ikeda do + GM + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Souza + Priscila Bochi de + PB + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Wada + Marcelo Yoshito + MY + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Oliveira + Wanderson Kleber de + WK + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Henriques + Cláudio Maierovitch Pessanha + CM + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + Percio + Jadher + J + + Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília-DF, Brasil. + + + + eng + por + + Journal Article + + Características dos primeiros casos de microcefalia possivelmente relacionados ao vírus Zika notificados na Região Metropolitana de Recife, Pernambuco. + + 2016 + 09 + 26 + +
+ + Brazil + Epidemiol Serv Saude + 101248287 + 1679-4974 + +
+ + + + 2016 + 06 + 24 + + + 2016 + 06 + 30 + + + 2016 + 11 + 22 + 6 + 0 + + + 2016 + 11 + 22 + 6 + 0 + + + 2016 + 11 + 22 + 6 + 0 + + + ppublish + + 27869982 + S2237-96222016005001102 + 10.5123/S1679-49742016000400003 + + +
+ + + + + 27865425 + + 2017 + 04 + 01 + +
+ + 1578-1860 + + 217 + 3 + + 2017 + Apr + + + Revista clinica espanola + Rev Clin Esp + + Zika virus infection during the Olympic Games in Rio: A fear or an actual risk? + + 155-160 + + S0014-2565(16)30159-X + 10.1016/j.rce.2016.10.004 + + The recent outbreak of Zika virus infection in Brazil has aroused considerable media interest due to its association with neurological malformations in children born from mothers infected by the virus and to its association with Guillain-Barre syndrome in adults. This relationship has led to the World Health Organisation declaring the current epidemic as a "Public Health Emergency of International Concern". Controversy also emerged on the advisability of delaying or changing the location of the Olympic and Paralympic Games, which were held in August at various locations in Brazil. In this article, we review the available evidence on the risk of Zika and dengue virus infection in individuals who travel to endemic countries, especially for multitudinous events. + Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved. + + + + Díaz-Menéndez + M + M + + Unidad de Medicina Tropical y del Viajero, Hospital Universitario La Paz-CarlosIII Madrid, España. Electronic address: marta.diaz@salud.madrid.org. + + + + Trigo + E + E + + Unidad de Medicina Tropical y del Viajero, Hospital Universitario La Paz-CarlosIII Madrid, España. + + + + de la Calle-Prieto + F + F + + Unidad de Medicina Tropical y del Viajero, Hospital Universitario La Paz-CarlosIII Madrid, España. + + + + Arsuaga + M + M + + Unidad de Medicina Tropical y del Viajero, Hospital Universitario La Paz-CarlosIII Madrid, España. + + + + eng + spa + + Journal Article + + Infección por virus Zika durante los Juegos Olímpicos de Río: ¿alarma o riesgo real? + + 2016 + 11 + 17 + +
+ + Spain + Rev Clin Esp + 8608576 + 0014-2565 + + + Arboviriasis + Arbovirosis + Flavivirus + Guillain-Barré + Microcefalia + Microcephaly + Virus Zika + Zika virus + +
+ + + + 2016 + 07 + 04 + + + 2016 + 09 + 13 + + + 2016 + 10 + 16 + + + 2016 + 11 + 21 + 6 + 0 + + + 2016 + 11 + 21 + 6 + 0 + + + 2016 + 11 + 21 + 6 + 0 + + + ppublish + + 27865425 + S0014-2565(16)30159-X + 10.1016/j.rce.2016.10.004 + + +
+ + + + + 27853521 + + 2017 + 09 + 05 + +
+ + 2046-1402 + + 5 + + 2016 + + + F1000Research + F1000Res + + Zika mosquito vectors: the jury is still out. + + 2546 + + + After a 40-year hiatus, the International Congress of Entomology (ICE 2016) convened in Orlando, Florida (September 25-30, 2016). One of the symposia at ICE 2016, the Zika Symposium, covered multiple aspects of the Zika epidemic, including epidemiology, sexual transmission, genetic tools for reducing transmission, and particularly vector competence. While there was a consensus among participants that the yellow fever mosquito,Aedes aegypti, is a vector of the Zika virus, there is growing evidence indicating that the range of mosquito vectors might be wider than anticipated. In particular, three independent groups from Canada, China, and Brazil presented and discussed laboratory and field data strongly suggesting that the southern house mosquito,Culex quinquefasciatus, also known as the common mosquito, is highly likely to be a vector in certain environments. + + + + Leal + Walter S + WS + + Department of Molecular and Cellular Biology, University of California-Davis, Davis, USA. + + + + eng + + Journal Article + + + 2016 + 10 + 20 + +
+ + England + F1000Res + 101594320 + 2046-1402 + + + + PLoS Negl Trop Dis. 2016 Sep 06;10 (9):e0004993 + 27598421 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Emerg Microbes Infect. 2016 Sep 07;5(9):e102 + 27599470 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Lancet. 2016 Mar 12;387(10023):1051-1052 + 26944027 + + + Emerg Infect Dis. 2016 Oct;22(10):1857-9 + 27434194 + + + Lancet Infect Dis. 2016 Mar;16(3):278-9 + 26852727 + + + Vector Borne Zoonotic Dis. 2016 Oct;16(10 ):673-6 + 27556838 + + + Emerg Infect Dis. 2016 Dec;22(12 ):2228-2230 + 27617352 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Emerg Microbes Infect. 2017 Aug 9;6(8):e69 + 28790458 + + + Euro Surveill. 2016 Aug 11;21(32): + 27541989 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Aedes aegypti + Chikungunya + Culex quinquefasciatus + Guillain-Barré syndrome + Zika + microcephaly + + W.S.L. has a long-term collaboration with FIOCRUZ-PE and is a co-author of the paper by Guedes et al. 21 , currently under consideration for publication. +
+ + + + 2016 + 10 + 19 + + + 2016 + 11 + 18 + 6 + 0 + + + 2016 + 11 + 18 + 6 + 0 + + + 2016 + 11 + 18 + 6 + 1 + + + epublish + + 27853521 + 10.12688/f1000research.9839.1 + PMC5105876 + + +
+ + + + + 27852587 + + 2017 + 04 + 03 + + + 2017 + 08 + 17 + +
+ + 1756-1833 + + 355 + + 2016 + Nov + 16 + + + BMJ (Clinical research ed.) + BMJ + + Babies with microcephaly in Brazil are struggling to access care. + + i6157 + + 10.1136/bmj.i6157 + + + Collucci + Cláudia + C + + São Paulo. + + + + eng + + News + + + 2016 + 11 + 16 + +
+ + England + BMJ + 8900488 + 0959-535X + + AIM + IM + + + Brazil + epidemiology + + + Female + + + Health Services Accessibility + + + Humans + + + Infant + + + Infant, Newborn + + + Male + + + Microcephaly + epidemiology + therapy + virology + + + Zika Virus Infection + epidemiology + therapy + + +
+ + + + 2016 + 11 + 18 + 6 + 0 + + + 2016 + 11 + 18 + 6 + 0 + + + 2017 + 4 + 4 + 6 + 0 + + + epublish + + 27852587 + + +
+ + + + + 27835966 + + 2017 + 05 + 15 + + + 2017 + 05 + 15 + +
+ + 1471-2334 + + 16 + 1 + + 2016 + Nov + 11 + + + BMC infectious diseases + BMC Infect. Dis. + + Three cases of Zika virus imported in Italy: need for a clinical awareness and evidence-based knowledge. + + 669 + + + Since early 2015, a large epidemic of Zika Virus (ZIKV) is spreading across South and Central America. An association between congenital neurological malformations (mainly microcephaly), other neurological manifestations such as Guillain-Barrè Syndrome, and ZIKV infection is suspected. + Three confirmed cases of ZIKV in travelers returning from Brazil between May 2015 and January 2016 are described. All patients had mild symptoms with no neurological complications. + An increasing awareness among clinicians about this emerging disease is advisable, both for the need to provide correct additional information to the patients and to travelers, with a special focus on pregnant women, and for the presence of the competent vector in Southern Europe. + + + + Nicastri + Emanuele + E + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + Pisapia + Raffaella + R + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + Corpolongo + Angela + A + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + Fusco + Francesco Maria + FM + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + Cicalini + Stefania + S + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + Scognamiglio + Paola + P + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + Castilletti + Concetta + C + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + Bordi + Licia + L + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + Di Caro + Antonino + A + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + Capobianchi + Maria Rosaria + MR + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + Puro + Vincenzo + V + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. vincenzo.puro@inmi.it. + + + Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani", Via Portuense 292, 00149, Rome, Italy. vincenzo.puro@inmi.it. + + + + Ippolito + Giuseppe + G + + National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292- 00149, Rome, Italy. + + + + eng + + Case Reports + Journal Article + + + 2016 + 11 + 11 + +
+ + England + BMC Infect Dis + 100968551 + 1471-2334 + + IM + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):120-1 + 26866485 + + + J Gen Virol. 2011 Dec;92(Pt 12):2821-9 + 21900425 + + + Euro Surveill. 2016 May 5;21(18): + 27171034 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3 + 26796813 + + + Vector Borne Zoonotic Dis. 2007 Winter;7(4):467-77 + 18020965 + + + Eur J Intern Med. 2015 Jul;26(6):451-2 + 25818036 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + Clin Infect Dis. 2008 Aug 1;47(3):428-9 + 18605910 + + + J Virol Methods. 2005 Mar;124(1-2):65-71 + 15664052 + + + Euro Surveill. 2008 Feb 14;13(7):null + 18445417 + + + Swiss Med Wkly. 2016 Feb 09;146:w14296 + 26859285 + + + Euro Surveill. 2014 Jan 30;19(4):null + 24507467 + + + + + Adult + + + Aged + + + Brazil + epidemiology + + + Female + + + Humans + + + Italy + epidemiology + + + Male + + + Middle Aged + + + Pregnancy + + + Travel + + + Zika Virus + + + Zika Virus Infection + epidemiology + pathology + + + + Emerging or re-emerging diseases + Imported viral diseases + Pregnancy + Surveillance + Travel + Zika virus + +
+ + + + 2016 + 03 + 09 + + + 2016 + 10 + 25 + + + 2016 + 11 + 13 + 6 + 0 + + + 2016 + 11 + 12 + 6 + 0 + + + 2017 + 5 + 16 + 6 + 0 + + + epublish + + 27835966 + 10.1186/s12879-016-1973-5 + 10.1186/s12879-016-1973-5 + PMC5106818 + + +
+ +
+ + + + + 27835759 + + 2018 + 01 + 02 + + + 2018 + 03 + 09 + +
+ + 1873-5967 + + 85 + + 2016 + 12 + + + Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology + J. Clin. Virol. + + Zika virus epidemic in Brazil. I. Fatal disease in adults: Clinical and laboratorial aspects. + + 56-64 + + S1386-6532(16)30585-6 + 10.1016/j.jcv.2016.10.024 + + Zika virus (ZIKV) was first detected in Brazil in May 2015 and the country experienced an explosive epidemic. However, recent studies indicate that the introduction of ZIKV occurred in late 2013. Cases of microcephaly and deaths associated with ZIKV infection were identified in Brazil in November, 2015. + To determine the etiology of three fatal adult cases. + Here we report three fatal adult cases of ZIKV disease. ZIKV infection in these patients was confirmed by cells culture and/or real-time reverse transcriptase polymerase chain reaction (RT-qPCR) and by antigen detection using immunohistochemical assay. Samples of brain and other selected organs taken at autopsy from three patients were also analyzed by histopathological and immunohistological examination. + The first patient, a 36-year-old man with lupus and receiving prednisone therapy, developed a fulminant ZIKV infection. At autopsy, RT-qPCR of blood and tissues was positive for ZIKV RNA, and the virus was cultured from an organ homogenate. The second patient, a previously healthy female, 16 years of age, presented classic symptoms of Zika fever, but later developed severe thrombocytopenia, anemia and hemorrhagic manifestations and died. A blood sample taken on the seventh day of her illness was positive RT-PCR for ZIKV RNA and research in the serum was positive for antinuclear factor fine speckled (1/640), suggesting Evans syndrome (hemolytic anemia an autoimmune disorder with immune thrombocytopenic purpura) secondary to ZIKV infection. The third patient was a 20-year-old woman hospitalized with fever, pneumonia and hemorrhages, who died on 13days after admission. Histopathological changes were observed in all viscera examined. ZIKV antigens were detected by immunohistochemistry in viscera specimens of patients 1 and 3. These three cases demonstrate other potential complications of ZIKV infection, in addition to microcephaly and Guillain-Barre syndrome (GBS), and they suggest that individuals with immune suppression and/or autoimmune disorders may be at higher risk of developing severe disease, if infected with ZIKV. + Copyright © 2016 Elsevier B.V. All rights reserved. + + + + Azevedo + Raimunda S S + RS + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil; Programa de Pós-graduação em Virologia (PPGV) do Instituto Evandro Chagas, Ananindeua, Pará, Brazil. Electronic address: raimundaazevedo@iec.pa.gov.br. + + + + Araujo + Marialva T + MT + + Seção de Patologia, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: marialvaaraujo@iec.pa.gov.br. + + + + Martins Filho + Arnaldo J + AJ + + Seção de Patologia, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: arnaldofilho@iec.pa.gov.br. + + + + Oliveira + Consuelo S + CS + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: consuelooliveira@iec.pa.gov.br. + + + + Nunes + Bruno T D + BT + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: brunonunes@iec.pa.gov.br. + + + + Cruz + Ana C R + AC + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil; Departamento de Patologia, Universidade do Estado do Pará, Belém, Pará, Brazil. Electronic address: anacecilia@iec.pa.gov.br. + + + + Nascimento + Ana G P A C + AG + + Universidade Federal do Maranhão, São Luiz, Maranhão, Brazil. Electronic address: ana.giselia@globo.com. + + + + Medeiros + Rita C + RC + + Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, Pará, Brazil. Electronic address: ritaclosset@uol.com.br. + + + + Caldas + Cezar A M + CA + + Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, Pará, Brazil. Electronic address: cezar_caldas@yahoo.com.br. + + + + Araujo + Fernando C + FC + + Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, Pará, Brazil. Electronic address: fernando.stm@hotmail.com. + + + + Quaresma + Juarez A S + JA + + Departamento de Patologia, Universidade do Estado do Pará, Belém, Pará, Brazil. Electronic address: juarez.quaresma@gmail.com. + + + + Vasconcelos + Barbara C B + BC + + Departamento de Patologia, Universidade do Estado do Pará, Belém, Pará, Brazil. Electronic address: barbaravasconcelos@globo.com. + + + + Queiroz + Maria G L + MG + + Laboratório Central, Secretaria de Saúde Pública do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. Electronic address: lacenrn@yahoo.com.br. + + + + da Rosa + Elizabeth S Travassos + ES + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: elizabethsalbe@iec.pa.gov.br. + + + + Henriques + Daniele F + DF + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: danielehenriques@iec.pa.gov.br. + + + + Silva + Eliana V P + EV + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: elianapinto@iec.pa.gov.br. + + + + Chiang + Jannifer O + JO + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: anniferchiang@iec.pa.gov.br. + + + + Martins + Lívia C + LC + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: liviamartins@iec.pa.gov.br. + + + + Medeiros + Daniele B A + DB + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: danielemedeiros@iec.pa.gov.br. + + + + Lima + Juliana A + JA + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: julianaabreulima@hotmail.com. + + + + Nunes + Márcio R T + MR + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: marcionunesbrasil@yahoo.com.br. + + + + Cardoso + Jedson F + JF + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil; Programa de Pós-graduação em Virologia (PPGV) do Instituto Evandro Chagas, Ananindeua, Pará, Brazil. Electronic address: jedson.cardoso@gmail.com. + + + + Silva + Sandro P + SP + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: spatroca@gmail.com. + + + + Shi + Pei-Yong + PY + + Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: peshi@utmb.edu. + + + + Tesh + Robert B + RB + + Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: rtesh@utmb.edu. + + + + Rodrigues + Sueli G + SG + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil. Electronic address: suelirodrigues@iec.pa.gov.br. + + + + Vasconcelos + Pedro F C + PF + + Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil; Departamento de Patologia, Universidade do Estado do Pará, Belém, Pará, Brazil. Electronic address: pedrovasconcelos@iec.pa.gov.br. + + + + eng + + + R24 AI120942 + AI + NIAID NIH HHS + United States + + + + Case Reports + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + + + 2016 + 11 + 05 + +
+ + Netherlands + J Clin Virol + 9815671 + 1386-6532 + + + + 0 + Antigens, Viral + + + 0 + RNA, Viral + + + IM + + + Arch Neurol. 2004 Aug;61(8):1210-20 + 15313837 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + MMWR Morb Mortal Wkly Rep. 2016 May 06;65(17 ):451-5 + 27149205 + + + J Histochem Cytochem. 1981 Apr;29(4):577-80 + 6166661 + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + Am J Trop Med Hyg. 2006 Aug;75(2):356-62 + 16896148 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + Lancet. 2016 Mar 5;387(10022):939-40 + 26906627 + + + J Med Virol. 2014 Jul;86(7):1193-7 + 24114877 + + + Lancet. 2016 Feb 20;387(10020):719-21 + 26876373 + + + Acta Trop. 2005 May;94(2):116-27 + 15829426 + + + Emerg Infect Dis. 2016 Jul;22(7):1185-92 + 27070380 + + + Vector Borne Zoonotic Dis. 2016 May;16(5):295-301 + 26991057 + + + J Virol. 2016 Apr 29;90(10 ):4864-75 + 26962217 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Nature. 2011 Jul 20;475(7356):348-52 + 21776081 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Emerg Infect Dis. 2016 May;22(5):933-5 + 27088323 + + + Brain Pathol. 2007 Oct;17(4):354-62 + 17610522 + + + Lancet Infect Dis. 2016 May;16(5):523-4 + 27068488 + + + J Clin Virol. 2016 Feb;75:16-20 + 26741825 + + + Am J Trop Med Hyg. 1991 Oct;45(4):408-17 + 1951849 + + + Virology. 2006 Feb 5;345(1):22-30 + 16278000 + + + Am J Trop Med Hyg. 1979 Nov;28(6):1053-9 + 41456 + + + J Clin Virol. 2008 Sep;43(1):96-101 + 18674965 + + + Emerg Infect Dis. 2016 May;22(5):925-7 + 27089120 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Nature. 2005 Sep 15;437(7057):376-80 + 16056220 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Adolescent + + + Adult + + + Antigens, Viral + analysis + + + Autopsy + + + Brain + virology + + + Brazil + + + Fatal Outcome + + + Female + + + Humans + + + Immunohistochemistry + + + Male + + + RNA, Viral + blood + + + Real-Time Polymerase Chain Reaction + + + Virus Cultivation + + + Viscera + virology + + + Young Adult + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + pathology + + + + Autoimmune disorders + Erythematous lupus + Evans syndrome + Histopathology + Immunohistochemistry + Zika virus + + Authors declare they have not conflict of interest. +
+ + + + 2016 + 08 + 16 + + + 2016 + 10 + 26 + + + 2016 + 10 + 31 + + + 2016 + 11 + 12 + 6 + 0 + + + 2018 + 1 + 3 + 6 + 0 + + + 2016 + 11 + 12 + 6 + 0 + + + ppublish + + 27835759 + S1386-6532(16)30585-6 + 10.1016/j.jcv.2016.10.024 + PMC5233712 + NIHMS840576 + + +
+ + + + + 27812690 + + 2017 + 07 + 05 + + + 2018 + 03 + 03 + +
+ + 2168-6211 + + 171 + 3 + + 2017 + Mar + 01 + + + JAMA pediatrics + JAMA Pediatr + + Characterizing the Pattern of Anomalies in Congenital Zika Syndrome for Pediatric Clinicians. + + 288-295 + + 10.1001/jamapediatrics.2016.3982 + + Zika virus infection can be prenatally passed from a pregnant woman to her fetus. There is sufficient evidence to conclude that intrauterine Zika virus infection is a cause of microcephaly and serious brain anomalies, but the full spectrum of anomalies has not been delineated. To inform pediatric clinicians who may be called on to evaluate and treat affected infants and children, we review the most recent evidence to better characterize congenital Zika syndrome. + We reviewed published reports of congenital anomalies occurring in fetuses or infants with presumed or laboratory-confirmed intrauterine Zika virus infection. We conducted a comprehensive search of the English literature using Medline and EMBASE for Zika from inception through September 30, 2016. Congenital anomalies were considered in the context of the presumed pathogenetic mechanism related to the neurotropic properties of the virus. We conclude that congenital Zika syndrome is a recognizable pattern of structural anomalies and functional disabilities secondary to central and, perhaps, peripheral nervous system damage. Although many of the components of this syndrome, such as cognitive, sensory, and motor disabilities, are shared by other congenital infections, there are 5 features that are rarely seen with other congenital infections or are unique to congenital Zika virus infection: (1) severe microcephaly with partially collapsed skull; (2) thin cerebral cortices with subcortical calcifications; (3) macular scarring and focal pigmentary retinal mottling; (4) congenital contractures; and (5) marked early hypertonia and symptoms of extrapyramidal involvement. + Although the full spectrum of adverse reproductive outcomes caused by Zika virus infection is not yet determined, a distinctive phenotype-the congenital Zika syndrome-has emerged. Recognition of this phenotype by clinicians for infants and children can help ensure appropriate etiologic evaluation and comprehensive clinical investigation to define the range of anomalies in an affected infant as well as determine essential follow-up and ongoing care. + + + + Moore + Cynthia A + CA + + National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia. + + + + Staples + J Erin + JE + + National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Ft Collins, Colorado. + + + + Dobyns + William B + WB + + University of Washington and Seattle Children's Research Institute, Seattle. + + + + Pessoa + André + A + + Hospital Infantil Albert Sabin, Fortaleza, Ceará, Brazil. + + + + Ventura + Camila V + CV + + Altino Ventura Foundation, Recife, Pernambuco, Brazil6HOPE Eye Hospital, Recife, Pernambuco, Brazil7Federal University of São Paulo, São Paulo, Brazil. + + + + Fonseca + Eduardo Borges da + EB + + NOVA Diagnóstico Por Imagem, João Pessoa, Paraíba, Brazil9Federal University of Paraiba, João Pessoa, Paraíba, Brazil. + + + + Ribeiro + Erlane Marques + EM + + Hospital Infantil Albert Sabin, Fortaleza, Ceará, Brazil10Estacio Faculdade de Medicina de Juazeiro do Norte, Juazeiro do Norte, Ceará, Brazil. + + + + Ventura + Liana O + LO + + Altino Ventura Foundation, Recife, Pernambuco, Brazil6HOPE Eye Hospital, Recife, Pernambuco, Brazil. + + + + Neto + Norberto Nogueira + NN + + NOVA Diagnóstico Por Imagem, João Pessoa, Paraíba, Brazil. + + + + Arena + J Fernando + JF + + Carter Consulting, Atlanta, Georgia. + + + + Rasmussen + Sonja A + SA + + Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, Georgia. + + + + eng + + + R01 NS050375 + NS + NINDS NIH HHS + United States + + + R01 NS058721 + NS + NINDS NIH HHS + United States + + + U54 HD083091 + HD + NICHD NIH HHS + United States + + + + Journal Article + Review + +
+ + United States + JAMA Pediatr + 101589544 + 2168-6203 + + AIM + IM + + + Eur J Pediatr. 1995 Aug;154(8):654-7 + 7588968 + + + Euro Surveill. 2016 Jun 16;21(24): + 27336620 + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + Am J Hum Genet. 2010 Sep 10;87(3):354-64 + 20727516 + + + Clin Infect Dis. 2016 Sep 15;63(6):805-11 + 27193747 + + + Am J Med Genet A. 2004 Jun 1;127A(2):172-82 + 15108206 + + + BMJ. 2016 Sep 14;354:i4850 + 27629599 + + + MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65(33):870-878 + 27559830 + + + Cell Stem Cell. 2016 May 5;18(5):591-6 + 27038591 + + + Am J Med Genet A. 2008 Dec 15;146A(24):3173-80 + 19012351 + + + Neurology. 2016 Jan 5;86(1):28-35 + 26581299 + + + Cell. 2016 May 19;165(5):1238-54 + 27118425 + + + Cell Biochem Funct. 2014 Jan;32(1):77-86 + 23657822 + + + Teratology. 1982 Apr;25(2):173-91 + 7101197 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + JAMA Ophthalmol. 2016 Feb 9;: + 26865554 + + + Ophthalmology. 2016 Aug;123(8):1788-94 + 27236271 + + + Ultrasound Obstet Gynecol. 2016 Sep 19;:null + 27644020 + + + Am J Hum Genet. 2010 Dec 10;87(6):882-9 + 21109224 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + Lancet Infect Dis. 2016 Dec;16(12 ):1356-1363 + 27641777 + + + MMWR Morb Mortal Wkly Rep. 2016 Sep 02;65(34):917-9 + 27585248 + + + Lancet. 2016 Aug 27;388(10047):898-904 + 27372395 + + + N Engl J Med. 2016 Sep 22;375(12 ):1202-4 + 27653589 + + + Am J Public Health. 2016 Apr;106(4):598-600 + 26959258 + + + Ultrasound Obstet Gynecol. 2016 May;47(5):657-60 + 26923098 + + + Semin Ultrasound CT MR. 2015 Dec;36(6):476-86 + 26614131 + + + Clin Infect Dis. 2016 Dec 15;63(12 ):1622-1625 + 27601223 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Neurology. 2016 Jul 5;87(1):118-9 + 27378805 + + + J Bone Joint Surg Am. 2009 Jul;91 Suppl 4:40-6 + 19571066 + + + Am J Med Genet A. 2013 Jul;161A(7):1523-30 + 23704059 + + + Emerg Infect Dis. 2016 Jun;22(6):1090-3 + 27071041 + + + Lancet. 2016 Jun 18;387(10037):2502 + 27287830 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Surv Ophthalmol. 2008 Mar-Apr;53(2):95-111 + 18348876 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Arch Med Sci. 2016 Feb 1;12(1):10-24 + 26925114 + + + J Pediatric Infect Dis Soc. 2016 Sep;5(3):323-8 + 27405738 + + + J Infect. 2016 May;72 (5):507-24 + 26940504 + + + Euro Surveill. 2016;21(13):null + 27063794 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Am J Med Genet. 1984 Feb;17(2):509-21 + 6702901 + + + Obstet Gynecol Surv. 2006 May;61(5):329-36 + 16635273 + + + BMJ. 2016 Aug 09;354:i3899 + 27509902 + + + JAMA Ophthalmol. 2016 Aug 1;134(8):912-8 + 27228275 + + + J Med Virol. 2007 Jun;79(6):754-7 + 17457913 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Pediatr Radiol. 2016 Jun;46(7):1032-9 + 27090801 + + + Prenat Diagn. 2016 Aug;36(8):785-9 + 27316349 + + + Emerg Infect Dis. 2016 Nov;22(11):1953-1956 + 27767931 + + + Eur J Pediatr. 2001 Nov;160(11):664-7 + 11760023 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + BJOG. 2016 Jul;123(8):1265-1269 + 27150580 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Am J Med Genet A. 2015 May;167A(5):1089-99 + 25755095 + + + Neuroimaging Clin N Am. 2012 Nov;22(4):707-25 + 23122263 + + + Childs Nerv Syst. 2016 Jun;32(6):1057-60 + 27080092 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Acta Paediatr. 2015 Sep;104(9):e388-94 + 26018986 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + N Engl J Med. 2016 Jun 15;:null + 27305043 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + Braz J Otorhinolaryngol. 2016 Jun 30;:null + 27444419 + + + Cell. 2014 Sep 25;159(1):200-14 + 25259927 + + + + + Diagnosis, Differential + + + Female + + + Humans + + + Infant + + + Nervous System Malformations + diagnosis + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + virology + + + Zika Virus + + + Zika Virus Infection + complications + + +
+ + + + 2016 + 11 + 5 + 6 + 0 + + + 2017 + 7 + 6 + 6 + 0 + + + 2016 + 11 + 5 + 6 + 0 + + + ppublish + + 27812690 + 2579543 + 10.1001/jamapediatrics.2016.3982 + PMC5561417 + NIHMS882792 + + +
+ + + + + 27812648 + + 2016 + 12 + 20 + + + 2016 + 12 + 30 + +
+ + 1678-9849 + + 49 + 5 + + 2016 Sep-Oct + + + Revista da Sociedade Brasileira de Medicina Tropical + Rev. Soc. Bras. Med. Trop. + + Zika in Pernambuco: rewriting the first outbreak. + + 553-558 + + S0037-86822016000500553 + 10.1590/0037-8682-0245-2016 + + A Zika virus epidemic was registered in 2015 in Northeast Brazil. In the State of Pernambuco, thousands of classical cases transpired, and in the following months, neurological disturbances in adults and microcephaly in newborns emerged as complications. After the peak of the epidemic, the official system reported only four cases of Zika virus but over 100,000 cases of dengue virus. The vigilance system was unable to retrospectively estimate cases or to issue an alert to officially notified cases with possible inconsistence concerning specific arbovirosis diagnoses. + To evaluate the frequency of different arbovirosis diagnoses based on clinical-epidemiologic criteria, from January to April 2015, we conducted a hospital-based cross-sectional study retrospectively analyzing suspected cases of arbovirosis. + Of 1 , 046 total suspected cases of arbovirus, 895 (86%) were classified as probable Zika virus cases, and 151 (14%) as probable dengue virus cases. The most frequent manifestations in probable Zika virus cases were exanthema (100%), pruritus (50.7%), fever (20.4%) and arthralgia (27.7%). + In contrast to the official data, during the peak months of the arbovirosis epidemic of 2015, most cases were compatible with Zika virus infections. Hospital-based studies, although retrospective and based on secondary data from clinical files, might provide a better estimate of the number of cases relative to currently available data, if derived from several urgent care units of representative areas of a city or state.This would partially retrospectively correct some inconsistences regarding official notifications. + + + + Brito + Carlos Alexandre Antunes de + CA + + Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil. + + + + Brito + Cecilia Coelho Moraes de + CC + + Programa de Graduação em Medicina, Universidade de Pernambuco, Recife, Pernambuco, Brazil. + + + + Oliveira + Augusto César + AC + + Programa de Graduação em Medicina, Universidade de Pernambuco, Recife, Pernambuco, Brazil. + + + + Rocha + Marilia + M + + Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil. + + + + Atanásio + Caio + C + + Programa de Graduação em Medicina, Universidade de Pernambuco, Recife, Pernambuco, Brazil. + + + + Asfora + Carolina + C + + Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil. + + + + Matos + Júlio Dourado + JD + + Programa de Graduação em Medicina, Faculdade Pernambucana de Saúde, Recife, Pernambuco, Brazil. + + + + Lima + Anton Saraiva + AS + + Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil. + + + + Albuquerque + Maria Fátima Militão + MF + + Departamento de Saúde Pública, Centro de Pesquisa Aggeu Magalhães, Recife, Pernambuco, Brazil. + + + + eng + + Journal Article + +
+ + Brazil + Rev Soc Bras Med Trop + 7507456 + 0037-8682 + + IM + + + Adolescent + + + Adult + + + Brazil + epidemiology + + + Child + + + Child, Preschool + + + Cross-Sectional Studies + + + Disease Outbreaks + + + Female + + + Humans + + + Infant + + + Infant, Newborn + + + Male + + + Middle Aged + + + Retrospective Studies + + + Seasons + + + Young Adult + + + Zika Virus Infection + epidemiology + + +
+ + + + 2016 + 07 + 02 + + + 2016 + 09 + 13 + + + 2016 + 11 + 5 + 6 + 0 + + + 2016 + 12 + 21 + 6 + 0 + + + 2016 + 11 + 5 + 6 + 0 + + + ppublish + + 27812648 + S0037-86822016000500553 + 10.1590/0037-8682-0245-2016 + + +
+ + + + + 27812646 + + 2016 + 12 + 20 + + + 2016 + 12 + 30 + +
+ + 1678-9849 + + 49 + 5 + + 2016 Sep-Oct + + + Revista da Sociedade Brasileira de Medicina Tropical + Rev. Soc. Bras. Med. Trop. + + One year after the Zika virus outbreak in Brazil: from hypotheses to evidence. + + 537-543 + + S0037-86822016000500537 + 10.1590/0037-8682-0328-2016 + + Zika virusis an arbovirus of the Flaviviridae family with two major strains, an Asian and an African strain. The main vectors involved in the transmission of Zika virus are the Aedes aegypti and Aedes albopictus mosquitoes. Despite its identification, discovered in 1947 in the Zika forest in Uganda, only isolated and sporadic occurrences of human infection were reported within a largely asymptomatic proportion of individuals. The first reported outbreak occurred in 2007 in the Yap Island, which belongs to the Federated States of Micronesia in the Pacific Ocean, and in French Polynesia, where high attack rates occurred and the first cases of associated Guillain-Barré syndrome were reported. From November 2014 to early 2015, the Northeast states of Brazil reported the first outbreaks of Zika virus infection, with laboratory confirmation of Zika virus circulation in April 2015. In the second quarter of 2015, the association between Zika virus infection and neurological symptoms was confirmed in adults. Moreover, in October 2015 a novel suspicion was raised based on clinical and epidemiological observations: that an association between Zika virus infection and neonatal microcephaly may exist. A year after the first reports on Zika virus in Brazil, many hypotheses and much evidence on the patterns of involvement of the disease and its complications have been produced, both in this country and others; other hypotheses still need to be clarified. This review is a synthesis of a new chapter in the history of medicine; it outlines the main results produced. + + + + Brito + Carlos Alexandre Antunes de + CA + + Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil. + + + + Cordeiro + Marli Tenorio + MT + + Departamento de Virologia, Centro de Pesquisa Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil. + + + + eng + + Journal Article + Review + +
+ + Brazil + Rev Soc Bras Med Trop + 7507456 + 0037-8682 + + IM + + + Aedes + virology + + + Animals + + + Brazil + epidemiology + + + Disease Outbreaks + + + Humans + + + Insect Vectors + virology + + + Microcephaly + epidemiology + virology + + + Zika Virus Infection + complications + epidemiology + transmission + + +
+ + + + 2016 + 08 + 16 + + + 2016 + 10 + 07 + + + 2016 + 11 + 5 + 6 + 0 + + + 2016 + 12 + 21 + 6 + 0 + + + 2016 + 11 + 5 + 6 + 0 + + + ppublish + + 27812646 + S0037-86822016000500537 + 10.1590/0037-8682-0328-2016 + + +
+ + + + + 27812601 + + 2017 + 07 + 31 + + + 2017 + 07 + 31 + +
+ + 1678-8060 + + 111 + 12 + + 2016 + Dec + + + Memorias do Instituto Oswaldo Cruz + Mem. Inst. Oswaldo Cruz + + Pyriproxyfen and the microcephaly epidemic in Brazil - an ecological approach to explore the hypothesis of their association. + + 774-776 + + S0074-02762016001200774 + 10.1590/0074-02760160291 + + The microcephaly epidemic in Brazil generated intense debate regarding its causality, and one hypothesised cause of this epidemic, now recognised as congenital Zika virus syndrome, was the treatment of drinking water tanks with pyriproxyfen to control Aedes aegypti larvae. We present the results of a geographical analysis of the association between the prevalence of microcephaly confirmed by Fenton growth charts and the type of larvicide used in the municipalities that were home to the mothers of the affected newborns in the metropolitan region of Recife in Pernambuco, the state in Brazil where the epidemic was first detected. The overall prevalence of microcephaly was 82 per 10,000 live births in the three municipalities that used the larvicide Bti (Bacillus thuringiensis israelensis) instead of pyriproxyfen, and 69 per 10,000 live births in the eleven municipalities that used pyriproxyfen. The difference was not statistically significant. Our results show that the prevalence of microcephaly was not higher in the areas in which pyriproxyfen was used. In this ecological approach, there was no evidence of a correlation between the use of pyriproxyfen in the municipalities and the microcephaly epidemic. + + + + Albuquerque + Maria de Fatima P Militão de + MF + + Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Departamento de Saúde Coletiva, Recife, PE, Brasil. + + + + Souza + Wayner V de + WV + + Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Departamento de Saúde Coletiva, Recife, PE, Brasil. + + + + Mendes + Antônio da Cruz G + AD + + Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Departamento de Saúde Coletiva, Recife, PE, Brasil. + + + + Lyra + Tereza M + TM + + Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Departamento de Saúde Coletiva, Recife, PE, Brasil. + + + + Ximenes + Ricardo Aa + RA + + Universidade Federal de Pernambuco, Recife, PE, Brasil. + + + Universidade de Pernambuco, Recife, PE, Brasil. + + + + Araújo + Thália Vb + TV + + Universidade de Pernambuco, Recife, PE, Brasil. + + + + Braga + Cynthia + C + + Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Departamento de Saúde Coletiva, Recife, PE, Brasil. + + + + Miranda-Filho + Demócrito B + DB + + Universidade de Pernambuco, Recife, PE, Brasil. + + + + Martelli + Celina Mt + CM + + Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Departamento de Saúde Coletiva, Recife, PE, Brasil. + + + + Rodrigues + Laura C + LC + + London School of Hygiene and Tropical Medicine, London, UK. + + + + eng + + Journal Article + + + 2016 + 10 + 31 + +
+ + Brazil + Mem Inst Oswaldo Cruz + 7502619 + 0074-0276 + + + + 0 + Insecticides + + + 0 + Pyridines + + + 3Q9VOR705O + pyriproxyfen + + + IM + + + Acta Trop. 2014 Sep;137:80-7 + 24832009 + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Lancet. 2016 Mar 12;387(10023):1052-3 + 26944024 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + + + Aedes + drug effects + virology + + + Animals + + + Brazil + epidemiology + + + Epidemics + + + Humans + + + Infant, Newborn + + + Insecticides + adverse effects + + + Microcephaly + chemically induced + epidemiology + virology + + + Mosquito Control + + + Prevalence + + + Pyridines + adverse effects + + + Zika Virus Infection + prevention & control + + +
+ + + + 2016 + 06 + 30 + + + 2016 + 09 + 14 + + + 2016 + 11 + 5 + 6 + 0 + + + 2017 + 8 + 2 + 6 + 0 + + + 2016 + 11 + 5 + 6 + 0 + + + ppublish + + 27812601 + S0074-02762016005022104 + 10.1590/0074-02760160291 + PMC5146741 + + +
+ + + + + 27805221 + + 2017 + 07 + 26 + + + 2017 + 07 + 26 + +
+ + 1742-2051 + + 13 + 1 + + 2016 + Dec + 20 + + + Molecular bioSystems + Mol Biosyst + + Analysis of worldwide sequence mutations in Zika virus proteins E, NS1, NS3 and NS5 from a structural point of view. + + 122-131 + + + Zika virus (ZIKV) is an emergent arbovirus that has attracted attention in the last year as a possible causative agent of congenital malformation; it shows a remarkably increased microcephaly risk during otherwise healthy pregnancies. We present here an analysis of all ZIKV sequences available in Genbank up to April 2016, studying the mutations in the whole polyprotein and their possible structural implications for the proteins E, NS1, NS3 and NS5. This study suggests that microcephaly is not a consequence of any particular amino acid substitution but, conceivably, is a feature of ZIKV itself. Moreover, the structural analysis of ZIKV proteins, together with the mutational landscape of ZIKV and a structure-sequence comparison with other flaviviruses, allows the suggestion of regions that could be exploited as anti-ZIKV targets, including some allosteric sites found in the NS3 and NS5 proteins of DENV. + + + + Baez + C F + CF + + Preventive Medicine Department, Rio de Janeiro Federal University Hospital, Brazil. + + + + Barel + V A + VA + + ModMolQSAR Laboratory, Faculty of Pharmaceutical Sciences, Rio de Janeiro Federal University, Brazil. cirauquipharma@gmail.com. + + + + de Souza + A M T + AM + + ModMolQSAR Laboratory, Faculty of Pharmaceutical Sciences, Rio de Janeiro Federal University, Brazil. cirauquipharma@gmail.com. + + + + Rodrigues + C R + CR + + ModMolQSAR Laboratory, Faculty of Pharmaceutical Sciences, Rio de Janeiro Federal University, Brazil. cirauquipharma@gmail.com. + + + + Varella + R B + RB + + Microbiology and Parasitology Department, Biomedical Institute, Fluminense Federal University, Brazil. + + + + Cirauqui + N + N + http://orcid.org/0000-0003-4752-9916 + + ModMolQSAR Laboratory, Faculty of Pharmaceutical Sciences, Rio de Janeiro Federal University, Brazil. cirauquipharma@gmail.com. + + + + eng + + Journal Article + +
+ + England + Mol Biosyst + 101251620 + 1742-2051 + + + + 0 + Viral Proteins + + + IM + + + DNA Mutational Analysis + + + Models, Molecular + + + Mutation + + + Phylogeny + + + Phylogeography + + + Protein Conformation + + + Viral Proteins + chemistry + genetics + + + Zika Virus + classification + genetics + + +
+ + + + 2016 + 11 + 3 + 6 + 0 + + + 2017 + 7 + 27 + 6 + 0 + + + 2016 + 11 + 3 + 6 + 0 + + + ppublish + + 27805221 + 10.1039/c6mb00645k + + +
+ + + + + 27726416 + + 2017 + 03 + 06 + + + 2017 + 08 + 17 + +
+ + 1543-2165 + + 141 + 1 + + 2017 + Jan + + + Archives of pathology & laboratory medicine + Arch. Pathol. Lab. Med. + + Zika Virus-Associated Micrencephaly: A Thorough Description of Neuropathologic Findings in the Fetal Central Nervous System. + + 73-81 + + 10.5858/arpa.2016-0341-SA + + -The 2015 outbreak of Zika virus in Brazil resulted in a 20-times increased prevalence of congenital microcephaly in stillborns and neonates and was instrumental in raising the suspicion of a causal association between Zika virus and microcephaly. + -To provide a comprehensive description of the neuropathologic features of congenital Zika virus infection. + -Autopsy evaluation of the brain from a fetus of 32 weeks and 6 days of gestation, with a prenatal diagnosis of microcephaly associated with polymerase chain reaction-confirmed, fetal, Zika virus infection. + -Multiple severe pathology findings were present. These included lissencephaly, except for the occipital lobes, where some pachygyria was observed. Also present was reduction and thinning of white matter, ventriculomegaly of the lateral ventricles, and coalescent calcifications in the cortical-subcortical white matter border associated with glioneuronal outbursting into the subarachnoid space above and heterotopias below. There were small, scattered calcifications in the basal ganglia, with fewer in the white matter and germinal matrix, and none in the cerebellum and brainstem. The cerebellum and pontine base were atrophic because of Wallerian degeneration or maldevelopment of descending tracts and pontocerebellar connections. + -Our findings are in agreement with neuroimaging of Zika virus-associated fetal and infant micrencephalic brains and, to some extent, with neuroimaging of other intrauterine infections causing microcephaly. + + + + Štrafela + Peter + P + + + Vizjak + Alenka + A + + + Mraz + Jerica + J + + + Mlakar + Jernej + J + + + Pižem + Jože + J + + + Tul + Nataša + N + + + Županc + Tatjana Avšič + TA + + + Popović + Mara + M + + From the Department of Pathology, University Clinical Centre, Maribor, Slovenia (Dr Štrafela); the Institutes of Pathology (Drs Vizjak, Mlakar, Pižem, and Popović and Mrs Mraz) and Microbiology and Immunology (Dr Županc), Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; and the Department of Perinatology, Division of Gynecology and Obstetrics, University Medical Centre, Ljubljana, Slovenia (Dr Tul). + + + + eng + + Case Reports + Journal Article + + + 2016 + 10 + 11 + +
+ + United States + Arch Pathol Lab Med + 7607091 + 0003-9985 + + AIM + IM + + + Abortion, Eugenic + + + Adult + + + Autopsy + + + Brain + embryology + pathology + virology + + + Central Nervous System + embryology + pathology + virology + + + Fatal Outcome + + + Female + + + Fetal Death + + + Fetal Diseases + diagnostic imaging + pathology + virology + + + Gestational Age + + + Host-Pathogen Interactions + + + Humans + + + Hydrocephalus + chemically induced + diagnostic imaging + pathology + + + Infant, Newborn + + + Lissencephaly + diagnostic imaging + pathology + virology + + + Magnetic Resonance Imaging + methods + + + Male + + + Microcephaly + diagnostic imaging + pathology + virology + + + Pregnancy + + + Zika Virus + physiology + + + Zika Virus Infection + diagnostic imaging + pathology + virology + + +
+ + + + 2016 + 11 + 1 + 6 + 0 + + + 2017 + 3 + 7 + 6 + 0 + + + 2016 + 10 + 12 + 6 + 0 + + + ppublish + + 27726416 + 10.5858/arpa.2016-0341-SA + + +
+ + + + + 27714487 + + 2017 + 06 + 09 + + + 2017 + 11 + 04 + +
+ + 1867-108X + + 34 + 12 + + 2016 + Dec + + + Japanese journal of radiology + Jpn J Radiol + + Neuroimaging findings of Zika virus infection: a review article. + + 765-770 + + + Zika virus (ZIKV) is an arbovirus from the Flaviviridae family. It is usually transmitted by mosquito bite. There have been no reports of severe symptoms caused by ZIKV infection up until the last few years. In October 2013 an outbreak was reported in French Polynesia with severe neurological complications in some affected cases. In November 2015, the Ministry of Health of Brazil attributed the increased number of neonatal microcephaly cases in northeastern Brazil to congenital ZIKV infection. The rapid spread of the virus convinced the World Health Organization to announce ZIKV infection as a "Public Health Emergency of International Concern" in February 2016. The main neuroimaging findings in congenital ZIKV infection include microcephaly which is the hallmark of the disease, other malformations of cortical development (e.g., lissencephaly, heterotopia, etc.), parenchymal calcifications, unilateral or bilateral ventriculomegaly, enlarged extra-axial CSF spaces, dysgenesis of the corpus callosum, agenesis of the cavum septum pellucidum, cerebellar and brainstem hypoplasia, and ocular abnormalities. ZIKV infection may also cause Guillain-Barré syndrome and acute disseminated encephalomyelitis in adults. Familiarity with neuroimaging findings of congenital and acquired ZIKV infection is crucial to suspect this disease in residents of endemic regions and travelers to these areas. + + + + Zare Mehrjardi + Mohammad + M + http://orcid.org/0000-0001-5793-5323 + + Department of Radiology, Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. zare@sbmu.ac.ir. + + + + Keshavarz + Elham + E + + Department of Radiology, Mahdieh Women's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. + + + + Poretti + Andrea + A + + Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. + + + + Hazin + Adriano N + AN + + Instituto de Medicina Integral Professor Fernando Figueira, Recife, Brazil. + + + + eng + + Journal Article + Review + + + 2016 + 10 + 06 + +
+ + Japan + Jpn J Radiol + 101490689 + 1867-1071 + + IM + + + Jpn J Radiol. 2017 Feb;35(2):86 + 27896560 + + + Jpn J Radiol. 2017 Feb;35(2):87-88 + 28074378 + + + Jpn J Radiol. 2017 Jan;35(1):40 + 27804004 + + + Jpn J Radiol. 2017 Jan;35(1):41-42 + 27830429 + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + Am J Med. 2016 Aug;129(8):879.e7-879.e12 + 26994509 + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Cell. 2016 May 19;165(5):1238-1254 + 27118425 + + + JAMA Ophthalmol. 2016 Feb 9;: + 26865554 + + + Ann Intern Med. 2016 Aug 2;165(3):175-83 + 27135717 + + + Lancet. 2016 Apr 9;387(10027):1587-90 + 26952548 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + Pediatr Radiol. 2009 Aug;39(8):772-80; quiz 888-9 + 19437006 + + + BMJ. 2016 Feb 02;352:i657 + 26839247 + + + BMJ. 2016 Apr 15;353:i2194 + 27083981 + + + Lancet. 2016 May 21;387(10033):2125-2132 + 26993883 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Neuropsychiatr Dis Treat. 2016 Jul 14;12:1747-60 + 27478378 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Virol J. 2013 Oct 22;10:311 + 24148652 + + + Vet Q. 2016 Sep;36(3):150-75 + 27158761 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Pediatr Radiol. 2016 Jun;46(7):1032-9 + 27090801 + + + Semin Neurol. 2008 Feb;28(1):84-94 + 18256989 + + + Neuroradiology. 2016 Aug;58(8):837-8 + 27067205 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + BMC Med Res Methodol. 2012 Nov 27;12:181 + 23185978 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Neurology. 2001 May 22;56(10):1308-12 + 11376179 + + + Childs Nerv Syst. 2016 Jun;32(6):1057-60 + 27080092 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):122-7 + 26866840 + + + + + Brain + diagnostic imaging + microbiology + + + Humans + + + Magnetic Resonance Imaging + + + Neuroimaging + methods + + + Tomography, X-Ray Computed + + + Ultrasonography + + + Zika Virus Infection + diagnostic imaging + + + + Computed tomography (CT) + Magnetic resonance imaging (MRI) + Neuroimaging + Ultrasound + Zika virus (ZIKV) + +
+ + + + 2016 + 08 + 12 + + + 2016 + 09 + 22 + + + 2016 + 11 + 1 + 6 + 0 + + + 2017 + 6 + 10 + 6 + 0 + + + 2016 + 10 + 8 + 6 + 0 + + + ppublish + + 27714487 + 10.1007/s11604-016-0588-5 + 10.1007/s11604-016-0588-5 + + +
+ + + + + 27783802 + + 2018 + 03 + 06 + + + 2018 + 03 + 06 + +
+ + 1678-4561 + + 21 + 10 + + 2016 + Oct + + + Ciencia & saude coletiva + Cien Saude Colet + + Microcephaly and other Zika virus related events: the impact on children, families and health teams. + + 3297-3302 + + S1413-81232016001003297 + 10.1590/1413-812320152110.16832016 + + The present study aimed to present an overview of recent national and international research on the Zika virus (ZIKV), as well as to explore possible action plans focused on children, their families and the health teams involved.Therefore, the study proposes the implementation of tracking systems in order to identify, describe and characterize the potential correlates of prenatal exposure to ZIKV, divided into three lines of action: 1. Diagnostic and etiological evaluation as well as screening of developmental problems in children confirmed or suspected of prenatal ZIKV infection. 2. Investigation of the emotional impact, quality of life, coping strategies and support network of the affected children and their families. 3. Training of multidisciplinary teams to conduct assessments and intervention programs throughout these children's development, especially in the first three years of life. In conclusion, the recent ZIKV outbreak in Brazil and several other Latin American countries places a significant burden on the health care systems: to understand the real meaning of a potential new teratogen; to unravel the pathogenic mechanisms of ZIKV, particularly in a prevention perspective; and to recognize the broad spectrum of clinical manifestations in order to devise intervention programs. + + + + Brunoni + Decio + D + + Programa de Pós-Graduação em Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie. R. Consolação 930, Consolação. 01302-907 São Paulo SP Brasil. disturbios.pos@mackenzie.br. + + + + Blascovi-Assis + Silvana Maria + SM + + Programa de Pós-Graduação em Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie. R. Consolação 930, Consolação. 01302-907 São Paulo SP Brasil. disturbios.pos@mackenzie.br. + + + + Osório + Ana Alexandra Caldas + AA + + Programa de Pós-Graduação em Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie. R. Consolação 930, Consolação. 01302-907 São Paulo SP Brasil. disturbios.pos@mackenzie.br. + + + + Seabra + Alessandra Gotuzo + AG + + Programa de Pós-Graduação em Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie. R. Consolação 930, Consolação. 01302-907 São Paulo SP Brasil. disturbios.pos@mackenzie.br. + + + + Amato + Cibelle Albuquerque de la Higuera + CA + + Programa de Pós-Graduação em Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie. R. Consolação 930, Consolação. 01302-907 São Paulo SP Brasil. disturbios.pos@mackenzie.br. + + + + Teixeira + Maria Cristina Triguero Veloz + MC + + Programa de Pós-Graduação em Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie. R. Consolação 930, Consolação. 01302-907 São Paulo SP Brasil. disturbios.pos@mackenzie.br. + + + + Rocha + Marina Monzani da + MM + + Programa de Pós-Graduação em Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie. R. Consolação 930, Consolação. 01302-907 São Paulo SP Brasil. disturbios.pos@mackenzie.br. + + + + Carreiro + Luiz Renato Rodrigues + LR + + Programa de Pós-Graduação em Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie. R. Consolação 930, Consolação. 01302-907 São Paulo SP Brasil. disturbios.pos@mackenzie.br. + + + + por + eng + + Journal Article + + Microcefalia e outras manifestações relacionadas ao vírus Zika: impacto nas crianças, nas famílias e nas equipes de saúde. +
+ + Brazil + Cien Saude Colet + 9713483 + 1413-8123 + + IM + + + Attitude to Health + + + Child + + + Family + + + Health Personnel + + + Humans + + + Microcephaly + virology + + + Zika Virus Infection + complications + + +
+ + + + 2016 + 03 + 10 + + + 2016 + 06 + 27 + + + 2016 + 10 + 27 + 6 + 0 + + + 2018 + 3 + 7 + 6 + 0 + + + 2016 + 10 + 27 + 6 + 0 + + + ppublish + + 27783802 + S1413-81232016001003297 + 10.1590/1413-812320152110.16832016 + + +
+ + + + + 27702683 + + 2017 + 05 + 02 + + + 2017 + 08 + 17 + +
+ + 1873-0442 + + 14 + 5 + + 2016 Sep - Oct + + + Travel medicine and infectious disease + Travel Med Infect Dis + + Trends of the microcephaly and Zika virus outbreak in Brazil, January-July 2016. + + 458-463 + + S1477-8939(16)30124-7 + 10.1016/j.tmaid.2016.09.006 + + In the last two months, there have been indications that the Zika virus epidemic is on the decline in Brazil. We reviewed the surveillance data published by the Brazilian Ministry of Health to assess trends of microcephaly and neurological abnormalities suggestive of congenital infection, as well as Zika virus disease in Brazil as a whole and its various regions. From November 2015 to July 2016, 8301 cases of microcephaly were reported in Brazil, mainly in the Northeast region. The number of newly reported cases is declining throughout the country, except in the Southeast region. The numbers of cases that remain under investigation still represent 37.7% of all reported cases in early July. Meanwhile, from January to June, 2016, 165,241 cases of Zika virus disease were reported in Brazil. The state of Rio de Janeiro (Southeast) experienced the third highest incidence, lagging behind only the states of Bahia (Northeast) and Mato Grosso (Midwest). In early June, the number of new Zika virus cases showed a marked decline in all of the regions, except the North. Although the Zika epidemic seems to be diminishing, continued monitoring and surveillance of reported microcephaly and neurological abnormality cases is essential, and investigation efforts need to be vastly improved, as some states still reported high incidences of Zika disease in the first half of 2016. + Copyright © 2016 Elsevier Ltd. All rights reserved. + + + + Magalhães-Barbosa + Maria Clara de + MC + + Instituto D'Or de Pesquisa e Ensino (IDOR), Departamento de Pediatria, Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, Rio de Janeiro, 22281-100, Brazil. Electronic address: mariaclaramb@globo.com. + + + + Prata-Barbosa + Arnaldo + A + + Instituto D'Or de Pesquisa e Ensino (IDOR), Departamento de Pediatria, Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, Rio de Janeiro, 22281-100, Brazil; Faculdade de Medicina da Universidade Federal do Rio de Janeiro, Departamento de Pediatria, Rua Bruno Lobo, n° 50, Cidade Universitária, Rio de Janeiro, Rio de Janeiro, 21941-612, Brazil. Electronic address: arnaldoprata@globo.com. + + + + Robaina + Jaqueline Rodrigues + JR + + Instituto D'Or de Pesquisa e Ensino (IDOR), Departamento de Pediatria, Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, Rio de Janeiro, 22281-100, Brazil. Electronic address: jaque.robaina@gmail.com. + + + + Raymundo + Carlos Eduardo + CE + + Instituto D'Or de Pesquisa e Ensino (IDOR), Departamento de Pediatria, Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, Rio de Janeiro, 22281-100, Brazil. Electronic address: caducer@gmail.com. + + + + Lima-Setta + Fernanda + F + + Instituto D'Or de Pesquisa e Ensino (IDOR), Departamento de Pediatria, Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, Rio de Janeiro, 22281-100, Brazil. Electronic address: felimasetta@gmail.com. + + + + Cunha + Antonio José Ledo Alves da + AJ + + Faculdade de Medicina da Universidade Federal do Rio de Janeiro, Departamento de Pediatria, Rua Bruno Lobo, n° 50, Cidade Universitária, Rio de Janeiro, Rio de Janeiro, 21941-612, Brazil. Electronic address: acunha@hucff.ufrj.br. + + + + eng + + Journal Article + Review + + + 2016 + 10 + 01 + +
+ + Netherlands + Travel Med Infect Dis + 101230758 + 1477-8939 + + IM + + + Brazil + epidemiology + + + Disease Outbreaks + + + Epidemics + + + Female + + + Humans + + + Incidence + + + Microcephaly + diagnosis + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + congenital + epidemiology + virology + + + + Congenital abnormalities + Microcephaly + Outbreak + Zika virus + +
+ + + + 2016 + 07 + 24 + + + 2016 + 09 + 09 + + + 2016 + 09 + 13 + + + 2016 + 10 + 25 + 6 + 0 + + + 2017 + 5 + 4 + 6 + 0 + + + 2016 + 10 + 6 + 6 + 0 + + + ppublish + + 27702683 + S1477-8939(16)30124-7 + 10.1016/j.tmaid.2016.09.006 + + +
+ + + + + 27021935 + + 2017 + 11 + 27 + + + 2017 + 12 + 01 + +
+ + 1938-744X + + 10 + 5 + + 2016 + 10 + + + Disaster medicine and public health preparedness + Disaster Med Public Health Prep + + Zika Virus: A Basic Overview of an Emerging Arboviral Infection in the Western Hemisphere. + + 707-712 + + + Since February 2015, Zika virus has spread throughout the Western Hemisphere, starting in Brazil. As of March 2016, autochthonous transmission has been reported in at least 31 countries or territories. For countries in the Americas, the spread of Zika virus, a previously unfamiliar disease, follows similar emerging infection introductions of West Nile virus and Chikungunya virus and their spread throughout the American continents and the Caribbean nations. The Pan American Health Organization and the World Health Organization have issued alerts and a Public Health Emergency of International Concern announcement related to the recent cluster of microcephaly cases and other neurological disorders in Brazil that are temporally associated with Zika virus, which highlights the possible adverse impact of viral infection. This article provides an overview of the Zika virus infection and presents the historical background of the virus, a description of the pathogen, the epidemiology and clinical spectrum of Zika virus infection, diagnosis and treatment approaches, and prevention and control measures. Understanding what is known about the virus and its clinical presentation will assist in prevention, detection, and response measures to reduce and control the spread of the virus throughout the Western Hemisphere. (Disaster Med Public Health Preparedness. 2016;page 1 of 6). + + + + Vest + Kelly G + KG + + Center for Global Health Engagement,Uniformed Services University of the Health Sciences,Rockville,Maryland. + + + + eng + + Journal Article + + + 2016 + 03 + 29 + +
+ + United States + Disaster Med Public Health Prep + 101297401 + 1935-7893 + + IM + + + Americas + epidemiology + + + Disease Outbreaks + prevention & control + statistics & numerical data + + + Female + + + Humans + + + Mass Screening + methods + standards + + + Pregnancy + + + Public Health + methods + + + Zika Virus + pathogenicity + + + Zika Virus Infection + diagnosis + epidemiology + + + + Zika virus + arbovirus + epidemic + +
+ + + + 2016 + 10 + 25 + 6 + 0 + + + 2017 + 11 + 29 + 6 + 0 + + + 2016 + 3 + 30 + 6 + 0 + + + ppublish + + 27021935 + S1935789316000434 + 10.1017/dmp.2016.43 + + +
+ + + + + 27767931 + + 2018 + 01 + 12 + + + 2018 + 01 + 12 + +
+ + 1080-6059 + + 22 + 11 + + 2016 + 11 + + + Emerging infectious diseases + Emerging Infect. Dis. + + Early Growth and Neurologic Outcomes of Infants with Probable Congenital Zika Virus Syndrome. + + 1953-1956 + + 10.3201/eid2211.160956 + + We report the early growth and neurologic findings of 48 infants in Brazil diagnosed with probable congenital Zika virus syndrome and followed to age 1-8 months. Most of these infants had microcephaly (86.7%) and craniofacial disproportion (95.8%). The clinical pattern included poor head growth with increasingly negative z-scores, pyramidal/extrapyramidal symptoms, and epilepsy. + + + + Moura da Silva + Antonio Augusto + AA + + + Ganz + Jucelia Sousa Santos + JS + + + Sousa + Patricia da Silva + PD + + + Doriqui + Maria Juliana Rodvalho + MJ + + + Ribeiro + Marizelia Rodrigues Costa + MR + + + Branco + Maria Dos Remédios Freitas Carvalho + MD + + + Queiroz + Rejane Christine de Sousa + RC + + + Pacheco + Maria de Jesus Torres + MJ + + + Vieira da Costa + Flavia Regina + FR + + + Silva + Francelena de Sousa + FS + + + Simões + Vanda Maria Ferreira + VM + + + Pacheco + Marcos Antonio Barbosa + MA + + + Lamy-Filho + Fernando + F + + + Lamy + Zeni Carvalho + ZC + + + Soares de Britto E Alves + Maria Teresa Seabra + MT + + + eng + + Journal Article + +
+ + United States + Emerg Infect Dis + 9508155 + 1080-6040 + + IM + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + PLoS Med. 2008 Mar 18;5(3):e60 + 18351797 + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + Lancet. 2014 Sep 6;384(9946):857-68 + 25209487 + + + Emerg Infect Dis. 2016 Jun;22(6):1090-3 + 27071041 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Eur J Pediatr. 2001 Nov;160(11):664-7 + 11760023 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + + + Birth Weight + + + Body Weights and Measures + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant + + + Infant, Newborn + + + Nervous System Malformations + diagnosis + epidemiology + etiology + + + Patient Outcome Assessment + + + Phenotype + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Zika Virus + + + Zika Virus Infection + complications + virology + + + + Zika virus infection + birthweight + congenital abnormalities + epilepsy + growth + infants + microcephaly + neurologic + outcomes + viruses + +
+ + + + 2016 + 10 + 22 + 6 + 0 + + + 2018 + 1 + 13 + 6 + 0 + + + 2016 + 10 + 22 + 6 + 0 + + + ppublish + + 27767931 + 10.3201/eid2211.160956 + PMC5088045 + + +
+ + + + + 27763795 + + 2017 + 03 + 06 + + + 2017 + 08 + 17 + +
+ + 1543-2165 + + 141 + 1 + + 2017 + Jan + + + Archives of pathology & laboratory medicine + Arch. Pathol. Lab. Med. + + Zika Virus: The Agent and Its Biology, With Relevance to Pathology. + + 33-42 + + 10.5858/arpa.2016-0409-RA + + Once obscure, Zika virus (ZIKV) has attracted significant medical and scientific attention in the past year because of large outbreaks associated with the recent introduction of this virus into the Western hemisphere. In particular, the occurrence of severe congenital infections and cases of Guillain-Barré syndrome has placed this virus squarely in the eyes of clinical and anatomic pathologists. This review article provides a basic introduction to ZIKV, its genetics, its structural characteristics, and its biology. A multidisciplinary effort will be essential to establish clinicopathologic correlations of the basic virology of ZIKV in order to advance development of diagnostics, therapeutics, and vaccines. + + + + Medin + Carey L + CL + + + Rothman + Alan L + AL + + From the Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence. Drs Medin and Rothman both contributed equally to the manuscript. + + + + eng + + Journal Article + Review + + + 2016 + 10 + 20 + +
+ + United States + Arch Pathol Lab Med + 7607091 + 0003-9985 + + AIM + IM + + + Brazil + epidemiology + + + Disease Outbreaks + + + Genome, Viral + genetics + + + Guillain-Barre Syndrome + complications + epidemiology + + + Humans + + + Microcephaly + complications + epidemiology + + + Polynesia + epidemiology + + + Uganda + epidemiology + + + Zika Virus + genetics + isolation & purification + physiology + + + Zika Virus Infection + complications + epidemiology + virology + + +
+ + + + 2016 + 10 + 21 + 6 + 0 + + + 2017 + 3 + 7 + 6 + 0 + + + 2016 + 10 + 21 + 6 + 0 + + + ppublish + + 27763795 + 10.5858/arpa.2016-0409-RA + + +
+ + + + + 27763483 + + 2017 + 01 + 02 + + + 2017 + 02 + 20 + +
+ + 0972-2823 + + 62 + 4 + + 2016 Oct-Dec + + + Journal of postgraduate medicine + J Postgrad Med + + The mysterious Zika virus: Adding to the tropical flavivirus mayhem. + + 249-254 + + 10.4103/0022-3859.191006 + + Until now, known as the demure cousin of dengue virus (DENV) inhabiting Africa, Zika virus (ZIKV) has reinvented itself to cause explosive epidemics captivating the Western hemisphere. The outbreak causing potential for ZIKV was realized when it made its way from Africa to Yap Island Micronesia in 2007, and in French Polynesia in 2013. From there, it moved on to Brazil in 2015. Now ZIKV has infected people in more than 33 countries in Central and South America and the Caribbean. Moreover the epidemiological and subsequent virological association with microcephaly cases in Brazil has prompted the World Health Organization to declare a public health emergency of International Concern. ZIKV shares not only its vector Aedes aegypti with dengue and chikungunya but also the geographic distribution and clinical features, which makes the laboratory confirmation mandatory for definitive diagnosis. The serological cross-reactivity with other Flavivirus, particularly with DENV makes laboratory confirmation challenging and will place additional burden on health systems to establish molecular diagnostic facilities. The evidence of additional nonvector modes of transmission, such as perinatal, sexual as well as transfusion has made preventative strategies more difficult. As ZIKV disease continues to mystify us with several unanswered questions, it calls for coordinated effort of global scientific community to address the ever growing arboviral threat to mankind. + + + + Mishra + B + B + + Department of Microbiology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India. + + + + Behera + B + B + + Department of Microbiology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India. + + + + eng + + Journal Article + Review + +
+ + India + J Postgrad Med + 2985196R + 0022-3859 + + IM + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Ann Trop Med Parasitol. 1975 Mar;69(1):49-64 + 1124969 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):120-1 + 26866485 + + + Am J Trop Med Hyg. 2016 Jul 6;95(1):15-8 + 26903610 + + + PLoS Negl Trop Dis. 2013 Aug 01;7(8):e2348 + 23936579 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3 + 26796813 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + Emerg Microbes Infect. 2016 Mar 16;5:e22 + 26980239 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + J Clin Virol. 2015 Jul;68:53-5 + 26071336 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Rev Soc Bras Med Trop. 2016 Feb;49(1):4-10 + 26689277 + + + New Microbes New Infect. 2016 Feb 11;11:6-7 + 27006779 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Aedes + + + Animals + + + Disease Outbreaks + + + Epidemics + + + Flavivirus + + + Humans + + + Insect Vectors + + + Microcephaly + epidemiology + + + Pandemics + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + epidemiology + transmission + + +
+ + + + 2016 + 10 + 21 + 6 + 0 + + + 2017 + 1 + 4 + 6 + 0 + + + 2016 + 10 + 21 + 6 + 0 + + + ppublish + + 27763483 + jpgm_2016_62_4_249_191006 + 10.4103/0022-3859.191006 + PMC5105211 + + +
+ + + + + 27746901 + + 2017 + 08 + 16 + +
+ + 2046-1402 + + 5 + + 2016 + + + F1000Research + F1000Res + + Illustrating and homology modeling the proteins of the Zika virus. + + 275 + + + The Zika virus (ZIKV) is a flavivirus of the familyFlaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it eitherin vitroorin vivo. ZIKV therefore epitomizes a neglected disease. Several suggested steps have been proposed which could be taken to initiate ZIKV antiviral drug discovery using both high throughput screens as well as structure-based design based on homology models for the key proteins. We now describe preliminary homology models created for NS5, FtsJ, NS4B, NS4A, HELICc, DEXDc, peptidase S7, NS2B, NS2A, NS1, E stem, glycoprotein M, propeptide, capsid and glycoprotein E using SWISS-MODEL. Eleven out of 15 models pass our model quality criteria for their further use. While a ZIKV glycoprotein E homology model was initially described in the immature conformation as a trimer, we now describe the mature dimer conformer which allowed the construction of an illustration of the complete virion. By comparing illustrations of ZIKV based on this new homology model and the dengue virus crystal structure we propose potential differences that could be exploited for antiviral and vaccine design. The prediction of sites for glycosylation on this protein may also be useful in this regard. While we await a cryo-EM structure of ZIKV and eventual crystal structures of the individual proteins, these homology models provide the community with a starting point for structure-based design of drugs and vaccines as well as a for computational virtual screening. + + + + Ekins + Sean + S + + Collaborations in Chemistry, Fuquay-Varina, NC, USA; Collaborations Pharmaceuticals Inc., Fuquay-Varina, NC, USA; Collaborative Drug Discovery Inc, Burlingame, CA, USA. + + + + Liebler + John + J + + Art of the Cell, Guilford, CT, USA. + + + + Neves + Bruno J + BJ + + LabMol - Laboratory for Molecular Modeling and Drug Design, Faculty of Pharmacy, Federal University of Goias, GO, Brazil. + + + + Lewis + Warren G + WG + + Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. + + + + Coffee + Megan + M + + The International Rescue Committee, New York, NY, USA. + + + + Bienstock + Rachelle + R + + RJB Computational Modeling LLC, Chapel Hill, NC, USA. + + + + Southan + Christopher + C + + Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK. + + + + Andrade + Carolina H + CH + + LabMol - Laboratory for Molecular Modeling and Drug Design, Faculty of Pharmacy, Federal University of Goias, GO, Brazil. + + + + eng + + Journal Article + + + 2016 + 03 + 03 + +
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virus + flavivirus + microcephaly + yellow fever + +
+ + + + 2016 + 08 + 30 + + + 2016 + 10 + 21 + 6 + 0 + + + 2016 + 10 + 21 + 6 + 1 + + + 2016 + 10 + 21 + 6 + 0 + + + epublish + + 27746901 + 10.12688/f1000research.8213.2 + PMC5040154 + + +
+ + + + + 27749669 + + 2017 + 04 + 24 + + + 2018 + 02 + 07 + +
+ + 1535-1815 + + 32 + 10 + + 2016 + Oct + + + Pediatric emergency care + Pediatr Emerg Care + + Zika Virus Disease: Case Report and Review of Literature. + + 705-709 + + + Zika virus (ZIKV) infection and its associated complications have become a significant public health concern. Zika virus is a Flavivirus, and is transmitted to humans by Aedes species mosquitoes. In May 2015, the World Health Organization reported the first locally acquired transmission of ZIKV in Brazil, the first case in the Western Hemisphere. There have also been reports of increased incidence of microcephaly and other neurologic complications associated with ZIKV infection, as well as a 20-fold increase in the incidence of Guillain-Barre Syndrome during ZIKV outbreaks. In light of the clusters of microcephaly and neurologic manifestations in areas of ZIKV transmission, the World Health Organization declared ZIKV and associated complications an international public health emergency. The clinical presentations of ZIKV disease resemble many common infections, making the diagnosis of ZIKV disease a clinical challenge. Patients with ZIKV infection may have other coinfections that can distract clinicians from suspecting ZIKV disease in their patients. Complications from ZIKV, although uncommon, may be severe. Therefore, it is important for health care providers to remain alert and up to date in the efforts to control this emerging global health crisis. It is critical for physicians and other providers to know the growing list of countries and territories on the US Centers for Disease Control and Prevention list of nations with endemic ZIKV disease and to work closely with local health departments to prevent spread. In this article, we present a case of ZIKV disease in a pediatric patient and review of the current literature. + + + + Darko + Richmond + R + + From the Pediatric Urgent Care Medicine, Division of Pediatric Hospital Medicine, Nicklaus Children's Hospital, Miami, FL. + + + + Mashburn + Jessica L + JL + + + eng + + Case Reports + Journal Article + Review + +
+ + United States + Pediatr Emerg Care + 8507560 + 0749-5161 + + + + RIT82F58GK + Penicillin G Benzathine + + + IM + + + Pediatr Emerg Care. 2017 Jun;33(6):e6 + 28441244 + + + + + Adolescent + + + Diagnosis, Differential + + + Female + + + Humans + + + Incidence + + + Insect Bites and Stings + virology + + + Penicillin G Benzathine + therapeutic use + + + Treatment Outcome + + + United States + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + drug therapy + epidemiology + transmission + + +
+ + + + 2016 + 10 + 18 + 6 + 0 + + + 2017 + 4 + 25 + 6 + 0 + + + 2016 + 10 + 18 + 6 + 0 + + + ppublish + + 27749669 + 10.1097/PEC.0000000000000932 + 00006565-201610000-00014 + + +
+ + + + + 27746903 + + 2017 + 09 + 05 + +
+ + 2046-1402 + + 5 + + 2016 + + + F1000Research + F1000Res + + Navigating the Zika panic. + + 1914 + + + The epidemics of Ebola virus in West Africa and Zika virus in America highlight how viruses can explosively emerge into new territories. These epidemics also exposed how unprepared we are to handle infectious disease emergencies. This is also true when we consider hypothesized new clinical features of infection, such as the associations between Zika virus infection and severe neurological disease, including microcephaly and Guillain-Barré syndrome. On the surface, these pathologies appear to be new features of Zika virus infection, however, causal relationships have not yet been established. Decades of limited Zika virus research are making us scramble to determine the true drivers behind the epidemic, often at the expense of over-speculation without credible evidence. Here we review the literature and find no conclusive evidence at this time for significant biological differences between the American Zika virus strains and those circulating elsewhere. Rather, the epidemic scale in the Americas may be facilitated by an abnormally warm climate, dense human and mosquito populations, and previous exposure to other viruses. Severe disease associated with Zika virus may therefore not be a new trait for the virus, rather it may have been overlooked due to previously small outbreaks. Much of the recent panic regarding Zika virus has been about the Olympics in Brazil. We do not find any substantial evidence that the Olympics will result in a significant number of new Zika virus infections (~10 predicted) or that the Olympics will promote further epidemic spread over what is already expected. The Zika virus epidemic in the Americas is a serious situation and decisions based on solid scientific evidence - not hyped media speculations - are required for effective outbreak response. + + + + Grubaugh + Nathan D + ND + + Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA. + + + + Andersen + Kristian G + KG + + Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA; Scripps Translational Science Institute, La Jolla, CA, 92037, USA; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. + + + + eng + + Journal Article + + + 2016 + 08 + 04 + +
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+ + + + 2016 + 08 + 03 + + + 2016 + 10 + 18 + 6 + 0 + + + 2016 + 10 + 18 + 6 + 0 + + + 2016 + 10 + 18 + 6 + 1 + + + epublish + + 27746903 + 10.12688/f1000research.9370.1 + PMC5040150 + + +
+ + + + + 27729840 + + 2018 + 01 + 24 + +
+ + 1598-866X + + 14 + 3 + + 2016 + Sep + + + Genomics & informatics + Genomics Inform + + Virtual Screening for Potential Inhibitors of NS3 Protein of Zika Virus. + + 104-111 + + + Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3) protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of -5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl)-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H)-one) was found to interact with NS3 protein with binding energy of -7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection. + + + + Sahoo + Maheswata + M + + Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India. + + + + Jena + Lingaraja + L + + Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India. + + + + Daf + Sangeeta + S + + Obstetrics & Gynaecology, Datta Meghe Institute of Medical Sciences (Deemed University), Nagpur 440-022, India. + + + + Kumar + Satish + S + + Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India. + + + + eng + + Journal Article + + + 2016 + 09 + 30 + +
+ + Korea (South) + Genomics Inform + 101223836 + 1598-866X + + + + Nat Protoc. 2009;4(3):363-71 + 19247286 + + + Nucleic Acids Res. 2010 Jan;38(Database issue):D255-66 + 19933261 + + + Virology. 1989 Apr;169(2):365-76 + 2705302 + + + Antiviral Res. 2014 Jun;106:125-34 + 24680954 + + + Proc Natl Acad Sci U S A. 1990 Mar;87(6):2057-61 + 2156259 + + + J Virol. 2006 Sep;80(17):8362-70 + 16912287 + + + J Gen Virol. 1988 Jan;69 ( Pt 1):23-34 + 2826667 + + + Protein Sci. 1993 Sep;2(9):1511-9 + 8401235 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + J Biol Chem. 2007 Apr 27;282(17):12883-92 + 17337448 + + + Genome Announc. 2014 Jun 05;2(3):null + 24903869 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + J Biol Chem. 2001 Dec 7;276(49):45762-71 + 11581268 + + + EMBO J. 2002 Jun 3;21(11):2757-68 + 12032088 + + + Protein Sci. 2003 May;12(5):1073-86 + 12717029 + + + J Mol Biol. 1990 Oct 5;215(3):403-10 + 2231712 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W362-5 + 16845026 + + + J Comput Chem. 2010 Jan 30;31(2):455-61 + 19499576 + + + Nucleic Acids Res. 2007 Jul;35(Web Server issue):W407-10 + 17517781 + + + Antiviral Res. 2010 Aug;87(2):125-48 + 19945487 + + + J Virol. 1995 Nov;69(11):7232-43 + 7474145 + + + Assay Drug Dev Technol. 2010 Oct;8(5):553-70 + 20973722 + + + F1000Res. 2015 Oct 20;4:1091 + 26834994 + + + Methods Mol Biol. 2015;1263:243-50 + 25618350 + + + J Infect Dis. 2015 Feb 1;211(3):394-404 + 25028694 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + F1000Res. 2015 Oct 20;4:1091 + 26834994 + + + Adv Virus Res. 2000;55:135-84 + 11050942 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + NS3 protein + drug design + flavivirus + high throughput screening methods + zika virus + +
+ + + + 2016 + 05 + 23 + + + 2016 + 06 + 16 + + + 2016 + 06 + 29 + + + 2016 + 10 + 13 + 6 + 0 + + + 2016 + 10 + 13 + 6 + 0 + + + 2016 + 10 + 13 + 6 + 1 + + + ppublish + + 27729840 + 10.5808/GI.2016.14.3.104 + PMC5056895 + + +
+ + + + + 27723844 + + 2017 + 04 + 28 + + + 2017 + 04 + 28 + +
+ + 1932-6203 + + 11 + 10 + + 2016 + + + PloS one + PLoS ONE + + A Lipidomics Approach in the Characterization of Zika-Infected Mosquito Cells: Potential Targets for Breaking the Transmission Cycle. + + e0164377 + + 10.1371/journal.pone.0164377 + + Recent outbreaks of Zika virus in Oceania and Latin America, accompanied by unexpected clinical complications, made this infection a global public health concern. This virus has tropism to neural tissue, leading to microcephaly in newborns in a significant proportion of infected mothers. The clinical relevance of this infection, the difficulty to perform accurate diagnosis and the small amount of data in literature indicate the necessity of studies on Zika infection in order to characterize new biomarkers of this infection and to establish new targets for viral control in vertebrates and invertebrate vectors. Thus, this study aims at establishing a lipidomics profile of infected mosquito cells compared to a control group to define potential targets for viral control in mosquitoes. Thirteen lipids were elected as specific markers for Zika virus infection (Brazilian strain), which were identified as putatively linked to the intracellular mechanism of viral replication and/or cell recognition. Our findings bring biochemical information that may translate into useful targets for breaking the transmission cycle. + + + + Melo + Carlos Fernando Odir Rodrigues + CF + + Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, 13083-877, Brazil. + + + + de Oliveira + Diogo Noin + DN + + Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, 13083-877, Brazil. + + + + Lima + Estela de Oliveira + EO + + Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, 13083-877, Brazil. + + + + Guerreiro + Tatiane Melina + TM + + Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, 13083-877, Brazil. + + + + Esteves + Cibele Zanardi + CZ + + Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, 13083-877, Brazil. + + + + Beck + Raissa Marques + RM + + Animal viruses Laboratory, Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, 13083-862, Brazil. + + + + Padilla + Marina Aiello + MA + + Animal viruses Laboratory, Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, 13083-862, Brazil. + + + + Milanez + Guilherme Paier + GP + + Emerging viruses study Laboratory, Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, 13083-862, Brazil. + + + + Arns + Clarice Weis + CW + + Animal viruses Laboratory, Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, 13083-862, Brazil. + + + + Proença-Modena + José Luiz + JL + + Emerging viruses study Laboratory, Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, 13083-862, Brazil. + + + + Souza-Neto + Jayme Augusto + JA + + Vector Functional Genomics & Microbiology Laboratory, UNESP Institute of Biotechnology, São Paulo State University, Alameda das Tecomarias s/n, Botucatu, 18607-440, Brazil. + + + Department of Bioprocesses and Biotechnology, Faculty of Agronomical Sciences, São Paulo State University, Rua José Barbosa 1780, Botucatu, 18610-307, Brazil. + + + + Catharino + Rodrigo Ramos + RR + + Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, 13083-877, Brazil. + + + + eng + + Journal Article + + + 2016 + 10 + 10 + +
+ + United States + PLoS One + 101285081 + 1932-6203 + + IM + + + Nucleic Acids Res. 2015 Jul 1;43(W1):W251-7 + 25897128 + + + PLoS Pathog. 2012;8(3):e1002584 + 22457619 + + + Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14682-7 + 26575624 + + + Osong Public Health Res Perspect. 2016 Apr;7(2):77-82 + 27169004 + + + PLoS Pathog. 2008 Jul 04;4(7):e1000098 + 18604274 + + + Travel Med Infect Dis. 2016 Jan-Feb;14 (1):16-20 + 26876061 + + + Nat Med. 2015 Dec;21(12 ):1464-72 + 26523970 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Nature. 2009 Apr 23;458(7241):1047-50 + 19396146 + + + J Am Coll Surg. 2016 Mar;222(3):269-280.e10 + 26922601 + + + J Infect. 2015 May;70(5):433-44 + 25727996 + + + Annu Rev Physiol. 2003;65:701-34 + 12471163 + + + Apoptosis. 2015 Apr;20(4):466-80 + 25577277 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Blood. 1997 Feb 15;89(4):1121-32 + 9028933 + + + Nat Med. 2008 Dec;14(12):1357-62 + 19029986 + + + J Gen Virol. 1993 Nov;74 ( Pt 11):2347-55 + 7504071 + + + Am J Physiol. 1998 Jan;274(1 Pt 2):H242-8 + 9458873 + + + Adv Virus Res. 2003;59:23-61 + 14696326 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + J Virol. 1975 Oct;16(4):913-26 + 170422 + + + J Virol. 2015 Oct 14;90(1):92-102 + 26468529 + + + J Autoimmun. 2016 Apr;68:1-13 + 26925496 + + + J Virol. 2014 Apr;88(8):4275-90 + 24478428 + + + IUBMB Life. 2010 Jun;62(6):414-28 + 20503434 + + + Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):E1064-73 + 26858414 + + + Antimicrob Agents Chemother. 2015 Jan;59(1):85-95 + 25313218 + + + Cell Host Microbe. 2012 Oct 18;12(4):544-57 + 23084921 + + + J Virol. 2003 Jul;77(14):7856-62 + 12829825 + + + Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17841-6 + 19805194 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + J Biol Chem. 1995 Mar 17;270(11):6062-70 + 7890739 + + + Cell Death Differ. 2013 Jan;20(1):64-76 + 22858544 + + + J Infect Dis. 2008 Feb 1;197(3):361-70 + 18248300 + + + J Bacteriol. 1991 Mar;173(6):2026-34 + 2002005 + + + Cell Host Microbe. 2011 Apr 21;9(4):286-98 + 21501828 + + + Sci Rep. 2016 Feb 18;6:19928 + 26887863 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Insect Biochem Mol Biol. 2015 Jul;62:194-210 + 25263765 + + + J Virol. 2013 Aug;87(15):8327-41 + 23698310 + + + Science. 2008 Apr 25;320(5875):531-5 + 18436786 + + + PLoS Pathog. 2009 Feb;5(2):e1000299 + 19214215 + + + FEBS Lett. 2004 Jul 2;569(1-3):173-7 + 15225629 + + + Cell Death Differ. 1998 Jul;5(7):551-62 + 10200509 + + + Biochem Biophys Res Commun. 2006 Jul 21;346(1):67-73 + 16750511 + + + + + Aedes + metabolism + virology + + + Animals + + + Cell Line + + + Female + + + Humans + + + Latin America + epidemiology + + + Lipid Metabolism + + + Male + + + Oceania + epidemiology + + + Zika Virus + metabolism + + + Zika Virus Infection + epidemiology + metabolism + transmission + + + The authors declare no competing financial interests. +
+ + + + 2016 + 07 + 19 + + + 2016 + 09 + 24 + + + 2016 + 10 + 11 + 6 + 0 + + + 2016 + 10 + 11 + 6 + 0 + + + 2017 + 4 + 30 + 6 + 0 + + + epublish + + 27723844 + 10.1371/journal.pone.0164377 + PONE-D-16-28918 + PMC5056752 + + +
+ + + + + 27719988 + + 2017 + 06 + 14 + + + 2017 + 12 + 05 + +
+ + 1557-9875 + + 34 + 4 + + 2016 + 11 + + + Neurologic clinics + Neurol Clin + + Epidemiology of Zika Virus. + + 1049-1056 + + S0733-8619(16)30030-5 + 10.1016/j.ncl.2016.06.008 + + Zika virus is an arbovirus belonging to the Flaviviridae family known to cause mild clinical symptoms similar to those of dengue and chikungunya. Zika is transmitted by different species of Aedes mosquitoes. Nonhuman primates and possibly rodents play a role as reservoirs. Direct interhuman transmission has also been reported. Human cases have been reported in Africa and Asia, Easter Island, the insular Pacific region, and Brazil. Its clinical profile is that of a dengue-like febrile illness, but recently associated Guillain-Barre syndrome and microcephaly have appeared. There is neither a vaccine nor prophylactic medications available to prevent Zika virus infection. + Copyright © 2016 Elsevier Inc. All rights reserved. + + + + Younger + David S + DS + + Division of Neuroepidemiology, Department of Neurology, New York University School of Medicine, New York, NY, USA; College of Global Public Health, New York University, New York, NY, USA. Electronic address: david.younger@nyumc.org. + + + + eng + + Journal Article + Review + + + 2016 + 08 + 18 + +
+ + United States + Neurol Clin + 8219232 + 0733-8619 + + IM + + + Animal Diseases + + + Animals + + + Humans + + + Public Health + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + epidemiology + prevention & control + transmission + + + + Neuroepidemiology + Public health + Zika virus + +
+ + + + 2016 + 10 + 11 + 6 + 0 + + + 2016 + 10 + 11 + 6 + 0 + + + 2017 + 6 + 15 + 6 + 0 + + + ppublish + + 27719988 + S0733-8619(16)30030-5 + 10.1016/j.ncl.2016.06.008 + + +
+ + + + + 27717627 + + 2017 + 02 + 14 + + + 2017 + 09 + 19 + +
+ + 2352-3964 + + 13 + + 2016 + Nov + + + EBioMedicine + EBioMedicine + + Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation. + + 315-320 + + S2352-3964(16)30451-0 + 10.1016/j.ebiom.2016.09.028 + + Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA). The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%). No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease. + Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved. + + + + Kim + Eun + E + + Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. + + + + Erdos + Geza + G + + Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. + + + + Huang + Shaohua + S + + Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. + + + + Kenniston + Thomas + T + + Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. + + + + Falo + Louis D + LD + Jr + + Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. + + + + Gambotto + Andrea + A + + Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: gambottoa@upmc.edu. + + + + eng + + + P50 CA121973 + CA + NCI NIH HHS + United States + + + + Journal Article + + + 2016 + 10 + 03 + +
+ + Netherlands + EBioMedicine + 101647039 + 2352-3964 + + + + 0 + Antibodies, Viral + + + 0 + Vaccines, Subunit + + + 0 + Viral Envelope Proteins + + + 0 + Viral Vaccines + + + IM + + + Biotechnol Prog. 2004 Mar-Apr;20(2):443-8 + 15058988 + + + Virology. 2016 Sep;496:186-93 + 27336950 + + + Science. 2016 Sep 9;353(6304):1129-32 + 27492477 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Curr Opin Immunol. 2009 Jun;21(3):308-13 + 19520559 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Pharm Res. 2014 Jan;31(1):117-35 + 23904139 + + + Neurotox Res. 2016 Aug;30(2):131-4 + 27260223 + + + PLoS One. 2012;7(7):e41501 + 22848514 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + Antiviral Res. 2008 Apr;78(1):116-24 + 18061688 + + + J Virol. 2014 May;88(10):5406-20 + 24574402 + + + PLoS Negl Trop Dis. 2016 May 05;10(5):e0004658 + 27149521 + + + J Virol. 1997 Mar;71(3):1842-9 + 9032314 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + Acta Biomater. 2015 Sep;24:96-105 + 26093066 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + J Virol. 2014 May;88(9):5100-8 + 24574396 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + J Virol. 2013 Aug;87(16):9379-83 + 23785207 + + + N Engl J Med. 2011 Apr 7;364(14):1326-33 + 21470010 + + + + + Adenoviridae + genetics + + + Animals + + + Antibodies, Viral + immunology + + + Cell Line + + + Disease Models, Animal + + + Disease Outbreaks + + + Female + + + Genetic Vectors + genetics + + + Humans + + + Immunization + + + Mice + + + Vaccines, Subunit + immunology + + + Viral Envelope Proteins + genetics + immunology + + + Viral Vaccines + administration & dosage + genetics + immunology + + + Zika Virus + genetics + immunology + + + Zika Virus Infection + epidemiology + prevention & control + + + + Adenovirus + Microneedles + Vaccine + ZIKV-E + Zika virus + +
+ + + + 2016 + 08 + 11 + + + 2016 + 09 + 26 + + + 2016 + 09 + 29 + + + 2016 + 10 + 9 + 6 + 0 + + + 2017 + 2 + 15 + 6 + 0 + + + 2016 + 10 + 9 + 6 + 0 + + + ppublish + + 27717627 + S2352-3964(16)30451-0 + 10.1016/j.ebiom.2016.09.028 + PMC5264651 + + +
+ + + + + 27704051 + + 2018 + 01 + 10 + +
+ + 2379-5042 + + 1 + 5 + + 2016 Sep-Oct + + + mSphere + mSphere + + Rescue of the 1947 Zika Virus Prototype Strain with a Cytomegalovirus Promoter-Driven cDNA Clone. + e00246-16 + + The recent Zika virus (ZIKV) outbreak has been linked to severe pathogenesis. Here, we report the construction of a plasmid carrying a cytomegalovirus (CMV) promoter-expressed prototype 1947 Uganda MR766 ZIKV cDNA that can initiate infection following direct plasmid DNA transfection of mammalian cells. Incorporation of a synthetic intron in the nonstructural protein 1 (NS1) region of the ZIKV polyprotein reduced viral cDNA-associated toxicity in bacteria. High levels of infectious virus were produced following transfection of the plasmid bearing the wild-type MR766 ZIKV genome, but not one with a disruption to the viral nonstructural protein 5 (NS5) polymerase active site. Multicycle growth curve and plaque assay experiments indicated that the MR766 virus resulting from plasmid transfection exhibited growth characteristics that were more similar to its parental isolate than previously published 2010 Cambodia and 2015 Brazil cDNA-rescued ZIKV. This ZIKV infectious clone will be useful for investigating the genetic determinants of ZIKV infection and pathogenesis and should be amenable to construction of diverse infectious clones expressing reporter proteins and representing a range of ZIKV isolates.IMPORTANCEThe study of ZIKV, which has become increasingly important with the recent association of this virus with microcephaly and Guillain-Barré syndrome, would benefit from an efficient strategy to genetically manipulate the virus. This work describes a model system to produce infectious virus in cell culture. We created a plasmid carrying the prototype 1947 Uganda MR766 ZIKV genome that both was stable in bacteria and could produce high levels of infectious virus in mammalian cells through direct delivery of this DNA. Furthermore, growth properties of this rescued virus closely resembled those of the viral isolate from which it was derived. This model system will provide a simple and effective means to study how ZIKV genetics impact viral replication and pathogenesis. + + + + Schwarz + Megan C + MC + + Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. + + + + Sourisseau + Marion + M + + Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. + + + + Espino + Michael M + MM + + Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. + + + + Gray + Essanna S + ES + + Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. + + + + Chambers + Matthew T + MT + + Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. + + + + Tortorella + Domenico + D + + Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. + + + + Evans + Matthew J + MJ + + Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. + + + + eng + + + F30 DK112514 + DK + NIDDK NIH HHS + United States + + + R01 DK095125 + DK + NIDDK NIH HHS + United States + + + R25 GM064118 + GM + NIGMS NIH HHS + United States + + + T32 AI007647 + AI + NIAID NIH HHS + United States + + + + Journal Article + + + 2016 + 09 + 28 + +
+ + United States + mSphere + 101674533 + 2379-5042 + + + + J Virol. 2002 May;76(9):4655-61 + 11932433 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Arch Virol. 2007;152(4):687-96 + 17195954 + + + Adv Virus Res. 1999;53:183-207 + 10582099 + + + J Virol. 2010 Nov;84(22):11696-708 + 20844048 + + + Virology. 2006 Mar 1;346(1):53-65 + 16325883 + + + Antiviral Res. 2015 Feb;114:67-85 + 25512228 + + + Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10460-4 + 12917491 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Science. 2005 Jul 22;309(5734):623-6 + 15947137 + + + MBio. 2016 Aug 23;7(4):null + 27555311 + + + PLoS Pathog. 2013 Mar;9(3):e1003244 + 23555257 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):154-8 + 26890470 + + + Cell Host Microbe. 2016 Jun 8;19(6):891-900 + 27198478 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Hepatology. 2015 Oct;62(4):1059-69 + 25820616 + + + Virology. 2001 Mar 15;281(2):272-80 + 11277699 + + + Virology. 2016 Oct;497:157-62 + 27471954 + + + + Zika virus + cell culture + flavivirus + infectious clones + +
+ + + + 2016 + 08 + 18 + + + 2016 + 09 + 06 + + + 2016 + 10 + 6 + 6 + 0 + + + 2016 + 10 + 6 + 6 + 0 + + + 2016 + 10 + 6 + 6 + 1 + + + epublish + + 27704051 + PMC5040786 + 10.1128/mSphere.00246-16 + mSphere00246-16 + + +
+ + + + + 27703544 + + 2017 + 08 + 16 + +
+ + 0351-0026 + + 55 + 4 + + 2016 + Dec + 01 + + + Zdravstveno varstvo + Zdr Varst + + Zika: an old virus with a new face. + + 228-230 + + + Zika virus is a mosquito-borne flavivirus that represents a public health emergency at the ongoing epidemic. This obscure virus was limited to sporadic cases in Africa and Asia, until the emergence of Zika virus in Brazil in 2015, when it rapidly spread throughout the Americas. Most Zika virus infections are subclinical or characterized by mild febrile illness. However, neurological complications, including Guillain-Barré syndrome in adults, and congenital anomalies, including microcephaly in babies born to infected mothers, raised a grave concern. Currently, there is no specific antiviral treatment or vaccine available for Zika virus infection. Thus, international public health response is primarily focused on preventing infection, particularly in pregnant women, and on providing up-to-date recommendations to reduce the risk of non-vector transmission of Zika virus. + + + + Avšic Županc + Tatjana + T + + University of Ljubljana, Faculty of Medicine, Institute of Microbiology and Immunology, Zaloška 4, 1000 Ljubljana, Slovenia. + + + + Petrovec + Miroslav + M + + University of Ljubljana, Faculty of Medicine, Institute of Microbiology and Immunology, Zaloška 4, 1000 Ljubljana, Slovenia. + + + + eng + + Journal Article + + + 2016 + 09 + 13 + +
+ + Slovenia + Zdr Varst + 9412992 + 0351-0026 + + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + Transfusion. 2016 Jul;56(7):1907-14 + 27282638 + + + Emerg Infect Dis. 2016 Jul;22(7):1185-92 + 27070380 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Travel Med Infect Dis. 2016 Jul-Aug;14 (4):313-30 + 27425793 + + + Antiviral Res. 2016 Jun;130:69-80 + 26996139 + + + Neuropathol Appl Neurobiol. 2016 Jun;42(4):317-25 + 27029817 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + + Zika je virus iz rodu flavivirusov, ki se prenaša s komarjevim pikom, in predstavlja javnozdravstveno grožnjo v trenutni epidemiji. Ta nepoznan virus je bil omejen na sporadične primere v Afriki in Aziji vse do pojava v Braziliji leta 2015, ko se je bliskovito razširil v obeh Amerikah. Večina okužb z virusom Zika je subkliničnih in se kažejo kot blaga bolezen z vročinskim stanjem. Najbolj zaskrbljujoči pa so nevrološki zapleti, vključno s sindromom Guillain-Barré pri odraslih ter prirojene nepravilnosti, kot je mikrocefalija pri novorojenčkih, ki se rodijo okuženim materam. Trenutno ne obstaja specifično protivirusno zdravljenje ali cepivo proti okužbi z virusom Zika. Odziv mednarodnega javnega zdravja se osredotoča na preprečevanje infekcije, predvsem pri nosečih ženskah in podajanju posodobljenih priporočil za zmanjšanje tveganja za nevektorsko prenašanje virusa Zika. + + + Zika virus + emerging infection + microcephaly + neurological complication + sexual transmission + + The authors declare that no conflicts of interest exist. +
+ + + + 2016 + 08 + 05 + + + 2016 + 08 + 12 + + + 2016 + 10 + 6 + 6 + 0 + + + 2016 + 10 + 6 + 6 + 0 + + + 2016 + 10 + 6 + 6 + 1 + + + epublish + + 27703544 + 10.1515/sjph-2016-0031 + sjph-2016-0031 + PMC5030833 + + +
+ + + + + 27695855 + + 2017 + 05 + 29 + + + 2017 + 05 + 29 + +
+ + 2168-6157 + + 73 + 12 + + 2016 + Dec + 01 + + + JAMA neurology + JAMA Neurol + + Congenital Zika Virus Infection: Beyond Neonatal Microcephaly. + + 1407-1416 + + 10.1001/jamaneurol.2016.3720 + + Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects. + To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil. + We observed 11 infants with congenital ZIKV infection from gestation to 6 months in the state of Paraíba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis. + Description of the major lesions caused by ZIKV congenital infection. + Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and brain). Phylogenetic analyses showed an intrahost virus variation with some polymorphisms in envelope genes associated with different tissues. + Combined findings from clinical, laboratory, imaging, and pathological examinations provided a more complete picture of the severe damage and developmental abnormalities caused by ZIKV infection than has been previously reported. The term congenital Zika syndrome is preferable to refer to these cases, as microcephaly is just one of the clinical signs of this congenital malformation disorder. + + + + Melo + Adriana Suely de Oliveira + AS + + Instituto de Pesquisa Professor Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil2Instituto de Saúde Elpidio de Almeida, Campina Grande, Paraíba, Brazil3Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil4Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil. + + + + Aguiar + Renato Santana + RS + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Amorim + Melania Maria Ramos + MM + + Instituto de Pesquisa Professor Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil2Instituto de Saúde Elpidio de Almeida, Campina Grande, Paraíba, Brazil3Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil6Universidade Federal de Campina Grande, Paraíba, Brazil. + + + + Arruda + Monica B + MB + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Melo + Fabiana de Oliveira + FO + + Instituto de Pesquisa Professor Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil2Instituto de Saúde Elpidio de Almeida, Campina Grande, Paraíba, Brazil. + + + + Ribeiro + Suelem Taís Clementino + ST + + Instituto de Saúde Elpidio de Almeida, Campina Grande, Paraíba, Brazil3Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil. + + + + Batista + Alba Gean Medeiros + AG + + Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil. + + + + Ferreira + Thales + T + + Universidade Federal de Campina Grande, Paraíba, Brazil. + + + + Dos Santos + Mayra Pereira + MP + + Instituto de Saúde Elpidio de Almeida, Campina Grande, Paraíba, Brazil. + + + + Sampaio + Virgínia Vilar + VV + + Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil4Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil. + + + + Moura + Sarah Rogéria Martins + SR + + Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil4Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil. + + + + Rabello + Luciana Portela + LP + + Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil4Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil. + + + + Gonzaga + Clarissa Emanuelle + CE + + Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil. + + + + Malinger + Gustavo + G + + Division of Ultrasound in Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. + + + + Ximenes + Renato + R + + Fundação de Medicina Fetal Latino Americana, Campinas, São Paulo, Brazil. + + + + de Oliveira-Szejnfeld + Patricia Soares + PS + + Fundação Instituto de Pesquisa e Ensino de Diagnostico por Imagem, Universidade Federal de São Paulo, São Paulo, Brazil. + + + + Tovar-Moll + Fernanda + F + + Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil11Instituto D'Or de Pesquisa e Ensino, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Chimelli + Leila + L + + Laboratório de Neuropatologia do Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. + + + + Silveira + Paola Paz + PP + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Delvechio + Rodrigo + R + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Higa + Luiza + L + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Campanati + Loraine + L + + Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Nogueira + Rita M R + RM + + Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Filippis + Ana Maria Bispo + AM + + Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Szejnfeld + Jacob + J + + Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo, São Paulo, Brazil. + + + + Voloch + Carolina Moreira + CM + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Ferreira + Orlando C + OC + Jr + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Brindeiro + Rodrigo M + RM + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Tanuri + Amilcar + A + + Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + +
+ + United States + JAMA Neurol + 101589536 + 2168-6149 + + AIM + IM + + + JAMA. 2017 Apr 4;317(13):1368-1369 + 28384812 + + + + + Abnormalities, Multiple + etiology + + + Arthrogryposis + etiology + + + Brazil + + + Cerebellum + pathology + + + Cerebrum + pathology + + + Female + + + Follow-Up Studies + + + Humans + + + Hydrocephalus + etiology + + + Infant + + + Infant Death + + + Infant, Newborn + + + Lissencephaly + etiology + + + Male + + + Microcephaly + etiology + + + Nervous System Malformations + etiology + + + Perinatal Death + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Zika Virus + genetics + isolation & purification + pathogenicity + + + Zika Virus Infection + complications + congenital + + +
+ + + + 2016 + 10 + 4 + 6 + 0 + + + 2017 + 5 + 30 + 6 + 0 + + + 2016 + 10 + 4 + 6 + 0 + + + ppublish + + 27695855 + 2557231 + 10.1001/jamaneurol.2016.3720 + + +
+ + + + + 27690200 + + 2017 + 06 + 02 + + + 2017 + 10 + 01 + +
+ + 2047-7732 + + 110 + 7-8 + + 2016 Oct - Dec + + + Pathogens and global health + Pathog Glob Health + + Zika virus infection and pregnancy: what we do and do not know. + + 262-268 + + + Recent data strongly suggest an association between the current outbreak of ZIKA virus (ZIKV) in many countries of Central and South America and a sharp increase in the detection of microcephaly and fetal malformations. The link with brain defect, which has been detected mainly in some areas of Brazil, is supported by the following evidence: (1) ZIKV transmission from infected pregnant women to their fetuses; (2) the potential of ZIKV to determine a specific congenital fetal syndrome characterized by abnormalities involving primarily the developing brain and eye. In particular, the risk of transmission and congenital disease appears to be restricted to mother's infection during the first trimester of pregnancy. Among brain defects, microcephaly, brain calcifications, and ventriculomegaly are the most frequent abnormalities of the central nervous system detected so far. However, relevant information on effect of maternal infection with ZIKV on the fetus is still limited. In this review, we focus our attention on current knowledge about ZIKV infection in pregnancy, discussing relevant issues and open problems which merit further investigation. + + + + Ticconi + Carlo + C + + a Section of Gynecology and Obstetrics, Department of Biomedicine and Prevention , University of Rome Tor Vergata , Rome , Italy. + + + + Pietropolli + Adalgisa + A + + a Section of Gynecology and Obstetrics, Department of Biomedicine and Prevention , University of Rome Tor Vergata , Rome , Italy. + + + + Rezza + Giovanni + G + + b Department of Infectious Diseases , Istituto Superiore di Sanità , Rome , Italy. + + + + eng + + Journal Article + Review + + + 2016 + 09 + 30 + +
+ + England + Pathog Glob Health + 101583421 + 2047-7724 + + IM + + + Pediatr Neurol Briefs. 2016 Jan;30(1):8 + 27004142 + + + Clin Infect Dis. 2016 Sep 15;63(6):805-11 + 27193747 + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Int J Infect Dis. 2016 Mar;44:11-5 + 26854199 + + + Emerg Infect Dis. 2016 May;22(5):828-32 + 27088494 + + + Epidemiol Infect. 2016 Jan;144(2):381-8 + 26113247 + + + Obstet Gynecol. 2016 Apr;127(4):642-8 + 26889662 + + + Arch Virol. 2016 Mar;161(3):665-8 + 26611910 + + + Reprod Toxicol. 2006 May;21(4):390-8 + 16580940 + + + Cell Biosci. 2016 Jun 10;6:42 + 27293547 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):63-7 + 26820387 + + + Am J Ophthalmol. 2003 Oct;136(4):733-5 + 14516816 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3 + 26796813 + + + MMWR Morb Mortal Wkly Rep. 2016 Apr 01;65(12):315-22 + 27031943 + + + Cell Stem Cell. 2016 Aug 4;19(2):258-65 + 27162029 + + + Epidemics. 2016 Jun;15:66-70 + 27288540 + + + J Glob Infect Dis. 2016 Jan-Mar;8(1):3-15 + 27013839 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Neurology. 2009 Sep 15;73(11):887-97 + 19752457 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + BMC Med. 2016 Jun 06;14 :84 + 27268016 + + + PLoS Negl Trop Dis. 2016 Apr 19;10(4):e0004682 + 27093158 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Acta Med Port. 2015 Nov-Dec;28(6):760-5 + 26849762 + + + J Infect. 2016 May;72 (5):507-24 + 26940504 + + + JAMA Ophthalmol. 2016 Aug 1;134(8):912-8 + 27228275 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Nature. 2016 Feb 4;530(7588):13-4 + 26842033 + + + Cell Host Microbe. 2016 Jul 13;20(1):83-90 + 27247001 + + + Emerg Infect Dis. 2011 Sep;17(9):1779-80 + 21888828 + + + Aust N Z J Obstet Gynaecol. 2016 Feb;56(1):9-18 + 26391432 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):55-8 + 26820163 + + + Eur J Pediatr. 2001 Nov;160(11):664-7 + 11760023 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Arch Dis Child. 2013 Sep;98(9):707-13 + 23814088 + + + Childs Nerv Syst. 2016 Jun;32(6):1057-60 + 27080092 + + + MMWR Morb Mortal Wkly Rep. 2016 Apr 08;65(13):352 + 27054688 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + N Engl J Med. 2016 Jun 15;:null + 27305043 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + J Infect Dev Ctries. 2010 Nov 24;4(11):767-75 + 21252457 + + + Am J Perinatol. 2016 Jun;33(7):625-39 + 26939047 + + + + + Animals + + + Brain + pathology + virology + + + Culicidae + virology + + + Eye Abnormalities + pathology + virology + + + Female + + + Fetus + abnormalities + + + Humans + + + Infectious Disease Transmission, Vertical + + + Insect Vectors + virology + + + Microcephaly + pathology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + pathology + virology + + + Zika Virus + physiology + + + Zika Virus Infection + complications + transmission + virology + + + + Congenital malformations + Microcephaly + Pregnancy + Zika Virus + +
+ + + + 2016 + 10 + 1 + 6 + 0 + + + 2017 + 6 + 3 + 6 + 0 + + + 2016 + 10 + 1 + 6 + 0 + + + ppublish + + 27690200 + 10.1080/20477724.2016.1234804 + PMC5189862 + + +
+ + + + + 27686610 + + 2017 + 02 + 20 + +
+ + 1476-0711 + + 15 + 1 + + 2016 + Sep + 29 + + + Annals of clinical microbiology and antimicrobials + Ann. Clin. Microbiol. Antimicrob. + + Management of infection by the Zika virus. + + 57 + + + A panel of national experts was convened by the Brazilian Infectious Diseases Society in order to organize the national recommendations for the management of zika virus infection. The focus of this document is the diagnosis, both clinical and laboratorial, and appropriate treatment of the diverse manifestations of this infection, ranging from acute mild disease to Guillain-Barré syndrome and also microcephaly and congenital malformations. + + + + Falcao + Melissa Barreto + MB + + Universidade Estadual de Feira de Santana, Avenida Transnordestina, s/n, Feira de Santana, BA, CEP 44036-900, Brazil. + + + + Cimerman + Sergio + S + + Instituto de Infectologia Emilio Ribas, Avenida Doutor Arnaldo, 165, São Paulo, SP, CEP 01246-000, Brazil. + + + + Luz + Kleber Giovanni + KG + + Universidade Federal do Rio Grande do Norte, Rua Conego Monte, s/n, Natal, RN, CEP 59037-170, Brazil. + + + + Chebabo + Alberto + A + + Universidade Federal do Rio de Janeiro, Avenida Professor Rodolpho Paulo Rocco, 255, 50. andar, Rio de Janeiro, RJ, CEP 21941-913, Brazil. + + + + Brigido + Helena Andrade + HA + + Universidade Federal do Para, Rua dos Mundurucus, s/n, Belem, PA, CEP 66060-060, Brazil. + + + + Lobo + Iza Maria + IM + + Universidade Federal de Sergipe, Avenida Claudio Batista, s/n, 3o. andar, Aracaju, SE, CEP 49060-100, Brazil. + + + + Timerman + Artur + A + + Hospital Professor Edmundo Vasconcelos, Rua Borges Lagoa, 1450, Sao Paulo, SP, CEP 04038-905, Brazil. + + + + Angerami + Rodrigo Nogueira + RN + + Universidade Estadual de Campinas, Rua Alexander Fleming, 181, Campinas, SP, CEP 13083-970, Brazil. + + + + da Cunha + Clovis Arns + CA + + Universidade Federal do Parana, Rua General Carneiro, 181, Curitiba, PR, CEP 80060-900, Brazil. + + + + Bacha + Helio Arthur + HA + + Hospital Israelita Albert Einstein, Avenida Albert Einstein, 627, Bloco A1, Sala 220, Sao Paulo, SP, CEP 05651-901, Brazil. + + + + Alves + Jesse Reis + JR + + Instituto de Infectologia Emilio Ribas, Avenida Doutor Arnaldo, 165, São Paulo, SP, CEP 01246-000, Brazil. + + + + Barbosa + Alexandre Naime + AN + + Universidade Estadual Paulista Julio de Mesquita Filho, Distrito de Rubiao Jr, s/n, Botucatu, SP, CEP 18618-970, Brazil. + + + + Teixeira + Ralcyon Francis + RF + + Instituto de Infectologia Emilio Ribas, Avenida Doutor Arnaldo, 165, São Paulo, SP, CEP 01246-000, Brazil. + + + + Weissmann + Leonardo + L + + Instituto de Infectologia Emilio Ribas, Avenida Doutor Arnaldo, 165, São Paulo, SP, CEP 01246-000, Brazil. + + + + Oliveira + Priscila Rosalba + PR + + Universidade de São Paulo, Rua Doutor Ovidio Pires de Campos, 333, Sao Paulo, SP, CEP 05403-010, Brazil. priscila.rosalba@hc.fm.usp.br. + + + + Cyrillo + Marco Antonio + MA + + Hospital do Servidor Publico Municipal, Rua Castro Alves, 60, São Paulo, SP, CEP 01532-000, Brazil. + + + + Bandeira + Antonio Carlos + AC + + Hospital Aliança, R. Juracy Magalhães Júnior, 2096, Salvador, BA, CEP 41920-000, Brazil. + + + + eng + + Review + Journal Article + + + 2016 + 09 + 29 + +
+ + England + Ann Clin Microbiol Antimicrob + 101152152 + 1476-0711 + + + + Ann Clin Microbiol Antimicrob. 2016 Mar 03;15:13 + 26939897 + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + Lancet. 2016 Mar 12;387(10023):1051 + 26944028 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + MMWR Morb Mortal Wkly Rep. 2016 Jun 03;65(21):543-6 + 27254248 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Arch Virol. 2016 Mar;161(3):665-8 + 26611910 + + + N Engl J Med. 2012 Jun 14;366(24):2294-304 + 22694000 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3 + 26796813 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Obstet Gynecol. 2016 Oct;128(4):724-30 + 27479770 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Mem Inst Oswaldo Cruz. 2016 May;111(5):287-93 + 27143490 + + + Lancet. 2016 Feb 27;387(10021):844-5 + 26898853 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Am J Public Health. 2016 Apr;106(4):606-12 + 26959260 + + + J Clin Virol. 2015 Jul;68:53-5 + 26071336 + + + Ann Clin Microbiol Antimicrob. 2016 Jul 22;15(1):42 + 27449770 + + + J Clin Microbiol. 2016 Sep;54(9):2348-53 + 27413190 + + + Lancet Infect Dis. 2016 Sep;16(9):1000-1 + 27427201 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Euro Surveill. 2014 Mar 13;19(10):null + 24650864 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Travel Med Infect Dis. 2016 Jan-Feb;14 (1):5-6 + 26879565 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Diagnosis + Guideline + Therapeutics + Zika virus infection + +
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+ + + + + 27653589 + + 2016 + 12 + 13 + + + 2016 + 12 + 30 + +
+ + 1533-4406 + + 375 + 12 + + 2016 + Sep + 22 + + + The New England journal of medicine + N. Engl. J. Med. + + Prolonged Shedding of Zika Virus Associated with Congenital Infection. + + 1202-4 + + 10.1056/NEJMc1607583 + + + Oliveira + Danielle B L + DB + + Universidade de São Paulo, São Paulo, Brazil. + + + + Almeida + Flávia J + FJ + + Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil. + + + + Durigon + Edison L + EL + + Universidade de São Paulo, São Paulo, Brazil eldurigo@usp.br. + + + + Mendes + Érica A + ÉA + + Universidade de São Paulo, São Paulo, Brazil eldurigo@usp.br. + + + + Braconi + Carla T + CT + + Universidade de São Paulo, São Paulo, Brazil eldurigo@usp.br. + + + + Marchetti + Ivan + I + + Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil. + + + + Andreata-Santos + Robert + R + + Universidade de São Paulo, São Paulo, Brazil. + + + + Cunha + Marielton P + MP + + Universidade de São Paulo, São Paulo, Brazil. + + + + Alves + Rúbens P S + RP + + Universidade de São Paulo, São Paulo, Brazil. + + + + Pereira + Lennon R + LR + + Universidade de São Paulo, São Paulo, Brazil. + + + + Melo + Stella R + SR + + Universidade de São Paulo, São Paulo, Brazil. + + + + Neto + Daniel F L + DF + + Universidade de São Paulo, São Paulo, Brazil. + + + + Mesquita + Flávio S + FS + + Universidade de São Paulo, São Paulo, Brazil. + + + + Araujo + Danielle B + DB + + Instituto Pasteur de São Paulo, São Paulo, Brazil. + + + + Favoretto + Silvana R + SR + + Instituto Pasteur de São Paulo, São Paulo, Brazil. + + + + Sáfadi + Marco A P + MA + + Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil. + + + + Ferreira + Luís C S + LC + + Universidade de São Paulo, São Paulo, Brazil. + + + + Zanotto + Paolo M A + PM + + Universidade de São Paulo, São Paulo, Brazil. + + + + Botosso + Viviane F + VF + + Instituto Butantan, São Paulo, Brazil. + + + + Berezin + Eitan N + EN + + Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil. + + + + eng + + Case Reports + Letter + + + 2016 + 08 + 24 + +
+ + United States + N Engl J Med + 0255562 + 0028-4793 + + AIM + IM + + + Female + + + Humans + + + Infant, Newborn + + + Male + + + Microcephaly + diagnostic imaging + virology + + + Pregnancy + + + Virus Shedding + + + Zika Virus + genetics + physiology + + + Zika Virus Infection + congenital + transmission + virology + + +
+ + + + 2016 + 9 + 23 + 6 + 0 + + + 2016 + 9 + 23 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + ppublish + + 27653589 + 10.1056/NEJMc1607583 + + +
+ + + + + 27651092 + + 2017 + 01 + 23 + + + 2017 + 02 + 20 + +
+ + 2222-1751 + + 5 + 9 + + 2016 + Sep + 21 + + + Emerging microbes & infections + Emerg Microbes Infect + + Zika virus-associated brain damage: animal models and open issues. + + e106 + + 10.1038/emi.2016.103 + + + Di Guardo + Giovanni + G + + Faculty of Veterinary Medicine, University of Teramo, Località Piano d'Accio, Teramo 64100, Italy. + + + + Braga + Patrícia Baleeiro Beltrão + PB + + Department of Surgery, Stem Cell Laboratory, University of São Paulo, Saint Paul 05508-270, Brazil. + + + + Peron + Jean Pierre Schatzmann + JP + + Department of Immunology, Neuroimmune Interactions Laboratory, University of São Paulo, Saint Paul 05508-000, Brazil. + + + + eng + + Journal Article + + + 2016 + 09 + 21 + +
+ + United States + Emerg Microbes Infect + 101594885 + 2222-1751 + + IM + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + Nature. 2016 Feb 11;530(7589):142-3 + 26863963 + + + Cell Stem Cell. 2016 May 5;18(5):591-6 + 27038591 + + + Cell. 2016 May 19;165(5):1238-54 + 27118425 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + Am J Public Health. 2016 Apr;106(4):606-12 + 26959260 + + + Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59 + 17315033 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Glia. 2007 Aug 1;55(10):1001-10 + 17503442 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + + + Animals + + + Brain + pathology + virology + + + Disease Models, Animal + + + Humans + + + Microcephaly + virology + + + South America + + + Viral Tropism + + + White Matter + pathology + + + Zika Virus + pathogenicity + + + Zika Virus Infection + pathology + virology + + +
+ + + + 2016 + 06 + 01 + + + 2016 + 07 + 15 + + + 2016 + 07 + 30 + + + 2016 + 9 + 22 + 6 + 0 + + + 2016 + 9 + 22 + 6 + 0 + + + 2017 + 1 + 24 + 6 + 0 + + + epublish + + 27651092 + emi2016103 + 10.1038/emi.2016.103 + PMC5113054 + + +
+ + + + + 27648063 + + 2016 + 09 + 20 + + + 2017 + 02 + 24 + +
+ + 1682-024X + + 32 + 4 + + 2016 Jul-Aug + + + Pakistan journal of medical sciences + Pak J Med Sci + + Zika virus: Epidemiology, current phobia and preparedness for upcoming mass gatherings, with examples from World Olympics and Pilgrimage. + + 1038-43 + + 10.12669/pjms.324.10038 + + To describe Zika Virus (ZIKV) epidemiology, current phobia, and the required preparedness for its prevention during the upcoming Mass Gathering (MG) events. + Electronic databases of PubMed, WHO, CDC, Pan American Health Organization (PAHO), Google, and Cochrane library were extensively searched for ZIKV. Articles were reviewed, scrutinized and critically appraised and the most relevant articles were utilized. + ZIKV is an emerging Flavivirus which was first isolated from Uganda in 1947. It is transmitted mainly through bite of Aedes mosquitoes. Sexual, perinatal and blood-borne transmissions are implicated. ZIKV is incriminated to cause microcephaly and Guillain-Barré syndrome. The spiky spread of ZIKV and its epidemic potential are especially problematic in countries which host big MGs with endogenous ZIKV circulation. This put millions of international travelers and local inhabitants at risk of acquiring ZIKV, especially in absence of vaccine until now. Brazil Olympic and Paralympics Games, and Muslims Hajj in Saudi Arabia are important upcoming MGs. Regarding Brazil, swiftly epidemic of ZIKV causes phobia and provokes claims and counter-claims about possible postponing or cancellation of such events. + Intensifying ZIKV epidemiological surveillance (sentinel, syndromic, environmental, laboratory and electronic), and conduction of educational programs are required. Controlling Aedes vector (chemically & biologically) is essential. Multidisciplinary cooperation is required to win the war against ZIKV. + + + + Ibrahim + Nahla Khamis + NK + + Prof. Nahla Khamis Ibrahim, MBBCh, MPH, Dr.PH, DHPE, JMHPE. Professor of Epidemiology, Family & Community Medicine Department, King Abdulaziz University, Jeddah, Saudi Arabia. Epidemiology Department, High Institute of Public Health, Alexandria University, Alexandria, Egypt. + + + + eng + + Journal Article + Review + +
+ + Pakistan + Pak J Med Sci + 100913117 + 1681-715X + + + + Lancet Infect Dis. 2012 Mar;12(3):231-9 + 22252148 + + + J Egypt Public Health Assoc. 2008;83(1-2):15-33 + 18992201 + + + Prehosp Disaster Med. 2013 Jun;28(3):292-7 + 23507042 + + + MMWR Morb Mortal Wkly Rep. 2016 May 06;65(17 ):451-5 + 27149205 + + + BMJ. 2005 Jan 15;330(7483):133-7 + 15649928 + + + Int J Infect Dis. 2016 Mar;44:11-5 + 26854199 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):120-1 + 26866485 + + + Euro Surveill. 2016;21(2):null + 26794427 + + + Glob Health Action. 2015 Jan 21;8:25929 + 25613346 + + + Front Public Health. 2015 Jun 08;3:157 + 26106592 + + + BMJ. 2016 Feb 02;352:i657 + 26839247 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + J Nepal Health Res Counc. 2015 Sep-Dec;13(31):248-51 + 27005721 + + + East Mediterr Health J. 2013;19 Suppl 2:S5-6 + 24673090 + + + J Autoimmun. 2016 Apr;68:1-13 + 26925496 + + + J Med Entomol. 2014 Jan;51(1):145-54 + 24605464 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + PLoS Curr. 2016 Mar 16;8:null + 27066299 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Prehosp Disaster Med. 2016 Apr;31(2):220-3 + 26843271 + + + Int J Infect Dis. 2016 Jul;48:85-90 + 27208633 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):55-8 + 26820163 + + + J Infect Public Health. 2009;2(1):30-40 + 20701858 + + + Lancet. 2016 Feb 13;387(10019):630-2 + 26864962 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):122-7 + 26866840 + + + + Emerging diseases + Epidemiology + Mass gathering + Phobia + Preparedness + Surveillance + Vaccine trials + Zika + + Declaration of interests: The author declares that there was no funding or conflict of interests. +
+ + + + 2016 + 9 + 21 + 6 + 0 + + + 2016 + 9 + 21 + 6 + 0 + + + 2016 + 9 + 21 + 6 + 1 + + + ppublish + + 27648063 + 10.12669/pjms.324.10038 + PJMS-32-1038 + PMC5017074 + + +
+ + + + + 27644020 + + 2017 + 12 + 05 + +
+ + 1469-0705 + + 50 + 6 + + 2017 + Dec + + + Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology + Ultrasound Obstet Gynecol + + Progressive lesions of central nervous system in microcephalic fetuses with suspected congenital Zika virus syndrome. + + 717-722 + + 10.1002/uog.17303 + + To describe the pattern and progression of central nervous system (CNS) lesions in microcephalic fetuses with suspected Zika virus (ZIKV) infection. + In this prospective study in Salvador, Brazil, we analyzed fetuses diagnosed with microcephaly and suspected ZIKV infection after a routine primary care ultrasound scan between July 2015 and February 2016 raised suspicion of fetal microcephaly. The pregnancies were followed with serial ultrasound scans until delivery at one of the three main referral centers for fetal abnormalities in Salvador, Brazil. Microcephaly was diagnosed when the head circumference was two or more SDs below the mean for gestational age and its relationship with ZIKV infection was defined according to the World Health Organization's criteria. All women were interviewed, to assess potential factors associated with fetal microcephaly. Serology test results for toxoplasmosis, cytomegalovirus, rubella, syphilis and human immunodeficiency virus (HIV) were recorded, as were previous routine ultrasound results. Signs/symptoms of infection during the pregnancy were noted. + Of 60 cases of suspected ZIKV-related fetal microcephaly seen during the study period, eight were excluded due to serological evidence of other congenital infections or major ultrasound chromosomal markers. In the remaining 52 fetuses, microcephaly was diagnosed between 19 and 40 (median, 27.7; interquartile range, 23.4-32.0) weeks of gestation. The main ultrasound findings were: ventriculomegaly (65.4% of cases), cerebral calcifications (44.2%) and posterior fossa abnormalities (32.7%). 9.6% presented with arthrogryposis as an associated finding. Microcephaly was an isolated finding in four cases (7.7%). While ventriculomegaly was progressive in 41.2% of cases with this finding, the velocity of head circumference increase decreased progressively in almost all cases. Exanthematic disease was present in the majority (86.5%) of the women, 67.3% presenting in the first trimester of pregnancy. Additional lesions were detected after birth in 71.4% of the 35 cases with neonatal follow-up. + The majority of cases of congenital ZIKV syndrome have other ultrasonographic findings in addition to microcephaly. ZIKV-related CNS anomalies present mainly as progressive CNS lesions and slowing rate of growth of the fetal head, and this seems to be evident only in the late second trimester, even when maternal infection occurs in the first trimester. Other ultrasound findings, such as ventriculomegaly, brain calcifications and posterior fossa destruction lesions, are also common in this congenital syndrome. Posterior fossa destruction lesions and arthrogryposis are an uncommon finding in other congenital infections, perhaps suggesting a novel severe congenital syndrome associated with fetal ZIKV. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. + Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. + + + + Sarno + M + M + http://orcid.org/0000-0002-2312-0932 + + Maternidade Climério de Oliveira, Federal University of Bahia, Salvador, Brazil. + + + Caliper Escola de Imagem - Ultrasound Training Center, Salvador, Brazil. + + + Hospital Geral Roberto Santos, Secretaria Estadual da Saúde da Bahia, Salvador, Brazil. + + + + Aquino + M + M + + Maternidade Climério de Oliveira, Federal University of Bahia, Salvador, Brazil. + + + Caliper Escola de Imagem - Ultrasound Training Center, Salvador, Brazil. + + + + Pimentel + K + K + + Maternidade Climério de Oliveira, Federal University of Bahia, Salvador, Brazil. + + + Caliper Escola de Imagem - Ultrasound Training Center, Salvador, Brazil. + + + Hospital Geral Roberto Santos, Secretaria Estadual da Saúde da Bahia, Salvador, Brazil. + + + + Cabral + R + R + + Maternidade Climério de Oliveira, Federal University of Bahia, Salvador, Brazil. + + + + Costa + G + G + + Federal University of Bahia, Salvador, Brazil. + + + + Bastos + F + F + + Federal University of Bahia, Salvador, Brazil. + + + + Brites + C + C + http://orcid.org/0000-0002-4673-6991 + + Federal University of Bahia, Salvador, Brazil. + + + + eng + + Journal Article + + + 2017 + 11 + 08 + +
+ + England + Ultrasound Obstet Gynecol + 9108340 + 0960-7692 + + + Brazil + Zika virus + congenital Zika virus syndrome + fetal defects + microcephaly + ultrasound + +
+ + + + 2016 + 05 + 10 + + + 2016 + 08 + 31 + + + 2016 + 09 + 01 + + + 2016 + 9 + 20 + 6 + 0 + + + 2016 + 9 + 20 + 6 + 0 + + + 2016 + 9 + 20 + 6 + 0 + + + ppublish + + 27644020 + 10.1002/uog.17303 + + +
+ + + + + 27641777 + + 2017 + 05 + 16 + + + 2017 + 08 + 07 + +
+ + 1474-4457 + + 16 + 12 + + 2016 + Dec + + + The Lancet. Infectious diseases + Lancet Infect Dis + + Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study. + + 1356-1363 + + S1473-3099(16)30318-8 + 10.1016/S1473-3099(16)30318-8 + + The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy. + We did this case-control study in eight public hospitals in Recife, Brazil. Cases were neonates with microcephaly. Two controls (neonates without microcephaly), matched by expected date of delivery and area of residence, were selected for each case. Serum samples of cases and controls and cerebrospinal fluid samples of cases were tested for Zika virus-specific IgM and by quantitative RT-PCR. Laboratory-confirmed Zika virus infection during pregnancy was defined as detection of Zika virus-specific IgM or a positive RT-PCR result in neonates. Maternal serum samples were tested by plaque reduction neutralisation assay for Zika virus and dengue virus. We estimated crude odds ratios (ORs) and 95% CIs using a median unbiased estimator for binary data in an unconditional logistic regression model. We estimated ORs separately for cases with and without radiological evidence of brain abnormalities. + Between Jan 15, 2016, and May 2, 2016, we prospectively recruited 32 cases and 62 controls. 24 (80%) of 30 mothers of cases had Zika virus infection compared with 39 (64%) of 61 mothers of controls (p=0·12). 13 (41%) of 32 cases and none of 62 controls had laboratory-confirmed Zika virus infection; crude overall OR 55·5 (95% CI 8·6-∞); OR 113·3 (95% CI 14·5-∞) for seven cases with brain abnormalities; and OR 24·7 (95% CI 2·9-∞) for four cases without brain abnormalities. + Our data suggest that the microcephaly epidemic is a result of congenital Zika virus infection. We await further data from this ongoing study to assess other potential risk factors and to confirm the strength of association in a larger sample size. + Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. + Copyright This is an Open Access article published under the CC BY 3.0 IGO license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL. + + + + de Araújo + Thalia Velho Barreto + TVB + + Department of Social Medicine, Federal University of Pernambuco, Recife, Brazil. Electronic address: thalia@ufpe.br. + + + + Rodrigues + Laura Cunha + LC + + Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. + + + + de Alencar Ximenes + Ricardo Arraes + RA + + Department of Tropical Medicine, Federal University of Pernambuco, Recife, Brazil; University of Pernambuco, Recife, Brazil. + + + + de Barros Miranda-Filho + Demócrito + D + + University of Pernambuco, Recife, Brazil. + + + + Montarroyos + Ulisses Ramos + UR + + University of Pernambuco, Recife, Brazil. + + + + de Melo + Ana Paula Lopes + APL + + Department of Community Health, Federal University of Pernambuco, Vitória de Santo Antão, Brazil. + + + + Valongueiro + Sandra + S + + Department of Social Medicine, Federal University of Pernambuco, Recife, Brazil. + + + + de Albuquerque + Maria de Fátima Pessoa Militão + MFPM + + The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Souza + Wayner Vieira + WV + + The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Braga + Cynthia + C + + The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Filho + Sinval Pinto Brandão + SPB + + The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Cordeiro + Marli Tenório + MT + + The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Vazquez + Enrique + E + + Pan American Health Organization, Brasília, Brazil. + + + + Di Cavalcanti Souza Cruz + Danielle + D + + Instituto Materno Infantil Fernando Figueira, Recife, Brazil. + + + + Henriques + Cláudio Maierovitch Pessanha + CMP + + Fiocruz Brasília, Brasília, Brazil. + + + + Bezerra + Luciana Caroline Albuquerque + LCA + + Pernambuco State Health Department, Recife, Brazil. + + + + da Silva Castanha + Priscila Mayrelle + PM + + The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Dhalia + Rafael + R + + The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Marques-Júnior + Ernesto Torres Azevedo + ETA + + The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Martelli + Celina Maria Turchi + CMT + + The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil; Department of Community Health, Federal University of Goiás, Goiânia, Brazil. + + + + investigators from the Microcephaly Epidemic Research Group + + + Brazilian Ministry of Health + + + Pan American Health Organization + + + Instituto de Medicina Integral Professor Fernando Figueira + + + State Health Department of Pernambuco + + + eng + + Journal Article + + + 2016 + 09 + 16 + +
+ + United States + Lancet Infect Dis + 101130150 + 1473-3099 + + IM + + + Brazil + epidemiology + + + Case-Control Studies + + + Female + + + Gestational Age + + + Humans + + + Microcephaly + epidemiology + pathology + virology + + + Neuroimaging + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + pathology + virology + + + Prospective Studies + + + Risk Factors + + + Zika Virus + isolation & purification + + + Zika Virus Infection + congenital + diagnosis + epidemiology + pathology + + +
+ + + + 2016 + 06 + 10 + + + 2016 + 08 + 03 + + + 2016 + 08 + 08 + + + 2016 + 9 + 20 + 6 + 0 + + + 2017 + 5 + 17 + 6 + 0 + + + 2016 + 9 + 20 + 6 + 0 + + + ppublish + + 27641777 + S1473-3099(16)30318-8 + 10.1016/S1473-3099(16)30318-8 + + +
+ + + + + 27641776 + + 2017 + 08 + 07 + +
+ + 1474-4457 + + 16 + 12 + + 2016 + Dec + + + The Lancet. Infectious diseases + Lancet Infect Dis + + More pieces to the microcephaly-Zika virus puzzle in Brazil. + + 1307-1309 + + S1473-3099(16)30372-3 + 10.1016/S1473-3099(16)30372-3 + + + Brasil + Patricia + P + + Fiocruz RJ, Rio de Janeiro, 22010122, Brazil. Electronic address: patricia.brasil@ini.fiocruz.br. + + + + Nielsen-Saines + Karin + K + + Department of Pediatrics, UCLA, Los Angeles, CA, USA. + + + + eng + + Journal Article + + + 2016 + 09 + 16 + +
+ + United States + Lancet Infect Dis + 101130150 + 1473-3099 + +
+ + + + 2016 + 08 + 23 + + + 2016 + 08 + 24 + + + 2016 + 9 + 20 + 6 + 0 + + + 2016 + 9 + 20 + 6 + 0 + + + 2016 + 9 + 20 + 6 + 0 + + + ppublish + + 27641776 + S1473-3099(16)30372-3 + 10.1016/S1473-3099(16)30372-3 + + +
+ + + + + 27631604 + + 2017 + 01 + 11 + + + 2017 + 01 + 12 + +
+ + 1545-861X + + 65 + 36 + + 2016 + Sep + 16 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Zika Virus Disease Cases - 50 States and the District of Columbia, January 1-July 31, 2016. + + 983-6 + + 10.15585/mmwr.mm6536e5 + + Zika virus is a mosquito-borne flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes (1). Zika virus infections have also been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure (1-5). Most Zika virus infections are asymptomatic (1,6). Clinical illness, when it occurs, is generally mild and characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis. However, Zika virus infection during pregnancy can cause adverse outcomes such as fetal loss, and microcephaly and other serious brain anomalies (1-3). Guillain-Barré syndrome, a rare autoimmune condition affecting the peripheral nervous system, also has been associated with Zika virus infection (1). Following the identification of local transmission of Zika virus in Brazil in May 2015, the virus has continued to spread throughout the Region of the Americas, and travel-associated cases have increased (7). In 2016, Zika virus disease and congenital infections became nationally notifiable conditions in the United States (8). As of September 3, 2016, a total of 2,382 confirmed and probable cases of Zika virus disease with symptom onset during January 1-July 31, 2016, had been reported from 48 of 50 U.S. states and the District of Columbia. Most cases (2,354; 99%) were travel-associated, with either direct travel or an epidemiologic link to a traveler to a Zika virus-affected area. Twenty-eight (1%) cases were reported as locally acquired, including 26 associated with mosquito-borne transmission, one acquired in a laboratory, and one with an unknown mode of transmission. Zika virus disease should be considered in patients with compatible clinical signs or symptoms who traveled to or reside in areas with ongoing Zika virus transmission or who had unprotected sex with someone who traveled to those areas. Health care providers should continue to educate patients, especially pregnant women, about the importance of avoiding infection with Zika virus, and all pregnant women should be assessed for possible Zika virus exposure at each prenatal visit (2). + + + + Walker + William L + WL + + + Lindsey + Nicole P + NP + + + Lehman + Jennifer A + JA + + + Krow-Lucal + Elisabeth R + ER + + + Rabe + Ingrid B + IB + + + Hills + Susan L + SL + + + Martin + Stacey W + SW + + + Fischer + Marc + M + + + Staples + J Erin + JE + + + eng + + Journal Article + + + 2016 + 09 + 16 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + Adolescent + + + Adult + + + Aged + + + Aged, 80 and over + + + Child + + + Child, Preschool + + + District of Columbia + epidemiology + + + Female + + + Humans + + + Infant + + + Infant, Newborn + + + Male + + + Middle Aged + + + Pregnancy + + + Travel + statistics & numerical data + + + United States + epidemiology + + + Young Adult + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + prevention & control + transmission + + +
+ + + + 2016 + 9 + 16 + 6 + 0 + + + 2016 + 9 + 16 + 6 + 0 + + + 2017 + 1 + 12 + 6 + 0 + + + epublish + + 27631604 + 10.15585/mmwr.mm6536e5 + + +
+ + + + + 27630846 + + 2016 + 09 + 16 + + + 2017 + 02 + 20 + +
+ + 2249-782X + + 10 + 7 + + 2016 + Jul + + + Journal of clinical and diagnostic research : JCDR + J Clin Diagn Res + + Zika Virus: An Emergence of a New Arbovirus. + + DM01-3 + + 10.7860/JCDR/2016/19170.8133 + + The world is facing a new pandemic in progress due to a mosquito-borne flavivirus popularly known as Zika virus. The emergence of this new virus is really alarming with the sudden increment in the cases of microcephaly reported from Brazil. The findings attributing the involvement of Zika virus as the reason for congenital deformations in the babies born in afflicted areas have really shocked the world. The present knowledge about this virus is very limited and in the absence of further studies the precautions seems to be the best way of protection from this virus. The present article is a short review about this new virus. + + + + Yadav + Sankalp + S + + General Duty Medical Officer-II, Department of Medicine and TB, Chest Clinic Moti Nagar, North Delhi Municipal Corporation New Delhi, India . + + + + Rawal + Gautam + G + + Attending Consultant-Respiratory Intensive Care, Care, Max Super Specialty Hospital , Saket, New Delhi, India . + + + + Baxi + Mudit + M + + Postgraduate Student, Department of Orthopedics, Sri Aurobindo Medical College and Postgraduate Institute , Indore, Madhya Pradesh, India . + + + + eng + + Journal Article + + + 2016 + 07 + 01 + +
+ + India + J Clin Diagn Res + 101488993 + 0973-709X + + + + Pan Afr Med J. 2015 Oct 12;22:118 + 26848365 + + + Bull Soc Pathol Exot. 1993;86(1):21-8 + 8099299 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + PLoS One. 2014 Oct 13;9(10):e109442 + 25310102 + + + PLoS Negl Trop Dis. 2014 Feb 06;8(2):e2681 + 24516683 + + + Ann Trop Med Parasitol. 1975 Mar;69(1):49-64 + 1124969 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + Emerg Infect Dis. 2015 Feb;21(2):381-2 + 25625687 + + + Trans R Soc Trop Med Hyg. 1964 Jul;58:335-8 + 14175744 + + + Lancet. 2016 Jan 23;387(10016):335-6 + 26777915 + + + J Immunol. 1954 Apr;72(4):248-57 + 13163397 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3 + 26796813 + + + Bull Soc Pathol Exot Filiales. 1982 May-Jul;75(3):262-6 + 6809352 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + Arch Gesamte Virusforsch. 1973;43(4):315-9 + 4799154 + + + Bull Soc Pathol Exot Filiales. 1978 Mar-Apr;71(2):140-6 + 743766 + + + Bull Soc Pathol Exot. 2001 Aug;94(3):227-30 + 11681215 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + J Clin Virol. 2015 Feb;63:32-5 + 25600600 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + Am J Obstet Gynecol. 2011 Jun;204(6 Suppl 1):S13-20 + 21333967 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + J Hyg (Lond). 1979 Oct;83(2):213-9 + 489960 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Trans R Soc Trop Med Hyg. 1983;77(4):442-5 + 6314612 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Rev Soc Bras Med Trop. 2016 Feb;49(1):4-10 + 26689277 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Bull Soc Pathol Exot Filiales. 1981 Sep-Oct;74(5):490-9 + 6274526 + + + Trans R Soc Trop Med Hyg. 1956 May;50(3):238-42 + 13337908 + + + J Infect. 2001 Feb;42(2):104-15 + 11531316 + + + Trop Geogr Med. 1977 Jun;29(2):187-91 + 906078 + + + Bull Soc Pathol Exot Filiales. 1975 May-Jun;68(3):249-58 + 1243735 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Aedes + Flavivirus + French polynesia + Serum + Yap + +
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+ + 1678-2925 + + 79 + 4 + + 2016 Jul-Aug + + + Arquivos brasileiros de oftalmologia + Arq Bras Oftalmol + + Ocular finding in Zika virus infectionResponse letter: Serological evidence confirms the presumed diagnosis of Zika virus congenital infection in infants with microcephaly and ocular findingsZika virus outbreak in the Americas: the need for novel mosquito control methodsThe Brazilian Zika virus strain causes birth defects in experimental modelsOphthalmologic findings in infants with microcephaly and presumable intra-uterus Zika virus infectionZika virus in Brazil and macular atrophy in a child with microcephalyVariables related to the ophthalmoscopic findings identified in infants with presumed Zika virus congenital infection. + + 280 + + 10.5935/0004-2749.20160081 + S0004-27492016000400280 + + + Wiwanitkit + Viroj + V + + Hainan Medical University, Haikou, Hainan, China. + + + Faculty of Medicine, University of Nis, Nis, Serbia. + + + Joseph Ayobabalola University, Ilesa, Osun State, Nigeria. + + + Dr DY Patil Medical University, Pimpri, Maharashtra, India. + + + + eng + + Letter + +
+ + Brazil + Arq Bras Oftalmol + 0400645 + 0004-2749 + + IM + + + Atrophy + + + Brazil + epidemiology + + + Child + + + Disease Outbreaks + + + Female + + + Humans + + + Infant + + + Microcephaly + epidemiology + + + Mosquito Control + + + Uterus + + + Zika Virus + + +
+ + + + 2016 + 9 + 15 + 6 + 0 + + + 2016 + 9 + 15 + 6 + 0 + + + 2017 + 10 + 27 + 6 + 0 + + + ppublish + + 27626161 + S0004-27492016000400280 + 10.5935/0004-2749.20160081 + + +
+ + + + + 27623958 + + 2017 + 04 + 13 + + + 2017 + 08 + 17 + +
+ + 1756-1833 + + 354 + + 2016 + Sep + 13 + + + BMJ (Clinical research ed.) + BMJ + + Population surveillance for microcephaly. + + i4815 + + 10.1136/bmj.i4815 + + + Kirby + Russell S + RS + + Department of Community and Family Health, College of Public Health, University of South Florida, Tampa, FL, USA. + + + + eng + + Editorial + + + 2016 + 09 + 13 + +
+ + England + BMJ + 8900488 + 0959-535X + + AIM + IM + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + Neurology. 2009 Sep 15;73(11):887-97 + 19752457 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Emerg Infect Dis. 2016 Nov;22(11):1894-1899 + 27603576 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Birth Defects Res A Clin Mol Teratol. 2010 Dec;88(12):1008-16 + 20878909 + + + Birth Defects Res A Clin Mol Teratol. 2013 Nov;97(11):709-25 + 24265125 + + + + + Brazil + epidemiology + + + Europe + epidemiology + + + Female + + + Humans + + + Infant + + + Infant, Newborn + + + Microcephaly + diagnosis + epidemiology + virology + + + Population Surveillance + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + epidemiology + virology + + + United States + epidemiology + + + Zika Virus + + + Zika Virus Infection + complications + + + I have read and understood the BMJ policy on declaration of interests and declare the following: none. +
+ + + + 2016 + 9 + 15 + 6 + 0 + + + 2016 + 9 + 15 + 6 + 0 + + + 2017 + 4 + 14 + 6 + 0 + + + epublish + + 27623958 + PMC5021823 + + +
+ + + + + 27623840 + + 2017 + 04 + 13 + + + 2017 + 08 + 17 + +
+ + 1756-1833 + + 354 + + 2016 + Sep + 13 + + + BMJ (Clinical research ed.) + BMJ + + Prevalence of microcephaly in Europe: population based study. + + i4721 + + 10.1136/bmj.i4721 + +  To provide contemporary estimates of the prevalence of microcephaly in Europe, determine if the diagnosis of microcephaly is consistent across Europe, and evaluate whether changes in prevalence would be detected using the current European surveillance performed by EUROCAT (the European Surveillance of Congenital Anomalies). +  Questionnaire and population based observational study. +  24 EUROCAT registries covering 570 000 births annually in 15 countries. +  Cases of microcephaly not associated with a genetic condition among live births, fetal deaths from 20 weeks' gestation, and terminations of pregnancy for fetal anomaly at any gestation. +  Prevalence of microcephaly (1 Jan 2003-31 Dec 2012) analysed with random effects Poisson regression models to account for heterogeneity across registries. +  16 registries responded to the questionnaire, of which 44% (7/16) used the EUROCAT definition of microcephaly (a reduction in the size of the brain with a skull circumference more than 3 SD below the mean for sex, age, and ethnic origin), 19% (3/16) used a 2 SD cut off, 31% (5/16) were reliant on the criteria used by individual clinicians, and one changed criteria between 2003 and 2012. Prevalence of microcephaly in Europe was 1.53 (95% confidence interval 1.16 to 1.96) per 10 000 births, with registries varying from 0.4 (0.2 to 0.7) to 4.3 (3.6 to 5.0) per 10 000 (χ(2)=338, df=23, I(2)=93%). Registries with a 3 SD cut off reported a prevalence of 1.74 per 10 000 (0.86 to 2.93) compared with those with the less stringent 2 SD cut off of 1.21 per 10 000 (0.21 to 2.93). The prevalence of microcephaly would need to increase in one year by over 35% in Europe or by over 300% in a single registry to reach statistical significance (P<0.01). +  EUROCAT could detect increases in the prevalence of microcephaly from the Zika virus of a similar magnitude to those observed in Brazil. Because of the rarity of microcephaly and discrepant diagnostic criteria, however, the smaller increases expected in Europe would probably not be detected. Clear diagnostic criteria for microcephaly must be adopted across Europe. + Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. + + + + Morris + Joan K + JK + + Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK. + + + + Rankin + Judith + J + + Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK. + + + + Garne + Ester + E + + Paediatric Department, Hospital Lillebaelt, Kolding, Denmark. + + + + Loane + Maria + M + + University of Ulster, Newtownabbey, Co Antrim, Northern Ireland, UK. + + + + Greenlees + Ruth + R + + University of Ulster, Newtownabbey, Co Antrim, Northern Ireland, UK. + + + + Addor + Marie-Claude + MC + + Division of Medical Genetics, Lausanne, Switzerland. + + + + Arriola + Larraitz + L + + Public Health Division of Gipuzkoa, Instituto BIO-Donostia, Basque Government, CIBER Epidemiologia y Salud Publica - CIBERESP, Spain. + + + + Barisic + Ingeborg + I + + Children's Hospital Zagreb, Medical School University of Zagreb, Zagreb, Croatia. + + + + Bergman + Jorieke E H + JE + + University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, Netherlands. + + + + Csaky-Szunyogh + Melinda + M + + National Public Health and Medical Officer Service, Hungarian Congenital Abnormality Registry, Budapest, Hungary. + + + + Dias + Carlos + C + + Centro de Estudos e registo de A C, Lisbon, Portugal. + + + + Draper + Elizabeth S + ES + + University of Leicester, Leicester, UK. + + + + Gatt + Miriam + M + + Department of Health Information and Research, Guardamangia, Malta. + + + + Khoshnood + Babak + B + + INSERM, Paris, France. + + + + Klungsoyr + Kari + K + + Department of Global Public Health and Primary Care, University of Bergen, and Medical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway. + + + + Kurinczuk + Jennifer J + JJ + + National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK. + + + + Lynch + Catherine + C + + Health Service Executive, Kilkenny, Republic of Ireland. + + + + McDonnell + Robert + R + + Health Service Executive, Dublin, Republic of Ireland. + + + + Nelen + Vera + V + + Provincial Institute for Hygiene, Antwerp, Belgium. + + + + Neville + Amanda J + AJ + + IMER Registry, Centre for Clinical and Epidemiological Research, University of Ferrara and Azienda Ospedaliero- Universitaria di Ferrara, Ferrara, Italy. + + + + O'Mahony + Mary T + MT + + Health Service Executive, Cork, Republic of Ireland. + + + + Pierini + Anna + A + + CNR Institute of Clinical Physiology, Pisa, Italy. + + + + Randrianaivo + Hanitra + H + + Registre des Malformations Congenitales de la Reunion, Saint-Pierre, Reunion. + + + + Rissmann + Anke + A + + Malformation Monitoring Centre Saxony-Anhalt, Medical Faculty Otto-von-Guericke University Magdeburg, Magdeburg, Germany. + + + + Tucker + David + D + + Public Health Wales, Swansea, UK. + + + + Verellen-Dumoulin + Christine + C + + Institut de Pathologie at de Genetique, Charleroi, Belgium. + + + + de Walle + Hermien E K + HE + + University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, Netherlands. + + + + Wellesley + Diana + D + + University of Southampton and Wessex Clinical Genetics Service, Southampton, UK. + + + + Wiesel + Awi + A + + Birth Registry Mainz Model, University Medical Centre of Johannes Gutenberg University, Mainz, Germany. + + + + Dolk + Helen + H + + University of Ulster, Newtownabbey, Co Antrim, Northern Ireland, UK. + + + + eng + + Comparative Study + Journal Article + Multicenter Study + Observational Study + + + 2016 + 09 + 13 + +
+ + England + BMJ + 8900488 + 0959-535X + + AIM + IM + + + Am J Med Genet A. 2015 Dec;167A(12 ):3062-9 + 26347425 + + + N Engl J Med. 2016 Aug 4;375(5):481-4 + 27433842 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + Birth Defects Res A Clin Mol Teratol. 2011 Mar;91 Suppl 1:S2-15 + 21384531 + + + Dev Med Child Neurol. 1991 Nov;33(11):974-83 + 1743426 + + + Lancet. 2014 Sep 6;384(9946):857-68 + 25209487 + + + Eur J Epidemiol. 2015 Nov;30(11):1165-73 + 26026722 + + + Arch Dis Child. 2008 Jul;93(7):566-9 + 17908712 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Birth Defects Res A Clin Mol Teratol. 2011 Mar;91 Suppl 1:S23-30 + 21384530 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Arch Dis Child. 2011 Oct;96(10):916-21 + 19948662 + + + Dev Med Child Neurol. 2014 Aug;56(8):732-41 + 24617602 + + + + + Europe + epidemiology + + + Female + + + Fetal Death + + + Humans + + + Male + + + Microcephaly + diagnosis + epidemiology + + + Population Surveillance + + + Pregnancy + + + Prenatal Diagnosis + + + Prevalence + + + Registries + + + Retrospective Studies + + + Surveys and Questionnaires + + + All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. All authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. +
+ + + + 2016 + 9 + 15 + 6 + 0 + + + 2016 + 9 + 15 + 6 + 0 + + + 2017 + 4 + 14 + 6 + 0 + + + epublish + + 27623840 + PMC5021822 + + +
+ + + + + 27617166 + + 2016 + 09 + 12 + + + 2017 + 12 + 12 + +
+ + 2157-3999 + + 8 + + 2016 + Jun + 08 + + + PLoS currents + PLoS Curr + + Radiological Characterization of Cerebral Phenotype in Newborn Microcephaly Cases from 2015 Outbreak in Brazil. + 10.1371/currents.outbreaks.e854dbf51b8075431a05b39042c00244 + ecurrents.outbreaks.e854dbf51b8075431a05b39042c00244 + + Brazil is facing, since October of 2015, an outbreak of microcephalic fetuses. This outbreak is correlated with the beginning of circulation of Zika virus (ZIKV) in the country. Although it is clear that the size of the head is diminished in these fetuses, the brain phenotype associated with these malformations is unknown. + We collected computed tomography images of the microcephaly cases from the region of Natal, Rio Grande do Norte, from September 2015 to February 2016. + The microcephalies derived from the current outbreak are associated with intracerebral calcifications, malformation of the ventricular system, migratory disorders in the telencephalon and, in a lower frequency, malformation of the cerebellum and brainstem. + The characteristics described herein are not usually found in other types of microcephaly. We suggest that this work can be used as a guideline to identify microcephaly cases associated to the current outbreak. + + + + Ramalho Rocha + Yuri Raoni + YR + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Cavalcanti Costa + José Ricardo + JR + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Almeida Costa + Pericles + P + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Maia + Gessica + G + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Vasconcelos + Rafael de Medeiros + Rde M + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Ramos Tejo + Cynthia + C + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Martins Batista + Rafaella + R + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Lima Neto + Manoel + M + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Martins de Lima + Gustavo Graco + GG + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Negromonte + Francisco + F + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Borba + Marcelle + M + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Bezerra Jeronimo + Selma Maria + SM + + Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil; Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil; Institute of Science and Technology of Tropical Diseases, Brazil. + + + + Sequerra + Eduardo Bouth + EB + + Brain Institute, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + Moreira Neto + Manuel + M + + Radiologia e Diagnóstico por Imagem, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + eng + + Journal Article + + + 2016 + 06 + 08 + +
+ + United States + PLoS Curr + 101515638 + 2157-3999 + + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Semin Dermatol. 1995 Jun;14(2):179-86 + 7640200 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Neurology. 2009 Sep 15;73(11):887-97 + 19752457 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Prenat Diagn. 2000 Apr;20(4):328-32 + 10740206 + + + Euro Surveill. 2015 Jun 11;20(23):null + 26084316 + + + Bull World Health Organ. 2016 Sep 1;94(9):675-686C + 27708473 + + + Lancet. 2016 Apr 9;387(10027):1531-1539 + 26948433 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + + Brazil + Outbreak + computed tomography + microcephaly + zika virus + +
+ + + + 2016 + 9 + 13 + 6 + 0 + + + 2016 + 9 + 13 + 6 + 0 + + + 2016 + 9 + 13 + 6 + 1 + + + epublish + + 27617166 + 10.1371/currents.outbreaks.e854dbf51b8075431a05b39042c00244 + PMC4999355 + + +
+ + + + + 27615590 + + 2017 + 10 + 26 + + + 2017 + 10 + 26 + +
+ + 2046-2344 + + 28 + 7 + + 2016 + Sep + 12 + + + Nursing children and young people + Nurs Child Young People + + Microcephaly and the Zika virus. + + 51 + + 10.7748/ncyp.28.7.51.s29 + + Cases of microcephaly brought about by the Zika virus have brought professional and personal challenges for nurses in Brazil. Paediatric nurses, such as Roberta Seabra (pictured), take over as part of the multidisciplinary team once the baby is born. In this article health writer Jacqui Thornton presents some personal stories. + + eng + + Journal Article + +
+ + England + Nurs Child Young People + 101554473 + 2046-2336 + + N + + + Brazil + + + Humans + + + Microcephaly + virology + + + Zika Virus + + + Zika Virus Infection + + +
+ + + + 2016 + 9 + 13 + 6 + 0 + + + 2016 + 9 + 13 + 6 + 0 + + + 2017 + 10 + 27 + 6 + 0 + + + ppublish + + 27615590 + 10.7748/ncyp.28.7.51.s29 + + +
+ + + + + 27601223 + + 2017 + 11 + 29 + + + 2017 + 11 + 29 + +
+ + 1537-6591 + + 63 + 12 + + 2016 + Dec + 15 + + + Clinical infectious diseases : an official publication of the Infectious Diseases Society of America + Clin. Infect. Dis. + + Fetal Infection by Zika Virus in the Third Trimester: Report of 2 Cases. + + 1622-1625 + + + Zika virus (ZIKV) infection acquired during pregnancy is associated with congenital microcephaly. We describe 2 cases of ZIKV infection in women in their 36th week of pregnancy whose fetuses had preserved head circumference at birth and findings of subependymal cysts and lenticulostriate vasculopathy in postnatal imaging. These represent the first signs of congenital brain injury acquired due to ZIKV in the third trimester. + © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com. + + + + Soares de Souza + Antonio + A + + Department of Radiology, Faculdade de Medicina de São José do Rio Preto (FAMERP). + + + Hospital da Criança e Maternidade. + + + + Moraes Dias + Cristiane + C + + Hospital da Criança e Maternidade. + + + + Braga + Fernanda Del Campo Braojos + FD + + Hospital da Criança e Maternidade. + + + + Terzian + Ana Carolina Bernardes + AC + + Laboratory of Virology, Department of Infectious and Dermatological Disease. + + + + Estofolete + Cássia Fernanda + CF + + Laboratory of Virology, Department of Infectious and Dermatological Disease. + + + + Oliani + Antonio Hélio + AH + + Department of Obstetrics and Gynecology. + + + + Oliveira + Gustavo Henrique + GH + + Hospital da Criança e Maternidade. + + + + Brandão de Mattos + Cinara Cássia + CC + + Immunogenetics Laboratory, Department of Molecular Biology, FAMERP, São José do Rio Preto, São Paulo, Brazil. + + + + de Mattos + Luiz Carlos + LC + + Immunogenetics Laboratory, Department of Molecular Biology, FAMERP, São José do Rio Preto, São Paulo, Brazil. + + + + Nogueira + Maurício Lacerda + ML + + Laboratory of Virology, Department of Infectious and Dermatological Disease. + + + + Vaz-Oliani + Denise Cristina Mós + DC + + Hospital da Criança e Maternidade. + + + Department of Obstetrics and Gynecology. + + + + eng + + Case Reports + Journal Article + + + 2016 + 09 + 06 + +
+ + United States + Clin Infect Dis + 9203213 + 1058-4838 + + IM + + + Adolescent + + + Adult + + + Brain Diseases + congenital + diagnostic imaging + virology + + + Central Nervous System Cysts + congenital + diagnostic imaging + + + Female + + + Fetal Diseases + diagnostic imaging + drug therapy + virology + + + Humans + + + Infant, Newborn + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnostic imaging + + + Pregnancy Trimester, Third + + + Ultrasonography, Doppler, Transcranial + + + Zika Virus Infection + complications + + + + Zika virus infection + central nervous system cysts + infection/congenital + lenticulostriate vasculopathy + ultrasonography + +
+ + + + 2016 + 07 + 13 + + + 2016 + 08 + 29 + + + 2016 + 9 + 8 + 6 + 0 + + + 2017 + 12 + 1 + 6 + 0 + + + 2016 + 9 + 8 + 6 + 0 + + + ppublish + + 27601223 + ciw613 + 10.1093/cid/ciw613 + + +
+ + + + + 27598870 + + 2018 + 01 + 08 + + + 2018 + 03 + 09 + +
+ + 1873-5967 + + 83 + + 2016 + 10 + + + Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology + J. Clin. Virol. + + Fatal encephalitis associated with Zika virus infection in an adult. + + 63-5 + + 10.1016/j.jcv.2016.08.297 + S1386-6532(16)30513-3 + + Zika virus (ZIKV) was first identified in the Americas in 2015, when an outbreak of an exanthematous illness occurred in Brazil. Subsequentely, there was an increase of microcephaly cases, suggesting an association between ZIKV and this neurological complication. Currently, ZIKV has been recognised as causing a wide range of neurological complications including Guillain Barré syndrome, and myelitis. + In this report, we describe the first fatal case of encephalitis in a 47 years old non pregnant woman, infected during the Brazilian zika epidemic of 2016. + The diagnosis of encephalitis was determined by the presence of a disturbed level of consciousness and focal neurological signs during an exanthemous viral infection. + CSF analysis supported the diagnosis of viral encephalitis, revealing lymphocytic pleocytosis, a high protein concentration, and the presence of IgM zika antibodies. RT-PCR analysis for ZIKV was positive in the urine. A brain computed tomography showed massive brain swelling. Our case differs from previous reports, because her neurological picture developed rapidly and in a very aggressive manner leading to brain death after eleven days of admission. + In endemic areas, ZIKV should be considered as an aetiological agent in cases of encephalitis, and clinicians should be aware of its potential severity. + Copyright © 2016 Elsevier B.V. All rights reserved. + + + + Soares + Cristiane N + CN + + Hospital Federal dos Servidores do Estado, Neurology Service, Rua Sacadura Cabral 176, Rio de Janeiro, RJ, Brazil. Electronic address: crist_nsoares@yahoo.com.br. + + + + Brasil + Patrícia + P + + Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Carrera + Raquel Medialdea + RM + + Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK. + + + + Sequeira + Patricia + P + + Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + de Filippis + Ana Bispo + AB + + Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + Borges + Vitor A + VA + + Hospital Badim, Rio de Janeiro, Brazil. + + + + Theophilo + Fernando + F + + Hospital Badim, Rio de Janeiro, Brazil. + + + + Ellul + Mark A + MA + + Institute of Infection and Global Health, University of Liverpool, Liverpool, UK; Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; Walton Centre NHS Foundation Trust, Liverpool, UK. + + + + Solomon + Tom + T + + Institute of Infection and Global Health, University of Liverpool, Liverpool, UK; Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; Walton Centre NHS Foundation Trust, Liverpool, UK. + + + + eng + + + RP-PG-0108-10048 + Department of Health + United Kingdom + + + + Case Reports + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 08 + 30 + +
+ + Netherlands + J Clin Virol + 9815671 + 1386-6532 + + IM + + + Brain + diagnostic imaging + pathology + + + Encephalitis, Viral + + + Fatal Outcome + + + Female + + + Humans + + + Middle Aged + + + Tomography, X-Ray Computed + + + Zika Virus + + + Zika Virus Infection + + + + Encephalitis + Neurological manifestations + Zika virus + +
+ + + + 2016 + 05 + 26 + + + 2016 + 08 + 24 + + + 2016 + 08 + 27 + + + 2016 + 9 + 7 + 6 + 0 + + + 2016 + 9 + 7 + 6 + 0 + + + 2018 + 1 + 9 + 6 + 0 + + + ppublish + + 27598870 + S1386-6532(16)30513-3 + 10.1016/j.jcv.2016.08.297 + + +
+ + + + + 27585248 + + 2017 + 01 + 10 + + + 2017 + 01 + 11 + +
+ + 1545-861X + + 65 + 34 + + 2016 + Sep + 02 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Hearing Loss in Infants with Microcephaly and Evidence of Congenital Zika Virus Infection - Brazil, November 2015-May 2016. + + 917-9 + + 10.15585/mmwr.mm6534e3 + + Congenital infection with Zika virus causes microcephaly and other brain abnormalities (1). Hearing loss associated with other congenital viral infections is well described; however, little is known about hearing loss in infants with congenital Zika virus infection. A retrospective assessment of a series of 70 infants aged 0-10 months with microcephaly and laboratory evidence of Zika virus infection was conducted by the Hospital Agamenon Magalhães in Brazil and partners. The infants were enrolled during November 2015-May 2016 and had screening and diagnostic hearing tests. Five (7%) infants had sensorineural hearing loss, all of whom had severe microcephaly; however, one child was tested after receiving treatment with an ototoxic antibiotic. If this child is excluded, the prevalence of sensorineural hearing loss was 5.8% (four of 69), which is similar to that seen in association with other congenital viral infections. Additional information is needed to understand the prevalence and spectrum of hearing loss in children with congenital Zika virus infection; all infants born to women with evidence of Zika virus infection during pregnancy should have their hearing tested, including infants who appear normal at birth. + + + + Leal + Mariana C + MC + + + Muniz + Lilian F + LF + + + Ferreira + Tamires S A + TS + + + Santos + Cristiane M + CM + + + Almeida + Luciana C + LC + + + Van Der Linden + Vanessa + V + + + Ramos + Regina C F + RC + + + Rodrigues + Laura C + LC + + + Neto + Silvio S Caldas + SS + + + eng + + Journal Article + + + 2016 + 09 + 02 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + Brazil + epidemiology + + + Female + + + Hearing Loss + epidemiology + virology + + + Hearing Tests + + + Humans + + + Infant + + + Infant, Newborn + + + Infectious Disease Transmission, Vertical + + + Male + + + Microcephaly + epidemiology + virology + + + Neonatal Screening + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Retrospective Studies + + + Zika Virus + isolation & purification + + + Zika Virus Infection + congenital + diagnosis + epidemiology + transmission + + +
+ + + + 2016 + 9 + 2 + 6 + 0 + + + 2016 + 9 + 2 + 6 + 0 + + + 2017 + 1 + 11 + 6 + 0 + + + epublish + + 27585248 + 10.15585/mmwr.mm6534e3 + + +
+ + + + + 27584610 + + 2018 + 01 + 12 + + + 2018 + 01 + 12 + +
+ + 1518-0557 + + 20 + 3 + + 2016 + Aug + 01 + + + JBRA assisted reproduction + JBRA Assist Reprod + + Reproductive planning in times of Zika: getting pregnant or delaying plans? The opinion of the Brazilian Society of Assisted Reproduction Committee - a basis for a bioethical discussion. + + 159-64 + + 10.5935/1518-0557.20160034 + + Although the causality between Zika virus, microcephaly, and other central nervous system disorders has been taken for granted by the scientific community, many uncertainties remain. The gap of knowledge at the moment is large enough to remove part of the confidence physicians have on the advice given to patients - and infertile women in particular - on their reproductive plans. Pretreatment serologic screening is a possible strategy to offer more confidence for individuals choosing to bear children regardless of the Zika virus, but the tests currently available do not seem to be sufficiently adequate. Until now, there is no formal recommendation to avoid pregnancy solely because of the Zika virus outbreak, and the choice of becoming pregnant has been regarded as a personal decision to be made by each woman and her family. + + + + Carvalho + Bruno R de + BR + + GENESIS - Center for Assistance in Human Reproduction, Brasília, DF, Brazil. + + + + Taitson + Paulo F + PF + + Pontifical Catholic University of Minas Gerais, Belo Horizonte, MG, Brazil. + + + + Brandão + Karina S A G + KS + + CENAFERT, Salvador, BA, Brazil. + + + + Ferriani + Rui Alberto + RA + + School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. + + + + Nakagawa + Hitomi M + HM + + GENESIS - Center for Assistance in Human Reproduction, Brasília, DF, Brazil. + + + President of SBRA - Brazilian Society of Assisted Reproduction. + + + + Silva + Adelino A + AA + + GENESIS - Center for Assistance in Human Reproduction, Brasília, DF, Brazil. + + + + Lopes + Joaquim R C + JR + + CENAFERT, Salvador, BA, Brazil. + + + + SBRA - Brazilian Society of Assisted Reproduction Committee + + + eng + + Journal Article + + + 2016 + 08 + 01 + +
+ + Brazil + JBRA Assist Reprod + 101684552 + 1517-5693 + + IM + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + Microbes Infect. 2016 Mar;18(3):167-8 + 26774330 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + J Glob Infect Dis. 2016 Jan-Mar;8(1):3-15 + 27013839 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + Emerg Infect Dis. 2016 Jun;22(6):1090-3 + 27071041 + + + Wkly Epidemiol Rec. 2015 Nov 6;90(45):609-10 + 26552108 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Nature. 2016 Feb 4;530(7588):13-4 + 26842033 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + + + Bioethics + + + Brazil + + + Female + + + Humans + + + Infant, Newborn + + + Infertility, Female + + + Microcephaly + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Reproductive Techniques, Assisted + ethics + + + Zika Virus + + + Zika Virus Infection + + + + Zika + bioethics + central nervous system disorders + human reproduction + microcephaly + + CONFLICT OF INTERESTS No conflict of interest have been declared. +
+ + + + 2016 + 9 + 2 + 6 + 0 + + + 2016 + 9 + 2 + 6 + 0 + + + 2018 + 1 + 13 + 6 + 0 + + + epublish + + 27584610 + 10.5935/1518-0557.20160034 + PMC5264382 + + +
+ + + + + 27582188 + + 2016 + 09 + 21 + + + 2016 + 12 + 16 + +
+ + 1476-4687 + + 537 + 7618 + + 2016 + 09 + 01 + + + Nature + Nature + + Zika response must not drain research funds. + + 7 + + 10.1038/537007a + eng + + Comment + Editorial + +
+ + England + Nature + 0410462 + 0028-0836 + + IM + + + Emerg Infect Dis. 2016 Mar;22(3):433-41 + 26886846 + + + + + Brazil + + + Centers for Disease Control and Prevention (U.S.) + + + Disease Outbreaks + + + Financial Management + + + Humans + + + Infant + + + Microcephaly + + + Pregnancy Complications, Infectious + + + United States + + + Zika Virus + + + Zika Virus Infection + + +
+ + + + 2016 + 9 + 2 + 6 + 0 + + + 2016 + 9 + 2 + 6 + 0 + + + 2016 + 9 + 23 + 6 + 0 + + + ppublish + + 27582188 + 537007a + 10.1038/537007a + + +
+ + + + + 27569055 + + 2018 + 03 + 09 + + + 2018 + 03 + 09 + +
+ + 1532-9496 + + 31 + 1 + + 2017 + Jan + + + Transfusion medicine reviews + Transfus Med Rev + + Zika Virus and the Blood Supply: What Do We Know? + + 1-10 + + S0887-7963(16)30094-3 + 10.1016/j.tmrv.2016.08.001 + + Zika virus (ZIKV), a mosquito-borne Flavivirus and emerging infectious disease, is the focus of an international public health emergency after its rapid spread through the Americas and the Caribbean. Although most ZIKV infections are subclinical or characterized by mild febrile illness, ZIKV has been implicated in severe complications, most notably microcephaly in babies born to incident infected mothers during pregnancy. As yet, the extent to which ZIKV is transfusion transmissible remains undefined. Nonetheless, a high prevalence of asymptomatic infection during outbreaks, the demonstration of ZIKV in blood donors, and 4 possible cases of transfusion-transmitted ZIKV in Brazil have raised concern for risk to the blood supply. Consequently, a proactive response is underway by blood collection agencies, regulatory bodies, national funding agencies, and industry alike. Mitigation strategies differ between endemic and nonendemic areas. In the continental United States, the American Association of Blood Banks and Food and Drug Administration guidelines recommend travel-based deferral for those returning from affected areas, and nucleic acid testing is being initiated under an investigational new drug application in Puerto Rico and selected areas of the United States. Options are less clear for countries where autochthonous vector-borne transmission is active. The burden of Zika falls in low-resource countries where high cost and technical barriers associated with testing and pathogen reduction pose barriers to implementation. Additional strategies include maintaining selective inventory for high-risk recipients (eg, pregnant women). We review the available data as of July 2016 on ZIKV in relation to the blood supply including risk, mitigation strategies, and barriers to implementation in addition to the research that is needed to address current uncertainty. + Copyright © 2016 Elsevier Inc. All rights reserved. + + + + Jimenez + Alexandra + A + + New York Blood Center, New York, NY. + + + + Shaz + Beth H + BH + + Columbia University Medical Center and New York Blood Center, New York, NY. + + + + Bloch + Evan M + EM + + Johns Hopkins University, Baltimore, MD. Electronic address: ebloch2@jhmi.edu. + + + + eng + + Journal Article + Review + + + 2016 + 08 + 09 + +
+ + United States + Transfus Med Rev + 8709027 + 0887-7963 + + IM + + + Blood Donors + statistics & numerical data + supply & distribution + + + Communicable Diseases, Emerging + blood + epidemiology + virology + + + Disease Outbreaks + + + Female + + + Humans + + + Infant, Newborn + + + Pregnancy + + + Risk Factors + + + Travel + statistics & numerical data + + + United States + + + Zika Virus + pathogenicity + physiology + + + Zika Virus Infection + blood + epidemiology + transmission + + + + Arbovirus + Blood safety + Blood transfusion + Communicable diseases + Emerging + Transfusion-transmitted virus + Zika virus + +
+ + + + 2016 + 06 + 21 + + + 2016 + 07 + 30 + + + 2016 + 08 + 01 + + + 2016 + 8 + 30 + 6 + 0 + + + 2018 + 3 + 10 + 6 + 0 + + + 2016 + 8 + 30 + 6 + 0 + + + ppublish + + 27569055 + S0887-7963(16)30094-3 + 10.1016/j.tmrv.2016.08.001 + + +
+ + + + + 27562089 + + 2017 + 03 + 20 + + + 2017 + 08 + 17 + +
+ + 1756-1833 + + 354 + + 2016 + Aug + 25 + + + BMJ (Clinical research ed.) + BMJ + + Brazilian attorneys demand abortion rights for women infected with Zika. + + i4657 + + 10.1136/bmj.i4657 + + + Collucci + Cláudia + C + + São Paulo. + + + + eng + + News + + + 2016 + 08 + 25 + +
+ + England + BMJ + 8900488 + 0959-535X + + AIM + IM + + + Abortion, Legal + legislation & jurisprudence + + + Brazil + epidemiology + + + Child + + + Contraception + + + Disabled Children + legislation & jurisprudence + + + Female + + + Health Services Accessibility + legislation & jurisprudence + + + Humans + + + Infant, Newborn + + + Lawyers + + + Microcephaly + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Social Security + legislation & jurisprudence + + + Zika Virus Infection + epidemiology + + +
+ + + + 2016 + 8 + 27 + 6 + 0 + + + 2016 + 8 + 27 + 6 + 0 + + + 2017 + 3 + 21 + 6 + 0 + + + epublish + + 27562089 + + +
+ + + + + 27555815 + + 2016 + 08 + 24 + + + 2018 + 03 + 08 + +
+ + 1662-5161 + + 10 + + 2016 + + + Frontiers in human neuroscience + Front Hum Neurosci + + A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome. + + 403 + + 10.3389/fnhum.2016.00403 + + Owing to the reports of microcephaly as a consistent outcome in the fetuses of pregnant women infected with ZIKV in Brazil, Zika virus (ZIKV)-microcephaly etiomechanistic relationship has recently been implicated. Researchers, however, are still struggling to establish an embryological basis for this interesting causal handcuff. The present study reveals robust evidence in favor of a plausible ZIKV-microcephaly cause-effect liaison. The rationale is based on: (1) sequence homology between ZIKV genome and the response element of an early neural tube developmental marker "retinoic acid" in human DNA and (2) comprehensive similarities between the details of brain defects in ZIKV-microcephaly and retinoic acid embryopathy. Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE) consensus sequence (5'-AGGTCA-3') in promoter regions of retinoic acid-dependent genes. We screened genomic sequences of already reported virulent ZIKV strains (including those linked to microcephaly) and other viruses available in National Institute of Health genetic sequence database (GenBank) for the RARE consensus repeats and obtained results strongly bolstering our hypothesis that ZIKV strains associated with microcephaly may act through precipitation of dysregulation in retinoic acid-dependent genes by introducing extra stretches of RARE consensus sequence repeats in the genome of developing brain cells. Additional support to our hypothesis comes from our findings that screening of other viruses for RARE consensus sequence repeats is positive only for those known to display neurotropism and cause fetal brain defects (for which maternal-fetal transmission during developing stage may be required). The numbers of RARE sequence repeats appeared to match with the virulence of screened positive viruses. Although, bioinformatic evidence and embryological features are in favor of our hypothesis, additional studies including animal models are warranted to validate our proposition. Such studies are likely to unfold ZIKV-microcephaly association and may help in devising methods to combat it. + + + + Kumar + Ashutosh + A + + Department of Anatomy, All India Institute of Medical Sciences New Delhi, India. + + + + Singh + Himanshu N + HN + + Department of Biochemistry, All India Institute of Medical Sciences New Delhi, India. + + + + Pareek + Vikas + V + + Computational Neuroscience and Neuroimaging Division, National Brain Research Centre Manesar, India. + + + + Raza + Khursheed + K + + Department of Anatomy, All India Institute of Medical Sciences New Delhi, India. + + + + Dantham + Subrahamanyam + S + + Department of Biochemistry, All India Institute of Medical Sciences New Delhi, India. + + + + Kumar + Pavan + P + + Department of Anatomy, All India Institute of Medical Sciences New Delhi, India. + + + + Mochan + Sankat + S + + Department of Anatomy, All India Institute of Medical Sciences New Delhi, India. + + + + Faiq + Muneeb A + MA + + Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical SciencesNew Delhi, India; Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of medical SciencesNew Delhi, India; Medical Biotechnology Laboratory, Dr. B. R. Ambedkar Centre for Biomedical Research, University of DelhiNew Delhi, India. + + + + eng + + Journal Article + + + 2016 + 08 + 09 + +
+ + Switzerland + Front Hum Neurosci + 101477954 + 1662-5161 + + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + J Virol. 2007 Feb;81(3):1401-11 + 17108032 + + + J Lipid Res. 2002 Nov;43(11):1773-808 + 12401878 + + + J Infect Dis. 1999 Feb;179 Suppl 1:S11-2 + 9988157 + + + J Clin Microbiol. 2006 Jun;44(6):2063-71 + 16757599 + + + Curr Opin Neurol. 2001 Apr;14(2):151-6 + 11262728 + + + Dis Model Mech. 2009 May-Jun;2(5-6):295-305 + 19380308 + + + Cell Biosci. 2012 Mar 22;2(1):11 + 22439772 + + + Dev Biol. 2008 Apr 15;316(2):371-82 + 18329011 + + + J Neuropathol Exp Neurol. 1983 Jul;42(4):439-52 + 6864237 + + + J Virol. 2003 Nov;77(21):11616-24 + 14557647 + + + J Cell Biol. 2011 Aug 8;194(3):489-503 + 21807879 + + + Development. 2012 Mar;139(5):843-58 + 22318625 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Dev Dyn. 2004 Oct;231(2):270-7 + 15366004 + + + Front Microbiol. 2012 Jun 20;3:201 + 22723794 + + + PLoS Med. 2008 Mar 18;5(3):e60 + 18351797 + + + Emerg Infect Dis. 2010 Mar;16(3):418-25 + 20202416 + + + Arch Virol. 1993;130(3-4):477-84 + 8517798 + + + Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8229-33 + 7667273 + + + Am J Trop Med Hyg. 2009 Dec;81(6):1141-3 + 19996449 + + + Development. 1998 Apr;125(7):1173-81 + 9477316 + + + Chem Res Toxicol. 2010 Oct 18;23(10):1586-95 + 20695457 + + + Cell Stem Cell. 2016 Aug 4;19(2):258-65 + 27162029 + + + J Chem Neuroanat. 2012 Mar;43(2):120-32 + 22306550 + + + J Neurochem. 2011 Nov;119(4):723-35 + 21895658 + + + ScientificWorldJournal. 2013 Nov 04;2013:904067 + 24302878 + + + Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17140-5 + 17939996 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + J Neuropathol Exp Neurol. 2014 Feb;73(2):143-58 + 24423639 + + + Development. 2015 Apr 1;142(7):1293-8 + 25758461 + + + BMJ Case Rep. 2009;2009:null + 21901115 + + + Genome Announc. 2014 Jun 05;2(3):null + 24903869 + + + Clin Infect Dis. 2005 Oct 15;41(8):1089-96 + 16163626 + + + Pediatr Neurosurg. 1991-1992;17(2):104-12 + 1815729 + + + N Engl J Med. 1985 Oct 3;313(14):837-41 + 3162101 + + + Trends Immunol. 2014 Feb;35(2):79-87 + 24316012 + + + Reproduction. 2013 Oct 01;146(5):R151-62 + 23884862 + + + J Matern Fetal Neonatal Med. 2017 Feb;30(3):274-278 + 27002428 + + + Int J Pediatr Endocrinol. 2011 Oct 13;2011:11 + 21995344 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + J Viral Hepat. 2012 Feb;19(2):e89-96 + 22239531 + + + PLoS Negl Trop Dis. 2014 Jul 17;8(7):e2996 + 25033077 + + + Hum Mol Genet. 2014 Jan 15;23(2):434-48 + 24026680 + + + Nature. 1989 Jul 13;340(6229):140-4 + 2739735 + + + Dev Med Child Neurol. 1991 Oct;33(10):916-20 + 1743417 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Cell. 2009 Oct 30;139(3):597-609 + 19879845 + + + Dev Biol. 2007 Mar 1;303(1):362-75 + 17184764 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + J Perinatol. 2000 Dec;20(8 Pt 1):548-54 + 11190597 + + + Nat Neurosci. 2011 Jan;14 (1):45-53 + 21131950 + + + AIDS Patient Care STDS. 2012 Jul;26(7):383-7 + 22694171 + + + Mech Dev. 2003 Jun;120(6):701-9 + 12834869 + + + Cell Host Microbe. 2013 Apr 17;13(4):379-93 + 23601101 + + + BMC Dev Biol. 2007 Dec 19;7:138 + 18093305 + + + Lancet. 2001 Jul 7;358(9275):38-9 + 11454379 + + + Teratology. 1986 Oct;34(2):141-53 + 3465061 + + + Infect Dis Obstet Gynecol. 2012;2012:385697 + 22566740 + + + Virol J. 2011 Aug 11;8:398 + 21835036 + + + Acta Neuropathol. 2016 Feb;131(2):159-84 + 26659576 + + + PLoS Pathog. 2010 Nov 04;6(11):e1001178 + 21079690 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Nature. 2013 Apr 18;496(7445):363-6 + 23563268 + + + PLoS One. 2013;8(3):e58219 + 23472160 + + + Lancet. 2016 Feb 6;387(10018):521-4 + 26852261 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + Neuroreport. 1999 Aug 2;10(11):2215-21 + 10439437 + + + Front Microbiol. 2018 Feb 20;9:190 + 29515529 + + + + fetal brain malformation + microcephaly + neurotropism + retinoic acid response element (RARE) + zika virus (ZIKV) + +
+ + + + 2016 + 05 + 23 + + + 2016 + 07 + 27 + + + 2016 + 8 + 25 + 6 + 0 + + + 2016 + 8 + 25 + 6 + 0 + + + 2016 + 8 + 25 + 6 + 1 + + + epublish + + 27555815 + 10.3389/fnhum.2016.00403 + PMC4977292 + + +
+ + + + + 27538400 + + 2017 + 10 + 23 + + + 2017 + 10 + 23 + +
+ + 1435-1102 + + 19 + 6 + + 2016 + 12 + + + Archives of women's mental health + Arch Womens Ment Health + + Anxiety, depression, and quality of life in mothers of newborns with microcephaly and presumed congenital Zika virus infection. + + 1149-1151 + + 10.1007/s00737-016-0654-0 + + + Dos Santos Oliveira + Sheila Jaqueline Gomes + SJG + + Federal University of Sergipe, Aracaju, Sergipe, Brazil. + + + + de Melo + Emanuela Santos + ES + + Tiradentes University, Aracaju, Sergipe, Brazil. + + + + Reinheimer + Daniele Machado + DM + + Federal University of Sergipe, Aracaju, Sergipe, Brazil. + + + + Gurgel + Ricardo Queiroz + RQ + + Federal University of Sergipe, Aracaju, Sergipe, Brazil. + + + + Santos + Victor Santana + VS + + Federal University of Sergipe, Aracaju, Sergipe, Brazil. + + + + Martins-Filho + Paulo Ricardo Saquete + PRS + + Federal University of Sergipe, Aracaju, Sergipe, Brazil. martins-filho@ufs.br. + + + Universidade Federal de Sergipe, Hospital Universitário, Laboratório de Patologia Investigativa, Rua Cláudio Batista, s/n. Bairro Sanatório, Aracaju, Sergipe, CEP: 49060-100, Brazil. martins-filho@ufs.br. + + + + eng + + Letter + + + 2016 + 08 + 18 + +
+ + Austria + Arch Womens Ment Health + 9815663 + 1434-1816 + + IM + + + Adolescent + + + Adult + + + Anxiety + diagnosis + psychology + + + Brazil + + + Case-Control Studies + + + Depression + diagnosis + psychology + + + Female + + + Humans + + + Infant, Newborn + + + Male + + + Microcephaly + epidemiology + + + Mothers + psychology + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Psychiatric Status Rating Scales + + + Quality of Life + + + Young Adult + + + Zika Virus Infection + congenital + diagnosis + + +
+ + + + 2016 + 07 + 18 + + + 2016 + 08 + 10 + + + 2016 + 8 + 20 + 6 + 0 + + + 2017 + 10 + 24 + 6 + 0 + + + 2016 + 8 + 20 + 6 + 0 + + + ppublish + + 27538400 + 10.1007/s00737-016-0654-0 + 10.1007/s00737-016-0654-0 + + +
+ + + + + 27538321 + + 2016 + 09 + 22 + + + 2016 + 08 + 19 + +
+ + 0035-2640 + + 66 + 6 + + 2016 + Jun + + + La Revue du praticien + Rev Prat + + [A NEW PANDEMIC: ZIKA VIRUS INFECTION]. + + 641-7 + + + Zika virus is a flavivirus isolated in non human primates in 1647, then in humans 1954 (Uganda). It emerged on Micronesia (island af Yap) in 2007, then in French Polynesia in 2013-2014, in South America (mostly in Brazil and Colombia) in 2015 and in French West Indies in 2016. It is transmitted by the bite of Aedes mosquitoes. Zika virus infection is symptomatic in only 20% of cases and clinical presentation is associated with mild illness. But several neurological complications are reported (as Guillain-Barré syndrome: 48 cases in French Polynesia) and congenital malformations (microcephaly). Laboratory diagnosis is based on virus isolation by PCR. There is no specific treatment or vaccine available against the Zika virs. Prevention is based on measures of protection from mosquitoes bites. + + + + Bourée + Patrice + P + + + fre + + English Abstract + Journal Article + + Une nouvelle pandémie: la fièvre due au virus Zika. +
+ + France + Rev Prat + 0404334 + 0035-2640 + + IM + + + Global Health + + + Humans + + + Pandemics + + + Polynesia + + + Zika Virus Infection + complications + epidemiology + transmission + + +
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+ + + + + 27532747 + + 2017 + 10 + 31 + + + 2017 + 10 + 31 + +
+ + 1980-5497 + + 19 + 2 + + 2016 Apr-Jun + + + Revista brasileira de epidemiologia = Brazilian journal of epidemiology + Rev Bras Epidemiol + + Zika virus: challenges of public health in Brazil. + + 225-8 + + 10.1590/1980-5497201600020001 + S1415-790X2016000200225 + + + Comissão de Epidemiologia da Abrasco + + + eng + por + + Editorial + + Zika vírus: desafios da saúde pública no Brasil. +
+ + Brazil + Rev Bras Epidemiol + 100954576 + 1415-790X + + IM + + + Brazil + epidemiology + + + Female + + + Humans + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Public Health + + + Zika Virus Infection + epidemiology + + +
+ + + + 2016 + 8 + 18 + 6 + 0 + + + 2016 + 8 + 18 + 6 + 0 + + + 2017 + 11 + 1 + 6 + 0 + + + ppublish + + 27532747 + S1415-790X2016000200225 + 10.1590/1980-5497201600020001 + + +
+ + + + + 27526251 + + 2017 + 10 + 31 + +
+ + 1536-3732 + + 27 + 6 + + 2016 + Sep + + + The Journal of craniofacial surgery + J Craniofac Surg + + Microcephaly: Consequence of the Zika Virus Global Outbreak. + + 1383-4 + + 10.1097/SCS.0000000000002997 + + + Raposo-Amaral + Cassio Eduardo + CE + + Institute of Plastic and Craniofacial Surgery, SOBRAPAR Hospital, Campinas, Brazil. + + + + eng + + Journal Article + +
+ + United States + J Craniofac Surg + 9010410 + 1049-2275 + + D +
+ + + + 2016 + 8 + 16 + 6 + 0 + + + 2016 + 8 + 16 + 6 + 0 + + + 2016 + 8 + 16 + 6 + 1 + + + ppublish + + 27526251 + 10.1097/SCS.0000000000002997 + + +
+ + + + + 27525286 + + 2017 + 02 + 20 + +
+ + 2314-7334 + + 7 + 2 + + 2016 + Jun + + + Journal of neuroinfectious diseases + J Neuroinfect Dis + + Neuropathology of Zika Virus Infection. + 220 + + Zika virus (ZIKV) is a member of the Flaviviridae family that had been associated only with mild disease prior to the 2015 outbreak in Brazil. A dramatic increase in reported cases of microcephaly and Guillain-Barré syndrome during this time prompted significant research into possible associations with ZIKV and its neurotropic properties. Infection of neural progenitor cells and organoids have been shown to induce apoptosis and dysregulation of growth, and mouse studies have demonstrated viral replication in brain tissue in adults, as well as vertical transmission resulting in embryonic brain abnormalities. Large case series of clinical and radiological findings of congenital ZIKV infection have begun to be published; however, pathology reports have been limited to two case reports and two small case series. Thus far, the findings have largely been restricted to the brain and include diffuse grey and white matter involvement consisting of dystrophic calcifications, gliosis, microglial nodules, neuronophagia, and scattered lymphocytes. Mild chronic villitis was observed in the placental tissue in some cases, and the remaining organs were essentially uninvolved. Larger, systematic studies, including correlation of histological findings with gestational age at the time of maternal infection, will be required to determine the full range of Zika virus-induced abnormalities and to help guide future clinical decision making. + + + + Solomon + Isaac H + IH + + Department of Pathology, Brigham and Women's Hospital, Boston, USA. + + + + Milner + Danny A + DA + + Department of Pathology, Brigham and Women's Hospital, Boston, USA. + + + + Folkerth + Rebecca D + RD + + Department of Pathology, Brigham and Women's Hospital, Boston, USA. + + + + eng + + + R21 AI117304 + AI + NIAID NIH HHS + United States + + + + Journal Article + + + 2016 + 06 + 23 + +
+ + Egypt + J Neuroinfect Dis + 101609701 + + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Blood Transfus. 2016 Mar;14 (2):95-100 + 26674815 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Lancet. 2016 Apr 9;387(10027):1587-90 + 26952548 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + Cell Stem Cell. 2016 Aug 4;19(2):258-65 + 27162029 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Mem Inst Oswaldo Cruz. 2016 May;111(5):287-93 + 27143490 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + J Clin Virol. 2015 Jul;68:53-5 + 26071336 + + + Lancet. 2016 Apr 2;387(10026):1481 + 26946926 + + + Euro Surveill. 2016;21(13):null + 27063794 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Cell Res. 2016 Jun;26(6):645-54 + 27174054 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + N Engl J Med. 2016 Apr 21;374(16):1595-6 + 26958738 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + + Guillain-Barré syndrome + Histology + Microcephaly + Neuropathology + Zika virus + +
+ + + + 2016 + 8 + 16 + 6 + 0 + + + 2016 + 8 + 16 + 6 + 0 + + + 2016 + 8 + 16 + 6 + 0 + + + ppublish + + 27525286 + 10.4172/2314-7326.1000220 + PMC4982465 + NIHMS808176 + + + +
+ + + + + 27515384 + + 2017 + 03 + 20 + + + 2017 + 08 + 17 + +
+ + 1756-1833 + + 354 + + 2016 + Aug + 11 + + + BMJ (Clinical research ed.) + BMJ + + Brazil to investigate if other factors act with Zika to cause congenital defects. + + i4439 + + 10.1136/bmj.i4439 + + + Collucci + Cláudia + C + + São Paulo. + + + + eng + + News + + + 2016 + 08 + 11 + +
+ + England + BMJ + 8900488 + 0959-535X + + AIM + IM + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Zika Virus Infection + epidemiology + + +
+ + + + 2016 + 8 + 13 + 6 + 0 + + + 2016 + 8 + 16 + 6 + 0 + + + 2017 + 3 + 21 + 6 + 0 + + + epublish + + 27515384 + + +
+ + + + + 27509902 + + 2017 + 03 + 23 + + + 2017 + 08 + 17 + +
+ + 1756-1833 + + 354 + + 2016 + Aug + 09 + + + BMJ (Clinical research ed.) + BMJ + + Congenital Zika syndrome with arthrogryposis: retrospective case series study. + + i3899 + + 10.1136/bmj.i3899 + + To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus. + Retrospective case series study. + Association for Assistance of Disabled Children, Pernambuco state, Brazil. + Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic. + Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities. + The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots. + Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis. The arthrogryposis was unrelated to the abnormalities of the joints themselves, but was possibly of neurogenic origin, with chronic involvement of central and peripheral motor neurones leading to deformities as a result of fixed postures in utero. Based on the neurophysiological observations, we suggest two possible mechanisms: tropism of neurones, with involvement of peripheral and central motor neurones, or a relation with vascular disorders. + Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. + + + + van der Linden + Vanessa + V + + Association for Assistance of Disabled Children, AACD, Recife, Brazil Barão de Lucena Hospital, HBL, Recife, Brazil vanessavdlinden@hotmail.com. + + + + Filho + Epitacio Leite Rolim + EL + + Association for Assistance of Disabled Children, AACD, Recife, Brazil Federal University of Pernambuco, UFPE, Recife, Brazil. + + + + Lins + Otavio Gomes + OG + + Federal University of Pernambuco, UFPE, Recife, Brazil. + + + + van der Linden + Ana + A + + Prof Fernando Figueira Integral Medicine Institute, IMIP, Recife, Brazil vanessavdlinden@hotmail.com. + + + + Aragão + Maria de Fátima Viana Vasco + Mde F + + Centro Diagnóstico Multimagem, Recife, Brazil Mauricio de Nassau University, Recife, Brazil. + + + + Brainer-Lima + Alessandra Mertens + AM + + Mauricio de Nassau University, Recife, Brazil University of Pernambuco, UPE, Recife, Brazil. + + + + Cruz + Danielle Di Cavalcanti Sousa + DD + + Prof Fernando Figueira Integral Medicine Institute, IMIP, Recife, Brazil. + + + + Rocha + Maria Angela Wanderley + MA + + Oswaldo Cruz University Hospital, HUOC, Recife, Brazil. + + + + Sobral da Silva + Paula Fabiana + PF + + Oswaldo Cruz University Hospital, HUOC, Recife, Brazil. + + + + Carvalho + Maria Durce Costa Gomes + MD + + Oswaldo Cruz University Hospital, HUOC, Recife, Brazil. + + + + do Amaral + Fernando José + FJ + + Barão de Lucena Hospital, HBL, Recife, Brazil. + + + + Gomes + Joelma Arruda + JA + + Barão de Lucena Hospital, HBL, Recife, Brazil. + + + + Ribeiro de Medeiros + Igor Colaço + IC + + Hospital Infantil Jorge de Medeiros Recife, Brazil. + + + + Ventura + Camila V + CV + + Altino Ventura Foundation, FAV, Recife, Brazil Pernambuco's Eye Hospital, Recife, Brazil. + + + + Ramos + Regina Coeli + RC + + Oswaldo Cruz University Hospital, HUOC, Recife, Brazil. + + + + eng + + Journal Article + + + 2016 + 08 + 09 + +
+ + England + BMJ + 8900488 + 0959-535X + + AIM + IM + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + J Infect Dev Ctries. 2016 Feb 28;10 (2):116-20 + 26927450 + + + J Child Orthop. 2015 Dec;9(6):425-6 + 26482521 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + ISRN Obstet Gynecol. 2012;2012:264918 + 23050160 + + + Arch Virol. 2016 Mar;161(3):665-8 + 26611910 + + + J Pediatr (Rio J). 1999 Jul;75 Suppl 1:S15-30 + 14685480 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2014 Sep 6;384(9946):857-68 + 25209487 + + + J Bone Joint Surg Am. 2009 Jul;91 Suppl 4:40-6 + 19571066 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + Brain Dev. 2010 Aug;32(7):550-5 + 19751967 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + J Clin Microbiol. 2000 May;38(5):1823-6 + 10790107 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Am J Med Genet. 1984 Feb;17(2):509-21 + 6702901 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Pediatr Neurol. 1993 Sep-Oct;9(5):343-8 + 8292208 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Arthrogryposis + complications + diagnostic imaging + + + Calcinosis + diagnostic imaging + + + Electromyography + + + Humans + + + Joints + abnormalities + diagnostic imaging + + + Magnetic Resonance Imaging + + + Microcephaly + complications + diagnostic imaging + + + Retrospective Studies + + + Spinal Cord + diagnostic imaging + + + Syndrome + + + Tomography, X-Ray Computed + + + Ultrasonography + + + Zika Virus Infection + complications + congenital + diagnostic imaging + + +
+ + + + 2016 + 8 + 12 + 6 + 0 + + + 2016 + 8 + 12 + 6 + 0 + + + 2017 + 3 + 24 + 6 + 0 + + + epublish + + 27509902 + PMC4979356 + + +
+ + + + + 27504949 + + 2017 + 03 + 03 + +
+ + 0017-0011 + + 87 + 7 + + 2016 + + + Ginekologia polska + Ginekol. Pol. + + Zika virus intrauterine infections from the obstetrician's perspective. + + 538-9 + + 10.5603/GP.2016.0040 + + Zika virus (ZIKAV) infections could potentially occur in Poland due to international travel made by its nationals to regions where the Aedes mosquito is active. A causal relationship between prenatal ZIKAV infection and microcephaly and other serious brain anomalies has been found due to the time association between the infection in pregnancy and a presence of congenital nervous system malformations, together with the detectable pathogen in amniotic fluid and fetus's tissues. Two ZIKAV infection cases of pregnant women who were diagnosed with fetal microcephaly in the state of Paraiba, Brazil, later described in Ultrasound Obstetrics and Gynecology by Oliveira Mello et al. are discussed, in the context of the possible introduction of ZIKAV into Poland and the role the obstetrician should play in the detection and rapid reaction to potential threats. According to recommendations of international agencies for disease control and prevention, Polish obstetricians who take care of pregnant women and of those planning to become pregnant in the nearest future, and declaring travels to areas of the Aedes mosquito activity, should advise their patients to consider postponing travel or if they must travel, to take necessary precautionary measures to avoid mosquito bites. Pregnant women who have travelled to areas with ZIKAV transmission, or whose male partners had travelled to such areas and returned in the period of their female part-ner's pregnancy, should be monitored appropriately in the context of congenital abnormalities, including microcephaly. + + + + Gańczak + Maria + M + + Department of Epidemiology and Management, Pomeranian Medical University, Szczecin, Poland. mganczak@pum.edu.pl. + + + + Brodowska + Agnieszka + A + + + eng + + Journal Article + +
+ + Poland + Ginekol Pol + 0374641 + 0017-0011 + + IM + + Zika virus + clinical manifestation + diagnosis + infection + pregnancy + prevention + +
+ + + + 2016 + 07 + 29 + + + 2016 + 07 + 29 + + + 2016 + 8 + 10 + 6 + 0 + + + 2016 + 8 + 10 + 6 + 0 + + + 2016 + 8 + 10 + 6 + 0 + + + ppublish + + 27504949 + VM/OJS/J/48291 + 10.5603/GP.2016.0040 + + +
+ + + + + 27496713 + + 2017 + 10 + 02 + + + 2017 + 10 + 02 + +
+ + 1473-6527 + + 29 + 5 + + 2016 + Oct + + + Current opinion in infectious diseases + Curr. Opin. Infect. Dis. + + Zika virus infection: epidemiology, clinical manifestations and diagnosis. + + 459-66 + + 10.1097/QCO.0000000000000301 + + Zika virus (ZIKV) is an arbovirus previously believed to cause only a mild and self-limiting illness. Recently, it has emerged as a new public health threat that caused a large outbreak in French Polynesia in 2013-2014 and since 2015 an explosive outbreak in Brazil, with an increase in severe congenital malformations (microcephaly) and neurological complications, mainly Guillain-Barré syndrome (GBS). Since then, it has spread through the Americas. On 1 February 2016, the WHO declared the ZIKV epidemic in Brazil a Public Health Emergency of International Concern. We reviewed the epidemiology of ZIKV infection, clinical presentations and diagnosis. We highlighted the clinical features and nonvector borne transmission of the virus. + Association between ZIKV infection and severe foetal outcomes, including microcephaly and other birth defects; increased rate of GBS and other neurological complications due to the ongoing ZIKV outbreak; increased evidence to date of ZIKV being the only arbovirus linked to sexual transmission; the challenge of ZIKV diagnosis; and the need for a specific point-of care test in epidemic scenarios. + The findings illustrate the emergence of a viral disease with the identification of new associated disorders, new modes of transmission, including maternal-foetal and sexual transmission. + + + + Calvet + Guilherme Amaral + GA + + aAcute Febrile Illnesses Laboratory, Evandro Chagas National Institute of Infectious Diseases/Oswaldo Cruz Foundation bFlavivirus Laboratory, Oswaldo Cruz Institute/Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. + + + + Santos + Flavia Barreto Dos + FB + + + Sequeira + Patricia Carvalho + PC + + + eng + + Journal Article + Review + +
+ + United States + Curr Opin Infect Dis + 8809878 + 0951-7375 + + IM + + + Americas + epidemiology + + + Brazil + epidemiology + + + Guillain-Barre Syndrome + virology + + + Humans + + + Microcephaly + virology + + + Sexually Transmitted Diseases, Viral + virology + + + Zika Virus + + + Zika Virus Infection + complications + diagnosis + epidemiology + virology + + +
+ + + + 2016 + 8 + 7 + 6 + 0 + + + 2016 + 8 + 9 + 6 + 0 + + + 2017 + 10 + 3 + 6 + 0 + + + ppublish + + 27496713 + 10.1097/QCO.0000000000000301 + + +
+ + + + + 27495823 + + 2017 + 04 + 28 + + + 2017 + 04 + 28 + +
+ + 1473-6810 + + 21 + 5 + + 2016 + 10 + + + Evidence-based medicine + Evid Based Med + + Prospective cohort study of pregnant Brazilian women elucidates link between Zika virus infection and fetal abnormalities. + + 193 + + 10.1136/ebmed-2016-110476 + + + Bhadelia + Nahid + N + + + eng + + Journal Article + Comment + + + 2016 + 08 + 05 + +
+ + England + Evid Based Med + 9608386 + 1356-5524 + + IM + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + + + Brazil + + + Congenital Abnormalities + virology + + + Female + + + Fetal Death + + + Humans + + + Infant + + + Microcephaly + virology + + + Practice Guidelines as Topic + + + Pregnancy + + + Pregnancy Complications, Infectious + virology + + + Pregnant Women + + + Prospective Studies + + + United States + + + Zika Virus + + + Zika Virus Infection + + +
+ + + + 2016 + 8 + 7 + 6 + 0 + + + 2016 + 8 + 9 + 6 + 0 + + + 2017 + 4 + 30 + 6 + 0 + + + ppublish + + 27495823 + ebmed-2016-110476 + 10.1136/ebmed-2016-110476 + + +
+ + + + + 27492477 + + 2017 + 03 + 16 + + + 2017 + 03 + 16 + +
+ + 1095-9203 + + 353 + 6304 + + 2016 + 09 + 09 + + + Science (New York, N.Y.) + Science + + Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys. + + 1129-32 + + 10.1126/science.aah6157 + + Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys also conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector vaccine, both expressing ZIKV premembrane and envelope, also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans. + Copyright © 2016, American Association for the Advancement of Science. + + + + Abbink + Peter + P + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Larocca + Rafael A + RA + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + De La Barrera + Rafael A + RA + + Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. + + + + Bricault + Christine A + CA + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Moseley + Edward T + ET + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Boyd + Michael + M + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Kirilova + Marinela + M + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Li + Zhenfeng + Z + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Ng'ang'a + David + D + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Nanayakkara + Ovini + O + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Nityanandam + Ramya + R + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Mercado + Noe B + NB + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Borducchi + Erica N + EN + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Agarwal + Arshi + A + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Brinkman + Amanda L + AL + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Cabral + Crystal + C + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Chandrashekar + Abishek + A + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Giglio + Patricia B + PB + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Jetton + David + D + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Jimenez + Jessica + J + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Lee + Benjamin C + BC + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Mojta + Shanell + S + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Molloy + Katherine + K + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Shetty + Mayuri + M + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Neubauer + George H + GH + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Stephenson + Kathryn E + KE + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. + + + + Peron + Jean Pierre S + JP + + University of São Paulo, São Paulo 05508-000, Brazil. + + + + Zanotto + Paolo M de A + PM + + University of São Paulo, São Paulo 05508-000, Brazil. + + + + Misamore + Johnathan + J + + Bioqual, Rockville, MD 20852, USA. + + + + Finneyfrock + Brad + B + + Bioqual, Rockville, MD 20852, USA. + + + + Lewis + Mark G + MG + + Bioqual, Rockville, MD 20852, USA. + + + + Alter + Galit + G + + Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. + + + + Modjarrad + Kayvon + K + + Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Henry M. Jackson Foundation, Bethesda, MD 20817, USA. + + + + Jarman + Richard G + RG + + Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. + + + + Eckels + Kenneth H + KH + + Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. + + + + Michael + Nelson L + NL + + Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. + + + + Thomas + Stephen J + SJ + + Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. + + + + Barouch + Dan H + DH + + Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. dbarouch@bidmc.harvard.edu. + + + + eng + + + U19 AI095985 + AI + NIAID NIH HHS + United States + + + U19 AI096040 + AI + NIAID NIH HHS + United States + + + UM1 AI100663 + AI + NIAID NIH HHS + United States + + + UM1 AI124377 + AI + NIAID NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + + + 2016 + 08 + 04 + +
+ + United States + Science + 0404511 + 0036-8075 + + + + 0 + Antibodies, Viral + + + 0 + Immunoglobulins + + + 0 + Vaccines, DNA + + + 0 + Vaccines, Inactivated + + + 0 + Viral Envelope Proteins + + + 0 + Viral Vaccines + + + 0 + prM protein, Flavivirus + + + IM + + + Science. 2016 Sep 9;353(6304):1094-5 + 27609872 + + + Cochrane Database Syst Rev. 2009 Jan 21;(1):CD000977 + 19160184 + + + Am J Trop Med Hyg. 2015 Apr;92(4):698-708 + 25646261 + + + Lancet. 2016 Apr 2;387(10026):1482 + 27115821 + + + Cell. 2016 May 19;165(5):1238-54 + 27118425 + + + Appl Microbiol. 1973 Apr;25(4):539-44 + 4633476 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 Aug 19;353(6301):823-6 + 27417494 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Expert Rev Vaccines. 2015;14(9):1167-79 + 26162529 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Am J Epidemiol. 2002 Jul 1;156(1):40-51 + 12076887 + + + J Immunol Methods. 2015 Jan;416:105-23 + 25445329 + + + Am J Trop Med Hyg. 2015 Sep;93(3):454-60 + 26149862 + + + Nature. 2016 Aug 4;536(7614):48-53 + 27338953 + + + Nat Commun. 2016 Jun 28;7:12204 + 27352279 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + Vaccine. 2005 Nov 1;23(45):5205-11 + 16055233 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Clin Exp Immunol. 1997 Dec;110(3):358-61 + 9409636 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Nat Immunol. 2016 Sep;17 (9):1102-8 + 27339099 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + PLoS Med. 2009 Oct;6(10):e1000171 + 19859541 + + + J Virol. 2015 Feb;89(3):1512-22 + 25410856 + + + Cochrane Database Syst Rev. 2000;(2):CD000977 + 10796566 + + + + + Adenoviridae + + + Adoptive Transfer + + + Animals + + + Antibodies, Viral + biosynthesis + immunology + + + Brazil + + + Female + + + Genetic Vectors + + + Humans + + + Immunogenicity, Vaccine + + + Immunoglobulins + immunology + isolation & purification + + + Macaca mulatta + + + Male + + + Mice + + + Mice, Inbred BALB C + + + Puerto Rico + + + Vaccines, DNA + administration & dosage + immunology + + + Vaccines, Inactivated + administration & dosage + immunology + + + Viral Envelope Proteins + genetics + immunology + + + Viral Vaccines + administration & dosage + immunology + + + Zika Virus + immunology + + + Zika Virus Infection + prevention & control + + +
+ + + + 2016 + 07 + 21 + + + 2016 + 07 + 28 + + + 2016 + 8 + 6 + 6 + 0 + + + 2016 + 8 + 6 + 6 + 0 + + + 2017 + 3 + 17 + 6 + 0 + + + ppublish + + 27492477 + science.aah6157 + 10.1126/science.aah6157 + PMC5237380 + NIHMS841026 + + +
+ + + + + 27491635 + + 2017 + 09 + 12 + + + 2017 + 10 + 30 + +
+ + 1097-0223 + + 36 + 9 + + 2016 + Sep + + + Prenatal diagnosis + Prenat. Diagn. + + Associated ultrasonographic findings in fetuses with microcephaly because of suspected Zika virus (ZIKV) infection during pregnancy. + + 882-7 + + 10.1002/pd.4882 + + To describe fetal ultrasonographic findings and outcomes in a series of cases of fetal microcephaly associated with Zika virus infection. + Retrospective case series of microcephaly with definite (laboratory evidence) or highly probable (specific neuroimaging findings and negative laboratory results) maternal Zika virus infection. Microcephaly was graded as mild if the head circumference was between 2 and 3 standard deviation (SD) below the mean, and severe if 3 or more SD below the mean. Associated central nervous system (CNS) and extracranial malformations are described. + Nineteen singleton pregnancies fulfilling the inclusion criteria were identified. Severe microcephaly and mild microcephaly were identified in 14 and 5 fetuses, respectively. Additional CNS malformations were present in 17 cases and 7 had extracranial congenital anomalies. Symptoms were reported in 13/19 cases at a gestational age between 5 and 16 weeks. Mean (±SD) gestational age at ultrasound diagnosis was 32.3 ± 5.1 weeks. Amniocentesis was performed in five cases at a median gestational age of 31 weeks (range 28-38) and was positive for Zika virus RT-PCR in two cases. There were three neonatal deaths and one stillbirth. + In the presence of fetal microcephaly associated with Zika virus infection, CNS malformations are frequently detected. © 2016 John Wiley & Sons, Ltd. + © 2016 John Wiley & Sons, Ltd. + + + + Carvalho + Francisco Herlânio Costa + FH + + Department of Maternal and Child Health, School of Medicine, Federal University of Ceará (UFC), Fortaleza, CE, Brazil. + + + + Cordeiro + Kárita Melo + KM + + Department of Maternal and Child Health, School of Medicine, Federal University of Ceará (UFC), Fortaleza, CE, Brazil. + + + + Peixoto + Alberto Borges + AB + + Mário Palmério University Hospital-University of Uberaba (UNIUBE), Uberaba, MG, Brazil. + + + Department of Obstetrics, Paulista School of Medicine-Federal University of São Paulo (EPM-UNIFESP), São Paulo, SP, Brazil. + + + + Tonni + Gabriele + G + + Department of Obstetrics and Gynecology, Prenatal Diagnostic Center, Guastalla Civil Hospital, Reggio Emilia, Italy. + + + + Moron + Antonio Fernandes + AF + + Department of Obstetrics, Paulista School of Medicine-Federal University of São Paulo (EPM-UNIFESP), São Paulo, SP, Brazil. + + + + Feitosa + Francisco Edson Lucena + FE + + Department of Maternal and Child Health, School of Medicine, Federal University of Ceará (UFC), Fortaleza, CE, Brazil. + + + + Feitosa + Helvécio Neves + HN + + Department of Maternal and Child Health, School of Medicine, Federal University of Ceará (UFC), Fortaleza, CE, Brazil. + + + + Araujo Júnior + Edward + E + + Department of Obstetrics, Paulista School of Medicine-Federal University of São Paulo (EPM-UNIFESP), São Paulo, SP, Brazil. araujojred@terra.com.br. + + + + eng + + Journal Article + + + 2016 + 08 + 23 + +
+ + England + Prenat Diagn + 8106540 + 0197-3851 + + IM + + + Prenat Diagn. 2017 Feb;37(2):206 + 28205300 + + + + + Adolescent + + + Adult + + + Female + + + Humans + + + Microcephaly + diagnostic imaging + virology + + + Pregnancy + + + Retrospective Studies + + + Ultrasonography, Prenatal + + + Young Adult + + + Zika Virus Infection + diagnostic imaging + + +
+ + + + 2016 + 05 + 04 + + + 2016 + 07 + 25 + + + 2016 + 07 + 29 + + + 2016 + 8 + 6 + 6 + 0 + + + 2016 + 8 + 6 + 6 + 0 + + + 2017 + 9 + 13 + 6 + 0 + + + ppublish + + 27491635 + 10.1002/pd.4882 + + +
+ + + + + 29333229 + + 2018 + 01 + 19 + +
+ + 2046-1402 + + 5 + + 2016 + + + F1000Research + F1000Res + + Predicted protein interactions of IFITMs may shed light on mechanisms of Zika virus-induced microcephaly and host invasion. + + 1919 + + 10.12688/f1000research.9364.2 + + After the first reported case of Zika virus (ZIKV) in Brazil, in 2015, a significant increase in the reported cases of microcephaly was observed. Microcephaly is a neurological condition in which the infant's head is significantly smaller with complications in brain development. Recently, two small membrane-associated interferon-inducible transmembrane proteins (IFITM1 and IFITM3) have been shown to repress members of the flaviviridae family which includes ZIKV. However, the exact mechanisms leading to the inhibition of the virus are yet unknown. Here, we assembled an interactome of IFITM1 and IFITM3 with known protein-protein interactions (PPIs) collected from publicly available databases and novel PPIs predicted using the High-confidence Protein-Protein Interaction Prediction (HiPPIP) model. We analyzed the functional and pathway associations of the interacting proteins, and found that there are several immunity pathways (toll-like receptor signaling, cd28 signaling in T-helper cells, crosstalk between dendritic cells and natural killer cells), neuronal pathways (axonal guidance signaling, neural tube closure and actin cytoskeleton signaling) and developmental pathways (neural tube closure, embryonic skeletal system development) that are associated with these interactors. Our novel PPIs associate cilia dysfunction in ependymal cells to microcephaly, and may also shed light on potential targets of ZIKV for host invasion by immunosuppression and cytoskeletal rearrangements. These results could help direct future research in elucidating the mechanisms underlying host defense to ZIKV and other flaviviruses. + + + + Ganapathiraju + Madhavi K + MK + + Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA, USA. + + + Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA. + + + + Karunakaran + Kalyani B + KB + + Supercomputer Education and Research Centre, Indian Institute of Science, Bangalore, India. + + + + Correa-Menéndez + Josefina + J + + Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA. + + + + eng + + Journal Article + + + 2016 + 08 + 05 + +
+ + England + F1000Res + 101594320 + 2046-1402 + + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + Am J Reprod Immunol. 2016 Nov;76(5):348-357 + 27613665 + + + NPJ Schizophr. 2016 Apr 27;2:16012 + 27336055 + + + J Virol. 2016 Aug 26;90(18):8212-25 + 27384652 + + + Vector Borne Zoonotic Dis. 2016 Feb;16(2):75-6 + 26824625 + + + BMC Dev Biol. 2010 May 11;10:50 + 20459838 + + + Viruses. 2013 Oct 30;5(11):2643-58 + 24178712 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Sci Signal. 2016 Jul 12;9(436):ra70 + 27405980 + + + Bioinformatics. 2006 May 1;22(9):1031-5 + 16443634 + + + Cold Spring Harb Perspect Biol. 2012 Mar 01;4(3):null + 22296764 + + + Front Immunol. 2017 Feb 20;8:160 + 28265274 + + + J Virol. 2006 Aug;80(16):8211-24 + 16873277 + + + Curr Opin Virol. 2014 Feb;4:71-7 + 24480526 + + + Dev Cell. 2009 May;16(5):649-60 + 19460342 + + + Hum Genet. 2008 Feb;123(1):77-82 + 18071751 + + + Arq Neuropsiquiatr. 2016 Mar;74(3):253-5 + 27050856 + + + Annu 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Mol Psychiatry. 2010 Aug;15(8):816-22 + 19274051 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + Immunity. 2014 Jun 19;40(6):936-48 + 24931123 + + + Cancer Lett. 2008 Nov 28;271(2):179-90 + 18550271 + + + BJOG. 2016 Jul;123(8):1265-1269 + 27150580 + + + PLoS One. 2014 Dec 22;9(12):e115908 + 25531106 + + + Proteomics. 2009 Dec;9(23):5243-55 + 19798668 + + + Rev Neurol. 2016 Apr 1;62(7):317-28 + 26988170 + + + Vet Pathol. 2012 Jan;49(1):166-81 + 21746835 + + + Mol Cell Biol. 2004 Mar;24(5):2074-82 + 14966286 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Am J Hum Genet. 2014 May 1;94(5):649-61 + 24726472 + + + DNA Repair (Amst). 2008 Jul 1;7(7):1039-50 + 18458003 + + + + Zika + interferon-inducible transmembrane proteins + protein interaction + virus infection + + No competing interests were disclosed. +
+ + + + 2017 + 10 + 04 + + + 2018 + 1 + 19 + 6 + 0 + + + 2016 + 8 + 5 + 0 + 0 + + + 2016 + 8 + 5 + 0 + 1 + + + epublish + + 29333229 + 10.12688/f1000research.9364.2 + PMC5747333 + + +
+ + + + + 27478378 + + 2016 + 08 + 01 + + + 2017 + 02 + 20 + +
+ + 1176-6328 + + 12 + + 2016 + + + Neuropsychiatric disease and treatment + Neuropsychiatr Dis Treat + + Zika virus challenges for neuropsychiatry. + + 1747-60 + + 10.2147/NDT.S113037 + + Before 2007, Zika virus (ZIKV) was generally considered as an arbovirus of low clinical relevance, causing a mild self-limiting febrile illness in tropical Africa and Southeast Asia. Currently, a large, ongoing outbreak of ZIKV that started in Brazil in 2015 is spreading across the Americas. Virus infection during pregnancy has been potentially linked to congenital malformations, including microcephaly. In addition to congenital malformations, a temporal association between ZIKV infection and an increase in cases of Guillain-Barré syndrome is currently being observed in several countries. The mechanisms underlying these neurological complications are still unknown. Emerging evidence, mainly from in vitro studies, suggests that ZIKV may have direct effects on neuronal cells. The aim of this study was to critically review the literature available regarding the neurobiology of ZIKV and its potential neuropsychiatric manifestations. + + + + Simões E Silva + Ana Cristina + AC + + Interdisciplinary Laboratory of Medical Investigation; Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + Moreira + Janaina Matos + JM + + Interdisciplinary Laboratory of Medical Investigation; Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + Romanelli + Roberta Maia Castro + RM + + Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil. + + + + Teixeira + Antonio Lucio + AL + + Interdisciplinary Laboratory of Medical Investigation; Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA. + + + + eng + + Journal Article + Review + + + 2016 + 07 + 14 + +
+ + New Zealand + Neuropsychiatr Dis Treat + 101240304 + 1176-6328 + + + + N Engl J Med. 2016 Jun 2;374(22):2193-5 + 27050112 + + + Lancet Neurol. 2013 Sep;12(9):906-19 + 23948177 + + + PLoS Negl Trop Dis. 2016 Apr 12;10(4):e0004636 + 27070912 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + J Pediatr (Rio J). 2016 May-Jun;92 (3):230-40 + 27049675 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Arch Virol. 2007;152(4):687-96 + 17195954 + + + Semin Pediatr Neurol. 2007 Sep;14(3):118-27 + 17980308 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Ann Trop Med Parasitol. 1948 Sep;42(2):218-23 + 18891448 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Trans R Soc Trop Med Hyg. 1964 Jul;58:335-8 + 14175744 + + + Infect Genet Evol. 2016 Jul;41:142-5 + 27071531 + + + Medicine (Baltimore). 2016 Mar;95(12):e3201 + 27015222 + + + Nat Rev Neurol. 2014 Aug;10(8):469-82 + 25023340 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + Am J Public Health. 2016 Apr;106(4):598-600 + 26959258 + + + Ultrasound Obstet Gynecol. 2016 May;47(5):657-60 + 26923098 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + J Clin Virol. 2016 Jan;74:1-3 + 26615388 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Neurology. 2009 Sep 15;73(11):887-97 + 19752457 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Lancet. 2016 Apr 9;387(10027):1486-8 + 26948432 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + J Clin Virol. 2015 Feb;63:32-5 + 25600600 + + + Emerg Infect Dis. 2016 May;22(5):933-5 + 27088323 + + + Lancet. 2016 Mar 5;387(10022):919-21 + 26921913 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + Ultrasound Obstet Gynecol. 2010 Aug;36(2):154-8 + 20069548 + + + Antiviral Res. 2016 Jun;130:69-80 + 26996139 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Reprod Biol Endocrinol. 2003 Nov 14;1:110 + 14617366 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Am J Public Health. 2016 Apr;106(4):606-12 + 26959260 + + + Lancet. 2016 Apr 2;387(10026):1481 + 26946926 + + + Euro Surveill. 2016;21(13):null + 27063794 + + + Euro Surveill. 2015 Jun 11;20(23):null + 26084316 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Pediatr Radiol. 2016 Jun;46(7):1032-9 + 27090801 + + + Euro Surveill. 2016;21(8):null + 26939607 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Rev Neurol. 2016 Apr 1;62(7):317-28 + 26988170 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Childs Nerv Syst. 2016 Jun;32(6):1057-60 + 27080092 + + + J Gen Virol. 1976 Jan;30(1):123-30 + 1245842 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Trans R Soc Trop Med Hyg. 1956 May;50(3):238-42 + 13337908 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):211-4 + 26938703 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Guillain-Barré syndrome + Zika virus + microcephaly + neurodevelopmental disorders + +
+ + + + 2016 + 8 + 2 + 6 + 0 + + + 2016 + 8 + 2 + 6 + 0 + + + 2016 + 8 + 2 + 6 + 1 + + + epublish + + 27478378 + 10.2147/NDT.S113037 + ndt-12-1747 + PMC4951060 + + +
+ + + + + 27477156 + + 2016 + 08 + 08 + + + 2017 + 08 + 23 + +
+ + 1474-547X + + 388 + 10042 + + 2016 + Jul + 23 + + + Lancet (London, England) + Lancet + + Could clinical symptoms be a predictor of complications in Zika virus infection? + + 338 + + S0140-6736(16)31104-7 + 10.1016/S0140-6736(16)31104-7 + + + Freitas + André Ricardo Ribas + ARR + + Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, São Paulo 13015904, Brazil; Campinas Department of Health, Division of Health Surveillance, Campinas, São Paulo, Brazil. Electronic address: arrfreitas2010@gmail.com. + + + + Napimoga + Marcelo Henrique + MH + + Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, São Paulo 13015904, Brazil. + + + + Donalisio + Maria Rita + MR + + Laboratory of Spatial Analysis of Epidemiological Data, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil. + + + + eng + + Comment + Letter + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Lancet. 2016 Jul 23;388(10042):338-9 + 27477157 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + + + Female + + + Humans + + + Male + + + Microcephaly + epidemiology + + + Pregnancy + + + Zika Virus + + + Zika Virus Infection + epidemiology + + +
+ + + + 2016 + 8 + 2 + 6 + 0 + + + 2016 + 8 + 2 + 6 + 0 + + + 2016 + 8 + 9 + 6 + 0 + + + ppublish + + 27477156 + S0140-6736(16)31104-7 + 10.1016/S0140-6736(16)31104-7 + + +
+ + + + + 27474488 + + 2017 + 02 + 08 + +
+ + 1578-1283 + + 30 + 6 + + 2016 Nov - Dec + + + Gaceta sanitaria + Gac Sanit + + [Zika virus infection: a new public health emergency with great media impact]. + + 468-471 + + S0213-9111(16)30120-0 + 10.1016/j.gaceta.2016.05.015 + + Infection with Zika virus (ZV) has become a new epidemic, with great impact on the media, and is having a strong effect in Latin American countries. Its possible association with microcephaly and Guillain-Barré syndrome prompted the World Health Organization (WHO) to declare on 1 February 2016 that this epidemic is a public health emergency of international concern. Epidemiological data show an increasing incidence in countries like Brazil and Colombia, and that the epidemic is still expanding in many other countries. Between January 2007 and 27 April 2016, the WHO detected transmission in 55 countries (in 42 of these, this was the first outbreak of Zika) and 1,198 microcephalies and other neurological disorders in Brazil. Also, during 2015-2016, 13 countries detected an increase in Guillain-Barré syndrome and/or confirmation of ZV associated with Guillain-Barré syndrome. Research has already demonstrated a causal relationship between microcephaly and other serious brain disorders in newborns and ZV infection in the mother. Clinically, many cases are asymptomatic and it can be difficult to distinguish this diagnosis from that of other arboviruses. Vector control in Spain is a priority because of the presence of the Aedes albopictus (tiger mosquito). Early diagnosis is recommended, as is avoiding travel to endemic areas and unprotected sex, and ensuring that the high political profile, which can prevent this epidemic from becoming a high prevalence endemic disease, does not cause us to forget about other health problems. + Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved. + + + + Caylà + Joan A + JA + + Programa de Prevención, Vigilancia y Control de las Enfermedades Transmisibles (PREVICET) del CIBER de Epidemiología y Salud Pública (CIBERESP), España; Servicio de Epidemiología, Agència de Salut Pública de Barcelona, Barcelona, España. Electronic address: jcayla@aspb.cat. + + + + Domínguez + Ángela + Á + + Programa de Prevención, Vigilancia y Control de las Enfermedades Transmisibles (PREVICET) del CIBER de Epidemiología y Salud Pública (CIBERESP), España; Departament de Salut Pública, Facultad de Medicina, Universitat de Barcelona, Barcelona, España. + + + + Rodríguez Valín + Elena + E + + Programa de Prevención, Vigilancia y Control de las Enfermedades Transmisibles (PREVICET) del CIBER de Epidemiología y Salud Pública (CIBERESP), España; Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, España. + + + + de Ory + Fernando + F + + Programa de Prevención, Vigilancia y Control de las Enfermedades Transmisibles (PREVICET) del CIBER de Epidemiología y Salud Pública (CIBERESP), España; Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, España. + + + + Vázquez + Ana + A + + Programa de Prevención, Vigilancia y Control de las Enfermedades Transmisibles (PREVICET) del CIBER de Epidemiología y Salud Pública (CIBERESP), España; Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, España. + + + + Fortuny + Claudia + C + + Programa de Prevención, Vigilancia y Control de las Enfermedades Transmisibles (PREVICET) del CIBER de Epidemiología y Salud Pública (CIBERESP), España; Unitat d'Infeccions, Hospital Sant Joan de Déu, Esplugues de Llobregat (Barcelona), España. + + + + Grupo de trabajo sobre Zika del Programa de Prevención, Vigilancia y Control de Enfermedades Transmisibles (PREVICET) del CIBER de Epidemiología y Salud Pública (CIBERESP) + + + spa + + Journal Article + English Abstract + + La infección por virus Zika: una nueva emergencia de salud pública con gran impacto mediático. + + 2016 + 07 + 26 + +
+ + Spain + Gac Sanit + 8901623 + 0213-9111 + + + Emergencia + Emergency + Epidemias mediáticas + Guillain-Barré + Media epidemics + Microcefalia + Microcephaly + Public health + Salud pública + Vector, control + Vectores, control + Zika + +
+ + + + 2016 + 05 + 19 + + + 2016 + 05 + 24 + + + 2016 + 05 + 24 + + + 2016 + 7 + 31 + 6 + 0 + + + 2016 + 7 + 31 + 6 + 0 + + + 2016 + 7 + 31 + 6 + 0 + + + ppublish + + 27474488 + S0213-9111(16)30120-0 + 10.1016/j.gaceta.2016.05.015 + + +
+ + + + + 27471296 + + 2016 + 10 + 05 + + + 2016 + 12 + 30 + +
+ + 1095-9203 + + 353 + 6298 + + 2016 + Jul + 29 + + + Science (New York, N.Y.) + Science + + Clarifying samples in Zika analyses. + + 452 + + 10.1126/science.aah3733 + + + de Oliveira + João R M + JR + + Laboratório de Imunopatologia Keizo Asami, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil. joao.ricardo@ufpe.br. + + + + Moura + Denis A P + DA + + Laboratório de Imunopatologia Keizo Asami, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil. + + + + eng + + Letter + +
+ + United States + Science + 0404511 + 0036-8075 + + IM + + + Brazil + epidemiology + + + Child, Preschool + + + Clinical Coding + standards + + + Europe + epidemiology + + + Humans + + + Infant + + + Microcephaly + diagnosis + epidemiology + virology + + + North America + epidemiology + + + Zika Virus + + + Zika Virus Infection + complications + diagnosis + epidemiology + + +
+ + + + 2016 + 7 + 30 + 6 + 0 + + + 2016 + 7 + 30 + 6 + 0 + + + 2016 + 10 + 7 + 6 + 0 + + + ppublish + + 27471296 + 353/6298/452-a + 10.1126/science.aah3733 + + +
+ + + + + 27469112 + + 2017 + 02 + 10 + + + 2017 + 11 + 09 + +
+ + 1874-9356 + + 61 + 6 + + 2016 + Nov + + + Folia microbiologica + Folia Microbiol. (Praha) + + Zika virus: a new arboviral public health problem. + + 523-527 + + + Zika virus (ZIKV) is a single-stranded RNA virus in the Flaviviridae family and transmitted to human through infected mosquitos (Aedes aegypti and Aedes albopictus). Virus is closely related with other flaviviruses; dengue virus, yellow fever virus, West Nile virus, and Japanese encephalitis virus phylogenetically. Due to the possible relationship between virus and clinical features including microcephaly, ventricule, and eye deformities, Guillain-Barre syndrome increases the interest on this virus gradually. Along with the vector-borne transmission, exposure via blood transfusion and sexual contact are further concerns. Since December 2015, CDC reported 440.000-1.300.000 possible cases in Brazil and as of 19 January 2016, El Salvador, Venezuela, Colombia, Brazil, Surinam, French Guana, Honduras, Mexico, and Panama are the countries with active epidemic. CDC recommends ZIKV screening for all pregnants including asymptomatic cases those living in the active epidemic areas. Recently, virus is detected in the USA and most European countries including UK, Netherlands, Denmark, Switzerland, and Italy as a travel-associated infection. Owing to the changing world with increased capabilities for transportation globally, this vector-borne infection represents a valuable marker for the ability of spreading of any infection from its original area that it was first seen. In this review, we summarized the up-to-date data and reports in terms of the importance of the ZIKV infection in the public health. + + + + Demir + Tulin + T + + Public Health Institution of Turkey, National Reference Laboratories of Microbiology, Ankara, Turkey. drtulin@yahoo.com. + + + + Kilic + Selcuk + S + + Public Health Institution of Turkey, National Reference Laboratories of Microbiology, Ankara, Turkey. + + + + eng + + Journal Article + Review + + + 2016 + 07 + 28 + +
+ + United States + Folia Microbiol (Praha) + 0376757 + 0015-5632 + + IM + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + Int J Infect Dis. 2016 Mar;44:11-5 + 26854199 + + + PLoS Negl Trop Dis. 2013 Aug 01;7(8):e2348 + 23936579 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Annu Rev Microbiol. 1990;44:649-88 + 2174669 + + + Arq Bras Oftalmol. 2016 Feb;79(1):63 + 26840174 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Antiviral Res. 2008 Oct;80(1):11-22 + 18585795 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + Rev Soc Bras Med Trop. 2016 Feb;49(1):4-10 + 26689277 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + + + Animals + + + Culicidae + growth & development + virology + + + Disease Transmission, Infectious + + + Global Health + + + Humans + + + Insect Vectors + + + Public Health + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + transmission + + +
+ + + + 2016 + 05 + 16 + + + 2016 + 07 + 22 + + + 2016 + 7 + 30 + 6 + 0 + + + 2017 + 2 + 12 + 6 + 0 + + + 2016 + 7 + 30 + 6 + 0 + + + ppublish + + 27469112 + 10.1007/s12223-016-0467-6 + 10.1007/s12223-016-0467-6 + + +
+ + + + + 27466104 + + 2016 + 08 + 17 + + + 2016 + 12 + 16 + +
+ + 1476-4687 + + 535 + 7613 + + 2016 + 07 + 28 + + + Nature + Nature + + Brazil asks whether Zika acts alone to cause birth defects. + + 475-6 + + 10.1038/nature.2016.20309 + + + Butler + Declan + D + + + eng + + News + +
+ + England + Nature + 0410462 + 0028-0836 + + + + 0 + Yellow Fever Vaccine + + + IM + + + Animals + + + Artifacts + + + Brazil + epidemiology + + + Culicidae + microbiology + + + Dengue + immunology + + + Diarrhea Viruses, Bovine Viral + isolation & purification + metabolism + + + Female + + + Humans + + + Infant, Newborn + + + Maternal Age + + + Microcephaly + epidemiology + etiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + microbiology + + + Risk Factors + + + Socioeconomic Factors + + + Vaccination + statistics & numerical data + + + Yellow Fever Vaccine + administration & dosage + + + Zika Virus + genetics + isolation & purification + pathogenicity + + + Zika Virus Infection + complications + epidemiology + transmission + virology + + +
+ + + + 2016 + 7 + 29 + 6 + 0 + + + 2016 + 7 + 29 + 6 + 0 + + + 2016 + 8 + 18 + 6 + 0 + + + ppublish + + 27466104 + nature.2016.20309 + 10.1038/nature.2016.20309 + + +
+ + + + + 27464346 + + 2017 + 06 + 05 + + + 2017 + 06 + 05 + +
+ + 1531-8249 + + 80 + 4 + + 2016 + Oct + + + Annals of neurology + Ann. Neurol. + + Zika virus: An emergent neuropathological agent. + + 479-89 + + 10.1002/ana.24748 + + The emergence of Zika virus in the Americas has followed a pattern that is familiar from earlier epidemics of other viruses, where a new disease is introduced into a human population and then spreads rapidly with important public health consequences. In the case of Zika virus, an accumulating body of recent evidence implicates the virus in the etiology of serious pathologies of the human nervous system, that is, the occurrence of microcephaly in neonates and Guillain-Barré syndrome in adults. Zika virus is an arbovirus (arthropod-borne virus) and a member of the family Flaviviridae, genus Flavivirus. Zika virions are enveloped and icosahedral, and contain a nonsegmented, single-stranded, positive-sense RNA genome, which encodes 3 structural and 7 nonstructural proteins that are expressed as a single polyprotein that undergoes cleavage. Zika genomic RNA replicates in the cytoplasm of infected host cells. Zika virus was first detected in 1947 in the blood of a febrile monkey in Uganda's Zika Forest and in crushed suspensions of the Aedes mosquito, which is one of the vectors for Zika virus. The virus remained obscure, with a few human cases confined to Africa and Asia. There are two lineages of the Zika virus, African and Asian, with the Asian strain causing outbreaks in Micronesia in 2007 and French Polynesia in 2013-2014. From here, the virus spread to Brazil with the first report of autochthonous Zika transmission in the Americas in March 2015. The rapid advance of the virus in the Americas and its likely association with microcephaly and Guillain-Barré syndrome make Zika an urgent public health concern. Ann Neurol 2016;80:479-489. + © 2016 American Neurological Association. + + + + White + Martyn K + MK + + Department of Neuroscience, Center for Neurovirology, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA. + + + + Wollebo + Hassen S + HS + + Department of Neuroscience, Center for Neurovirology, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA. + + + + David Beckham + J + J + + Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO. + + + Department of Neurology, Anschutz Medical Campus, University of Colorado, Aurora, CO. + + + + Tyler + Kenneth L + KL + + Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO. + + + Department of Neurology, Anschutz Medical Campus, University of Colorado, Aurora, CO. + + + Department of Microbiology and Immunology, Anschutz Medical Campus, University of Colorado, Aurora, CO. + + + + Khalili + Kamel + K + + Department of Neuroscience, Center for Neurovirology, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA. kamel.khalili@temple.edu. + + + + eng + + + R33 AI101064 + AI + NIAID NIH HHS + United States + + + T32 AI052066 + AI + NIAID NIH HHS + United States + + + + Historical Article + Journal Article + Review + + + 2016 + 08 + 10 + +
+ + United States + Ann Neurol + 7707449 + 0364-5134 + + IM + + + Science. 2016 Mar 11;351(6278):1123-4 + 26965596 + + + N Engl J Med. 2016 Jun 2;374(22):2195-8 + 27074370 + + + Antiviral Res. 2015 Mar;115:48-70 + 25545072 + + + Travel Med Infect Dis. 2016 Jan-Feb;14 (1):16-20 + 26876061 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Lancet. 2016 Apr 30;387(10030):1811-2 + 27103126 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Virology. 1981 May;111(1):73-83 + 6263011 + + + Clin Infect Dis. 2009 Sep 15;49(6):942-8 + 19663604 + + + Euro Surveill. 2016 Apr 21;21(16): + 27126052 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Ann Trop Med Parasitol. 1975 Mar;69(1):49-64 + 1124969 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + Euro Surveill. 2008 Jun 26;13(26):null + 18761916 + + + Cell. 2016 May 19;165(5):1238-54 + 27118425 + + + JAMA. 2013 Jul 17;310(3):308-15 + 23860989 + + + J Clin Virol. 2016 Jul;80:8-11 + 27128355 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Wkly Epidemiol Rec. 2013 Jul 12;88(28):285-96 + 23909009 + + + Blood Transfus. 2016 Mar;14 (2):95-100 + 26674815 + + + Lancet Infect Dis. 2016 Apr;16(4):405 + 26949027 + + + Am J Trop Med Hyg. 2015 Aug;93(2):384-9 + 26033022 + + + Rev Bras Hematol Hemoter. 2016 Jan-Feb;38(1):90-1 + 26969782 + + + Curr Opin Hematol. 2015 Nov;22(6):547-53 + 26390164 + + + Lancet. 2016 Jan 23;387(10016):335-6 + 26777915 + + + Rev Med Virol. 2016 Mar;26(2):129-41 + 26695690 + + + PLoS Negl Trop Dis. 2016 Mar 02;10(3):e0004530 + 26934531 + + + N Engl J Med. 2012 Jun 14;366(24):2294-304 + 22694000 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + J Gen Virol. 1985 Sep;66 ( Pt 9):1969-82 + 4031825 + + + Am J Public Health. 2016 Apr;106(4):601-5 + 26959259 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Medicine (Baltimore). 2016 Apr;95(14):e3257 + 27057874 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Adv Virus Res. 2003;59:23-61 + 14696326 + + + Trans R Soc Trop Med Hyg. 1982;76(4):552-62 + 6304948 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Antiviral Res. 2013 Nov;100(2):500-19 + 24076358 + + + Infect Dis Clin North Am. 2008 Sep;22(3):561-75, x + 18755391 + + + Transfusion. 2016 Jan;56(1):33-40 + 26283013 + + + J Virol. 2016 Apr 29;90(10 ):4864-75 + 26962217 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + Int J Clin Pract. 2016 Mar;70(3):182-5 + 26918507 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + Virology. 1979 Jul 15;96(1):159-65 + 111410 + + + J Virol. 1998 Sep;72(9):7510-22 + 9696848 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + PLoS Negl Trop Dis. 2016 May 05;10(5):e0004658 + 27149521 + + + Euro Surveill. 2016 Apr 21;21(16): + 27123558 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Virology. 1986 Aug;153(1):113-21 + 3016981 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + Antiviral Res. 2016 Jun;130:69-80 + 26996139 + + + Emerg Microbes Infect. 2016 Mar 16;5:e22 + 26980239 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + J Infect. 2014 Sep;69(3):203-15 + 24880028 + + + J Infect. 2016 May;72 (5):507-24 + 26940504 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Virol Sin. 2016 Apr;31(2):118-30 + 27129451 + + + Viruses. 2015 Aug 13;7(8):4640-56 + 26287232 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Br Med J. 1928 Apr 28;1(3512):713-4 + 20773851 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + J Neurovirol. 2016 Jun;22(3):257-60 + 26903031 + + + Pediatr Radiol. 2016 Jun;46(7):1032-9 + 27090801 + + + Emerg Infect Dis. 2016 Aug;22(8):1438-44 + 27144515 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):55-8 + 26820163 + + + Lancet Infect Dis. 2015 Aug;15(8):951-9 + 26163373 + + + Neuroradiology. 2016 Aug;58(8):837-8 + 27067205 + + + Eur J Med Res. 2011 Jul 25;16(7):303-14 + 21813371 + + + Virology. 1981 Sep;113(2):544-55 + 7269253 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Curr Opin Virol. 2014 Aug;7:134-40 + 25063986 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Antiviral Res. 2015 Jun;118:148-58 + 25842996 + + + Childs Nerv Syst. 2016 Jun;32(6):1057-60 + 27080092 + + + J Gen Virol. 1976 Jan;30(1):123-30 + 1245842 + + + F1000Res. 2016 Jan 19;5:null + 26918159 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Annu Rev Entomol. 2007;52:209-29 + 16913829 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + N Engl J Med. 2016 Apr 21;374(16):1595-6 + 26958738 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + N Engl J Med. 2006 Aug 31;355(9):869-71 + 16943399 + + + Trop Med Health. 2011 Dec;39(4 Suppl):37-43 + 22500135 + + + + + Adult + + + Guillain-Barre Syndrome + etiology + + + History, 20th Century + + + History, 21st Century + + + Humans + + + Infant, Newborn + + + Microcephaly + etiology + + + Zika Virus + classification + genetics + pathogenicity + + + Zika Virus Infection + complications + epidemiology + history + + +
+ + + + 2016 + 03 + 30 + + + 2016 + 07 + 25 + + + 2016 + 07 + 25 + + + 2016 + 7 + 28 + 6 + 0 + + + 2016 + 7 + 28 + 6 + 0 + + + 2017 + 6 + 6 + 6 + 0 + + + ppublish + + 27464346 + PMC5086418 + 10.1002/ana.24748 + NIHMS824806 + + +
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+ + 2317-6385 + + 14 + 2 + + 2016 Apr-Jun + + + Einstein (Sao Paulo, Brazil) + Einstein (Sao Paulo) + + Bioethical considerations at times of Zika virus. + + 13-8 + + 10.1590/S1679-45082016ED3725 + S1679-45082016000200002 + + + Bueno + Marco Aurélio Scarpinella + MA + + Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. + + + + Grunspun + Henrique + H + + Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. + + + + eng + por + + Editorial + +
+ + Brazil + Einstein (Sao Paulo) + 101281800 + 1679-4508 + + IM + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + MMWR Morb Mortal Wkly Rep. 2016 Apr 01;65(12):315-22 + 27031943 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 18;65(10):267-8 + 26985965 + + + N Engl J Med. 2016 May 12;374(19):1801-3 + 27028782 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Einstein (Sao Paulo). 2016 Jul-Sep;14 (3):450 + 27759838 + + + + + Abortion, Eugenic + ethics + + + Bioethical Issues + + + Brazil + epidemiology + + + Female + + + Humans + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Prevalence + + + Travel + + + Zika Virus Infection + epidemiology + prevention & control + + +
+ + + + 2016 + 7 + 28 + 6 + 0 + + + 2016 + 7 + 28 + 6 + 0 + + + 2017 + 3 + 9 + 6 + 0 + + + ppublish + + 27462882 + S1679-45082016000200002 + 10.1590/S1679-45082016ED3725 + PMC4943367 + + +
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+ + 1678-4464 + + 32 + 7 + + 2016 + Jul + 21 + + + Cadernos de saude publica + Cad Saude Publica + + [Zika virus congenital syndrome]. + 10.1590/0102-311X00047716 + S0102-311X2016000700601 + + + Eickmann + Sophie Helena + SH + + Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, Brasil. + + + + Carvalho + Maria Durce Costa Gomes + MD + + Universidade de Pernambuco, Recife, Brasil. + + + + Ramos + Regina Coeli Ferreira + RC + + Universidade de Pernambuco, Recife, Brasil. + + + + Rocha + Maria Ângela Wanderley + + + Universidade de Pernambuco, Recife, Brasil. + + + + Linden + Vanessa van der + Vv + + Hospital Barão de Lucena, Recife, Brasil. + + + + Silva + Paula Fabiana Sobral da + PF + + Universidade de Pernambuco, Recife, Brasil. + + + + por + + Journal Article + + Síndrome da infecção congênita pelo vírus Zika. +
+ + Brazil + Cad Saude Publica + 8901573 + 0102-311X + + IM + + + Cad Saude Publica. 2016 Jul 21;32(7): + 27462858 + + + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Zika Virus Infection + congenital + epidemiology + + +
+ + + + 2016 + 03 + 22 + + + 2016 + 06 + 02 + + + 2016 + 7 + 28 + 6 + 0 + + + 2016 + 7 + 28 + 6 + 0 + + + 2017 + 3 + 31 + 6 + 0 + + + ppublish + + 27462846 + S0102-311X2016000700601 + 10.1590/0102-311X00047716 + + +
+ + + + + 27461305 + + 2017 + 04 + 13 + + + 2017 + 04 + 13 + +
+ + 2047-9018 + + 30 + 48 + + 2016 + Jul + 27 + + + Nursing standard (Royal College of Nursing (Great Britain) : 1987) + Nurs Stand + + Nursing on the Zika front line. + + 18-21 + + 10.7748/ns.30.48.18.s22 + + Paediatric nurse Roberta Seabra quickly and quietly takes control when the mother of baby Graziella breaks down. Ushering visitors from the room, she reassures Inabela Souza about her six-month-old daughter, who has been born with an abnormally small head and brain - one of 5,000 babies thought to be affected by microcephaly in Brazil. + + + + Thornton + Jacqui + J + + + eng + + Journal Article + +
+ + England + Nurs Stand + 9012906 + 0029-6570 + + N + + + Adult + + + Anniversaries and Special Events + + + Brazil + + + Female + + + Humans + + + Infant + + + Microcephaly + etiology + nursing + + + Mothers + education + psychology + + + Nurses + psychology + + + Pregnancy + + + Sports + + + Young Adult + + + Zika Virus + + + Zika Virus Infection + complications + diagnosis + nursing + + +
+ + + + 2016 + 7 + 28 + 6 + 0 + + + 2016 + 7 + 28 + 6 + 0 + + + 2017 + 4 + 14 + 6 + 0 + + + ppublish + + 27461305 + 10.7748/ns.30.48.18.s22 + + +
+ + + + + 27442184 + + 2017 + 01 + 11 + + + 2017 + 01 + 12 + +
+ + 1545-861X + + 65 + 28 + + 2016 + Jul + 22 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Projected Zika Virus Importation and Subsequent Ongoing Transmission after Travel to the 2016 Olympic and Paralympic Games - Country-Specific Assessment, July 2016. + + 711-5 + + 10.15585/mmwr.mm6528e1 + + Zika virus belongs to the genus Flavivirus of the family Flaviviridae; it is transmitted to humans primarily through the bite of an infected Aedes species mosquito (e.g., Ae. aegypti and Ae. albopictus) (1). Zika virus has been identified as a cause of congenital microcephaly and other serious brain defects (2). As of June 30, 2016, CDC had issued travel notices for 49 countries and U.S. territories across much of the Western hemisphere (3), including Brazil, where the 2016 Olympic and Paralympic Games (Games of the XXXI Olympiad, also known as Rio 2016; Games) will be hosted in Rio de Janeiro in August and September 2016. During the Games, mosquito-borne Zika virus transmission is expected to be low because August and September are winter months in Brazil, when cooler and drier weather typically reduces mosquito populations (4). CDC conducted a risk assessment to predict those countries susceptible to ongoing Zika virus transmission resulting from introduction by a single traveler to the Games. Whereas all countries are at risk for travel-associated importation of Zika virus, CDC estimated that 19 countries currently not reporting Zika outbreaks have the environmental conditions and population susceptibility to sustain mosquito-borne transmission of Zika virus if a case were imported from infection at the Games. For 15 of these 19 countries, travel to Rio de Janeiro during the Games is not estimated to increase substantially the level of risk above that incurred by the usual aviation travel baseline for these countries. The remaining four countries, Chad, Djibouti, Eritrea, and Yemen, are unique in that they do not have a substantial number of travelers to any country with local Zika virus transmission, except for anticipated travel to the Games. These four countries will be represented by a projected, combined total of 19 athletes (plus a projected delegation of about 60 persons), a tiny fraction of the 350,000-500,000 visitors expected at the Games.* Overall travel volume to the Games represents a very small fraction (<0.25%) of the total estimated 2015 travel volume to Zika-affected countries,(†) highlighting the unlikely scenario that Zika importation would be solely attributable to travel to the Games. To prevent Zika virus infection and its complications among athletes and visitors to the Games and importation of Zika virus into countries that could sustain local transmission, pregnant women should not travel to the Games, mosquito bites should be avoided while traveling and for 3 weeks after returning home, and measures should be taken to prevent sexual transmission (Box). + + + + Grills + Ardath + A + + + Morrison + Stephanie + S + + + Nelson + Bradley + B + + + Miniota + Jennifer + J + + + Watts + Alexander + A + + + Cetron + Martin S + MS + + + eng + + Journal Article + + + 2016 + 07 + 22 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + Anniversaries and Special Events + + + Athletes + + + Brazil + epidemiology + + + Disease Outbreaks + + + Global Health + + + Humans + + + Risk Assessment + + + Travel + + + Zika Virus Infection + epidemiology + transmission + + +
+ + + + 2016 + 7 + 22 + 6 + 0 + + + 2016 + 7 + 22 + 6 + 0 + + + 2017 + 1 + 12 + 6 + 0 + + + epublish + + 27442184 + 10.15585/mmwr.mm6528e1 + + +
+ + + + + 27435464 + + 2017 + 06 + 13 + + + 2018 + 01 + 04 + +
+ + 2150-7511 + + 7 + 4 + + 2016 + 07 + 19 + + + mBio + MBio + + Dengue Virus Envelope Dimer Epitope Monoclonal Antibodies Isolated from Dengue Patients Are Protective against Zika Virus. + 10.1128/mBio.01123-16 + e01123-16 + + Zika virus (ZIKV) is a mosquito-borne flavivirus responsible for thousands of cases of severe fetal malformations and neurological disease since its introduction to Brazil in 2013. Antibodies to flaviviruses can be protective, resulting in lifelong immunity to reinfection by homologous virus. However, cross-reactive antibodies can complicate flavivirus diagnostics and promote more severe disease, as noted after serial dengue virus (DENV) infections. The endemic circulation of DENV in South America and elsewhere raises concerns that preexisting flavivirus immunity may modulate ZIKV disease and transmission potential. Here, we report on the ability of human monoclonal antibodies and immune sera derived from dengue patients to neutralize contemporary epidemic ZIKV strains. We demonstrate that a class of human monoclonal antibodies isolated from DENV patients neutralizes ZIKV in cell culture and is protective in a lethal murine model. We also tested a large panel of convalescent-phase immune sera from humans exposed to primary and repeat DENV infection. Although ZIKV is most closely related to DENV compared to other human-pathogenic flaviviruses, most DENV immune sera (73%) failed to neutralize ZIKV, while others had low (50% effective concentration [EC50], <1:100 serum dilution; 18%) or moderate to high (EC50, >1:100 serum dilution; 9%) levels of cross-neutralizing antibodies. Our results establish that ZIKV and DENV share epitopes that are targeted by neutralizing, protective human antibodies. The availability of potently neutralizing human monoclonal antibodies provides an immunotherapeutic approach to control life-threatening ZIKV infection and also points to the possibility of repurposing DENV vaccines to induce cross-protective immunity to ZIKV. + ZIKV is an emerging arbovirus that has been associated with severe neurological birth defects and fetal loss in pregnant women and Guillain-Barré syndrome in adults. Currently, there is no vaccine or therapeutic for ZIKV. The identification of a class of antibodies (envelope dimer epitope 1 [EDE1]) that potently neutralizes ZIKV in addition to all four DENV serotypes points to a potential immunotherapeutic to combat ZIKV. This is especially salient given the precedent of antibody therapy to treat pregnant women infected with other viruses associated with microcephaly, such as cytomegalovirus and rubella virus. Furthermore, the identification of a functionally conserved epitope between ZIKV and DENV raises the possibility that a vaccine may be able to elicit neutralizing antibodies against both viruses. + Copyright © 2016 Swanstrom et al. + + + + Swanstrom + J A + JA + + Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. + + + + Plante + J A + JA + + Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. + + + + Plante + K S + KS + + Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. + + + + Young + E F + EF + + Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. + + + + McGowan + E + E + + Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. + + + + Gallichotte + E N + EN + + Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. + + + + Widman + D G + DG + + Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. + + + + Heise + M T + MT + + Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. + + + + de Silva + A M + AM + + Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. + + + + Baric + R S + RS + + Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA rbaric@email.unc.edu. + + + + eng + + + R01 AI107731 + AI + NIAID NIH HHS + United States + + + T32 AI007151 + AI + NIAID NIH HHS + United States + + + U19 AI100625 + AI + NIAID NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + + + 2016 + 07 + 19 + +
+ + United States + MBio + 101519231 + + + + 0 + Antibodies, Monoclonal + + + 0 + Antibodies, Neutralizing + + + 0 + Antibodies, Viral + + + 0 + Epitopes + + + IM + + + J Infect Dis. 2013 Sep;208(6):1026-33 + 23776195 + + + Science. 2015 Jul 3;349(6243):88-91 + 26138979 + + + Lancet. 2016 Apr 2;387(10026):1482 + 27115821 + + + PLoS Negl Trop Dis. 2016 Apr 12;10(4):e0004636 + 27070912 + + + Cochrane Database Syst Rev. 2015 Sep 09;(9):CD010586 + 26350479 + + + EMBO Mol Med. 2014 Mar;6(3):358-71 + 24421336 + + + Viruses. 2011 Dec;3(12):2374-95 + 22355444 + + + JAMA Neurol. 2016 Jul 1;73(7):875-9 + 27183312 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Am J Trop Med Hyg. 1982 Jul;31(4):830-6 + 6285749 + + + Arq Neuropsiquiatr. 2016 Mar;74(3):253-5 + 27050856 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Nat Commun. 2015 Feb 20;6:6341 + 25698059 + + + N Engl J Med. 2005 Sep 29;353(13):1350-62 + 16192480 + + + Lancet. 2012 Nov 3;380(9853):1559-67 + 22975340 + + + J Infect Dis. 2012 Jan 15;205(2):215-27 + 22140265 + + + J Virol. 2014 Aug;88(16):8826-42 + 24872579 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + PLoS Pathog. 2014 Oct 02;10(10):e1004386 + 25275316 + + + Cell Host Microbe. 2016 May 11;19(5):696-704 + 27158114 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Nature. 2016 Apr 19;533(7603):425-8 + 27093288 + + + J Virol. 2016 Apr 29;90(10 ):4864-75 + 26962217 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Nat Immunol. 2015 Feb;16(2):170-7 + 25501631 + + + Proc Natl Acad Sci U S A. 2012 May 8;109(19):7439-44 + 22499787 + + + J Virol. 2016 Apr 29;90(10 ):5090-7 + 26962223 + + + J Infect Dis. 2016 May 15;213(10):1562-72 + 26704612 + + + N Engl J Med. 2014 Apr 3;370(14):1316-26 + 24693891 + + + MBio. 2013 Nov 19;4(6):e00873-13 + 24255124 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + PLoS Comput Biol. 2010 Oct 07;6(10):e1000949 + 20949097 + + + Nature. 2015 Apr 2;520(7545):109-13 + 25581790 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + PLoS Med. 2008 Feb;5(2):e31 + 18271619 + + + Infect Genet Evol. 2016 Sep;43:43-9 + 27156653 + + + Expert Rev Vaccines. 2016 Jul;15(7):795-8 + 27171845 + + + Childs Nerv Syst. 2016 Jun;32(6):1057-60 + 27080092 + + + PLoS Med. 2015 Mar 24;12(3):e1001807 + 25803642 + + + Vaccine. 2016 Jun 3;34(26):2934-8 + 26973072 + + + MBio. 2015 Oct 13;6(5):e01461-15 + 26463165 + + + EMBO J. 2012 Feb 1;31(3):767-79 + 22139356 + + + Nat Immunol. 2016 Aug 19;17 (9):1010-2 + 27540984 + + + + + Animals + + + Antibodies, Monoclonal + administration & dosage + immunology + + + Antibodies, Neutralizing + administration & dosage + immunology + + + Antibodies, Viral + administration & dosage + immunology + + + Cross Reactions + + + Dengue Virus + immunology + + + Disease Models, Animal + + + Epitopes + immunology + + + Humans + + + Mice + + + Neutralization Tests + + + Treatment Outcome + + + Zika Virus + immunology + + + Zika Virus Infection + therapy + + +
+ + + + 2016 + 7 + 21 + 6 + 0 + + + 2016 + 7 + 21 + 6 + 0 + + + 2017 + 6 + 14 + 6 + 0 + + + epublish + + 27435464 + mBio.01123-16 + 10.1128/mBio.01123-16 + PMC4958264 + + +
+ + + + + 27417495 + + 2016 + 09 + 02 + + + 2017 + 11 + 10 + +
+ + 1095-9203 + + 353 + 6300 + + 2016 + Aug + 12 + + + Science (New York, N.Y.) + Science + + Assessing the global threat from Zika virus. + + aaf8160 + + 10.1126/science.aaf8160 + aaf8160 + + First discovered in 1947, Zika virus (ZIKV) infection remained a little-known tropical disease until 2015, when its apparent association with a considerable increase in the incidence of microcephaly in Brazil raised alarms worldwide. There is limited information on the key factors that determine the extent of the global threat from ZIKV infection and resulting complications. Here, we review what is known about the epidemiology, natural history, and public health effects of ZIKV infection, the empirical basis for this knowledge, and the critical knowledge gaps that need to be filled. + Copyright © 2016, American Association for the Advancement of Science. + + + + Lessler + Justin + J + + Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. justin@jhu.edu. + + + + Chaisson + Lelia H + LH + + Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. + + + + Kucirka + Lauren M + LM + + Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. + + + + Bi + Qifang + Q + + Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. + + + + Grantz + Kyra + K + + Department of Biology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA. + + + + Salje + Henrik + H + + Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris, France. + + + + Carcelen + Andrea C + AC + + Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. + + + + Ott + Cassandra T + CT + + Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. + + + + Sheffield + Jeanne S + JS + + Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. + + + + Ferguson + Neil M + NM + + Department of Medicine, School of Public Health, Imperial College London, London, UK. + + + + Cummings + Derek A T + DA + + Department of Biology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA. + + + + Metcalf + C Jessica E + CJ + + Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA. Office of Population Research, Princeton University, Princeton, NJ, USA. + + + + Rodriguez-Barraquer + Isabel + I + + Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. + + + + eng + + + U01 GM110721 + GM + NIGMS NIH HHS + United States + + + T32 GM007309 + GM + NIGMS NIH HHS + United States + + + MR/K010174/1 + Medical Research Council + United Kingdom + + + P2C HD047879 + HD + NICHD NIH HHS + United States + + + U54 GM088491 + GM + NIGMS NIH HHS + United States + + + + Journal Article + Review + + + 2016 + 07 + 14 + +
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+ + + + 2016 + 7 + 16 + 6 + 0 + + + 2016 + 7 + 16 + 6 + 0 + + + 2016 + 9 + 3 + 6 + 0 + + + ppublish + + 27417495 + science.aaf8160 + 10.1126/science.aaf8160 + PMC5467639 + NIHMS864470 + + +
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+ + 2261-2211 + + 26 + 2 + + 2016 + May + 01 + + + Medecine et sante tropicales + Med Sante Trop + + Zika virus infections. + + 145-50 + + 10.1684/mst.2016.0575 + + Since its discovery in 1947 in Uganda, the Zika virus (ZIKV) remained in the shadows emerging in 2007 in Micronesia, where hundreds of dengue-like syndromes were reported. Then, in 2013-2014, it was rife in French Polynesia, where the first neurological effects were observed. More recently, its arrival in Brazil was accompanied by an unusually high number of children with microcephaly born to mothers infected with ZIKV during the first trimester of pregnancy. In 2016, the World Health Organization declared ZIKV infection to be a public health emergency and now talks about a ZIKV pandemic. This review aims to summarize the current knowledge about ZIKV infection, successively addressing its transmission, epidemiology, clinical aspects, diagnosis, treatment, and prevention before discussing some perspectives. + + + + de Laval + F + F + + Centre d'épidémiologie et de santé publique des Armées, Camp militaire de Sainte-Marthe, BP 40026, 13568 Marseille cedex 02, France, Direction interarmées du service de santé en Guyane, Quartier La Madeleine, BP 6019, 97306 Cayenne cedex, Guyane française. + + + + Leparc-Goffart + I + I + + Institut de recherche biomédicale des Armées, Centre national de référence des arbovirus, Hôpital d'instruction des Armées Laveran, 34, boulevard Laveran 13013 Marseille, France. + + + + Meynard + J-B + JB + + Centre d'épidémiologie et de santé publique des Armées, Camp militaire de Sainte-Marthe, BP 40026, 13568 Marseille cedex 02, France. + + + + Daubigny + H + H + + Service de pathologie infectieuse et tropicale, Hôpital d'instruction des Armées Laveran, 34, boulevard Laveran 13013 Marseille, France. + + + + Simon + F + F + + Service de pathologie infectieuse et tropicale, Hôpital d'instruction des Armées Laveran, 34, boulevard Laveran 13013 Marseille, France. + + + + Briolant + S + S + + Direction interarmées du service de santé en Guyane, Quartier La Madeleine, BP 6019, 97306 Cayenne cedex, Guyane française, Institut Pasteur de la Guyane, Unité d'entomologie médicale, 23, avenue Pasteur, BP 6010, 97306 Cayenne cedex, Guyane française, Unité de recherche en maladies infectieuses et tropicales émergentes, UM 63, CNRS 7278, IRD 198, and Inserm 1095, Faculté de médecine La Timone, Aix-Marseille Université, 27, boulevard Jean-Moulin, Marseille, 13385, France, Institut de recherche biomédicale des Armées, Unité de parasitologie et d'entomologie médicale, Hôpital d'instruction des Armées Laveran, 34, boulevard Laveran 13013 Marseille, France. + + + + eng + + Journal Article + Review + + Infections à virus Zika. +
+ + France + Med Sante Trop + 101581406 + 2261-3684 + + IM + + + Female + + + Humans + + + Pregnancy + + + Pregnancy Complications, Infectious + virology + + + Zika Virus Infection + congenital + diagnosis + therapy + + + + Arbovirus + Exanthema + Flavivirus + Zika + Zika fever + microcephaly + +
+ + + + 2016 + 7 + 15 + 6 + 0 + + + 2016 + 7 + 15 + 6 + 0 + + + 2018 + 1 + 13 + 6 + 0 + + + ppublish + + 27412976 + mst.2016.0575 + 10.1684/mst.2016.0575 + + +
+ + + + + 27405738 + + 2016 + 12 + 19 + +
+ + 2048-7207 + + 5 + 3 + + 2016 + Sep + + + Journal of the Pediatric Infectious Diseases Society + J Pediatric Infect Dis Soc + + Zika Virus-Associated Microcephaly and Eye Lesions in the Newborn. + + 323-8 + + 10.1093/jpids/piw037 + + On February 1, 2016, Zika virus (ZIKV) was designated as a Public Health Emergency of International Concern by the director of the World Health Organization. Zika virus has spread to numerous countries throughout the Americas, affecting up to an estimated 1.3 million people since the first reports from Brazil in early 2015. Although ZIKV infections are self-limiting, fetal microcephaly and ophthalmic anomalies have been associated with ZIKV infection as a possible result of perinatal transmission. The causal link between maternal ZIKV infection and newborn microcephaly and eye lesions has not been proven beyond doubt and is currently debated. We discuss the possibility of causality by ZIKV using Koch's postulates and the more appropriate Bradford Hill criteria. In this review, we summarize and consolidate the current literature on newborn microcephaly and eye lesions associated with ZIKV infection and discuss current perspectives and controversies. + © The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. + + + + Valentine + Gregory + G + + Department of Pediatrics. + + + + Marquez + Lucila + L + + Department of Pediatrics, Section of Infectious Diseases. + + + + Pammi + Mohan + M + + Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, Texas. + + + + eng + + Journal Article + + + 2016 + 07 + 11 + +
+ + England + J Pediatric Infect Dis Soc + 101586049 + 2048-7193 + + IM + + Zika virus + global health + microcephaly + neonate + +
+ + + + 2016 + 03 + 01 + + + 2016 + 06 + 01 + + + 2016 + 7 + 14 + 6 + 0 + + + 2016 + 7 + 14 + 6 + 0 + + + 2016 + 7 + 14 + 6 + 0 + + + ppublish + + 27405738 + piw037 + 10.1093/jpids/piw037 + + +
+ + + + + 27393088 + + 2016 + 07 + 09 + + + 2018 + 02 + 19 + +
+ + 2352-4146 + + 9 + 7 + + 2016 + Jul + + + Asian Pacific journal of tropical medicine + Asian Pac J Trop Med + + Zika virus, a pathway to new challenges. + + 626-9 + + 10.1016/j.apjtm.2016.05.020 + S1995-7645(16)30109-2 + + The current Zika outbreak is largest of its kind with 1.4 million cases in Brazil alone. World Health Organization declared the current outbreak as the public health emergency of international concerns. The major route of Zika virus transmission is mosquito bites. Sexual transmission and monkey bites are also observed in few cases. There is dire need to evaluate the other routes of transmission like blood transfusion, lactation and contact with body fluids. Zika virus is infecting infants, not only causing microcephaly but also creating number of complications resulting in bad outcomes of pregnancy. In Brazil alone, 4000 cases of microcephaly have observed during the current outbreak. The incidence of Guillain-Barre (GB) syndrome is also observed during the current Zika virus outbreak. GB syndrome is acute medical condition leading the patients to death due to weakness of respiratory muscles or can cause the life time disability. There is no anti-viral drug or vaccine available for Zika virus. Zika infection can be prevented by using mosquito repellents, mosquito nets, cooling rooms by air conditions and wearing full sleeves or permethrin-treated clothes. The current outbreak of Zika has not only affected the health care but also caused great economic loss. Estimated loss in Latin America and Caribbean is US$3.5 billion. United Nation's sustainable development goal 3.d stresses the strengthening of early warning, risk reduction and management of national and global health risks. The world will keep on facing new challenges in the form of Ebola or Zika; there is strong need to prepare ourselves for any disease outbreak. + Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved. + + + + Jamil + Zubia + Z + + Fauji Foundation Hospital, Rawalpindi 46000, Pakistan. + + + + Waheed + Yasir + Y + + Foundation University Medical College, Foundation University Islamabad, DHA Phase I, Islamabad 44000, Pakistan. Electronic address: yasir_waheed_199@hotmail.com. + + + + Durrani + Taimoor Zeb + TZ + + Liver Clinic, Iftikhar Eye Hospital, Mayo Road, Islamabad 44000, Pakistan. + + + + eng + + Journal Article + Review + + + 2016 + 05 + 31 + +
+ + India + Asian Pac J Trop Med + 101533720 + 1995-7645 + + + Guillain-Barre syndrome + Microcephaly + Mosquito bites + Public health emergency + Zika virus + +
+ + + + 2016 + 04 + 15 + + + 2016 + 05 + 16 + + + 2016 + 05 + 23 + + + 2016 + 7 + 10 + 6 + 0 + + + 2016 + 7 + 10 + 6 + 0 + + + 2016 + 7 + 10 + 6 + 1 + + + ppublish + + 27393088 + S1995-7645(16)30109-2 + 10.1016/j.apjtm.2016.05.020 + + +
+ + + + + 27393087 + + 2016 + 07 + 09 + + + 2018 + 02 + 19 + +
+ + 2352-4146 + + 9 + 7 + + 2016 + Jul + + + Asian Pacific journal of tropical medicine + Asian Pac J Trop Med + + Zika virus infections: An overview of current scenario. + + 621-5 + + 10.1016/j.apjtm.2016.05.010 + S1995-7645(16)30098-0 + + Zika virus (ZIKV) was discovered more than half a century ago, recently it has gained unprecedented attention by the global health community. Until 2007, only 14 cases of human ZIKV infections were reported around the globe, while during the current outbreak, estimated cases mounted to approximately 1.5 million in Brazil alone, the virus was disseminated to wider South-American territories and travel-associated ZIKV infections were reported in USA, Europe and recently in China. ZIKV infections remain asymptomatic in approximately 80% of the individuals, and no anti-viral treatments were recommended. Yet, neurological complications associated with the infections, such as infant microcephaly and Guillain-Barré syndrome are major cause of the concern. Although, based on small numbers of cases, existing evidence strongly supports an exclusive link of viral infection and observed neurological complications. However, much work remains to assign exact numbers of complications caused by ZIKV. Regarding its structural attributes ZIKV shows remarkable resemblance with dengue virus and West-Nile virus. Despite, genomes of different ZIKV strains have already been decoded; role of the viral components in infection process and particularly pathogenesis of the disease remain widely unclear. In vulnerable areas, most viable strategy to ensure public health safety is vector control and enhanced public awareness about the transmission of the disease. + Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved. + + + + Dasti + Javid Iqbal + JI + + Department of Microbiology, Qauid-i-Azam University, Islamabad, Pakistan. Electronic address: iqbal78@hushmail.com. + + + + eng + + Journal Article + Review + + + 2016 + 05 + 31 + +
+ + India + Asian Pac J Trop Med + 101533720 + 1995-7645 + + + Aedes aegypti + Aedes albopictus + Guillain–Barré syndrome + Microcephaly + Neurological complications + Zika virus + +
+ + + + 2016 + 04 + 15 + + + 2016 + 05 + 16 + + + 2016 + 05 + 23 + + + 2016 + 7 + 10 + 6 + 0 + + + 2016 + 7 + 10 + 6 + 0 + + + 2016 + 7 + 10 + 6 + 1 + + + ppublish + + 27393087 + S1995-7645(16)30098-0 + 10.1016/j.apjtm.2016.05.010 + + +
+ + + + + 27390166 + + 2017 + 04 + 28 + + + 2017 + 08 + 17 + +
+ + 1758-1133 + + 46 + 3 + + 2016 + Jul + + + Tropical doctor + Trop Doct + + Zika virus infection and once again the risk from other neglected diseases. + + 159-65 + + 10.1177/0049475516656101 + + Since the first cases of Zika were identified and reported in Brazil, the magnitude and consequences of the outbreak in the Americas have increased tremendously, leading the World Health Organization to consider Zika and its link with clusters of microcephaly a Public Health Emergency of International Concern. Only a previous large outbreak in French Polynesia was known and no neurological anomalies have been reported. Differences in African and Asian lineage and differences in genetic evolution of the Zika virus may possibly provide an explanation for the development of the recent outbreaks and their variable presentation. However, the similar clinical presentation between Zika and other diseases like Dengue and Chikungunya can support that Zika has been circulating and spreading inadvertently. This hypothesis gains strength when rates of laboratory confirmation diagnosis for Dengue are observed in Brazil and Colombia, two of the most affected countries by Zika virus (ZIKV) infection.The lack of attention and resources on neglected diseases supposes a huge risk that new lethal pathogens camouflage themselves to spread into large areas and populations. + © The Author(s) 2016. + + + + Porrino + Pedro + P + + Medical Doctor; specialist in Tropical Medicine; Health Coordinator and Head of Mission, Doctors of The World pedro.porrino@gmail.com. + + + + eng + + Journal Article + +
+ + England + Trop Doct + 1301706 + 0049-4755 + + IM + + + Brazil + epidemiology + + + Chikungunya Fever + epidemiology + + + Communicable Diseases, Emerging + epidemiology + virology + + + Dengue + epidemiology + + + Disease Outbreaks + + + Epidemiological Monitoring + + + Humans + + + Microcephaly + epidemiology + + + Neglected Diseases + + + World Health Organization + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + epidemiology + transmission + virology + + + + Zika + dengue + epidemiological surveillance + neglected diseases + uutbreaks + +
+ + + + 2016 + 7 + 9 + 6 + 0 + + + 2016 + 7 + 9 + 6 + 0 + + + 2017 + 4 + 30 + 6 + 0 + + + ppublish + + 27390166 + 46/3/159 + 10.1177/0049475516656101 + + +
+ + + + + 27384821 + + 2017 + 03 + 01 + + + 2017 + 03 + 02 + +
+ + 1678-9849 + + 49 + 3 + + 2016 May-Jun + + + Revista da Sociedade Brasileira de Medicina Tropical + Rev. Soc. Bras. Med. Trop. + + Zika virus: what do we know about the viral structure, mechanisms of transmission, and neurological outcomes? + + 267-73 + + 10.1590/0037-8682-0150-2016 + S0037-86822016000300267 + + The Zika virus epidemic that started in Brazil in 2014 has spread to >30 countries and territories in Latin America, leading to a rapid rise in the incidence of microcephalic newborns and adults with neurological complications. At the beginning of the outbreak, little was known about Zika virus morphology, genome structure, modes of transmission, and its potential to cause neurological malformations and disorders. With the advancement of basic science, discoveries of the mechanisms of strain variability, viral transfer to the fetus, and neurovirulence were published. These will certainly lead to the development of strategies to block vertical viral transmission, neuronal invasion, and pathogenesis in the near future. This paper reviews the current literature on Zika virus infections, with the aim of gaining a holistic insight into their etiology and pathogenesis. We discuss Zika virus history and epidemiology in Brazil, viral structure and taxonomy, old and newly identified transmission modes, and neurological consequences of infection. + + + + Silva + Lucia Regina Cangussu da + LR + + Departamento de Ciências Biomédicas, Universidade Salgado de Oliveira, Juiz de Fora, Minas Gerais, Brasil. + + + + Souza + Adriano Miranda de + AM + + Departamento de Farmacologia, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brasil. + + + + eng + + Journal Article + Review + +
+ + Brazil + Rev Soc Bras Med Trop + 7507456 + 0037-8682 + + IM + + + Adult + + + Humans + + + Infant, Newborn + + + Microcephaly + virology + + + Nervous System Diseases + classification + virology + + + Viral Structures + + + Zika Virus + physiology + + + Zika Virus Infection + complications + transmission + virology + + +
+ + + + 2016 + 05 + 16 + + + 2016 + 06 + 14 + + + 2016 + 7 + 8 + 6 + 0 + + + 2016 + 7 + 8 + 6 + 0 + + + 2017 + 3 + 3 + 6 + 0 + + + ppublish + + 27384821 + S0037-86822016000300267 + 10.1590/0037-8682-0150-2016 + + +
+ + + + + 27383948 + + 2016 + 11 + 14 + + + 2016 + 12 + 30 + +
+ + 1476-4687 + + 535 + 7610 + + 2016 + 07 + 07 + + + Nature + Nature + + Use Zika to renew focus on birth-defect research. + + 8 + + 10.1038/535008a + eng + + Editorial + +
+ + England + Nature + 0410462 + 0028-0836 + + + + 0 + Rubella Vaccine + + + 935E97BOY8 + Folic Acid + + + IM + + + Biomedical Research + trends + + + Brazil + epidemiology + + + Congenital Abnormalities + diagnosis + epidemiology + etiology + prevention & control + + + Disease Eradication + trends + + + Epidemiological Monitoring + + + Folic Acid + administration & dosage + + + Humans + + + Microcephaly + epidemiology + etiology + prevention & control + + + Policy Making + + + Public Health Surveillance + + + Rubella + congenital + prevention & control + + + Rubella Vaccine + administration & dosage + + + Spina Bifida Occulta + prevention & control + + + Zika Virus + pathogenicity + + + Zika Virus Infection + complications + epidemiology + virology + + +
+ + + + 2016 + 7 + 8 + 6 + 0 + + + 2016 + 7 + 8 + 6 + 0 + + + 2016 + 11 + 15 + 6 + 0 + + + ppublish + + 27383948 + 535008a + 10.1038/535008a + + +
+ + + + + 27372398 + + 2016 + 09 + 19 + + + 2017 + 02 + 21 + +
+ + 1474-547X + + 388 + 10047 + + 2016 + Aug + 27 + + + Lancet (London, England) + Lancet + + Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation. + + 891-7 + + 10.1016/S0140-6736(16)30902-3 + S0140-6736(16)30902-3 + + In November, 2015, an epidemic of microcephaly was reported in Brazil, which was later attributed to congenital Zika virus infection. 7830 suspected cases had been reported to the Brazilian Ministry of Health by June 4, 2016, but little is known about their characteristics. We aimed to describe these newborn babies in terms of clinical findings, anthropometry, and survival. + We reviewed all 1501 liveborn infants for whom investigation by medical teams at State level had been completed as of Feb 27, 2016, and classified suspected cases into five categories based on neuroimaging and laboratory results for Zika virus and other relevant infections. Definite cases had laboratory evidence of Zika virus infection; highly probable cases presented specific neuroimaging findings, and negative laboratory results for other congenital infections; moderately probable cases had specific imaging findings but other infections could not be ruled out; somewhat probable cases had imaging findings, but these were not reported in detail by the local teams; all other newborn babies were classified as discarded cases. Head circumference by gestational age was assessed with InterGrowth standards. First week mortality and history of rash were provided by the State medical teams. + Between Nov 19, 2015, and Feb 27, 2015, investigations were completed for 1501 suspected cases reported to the Brazilian Ministry of Health, of whom 899 were discarded. Of the remainder 602 cases, 76 were definite, 54 highly probable, 181 moderately probable, and 291 somewhat probable of congenital Zika virus syndrome. Clinical, anthropometric, and survival differences were small among the four groups. Compared with these four groups, the 899 discarded cases had larger head circumferences (mean Z scores -1·54 vs -3·13, difference 1·58 [95% CI 1·45-1·72]); lower first-week mortality (14 per 1000 vs 51 per 1000; rate ratio 0·28 [95% CI 0·14-0·56]); and were less likely to have a history of rash during pregnancy (20·7% vs 61·4%, ratio 0·34 [95% CI 0·27-0·42]). Rashes in the third trimester of pregnancy were associated with brain abnormalities despite normal sized heads. One in five definite or probable cases presented head circumferences in the normal range (above -2 SD below the median of the InterGrowth standard) and for one third of definite and probable cases there was no history of a rash during pregnancy. The peak of the epidemic occurred in late November, 2015. + Zika virus congenital syndrome is a new teratogenic disease. Because many definite or probable cases present normal head circumference values and their mothers do not report having a rash, screening criteria must be revised in order to detect all affected newborn babies. + Brazilian Ministry of Health, Pan American Health Organization, and Wellcome Trust. + Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved. + + + + França + Giovanny V A + GV + + Secretariat of Health Surveillance, Ministry of Health, Brasilia, Brazil. + + + + Schuler-Faccini + Lavinia + L + + Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil. + + + + Oliveira + Wanderson K + WK + + Secretariat of Health Surveillance, Ministry of Health, Brasilia, Brazil. + + + + Henriques + Claudio M P + CM + + Secretariat of Health Surveillance, Ministry of Health, Brasilia, Brazil. + + + + Carmo + Eduardo H + EH + + Secretariat of Health Surveillance, Ministry of Health, Brasilia, Brazil. + + + + Pedi + Vaneide D + VD + + Secretariat of Health Surveillance, Ministry of Health, Brasilia, Brazil. + + + + Nunes + Marília L + ML + + Secretariat of Health Surveillance, Ministry of Health, Brasilia, Brazil. + + + + Castro + Marcia C + MC + + Harvard T H Chan School of Public Health, Boston, MA, USA. + + + + Serruya + Suzanne + S + + Latin American Center for Perinatology, Women and Reproductive Health, Montevideo, Uruguay. + + + + Silveira + Mariângela F + MF + + Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil. + + + + Barros + Fernando C + FC + + Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil; Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil. + + + + Victora + Cesar G + CG + + Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil. Electronic address: cvictora@equidade.org. + + + + eng + + + Wellcome Trust + United Kingdom + + + + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 06 + 29 + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Lancet. 2016 Aug 27;388(10047):846-7 + 27372396 + + + Lancet. 2017 Jan 14;389(10065):151-152 + 28102133 + + + + + Adult + + + Brazil + epidemiology + + + Cephalometry + + + Confounding Factors (Epidemiology) + + + Exanthema + virology + + + Female + + + Gestational Age + + + Humans + + + Infant + + + Infant Mortality + + + Infant, Newborn + + + Male + + + Microcephaly + epidemiology + pathology + virology + + + Neonatal Screening + methods + standards + trends + + + Neuroimaging + + + Odds Ratio + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + pathology + virology + + + Pregnancy Trimester, Third + + + Syndrome + + + Zika Virus + isolation & purification + + + Zika Virus Infection + congenital + diagnosis + epidemiology + pathology + + +
+ + + + 2016 + 7 + 4 + 6 + 0 + + + 2016 + 7 + 4 + 6 + 0 + + + 2016 + 9 + 20 + 6 + 0 + + + ppublish + + 27372398 + S0140-6736(16)30902-3 + 10.1016/S0140-6736(16)30902-3 + + +
+ + + + + 27372396 + + 2016 + 09 + 14 + + + 2016 + 09 + 06 + +
+ + 1474-547X + + 388 + 10047 + + 2016 + Aug + 27 + + + Lancet (London, England) + Lancet + + Surveillance of Zika virus infection and microcephaly in Brazil. + + 846-7 + + 10.1016/S0140-6736(16)30931-X + S0140-6736(16)30931-X + + + Heukelbach + Jörg + J + + Department of Community Health, School of Medicine, Federal University of Ceará, Rodolfo Teófilo, 60430-140 Fortaleza, CE, Brazil; Anton Breinl Centre for Public Health and College of Public Health, Medical and Veterinary Sciences, Division of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia. Electronic address: heukelbach@web.de. + + + + Werneck + Guilherme Loureiro + GL + + Department of Epidemiology, Social Medicine Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil. + + + + eng + + Comment + Journal Article + + + 2016 + 06 + 29 + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Lancet. 2016 Aug 27;388(10047):891-7 + 27372398 + + + + + Brazil + epidemiology + + + Humans + + + Microcephaly + + + Pregnancy Complications, Infectious + epidemiology + + + Zika Virus + + + Zika Virus Infection + + +
+ + + + 2016 + 7 + 4 + 6 + 0 + + + 2016 + 7 + 4 + 6 + 0 + + + 2016 + 9 + 15 + 6 + 0 + + + ppublish + + 27372396 + S0140-6736(16)30931-X + 10.1016/S0140-6736(16)30931-X + + +
+ + + + + 27372395 + + 2016 + 09 + 19 + + + 2016 + 11 + 26 + +
+ + 1474-547X + + 388 + 10047 + + 2016 + Aug + 27 + + + Lancet (London, England) + Lancet + + Pathology of congenital Zika syndrome in Brazil: a case series. + + 898-904 + + 10.1016/S0140-6736(16)30883-2 + S0140-6736(16)30883-2 + + Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection. + In this case series, formalin-fixed paraffin-embedded tissue samples from five cases, including two newborn babies with microcephaly and severe arthrogryposis who died shortly after birth, one 2-month-old baby, and two placentas from spontaneous abortions, from Brazil were submitted to the Infectious Diseases Pathology Branch at the US Centers for Disease Control and Prevention (Atlanta, GA, USA) between December, 2015, and March, 2016. Specimens were assessed by histopathological examination, immunohistochemical assays using a mouse anti-Zika virus antibody, and RT-PCR assays targeting the NS5 and envelope genes. Amplicons of RT-PCR positive cases were sequenced for characterisation of strains. + Viral antigens were localised to glial cells and neurons and associated with microcalcifications in all three fatal cases with microcephaly. Antigens were also seen in chorionic villi of one of the first trimester placentas. Tissues from all five cases were positive for Zika virus RNA by RT-PCR, and sequence analyses showed highest identities with Zika virus strains isolated from Brazil during 2015. + These findings provide strong evidence of a link between Zika virus infection and different congenital central nervous system malformations, including microcephaly as well as arthrogryposis and spontaneous abortions. + None. + Copyright © 2016 Elsevier Ltd. All rights reserved. + + + + Martines + Roosecelis Brasil + RB + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Bhatnagar + Julu + J + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + de Oliveira Ramos + Ana Maria + AM + + Department of Pathology, Federal University of Rio Grande do Norte, Natal, Brazil; Service for Ascertaining Death in the State of Rio Grande do Norte (SVO/RN), Natal/RN, Brazil. + + + + Davi + Helaine Pompeia Freire + HP + + Service for Ascertaining Death in the State of Rio Grande do Norte (SVO/RN), Natal/RN, Brazil. + + + + Iglezias + Silvia D'Andretta + SD + + Adolfo Lutz Institute, Sao Paulo, Brazil. + + + + Kanamura + Cristina Takami + CT + + Adolfo Lutz Institute, Sao Paulo, Brazil. + + + + Keating + M Kelly + MK + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Hale + Gillian + G + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Silva-Flannery + Luciana + L + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Muehlenbachs + Atis + A + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Ritter + Jana + J + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Gary + Joy + J + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Rollin + Dominique + D + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Goldsmith + Cynthia S + CS + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Reagan-Steiner + Sarah + S + + Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. + + + + Ermias + Yokabed + Y + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Suzuki + Tadaki + T + + Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan. + + + + Luz + Kleber G + KG + + Department of Infectious Diseases, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. + + + + de Oliveira + Wanderson Kleber + WK + + Ministry of Health, Brasilia, DF, Brazil. + + + + Lanciotti + Robert + R + + Arboviral Diseases Branch, Division of Vector-Borne Diseases, NCEZID, Centers for Disease Control and Prevention, Fort Collins, CO, USA. + + + + Lambert + Amy + A + + Arboviral Diseases Branch, Division of Vector-Borne Diseases, NCEZID, Centers for Disease Control and Prevention, Fort Collins, CO, USA. + + + + Shieh + Wun-Ju + WJ + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. + + + + Zaki + Sherif R + SR + + Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. Electronic address: szaki@cdc.gov. + + + + eng + + Case Reports + Journal Article + + + 2016 + 06 + 29 + +
+ + England + Lancet + 2985213R + 0140-6736 + + + + 0 + Antigens, Viral + + + 0 + RNA, Viral + + + AIM + IM + + + Lancet. 2016 Aug 27;388(10047):847-9 + 27372399 + + + + + Abortion, Spontaneous + virology + + + Adult + + + Antigens, Viral + isolation & purification + + + Autopsy + + + Brain + pathology + virology + + + Brazil + + + Fatal Outcome + + + Female + + + Humans + + + Immunohistochemistry + methods + + + Infant + + + Limb Deformities, Congenital + diagnostic imaging + virology + + + Male + + + Microcephaly + pathology + virology + + + Neuroglia + pathology + virology + + + Placenta + pathology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + pathology + virology + + + Pregnancy Trimester, First + + + Pregnancy Trimester, Second + + + Pregnancy Trimester, Third + + + RNA, Viral + isolation & purification + + + Reverse Transcriptase Polymerase Chain Reaction + + + Syndrome + + + Ultrasonography, Prenatal + + + Zika Virus + immunology + isolation & purification + + + Zika Virus Infection + congenital + pathology + + +
+ + + + 2016 + 7 + 4 + 6 + 0 + + + 2016 + 7 + 4 + 6 + 0 + + + 2016 + 9 + 20 + 6 + 0 + + + ppublish + + 27372395 + S0140-6736(16)30883-2 + 10.1016/S0140-6736(16)30883-2 + + +
+ + + + + 27367003 + + 2017 + 02 + 06 + + + 2017 + 02 + 06 + +
+ + 1972-2680 + + 10 + 6 + + 2016 + Jun + 30 + + + Journal of infection in developing countries + J Infect Dev Ctries + + Zika virus infection, associated microcephaly, and low yellow fever vaccination coverage in Brazil: is there any causal link? + + 563-6 + + 10.3855/jidc.8575 + + Since the end of 2014, Zika virus (ZIKV) infection has been rapidly spreading in Brazil. + To analyze the possible association of yellow fever vaccine with a protective effect against ZIKV-related microcephaly, the following spatial analyses were performed, using Brazilian municipalities as units: i) yellow fever vaccination coverage in Brazilian municipalities in individuals aged 15-49; ii) reported cases of microcephaly by municipality; and iii) confirmed cases of microcephaly related to ZIKV, by municipality. SaTScan software was used to identify clusters of municipalities for high risk of microcephaly. + There were seven significant high risk clusters of confirmed microcephaly cases, with four of them located in the Northeast where yellow fever vaccination rates were the lowest. The clusters harbored only 2.9% of the total population of Brazil, but 15.2% of confirmed cases of microcephaly. + We hypothesize that pregnant women in regions with high yellow fever vaccination coverage may pose their offspring to lower risk for development of microcephaly. There is an urgent need for systematic studies to confirm the possible link between low yellow fever vaccination coverage, Zika virus infection and microcephaly. + + + + De Góes Cavalcanti + Luciano Pamplona + LP + + Federal University of Ceará, Fortaleza, CE, Brazil. pamplona.luciano@gmail.com. + + + + Tauil + Pedro Luiz + PL + + + Alencar + Carlos Henrique + CH + + + Oliveira + Wanderson + W + + + Teixeira + Mauro Martins + MM + + + Heukelbach + Jorg + J + + + eng + + Journal Article + + + 2016 + 06 + 30 + +
+ + Italy + J Infect Dev Ctries + 101305410 + 1972-2680 + + + + 0 + Yellow Fever Vaccine + + + IM + + + Adolescent + + + Adult + + + Brazil + epidemiology + + + Female + + + Humans + + + Microcephaly + epidemiology + prevention & control + + + Middle Aged + + + Pregnancy + + + Risk Assessment + + + Spatial Analysis + + + Topography, Medical + + + Vaccination + utilization + + + Yellow Fever + prevention & control + + + Yellow Fever Vaccine + administration & dosage + + + Young Adult + + + Zika Virus Infection + complications + epidemiology + + +
+ + + + 2016 + 04 + 19 + + + 2016 + 06 + 09 + + + 2016 + 06 + 02 + + + 2016 + 7 + 2 + 6 + 0 + + + 2016 + 7 + 2 + 6 + 0 + + + 2017 + 2 + 7 + 6 + 0 + + + epublish + + 27367003 + + +
+ + + + + 27366760 + + 2016 + 07 + 01 + + + 2017 + 06 + 01 + +
+ + 2347-3584 + + 27 + 2 + + 2016 + Jun + + + Virusdisease + Virusdisease + + Zika virus outbreak: an overview of the experimental therapeutics and treatment. + + 111-5 + + 10.1007/s13337-016-0307-y + + Zika virus (ZIKV) infection is a new emerging threat around the globe which might be responsible for microcephaly and Guillain-Barre syndrome in the infants. Recently, ZIKV outbreak has caused a public health crisis in Brazil after being linked to a sharp increase in birth defects. ZIKV is ssRNA virus belongs to the family Flaviviridae. It is mainly transmitted by mosquito bite specifically Aedes species and disease symptoms include fever, joint pain, muscle pain, rash, conjunctivitis, and headache. The reservoir of ZIKV is still not known. Protection at personal level by avoiding mosquito bite would help to reduce the incidence of the disease. Control of ZIKV infection by vaccination or antiviral drug either from modern, complementary and alternative medicines may be considered to be one of the most effective strategies in the long run. Large scale immunization of susceptible human population is highly required to prevent this deadly disease. Attempts should be made as soon as possible to develop effective vaccines or antiviral to prevent ZIKV infection. This article provides a current overview of the experimental therapeutics and treatment options based on modern, complementary and alternative medicines. + + + + Saxena + Shailendra K + SK + 0000-0003-2856-4185 + + CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad, TS 500007 India. + + + + Elahi + Asif + A + + CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad, TS 500007 India. + + + + Gadugu + Srinivasulu + S + + CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad, TS 500007 India. + + + + Prasad + Anil K + AK + + CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad, TS 500007 India. + + + + eng + + + R01 MH085259 + MH + NIMH NIH HHS + United States + + + R37 DA025576 + DA + NIDA NIH HHS + United States + + + + Journal Article + Review + + + 2016 + 02 + 20 + +
+ + India + Virusdisease + 101624144 + 2347-3584 + + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Ann Trop Med Parasitol. 1975 Mar;69(1):49-64 + 1124969 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + Trans R Soc Trop Med Hyg. 1964 Jul;58:335-8 + 14175744 + + + J Ethnopharmacol. 2001 Mar 3;74(3):205-15 + 11274819 + + + Trans R Soc Trop Med Hyg. 1958 May;52(3):263-8 + 13556872 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + Cell Mol Life Sci. 2010 Aug;67(16):2773-86 + 20372965 + + + Virology. 2007 Sep 30;366(2):415-23 + 17543367 + + + Trans R Soc Trop Med Hyg. 1956 Sep;50(5):442-8 + 13380987 + + + J Virol. 2006 Dec;80(23):11418-31 + 16928749 + + + J Hyg (Lond). 1979 Oct;83(2):213-9 + 489960 + + + J Nat Prod. 1992 May;55(5):696-8 + 1517743 + + + Clin Microbiol Rev. 1999 Oct;12(4):564-82 + 10515903 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + BMJ. 2015 Dec 23;351:h6983 + 26698165 + + + + Aedes species + Infectious disease + Microcephaly + Risk assessment and prevention + Treatment + Zika virus + +
+ + + + 2016 + 02 + 05 + + + 2016 + 02 + 10 + + + 2016 + 7 + 2 + 6 + 0 + + + 2016 + 7 + 2 + 6 + 0 + + + 2016 + 7 + 2 + 6 + 1 + + + ppublish + + 27366760 + 10.1007/s13337-016-0307-y + 307 + PMC4909003 + + +
+ + + + + 27366020 + + 2017 + 02 + 22 + + + 2017 + 02 + 22 + +
+ + 1598-6357 + + 31 + 7 + + 2016 + Jul + + + Journal of Korean medical science + J. Korean Med. Sci. + + First Imported Case of Zika Virus Infection into Korea. + + 1173-7 + + 10.3346/jkms.2016.31.7.1173 + + Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil. + + + + Jang + Hee-Chang + HC + 0000-0002-3407-8493 + + Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Korea . + + + + Park + Wan Beom + WB + 0000-0003-0022-9625 + + Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea . + + + + Kim + Uh Jin + UJ + 0000-0002-8463-6297 + + Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Korea . + + + + Chun + June Young + JY + 0000-0001-9345-6645 + + Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea . + + + + Choi + Su-Jin + SJ + 0000-0001-8732-3950 + + Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea . + + + + Choe + Pyoeng Gyun + PG + 0000-0001-6794-7918 + + Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea . + + + + Jung + Sook-In + SI + 0000-0002-1577-678X + + Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Korea . + + + + Jee + Youngmee + Y + + Center for Pathology and Immunology, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong, Korea. + + + + Kim + Nam-Joong + NJ + 0000-0001-6793-9467 + + Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea . + + + + Choi + Eun Hwa + EH + 0000-0002-5857-0749 + + Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea . + + + + Oh + Myoung-Don + MD + 0000-0002-2344-7695 + + Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea . + + + + eng + + Case Reports + Journal Article + + + 2016 + 05 + 27 + +
+ + Korea (South) + J Korean Med Sci + 8703518 + 1011-8934 + + + + 0 + RNA, Viral + + + IM + + + MMWR Morb Mortal Wkly Rep. 2016 May 13;65(18):474 + 27171368 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Lancet Infect Dis. 2016 Apr;16(4):405 + 26949027 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Emerg Infect Dis. 2016 May;22(5):940 + 27088817 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Nat Protoc. 2007;2(10):2439-50 + 17947985 + + + MMWR Morb Mortal Wkly Rep. 2016 May 13;65(18):475-8 + 27171533 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + N Engl J Med. 2016 Apr 21;374(16):1595-6 + 26958738 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Adult + + + Brazil + + + Humans + + + Male + + + Microscopy, Electron, Transmission + + + RNA, Viral + analysis + blood + urine + + + Republic of Korea + + + Reverse Transcriptase Polymerase Chain Reaction + + + Saliva + virology + + + Semen + virology + + + Travel + + + Zika Virus + genetics + isolation & purification + + + Zika Virus Infection + diagnosis + virology + + + + Brazil + Korea + Travel + Virus Shedding + Zika Virus + +
+ + + + 2016 + 05 + 24 + + + 2016 + 05 + 25 + + + 2016 + 7 + 2 + 6 + 0 + + + 2016 + 7 + 2 + 6 + 0 + + + 2017 + 2 + 23 + 6 + 0 + + + ppublish + + 27366020 + 10.3346/jkms.2016.31.7.1173 + PMC4901014 + + +
+ + + + + 27364784 + + 2017 + 02 + 14 + + + 2017 + 02 + 20 + +
+ + 2352-3964 + + 10 + + 2016 + Aug + + + EBioMedicine + EBioMedicine + + Infectivity of Immature Neurons to Zika Virus: A Link to Congenital Zika Syndrome. + + 65-70 + + 10.1016/j.ebiom.2016.06.026 + S2352-3964(16)30282-1 + + Epidemiological data strongly suggest that microcephaly cases in Brazil are associated with the ongoing epidemic of Zika virus (ZIKV). In order to further solidify the possible link, we investigated the infectivity of ZIKV using various neuroblastoma (NB) cell lines. + Six undifferentiated, two terminally differentiated and two retinoic acid (RA) -induced, partially differentiated cell lines were exposed to ZIKV strain PRVABC59, which is genetically similar to the French Polynesia strain, with 97-100% genetic homology to the current ZIKV strain found in Brazil. All infections were confirmed by real-time PCR (RT-qPCR), immunofluorescence assay (IFA) probing with anti-flavivirus E antibody, and evaluation of cytopathic effects. + ZIKV infected all six undifferentiated NB cell lines. In five out of six NB cell lines, between 90 and 70% cells were positive by IFA whereas for one cell line, CCL-127, ~80% of cells were positive for ZIKV as determined by IFA but showed persistent infection. Two differentiated cell lines, JFEN and T-268, were highly resistant to ZIKV with <1% of the cells being susceptible, as determined by IFA and confirmed by qRT-PCR. Two retinoic acid (RA)-induced NB partially differentiated cell lines showed no difference in permissiveness as compared to their undifferentiated mother cell lines. + These findings strengthen the reported association between high incidences of microcephaly and ZIKV infection in newborns in Brazil. Our results suggest that the undifferentiated neurons are highly permissive to ZIKV infection, as one would expect during the early stages of neurogenesis in fetal brains; whereas differentiated neurons, representative of adult brain neurons, are relatively resistant to the virus, which explains the rare occurrence of neurological complications in adults infected with ZIKV. Our studies confirm the neurotropism of the ZIKV strain closely related to the current epidemic in Latin America. + Copyright © 2016 The Ohio State University Wexner Medical Center. Published by Elsevier B.V. All rights reserved. + + + + Hughes + Brandon W + BW + + Claflin University, South Carolina Center for Biotechnology, 400 Magnolia Street, 29115 Orangeburg, SC, United States. + + + + Addanki + Krishna C + KC + + Claflin University, South Carolina Center for Biotechnology, 400 Magnolia Street, 29115 Orangeburg, SC, United States. + + + + Sriskanda + Ahila N + AN + + Claflin University, South Carolina Center for Biotechnology, 400 Magnolia Street, 29115 Orangeburg, SC, United States. + + + + McLean + Ewen + E + + Claflin University, South Carolina Center for Biotechnology, 400 Magnolia Street, 29115 Orangeburg, SC, United States. + + + + Bagasra + Omar + O + + Claflin University, South Carolina Center for Biotechnology, 400 Magnolia Street, 29115 Orangeburg, SC, United States. Electronic address: obagasra@claflin.edu. + + + + eng + + Journal Article + + + 2016 + 06 + 23 + +
+ + Netherlands + EBioMedicine + 101647039 + 2352-3964 + + IM + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + PLoS One. 2013;8(4):e60874 + 23565282 + + + Curr Opin Immunol. 2010 Dec;22(6):740-6 + 21030229 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Emerg Infect Dis. 2016 Jul;22(7):1318-20 + 27070847 + + + Trans R Soc Trop Med Hyg. 1964 Jul;58:335-8 + 14175744 + + + PLoS Negl Trop Dis. 2013 Aug 01;7(8):e2348 + 23936579 + + + Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1038-43 + 8577710 + + + Emerg Infect Dis. 2016 Jul;22(7):1185-92 + 27070380 + + + Medicine (Baltimore). 2016 Apr;95(14):e3257 + 27057874 + + + Pediatrics. 2006 Mar;117(3):e537-45 + 16510632 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Methods Mol Biol. 2013;1078:9-21 + 23975817 + + + Case Rep Infect Dis. 2013;2013:351872 + 23533851 + + + Microbes Infect. 2016 Mar;18(3):169-71 + 26774331 + + + J Clin Virol. 2015 Feb;63:32-5 + 25600600 + + + Clin Microbiol Rev. 2000 Oct;13(4):571-87 + 11023958 + + + Trans R Soc Trop Med Hyg. 1956 Sep;50(5):442-8 + 13380987 + + + Acta Neuropathol. 2003 Dec;106(6):509-17 + 13680278 + + + EBioMedicine. 2016 May;7:267-77 + 27322480 + + + Emerg Microbes Infect. 2016 Mar 16;5:e22 + 26980239 + + + Cell Host Microbe. 2012 Oct 18;12(4):544-57 + 23084921 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Elife. 2015 Jun 30;4:e08347 + 26126267 + + + Blood. 2012 Mar 22;119(12):2799-809 + 22302738 + + + J Infect. 2016 May;72 (5):507-24 + 26940504 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Trans R Soc Trop Med Hyg. 1983;77(4):442-5 + 6314612 + + + Euro Surveill. 2016;21(8):null + 26939607 + + + Proc Natl Acad Sci U S A. 1980 May;77(5):2936-40 + 6930676 + + + Prog Neurobiol. 2009 Oct;89(2):162-75 + 19615423 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Pathog Dis. 2014 Jul;71(2):137-63 + 24737600 + + + + + Animals + + + Cell Line + + + Female + + + Fluorescent Antibody Technique + + + Humans + + + Infectious Disease Transmission, Vertical + + + Male + + + Neural Stem Cells + pathology + virology + + + Neurons + pathology + virology + + + Real-Time Polymerase Chain Reaction + + + Syndrome + + + Zika Virus + physiology + + + Zika Virus Infection + transmission + virology + + + + Microcephaly + Neuroblastoma + Neurogenesis + Terminally differentiated + Undifferentiated + Zika virus + +
+ + + + 2016 + 05 + 18 + + + 2016 + 06 + 18 + + + 2016 + 06 + 20 + + + 2016 + 7 + 2 + 6 + 0 + + + 2016 + 7 + 2 + 6 + 0 + + + 2017 + 2 + 15 + 6 + 0 + + + ppublish + + 27364784 + S2352-3964(16)30282-1 + 10.1016/j.ebiom.2016.06.026 + PMC5006602 + + +
+ + + + + 27359317 + + 2017 + 03 + 14 + + + 2017 + 08 + 17 + +
+ + 1439-4413 + + 141 + 13 + + 2016 + Jul + + + Deutsche medizinische Wochenschrift (1946) + Dtsch. Med. Wochenschr. + + [How dangerous is the Zika virus?]. + + 969-72 + + 10.1055/s-0042-109819 + + The Zika virus (ZIKV) may cause microcephaly and other serious birth defects. Due to a lack of epidemiological data, the teratogenic risk is unknown. The upcoming Olympic Games in Rio may cause it to spread to unprepared countries with underdeveloped healthcare systems. ZIKV is also sexually transmitted. The pathogenesis of sexual transmission and the duration of contagiousness are currently unknown. To minimize the risks caused by the Olympic Games in Rio, developing and emerging nations must be supported in disease prevention by the WHO and industrialized nations. In addition, the pathogenesis and risks of sexual ZIKV transmission require thorough investigation. + © Georg Thieme Verlag KG Stuttgart · New York. + + + + Kekulé + Alexander + A + + + ger + + Journal Article + + Wie gefährlich ist das Zika-Virus? + + 2016 + 06 + 30 + +
+ + Germany + Dtsch Med Wochenschr + 0006723 + 0012-0472 + + IM + + + Brazil + epidemiology + + + Communicable Diseases, Emerging + epidemiology + prevention & control + + + Female + + + Humans + + + Incidence + + + Male + + + Population Surveillance + methods + + + Risk Assessment + methods + + + Sports + statistics & numerical data + + + Zika Virus Infection + epidemiology + prevention & control + + +
+ + + + 2016 + 7 + 1 + 6 + 0 + + + 2016 + 7 + 1 + 6 + 0 + + + 2017 + 3 + 16 + 6 + 0 + + + ppublish + + 27359317 + 10.1055/s-0042-109819 + + +
+ + + + + 27357348 + + 2017 + 06 + 05 + + + 2017 + 06 + 05 + +
+ + 1460-2156 + + 139 + Pt 8 + + 2016 + Aug + + + Brain : a journal of neurology + Brain + + Zika virus-associated neurological disorders: a review. + + 2122-30 + + 10.1093/brain/aww158 + + Zika virus, an arbovirus transmitted by mosquitoes of the Aedes species, is now rapidly disseminating throughout the Americas and the ongoing Brazilian outbreak is the largest Zika virus epidemic so far described. In addition to being associated with a non-specific acute febrile illness, a number of neurological manifestations, mainly microcephaly and Guillain-Barré syndrome, have been associated with infection. These with other rarer neurological conditions suggest that Zika virus, similar to other flaviviruses, is neuropathogenic. The surge of Zika virus-related microcephaly cases in Brazil has received much attention and the role of the virus in this and in other neurological manifestations is growing. Zika virus has been shown to be transmitted perinatally and the virus can be detected in amniotic fluid, placenta and foetus brain tissue. A significant increase in Guillain-Barré syndrome incidence has also been reported during this, as well as in previous outbreaks. More recently, meningoencephalitis and myelitis have also been reported following Zika virus infection. In summary, while preliminary studies have suggested a clear relationship between Zika virus infection and certain neurological conditions, only longitudinal studies in this epidemic, as well as experimental studies either in animal models or in vitro, will help to better understand the role of the virus and the pathogenesis of these disorders. + © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com. + + + + Araujo + Abelardo Q C + AQ + + 1 Laboratory for Clinical Research in Neuroinfections (Lapclin-Neuro), The Evandro Chagas National Institute Of Infectious Diseases (INI), FIOCRUZ, Avenida Brasil 4365, CEP 21040-360, Rio de Janeiro - RJ, Brazil 2 The Deolindo Couto Institute of Neurology (INDC), The Federal University of Rio de Janeiro (UFRJ), Avenida Venceslau Bras 95, CEP 21941-901, Rio de Janeiro - RJ, Brazil abelardo@ufrj.br. + + + + Silva + Marcus Tulius T + MT + + 1 Laboratory for Clinical Research in Neuroinfections (Lapclin-Neuro), The Evandro Chagas National Institute Of Infectious Diseases (INI), FIOCRUZ, Avenida Brasil 4365, CEP 21040-360, Rio de Janeiro - RJ, Brazil. + + + + Araujo + Alexandra P Q C + AP + + 3 Neuropaediatrics Unit, the Martagão Gesteira Institute of Child Health and Paediatrics (IPPMG), The Federal University of Rio de Janeiro (UFRJ), Rua Bruno Lobo 50, CEP 21941-912, Rio de Janeiro - RJ, Brazil. + + + + eng + + Journal Article + Review + + + 2016 + 06 + 29 + +
+ + England + Brain + 0372537 + 0006-8950 + + AIM + IM + + + Guillain-Barre Syndrome + etiology + + + Humans + + + Microcephaly + etiology + + + Nervous System Diseases + etiology + + + Zika Virus + pathogenicity + + + Zika Virus Infection + complications + + + + Guillain-Barré syndrome + Zika virus + arbovirus + microcephaly + neurological complications + +
+ + + + 2016 + 04 + 30 + + + 2016 + 06 + 01 + + + 2016 + 7 + 1 + 6 + 0 + + + 2016 + 7 + 1 + 6 + 0 + + + 2017 + 6 + 6 + 6 + 0 + + + ppublish + + 27357348 + aww158 + 10.1093/brain/aww158 + + +
+ + + + + 27355570 + + 2016 + 09 + 27 + + + 2017 + 06 + 02 + +
+ + 1476-4687 + + 536 + 7617 + + 2016 + 08 + 25 + + + Nature + Nature + + Vaccine protection against Zika virus from Brazil. + + 474-8 + + + Zika virus (ZIKV) is a flavivirus that is responsible for the current epidemic in Brazil and the Americas. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans and mice. The rapid development of a safe and effective ZIKV vaccine is a global health priority, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization with a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a strain of ZIKV involved in the outbreak in northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice. We produced DNA vaccines expressing ZIKV pre-membrane and envelope (prM-Env), as well as a series of deletion mutants. The prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV, as measured by absence of detectable viraemia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and depletion of CD4 and CD8 T lymphocytes in vaccinated mice did not abrogate this protection. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans is likely to be achievable. + + + + Larocca + Rafael A + RA + + + Abbink + Peter + P + + + Peron + Jean Pierre S + JP + + + Zanotto + Paolo M de A + PM + + + Iampietro + M Justin + MJ + + + Badamchi-Zadeh + Alexander + A + + + Boyd + Michael + M + + + Ng'ang'a + David + D + + + Kirilova + Marinela + M + + + Nityanandam + Ramya + R + + + Mercado + Noe B + NB + + + Li + Zhenfeng + Z + + + Moseley + Edward T + ET + + + Bricault + Christine A + CA + + + Borducchi + Erica N + EN + + + Giglio + Patricia B + PB + + + Jetton + David + D + + + Neubauer + George + G + + + Nkolola + Joseph P + JP + + + Maxfield + Lori F + LF + + + De La Barrera + Rafael A + RA + + + Jarman + Richard G + RG + + + Eckels + Kenneth H + KH + + + Michael + Nelson L + NL + + + Thomas + Stephen J + SJ + + + Barouch + Dan H + DH + + + eng + + + UM1 AI100663 + AI + NIAID NIH HHS + United States + + + AI095985 + AI + NIAID NIH HHS + United States + + + AI096040 + AI + NIAID NIH HHS + United States + + + U19 AI095985 + AI + NIAID NIH HHS + United States + + + AI124377 + AI + NIAID NIH HHS + United States + + + U19 AI096040 + AI + NIAID NIH HHS + United States + + + AI100663 + AI + NIAID NIH HHS + United States + + + UM1 AI124377 + AI + NIAID NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + + + 2016 + 06 + 28 + +
+ + England + Nature + 0410462 + 0028-0836 + + + + 0 + Antibodies, Neutralizing + + + 0 + Antibodies, Viral + + + 0 + Immunoglobulin G + + + 0 + Vaccines, DNA + + + 0 + Vaccines, Inactivated + + + 0 + Vaccines, Subunit + + + 0 + Viral Envelope Proteins + + + 0 + Viral Vaccines + + + IM + + + Cochrane Database Syst Rev. 2009 Jan 21;(1):CD000977 + 19160184 + + + Am J Trop Med Hyg. 2015 Apr;92(4):698-708 + 25646261 + + + PLoS Pathog. 2016 Feb 05;12(2):e1005431 + 26849216 + + + Lancet. 2016 Apr 2;387(10026):1482 + 27115821 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Cell. 2016 May 19;165(5):1238-54 + 27118425 + + + Appl Microbiol. 1973 Apr;25(4):539-44 + 4633476 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Expert Rev Vaccines. 2015;14(9):1167-79 + 26162529 + + + Am J Trop Med Hyg. 2013 Jan;88(1):73-88 + 23208878 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + J Infect Dis. 2007 Dec 15;196(12):1732-40 + 18190252 + + + Am J Trop Med Hyg. 2015 Sep;93(3):454-60 + 26149862 + + + N Engl J Med. 2016 Jul 7;375(1):1-4 + 27222919 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + Vaccine. 2005 Nov 1;23(45):5205-11 + 16055233 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Clin Exp Immunol. 1997 Dec;110(3):358-61 + 9409636 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Cochrane Database Syst Rev. 2000;(2):CD000977 + 10796566 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + J Infect Dis. 2011 May 15;203(10):1396-404 + 21398392 + + + + + Adoptive Transfer + + + Animals + + + Antibodies, Neutralizing + immunology + + + Antibodies, Viral + immunology + + + Antibody Specificity + + + Brazil + + + CD4-Positive T-Lymphocytes + immunology + + + CD8-Positive T-Lymphocytes + immunology + + + Female + + + Gene Deletion + + + Humans + + + Immunoglobulin G + immunology + isolation & purification + + + Mice + + + Microcephaly + complications + virology + + + Vaccines, DNA + chemistry + genetics + immunology + + + Vaccines, Inactivated + chemistry + genetics + immunology + + + Vaccines, Subunit + chemistry + genetics + immunology + + + Viral Envelope Proteins + chemistry + genetics + immunology + + + Viral Vaccines + chemistry + genetics + immunology + + + Zika Virus + chemistry + genetics + immunology + + + Zika Virus Infection + complications + immunology + prevention & control + virology + + +
+ + + + 2016 + 05 + 30 + + + 2016 + 06 + 22 + + + 2017 + 02 + 25 + + + 2016 + 6 + 30 + 6 + 0 + + + 2016 + 6 + 30 + 6 + 0 + + + 2016 + 9 + 28 + 6 + 0 + + + ppublish + + 27355570 + nature18952 + 10.1038/nature18952 + PMC5003703 + NIHMS797899 + + +
+ + + + + 27355410 + + 2016 + 06 + 29 + +
+ + 1533-4406 + + + 2016 + Jun + 29 + + + The New England journal of medicine + N. Engl. J. Med. + + Zika Virus. + + + + + To the Editor: Petersen et al. (April 21 issue)1provide a detailed review of Zika virus. We have some concern regarding diagnostic criteria for microcephaly in fetuses and newborns exposed to the virus. According to the Centers for Disease Control and Prevention (CDC) recommendation that microcephaly should be defined as an occipitofrontal circumference below the third percentile, nearly 3% of newborns would be categorized as having microcephaly. In Brazil, where there are 3 million live births per year, the application of this definition would result in nearly 90,000 infants being labeled as having microcephaly - a far greater number than . . . + + + + FitzSimmons + Jack + J + + Virtua Health, Voorhees, NJ. + + + + Shah + Shailen + S + + Virtua Health, Voorhees, NJ. + + + + eng + + Journal Article + + + 2016 + 06 + 29 + +
+ + United States + N Engl J Med + 0255562 + 0028-4793 + +
+ + + + 2016 + 6 + 30 + 6 + 0 + + + 2016 + 6 + 30 + 6 + 0 + + + 2016 + 6 + 30 + 6 + 0 + + + aheadofprint + + 27355410 + 10.1056/NEJMc1606769#SA1 + + +
+ + + + + 27348136 + + 2017 + 01 + 25 + + + 2017 + 08 + 01 + +
+ + 1557-7430 + + 35 + 8 + + 2016 + Aug + + + DNA and cell biology + DNA Cell Biol. + + Mechanisms of Zika Virus Infection and Neuropathogenesis. + + 367-72 + + 10.1089/dna.2016.3404 + + A spotlight has been focused on the mosquito-borne Zika virus (ZIKV) because of its epidemic outbreak in Brazil and Latin America, as well as the severe neurological manifestations of microcephaly and Guillain-Barré syndrome associated with infection. In this review, we discuss the recent literature on ZIKV-host interactions, including new mechanistic insight concerning the basis of ZIKV-induced neuropathogenesis. + + + + Olagnier + David + D + + 1 Lady Davis Institute, Jewish General Hospital, McGill University , Montreal, Canada . + + + + Muscolini + Michela + M + + 2 Istituto Pasteur-Fondazione Cenci Bolognetti , Rome, Italy . + + + + Coyne + Carolyn B + CB + + 3 Department of Microbiology and Molecular Genetics, University of Pittsburgh , Pittsburgh, Pennsylvania. + + + + Diamond + Michael S + MS + + 4 Department of Medicine, Washington University School of Medicine , St. Louis, Missouri. + + + 5 Department of Molecular Microbiology, Washington University School of Medicine , St. Louis, Missouri. + + + 6 Department of Pathology and Immunology, The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine , St. Louis, Missouri. + + + + Hiscott + John + J + + 2 Istituto Pasteur-Fondazione Cenci Bolognetti , Rome, Italy . + + + + eng + + Journal Article + + + 2016 + 06 + 27 + +
+ + United States + DNA Cell Biol + 9004522 + 1044-5498 + + IM + + + Cell Host Microbe. 2016 Jun 8;19(6):882-90 + 27212660 + + + Lancet. 2016 Apr 2;387(10026):1482 + 27115821 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Lancet. 2016 Mar 12;387(10023):1051 + 26944028 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Cell Stem Cell. 2016 May 5;18(5):591-6 + 27038591 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + J Mol Biol. 2016 Aug 28;428(17):3429-48 + 27130436 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + PLoS Negl Trop Dis. 2016 Apr 25;10(4):e0004687 + 27111294 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Cell Host Microbe. 2016 May 11;19(5):705-12 + 27066743 + + + Cell Host Microbe. 2016 May 11;19(5):561-5 + 27091703 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + Nat Med. 2016 Mar;22(3):225-7 + 26937612 + + + Cell Host Microbe. 2016 May 11;19(5):696-704 + 27158114 + + + Cell Stem Cell. 2016 Aug 4;19(2):258-65 + 27162029 + + + Medicine (Baltimore). 2016 Apr;95(14):e3257 + 27057874 + + + Nature. 2016 Apr 19;533(7603):425-8 + 27093288 + + + PLoS Pathog. 2013 Mar;9(3):e1003265 + 23555265 + + + Nature. 2013 Sep 19;501(7467):373-9 + 23995685 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + PLoS Negl Trop Dis. 2016 May 05;10(5):e0004658 + 27149521 + + + PLoS Negl Trop Dis. 2016 Apr 19;10(4):e0004682 + 27093158 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15672-7 + 26644564 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + Emerg Infect Dis. 2015 May;21(5):911-3 + 25898277 + + + Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12048-53 + 23818581 + + + Trans R Soc Trop Med Hyg. 1952 Nov;46(6):600-18 + 13005679 + + + Science. 2016 Apr 22;352(6284):467-70 + 27033547 + + + J Virol. 2009 Jun;83(11):5408-18 + 19279106 + + + Cell Host Microbe. 2016 Jul 13;20(1):83-90 + 27247001 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + Nature. 2016 May 11;534(7606):267-71 + 27279226 + + + Cell Res. 2016 Jun;26(6):645-54 + 27174054 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + PLoS Negl Trop Dis. 2016 May 10;10(5):e0004695 + 27163257 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + N Engl J Med. 2016 Apr 21;374(16):1595-6 + 26958738 + + + Cell Stem Cell. 2016 Jul 7;19(1):120-6 + 27179424 + + + + + Aedes + virology + + + Animals + + + Disease Outbreaks + + + Female + + + Fetus + + + Guillain-Barre Syndrome + epidemiology + etiology + pathology + virology + + + Host-Pathogen Interactions + + + Humans + + + Latin America + epidemiology + + + Microcephaly + epidemiology + etiology + pathology + virology + + + Mosquito Vectors + virology + + + Placenta + pathology + virology + + + Pregnancy + + + Virion + pathogenicity + physiology + + + Zika Virus + pathogenicity + physiology + + + Zika Virus Infection + complications + epidemiology + transmission + virology + + +
+ + + + 2016 + 6 + 28 + 6 + 0 + + + 2016 + 6 + 28 + 6 + 0 + + + 2017 + 1 + 26 + 6 + 0 + + + ppublish + + 27348136 + 10.1089/dna.2016.3404 + PMC4971419 + + +
+ + + + + 27344138 + + 2017 + 05 + 04 + + + 2017 + 12 + 19 + +
+ + 1096-0341 + + 496 + + 2016 + 09 + + + Virology + Virology + + The green tea molecule EGCG inhibits Zika virus entry. + + 215-218 + + S0042-6822(16)30154-4 + 10.1016/j.virol.2016.06.012 + + During ZIKV the outbreak in Brazil it was observed an increase of almost 20 times the number of reported cases of microcephaly in newborn babies. There is no vaccine or approved drug available for the treatment and prevention of infections by this virus. EGCG, a polyphenol present in green tea has been shown to have an antiviral activity for many viruses. In view of the need for the development of a drug against a Brazilian strain of ZIKV, we assessed the effect of EGCG on ZIKV entry in Vero E6 cells. The drug was capable of inhibiting the virus entry by at least 1-log (>90%) at higher concentrations (>100μM). The pre-treatment of cells with EGCG did not show any effect on virus attachment. This is the first study to demonstrate the effect of EGCG on ZIKV indicating that this drug might be possibility to be used for prevention of Zika virus infections. + Copyright © 2016 Elsevier Inc. All rights reserved. + + + + Carneiro + Bruno M + BM + + Laboratory of Genomic Studies, Sao Paulo State University - UNESP, São José do Rio Preto, SP, Brazil. Electronic address: brunocopo@yahoo.com.br. + + + + Batista + Mariana N + MN + + Laboratory of Genomic Studies, Sao Paulo State University - UNESP, São José do Rio Preto, SP, Brazil. + + + + Braga + Ana Cláudia S + ACS + + Laboratory of Genomic Studies, Sao Paulo State University - UNESP, São José do Rio Preto, SP, Brazil. + + + + Nogueira + Maurício L + ML + + Departamento de Doenças Infecciosas e Parasitárias, FAMERP, 15090-000 São José do Rio Preto, SP, Brazil. + + + + Rahal + Paula + P + + Laboratory of Genomic Studies, Sao Paulo State University - UNESP, São José do Rio Preto, SP, Brazil. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 06 + 23 + +
+ + United States + Virology + 0110674 + 0042-6822 + + + + 0 + Antiviral Agents + + + 0 + Plant Extracts + + + 0 + Tea + + + 8R1V1STN48 + Catechin + + + BQM438CTEL + epigallocatechin gallate + + + IM + + + Animals + + + Antiviral Agents + chemistry + pharmacology + + + Catechin + analogs & derivatives + chemistry + pharmacology + + + Cell Survival + + + Cells, Cultured + + + Cercopithecus aethiops + + + Dose-Response Relationship, Drug + + + Molecular Structure + + + Plant Extracts + chemistry + pharmacology + + + Tea + chemistry + + + Vero Cells + + + Virus Internalization + drug effects + + + Zika Virus + drug effects + physiology + + + + (−)-Epigallocatechin gallate + Antiviral + Green-tea + Zika virus + +
+ + + + 2016 + 05 + 16 + + + 2016 + 06 + 14 + + + 2016 + 06 + 15 + + + 2016 + 6 + 27 + 6 + 0 + + + 2016 + 6 + 28 + 6 + 0 + + + 2017 + 5 + 5 + 6 + 0 + + + ppublish + + 27344138 + S0042-6822(16)30154-4 + 10.1016/j.virol.2016.06.012 + + +
+ + + + + 27341420 + + 2017 + 03 + 30 + + + 2017 + 03 + 30 + +
+ + 1935-2735 + + 10 + 6 + + 2016 + 06 + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + Isolation of Infective Zika Virus from Urine and Saliva of Patients in Brazil. + + e0004816 + + 10.1371/journal.pntd.0004816 + + Zika virus (ZIKV) is an emergent threat provoking a worldwide explosive outbreak. Since January 2015, 41 countries reported autochthonous cases. In Brazil, an increase in Guillain-Barré syndrome and microcephaly cases was linked to ZIKV infections. A recent report describing low experimental transmission efficiency of its main putative vector, Ae. aegypti, in conjunction with apparent sexual transmission notifications, prompted the investigation of other potential sources of viral dissemination. Urine and saliva have been previously established as useful tools in ZIKV diagnosis. Here, we described the presence and isolation of infectious ZIKV particles from saliva and urine of acute phase patients in the Rio de Janeiro state, Brazil. + Nine urine and five saliva samples from nine patients from Rio de Janeiro presenting rash and other typical Zika acute phase symptoms were inoculated in Vero cell culture and submitted to specific ZIKV RNA detection and quantification through, respectively, NAT-Zika, RT-PCR and RT-qPCR. Two ZIKV isolates were achieved, one from urine and one from saliva specimens. ZIKV nucleic acid was identified by all methods in four patients. Whenever both urine and saliva samples were available from the same patient, urine viral loads were higher, corroborating the general sense that it is a better source for ZIKV molecular diagnostic. In spite of this, from the two isolated strains, each from one patient, only one derived from urine, suggesting that other factors, like the acidic nature of this fluid, might interfere with virion infectivity. The complete genome of both ZIKV isolates was obtained. Phylogenetic analysis revealed similarity with strains previously isolated during the South America outbreak. + The detection of infectious ZIKV particles in urine and saliva of patients during the acute phase may represent a critical factor in the spread of virus. The epidemiological relevance of this finding, regarding the contribution of alternative non-vectorial ZIKV transmission routes, needs further investigation. + + + + Bonaldo + Myrna C + MC + 0000-0001-9899-3386 + + Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + Ribeiro + Ieda P + IP + + Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + Lima + Noemia S + NS + + Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + Dos Santos + Alexandre A C + AA + + Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + Menezes + Lidiane S R + LS + + Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + da Cruz + Stephanie O D + SO + + Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + de Mello + Iasmim S + IS + + Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + Furtado + Nathália D + ND + + Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + de Moura + Elaine E + EE + + Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + Damasceno + Luana + L + + Laboratório de Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil. + + + + da Silva + Kely A B + KA + + Laboratório de Mosquitos Transmissores de Hematozoários, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + de Castro + Marcia G + MG + + Laboratório de Mosquitos Transmissores de Hematozoários, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + Gerber + Alexandra L + AL + + Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro, Brazil. + + + + de Almeida + Luiz G P + LG + + Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro, Brazil. + + + + Lourenço-de-Oliveira + Ricardo + R + + Laboratório de Mosquitos Transmissores de Hematozoários, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. + + + + Vasconcelos + Ana Tereza R + AT + + Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro, Brazil. + + + + Brasil + Patrícia + P + + Laboratório de Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + + + 2016 + 06 + 24 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + + + 0 + RNA, Viral + + + IM + + + PLoS Negl Trop Dis. 2016 Apr 12;10(4):e0004636 + 27070912 + + + Lancet. 2016 Mar 12;387(10023):1051 + 26944028 + + + Euro Surveill. 2014 Jan 30;19(4):null + 24507466 + + + Am J Trop Med Hyg. 1980 Mar;29(2):265-8 + 6989277 + + + PLoS One. 2014 Feb 21;9(2):e88803 + 24586397 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + J Virol. 1998 Jan;72(1):73-83 + 9420202 + + + J Gen Virol. 2016 Feb;97(2):269-73 + 26684466 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + PLoS One. 2014 Oct 13;9(10):e109442 + 25310102 + + + PLoS Negl Trop Dis. 2014 Feb 06;8(2):e2681 + 24516683 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + J Clin Microbiol. 1992 Mar;30(3):545-51 + 1372617 + + + J Gen Virol. 2006 Oct;87(Pt 10):2755-66 + 16963734 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + J Clin Microbiol. 2011 Feb;49(2):760-2 + 21106799 + + + J Med Virol. 2002 Jul;67(3):370-4 + 12116030 + + + Periodontol 2000. 2016 Feb;70(1):93-110 + 26662485 + + + Blood Transfus. 2016 Mar;14 (2):95-100 + 26674815 + + + Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19333-8 + 23129628 + + + Dent Clin North Am. 2011 Jan;55(1):159-78 + 21094724 + + + PLoS Negl Trop Dis. 2016 Mar 03;10(3):e0004543 + 26938868 + + + J Clin Microbiol. 2014 Sep;52(9):3411-3 + 24951801 + + + PLoS Negl Trop Dis. 2015 Sep 25;9(9):e0004100 + 26406240 + + + J Infect Dis. 1999 May;179 Suppl 3:S431-5 + 10099113 + + + Southeast Asian J Trop Med Public Health. 2015 May;46(3):460-4 + 26521519 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Trans R Soc Trop Med Hyg. 2007 Jul;101(7):738-9 + 17418320 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + Mol Biol Evol. 2016 Jul;33(7):1870-4 + 27004904 + + + Am J Trop Med Hyg. 2012 Jul;87(1):165-70 + 22764309 + + + Emerg Infect Dis. 2016 May;22(5):933-5 + 27088323 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + Wkly Epidemiol Rec. 2016 Feb 19;91(7):73-81 + 26897760 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Virol J. 2013 Oct 22;10:311 + 24148652 + + + J Clin Virol. 2015 Jul;68:53-5 + 26071336 + + + Virology. 1994 Jan;198(1):109-17 + 8259646 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Euro Surveill. 2016;21(10):null + 26987769 + + + Euro Surveill. 2016;21(9):null + 26967758 + + + Int J Exp Pathol. 1995 Apr;76(2):103-9 + 7786760 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Bioinformatics. 2007 Nov 1;23(21):2947-8 + 17846036 + + + Emerg Infect Dis. 2005 Aug;11(8):1294-6 + 16102323 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Adult + + + Aged + + + Brazil + epidemiology + + + Female + + + Genome, Viral + + + Humans + + + Middle Aged + + + Phylogeny + + + Pregnancy + + + RNA, Viral + classification + isolation & purification + + + Reverse Transcriptase Polymerase Chain Reaction + + + Saliva + virology + + + Young Adult + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + epidemiology + urine + + +
+ + + + 2016 + 03 + 19 + + + 2016 + 05 + 24 + + + 2016 + 6 + 25 + 6 + 0 + + + 2016 + 6 + 25 + 6 + 0 + + + 2017 + 3 + 31 + 6 + 0 + + + epublish + + 27341420 + 10.1371/journal.pntd.0004816 + PNTD-D-16-00500 + PMC4920388 + + +
+ + + + + 27338953 + + 2016 + 08 + 29 + + + 2018 + 02 + 14 + +
+ + 1476-4687 + + 536 + 7614 + + 2016 + 08 + 04 + + + Nature + Nature + + Structural basis of potent Zika-dengue virus antibody cross-neutralization. + + 48-53 + + 10.1038/nature18938 + + Zika virus is a member of the Flavivirus genus that had not been associated with severe disease in humans until the recent outbreaks, when it was linked to microcephaly in newborns in Brazil and to Guillain-Barré syndrome in adults in French Polynesia. Zika virus is related to dengue virus, and here we report that a subset of antibodies targeting a conformational epitope isolated from patients with dengue virus also potently neutralize Zika virus. The crystal structure of two of these antibodies in complex with the envelope protein of Zika virus reveals the details of a conserved epitope, which is also the site of interaction of the envelope protein dimer with the precursor membrane (prM) protein during virus maturation. Comparison of the Zika and dengue virus immunocomplexes provides a lead for rational, epitope-focused design of a universal vaccine capable of eliciting potent cross-neutralizing antibodies to protect simultaneously against both Zika and dengue virus infections. + + + + Barba-Spaeth + Giovanna + G + + + Dejnirattisai + Wanwisa + W + + + Rouvinski + Alexander + A + + + Vaney + Marie-Christine + MC + + + Medits + Iris + I + + + Sharma + Arvind + A + + + Simon-Lorière + Etienne + E + + + Sakuntabhai + Anavaj + A + + + Cao-Lormeau + Van-Mai + VM + + + Haouz + Ahmed + A + + + England + Patrick + P + + + Stiasny + Karin + K + + + Mongkolsapaya + Juthathip + J + + + Heinz + Franz X + FX + + + Screaton + Gavin R + GR + + + Rey + Félix A + FA + + + eng + + + MR/N012658/1 + Medical Research Council + United Kingdom + + + Medical Research Council + United Kingdom + + + G0801508 + Medical Research Council + United Kingdom + + + G0600000 + Medical Research Council + United Kingdom + + + G0400720 + Medical Research Council + United Kingdom + + + I 1378 + Austrian Science Fund FWF + Austria + + + + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 06 + 23 + +
+ + England + Nature + 0410462 + 0028-0836 + + + + 0 + Antibodies, Monoclonal + + + 0 + Antibodies, Neutralizing + + + 0 + Antigen-Antibody Complex + + + 0 + Dengue Vaccines + + + 0 + Epitopes + + + 0 + Viral Envelope Proteins + + + 0 + Viral Vaccines + + + IM + + + Nature. 2016 Nov 10;539(7628):314 + 27626374 + + + Nat Immunol. 2016 Aug 19;17 (9):1010-2 + 27540984 + + + Science. 2003 Oct 10;302(5643):248 + 14551429 + + + Nucleic Acids Res. 2010 Jul;38(Web Server issue):W695-9 + 20439314 + + + EMBO J. 2009 Oct 21;28(20):3269-76 + 19713934 + + + J Virol. 2014 Dec;88(23):13845-57 + 25253341 + + + J Struct Biol. 2013 Jul;183(1):86-94 + 23602814 + + + Protein Eng Des Sel. 2010 Apr;23(4):169-74 + 20100703 + + + Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501 + 20383002 + + + Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14 + 23793146 + + + J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674 + 19461840 + + + Nat Struct Mol Biol. 2013 Jan;20(1):105-10 + 23241927 + + + PLoS Pathog. 2013;9(6):e1003458 + 23818856 + + + Virology. 2015 May;479-480:508-17 + 25835729 + + + Nature. 2013 Jan 24;493(7433):552-6 + 23292515 + + + Lancet. 2012 Nov 3;380(9853):1559-67 + 22975340 + + + J Virol. 2013 Dec;87(24):13729-40 + 24109224 + + + Nucleic Acids Res. 2014 Jul;42(Web Server issue):W252-8 + 24782522 + + + Cell Host Microbe. 2016 May 11;19(5):696-704 + 27158114 + + + Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42 + 21460441 + + + J Virol. 2014 Jul;88(13):7210-20 + 24741083 + + + Protein Eng Des Sel. 2012 Feb;25(2):59-66 + 22160929 + + + PLoS Pathog. 2010 Feb 12;6(2):e1000790 + 20168989 + + + Nature. 2016 Apr 19;533(7603):425-8 + 27093288 + + + J Virol. 2006 Oct;80(19):9557-68 + 16973559 + + + Nat Immunol. 2015 Feb;16(2):170-7 + 25501631 + + + J Gen Virol. 1989 Jan;70 ( Pt 1):37-43 + 2543738 + + + Nature. 2007 Sep 6;449(7158):101-4 + 17805298 + + + Nature. 2015 Apr 2;520(7545):109-13 + 25581790 + + + Proc Natl Acad Sci U S A. 2007 May 29;104(22):9422-7 + 17517625 + + + J Infect Dis. 1979 Oct;140(4):527-33 + 117061 + + + Science. 2016 Apr 22;352(6284):467-70 + 27033547 + + + Lancet. 2014 Oct 11;384(9951):1358-65 + 25018116 + + + J Mol Biol. 2007 Sep 21;372(3):774-97 + 17681537 + + + J Virol. 2014 Oct;88(20):11726-37 + 25078693 + + + Nat Immunol. 2016 Sep;17 (9):1102-8 + 27339099 + + + J Virol. 2011 Nov;85(22):11567-80 + 21917960 + + + Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32 + 20124692 + + + Vaccine. 2016 Jun 3;34(26):2934-8 + 26973072 + + + Syst Biol. 2010 May;59(3):307-21 + 20525638 + + + Bioinformatics. 1999 Apr;15(4):305-8 + 10320398 + + + Cell Host Microbe. 2010 Sep 16;8(3):271-83 + 20833378 + + + Bioinformatics. 2007 Nov 1;23(21):2947-8 + 17846036 + + + EMBO Rep. 2011 Jun;12(6):602-6 + 21566648 + + + Cell. 2002 Mar 8;108(5):717-25 + 11893341 + + + + + Antibodies, Monoclonal + immunology + + + Antibodies, Neutralizing + immunology + + + Antigen-Antibody Complex + chemistry + immunology + + + Brazil + + + Cross Reactions + immunology + + + Crystallography, X-Ray + + + Dengue + immunology + + + Dengue Vaccines + chemistry + immunology + + + Dengue Virus + chemistry + immunology + + + Epitopes + chemistry + immunology + + + Humans + + + Models, Molecular + + + Phylogeny + + + Viral Envelope Proteins + chemistry + immunology + + + Viral Vaccines + chemistry + immunology + + + Zika Virus + chemistry + immunology + + + Zika Virus Infection + immunology + prevention & control + + +
+ + + + 2016 + 05 + 19 + + + 2016 + 06 + 17 + + + 2016 + 6 + 25 + 6 + 0 + + + 2016 + 6 + 25 + 6 + 0 + + + 2016 + 8 + 30 + 6 + 0 + + + ppublish + + 27338953 + nature18938 + 10.1038/nature18938 + + +
+ + + + + 27337505 + + 2016 + 09 + 29 + +
+ + 1545-861X + + 65 + 24 + + 2016 + Jun + 24 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Zika Virus Surveillance and Preparedness - New York City, 2015-2016. + + 629-635 + + 10.15585/mmwr.mm6524e3 + + Zika virus has rapidly spread through the World Health Organization's Region of the Americas since being identified in Brazil in early 2015. Transmitted primarily through the bite of infected Aedes species mosquitoes, Zika virus infection during pregnancy can cause spontaneous abortion and birth defects, including microcephaly (1,2). New York City (NYC) is home to a large number of persons who travel frequently to areas with active Zika virus transmission, including immigrants from these areas. In November 2015, the NYC Department of Health and Mental Hygiene (DOHMH) began developing and implementing plans for managing Zika virus and on February 1, 2016, activated its Incident Command System. During January 1-June 17, 2016, DOHMH coordinated diagnostic laboratory testing for 3,605 persons with travel-associated exposure, 182 (5.0%) of whom had confirmed Zika virus infection. Twenty (11.0%) confirmed patients were pregnant at the time of diagnosis. In addition, two cases of Zika virus-associated Guillain-Barré syndrome were diagnosed. DOHMH's response has focused on 1) identifying and diagnosing suspected cases; 2) educating the public and medical providers about Zika virus risks, transmission, and prevention strategies, particularly in areas with large populations of immigrants from areas with ongoing Zika virus transmission; 3) monitoring pregnant women with Zika virus infection and their fetuses and infants; 4) detecting local mosquito-borne transmission through both human and mosquito surveillance; and 5) modifying existing Culex mosquito control measures by targeting Aedes species of mosquitoes through the use of larvicides and adulticides. + + + + Lee + Christopher T + CT + + + Vora + Neil M + NM + + + Bajwa + Waheed + W + + + Boyd + Lorraine + L + + + Harper + Scott + S + + + Kass + Daniel + D + + + Langston + Aileen + A + + + McGibbon + Emily + E + + + Merlino + Mario + M + + + Rakeman + Jennifer L + JL + + + Raphael + Marisa + M + + + Slavinski + Sally + S + + + Tran + Anthony + A + + + Wong + Ricky + R + + + Varma + Jay K + JK + + + NYC Zika Response Team + + + eng + + Journal Article + + + 2016 + 06 + 24 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + + + Abraham + Bisrat + B + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Ackelsberg + Joel + J + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Antwi + Mike + M + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Balter + Sharon + S + + Division of Disease Control, New York City Department of and Mental Hygiene. + + + + Baumgartner + Jennifer + J + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Benowitz + Isaac + I + + Division of Disease Control, New York City Department of Health and Mental Hygiene, Epidemic Intelligence Service, CDC. + + + + Bernard + MarieAntoinette + MA + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Bocour + Angelica + A + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Borges + Christine + C + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Burzynski + Joseph + J + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Cone + JamesE + JE + + Division of Epidemiology, New York City Department of Health and Mental Hygiene. + + + + Davidson + Alexander + A + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Del Rosso + Paula + P + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Dentinger + Catherine + C + + Division of Disease Control, New York City Department of Health and Mental Hygiene, Office of Public Health Preparedness and Response, CDC. + + + + Deocharan + Bisram + B + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Dorsinville + Marie + M + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Ephross + Peter + P + + Division of Epidemiology, New York City Department of Health and Mental Hygiene. + + + + Ezeoke + Ifeoma + I + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Fine + Anne + A + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Fireteanu + AnaMaria + AM + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Fu + Jie + J + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Greene + SharonK + SK + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Hughes + Scott + S + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Iqbal + Maryam + M + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Jacobs-Wingo + Jasmine + J + + Office of Emergency Public Health Preparedness and Response, New York City Department of Health and Mental Hygiene, Office of Public Health Preparedness and Response, CDC. + + + + Johnson + Kimberly + K + + Division of Environmental Health, New York City Department of Health and Mental Hygiene. + + + + Jones + Lucretia + L + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Jordan + HannahT + HT + + Division of Epidemiology, New York City Department of Health and Mental Hygiene. + + + + Laraque + Fabienne + F + + Division of Disease Control, New York City Department of Health, and Mental Hygiene. + + + + Layton + Marcelle + M + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Lee + David + D + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Lee + Ellen + E + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Lee + Kristen + K + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Liu + Dakai + D + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Lucero + DavidE + DE + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Macaraig + Michelle + M + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + McIntosh + Natasha + N + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + McNamee + Paul + P + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Myers + Julie + J + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Ngai + Stephanie + S + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Papadopolous + Pete + P + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Parton + Hilary + H + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Peterson + Eric + E + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Pichardo + Carolina + C + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Pirillo + Robert + R + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Quinn + Celia + C + + Office of Emergency Preparedness and Response, New York City Department of Health and Mental Hygiene, Office of Public Health Preparedness and Response, CDC. + + + + Reddy + Vasudha + V + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Saffa + Alhaji + A + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Shaikh + Altaf + A + + Division of Informatics and Information Technology, New York City Department of Health and Mental Hygiene. + + + + Stoute + Alaina + A + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Tate + Anna + A + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Toro + Brian + B + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Tran + OliviaC + OC + + Division of Disease Control, New York City Department of Health, and Mental Hygiene. + + + + Vernetti + Elaine + E + + Office of Emergency Preparedness and Response, New York City Department of Health and Mental Hygiene. + + + + Weiss + Don + D + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Westheimer + Emily + E + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Wilson + Eliza + E + + Division of Disease Control, New York City Department of Health, and Mental Hygiene. + + + + Winters + Ann + A + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Wong + Marie + M + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Wu + WinfredY + WY + + Division of Prevention and Primary Care, New York City Department of Health and Mental Hygiene. + + + + Yang + David + D + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Younis + Mohammad + M + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + + Yung + Janette + J + + Division of Disease Control, New York City Department of Health and Mental Hygiene. + + + +
+ + + + 2016 + 6 + 24 + 6 + 0 + + + 2016 + 6 + 24 + 6 + 0 + + + 2016 + 6 + 24 + 6 + 0 + + + epublish + + 27337505 + 10.15585/mmwr.mm6524e3 + + +
+ + + + + 27337468 + + 2017 + 07 + 05 + + + 2017 + 12 + 13 + +
+ + 2165-0497 + + 4 + 3 + + 2016 + 06 + + + Microbiology spectrum + Microbiol Spectr + + Zika Virus Disease. + 10.1128/microbiolspec.EI10-0019-2016 + + The history of Zika virus disease serves as a paradigm of a typical emerging viral infection. Zika virus disease, a mosquito-borne flavivirus, was first isolated in 1947 in the Zika forest of Uganda. The same virus was also isolated from jungle-dwelling mosquitoes (Aedes [Stegomyia] africanus). In many areas of Africa and South Asia human infections with Zika virus were detected by both serology and virus isolation. About 80% of infections are asymptomatic, and in 20% a mostly mild disease with fever, rash, arthralgia, and conjunctivitis may occur. Fetal infections with malformations were not recorded in Africa or Asia. Zika virus was imported to northern Brazil possibly during the world soccer championship that was hosted by Brazil in June through July 2014. A cluster of severe fetal malformations with microcephaly and ocular defects was noted in 2015 in the northeast of Brazil, and intrauterine infections with Zika virus were confirmed. The dramatic change in Zika virus pathogenicity upon its introduction to Brazil has remained an enigma. + + + + Slenczka + Werner + W + + + eng + + Journal Article + Review + +
+ + United States + Microbiol Spectr + 101634614 + 2165-0497 + + IM + + + Aedes + virology + + + Africa + epidemiology + + + Animals + + + Asia + epidemiology + + + Brazil + epidemiology + + + Communicable Diseases, Emerging + epidemiology + pathology + + + Humans + + + Microcephaly + epidemiology + pathology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + epidemiology + pathology + + +
+ + + + 2016 + 6 + 24 + 6 + 0 + + + 2016 + 6 + 24 + 6 + 0 + + + 2017 + 7 + 6 + 6 + 0 + + + ppublish + + 27337468 + 10.1128/microbiolspec.EI10-0019-2016 + + +
+ + + + + 27337368 + + 2016 + 12 + 26 + + + 2016 + 12 + 30 + +
+ + 1545-861X + + 65 + 24 + + 2016 + Jun + 24 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Screening of Blood Donations for Zika Virus Infection - Puerto Rico, April 3-June 11, 2016. + + 627-8 + + 10.15585/mmwr.mm6524e2 + + Transfusion-transmitted infections have been documented for several arboviruses, including West Nile and dengue viruses (1). Zika virus, a flavivirus transmitted primarily by Aedes aegypti mosquitoes that has been identified as a cause of congenital microcephaly and other serious brain defects (2), became recognized as a potential threat to blood safety after reports from a 2013-2014 outbreak in French Polynesia. Blood safety concerns were based on very high infection incidence in the population at large during epidemics, the high percentage of persons with asymptomatic infection, the high proportion of blood donations with evidence of Zika virus nucleic acid upon retrospective testing, and an estimated 7-10-day period of viremia (3). At least one instance of transfusion transmission of Zika virus has been documented in Brazil after the virus emerged there, likely in 2014 (4). Rapid epidemic spread has followed to other areas of the Americas, including Puerto Rico. + + + + Kuehnert + Matthew J + MJ + + + Basavaraju + Sridhar V + SV + + + Moseley + Robin R + RR + + + Pate + Lisa L + LL + + + Galel + Susan A + SA + + + Williamson + Phillip C + PC + + + Busch + Michael P + MP + + + Alsina + Jose O + JO + + + Climent-Peris + Consuelo + C + + + Marks + Peter W + PW + + + Epstein + Jay S + JS + + + Nakhasi + Hira L + HL + + + Hobson + J Peyton + JP + + + Leiby + David A + DA + + + Akolkar + Pradip N + PN + + + Petersen + Lyle R + LR + + + Rivera-Garcia + Brenda + B + + + eng + + Journal Article + + + 2016 + 06 + 24 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + Blood Safety + methods + + + Disease Outbreaks + prevention & control + + + Humans + + + Mass Screening + + + Puerto Rico + epidemiology + + + Zika Virus Infection + prevention & control + + +
+ + + + 2016 + 6 + 24 + 6 + 0 + + + 2016 + 6 + 24 + 6 + 0 + + + 2016 + 12 + 27 + 6 + 0 + + + epublish + + 27337368 + 10.15585/mmwr.mm6524e2 + + +
+ + + + + 27336960 + + 2017 + 02 + 07 + + + 2017 + 02 + 07 + +
+ + 0019-1639 + + 72 + 2 + + 2016 Mar-Apr + + + Igiene e sanita pubblica + Ig Sanita Pubbl + + [Zika virus: a public health overview on epidemiology, clinical practice and prevention]. + + 161-80 + + + Zika virus is an arbovirus mainly transmitted by mosquitoes bites. During the last months, the attention of Public Health Institutions has been drawn by a significant increase of microcephaly cases in Brasil and analyses highlighted a connection between Zika virus infection in pregnant women and fetal microcephaly. Since 2015, many Zika virus outbreaks have been identified in South America and there is concern about the spread of the virus in areas where competent vectors are present. Nowadays, vaccination is not available and prevention is based on individual measures and on vectors control. This review of the most recent studies give an overview on the Zika problem. + + + + D'Alò + Gian Loreto + GL + + Scuola di specializzazione in Igiene e Medicina Preventiva Università degli studi di Roma Tor Vergata, Italia. + + + + Ciabattini + Marco + M + + Scuola di specializzazione in Igiene e Medicina Preventiva Università degli studi di Roma Tor Vergata, Italia. + + + + Zaratti + Laura + L + + Dipartimento di Biomedicina e Prevenzione Università degli Studi di Roma Tor Vergata, Italia. + + + + Franco + Elisabetta + E + + Dipartimento di Biomedicina e Prevenzione Università degli Studi di Roma Tor Vergata, Italia. + + + + ita + + Journal Article + Review + + Virus Zika: una panoramica di sanità pubblica su epidemiologia, clinica e prevenzione. +
+ + Italy + Ig Sanita Pubbl + 0373022 + 0019-1639 + + + + 0 + Viral Vaccines + + + IM + + + Animals + + + Brazil + epidemiology + + + Culicidae + virology + + + Disease Outbreaks + prevention & control + + + Female + + + Guillain-Barre Syndrome + virology + + + Humans + + + Insect Vectors + virology + + + Italy + epidemiology + + + Microcephaly + virology + + + Pregnancy + + + Public Health + + + Vaccination + methods + + + Viral Vaccines + administration & dosage + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + prevention & control + transmission + virology + + +
+ + + + 2016 + 6 + 24 + 6 + 0 + + + 2016 + 6 + 24 + 6 + 0 + + + 2017 + 2 + 9 + 6 + 0 + + + ppublish + + 27336960 + + +
+ + + + + 27332714 + + 2017 + 03 + 31 + + + 2017 + 03 + 31 + +
+ + 1935-2735 + + 10 + 6 + + 2016 + 06 + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + ZIKV - CDB: A Collaborative Database to Guide Research Linking SncRNAs and ZIKA Virus Disease Symptoms. + + e0004817 + + 10.1371/journal.pntd.0004817 + + In early 2015, a ZIKA Virus (ZIKV) infection outbreak was recognized in northeast Brazil, where concerns over its possible links with infant microcephaly have been discussed. Providing a causal link between ZIKV infection and birth defects is still a challenge. MicroRNAs (miRNAs) are small noncoding RNAs (sncRNAs) that regulate post-transcriptional gene expression by translational repression, and play important roles in viral pathogenesis and brain development. The potential for flavivirus-mediated miRNA signalling dysfunction in brain-tissue development provides a compelling hypothesis to test the perceived link between ZIKV and microcephaly. + Here, we applied in silico analyses to provide novel insights to understand how Congenital ZIKA Syndrome symptoms may be related to an imbalance in miRNAs function. Moreover, following World Health Organization (WHO) recommendations, we have assembled a database to help target investigations of the possible relationship between ZIKV symptoms and miRNA-mediated human gene expression. + We have computationally predicted both miRNAs encoded by ZIKV able to target genes in the human genome and cellular (human) miRNAs capable of interacting with ZIKV genomes. Our results represent a step forward in the ZIKV studies, providing new insights to support research in this field and identify potential targets for therapy. + + + + Pylro + Victor Satler + VS + + Biosystems Informatics and Genomics Group, René Rachou Research Center (CPqRR-FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. + + + + Oliveira + Francislon Silva + FS + + Biosystems Informatics and Genomics Group, René Rachou Research Center (CPqRR-FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. + + + + Morais + Daniel Kumazawa + DK + + Biosystems Informatics and Genomics Group, René Rachou Research Center (CPqRR-FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. + + + + Cuadros-Orellana + Sara + S + + Biosystems Informatics and Genomics Group, René Rachou Research Center (CPqRR-FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. + + + + Pais + Fabiano Sviatopolk-Mirsky + FS + + Biosystems Informatics and Genomics Group, René Rachou Research Center (CPqRR-FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. + + + + Medeiros + Julliane Dutra + JD + + Biosystems Informatics and Genomics Group, René Rachou Research Center (CPqRR-FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. + + + + Geraldo + Juliana Assis + JA + + Biosystems Informatics and Genomics Group, René Rachou Research Center (CPqRR-FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. + + + + Gilbert + Jack + J + + Department of Ecology and Evolution, The University of Chicago, Chicago, Illinois, United States of America. + + + Argonne National Laboratory, Institute for Genomic and Systems Biology, Argonne, Illinois, United States of America. + + + Department of Surgery, The University of Chicago, Chicago, Illinois, United States of America. + + + + Volpini + Angela Cristina + AC + + Biosystems Informatics and Genomics Group, René Rachou Research Center (CPqRR-FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. + + + + Fernandes + Gabriel Rocha + GR + + Biosystems Informatics and Genomics Group, René Rachou Research Center (CPqRR-FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 06 + 22 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + + + 0 + MicroRNAs + + + 0 + RNA, Viral + + + IM + + + J Biol Chem. 2013 May 17;288(20):14522-30 + 23572525 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Annu Rev Microbiol. 2010;64:123-41 + 20477536 + + + Sci Rep. 2015 May 26;5:9912 + 26011078 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Biochim Biophys Acta. 2006 Dec;1763(12 ):1733-48 + 17055079 + + + Nucleic Acids Res. 2014 Jan;42(Database issue):D749-55 + 24316576 + + + Curr Mol Med. 2011 Mar;11(2):93-109 + 21342132 + + + Lancet. 2015 Nov 7;386(10006):1797-8 + 26843294 + + + BMC Bioinformatics. 2013;14 Suppl 14:S9 + 24267009 + + + Cell. 2006 Mar 10;124(5):877-81 + 16530032 + + + PLoS Pathog. 2012 Dec;8(12):e1003018 + 23308061 + + + Neuron. 2010 Jan 28;65(2):191-203 + 20152126 + + + Genome Res. 2009 Jan;19(1):92-105 + 18955434 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + Proc Natl Acad Sci U S A. 2012 Feb 21;109 (8):3077-82 + 22308400 + + + Trends Cell Biol. 2011 Aug;21(8):470-80 + 21632253 + + + BMC Bioinformatics. 2009 Jan 30;10 Suppl 1:S35 + 19208136 + + + Retrovirology. 2013 Feb 07;10:15 + 23391025 + + + Hum Mol Genet. 2013 Dec 20;22(25):5199-214 + 23918663 + + + Nucleic Acids Res. 2012 Mar;40(5):2210-23 + 22080551 + + + Genome Biol. 2003;5(1):R1 + 14709173 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Nucleic Acids Res. 2016 Jul 8;44(W1):W242-5 + 27095192 + + + + + Databases, Factual + + + Genome, Viral + + + Humans + + + MicroRNAs + genetics + + + Phylogeny + + + RNA, Viral + genetics + + + Zika Virus + genetics + + + Zika Virus Infection + pathology + virology + + +
+ + + + 2016 + 03 + 18 + + + 2016 + 06 + 07 + + + 2016 + 6 + 23 + 6 + 0 + + + 2016 + 6 + 23 + 6 + 0 + + + 2017 + 4 + 1 + 6 + 0 + + + epublish + + 27332714 + 10.1371/journal.pntd.0004817 + PNTD-D-16-00496 + PMC4917180 + + +
+ +
+ + + + + 27330653 + + 2017 + 06 + 22 + + + 2017 + 06 + 22 + +
+ + 1936-9018 + + 17 + 3 + + 2016 + May + + + The western journal of emergency medicine + West J Emerg Med + + Identify-Isolate-Inform: A Tool for Initial Detection and Management of Zika Virus Patients in the Emergency Department. + + 238-44 + + 10.5811/westjem.2016.3.30188 + + First isolated in 1947 from a monkey in the Zika forest in Uganda, and from mosquitoes in the same forest the following year, Zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. More than one million people have been infected since the appearance of the virus in Brazil in 2015. Approximately 80% of infected patients are asymptomatic. An association with microcephaly and other birth defects as well as Guillain-Barre Syndrome has led to a World Health Organization declaration of Zika virus as a Public Health Emergency of International Concern in February 2016. Zika virus is a vector-borne disease transmitted primarily by the Aedes aegypti mosquito. Male to female sexual transmission has been reported and there is potential for transmission via blood transfusions. After an incubation period of 2-7 days, symptomatic patients develop rapid onset fever, maculopapular rash, arthralgia, and conjunctivitis, often associated with headache and myalgias. Emergency department (ED) personnel must be prepared to address concerns from patients presenting with symptoms consistent with acute Zika virus infection, especially those who are pregnant or planning travel to Zika-endemic regions, as well as those women planning to become pregnant and their partners. The identify-isolate-inform (3I) tool, originally conceived for initial detection and management of Ebola virus disease patients in the ED, and later adjusted for measles and Middle East Respiratory Syndrome, can be adapted for real-time use for any emerging infectious disease. This paper reports a modification of the 3I tool for initial detection and management of patients under investigation for Zika virus. Following an assessment of epidemiologic risk, including travel to countries with mosquitoes that transmit Zika virus, patients are further investigated if clinically indicated. If after a rapid evaluation, Zika or other arthropod-borne diseases are the only concern, isolation (contact, droplet, airborne) is unnecessary. Zika is a reportable disease and thus appropriate health authorities must be notified. The modified 3I tool will facilitate rapid analysis and triggering of appropriate actions for patients presenting to the ED at risk for Zika. + + + + Koenig + Kristi L + KL + + University of California Irvine Medical Center, Department of Emergency Medicine, Center for Disaster Medical Sciences, Orange, California. + + + + Almadhyan + Abdulmajeed + A + + University of California Irvine Medical Center, Department of Emergency Medicine, Center for Disaster Medical Sciences, Orange, California; Qassim University, Department of Emergency Medicine, Saudi Arabia. + + + + Burns + Michael J + MJ + + University of California Irvine Medical Center, Department of Emergency Medicine and Department of Medicine, Division of Infectious Diseases, Orange, California. + + + + eng + + Journal Article + + + 2016 + 04 + 04 + +
+ + United States + West J Emerg Med + 101476450 + 1936-900X + + IM + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Ann Emerg Med. 2015 Mar;65(3):330-1 + 25499243 + + + Disaster Med Public Health Prep. 2015 Oct;9(5):547-53 + 25797363 + + + Disaster Med Public Health Prep. 2015 Feb;9(1):86-7 + 25351772 + + + JAMA. 2016 Mar 1;315(9):865-6 + 26818622 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + West J Emerg Med. 2015 Mar;16(2):212-9 + 25834659 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + West J Emerg Med. 2015 Sep;16(5):619-24 + 26587081 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Emerg Infect Dis. 2016 May;22(5):925-7 + 27089120 + + + West J Emerg Med. 2014 Nov;15(7):728-31 + 25493109 + + + Disaster Med Public Health Prep. 2015 Feb;9(1):57-8 + 25351634 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):122-7 + 26866840 + + + + + Communicable Disease Control + methods + + + Decision Support Techniques + + + Diagnosis, Differential + + + Disease Outbreaks + prevention & control + statistics & numerical data + + + Disease Transmission, Infectious + prevention & control + + + Emergency Service, Hospital + + + Female + + + Guideline Adherence + + + Humans + + + Infectious Disease Transmission, Vertical + prevention & control + + + Male + + + Patient Isolation + methods + + + Population Surveillance + + + Practice Guidelines as Topic + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + prevention & control + therapy + virology + + + Travel + + + World Health Organization + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + prevention & control + therapy + transmission + + +
+ + + + 2016 + 02 + 24 + + + 2016 + 03 + 21 + + + 2016 + 6 + 23 + 6 + 0 + + + 2016 + 6 + 23 + 6 + 0 + + + 2017 + 6 + 24 + 6 + 0 + + + ppublish + + 27330653 + 10.5811/westjem.2016.3.30188 + wjem-17-238 + PMC4899052 + + +
+ + + + + 27317825 + + 2016 + 09 + 06 + + + 2016 + 06 + 19 + +
+ + 1293-8505 + + 222 + + 2016 Jun-Jul + + + Revue de l'infirmiere + Rev Infirm + + Consequences of the Zika Outbreak in Brazil. + + 41-2 + + 10.1016/j.revinf.2016.04.012 + S1293-8505(16)30012-4 + + The Zika virus has been spreading in South America for almost a year. Sophie and Pierre are spending a month in Recife, Brazil, to help out at a local health organisation. + Copyright © 2016 Elsevier Masson SAS. All rights reserved. + + + + Clavagnier + Isabelle + I + + Lycée des métiers de la santé et du social François Rabelais, Ifsi, 9, rue Francis-de-Croisset, 75018 Paris, France. Electronic address: isabelle.clavagnier@laposte.net. + + + + eng + + Journal Article + +
+ + France + Rev Infirm + 1267175 + 1293-8505 + + N + + + Animals + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Humans + + + Infectious Disease Transmission, Vertical + + + Microcephaly + virology + + + Poverty Areas + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Zika Virus Infection + epidemiology + transmission + + +
+ + + + 2016 + 6 + 19 + 6 + 0 + + + 2016 + 6 + 19 + 6 + 0 + + + 2016 + 9 + 7 + 6 + 0 + + + ppublish + + 27317825 + S1293-8505(16)30012-4 + 10.1016/j.revinf.2016.04.012 + + +
+ + + + + 27316349 + + 2017 + 08 + 31 + + + 2017 + 08 + 31 + +
+ + 1097-0223 + + 36 + 8 + + 2016 + Aug + + + Prenatal diagnosis + Prenat. Diagn. + + First-trimester intrauterine Zika virus infection and brain pathology: prenatal and postnatal neuroimaging findings. + + 785-9 + + 10.1002/pd.4860 + + + Werner + Heron + H + + Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, RJ, Brazil. + + + + Sodré + Danielle + D + + Department of Obstetrics and Gynecology, Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil. + + + + Hygino + Celso + C + + Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, RJ, Brazil. + + + + Guedes + Bianca + B + + Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, RJ, Brazil. + + + + Fazecas + Tatiana + T + + Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, RJ, Brazil. + + + + Nogueira + Renata + R + + Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, RJ, Brazil. + + + + Daltro + Pedro + P + + Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI), Rio de Janeiro, RJ, Brazil. + + + + Tonni + Gabriele + G + + Department of Obstetrics and Gynecology, Guastalla Civil Hospital, AUSL Reggio Emilia, Italy. + + + + Lopes + Jorge + J + + Department of Arts and Design, Pontifícia Universidade Católica (PUC Rio), Rio de Janeiro, RJ, Brazil. + + + + Araujo Júnior + Edward + E + + Department of Obstetrics, Paulista School of Medicine Federal University of São Paulo (EPM-UNIFESP), São Paulo, SP, Brazil. + + + + eng + + Case Reports + Journal Article + + + 2016 + 07 + 21 + +
+ + England + Prenat Diagn + 8106540 + 0197-3851 + + + Colpocephaly + + IM + + + Adult + + + Brain + diagnostic imaging + + + Brain Diseases + diagnostic imaging + + + Calcinosis + diagnostic imaging + + + Female + + + Humans + + + Hydrocephalus + diagnostic imaging + + + Imaging, Three-Dimensional + + + Infant, Newborn + + + Lateral Ventricles + abnormalities + diagnostic imaging + + + Lissencephaly + diagnostic imaging + + + Magnetic Resonance Imaging + + + Male + + + Microcephaly + diagnostic imaging + + + Neuroimaging + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Pregnancy Trimester, First + + + Printing, Three-Dimensional + + + Tomography, X-Ray Computed + + + Ultrasonography, Prenatal + + + Zika Virus Infection + congenital + diagnostic imaging + + +
+ + + + 2016 + 04 + 18 + + + 2016 + 06 + 13 + + + 2016 + 06 + 14 + + + 2016 + 6 + 19 + 6 + 0 + + + 2016 + 6 + 19 + 6 + 0 + + + 2017 + 9 + 1 + 6 + 0 + + + ppublish + + 27316349 + 10.1002/pd.4860 + + +
+ + + + + 27314996 + + 2017 + 01 + 10 + + + 2017 + 01 + 11 + +
+ + 0717-6341 + + 33 + 2 + + 2016 + Apr + + + Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia + Rev Chilena Infectol + + [Zika virus, guilty or innocent?]. + + 189-90 + + 10.4067/S0716-10182016000200008 + S0716-10182016000200008 + + + Perret + Cecilia + C + + + spa + + Journal Article + + Virus Zika, ¿culpable o inocente? +
+ + Chile + Rev Chilena Infectol + 9305754 + 0716-1018 + + IM + + + Brazil + + + Guillain-Barre Syndrome + virology + + + Humans + + + Microcephaly + virology + + + Risk Factors + + + Zika Virus + pathogenicity + + + Zika Virus Infection + complications + transmission + + +
+ + + + 2016 + 6 + 18 + 6 + 0 + + + 2016 + 6 + 18 + 6 + 0 + + + 2017 + 1 + 11 + 6 + 0 + + + ppublish + + 27314996 + S0716-10182016000200008 + 10.4067/S0716-10182016000200008 + + +
+ + + + + 27288540 + + 2018 + 02 + 07 + + + 2018 + 02 + 07 + +
+ + 1878-0067 + + 15 + + 2016 + Jun + + + Epidemics + Epidemics + + A theoretical estimate of the risk of microcephaly during pregnancy with Zika virus infection. + + 66-70 + + 10.1016/j.epidem.2016.03.001 + S1755-4365(16)30009-3 + + There has been a growing concern over Zika virus (ZIKV) infection, particularly since a probable link between ZIKV infection during pregnancy and microcephaly in the baby was identified. The present study aimed to estimate a theoretical risk of microcephaly during pregnancy with ZIKV infection in Northeastern Brazil in 2015. + Temporal distributions of microcephaly, reported dengue-like illness and dengue seropositive in Brazil were extracted from secondary data sources. Using an integral equation model and a backcalculation technique, we estimated the risk of microcephaly during pregnancy with Zika virus infection. + If the fraction of Zika virus infections among a total of seronegative dengue-like illness cases is 30%, the risk of microcephaly following infection during the first trimester was estimated at 46.7% (95% CI: 9.1, 84.2), comparable to the risk of congenital rubella syndrome. However, the risk of microcephaly was shown to vary widely from 14.0% to 100%. The mean gestational age at delivery with microcephaly was estimated at 37.5 weeks (95% CI: 36.9, 39.3). + The time interval between peaks of reported dengue-like illness and microcephaly was consistent with cause-outcome relationship. Our modeling framework predicts that the incidence of microcephaly is expected to steadily decline in early 2016, Brazil. + Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved. + + + + Nishiura + Hiroshi + H + + Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1130033, Japan; CREST, Japan Science and Technology Agency, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan; Graduate School of Medicine, Hokkaido University, Kita 15 Jo Nishi 7 Chome, Kita-ku, Sapporo-shi, Hokkaido 060-8638, Japan. Electronic address: nishiurah@gmail.com. + + + + Mizumoto + Kenji + K + + Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1130033, Japan; Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 1538902, Japan; Graduate School of Medicine, Hokkaido University, Kita 15 Jo Nishi 7 Chome, Kita-ku, Sapporo-shi, Hokkaido 060-8638, Japan. + + + + Rock + Kat S + KS + + Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1130033, Japan. + + + + Yasuda + Yohei + Y + + Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1130033, Japan; CREST, Japan Science and Technology Agency, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan. + + + + Kinoshita + Ryo + R + + Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1130033, Japan; CREST, Japan Science and Technology Agency, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan; Graduate School of Medicine, Hokkaido University, Kita 15 Jo Nishi 7 Chome, Kita-ku, Sapporo-shi, Hokkaido 060-8638, Japan. + + + + Miyamatsu + Yuichiro + Y + + Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1130033, Japan; CREST, Japan Science and Technology Agency, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan; Graduate School of Medicine, Hokkaido University, Kita 15 Jo Nishi 7 Chome, Kita-ku, Sapporo-shi, Hokkaido 060-8638, Japan. + + + + eng + + Journal Article + + + 2016 + 03 + 18 + +
+ + Netherlands + Epidemics + 101484711 + 1878-0067 + + IM + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Retrospective Studies + + + Risk Assessment + + + Zika Virus Infection + diagnosis + epidemiology + transmission + + + + Brazil + Gestation + Microcephaly + Statistical estimation + Zika infection + +
+ + + + 2016 + 02 + 22 + + + 2016 + 03 + 05 + + + 2016 + 03 + 07 + + + 2016 + 6 + 12 + 6 + 0 + + + 2016 + 6 + 12 + 6 + 0 + + + 2018 + 2 + 8 + 6 + 0 + + + ppublish + + 27288540 + S1755-4365(16)30009-3 + 10.1016/j.epidem.2016.03.001 + + +
+ + + + + 27287830 + + 2016 + 08 + 01 + + + 2016 + 06 + 29 + +
+ + 1474-547X + + 387 + 10037 + + 2016 + Jun + 18 + + + Lancet (London, England) + Lancet + + Zika: neurological and ocular findings in infant without microcephaly. + + 2502 + + 10.1016/S0140-6736(16)30776-0 + S0140-6736(16)30776-0 + + + Ventura + Camila V + CV + + Altino Ventura Foundation, Recife, Brazil; Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of São Paulo and Vision Institute, São Paulo, Brazil. + + + + Maia + Mauricio + M + + HOPE Eye Hospital, Recife, Brazil. + + + + Dias + Natalia + N + + Altino Ventura Foundation, Recife, Brazil. + + + + Ventura + Liana O + LO + + Altino Ventura Foundation, Recife, Brazil; Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of São Paulo and Vision Institute, São Paulo, Brazil. + + + + Belfort + Rubens + R + Jr + + HOPE Eye Hospital, Recife, Brazil. Electronic address: clinbelf@uol.com.br. + + + + eng + + Case Reports + Letter + + + 2016 + 06 + 07 + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Central Nervous System Viral Diseases + virology + + + Eye Infections, Viral + virology + + + Humans + + + Infant + + + Spasms, Infantile + virology + + + Zika Virus Infection + + +
+ + + + 2016 + 6 + 12 + 6 + 0 + + + 2016 + 6 + 12 + 6 + 0 + + + 2016 + 8 + 2 + 6 + 0 + + + ppublish + + 27287830 + S0140-6736(16)30776-0 + 10.1016/S0140-6736(16)30776-0 + + +
+ + + + + 27283140 + + 2017 + 02 + 24 + + + 2017 + 02 + 24 + +
+ + 2092-7193 + + 38 + + 2016 + + + Epidemiology and health + Epidemiol Health + + Zika: what we do and do not know based on the experiences of Brazil. + + e2016023 + + 10.4178/epih.e2016023 + + Zika virus, which was first discovered in 1947, has become a global threat to human health as it is rapidly spreading through Latin America, the Caribbean, the US and Asia, after causing a large outbreak in the Northeast region of Brazil in 2015. There is ample evidence to support that Zika virus is associated with neurological complications such as microcephaly. The review aims to provide an overview on the complex issues involved in the emergence of Zika virus's neurological disorders and to discuss possible explanations of Zika virus introduction and dissemination in Brazil. We also suggest national and global strategies to adequately respond to the Zika virus emergence. + We provide an analytical evaluation of the main issues related to the Zika outbreak in Brazil, based on available scientific literature, including government documents, and on epidemiological information from national surveillance databases. + The studies on the clinical manifestations of the Zika virus infection coupled with the epidemiological surveillance information in Brazil have provided significant evidence that the Zika virus is associated with neurological disorders such as microcephaly and Guillain-Barré syndrome. Based on phylogenetic and molecular analysis, the hypothesis regarding the introduction of Zika virus in the country is that it took place following international events in 2013 and 2014, when many foreign visitors could have brought Zika virus into Brazil. The immunologically naïve status of populations in the Americas, previous infection with dengue virus, and the increased activity of Aedes aegypti might be the contributing factors for such an outbreak in Brazil. The Zika virus emergence emphasized the importance of cross-disciplinary perspective. Besides the scientific-based vector control strategies, it is important to understand the nature of the evolutionary processes involved in the viral evolution in complex ecosystems and to have social and anthropological knowledge on the conditions related to the spread of the disease in order to properly respond to the spread of the Zika virus. + The experiences of Brazil have demonstrated the significance of multi-disciplinary approach in response to new and resurgent arboviral diseases and provided important lessons that could be applied to other developing countries. + + + + Possas + Cristina + C + 0000-0002-2886-2812 + + Bio-Manguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + Review + + + 2016 + 05 + 31 + +
+ + Korea (South) + Epidemiol Health + 101519472 + 2092-7193 + + IM + + + PLoS Negl Trop Dis. 2014 Feb 06;8(2):e2681 + 24516683 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + MMWR Morb Mortal Wkly Rep. 2016 Apr 15;65(14):372-4 + 27078057 + + + Obstet Gynecol. 2016 Apr;127(4):642-8 + 26889662 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + PLoS Negl Trop Dis. 2016 Jun 24;10(6):e0004816 + 27341420 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Cad Saude Publica. 2001 Jan-Feb;17(1):31-41 + 11241925 + + + Arq Bras Oftalmol. 2016 Feb;79(1):63 + 26840174 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Cell Host Microbe. 2016 Jun 8;19(6):771-4 + 27156023 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Braz J Infect Dis. 2016 May-Jun;20(3):282-9 + 27102780 + + + Lancet. 2016 Jan 16;387(10015):227-8 + 26775124 + + + Lancet Infect Dis. 2016 Mar;16(3):278-9 + 26852727 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + BMJ. 2016 Feb 04;352:i720 + 26848011 + + + + + Aedes + virology + + + Animals + + + Brazil + epidemiology + + + Developing Countries + statistics & numerical data + + + Disease Outbreaks + statistics & numerical data + + + Evolution, Molecular + + + Global Health + + + Guillain-Barre Syndrome + epidemiology + virology + + + Humans + + + Microcephaly + epidemiology + virology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + transmission + + + + Epidemiology + Guillain-Barré syndrome + Immunity + Microcephaly + Pathogenesis + Zika virus + +
+ + + + 2016 + 05 + 12 + + + 2016 + 05 + 22 + + + 2016 + 6 + 11 + 6 + 0 + + + 2016 + 6 + 11 + 6 + 0 + + + 2017 + 2 + 25 + 6 + 0 + + + epublish + + 27283140 + 10.4178/epih.e2016023 + epih.e2016023 + PMC4974447 + + +
+ + + + + 27281741 + + 2016 + 12 + 13 + + + 2017 + 07 + 14 + +
+ + 1098-6618 + + 29 + 3 + + 2016 + Jul + + + Clinical microbiology reviews + Clin. Microbiol. Rev. + + Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes. + + 659-94 + + 10.1128/CMR.00014-16 + + The rapid spread of the Zika virus (ZIKV) in the Americas and its potential association with thousands of suspected cases of microcephaly in Brazil and higher rates of Guillain-Barré syndrome meet the conditions for a Public Health Emergency of International Concern, as stated by the World Health Organization in February 2016. Two months later, the Centers for Disease Control and Prevention (CDC) announced that the current available evidence supports the existence of a causal relationship between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Microcephaly can be caused by several factors, and its clinical course and prognosis are difficult to predict. Other pathogens with proven teratogenicity have been identified long before the current ZIKV epidemic. Despite the growing number of cases with maternal signs of infection and/or presence of ZIKV in tissues of affected newborns or fetuses, it is currently difficult to assess the magnitude of increase of microcephaly prevalence in Brazil, as well as the role of other factors in the development of congenital neurological conditions. Meanwhile, health agencies and medical organizations have issued cautious guidelines advising health care practitioners and expectant couples traveling to, returning from, or living in affected areas. Analogous to dengue virus (DENV) epidemics, ZIKV has the potential to become endemic in all countries infested by Aedes mosquitoes, while new mutations could impact viral replication in humans, leading to increased virulence and consequently heightened chances of viral transmission to additional naive mosquito vectors. Studies are urgently needed to answer the questions surrounding ZIKV and its role in congenital neurological conditions. + Copyright © 2016, American Society for Microbiology. All Rights Reserved. + + + + Panchaud + Alice + A + + School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva, Switzerland Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA Swiss Teratogen Information Service and Division of Clinical Pharmacology, University of Lausanne and University Hospital, Lausanne, Switzerland. + + + + Stojanov + Miloš + M + + Institute of Microbiology, Faculty of Biology and Medicine, University of Lausanne and University Hospital, Lausanne, Switzerland Materno-fetal and Obstetrics Research Unit, Department Femme-Mère-Enfant, University of Lausanne and University Hospital, Lausanne, Switzerland. + + + + Ammerdorffer + Anne + A + + Institute of Microbiology, Faculty of Biology and Medicine, University of Lausanne and University Hospital, Lausanne, Switzerland Materno-fetal and Obstetrics Research Unit, Department Femme-Mère-Enfant, University of Lausanne and University Hospital, Lausanne, Switzerland. + + + + Vouga + Manon + M + + Institute of Microbiology, Faculty of Biology and Medicine, University of Lausanne and University Hospital, Lausanne, Switzerland Materno-fetal and Obstetrics Research Unit, Department Femme-Mère-Enfant, University of Lausanne and University Hospital, Lausanne, Switzerland. + + + + Baud + David + D + + Institute of Microbiology, Faculty of Biology and Medicine, University of Lausanne and University Hospital, Lausanne, Switzerland Materno-fetal and Obstetrics Research Unit, Department Femme-Mère-Enfant, University of Lausanne and University Hospital, Lausanne, Switzerland david.baud@chuv.ch. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + Review + +
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+ + + + 2016 + 6 + 10 + 6 + 0 + + + 2016 + 6 + 10 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + ppublish + + 27281741 + 29/3/659 + 10.1128/CMR.00014-16 + PMC4978612 + + +
+ + + + + 27279226 + + 2016 + 07 + 06 + + + 2017 + 04 + 18 + +
+ + 1476-4687 + + 534 + 7606 + + 2016 + 06 + 09 + + + Nature + Nature + + The Brazilian Zika virus strain causes birth defects in experimental models. + + 267-71 + + 10.1038/nature18296 + + Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment. + + + + Cugola + Fernanda R + FR + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo 05508-270, Brazil. + + + + Fernandes + Isabella R + IR + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo 05508-270, Brazil. + + + University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular &Molecular Medicine, Stem Cell Program, La Jolla, California 92037-0695, USA. + + + + Russo + Fabiele B + FB + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo 05508-270, Brazil. + + + Tismoo, The Biotech Company, São Paulo, São Paulo 01401-000, Brazil. + + + + Freitas + Beatriz C + BC + + University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular &Molecular Medicine, Stem Cell Program, La Jolla, California 92037-0695, USA. + + + + Dias + João L M + JL + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo 05508-270, Brazil. + + + + Guimarães + Katia P + KP + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo 05508-270, Brazil. + + + + Benazzato + Cecília + C + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo 05508-270, Brazil. + + + + Almeida + Nathalia + N + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo 05508-270, Brazil. + + + + Pignatari + Graciela C + GC + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo 05508-270, Brazil. + + + Tismoo, The Biotech Company, São Paulo, São Paulo 01401-000, Brazil. + + + + Romero + Sarah + S + + University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular &Molecular Medicine, Stem Cell Program, La Jolla, California 92037-0695, USA. + + + + Polonio + Carolina M + CM + + University of São Paulo, Department of Immunology, Neuroimmune Interactions Laboratory, São Paulo, São Paulo 05508-000, Brazil. + + + + Cunha + Isabela + I + + University of São Paulo, Department of Immunology, Neuroimmune Interactions Laboratory, São Paulo, São Paulo 05508-000, Brazil. + + + + Freitas + Carla L + CL + + University of São Paulo, Department of Immunology, Neuroimmune Interactions Laboratory, São Paulo, São Paulo 05508-000, Brazil. + + + + Brandão + Wesley N + WN + + University of São Paulo, Department of Immunology, Neuroimmune Interactions Laboratory, São Paulo, São Paulo 05508-000, Brazil. + + + + Rossato + Cristiano + C + + University of São Paulo, Department of Immunology, Neuroimmune Interactions Laboratory, São Paulo, São Paulo 05508-000, Brazil. + + + + Andrade + David G + DG + + University of São Paulo, Department of Immunology, Neuroimmune Interactions Laboratory, São Paulo, São Paulo 05508-000, Brazil. + + + + Faria + Daniele de P + Dde P + + University of São Paulo, Department of Radiology and Oncology, USP School of Medicine, São Paulo, São Paulo 05403-010, Brazil. + + + + Garcez + Alexandre T + AT + + University of São Paulo, Department of Radiology and Oncology, USP School of Medicine, São Paulo, São Paulo 05403-010, Brazil. + + + + Buchpigel + Carlos A + CA + + University of São Paulo, Department of Radiology and Oncology, USP School of Medicine, São Paulo, São Paulo 05403-010, Brazil. + + + + Braconi + Carla T + CT + + University of São Paulo, Department of Microbiology, Institute of Microbiology Sciences, Laboratory of Molecular Evolution and Bioinformatics, São Paulo, São Paulo 05508-000, Brazil. + + + + Mendes + Erica + E + + University of São Paulo, Department of Microbiology, Institute of Microbiology Sciences, Laboratory of Molecular Evolution and Bioinformatics, São Paulo, São Paulo 05508-000, Brazil. + + + + Sall + Amadou A + AA + + Institute Pasteur in Dakar, Dakar 220, Sénégal. + + + + Zanotto + Paolo M de A + PM + + University of São Paulo, Department of Microbiology, Institute of Microbiology Sciences, Laboratory of Molecular Evolution and Bioinformatics, São Paulo, São Paulo 05508-000, Brazil. + + + + Peron + Jean Pierre S + JP + + University of São Paulo, Department of Immunology, Neuroimmune Interactions Laboratory, São Paulo, São Paulo 05508-000, Brazil. + + + + Muotri + Alysson R + AR + + University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular &Molecular Medicine, Stem Cell Program, La Jolla, California 92037-0695, USA. + + + + Beltrão-Braga + Patricia C B + PC + + University of São Paulo, Department of Surgery, Stem Cell Laboratory, São Paulo, São Paulo 05508-270, Brazil. + + + University of São Paulo, School of Arts, Sciences and Humanities, Department of Obstetrics, São Paulo, São Paulo 03828-000, Brazil. + + + + eng + + + R01 MH094753 + MH + NIMH NIH HHS + United States + + + U19 MH107367 + MH + NIMH NIH HHS + United States + + + R01MH094753 + MH + NIMH NIH HHS + United States + + + U19MH107367 + MH + NIMH NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + + + 2016 + 05 + 11 + +
+ + England + Nature + 0410462 + 0028-0836 + + IM + + + PLoS Negl Trop Dis. 2016 Apr 12;10(4):e0004636 + 27070912 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9 + 27022155 + + + Cell Stem Cell. 2016 May 5;18(5):591-6 + 27038591 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Cell. 2016 May 19;165(5):1238-54 + 27118425 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + J Virol. 2013 Mar;87(5):2895-907 + 23269797 + + + PLoS One. 2007 Sep 19;2(9):e898 + 17878933 + + + Front Physiol. 2015 Jun 08;6:176 + 26106333 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Development. 2010 Jun;137(11):1907-17 + 20460369 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Nature. 2013 Sep 19;501(7467):373-9 + 23995685 + + + Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16595-600 + 20823249 + + + Nature. 2013 Nov 28;503(7477):525-9 + 24153179 + + + Cell. 2010 Nov 12;143(4):527-39 + 21074045 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Cell Transplant. 2011;20(11-12):1707-19 + 21457612 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + BMJ. 2016 Apr 13;353:i1901 + 27075009 + + + Science. 2014 Jul 18;345(6194):1247125 + 25035496 + + + Temperature (Austin). 2016 Aug 5;4(1):13-14 + 28417097 + + + + + Animals + + + Apoptosis + + + Autophagy + + + Brain + pathology + virology + + + Brazil + epidemiology + + + Cell Proliferation + + + Disease Models, Animal + + + Female + + + Fetal Growth Retardation + pathology + virology + + + Fetus + virology + + + Mice + + + Microcephaly + epidemiology + etiology + pathology + virology + + + Neural Stem Cells + pathology + virology + + + Organoids + pathology + virology + + + Placenta + virology + + + Pregnancy + + + Zika Virus + pathogenicity + + + Zika Virus Infection + complications + epidemiology + pathology + virology + + +
+ + + + 2015 + 03 + 08 + + + 2016 + 05 + 04 + + + 2016 + 6 + 10 + 6 + 0 + + + 2016 + 6 + 10 + 6 + 0 + + + 2016 + 7 + 7 + 6 + 0 + + + ppublish + + 27279226 + nature18296 + 10.1038/nature18296 + PMC4902174 + NIHMS784700 + + +
+ + + + + 27278855 + + 2017 + 07 + 31 + + + 2018 + 01 + 09 + +
+ + 1096-9071 + + 88 + 10 + + 2016 + 10 + + + Journal of medical virology + J. Med. Virol. + + Bayesian coalescent inference reveals high evolutionary rates and diversification of Zika virus populations. + + 1672-6 + + 10.1002/jmv.24596 + + Zika virus (ZIKV) is a member of the family Flaviviridae. In 2015, ZIKV triggered an epidemic in Brazil and spread across Latin America. By May of 2016, the World Health Organization warns over spread of ZIKV beyond this region. Detailed studies on the mode of evolution of ZIKV strains are extremely important for our understanding of the emergence and spread of ZIKV populations. In order to gain insight into these matters, a Bayesian coalescent Markov Chain Monte Carlo analysis of complete genome sequences of recently isolated ZIKV strains was performed. The results of these studies revealed a mean rate of evolution of 1.20 × 10(-3) nucleotide substitutions per site per year (s/s/y) for ZIKV strains enrolled in this study. Several variants isolated in China are grouped together with all strains isolated in Latin America. Another genetic group composed exclusively by Chinese strains were also observed, suggesting the co-circulation of different genetic lineages in China. These findings indicate a high level of diversification of ZIKV populations. Strains isolated from microcephaly cases do not share amino acid substitutions, suggesting that other factors besides viral genetic differences may play a role for the proposed pathogenesis caused by ZIKV infection. J. Med. Virol. 88:1672-1676, 2016. © 2016 Wiley Periodicals, Inc. + © 2016 Wiley Periodicals, Inc. + + + + Fajardo + Alvaro + A + + Molecular Virology Laboratory, CIN, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay. + + + + Soñora + Martín + M + + Molecular Virology Laboratory, CIN, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay. + + + + Moreno + Pilar + P + + Molecular Virology Laboratory, CIN, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay. + + + + Moratorio + Gonzalo + G + + Molecular Virology Laboratory, CIN, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay. + + + Viral Populations and Pathogenesis laboratory. Institut Pasteur, Paris, France. + + + + Cristina + Juan + J + + Molecular Virology Laboratory, CIN, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 06 + 20 + +
+ + United States + J Med Virol + 7705876 + 0146-6615 + + IM + + + Amino Acid Substitution + + + Bayes Theorem + + + Brazil + epidemiology + + + China + epidemiology + + + Evolution, Molecular + + + Genetic Variation + + + Genome, Viral + + + Humans + + + Markov Chains + + + Microcephaly + virology + + + Monte Carlo Method + + + Zika Virus + genetics + + + Zika Virus Infection + epidemiology + virology + + + + Zika + bayesian + coalescent + evolution + microcephaly + +
+ + + + 2016 + 06 + 02 + + + 2016 + 6 + 10 + 6 + 0 + + + 2016 + 6 + 10 + 6 + 0 + + + 2017 + 8 + 2 + 6 + 0 + + + ppublish + + 27278855 + 10.1002/jmv.24596 + + +
+ + + + + 27254835 + + 2016 + 08 + 12 + +
+ + 2168-6173 + + 134 + 8 + + 2016 + Aug + 01 + + + JAMA ophthalmology + JAMA Ophthalmol + + Zika Virus, Microcephaly, and Ocular Findings. + + 945 + + 10.1001/jamaophthalmol.2016.1303 + + + Moshfeghi + Darius M + DM + + Byers Eye Institute, Horngren Family Vitreoretinal Center, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California. + + + + de Miranda + Homero Augusto + HA + 2nd + + Ophthalmic Telemedicine Santa Casa of São Paulo, São Paulo, Brazil. + + + + Costa + Marcelo Cavalcante + MC + + Ophthalmic Telemedicine Santa Casa of São Paulo, São Paulo, Brazil. + + + + eng + + Journal Article + +
+ + United States + JAMA Ophthalmol + 101589539 + 2168-6165 + + AIM + IM +
+ + + + 2016 + 6 + 3 + 6 + 0 + + + 2016 + 6 + 3 + 6 + 0 + + + 2016 + 6 + 3 + 6 + 0 + + + ppublish + + 27254835 + 2526355 + 10.1001/jamaophthalmol.2016.1303 + + +
+ + + + + 27253365 + + 2016 + 08 + 12 + +
+ + 2168-6173 + + 134 + 8 + + 2016 + Aug + 01 + + + JAMA ophthalmology + JAMA Ophthalmol + + Zika Virus, Microcephaly, and Ocular Findings-Reply. + + 946-7 + + 10.1001/jamaophthalmol.2016.1305 + + + Belfort + Rubens + R + Jr + + Vision Institute, Department of Ophthalmology, Paulista Medical School, Federal University of São Paulo, São Paulo, Brazil. + + + + de Paula Freitas + Bruno + B + + Department of Ophthalmology, Hospital Geral Roberto Santos, Salvador, Brazil. + + + + de Oliveira Dias + João Rafael + JR + + Vision Institute, Department of Ophthalmology, Paulista Medical School, Federal University of São Paulo, São Paulo, Brazil. + + + + eng + + Journal Article + +
+ + United States + JAMA Ophthalmol + 101589539 + 2168-6165 + + AIM + IM +
+ + + + 2016 + 6 + 3 + 6 + 0 + + + 2016 + 6 + 3 + 6 + 0 + + + 2016 + 6 + 3 + 6 + 0 + + + ppublish + + 27253365 + 2526357 + 10.1001/jamaophthalmol.2016.1305 + + +
+ + + + + 27253205 + + 2016 + 08 + 12 + +
+ + 2168-6173 + + 134 + 8 + + 2016 + Aug + 01 + + + JAMA ophthalmology + JAMA Ophthalmol + + Zika Virus, Microcephaly, and Ocular Findings. + + 946 + + 10.1001/jamaophthalmol.2016.1313 + + + Vasconcelos-Santos + Daniel Vítor + DV + + Department of Ophthalmology, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil2Núcleo de Ações em Pesquisa e Apoio Diagnóstico, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. + + + + Andrade + Gláucia Manzan Queiroz + GM + + Núcleo de Ações em Pesquisa e Apoio Diagnóstico, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil3Department of Pediatrics, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. + + + + Caiaffa + Waleska Teixeira + WT + + Núcleo de Ações em Pesquisa e Apoio Diagnóstico, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil4Department of Preventive and Social Medicine, Observatory of Urban Health, School of Medicine, Universidade Federal de Minas. + + + + eng + + Journal Article + +
+ + United States + JAMA Ophthalmol + 101589539 + 2168-6165 + + AIM + IM +
+ + + + 2016 + 6 + 3 + 6 + 0 + + + 2016 + 6 + 3 + 6 + 0 + + + 2016 + 6 + 3 + 6 + 0 + + + ppublish + + 27253205 + 2526356 + 10.1001/jamaophthalmol.2016.1313 + + +
+ + + + + 27247001 + + 2017 + 08 + 25 + + + 2017 + 09 + 19 + +
+ + 1934-6069 + + 20 + 1 + + 2016 + Jul + 13 + + + Cell host & microbe + Cell Host Microbe + + Zika Virus Infects Human Placental Macrophages. + + 83-90 + + 10.1016/j.chom.2016.05.015 + S1931-3128(16)30211-6 + + The recent Zika virus (ZIKV) outbreak in Brazil has been directly linked to increased cases of microcephaly in newborns. Current evidence indicates that ZIKV is transmitted vertically from mother to fetus. However, the mechanism of intrauterine transmission and the cell types involved remain unknown. We demonstrate that the contemporary ZIKV strain PRVABC59 (PR 2015) infects and replicates in primary human placental macrophages, called Hofbauer cells, and to a lesser extent in cytotrophoblasts, isolated from villous tissue of full-term placentae. Viral replication coincides with induction of type I interferon (IFN), pro-inflammatory cytokines, and antiviral gene expression, but with minimal cell death. Our results suggest a mechanism for intrauterine transmission in which ZIKV gains access to the fetal compartment by directly infecting placental cells and disrupting the placental barrier. + Copyright © 2016 Elsevier Inc. All rights reserved. + + + + Quicke + Kendra M + KM + + Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. + + + + Bowen + James R + JR + + Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. + + + + Johnson + Erica L + EL + + Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA. + + + + McDonald + Circe E + CE + + Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. + + + + Ma + Huailiang + H + + Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. + + + + O'Neal + Justin T + JT + + Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. + + + + Rajakumar + Augustine + A + + Department of Gynecology and Obstetrics, Division of Maternal Fetal Medicine and Reproductive Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30329, USA. + + + + Wrammert + Jens + J + + Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. + + + + Rimawi + Bassam H + BH + + Department of Gynecology and Obstetrics, Division of Maternal Fetal Medicine and Reproductive Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30329, USA. + + + + Pulendran + Bali + B + + Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. + + + + Schinazi + Raymond F + RF + + Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA. + + + + Chakraborty + Rana + R + + Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA. + + + + Suthar + Mehul S + MS + + Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. Electronic address: msuthar@emory.edu. + + + + eng + + + R37 AI048638 + AI + NIAID NIH HHS + United States + + + P30 AI050409 + AI + NIAID NIH HHS + United States + + + U19 AI090023 + AI + NIAID NIH HHS + United States + + + U19 AI083019 + AI + NIAID NIH HHS + United States + + + R56 AI110516 + AI + NIAID NIH HHS + United States + + + R21 AI113485 + AI + NIAID NIH HHS + United States + + + U19 AI057266 + AI + NIAID NIH HHS + United States + + + R37 DK057665 + DK + NIDDK NIH HHS + United States + + + + Journal Article + + + 2016 + 05 + 27 + +
+ + United States + Cell Host Microbe + 101302316 + 1931-3128 + + + + 0 + Cytokines + + + IM + + + Lancet. 2016 Apr 30;387(10030):1811-2 + 27103126 + + + Nat Rev Microbiol. 2013 Feb;11(2):115-28 + 23321534 + + + PLoS Pathog. 2009 Oct;5(10):e1000607 + 19798431 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Clin Liver Dis. 2008 Aug;12(3):713-26, xi + 18625436 + + + Emerg Infect Dis. 2016 May;22(5):828-32 + 27088494 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + J Virol. 2008 Jan;82(1):335-45 + 17942531 + + + Cell Host Microbe. 2016 May 11;19(5):705-12 + 27066743 + + + J Virol. 2015 Dec;89(23):11884-98 + 26378171 + + + Retrovirology. 2012 Dec 05;9:101 + 23217137 + + + Mem Inst Oswaldo Cruz. 2016 May;111(5):287-93 + 27143490 + + + J Virol. 2016 Apr 29;90(10 ):4864-75 + 26962217 + + + Cell Host Microbe. 2009 Apr 23;5(4):365-75 + 19380115 + + + PLoS Pathog. 2010 Feb 05;6(2):e1000757 + 20140199 + + + Cell Host Microbe. 2010 May 20;7(5):354-61 + 20478537 + + + Cell. 2016 May 19;165(5):1081-91 + 27180225 + + + Nat Immunol. 2009 Jan;10(1):116-25 + 19029902 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12048-53 + 23818581 + + + Lancet. 1990 Mar 10;335(8689):565-8 + 1689792 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Ann N Y Acad Sci. 2001 Sep;943:148-56 + 11594535 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Cell Host Microbe. 2016 Jul 13;20(1):9-11 + 27414496 + + + + + Cell Death + + + Cells, Cultured + + + Cytokines + secretion + + + Female + + + Humans + + + Macrophages + virology + + + Placenta + cytology + + + Pregnancy + + + Trophoblasts + virology + + + Viral Tropism + + + Virus Replication + + + Zika Virus + physiology + + +
+ + + + 2016 + 05 + 02 + + + 2016 + 05 + 16 + + + 2016 + 05 + 19 + + + 2016 + 6 + 2 + 6 + 0 + + + 2016 + 6 + 2 + 6 + 0 + + + 2017 + 8 + 26 + 6 + 0 + + + ppublish + + 27247001 + S1931-3128(16)30211-6 + 10.1016/j.chom.2016.05.015 + PMC5166429 + NIHMS836036 + + +
+ + + + + 27244952 + + 2016 + 06 + 30 + + + 2016 + 06 + 01 + +
+ + 0360-1293 + + 41 + 1 + + 2016 + + + Acupuncture & electro-therapeutics research + Acupunct Electrother Res + + Optimal Dose of Vitamin D3 400 I.U. for Average Adults has A Significant Anti-Cancer Effect, While Widely Used 2000 I.U. or Higher Promotes Cancer: Marked Reduction of Taurine & 1α, 25(OH)2D3 Was Found In Various Cancer Tissues and Oral Intake of Optimal Dose of Taurine 175mg for Average Adults, Rather Than 500mg, Was Found to Be A New Potentially Safe and More Effective Method of Cancer Treatment. + + 39-60 + + + During the past 10 years, the author had found that the optimal dose of Vitamin D3 400 I.U. has safe & effective anticancer effects, while commonly used 2000-5000 I.U. of Vit. D3 often creates a 2-3 time increase in cancer markers. We examined the concentration of Taurine in normal internal organs and in cancer using Bi-Digital O-Ring Test. We found that Taurine levels in normal tissue are 4-6ng. But, the amount of Taurine of average normal value of 5.0-5.25ng was strikingly reduced to 0.0025-0.0028ng in this study of several examples in adenocarcinomas of the esophagus, stomach, pancreas, colon, prostate, and lung, as well as breast cancer. The lowest Taurine levels of 0.0002-0.0005ng were found in so called Zika virus infected babies from Brazil with microcephaly. While Vitamin D3 receptor stimulant 1α, 25 (OH)2D3 in normal tissues was 0.45-0.53ng, they were reduced to 0.025-0.006ng in cancers (1/100th-1/200th of normal value), particularly in various adenocarcinomas. All of these adenocarcinomas had about 1500ng HPV-16 viral infection. In 500 breast cancers, about 97% had HPV-16. The optimal dose of Taurine for average adult has been found to be about 175mg, rather than the widely used 500mg. In addition, since Taurine is markedly reduced to close to 1/1000th-1/2000th of its normal value in these cancer tissues, we examined the effect of the optimal dose of Taurine on cancer patients. Optimal dose of Taurine produced a very significant decrease in cancer-associated parameters, such as Oncogene C-fosAb2 & Integrin α5β1 being reduced to less than 1/1,000th, and 8-OH-dG (which increases in the presence of DNA mutation) reduced to less than 1/10th. The optimal dose of Taurine 175mg for average adult various cancer patient 3 times a day alone provide beneficial effects with very significant anti-cancer effects with strikingly increased urinary excretion of bacteria, viruses, & funguses, asbestos, toxic metals & other toxic substances. However, optimal doses of Taurine combined with optimal individualized doses of ψ3 fish oil [EPA 180mg & DHA 120mg] & special cilantro tablet 3 times/day without creating harmful drug interactions among them including other essential drugs, is often extremely safe, more effective, economical & non-invasive new treatment for various cancer patients. + + + + Omura + Yoshiaki + Y + + + Lu + Dominic + D + + + Jones + Marilyn K + MK + + + Nihrane + Abdallah + A + + + Duvvi + Harsha + H + + + Yapor + Dario + D + + + Shimotsuura + Yasuhiro + Y + + + Ohki + Motomu + M + + + eng + + Journal Article + +
+ + United States + Acupunct Electrother Res + 7610364 + 0360-1293 + + + + 1C6V77QF41 + Cholecalciferol + + + 1EQV5MLY3D + Taurine + + + IM + + + Adult + + + Cholecalciferol + administration & dosage + adverse effects + + + Dietary Supplements + analysis + + + Dose-Response Relationship, Drug + + + Female + + + Humans + + + Male + + + Middle Aged + + + Neoplasms + drug therapy + prevention & control + + + Taurine + administration & dosage + adverse effects + + + Young Adult + + +
+ + + + 2016 + 6 + 2 + 6 + 0 + + + 2016 + 6 + 2 + 6 + 0 + + + 2016 + 7 + 1 + 6 + 0 + + + ppublish + + 27244952 + + +
+ + + + + 27236271 + + 2017 + 06 + 30 + + + 2018 + 01 + 11 + +
+ + 1549-4713 + + 123 + 8 + + 2016 + 08 + + + Ophthalmology + Ophthalmology + + Expanded Spectrum of Congenital Ocular Findings in Microcephaly with Presumed Zika Infection. + + 1788-1794 + + S0161-6420(16)30277-9 + 10.1016/j.ophtha.2016.05.001 + + To describe the ocular findings of 3 cases of suspected congenital Zika viral infection with microcephaly and maculopathy. + Retrospective, consecutive case series. + Three male infants born in northern Brazil whose mothers demonstrated a viral syndrome during the first trimester and who subsequently were born with microcephaly. + Observational report of macular findings. + Continued observation. + Three male infants were born with microcephaly to mothers who had a viral syndrome during the first trimester of gestation in an area that subsequently has demonstrated epidemic Zika infection, a flavivirus related to Dengue. Ocular examination was performed. All 6 eyes demonstrated a pigmentary maculopathy ranging from mild to pronounced. In 4 eyes, well-delineated macular chorioretinal atrophy with a hyperpigmented ring developed. Three eyes demonstrated vascular tortuosity and 2 eyes demonstrated a pronounced early termination of the retinal vasculature on photographic evaluation. Two eyes demonstrated a washed out peripheral retina with a hypolucent spot. One eye had scattered subretinal hemorrhages external to the macula. Finally, 1 eye demonstrated peripheral pigmentary changes and clustered atrophic lesions resembling grouped congenital albinotic spots (polar bear tracks). + Zika virus has been linked to microcephaly in children of mothers with a viral syndrome during the first trimester of pregnancy. Ocular findings previously described a pigmentary retinopathy and atrophy that now can be expanded to include torpedo maculopathy, vascular changes, and hemorrhagic retinopathy. Ophthalmologic screening guidelines need to be defined to determine which children would benefit from newborn screening in affected regions. + Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. + + + + Miranda + Homero Augusto de + HA + 2nd + + Ophthalmic Telemedicine Santa Casa of São Paulo, São Paulo, Brazil. + + + + Costa + Marcelo Cavalcante + MC + + Ophthalmic Telemedicine Santa Casa of São Paulo, São Paulo, Brazil. + + + + Frazão + Maria Auxiliadora Monteiro + MAM + + Ophthalmic Telemedicine Santa Casa of São Paulo, São Paulo, Brazil. + + + + Simão + Natália + N + + Department of Ophthalmology, University of São Paulo, São Paulo, Brazil. + + + + Franchischini + Sandra + S + + Department of Ophthalmology, University of Santo Amaro, São Paulo, Brazil. + + + + Moshfeghi + Darius M + DM + + Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California. Electronic address: dariusm@stanford.edu. + + + + eng + + Case Reports + Journal Article + + + 2016 + 05 + 25 + +
+ + United States + Ophthalmology + 7802443 + 0161-6420 + + + Chorioretinal atrophy, progressive bifocal + + IM + + + Brazil + + + Corneal Dystrophies, Hereditary + diagnosis + + + Eye Infections, Viral + diagnosis + virology + + + Female + + + Gestational Age + + + Humans + + + Infant, Newborn + + + Male + + + Microcephaly + diagnosis + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + virology + + + Retinal Diseases + diagnosis + virology + + + Retinal Hemorrhage + diagnosis + + + Retinal Vessels + pathology + + + Retrospective Studies + + + Zika Virus Infection + diagnosis + virology + + +
+ + + + 2016 + 01 + 30 + + + 2016 + 05 + 02 + + + 2016 + 05 + 02 + + + 2016 + 5 + 30 + 6 + 0 + + + 2016 + 5 + 30 + 6 + 0 + + + 2017 + 7 + 1 + 6 + 0 + + + ppublish + + 27236271 + S0161-6420(16)30277-9 + 10.1016/j.ophtha.2016.05.001 + + +
+ + + + + 27232529 + + 2017 + 11 + 06 + + + 2017 + 11 + 06 + +
+ + 1806-9339 + + 38 + 6 + + 2016 + Jun + + + Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia + Rev Bras Ginecol Obstet + + Challenges of Zika Virus Infection in Pregnant Women. + + 263-5 + + 10.1055/s-0036-1584206 + + + Duarte + Geraldo + G + + Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. + + + + eng + + Editorial + + + 2016 + 05 + 27 + +
+ + Brazil + Rev Bras Ginecol Obstet + 9214757 + 0100-7203 + + IM + + + Female + + + Fetal Diseases + virology + + + Humans + + + Microcephaly + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + epidemiology + + + Zika Virus Infection + diagnosis + epidemiology + + +
+ + + + 2016 + 5 + 28 + 6 + 0 + + + 2016 + 5 + 28 + 6 + 0 + + + 2017 + 11 + 7 + 6 + 0 + + + ppublish + + 27232529 + 10.1055/s-0036-1584206 + + +
+ + + + + 27232461 + + 2017 + 09 + 22 + + + 2017 + 09 + 22 + +
+ + 1601-0825 + + 23 + 1 + + 2017 + Jan + + + Oral diseases + Oral Dis + + Zika virus: oral healthcare implications. + + 12-17 + + 10.1111/odi.12512 + + Zika virus (ZIKV) infection has been recognised since 1947, but just recently it became a worldwide major public health problem. The most common features of ZIKV infection are fever, cutaneous rash, arthralgia and conjunctivitis but most affected patients with the clinical disease present with only mild symptoms. However, severe neurological complications have been described: there is an occasional association with Guillain-Barre syndrome, and emerging data indicate an association between vertical transmission of ZIKV infection and microcephaly, but no specific orofacial manifestations have yet been reported. ZIKV is present in body fluids and has also been demonstrated in the saliva, but there is as yet no reliable evidence to support ZIKV transmission via this pathway. Transmission in oral health care should be effectively prevented using standard infection control measures. There are currently no specific treatments for Zika virus disease and no vaccines available, so prevention of ZIKV is based on vector control. + © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. + + + + Leão + J C + JC + + Oral Medicine Unit, Departamento de Clínica e Odontologia Preventiva, Universidade Federal de Pernamuco, Recife, Brazil. + + + + Gueiros + L A + LA + http://orcid.org/0000-0003-4979-4318 + + Oral Medicine Unit, Departamento de Clínica e Odontologia Preventiva, Universidade Federal de Pernamuco, Recife, Brazil. + + + + Lodi + G + G + + Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Milan, Italy. + + + + Robinson + N A + NA + + Discipline of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore, Singapore. + + + + Scully + C + C + + WHO Collaborating Centre for Oral Health-General Health, UCL, London, UK. + + + + eng + + Journal Article + Review + + + 2016 + 07 + 12 + +
+ + Denmark + Oral Dis + 9508565 + 1354-523X + + D + + + Dental Care + methods + standards + + + Humans + + + Infectious Disease Transmission, Patient-to-Professional + prevention & control + + + Zika Virus + + + Zika Virus Infection + epidemiology + prevention & control + transmission + + + + Arboviruses + Zika virus + dental + epidemiology + oral + +
+ + + + 2016 + 05 + 02 + + + 2016 + 05 + 20 + + + 2016 + 05 + 23 + + + 2016 + 5 + 28 + 6 + 0 + + + 2017 + 9 + 25 + 6 + 0 + + + 2016 + 5 + 28 + 6 + 0 + + + ppublish + + 27232461 + 10.1111/odi.12512 + + +
+ + + + + 27228275 + + 2017 + 05 + 22 + + + 2017 + 05 + 22 + +
+ + 2168-6173 + + 134 + 8 + + 2016 + Aug + 01 + + + JAMA ophthalmology + JAMA Ophthalmol + + Risk Factors Associated With the Ophthalmoscopic Findings Identified in Infants With Presumed Zika Virus Congenital Infection. + + 912-8 + + 10.1001/jamaophthalmol.2016.1784 + + The Zika virus (ZIKV) might cause microcephaly and ophthalmoscopic findings in infants of mothers infected during pregnancy. + To assess and identify possible risk factors for ophthalmoscopic findings in infants born with microcephaly and a presumed clinical diagnosis of ZIKV intrauterine infection. + We conducted a cross-sectional study at the Altino Ventura Foundation in Recife, Brazil, that included 40 infants with microcephaly born in Pernambuco state, Brazil, between May and December 2015. Toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus were ruled out in all of them. Testing of cerebrospinal fluid for ZIKV using IgM antibody-capture enzyme-linked immunosorbent assay was performed in 24 of 40 infants (60.0%). The infants and mothers underwent ocular examinations. The infants were divided into 2 groups, those with and without ophthalmoscopic alterations, for comparison. + Identification of risk factors for ophthalmoscopic findings in infants born with microcephaly and ZIKV intrauterine infection. + Among the 40 infants, the mean (SD) age was 2.2 (1.2) months (range, 0.1-7.3 months). Of the 24 infants tested, 100% had positive results for ZIKV infection: 14 of 22 infants (63.6%) from the group with ophthalmoscopic findings and 10 of 18 infants (55.6%) from the group without ophthalmoscopic findings. The major symptoms reported in both groups were rash by 26 mothers (65.0%), fever by 9 mothers (22.5%), headache by 9 mothers (22.5%), and arthralgia by 8 mothers (20.0%). No mothers reported conjunctivitis or other ocular symptoms during pregnancy or presented signs of uveitis at the time of examination. Thirty-seven eyes (46.3%) of 22 infants (55.0%) had ophthalmoscopic alterations. Ten mothers (71.4%) of infants with ocular findings reported symptoms during the first trimester (frequency, 0.48; 95% CI, 0.02-0.67; P = .04). A difference was also observed between the groups of infants with and without ocular findings regarding the cephalic perimeter: mean (SD) of 28.8 (1.7) and 30.3 (1.5), respectively (frequency, -1.50; 95% CI, -2.56 to -0.51; P = .004). + Ocular involvement in infants with presumed ZIKV congenital infection were more often seen in infants with smaller cephalic diameter at birth and in infants whose mothers reported symptoms during the first trimester. + + + + Ventura + Camila V + CV + + Altino Ventura Foundation, Recife, Brazil2Pernambuco's Eye Hospital (HOPE), Recife, Brazil3Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of São Paulo and Vision Institute, São Paulo, Brazil. + + + + Maia + Mauricio + M + + Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of São Paulo and Vision Institute, São Paulo, Brazil. + + + + Travassos + Simone B + SB + + Altino Ventura Foundation, Recife, Brazil2Pernambuco's Eye Hospital (HOPE), Recife, Brazil. + + + + Martins + Thayze T + TT + + Altino Ventura Foundation, Recife, Brazil2Pernambuco's Eye Hospital (HOPE), Recife, Brazil. + + + + Patriota + Felipe + F + + Altino Ventura Foundation, Recife, Brazil2Pernambuco's Eye Hospital (HOPE), Recife, Brazil. + + + + Nunes + Marcos Eugênio + ME + + Altino Ventura Foundation, Recife, Brazil2Pernambuco's Eye Hospital (HOPE), Recife, Brazil. + + + + Agra + Cristiana + C + + Pernambuco's Eye Hospital (HOPE), Recife, Brazil. + + + + Torres + Virginia L + VL + + Altino Ventura Foundation, Recife, Brazil2Pernambuco's Eye Hospital (HOPE), Recife, Brazil. + + + + van der Linden + Vanessa + V + + Barão de Lucena Hospital, Recife, Brazil. + + + + Ramos + Regina C + RC + + Oswaldo Cruz University Hospital, Recife, Brazil. + + + + Rocha + Maria Ângela W + + + Oswaldo Cruz University Hospital, Recife, Brazil. + + + + Silva + Paula S + PS + + Oswaldo Cruz University Hospital, Recife, Brazil. + + + + Ventura + Liana O + LO + + Altino Ventura Foundation, Recife, Brazil2Pernambuco's Eye Hospital (HOPE), Recife, Brazil. + + + + Belfort + Rubens + R + Jr + + Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of São Paulo and Vision Institute, São Paulo, Brazil. + + + + eng + + Journal Article + Multicenter Study + +
+ + United States + JAMA Ophthalmol + 101589539 + 2168-6165 + + + + 0 + Antibodies, Viral + + + AIM + IM + + + Adult + + + Antibodies, Viral + analysis + + + Brazil + epidemiology + + + Cross-Sectional Studies + + + Diagnosis, Differential + + + Enzyme-Linked Immunosorbent Assay + + + Eye Infections, Viral + congenital + diagnosis + epidemiology + + + Female + + + Fetal Diseases + diagnosis + virology + + + Follow-Up Studies + + + Humans + + + Incidence + + + Infant + + + Infant, Newborn + + + Male + + + Ophthalmoscopy + methods + + + Pregnancy + + + Reproducibility of Results + + + Retrospective Studies + + + Risk Factors + + + Zika Virus + immunology + + + Zika Virus Infection + congenital + diagnosis + epidemiology + + +
+ + + + 2016 + 5 + 27 + 6 + 0 + + + 2016 + 5 + 27 + 6 + 0 + + + 2017 + 5 + 23 + 6 + 0 + + + ppublish + + 27228275 + 2525773 + 10.1001/jamaophthalmol.2016.1784 + + +
+ + + + + 27224278 + + 2016 + 12 + 22 + + + 2016 + 12 + 30 + +
+ + 1806-9460 + + 134 + 2 + + 2016 + 04 + + + Sao Paulo medical journal = Revista paulista de medicina + Sao Paulo Med J + + Zika epidemic and social inequalities: Brazil and its fate. + + 95-6 + + 10.1590/1516-3180.2016.13421602 + S1516-31802016000200095 + + + Lotufo + Paulo Andrade + PA + + Department of Internal Medicine, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. + + + + eng + + Editorial + Comment + +
+ + Brazil + Sao Paulo Med J + 100897261 + 1516-3180 + + IM + + + Sao Paulo Med J. 2001 May 3;119(3):94-6 + 11391449 + + + + + Brazil + epidemiology + + + Humans + + + Microcephaly + epidemiology + + + Socioeconomic Factors + + + Zika Virus + + + Zika Virus Infection + + +
+ + + + 2016 + 02 + 15 + + + 2016 + 02 + 15 + + + 2016 + 5 + 26 + 6 + 0 + + + 2016 + 5 + 26 + 6 + 0 + + + 2016 + 12 + 23 + 6 + 0 + + + ppublish + + 27224278 + S1516-31802016000200095 + 10.1590/1516-3180.2016.13421602 + + +
+ + + + + 27222919 + + 2016 + 07 + 26 + + + 2017 + 07 + 14 + +
+ + 1533-4406 + + 375 + 1 + + 2016 + Jul + 07 + + + The New England journal of medicine + N. Engl. J. Med. + + Zika and the Risk of Microcephaly. + + 1-4 + + 10.1056/NEJMp1605367 + + + Johansson + Michael A + MA + + From the Division of Vector-Borne Diseases (M.A.J., L.M.-T.-R., S.L.H.) and the Division of Congenital and Developmental Disorders (J.R., S.M.G.), Centers for Disease Control and Prevention, Atlanta; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston (M.A.J.). + + + + Mier-y-Teran-Romero + Luis + L + + From the Division of Vector-Borne Diseases (M.A.J., L.M.-T.-R., S.L.H.) and the Division of Congenital and Developmental Disorders (J.R., S.M.G.), Centers for Disease Control and Prevention, Atlanta; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston (M.A.J.). + + + + Reefhuis + Jennita + J + + From the Division of Vector-Borne Diseases (M.A.J., L.M.-T.-R., S.L.H.) and the Division of Congenital and Developmental Disorders (J.R., S.M.G.), Centers for Disease Control and Prevention, Atlanta; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston (M.A.J.). + + + + Gilboa + Suzanne M + SM + + From the Division of Vector-Borne Diseases (M.A.J., L.M.-T.-R., S.L.H.) and the Division of Congenital and Developmental Disorders (J.R., S.M.G.), Centers for Disease Control and Prevention, Atlanta; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston (M.A.J.). + + + + Hills + Susan L + SL + + From the Division of Vector-Borne Diseases (M.A.J., L.M.-T.-R., S.L.H.) and the Division of Congenital and Developmental Disorders (J.R., S.M.G.), Centers for Disease Control and Prevention, Atlanta; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston (M.A.J.). + + + + eng + + + U54 GM088558 + GM + NIGMS NIH HHS + United States + + + + Journal Article + + + 2016 + 05 + 25 + +
+ + United States + N Engl J Med + 0255562 + 0028-4793 + + AIM + IM + + + N Engl J Med. 2016 Aug 4;375(5):498 + 27518688 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3 + 26796813 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Humans + + + Microcephaly + embryology + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Zika Virus + + + Zika Virus Infection + complications + epidemiology + + +
+ + + + 2016 + 5 + 26 + 6 + 0 + + + 2016 + 5 + 26 + 6 + 0 + + + 2016 + 7 + 28 + 6 + 0 + + + ppublish + + 27222919 + 10.1056/NEJMp1605367 + PMC4945401 + NIHMS797386 + + +
+ + + + + 27205899 + + 2017 + 03 + 30 + + + 2017 + 03 + 30 + +
+ + 1935-2735 + + 10 + 5 + + 2016 + 05 + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + A Cost-Effectiveness Tool for Informing Policies on Zika Virus Control. + + e0004743 + + 10.1371/journal.pntd.0004743 + + As Zika virus continues to spread, decisions regarding resource allocations to control the outbreak underscore the need for a tool to weigh policies according to their cost and the health burden they could avert. For example, to combat the current Zika outbreak the US President requested the allocation of $1.8 billion from Congress in February 2016. + Illustrated through an interactive tool, we evaluated how the number of Zika cases averted, the period during pregnancy in which Zika infection poses a risk of microcephaly, and probabilities of microcephaly and Guillain-Barré Syndrome (GBS) impact the cost at which an intervention is cost-effective. From Northeast Brazilian microcephaly incidence data, we estimated the probability of microcephaly in infants born to Zika-infected women (0.49% to 2.10%). We also estimated the probability of GBS arising from Zika infections in Brazil (0.02% to 0.06%) and Colombia (0.08%). We calculated that each microcephaly and GBS case incurs the loss of 29.95 DALYs and 1.25 DALYs per case, as well as direct medical costs for Latin America and the Caribbean of $91,102 and $28,818, respectively. We demonstrated the utility of our cost-effectiveness tool with examples evaluating funding commitments by Costa Rica and Brazil, the US presidential proposal, and the novel approach of genetically modified mosquitoes. Our analyses indicate that the commitments and the proposal are likely to be cost-effective, whereas the cost-effectiveness of genetically modified mosquitoes depends on the country of implementation. + Current estimates from our tool suggest that the health burden from microcephaly and GBS warrants substantial expenditures focused on Zika virus control. Our results justify the funding committed in Costa Rica and Brazil and many aspects of the budget outlined in the US president's proposal. As data continue to be collected, new parameter estimates can be customized in real-time within our user-friendly tool to provide updated estimates on cost-effectiveness of interventions and inform policy decisions in country-specific settings. + + + + Alfaro-Murillo + Jorge A + JA + + Center for Infectious Disease Modeling and Analysis, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + + Parpia + Alyssa S + AS + 0000-0002-9083-1929 + + Center for Infectious Disease Modeling and Analysis, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + + Fitzpatrick + Meagan C + MC + + Center for Infectious Disease Modeling and Analysis, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + + Tamagnan + Jules A + JA + + Center for Infectious Disease Modeling and Analysis, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + + Medlock + Jan + J + + Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, United States of America. + + + + Ndeffo-Mbah + Martial L + ML + + Center for Infectious Disease Modeling and Analysis, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + + Fish + Durland + D + + Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + + Ávila-Agüero + María L + ML + + Pediatric Infectious Diseases Department, Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera", San José, Costa Rica. + + + + Marín + Rodrigo + R + + Programa de Control de Vectores, Ministerio de Salud, San José, Costa Rica. + + + + Ko + Albert I + AI + + Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, Bahia, Brasil. + + + + Galvani + Alison P + AP + + Center for Infectious Disease Modeling and Analysis, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut, United States of America. + + + Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut, United States of America. + + + + eng + + + R01 AI121207 + AI + NIAID NIH HHS + United States + + + U01 GM087719 + GM + NIGMS NIH HHS + United States + + + U01 GM105627 + GM + NIGMS NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + + + 2016 + 05 + 20 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + IM + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + MMWR Morb Mortal Wkly Rep. 2004 Jan 30;53(3):57-9 + 14749614 + + + Lancet Glob Health. 2015 Nov;3(11):e712-23 + 26475018 + + + N Engl J Med. 2012 Jun 14;366(24):2294-304 + 22694000 + + + Emerg Infect Dis. 2016 Jul;22(7):1221-8 + 27070192 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Teratology. 2001 Nov;64(5):267-75 + 11745833 + + + Lancet Infect Dis. 2016 Jun;16(6):712-23 + 26874619 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Emerg Infect Dis. 2015 Dec;21(12):2274-6 + 26584464 + + + Med Decis Making. 1998 Apr-Jun;18(2 Suppl):S68-80 + 9566468 + + + Neurology. 2008 Jul 1;71(1):21-7 + 18591502 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Aedes + genetics + virology + + + Animals + + + Animals, Genetically Modified + + + Brazil + epidemiology + + + Caribbean Region + epidemiology + + + Cost of Illness + + + Cost-Benefit Analysis + legislation & jurisprudence + + + Costa Rica + epidemiology + + + Disease Outbreaks + economics + legislation & jurisprudence + prevention & control + + + Female + + + Health Care Costs + legislation & jurisprudence + + + Health Policy + + + Humans + + + Incidence + + + Infant + + + Microcephaly + etiology + prevention & control + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + economics + prevention & control + virology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + economics + epidemiology + prevention & control + virology + + +
+ + + + 2016 + 02 + 25 + + + 2016 + 05 + 05 + + + 2016 + 5 + 21 + 6 + 0 + + + 2016 + 5 + 21 + 6 + 0 + + + 2017 + 3 + 31 + 6 + 0 + + + epublish + + 27205899 + 10.1371/journal.pntd.0004743 + PNTD-D-16-00331 + PMC4874682 + + +
+ + + + + 27197772 + + 2016 + 05 + 20 + +
+ + 1557-3117 + + 35 + 5 + + 2016 + May + + + The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation + J. Heart Lung Transplant. + + The Zika epidemics and transplantation. + + 560-3 + + 10.1016/j.healun.2016.03.010 + S1053-2498(16)30058-4 + + In the last few months an epidemic of Zika virus (ZIKV) has affected several countries, and it continues to spread rapidly. This virus was initially thought to cause only a mild febrile illness; however, the current epidemic has shown that it is associated with serious complications. Increasing reports are linking ZIKV to devastating conditions such as microcephaly in newborns and important neurologic syndromes. Although ZIKV infection has not yet been reported in transplant recipients, it is likely that it will be reported soon because of the number of transplants performed in affected areas and global travel. We discuss the effect of ZIKV in transplantation and propose recommendations to prevent donor-derived infections. + Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved. + + + + Silveira + Fernanda P + FP + + Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: silveirafd@upmc.edu. + + + + Campos + Silvia V + SV + + Pulmonary Division, Lung Transplant Group, Heart Institute (InCor), University of São Paulo, São Paulo, Brazil. + + + + eng + + Editorial + + + 2016 + 03 + 29 + +
+ + United States + J Heart Lung Transplant + 9102703 + 1053-2498 + + IM + + Guillain-Barré syndrome + Zika virus + complications + donor-derived infection + microcephaly + transplantation + +
+ + + + 2016 + 03 + 16 + + + 2016 + 03 + 26 + + + 2016 + 5 + 21 + 6 + 0 + + + 2016 + 5 + 21 + 6 + 0 + + + 2016 + 5 + 21 + 6 + 0 + + + ppublish + + 27197772 + S1053-2498(16)30058-4 + 10.1016/j.healun.2016.03.010 + + +
+ + + + + 27193639 + + 2016 + 06 + 07 + + + 2016 + 12 + 16 + +
+ + 1476-4687 + + 533 + 7603 + + 2016 + 05 + 19 + + + Nature + Nature + + Zika must remain a high priority. + + 291 + + 10.1038/533291a + eng + + Editorial + +
+ + England + Nature + 0410462 + 0028-0836 + + IM + + + Biomedical Research + trends + + + Brain + pathology + virology + + + Brazil + epidemiology + + + Humans + + + Microcephaly + complications + + + Neural Stem Cells + pathology + virology + + + Organoids + pathology + virology + + + Sports + + + World Health Organization + + + Zika Virus + pathogenicity + + + Zika Virus Infection + complications + epidemiology + + +
+ + + + 2016 + 5 + 20 + 6 + 0 + + + 2016 + 5 + 20 + 6 + 0 + + + 2016 + 6 + 9 + 6 + 0 + + + ppublish + + 27193639 + 533291a + 10.1038/533291a + + +
+ + + + + 27192031 + + 2017 + 04 + 06 + + + 2017 + 08 + 17 + +
+ + 1678-4464 + + 32 + 5 + + 2016 + May + + + Cadernos de saude publica + Cad Saude Publica + + Zika in Cadernos de Saúde Pública / Reports in Public Health: again? + + eED010516 + + 10.1590/0102-311XED010516 + S0102-311X2016000500201 + + + Carvalho + Marilia Sá + MS + + + eng + por + spa + + Editorial + + Zika em Cadernos de Saúde Pública: novamente? + + 2016 + 05 + 13 + +
+ + Brazil + Cad Saude Publica + 8901573 + 0102-311X + + IM + + + Brazil + epidemiology + + + Female + + + Humans + + + Microcephaly + virology + + + Periodicals as Topic + + + Politics + + + Pregnancy + + + Public Health + + + Zika Virus + + + Zika Virus Infection + epidemiology + prevention & control + transmission + + +
+ + + + 2016 + 5 + 19 + 6 + 0 + + + 2016 + 5 + 19 + 6 + 0 + + + 2017 + 4 + 7 + 6 + 0 + + + ppublish + + 27192031 + S0102-311X2016000500201 + 10.1590/0102-311XED010516 + + +
+ + + + + 27192024 + + 2017 + 04 + 06 + + + 2017 + 08 + 17 + +
+ + 1678-4464 + + 32 + 5 + + 2016 + May + + + Cadernos de saude publica + Cad Saude Publica + + Zika virus and women. + + e00046316 + + 10.1590/0102-311X00046316 + S0102-311X2016000500601 + + + Diniz + Debora + D + + Faculdade de Direito, Universidade de Brasília, Brasília, Brazil. + + + + eng + por + + Journal Article + + Vírus Zika e mulheres. + + 2016 + 05 + 13 + +
+ + Brazil + Cad Saude Publica + 8901573 + 0102-311X + + IM + + + Brazil + epidemiology + + + Female + + + Humans + + + Microcephaly + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Zika Virus + + + Zika Virus Infection + complications + epidemiology + + +
+ + + + 2016 + 03 + 22 + + + 2016 + 04 + 06 + + + 2016 + 5 + 19 + 6 + 0 + + + 2016 + 5 + 19 + 6 + 0 + + + 2017 + 4 + 7 + 6 + 0 + + + ppublish + + 27192024 + S0102-311X2016000500601 + 10.1590/0102-311X00046316 + + +
+ + + + + 27179929 + + 2017 + 10 + 20 + + + 2018 + 02 + 21 + +
+ + 1879-6265 + + 18 + + 2016 + 06 + + + Current opinion in virology + Curr Opin Virol + + Zika crisis in Brazil: challenges in research and development. + + 76-81 + + 10.1016/j.coviro.2016.04.002 + S1879-6257(16)30044-X + + Infection with the Zika virus (ZIKV) usually causes a mild acute illness, but two major severe syndromes have been described during the epidemic in Brazil: microcephaly and the Guillain-Barré Syndrome. There is now much evidence to show that ZIKV can infect and damage neuronal cells in vitro. In experimental animals, ZIKV has significant neurotropism and can cause brain damage. At present, diagnosis is still a challenge in the field and there is no treatment available. Another major challenge is that one must devise therapies for pregnant women, at all stages of pregnancy. Devising adequate treatment for ZIKV infections represents a challenge that will only be met by the joint effort of the research community. + Copyright © 2016 Elsevier B.V. All rights reserved. + + + + Ribeiro + Lucas Secchim + LS + + Department of Microbiology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Immunopharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. + + + + Marques + Rafael Elias + RE + + Immunopharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. + + + + Jesus + Amélia Maria Ribeiro de + AM + + Laboratório de Biologia Molecular and Programa de Pós Graduação em Ciências da Saúde, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil. + + + + Almeida + Roque Pacheco de + RP + + Laboratório de Biologia Molecular and Programa de Pós Graduação em Ciências da Saúde, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil. + + + + Teixeira + Mauro Martins + MM + + Immunopharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: mmtex@icb.ufmg.br. + + + + eng + + Journal Article + Review + Research Support, Non-U.S. Gov't + + + 2016 + 05 + 12 + +
+ + Netherlands + Curr Opin Virol + 101560941 + 1879-6257 + + IM + + + Animals + + + Brazil + + + Disease Models, Animal + + + Female + + + Guillain-Barre Syndrome + virology + + + Humans + + + Infant, Newborn + + + Mice + + + Microcephaly + virology + + + Pregnancy + + + Primates + + + Zika Virus + isolation & purification + pathogenicity + + + Zika Virus Infection + drug therapy + immunology + therapy + virology + + +
+ + + + 2016 + 04 + 05 + + + 2016 + 04 + 28 + + + 2016 + 04 + 29 + + + 2016 + 5 + 16 + 6 + 0 + + + 2016 + 5 + 18 + 6 + 0 + + + 2017 + 10 + 21 + 6 + 0 + + + ppublish + + 27179929 + S1879-6257(16)30044-X + 10.1016/j.coviro.2016.04.002 + + +
+ + + + + 27175508 + + 2016 + 08 + 15 + + + 2016 + 05 + 14 + +
+ + 0374-9096 + + 50 + 2 + + 2016 + Apr + + + Mikrobiyoloji bulteni + Mikrobiyol Bul + + [Global spread of Zika virus epidemic: current knowledges and uncertainties]. + + 333-51 + + + Zika virus (ZIKV) is an enveloped RNA virus that belongs to the Flaviviridae family. Although more than 60 years have passed since the discovery and first reported human cases of the virus, only a small number (< 10) of cases had been encountered in the literature until the last 10 years. Zika virus was known as a virus which caused sporadic infections and was confined to Africa and Asia along a narrow equatorial line. In 2007, however, the first major outbreak of ZIKV occurred in Yap Island (Micronesia), and so it was reported for the first time outside of Africa and Asia. Between the years of 2007 and 2014, ZIKV spreaded to island groups located in Southeast Asia and the Pacific Ocean, and in 2015-2016, it has spread to South and Central America and the Caribbean. Today, travel-related imported cases is still been reported in Europe, North America, and other countries in the Far East. According to the data from the World Health Organization and the Centers for Disease Control and Prevention, as of March 2016, ZIKV infections have already spread locally in more than 30 countries, and travel alerts have been issued for the countries where the virus is present. Zika virus infections are generally asymptomatic or may present with a moderate clinical picture (e.g. acute onset of fever, maculopapular rash, arthralgia, and nonpurulent conjunctivitis). Although no deaths were attributed to ZIKV infection over the past 60 years, as of November 2015, it has been suggested that three deaths in Brazil, including the death of a newborn with microcephaly, may be attributed to ZIKV infection. In addition, concurrent with outbreaks in 2013 in French Polynesia and in 2015 in Brazil, there have been significant rises reported in the incidence of some autoimmune and neurodevelopmental disorders, including Guillain-Barre syndrome and microcephaly; these reports have caused considerable international concern. There are many points that are still unclear about ZIKV, including: (1) intrauterine transmission risk, frequency, and effects of the infection on fetal development; (2) the probability of perinatal transmission and if so the possible risks; (3) association with autoimmune and neurological diseases, and presence of long-term sequelae risks after infection; (4) possible routes of transmission other than mosquito bites, such as sexual contact, blood transfusion, and other body fluids (saliva, semen, or urine); (5) presence of reservoir(s) and different mosquito vectors; (6) diagnostic difficulties including cross reactivity in serological tests and standardization of testing procedures; (7) severity of the infection in immunocompromised patients; and (8) the potential effectiveness of antiviral therapy or preventive vaccines. In this review, updated information and recommendations regarding ZIKV outbreaks and risks, and the epidemiology, diagnosis and characteristics of ZIKV infections, are summarized in light of the most recent literature. + + + + Şahiner + Fatih + F + + Gulhane Military Medical Academy, Department of Medical Microbiology, Ankara, Turkey. fsvirol@gmail.com. + + + + tur + + English Abstract + Journal Article + Review + + Zika virus salgınının küresel yayılımı: Güncel bilgiler ve belirsizlikler. +
+ + Turkey + Mikrobiyol Bul + 7503830 + 0374-9096 + + IM + + + Epidemics + + + Global Health + trends + + + Humans + + + Risk Factors + + + Zika Virus Infection + epidemiology + + +
+ + + + 2016 + 5 + 14 + 6 + 0 + + + 2016 + 5 + 14 + 6 + 0 + + + 2016 + 8 + 16 + 6 + 0 + + + ppublish + + 27175508 + + +
+ + + + + 27172823 + + 2017 + 10 + 12 + + + 2017 + 10 + 12 + +
+ + 1432-1238 + + 42 + 9 + + 2016 + Sep + + + Intensive care medicine + Intensive Care Med + + Key points on Zika infection for the intensivist. + + 1490-2 + + 10.1007/s00134-016-4378-4 + + + Bozza + Fernando A + FA + + Intensive Care Lab, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Av. Brasil 4365, Rio De Janeiro, RJ, 21045-900, Brazil. fernando.bozza@ini.fiocruz.br. + + + + Grinsztejn + Beatriz + B + + HIV Lab, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio De Janeiro, Brazil. + + + + eng + + Journal Article + Review + + + 2016 + 05 + 12 + +
+ + United States + Intensive Care Med + 7704851 + 0342-4642 + + IM + + + Intensive Care Med. 2016 Sep;42(9):1522 + 27299353 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Euro Surveill. 2014 Oct 16;19(41):null + 25345518 + + + Lancet. 2016 Feb 20;387(10020):719-21 + 26876373 + + + Emerg Infect Dis. 2016 Jul;22(7):1318-20 + 27070847 + + + Genome Announc. 2016 Mar 03;4(2):null + 26941134 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + Lancet. 2016 Apr 2;387(10026):1481 + 26946926 + + + Lancet. 2016 Apr 9;387(10027):1531-1539 + 26948433 + + + Lancet Infect Dis. 2016 Jun;16(6):653-660 + 26897108 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Diagnosis, Differential + + + Female + + + Guillain-Barre Syndrome + + + Humans + + + Incidence + + + Intensive Care Units + + + Microcephaly + etiology + + + Pregnancy + + + Pregnancy Complications, Infectious + etiology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + diagnosis + epidemiology + transmission + + +
+ + + + 2016 + 03 + 16 + + + 2016 + 05 + 02 + + + 2016 + 5 + 14 + 6 + 0 + + + 2016 + 5 + 14 + 6 + 0 + + + 2017 + 10 + 13 + 6 + 0 + + + ppublish + + 27172823 + 10.1007/s00134-016-4378-4 + 10.1007/s00134-016-4378-4 + + +
+ + + + + 27167975 + + 2017 + 03 + 03 + + + 2017 + 03 + 03 + +
+ + 1961-9049 + + 109 + 2 + + 2016 + May + + + Bulletin de la Societe de pathologie exotique (1990) + Bull Soc Pathol Exot + + [Zika virus outbreak in Latin America: what are the challenges for French Guiana in April 2016?]. + + 114-25 + + 10.1007/s13149-016-0490-5 + + Started in 2015 in Brazil, an outbreak linked to a little known arbovirus, Zika virus spread throughout Latin America. This virus, considered until recently as responsible of only mild symptoms, made mention of previously unsuspected complications, with severe neurological manifestations in adults and malformations of the central nervous system, including microcephaly, in newborns of mother infected during the pregnancy. While the continent is more accustomed to the succession of arbovirus epidemics, suspected complications and the many unknowns keys of the latter arriving raise many public health issues. French Guiana, a French territory located in the north-east of the continent, combines both European level of resources and climate and issues specific to the Amazon region and Latin America. We discuss here the issues for 2016 Zika virus epidemic in our region, many of them are generalizable to neighboring countries. + + + + Epelboin + L + L + + Unité des maladies infectieuses et tropicales, Centre hospitalier Andrée Rosemon, Cayenne, Guyane française, France. epelboincrh@hotmail.fr. + + + Ecosystèmes amazoniens et pathologie tropicale (EPAT).EA3593., Université de la Guyane, Guyane Française, France. epelboincrh@hotmail.fr. + + + + Douine + M + M + + Ecosystèmes amazoniens et pathologie tropicale (EPAT).EA3593., Université de la Guyane, Guyane Française, France. + + + Centre d'investigation clinique Antilles-Guyane, Inserm 1424, Centre hospitalier Andrée Rosemon, 97300, Cayenne, Guyane française, France. + + + + Carles + G + G + + Service de gynécologie obstétrique, Centre hospitalier de l'Ouest guyanais, Saint-Laurent-du-Maroni cedex, Guyane française, France. + + + + Villemant + N + N + + Institut de géographie (UFR08), Université Paris 1 Panthéon-Sorbonne University, Paris, France. + + + + Nacher + M + M + + Ecosystèmes amazoniens et pathologie tropicale (EPAT).EA3593., Université de la Guyane, Guyane Française, France. + + + Centre d'investigation clinique Antilles-Guyane, Inserm 1424, Centre hospitalier Andrée Rosemon, 97300, Cayenne, Guyane française, France. + + + + Rousset + D + D + + Centre nationale des arbovirus, laboratoire de virologie, Institut Pasteur de la Guyane, Cayenne, Guyane française, France. + + + + Djossou + F + F + + Unité des maladies infectieuses et tropicales, Centre hospitalier Andrée Rosemon, Cayenne, Guyane française, France. + + + Ecosystèmes amazoniens et pathologie tropicale (EPAT).EA3593., Université de la Guyane, Guyane Française, France. + + + + Mosnier + E + E + + Unité des maladies infectieuses et tropicales, Centre hospitalier Andrée Rosemon, Cayenne, Guyane française, France. + + + Ecosystèmes amazoniens et pathologie tropicale (EPAT).EA3593., Université de la Guyane, Guyane Française, France. + + + Centres délocalisés de préventions et de soins, Centre hospitalier Andrée Rosemon, Cayenne, Guyane française, France. + + + + fre + + Journal Article + + Épidémie de virus Zika en Amérique latine : quels enjeux pour la Guyane française en avril 2016 ? + + 2016 + 05 + 12 + +
+ + France + Bull Soc Pathol Exot + 9212564 + 0037-9085 + + IM + + + Adult + + + Disease Outbreaks + prevention & control + statistics & numerical data + + + Female + + + French Guiana + epidemiology + + + Global Health + + + Humans + + + Infant, Newborn + + + Infectious Disease Transmission, Vertical + statistics & numerical data + + + Latin America + epidemiology + + + Male + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Public Health + + + Sexually Transmitted Diseases, Viral + epidemiology + transmission + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + prevention & control + transmission + + + + French Guiana + Latin America + Maternal-fetal infections + Microcephaly + Sexually transmitted diseases + Zika virus + +
+ + + + 2016 + 02 + 22 + + + 2016 + 03 + 18 + + + 2016 + 5 + 12 + 6 + 0 + + + 2016 + 5 + 12 + 6 + 0 + + + 2017 + 3 + 4 + 6 + 0 + + + ppublish + + 27167975 + 10.1007/s13149-016-0490-5 + 10.1007/s13149-016-0490-5 + + +
+ + + + + 27167538 + + 2017 + 01 + 04 + + + 2017 + 01 + 05 + +
+ + 1806-9282 + + 62 + 2 + + 2016 + Apr + + + Revista da Associacao Medica Brasileira (1992) + Rev Assoc Med Bras (1992) + + Zika virus infection and pregnancy. + + 108-15 + + 10.1590/1806-9282.62.02.108 + S0104-42302016000200108 + + + Simões + Ricardo + R + + Federação Brasileira das Associações de Ginecologia e Obstetrícia, Brazil. + + + + Buzzini + Renata + R + + Associação Médica Brasileira, Brazil. + + + + Bernardo + Wanderley + W + + Associação Médica Brasileira, Brazil. + + + + Cardoso + Florentino + F + + Associação Médica Brasileira, Brazil. + + + + Salomão + Antônio + A + + Federação Brasileira das Associações de Ginecologia e Obstetrícia, Brazil. + + + + Cerri + Giovanni + G + + Associação Médica Brasileira, Brazil. + + + + eng + + Journal Article + Practice Guideline + +
+ + Brazil + Rev Assoc Med Bras (1992) + 9308586 + 0104-4230 + + IM + + + Brazil + + + Female + + + Guillain-Barre Syndrome + therapy + virology + + + Humans + + + Microcephaly + therapy + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + therapy + + + Risk Factors + + + Zika Virus Infection + diagnosis + therapy + + +
+ + + + 2016 + 5 + 12 + 6 + 0 + + + 2016 + 5 + 12 + 6 + 0 + + + 2017 + 1 + 5 + 6 + 0 + + + ppublish + + 27167538 + S0104-42302016000200108 + 10.1590/1806-9282.62.02.108 + + +
+ + + + + 27165390 + + 2016 + 07 + 12 + + + 2016 + 05 + 11 + +
+ + 1354-5752 + + 24 + 2 + + 2016 + May + + + Emergency nurse : the journal of the RCN Accident and Emergency Nursing Association + Emerg Nurse + + Effects of Zika virus. + + 17 + + 10.7748/en.24.2.17.s22 + eng + + Journal Article + +
+ + England + Emerg Nurse + 9208913 + 1354-5752 + + N + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant, Newborn + + + Male + + + Microcephaly + epidemiology + + + Pregnancy + + + Pregnancy Complications + epidemiology + + + Prevalence + + + Zika Virus Infection + epidemiology + physiopathology + + +
+ + + + 2016 + 5 + 12 + 6 + 0 + + + 2016 + 5 + 12 + 6 + 0 + + + 2016 + 7 + 13 + 6 + 0 + + + ppublish + + 27165390 + 10.7748/en.24.2.17.s22 + + +
+ + + + + 27163257 + + 2017 + 03 + 29 + + + 2017 + 03 + 30 + +
+ + 1935-2735 + + 10 + 5 + + 2016 + 05 + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + The Viral Polymerase Inhibitor 7-Deaza-2'-C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model. + + e0004695 + + 10.1371/journal.pntd.0004695 + + Zika virus (ZIKV) is an emerging flavivirus typically causing a dengue-like febrile illness, but neurological complications, such as microcephaly in newborns, have potentially been linked to this viral infection. We established a panel of in vitro assays to allow the identification of ZIKV inhibitors and demonstrate that the viral polymerase inhibitor 7-deaza-2'-C-methyladenosine (7DMA) efficiently inhibits replication. Infection of AG129 (IFN-α/β and IFN-γ receptor knock-out) mice with ZIKV resulted in acute neutrophilic encephalitis with viral antigens accumulating in neurons of the brain and spinal cord. Additionally, high levels of viral RNA were detected in the spleen, liver and kidney, and levels of IFN-γ and IL-18 were systematically increased in serum of ZIKV-infected mice. Interestingly, the virus was also detected in testicles of infected mice. In line with its in vitro anti-ZIKV activity, 7DMA reduced viremia and delayed virus-induced morbidity and mortality in infected mice, which also validates this small animal model to assess the in vivo efficacy of novel ZIKV inhibitors. Since AG129 mice can generate an antibody response, and have been used in dengue vaccine studies, the model can also be used to assess the efficacy of ZIKV vaccines.  . + + + + Zmurko + Joanna + J + + Laboratory of Virology and Chemotherapy, KU Leuven - University of Leuven, Leuven, Belgium. + + + + Marques + Rafael E + RE + + Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. + + + + Schols + Dominique + D + + Laboratory of Virology and Chemotherapy, KU Leuven - University of Leuven, Leuven, Belgium. + + + + Verbeken + Erik + E + + Department of Pathology, University of Leuven and Leuven University Hospitals, Leuven, Belgium. + + + + Kaptein + Suzanne J F + SJ + + Laboratory of Virology and Chemotherapy, KU Leuven - University of Leuven, Leuven, Belgium. + + + + Neyts + Johan + J + + Laboratory of Virology and Chemotherapy, KU Leuven - University of Leuven, Leuven, Belgium. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 05 + 10 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + + + 0 + 7-deaza-2'-C-methyladenosine + + + 0 + Antiviral Agents + + + M351LCX45Y + Tubercidin + + + IM + + + J Biomol Screen. 2006 Apr;11(3):247-52 + 16490779 + + + Brain Pathol. 2003 Jul;13(3):279-90 + 12946018 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + Antiviral Res. 2011 Dec;92(3):453-60 + 22020302 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Curr Opin Virol. 2011 Dec;1(6):590-8 + 22440916 + + + Euro Surveill. 2014;19(4). pii: 20683 + 24507466 + + + PLoS Negl Trop Dis. 2014 Feb;8(2):e2681 + 24516683 + + + Euro Surveill. 2014;19(9). pii: 20720 + 24626205 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Emerg Infect Dis. 2014 Aug;20(8):1412-4 + 25062427 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + PLoS One. 2014;9(10):e109442 + 25310102 + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + J Virol. 2015 Jan 15;89(2):1254-66 + 25392217 + + + J Clin Virol. 2015 Feb;63:32-5 + 25600600 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Euro Surveill. 2015;20(23). pii: 21153 + 26084316 + + + J Virol. 2015 Sep;89(17):8880-96 + 26085147 + + + Antimicrob Agents Chemother. 2015 Sep;59(9):5483-93 + 26124166 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + Vaccine. 2015 Dec 10;33(50):7051-60 + 26478201 + + + BMJ. 2015;351:h6983 + 26698165 + + + BMJ. 2016;352:i212 + 26762624 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Antimicrob Agents Chemother. 2004 Oct;48(10):3944-53 + 15388457 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + J Infect Dis. 2007 Mar 1;195(5):665-74 + 17262707 + + + Med Microbiol Immunol. 2016 Jun;205(3):269-73 + 26702627 + + + J Infect Dev Ctries. 2015 Jun;9(6):684-5 + 26142684 + + + Curr Biol. 2005 Aug 9;15(15):R581 + 16085473 + + + + + Animals + + + Antiviral Agents + pharmacology + + + Cercopithecus aethiops + + + Disease Models, Animal + + + Male + + + Mice + + + Tubercidin + analogs & derivatives + pharmacology + + + Vero Cells + + + Virus Replication + drug effects + + + Zika Virus + drug effects + physiology + + + Zika Virus Infection + drug therapy + + +
+ + + + 2016 + 02 + 26 + + + 2016 + 04 + 15 + + + 2016 + 5 + 11 + 6 + 0 + + + 2016 + 5 + 11 + 6 + 0 + + + 2017 + 3 + 31 + 6 + 0 + + + epublish + + 27163257 + 10.1371/journal.pntd.0004695 + PNTD-D-16-00335 + PMC4862633 + + +
+ + + + + 27156023 + + 2017 + 09 + 21 + + + 2017 + 09 + 21 + +
+ + 1934-6069 + + 19 + 6 + + 2016 + Jun + 08 + + + Cell host & microbe + Cell Host Microbe + + Wolbachia Blocks Currently Circulating Zika Virus Isolates in Brazilian Aedes aegypti Mosquitoes. + + 771-4 + + 10.1016/j.chom.2016.04.021 + S1931-3128(16)30157-3 + + The recent association of Zika virus with cases of microcephaly has sparked a global health crisis and highlighted the need for mechanisms to combat the Zika vector, Aedes aegypti mosquitoes. Wolbachia pipientis, a bacterial endosymbiont of insect, has recently garnered attention as a mechanism for arbovirus control. Here we report that Aedes aegypti harboring Wolbachia are highly resistant to infection with two currently circulating Zika virus isolates from the recent Brazilian epidemic. Wolbachia-harboring mosquitoes displayed lower viral prevalence and intensity and decreased disseminated infection and, critically, did not carry infectious virus in the saliva, suggesting that viral transmission was blocked. Our data indicate that the use of Wolbachia-harboring mosquitoes could represent an effective mechanism to reduce Zika virus transmission and should be included as part of Zika control strategies. + Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved. + + + + Dutra + Heverton Leandro Carneiro + HL + + Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Centro de Pesquisas René Rachou-Fiocruz, Belo Horizonte, MG, 30190-002, Brazil. + + + + Rocha + Marcele Neves + MN + + Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Centro de Pesquisas René Rachou-Fiocruz, Belo Horizonte, MG, 30190-002, Brazil. + + + + Dias + Fernando Braga Stehling + FB + + Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Centro de Pesquisas René Rachou-Fiocruz, Belo Horizonte, MG, 30190-002, Brazil; Plataforma de Vetores de Doenças-Fiocruz, CE, 60190-800, Brazil. + + + + Mansur + Simone Brutman + SB + + Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Centro de Pesquisas René Rachou-Fiocruz, Belo Horizonte, MG, 30190-002, Brazil. + + + + Caragata + Eric Pearce + EP + + Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Centro de Pesquisas René Rachou-Fiocruz, Belo Horizonte, MG, 30190-002, Brazil. + + + + Moreira + Luciano Andrade + LA + + Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Centro de Pesquisas René Rachou-Fiocruz, Belo Horizonte, MG, 30190-002, Brazil. Electronic address: luciano@cpqrr.fiocruz.br. + + + + eng + + Journal Article + + + 2016 + 05 + 04 + +
+ + United States + Cell Host Microbe + 101302316 + 1931-3128 + + IM + + + Nature. 2011 Aug 24;476(7361):454-7 + 21866160 + + + PLoS Negl Trop Dis. 2014 Sep 11;8(9):e3115 + 25211492 + + + Science. 2015 Nov 27;350(6264):1012-3 + 26612926 + + + PLoS Pathog. 2016 Feb 18;12(2):e1005434 + 26891349 + + + Arq Neuropsiquiatr. 2016 Mar;74(3):253-5 + 27050856 + + + PLoS Pathog. 2013;9(6):e1003459 + 23825950 + + + PLoS Pathog. 2012 Feb;8(2):e1002548 + 22383881 + + + PLoS Negl Trop Dis. 2015 Jun 26;9(6):e0003894 + 26115104 + + + Acta Trop. 2014 Apr;132 Suppl:S150-63 + 24252486 + + + Am J Trop Med Hyg. 2005 Jan;72(1):67-73 + 15728869 + + + J Virol. 2014 Oct;88(20):11644-7 + 25078691 + + + Annu Rev Microbiol. 2008;62:71-92 + 18429680 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Trends Parasitol. 2016 Mar;32(3):207-18 + 26776329 + + + Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):E23-31 + 22123956 + + + Nature. 2011 Aug 24;476(7361):450-3 + 21866159 + + + PLoS Pathog. 2014 Sep 18;10(9):e1004369 + 25233341 + + + PLoS Negl Trop Dis. 2012;6(8):e1792 + 22953014 + + + Cell. 2009 Dec 24;139(7):1268-78 + 20064373 + + + Trans R Soc Trop Med Hyg. 2007 Apr;101(4):317-25 + 17084427 + + + Nat Rev Microbiol. 2008 Oct;6(10):741-51 + 18794912 + + + Enferm Infecc Microbiol Clin. 2016 Apr;34(4):247-52 + 26993436 + + + PLoS One. 2012;7(6):e38544 + 22685581 + + + PLoS One. 2014 Mar 27;9(3):e92424 + 24676277 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Science. 2013 May 10;340(6133):748-51 + 23661760 + + + Sci Transl Med. 2015 Mar 18;7(279):279ra37 + 25787763 + + + Microb Cell. 2016 Jun 27;3(7):293-295 + 28357366 + + + + + Aedes + microbiology + virology + + + Animals + + + Antibiosis + + + Brazil + + + Disease Transmission, Infectious + prevention & control + + + Female + + + Insect Vectors + microbiology + virology + + + Male + + + Saliva + microbiology + virology + + + Symbiosis + + + Wolbachia + physiology + + + Zika Virus + isolation & purification + physiology + + + Zika Virus Infection + microbiology + prevention & control + transmission + virology + + +
+ + + + 2016 + 04 + 15 + + + 2016 + 04 + 26 + + + 2016 + 04 + 26 + + + 2016 + 5 + 9 + 6 + 0 + + + 2016 + 5 + 9 + 6 + 0 + + + 2017 + 9 + 22 + 6 + 0 + + + ppublish + + 27156023 + S1931-3128(16)30157-3 + 10.1016/j.chom.2016.04.021 + PMC4906366 + + +
+ + + + + 27150580 + + 2016 + 06 + 08 + +
+ + 1471-0528 + + 123 + 8 + + 2016 + Jul + + + BJOG : an international journal of obstetrics and gynaecology + BJOG + + Microcephaly associated with maternal Zika virus infection. + + 1265-1269 + + 10.1111/1471-0528.14072 + + + Moron + A F + AF + + Department of Fetal Medicine, Hospital e Maternidade Santa Joana, São Paulo, Brazil. + + + + Cavalheiro + S + S + + Department of Paediatric Neurosurgery, Hospital e Maternidade Santa Joana, São Paulo, Brazil. + + + + Milani + Hjf + H + + Department of Fetal Medicine, Hospital e Maternidade Santa Joana, São Paulo, Brazil. + + + + Sarmento + Sgp + S + + Department of Fetal Medicine, Hospital e Maternidade Santa Joana, São Paulo, Brazil. + + + + Tanuri + C + C + + Neonatal Intensive Care Unit, Hospital e Maternidade Santa Joana, São Paulo, Brazil. + + + + de Souza + F F + FF + + Department of Diagnostic Imaging, Hospital e Maternidade Santa Joana, São Paulo, Brazil. + + + + Richtmann + R + R + + Department of Infectious Diseases, Hospital e Maternidade Santa Joana, São Paulo, Brazil. + + + + Witkin + S S + SS + + Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA. + + + + eng + + Case Reports + + + 2016 + 05 + 06 + +
+ + England + BJOG + 100935741 + 1470-0328 + +
+ + + + 2016 + 03 + 27 + + + 2016 + 5 + 7 + 6 + 0 + + + 2016 + 5 + 7 + 6 + 0 + + + 2016 + 5 + 7 + 6 + 0 + + + ppublish + + 27150580 + 10.1111/1471-0528.14072 + + +
+ + + + + 27148186 + + 2016 + 05 + 05 + + + 2017 + 02 + 20 + +
+ + 1664-302X + + 7 + + 2016 + + + Frontiers in microbiology + Front Microbiol + + Zika Virus: the Latest Newcomer. + + 496 + + 10.3389/fmicb.2016.00496 + + Since the beginning of this century, humanity has been facing a new emerging, or re-emerging, virus threat almost every year: West Nile, Influenza A, avian flu, dengue, Chikungunya, SARS, MERS, Ebola, and now Zika, the latest newcomer. Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, was identified in 1947 in a sentinel monkey in Uganda, and later on in humans in Nigeria. The virus was mainly confined to the African continent until it was detected in south-east Asia the 1980's, then in the Micronesia in 2007 and, more recently in the Americas in 2014, where it has displayed an explosive spread, as advised by the World Health Organization, which resulted in the infection of hundreds of thousands of people. ZIKV infection was characterized by causing a mild disease presented with fever, headache, rash, arthralgia, and conjunctivitis, with exceptional reports of an association with Guillain-Barre syndrome (GBS) and microcephaly. However, since the end of 2015, an increase in the number of GBS associated cases and an astonishing number of microcephaly in fetus and new-borns in Brazil have been related to ZIKV infection, raising serious worldwide public health concerns. Clarifying such worrisome relationships is, thus, a current unavoidable goal. Here, we extensively review what is currently known about ZIKV, from molecular biology, transmission routes, ecology, and epidemiology, to clinical manifestations, pathogenesis, diagnosis, prophylaxis, and public health. + + + + Saiz + Juan-Carlos + JC + + Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria Madrid, Spain. + + + + Vázquez-Calvo + Ángela + Á + + Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria Madrid, Spain. + + + + Blázquez + Ana B + AB + + Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria Madrid, Spain. + + + + Merino-Ramos + Teresa + T + + Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria Madrid, Spain. + + + + Escribano-Romero + Estela + E + + Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria Madrid, Spain. + + + + Martín-Acebes + Miguel A + MA + + Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria Madrid, Spain. + + + + eng + + Journal Article + Review + + + 2016 + 04 + 19 + +
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+ + + + 2016 + 02 + 23 + + + 2016 + 03 + 27 + + + 2016 + 5 + 6 + 6 + 0 + + + 2016 + 5 + 6 + 6 + 0 + + + 2016 + 5 + 6 + 6 + 1 + + + epublish + + 27148186 + 10.3389/fmicb.2016.00496 + PMC4835484 + + +
+ + + + + 27144515 + + 2018 + 01 + 08 + + + 2018 + 01 + 08 + +
+ + 1080-6059 + + 22 + 8 + + 2016 + 08 + + + Emerging infectious diseases + Emerging Infect. Dis. + + Time Lags between Exanthematous Illness Attributed to Zika Virus, Guillain-Barré Syndrome, and Microcephaly, Salvador, Brazil. + + 1438-44 + + 10.3201/eid2208.160496 + + Zika virus infection emerged as a public health emergency after increasing evidence for its association with neurologic disorders and congenital malformations. In Salvador, Brazil, outbreaks of acute exanthematous illness (AEI) attributed to Zika virus, Guillain-Barré syndrome (GBS), and microcephaly occurred in 2015. We investigated temporal correlations and time lags between these outbreaks to identify a common link between them by using epidemic curves and time series cross-correlations. Number of GBS cases peaked after a lag of 5-9 weeks from the AEI peak. Number of suspected cases of microcephaly peaked after a lag of 30-33 weeks from the AEI peak, which corresponded to time of potential infections of pregnant mothers during the first trimester. These findings support the association of GBS and microcephaly with Zika virus infection and provide evidence for a temporal relationship between timing of arboviral infection of pregnant women during the first trimester and birth outcome. + + + + Paploski + Igor A D + IA + + + Prates + Ana Paula P B + AP + + + Cardoso + Cristiane W + CW + + + Kikuti + Mariana + M + + + Silva + Monaise M O + MM + + + Waller + Lance A + LA + + + Reis + Mitermayer G + MG + + + Kitron + Uriel + U + + + Ribeiro + Guilherme S + GS + + + eng + + Journal Article + + + 2016 + 08 + 15 + +
+ + United States + Emerg Infect Dis + 9508155 + 1080-6040 + + IM + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + West Indian Med J. 1999 Mar;48(1):36-7 + 10375992 + + + Rev Bras Ginecol Obstet. 2010 Mar;32(3):105-11 + 20512256 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + Emerg Infect Dis. 2016 May;22(5):828-32 + 27088494 + + + Emerg Infect Dis. 2010 Mar;16(3):418-25 + 20202416 + + + Arq Neuropsiquiatr. 2004 Mar;62(1):144-6 + 15122449 + + + Euro Surveill. 2015;20(48):30079 + 26690898 + + + Emerg Infect Dis. 2010 Jan;16(1):1-7 + 20031035 + + + Ann Intern Med. 2016 May 17;164(10):689-91 + 26914810 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + PeerJ. 2016 Apr 05;4:e1904 + 27069825 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Rev Soc Bras Med Trop. 2016 Feb;49(1):1-3 + 27163559 + + + PLoS Negl Trop Dis. 2010 Oct 26;4(10):e858 + 21049010 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Antiviral Res. 2016 Jun;130:69-80 + 26996139 + + + PLoS Negl Trop Dis. 2014 Jul 17;8(7):e2996 + 25033077 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + Emerg Infect Dis. 2009 Mar;15(3):495-6 + 19239775 + + + Nature. 2016 Feb 4;530(7588):13-4 + 26842033 + + + Emerg Infect Dis. 2015 Dec;21(12):2274-6 + 26584464 + + + PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517 + 26914330 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Brazil + epidemiology + + + Disease Outbreaks + statistics & numerical data + + + Exanthema + complications + epidemiology + virology + + + Female + + + Guillain-Barre Syndrome + epidemiology + etiology + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Time Factors + + + Zika Virus Infection + complications + epidemiology + + + + Brazil + Guillain-Barré syndrome + Salvador + Zika virus + epidemiology + exanthematous illness + microcephaly + outbreaks + pregnant women + time lags + viruses + +
+ + + + 2016 + 5 + 5 + 6 + 0 + + + 2016 + 5 + 5 + 6 + 0 + + + 2018 + 1 + 9 + 6 + 0 + + + ppublish + + 27144515 + 10.3201/eid2208.160496 + PMC4982160 + + +
+ + + + + 27143490 + + 2017 + 02 + 01 + + + 2017 + 02 + 20 + +
+ + 1678-8060 + + 111 + 5 + + 2016 + May + + + Memorias do Instituto Oswaldo Cruz + Mem. Inst. Oswaldo Cruz + + Zika virus damages the human placental barrier and presents marked fetal neurotropism. + + 287-93 + + 10.1590/0074-02760160085 + S0074-02762016005006103 + + An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV) epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism. + + + + Noronha + Lucia de + Ld + + Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brasil. + + + + Zanluca + Camila + C + + Laboratório de Virologia Molecular, Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba, PR, Brasil. + + + + Azevedo + Marina Luize Viola + ML + + Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brasil. + + + + Luz + Kleber Giovanni + KG + + Instituto de Medicina Tropical, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil. + + + + Santos + Claudia Nunes Duarte Dos + CN + + Laboratório de Virologia Molecular, Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba, PR, Brasil. + + + + eng + + Case Reports + Journal Article + + + 2016 + 04 + 29 + +
+ + Brazil + Mem Inst Oswaldo Cruz + 7502619 + 0074-0276 + + + + 0 + RNA, Viral + + + IM + + + J Perinatol. 2001 Jun;21(4):255-7 + 11533844 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + N Engl J Med. 2016 Mar 10;374(10):951-8 + 26862926 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Vet Res. 2010 Nov-Dec;41(6):67 + 21188801 + + + Am J Ophthalmol. 2003 Oct;136(4):733-5 + 14516816 + + + Clin Perinatol. 2015 Mar;42(1):77-103, viii + 25677998 + + + J Neuroimmune Pharmacol. 2010 Sep;5(3):428-42 + 20652430 + + + PLoS Negl Trop Dis. 2016 Feb;10(2):e0004517 + 26914330 + + + Pediatr Dev Pathol. 2009 May-Jun;12(3):211-6 + 19018665 + + + Arch Dis Child Fetal Neonatal Ed. 1994 May;70(3):F163-5 + 8198407 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + J Infect Dis. 1993 Dec;168(6):1520-3 + 8245539 + + + Euro Surveill. 2014;19(9). pii: 20720 + 24626205 + + + Prog Neurobiol. 2010 Jun;91(2):108-20 + 20132860 + + + Am J Obstet Gynecol. 2015 Oct;213(4 Suppl):S53-69 + 26428503 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + J Clin Microbiol. 2000 May;38(5):1823-6 + 10790107 + + + Diagn Pathol. 2011;6:101 + 22024147 + + + MMWR Morb Mortal Wkly Rep. 2016;65(6):159-60 + 26890059 + + + Ginekol Pol. 2007 Jul;78(7):560-4 + 17915414 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + J Clin Virol. 2005 Apr;32(4):272-7 + 15780804 + + + + + Adult + + + Amniotic Fluid + virology + + + Brain + embryology + virology + + + Female + + + Humans + + + Immunohistochemistry + + + Infant, Newborn + + + Infectious Disease Transmission, Vertical + + + Male + + + Microcephaly + virology + + + Placenta + virology + + + Pregnancy + + + RNA, Viral + analysis + + + Viral Tropism + physiology + + + Zika Virus + physiology + + + Zika Virus Infection + congenital + + +
+ + + + 2016 + 03 + 04 + + + 2016 + 03 + 17 + + + 2016 + 5 + 5 + 6 + 0 + + + 2016 + 5 + 5 + 6 + 0 + + + 2017 + 2 + 2 + 6 + 0 + + + ppublish + + 27143490 + S0074-02762016005006103 + 10.1590/0074-02760160085 + PMC4878297 + + +
+ + + + + 27143306 + + 2017 + 04 + 20 + + + 2017 + 08 + 17 + +
+ + 1678-4464 + + 32 + 4 + + 2016 + + + Cadernos de saude publica + Cad Saude Publica + + Microcephaly in Pernambuco State, Brazil: epidemiological characteristics and evaluation of the diagnostic accuracy of cutoff points for reporting suspected cases. + + e00017216 + + 10.1590/0102-311X00017216 + S0102-311X2016000400801 + + The increase in the number of reported cases of microcephaly in Pernambuco State, and Northeast Brazil, characterized an epidemic that led the Brazilian Ministry of Health to declare a national public health emergency. The Brazilian Ministry of Health initially defined suspected cases as newborns with gestational age (GA) ≥ 37 weeks and head circumference (HC) ≤ 33cm, but in December 2015 this cutoff was lowered to 32cm. The current study aimed to estimate the accuracy, sensitivity, and specificity of different cutoff points for HC, using ROC curves, with the Fenton and Intergrowth (2014) curves as the gold standard. The study described cases reported in Pernambuco from August 8 to November 28, 2015, according to sex and GA categories. The Fenton and Intergrowth methods provide HC growth curves according to GA and sex, and microcephaly is defined as a newborn with HC below the 3rd percentile in these distributions. Of the 684 reported cases, 599 were term or post-term neonates. For these, the analyses with ROC curves show that according to the Fenton criterion the cutoff point with the largest area under the ROC curve, with sensitivity greater than specificity, is 32cm for both sexes. Using the Intergrowth method and following the same criteria, the cutoff points are 32cm and 31.5cm for males and females, respectively. The cutoff point identified by the Fenton method (32cm) coincided with the Brazilian Ministry of Health recommendation. Adopting Intergrowth as the standard, the choice would be 32cm for males and 31.5cm for females. The study identified the need to conduct critical and on-going analyses to evaluate cutoff points, including other characteristics for microcephaly case definition. + + + + Souza + Wayner Vieira de + WV + + Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brazil. + + + + Araújo + Thalia Velho Barreto de + TV + + Universidade Federal de Pernambuco, Recife, Brazil. + + + + Albuquerque + Maria de Fátima P Militão + Mde F + + Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brazil. + + + + Braga + Maria Cynthia + MC + + Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brazil. + + + + Ximenes + Ricardo Arraes de Alencar + RA + + Universidade Federal de Pernambuco, Recife, Brazil. + + + + Miranda-Filho + Demócrito de Barros + Dde B + + Universidade de Pernambuco, Recife, Brazil. + + + + Bezerra + Luciana Caroline Albuquerque + LC + + Secretaria Executiva de Vigilância em Saúde, Secretaria Estadual de Saúde de Pernambuco, Recife, Brasil. + + + + Dimech + George Santiago + GS + + Secretaria Executiva de Vigilância em Saúde, Secretaria Estadual de Saúde de Pernambuco, Recife, Brasil. + + + + Carvalho + Patrícia Ismael de + PI + + Secretaria Executiva de Vigilância em Saúde, Secretaria Estadual de Saúde de Pernambuco, Recife, Brasil. + + + + Assunção + Romildo Siqueira de + RS + + Secretaria Executiva de Vigilância em Saúde, Secretaria Estadual de Saúde de Pernambuco, Recife, Brasil. + + + + Santos + Roselene Hans + RH + + Secretaria Executiva de Vigilância em Saúde, Secretaria Estadual de Saúde de Pernambuco, Recife, Brasil. + + + + Oliveira + Wanderson Kleber de + WK + + Secretaria de Vigilância em Saúde, Ministério da Saúde, Brasília, Brazil. + + + + Rodrigues + Laura Cunha + LC + + London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom. + + + + Martelli + Celina Maria Turchi + CM + + Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brazil. + + + + eng + por + spa + + Journal Article + + Microcefalia no Estado de Pernambuco, Brasil: características epidemiológicas e avaliação da acurácia diagnóstica dos pontos de corte adotados para notificação de caso. + + 2016 + 04 + 29 + +
+ + Brazil + Cad Saude Publica + 8901573 + 0102-311X + + IM + + + Brazil + epidemiology + + + Female + + + Gestational Age + + + Humans + + + Infant, Newborn + + + Male + + + Microcephaly + diagnosis + epidemiology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + ROC Curve + + + Sensitivity and Specificity + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + epidemiology + + +
+ + + + 2016 + 02 + 01 + + + 2016 + 02 + 29 + + + 2016 + 5 + 5 + 6 + 0 + + + 2016 + 5 + 5 + 6 + 0 + + + 2017 + 4 + 21 + 6 + 0 + + + ppublish + + 27143306 + S0102-311X2016000400801 + 10.1590/0102-311X00017216 + + +
+ + + + + 27143305 + + 2017 + 04 + 20 + + + 2017 + 08 + 17 + +
+ + 1678-4464 + + 32 + 4 + + 2016 + + + Cadernos de saude publica + Cad Saude Publica + + The Zika epidemic in Cadernos de Saúde Pública / Reports in Public Health. + + e00010416 + + 10.1590/0102-311XED010416 + S0102-311X2016000400201 + + + Carvalho + Marilia Sá + MS + + + eng + por + spa + + Editorial + + Zika em Cadernos de Saúde Pública. + + 2016 + 04 + 29 + +
+ + Brazil + Cad Saude Publica + 8901573 + 0102-311X + + IM + + + Animals + + + Brazil + epidemiology + + + Disease Outbreaks + + + Editorial Policies + + + Humans + + + Microcephaly + epidemiology + virology + + + Periodicals as Topic + + + Zika Virus + + + Zika Virus Infection + + +
+ + + + 2016 + 5 + 5 + 6 + 0 + + + 2016 + 5 + 5 + 6 + 0 + + + 2017 + 4 + 21 + 6 + 0 + + + ppublish + + 27143305 + S0102-311X2016000400201 + 10.1590/0102-311XED010416 + + +
+ + + + + 27143174 + + 2017 + 06 + 30 + + + 2017 + 06 + 30 + +
+ + 1414-431X + + 49 + 5 + + 2016 + + + Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas + Braz. J. Med. Biol. Res. + + Overview of Zika virus (ZIKV) infection in regards to the Brazilian epidemic. + + e5420 + + 10.1590/1414-431X20165420 + S0100-879X2016000500201 + + Zika virus (ZIKV), a mosquito-borne flavivirus, belongs to the Flaviviridae family, genus Flavivirus. ZIKV was initially isolated in 1947 from a sentinel monkey in the Zika forest, Uganda. Little clinical importance was attributed to ZIKV, once only few symptomatic cases were reported in some African and Southeast Asiatic countries. This situation changed in 2007, when a large outbreak was registered on the Yap Island, Micronesia, caused by the Asian ZIKV lineage. Between 2013 and 2014, ZIKV spread explosively and caused many outbreaks in different islands of the Southern Pacific Ocean and in 2015 autochthonous transmission was reported in Brazil. Currently, Brazil is the country with the highest number of ZIKV-positive cases in Latin America. Moreover, for the first time after the discovery of ZIKV, the Brazilian scientists are studying the possibility for the virus to cause severe congenital infection related to microcephaly and serious birth defects due to the time-spatial coincidence of the alarming increase of newborns with microcephaly and the Brazilian ZIKV epidemic. The present review summarizes recent information for ZIKV epidemiology, clinical picture, transmission, diagnosis and the consequences of this emerging virus in Brazil. + + + + Slavov + S N + SN + + Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil. + + + + Otaguiri + K K + KK + + Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil. + + + + Kashima + S + S + + Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil. + + + + Covas + D T + DT + + Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + Review + + + 2016 + 04 + 29 + +
+ + Brazil + Braz J Med Biol Res + 8112917 + 0100-879X + + IM + + + J Travel Med. 2016 Jan;23(1). pii: tav011. doi: 10.1093/jtm/tav011 + 26782128 + + + PLoS Curr. 2014 Jun 02;6:null + 24944843 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Bull Soc Pathol Exot. 1993;86(1):21-8 + 8099299 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + PLoS Negl Trop Dis. 2014;8(1):e2636 + 24421913 + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + N Engl J Med. 2016 Mar 10;374(10):951-8 + 26862926 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Neuroepidemiology. 2009;32(2):150-63 + 19088488 + + + Euro Surveill. 2014;19(4). pii: 20685 + 24507467 + + + J Infect. 2016 May;72(5):507-24 + 26940504 + + + Lancet Infect Dis. 2010 Sep;10(9):643-51 + 20797646 + + + PLoS Negl Trop Dis. 2014 Feb;8(2):e2681 + 24516683 + + + N Engl J Med. 2012 Jun 14;366(24):2294-304 + 22694000 + + + Bull Soc Pathol Exot Filiales. 1982 May-Jul;75(3):262-6 + 6809352 + + + Virol J. 2013;10:311 + 24148652 + + + MMWR Morb Mortal Wkly Rep. 2016;65(3):59-62 + 26820244 + + + BMJ Case Rep. 2012;2012. pii: bcr2012007094. doi: 10.1136/bcr-2012-007094 + 23008381 + + + Ann Intern Med. 2016 May 17;164(10):689-91 + 26914810 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + Bull Soc Pathol Exot Filiales. 1978 Mar-Apr;71(2):140-6 + 743766 + + + PLoS Negl Trop Dis. 2016 Feb;10(2):e0004517 + 26914330 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Ann Trop Med Parasitol. 1983 Apr;77(2):131-7 + 6309104 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + Euro Surveill. 2014;19(13). pii: 20751 + 24721538 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + PLoS Negl Trop Dis. 2013;7(8):e2348 + 23936579 + + + Euro Surveill. 2014;19(9). pii: 20720 + 24626205 + + + Wkly Epidemiol Rec. 2016 Feb 19;91(7):73-81 + 26897760 + + + Trends Immunol. 2004 Feb;25(2):61-6 + 15102364 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + J Clin Microbiol. 2000 May;38(5):1823-6 + 10790107 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + J Clin Virol. 2015 Jul;68:53-5 + 26071336 + + + J Clin Virol. 2016 Apr;77:69-70 + 26921737 + + + Bull World Health Organ. 1970;43(4):539-52 + 5313066 + + + Am J Trop Med Hyg. 2001 May-Jun;64(5-6):310-6 + 11463123 + + + Lancet. 2016 Apr 2;387(10026):1481 + 26946926 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Arch Virol. 2006 Feb;151(2):309-25 + 16172840 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + BMJ Case Rep. 2012;2012. pii: bcr1220115378. doi: 10.1136/bcr.12.2011.5378 + 22605876 + + + PLoS One. 2007;2(4):e344 + 17406668 + + + Am J Epidemiol. 2011 Aug 1;174(3):326-35 + 21652600 + + + Rev Soc Bras Med Trop. 2016 Feb;49(1):4-10 + 26689277 + + + J Clin Virol. 2008 Sep;43(1):96-101 + 18674965 + + + Med Trop (Mars). 1981 Jan-Feb;41(1):53-61 + 6268925 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + AJNR Am J Neuroradiol. 2005 Feb;26(2):289-97 + 15709126 + + + Bull Soc Pathol Exot Filiales. 1981 Sep-Oct;74(5):490-9 + 6274526 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Bull Soc Pathol Exot Filiales. 1975 May-Jun;68(3):249-58 + 1243735 + + + Am J Perinatol. 2016 Jun;33(7):625-39 + 26939047 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Animals + + + Brazil + epidemiology + + + Epidemics + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Zika Virus + genetics + + + Zika Virus Infection + embryology + transmission + virology + + +
+ + + + 2016 + 03 + 21 + + + 2016 + 04 + 01 + + + 2016 + 5 + 5 + 6 + 0 + + + 2016 + 5 + 5 + 6 + 0 + + + 2017 + 7 + 1 + 6 + 0 + + + ppublish + + 27143174 + S0100-879X2016000500201 + 10.1590/1414-431X20165420 + PMC4855997 + + +
+ + + + + 27137695 + + 2017 + 07 + 05 + + + 2017 + 07 + 05 + +
+ + 1958-5381 + + 32 + 4 + + 2016 + Apr + + + Medecine sciences : M/S + Med Sci (Paris) + + [Zika virus, an emerging threat]. + + 378-86 + + 10.1051/medsci/20163204016 + + Zika virus, discovered in 1947, is particularly publicized because of its involvement in a major epidemic that began in 2015 and which epicenter is located in Latin America, mainly in Brazil. In the majority of cases (70-80 %) the infection is asymptomatic, however in some patients, moderate fever, skin rash, conjunctivitis and myalgia may occur. More alarming, neurological complications are reported, in particular cases of microcephaly probably resulting from the infection of women in the first or second trimester of pregnancy. Moreover, Guillain-Barré syndromes have also been identified in patients whose infection was confirmed. The extent of the current outbreak reveals the very primitive state of knowledge about the pathophysiology of this virus. Thus, a global effort is being undertaken in order to quickly characterize the molecular interaction of the virus with human cells, but also to develop specific diagnostic assays and vaccinal approaches. + © 2016 médecine/sciences – Inserm. + + + + Salinas + Sara + S + + UMR 1058, Inserm/université de Montpellier/Établissement français du sang, Pathogenesis and control of chronic infections, Inserm, 60, rue de Navacelles, 34394 Montpellier Cedex 5, France. + + + + Foulongne + Vincent + V + + UMR 1058, Inserm/université de Montpellier/Établissement français du sang, Pathogenesis and control of chronic infections, Inserm, 60, rue de Navacelles, 34394 Montpellier Cedex 5, France - Centre hospitalier universitaire de Montpellier, département de bactériologie-virologie, Montpellier, France. + + + + Loustalot + Fabien + F + + UMR 1058, Inserm/université de Montpellier/Établissement français du sang, Pathogenesis and control of chronic infections, Inserm, 60, rue de Navacelles, 34394 Montpellier Cedex 5, France. + + + + Fournier-Wirth + Chantal + C + + UMR 1058, Inserm/université de Montpellier/Établissement français du sang, Pathogenesis and control of chronic infections, Inserm, 60, rue de Navacelles, 34394 Montpellier Cedex 5, France - Établissement français du sang, parc Euromédecine, 34184 Montpellier Cedex 4, France. + + + + Molès + Jean-Pierre + JP + + UMR 1058, Inserm/université de Montpellier/Établissement français du sang, Pathogenesis and control of chronic infections, Inserm, 60, rue de Navacelles, 34394 Montpellier Cedex 5, France. + + + + Briant + Laurence + L + + CPBS, FRE3689, CNRS-université de Montpellier, 1919, route de Mende, 34293 Montpellier Cedex 5, France. + + + + Nagot + Nicolas + N + + UMR 1058, Inserm/université de Montpellier/Établissement français du sang, Pathogenesis and control of chronic infections, Inserm, 60, rue de Navacelles, 34394 Montpellier Cedex 5, France - Centre hospitalier universitaire de Montpellier, département de bactériologie-virologie, Montpellier, France. + + + + Van de Perre + Philippe + P + + UMR 1058, Inserm/université de Montpellier/Établissement français du sang, Pathogenesis and control of chronic infections, Inserm, 60, rue de Navacelles, 34394 Montpellier Cedex 5, France - Centre hospitalier universitaire de Montpellier, département de bactériologie-virologie, Montpellier, France. + + + + Simonin + Yannick + Y + + UMR 1058, Inserm/université de Montpellier/Établissement français du sang, Pathogenesis and control of chronic infections, Inserm, 60, rue de Navacelles, 34394 Montpellier Cedex 5, France - Université de Montpellier, 4, boulevard Henri IV, 34967 Montpellier Cedex 2, France. + + + + fre + + Journal Article + Review + + Le virus Zika - L'émergence d'une menace. + + 2016 + 05 + 02 + +
+ + France + Med Sci (Paris) + 8710980 + 0767-0974 + + IM + + + Brazil + epidemiology + + + Communicable Diseases, Emerging + epidemiology + + + Disease Outbreaks + statistics & numerical data + + + Epidemics + + + Female + + + Humans + + + Latin America + epidemiology + + + Male + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Zika Virus + physiology + + + Zika Virus Infection + epidemiology + + +
+ + + + 2016 + 5 + 4 + 6 + 0 + + + 2016 + 5 + 4 + 6 + 0 + + + 2017 + 7 + 6 + 6 + 0 + + + ppublish + + 27137695 + 10.1051/medsci/20163204016 + medsci20163204p378 + + +
+ + + + + 27135717 + + 2017 + 05 + 01 + + + 2017 + 05 + 01 + +
+ + 1539-3704 + + 165 + 3 + + 2016 + Aug + 02 + + + Annals of internal medicine + Ann. Intern. Med. + + The Emergence of Zika Virus: A Narrative Review. + + 175-83 + + 10.7326/M16-0617 + + Zika virus (ZIKV) is yet another arbovirus that is rapidly emerging on a global scale, on the heels of a chikungunya epidemic in the Americas that began in 2013. A ZIKV epidemic that began in Brazil in 2015 has now spread rapidly to more than 30 countries in the Americas and the Caribbean, infecting more than 2 million inhabitants. This epidemic currently continues unabated. The explosive nature of recent outbreaks and concerning links to Guillain-Barré syndrome and microcephaly are incompletely understood. Also unknown is the relative importance of sexual transmission of ZIKV and asymptomatic ZIKV infections to the overall burden of transmission. The limited understanding of ZIKV presents an enormous challenge for responses to this rapidly emerging threat to human health. This article reviews the existing literature on ZIKV and proposes critical questions for vaccine development and other areas of needed research. + + + + Anderson + Kathryn B + KB + + + Thomas + Stephen J + SJ + + + Endy + Timothy P + TP + + + eng + + Journal Article + Review + + + 2016 + 05 + 03 + +
+ + United States + Ann Intern Med + 0372351 + 0003-4819 + + + + 0 + Viral Vaccines + + + AIM + IM + + + Epidemics + prevention & control + + + Female + + + Humans + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Sexually Transmitted Diseases, Viral + epidemiology + + + Viral Vaccines + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + epidemiology + prevention & control + transmission + + +
+ + + + 2016 + 5 + 3 + 6 + 0 + + + 2016 + 5 + 3 + 6 + 0 + + + 2017 + 5 + 2 + 6 + 0 + + + ppublish + + 27135717 + 2520467 + 10.7326/M16-0617 + + +
+ + + + + 27134823 + + 2016 + 05 + 02 + + + 2017 + 02 + 20 + +
+ + 2214-2509 + + 4 + + 2016 + + + IDCases + IDCases + + Zika virus infections imported from Brazil to Portugal, 2015. + + 46-9 + + 10.1016/j.idcr.2016.03.004 + + Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present. + + + + Zé-Zé + L + L + + Centro de Estudos de Vectores e Doenças Infecciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge, Águas de Moura, Portugal; Biosystems & Integrative Sciences Institute, University of Lisbon, Faculty of Sciences, Campo Grande, Lisbon, Portugal. + + + + Prata + M B + MB + + Serviço de Doenças Infecciosas, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. + + + + Teixeira + T + T + + Unidade de Doenças Infecciosas/Serviço de Medicina Interna, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal. + + + + Marques + N + N + + Serviço de Doenças Infecciosas, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. + + + + Mondragão + A + A + + Unidade de Doenças Infecciosas/Serviço de Medicina Interna, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal. + + + + Fernandes + R + R + + Unidade de Doenças Infecciosas/Serviço de Medicina Interna, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal. + + + + Saraiva da Cunha + J + J + + Serviço de Doenças Infecciosas, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. + + + + Alves + M J + MJ + + Centro de Estudos de Vectores e Doenças Infecciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge, Águas de Moura, Portugal. + + + + eng + + Journal Article + + + 2016 + 04 + 07 + +
+ + Netherlands + IDCases + 101634540 + 2214-2509 + + + + Emerg Infect Dis. 2006 Oct;12(10):1493-9 + 17176562 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Travel Med Infect Dis. 2016 Jan-Feb;14 (1):13-5 + 26872416 + + + Lancet. 2016 Feb 20;387(10020):719-21 + 26876373 + + + Trans R Soc Trop Med Hyg. 1964 Jul;58:335-8 + 14175744 + + + J Med Virol. 2012 Sep;84(9):1501-5 + 22825831 + + + Mol Biol Evol. 2013 Dec;30(12):2725-9 + 24132122 + + + Arch Gesamte Virusforsch. 1973;43(4):315-9 + 4799154 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + Euro Surveill. 2013 Feb 07;18(6):null + 23410256 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Virol J. 2013 Oct 22;10:311 + 24148652 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 + 9254694 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Arbovirus + Imported cases + Zika virus + +
+ + + + 2016 + 03 + 14 + + + 2016 + 03 + 30 + + + 2016 + 03 + 30 + + + 2016 + 5 + 3 + 6 + 0 + + + 2016 + 5 + 3 + 6 + 0 + + + 2016 + 5 + 3 + 6 + 1 + + + epublish + + 27134823 + 10.1016/j.idcr.2016.03.004 + S2214-2509(16)30016-6 + PMC4833829 + + +
+ + + + + 27134728 + + 2016 + 05 + 02 + + + 2017 + 09 + 02 + +
+ + 2046-1402 + + 5 + + 2016 + + + F1000Research + F1000Res + + Open drug discovery for the Zika virus. + + 150 + + 10.12688/f1000research.8013.1 + + The Zika virus (ZIKV) outbreak in the Americas has caused global concern that we may be on the brink of a healthcare crisis. The lack of research on ZIKV in the over 60 years that we have known about it has left us with little in the way of starting points for drug discovery. Our response can build on previous efforts with virus outbreaks and lean heavily on work done on other flaviviruses such as dengue virus. We provide some suggestions of what might be possible and propose an open drug discovery effort that mobilizes global science efforts and provides leadership, which thus far has been lacking. We also provide a listing of potential resources and molecules that could be prioritized for testing as in vitro assays for ZIKV are developed. We propose also that in order to incentivize drug discovery, a neglected disease priority review voucher should be available to those who successfully develop an FDA approved treatment. Learning from the response to the ZIKV, the approaches to drug discovery used and the success and failures will be critical for future infectious disease outbreaks. + + + + Ekins + Sean + S + + Collaborations in Chemistry Inc, Fuquay-Varina, NC, USA; Collaborations Pharmaceuticals Inc., Fuquay-Varina, NC, USA; Collaborative Drug Discovery Inc., Burlingame, CA, USA. + + + + Mietchen + Daniel + D + + Open Knowledge Foundation Deutschland e.V., Berlin, Germany. + + + + Coffee + Megan + M + + The International Rescue Committee , NY, NY, USA. + + + + Stratton + Thomas P + TP + + Department of Pharmacology, Physiology and Neuroscience, Rutgers University-New Jersey Medical School, Newark, NJ, USA. + + + + Freundlich + Joel S + JS + + Department of Pharmacology, Physiology and Neuroscience, Rutgers University-New Jersey Medical School, Newark, NJ, USA; Division of Infectious Diseases, Department of Medicine, and the Ruy V. Lourenço Center for the Study of Emerging and Re-emerging Pathogens, Rutgers University-New Jersey Medical School, Newark, NJ, USA. + + + + Freitas-Junior + Lucio + L + + Chemical Biology and Screening Platform, Brazilian Laboratory of Biosciences (LNBio), CNPEM, Campinas, Brazil. + + + + Muratov + Eugene + E + + Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. + + + + Siqueira-Neto + Jair + J + + Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA. + + + + Williams + Antony J + AJ + + ChemConnector, Wake Forest, NC, USA. + + + + Andrade + Carolina + C + + LabMol - Laboratory for Molecular Modeling and Drug Design, Faculty of Pharmacy, Federal University of Goias, Goiânia, Brazil. + + + + eng + + Journal Article + + + 2016 + 02 + 09 + +
+ + England + F1000Res + 101594320 + 2046-1402 + + + + F1000Res. 2014 Nov 14;3:277 + 25653841 + + + PLoS Negl Trop Dis. 2013;7(2):e2073 + 23437413 + + + Nucleic Acids Res. 2009 Jan;37(Database issue):D387-92 + 18931379 + + + Drug Discov Today. 2014 Nov;19(11):1696-1698 + 25149597 + + + Parasitology. 2014 Jan;141(1):148-57 + 23985301 + + + Sci Transl Med. 2015 Apr 8;7(282):282ra49 + 25855495 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Arch Virol. 2007;152(4):687-96 + 17195954 + + + N Engl J Med. 2016 Jan 7;374(1):23-32 + 26735991 + + + J Virol. 2010 Jun;84(11):5678-86 + 20237086 + + + Sci Transl Med. 2013 Jun 19;5(190):190ra79 + 23785035 + + + PLoS One. 2013;8(4):e60579 + 23577127 + + + Bioinformatics. 2006 Jan 15;22(2):195-201 + 16301204 + + + J Chem Inf Model. 2015 Jun 22;55(6):1231-45 + 25994950 + + + PLoS One. 2010 Oct 04;5(10):null + 20957181 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Hepatology. 2014 May;59(5):1726-37 + 24375637 + + + Microbes Infect. 2016 Mar;18(3):167-8 + 26774330 + + + JAMA. 2015 Oct 27;314(16):1687-8 + 26414802 + + + Antiviral Res. 2014 Jun;106:125-34 + 24680954 + + + PLoS Negl Trop Dis. 2012;6(8):e1750 + 22953004 + + + JAMA. 2016 Mar 1;315(9):865-6 + 26818622 + + + Eur J Pharm Sci. 2015 Jan 23;66:1-9 + 25220493 + + + Tuberculosis (Edinb). 2011 Sep;91(5):479-86 + 21782516 + + + Eur J Med Chem. 2016 Mar 3;110:87-97 + 26807547 + + + PLoS Pathog. 2015 Dec 30;11(12):e1005350 + 26717518 + + + PLoS Negl Trop Dis. 2015 Jan 08;9(1):e3435 + 25569258 + + + Nucleic Acids Res. 2014 Jul;42(Web Server issue):W252-8 + 24782522 + + + Pharm Res. 2014 Feb;31(2):271-7 + 23990313 + + + Cell Syst. 2015 Dec 23;1(6):377-9 + 27136350 + + + Arch Gesamte Virusforsch. 1973;43(4):315-9 + 4799154 + + + Tuberculosis (Edinb). 2014 Mar;94(2):183-5 + 24388836 + + + Genome Announc. 2014 Jun 05;2(3):null + 24903869 + + + Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93 + 24841273 + + + N Engl J Med. 2016 Jan 7;374(1):33-42 + 26735992 + + + Pharm Res. 2016 Feb;33(2):433-49 + 26415647 + + + PLoS Pathog. 2012;8(4):e1002627 + 22496653 + + + J Med Chem. 2011 Mar 24;54(6):1704-14 + 21355607 + + + Antimicrob Agents Chemother. 2009 May;53(5):1823-31 + 19223625 + + + J Virol. 2012 Aug;86(16):8730-9 + 22674988 + + + Pharm Res. 2016 Apr;33(4):809-15 + 26666772 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + F1000Res. 2015 Feb 27;4:58 + 25949804 + + + J Virol. 2014 May;88(10):5533-42 + 24599995 + + + Virol J. 2015 Feb 08;12:16 + 25886260 + + + Antiviral Res. 2008 Oct;80(1):23-35 + 18611413 + + + Assay Drug Dev Technol. 2015 Dec;13(10 ):638-49 + 26192013 + + + Intervirology. 2014;57(3-4):151-7 + 25034482 + + + N Engl J Med. 2011 Aug 25;365(8):718-24 + 21793736 + + + Antiviral Res. 2009 Jan;81(1):6-15 + 18796313 + + + PLoS Negl Trop Dis. 2015 Jun 26;9(6):e0003878 + 26114876 + + + Lancet. 2016 Jan 16;387(10015):227-8 + 26775124 + + + J Hepatol. 2014 Apr;60(4):723-31 + 24295872 + + + ACS Chem Biol. 2008 Dec 19;3(12):765-75 + 19053243 + + + Assay Drug Dev Technol. 2010 Oct;8(5):553-70 + 20973722 + + + Drug Discov Today. 2011 Apr;16(7-8):298-310 + 21376136 + + + Antiviral Res. 2009 Dec;84(3):260-6 + 19800368 + + + Viruses. 2014 Feb 10;6(2):683-708 + 24517970 + + + ChemMedChem. 2013 Feb;8(2):313-21 + 23307663 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + F1000Res. 2015 Oct 20;4:1091 + 26834994 + + + Clin Pharmacokinet. 2016 Aug;55(8):907-23 + 26798032 + + + Biochem Biophys Res Commun. 2014 Jan 17;443(3):808-13 + 24342612 + + + J Infect Dis. 2015 Feb 1;211(3):394-404 + 25028694 + + + Drug Dev Ind Pharm. 2014 Nov;40(11):1429-34 + 24512098 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + J Med Chem. 2008 Aug 14;51(15):4660-71 + 18610998 + + + Antiviral Res. 2015 Jun;118:148-58 + 25842996 + + + Electrophoresis. 2009 Jun;30 Suppl 1:S162-73 + 19517507 + + + Discov Med. 2010 Dec;10(55):479-88 + 21189219 + + + F1000Res. 2015 Oct 20;4:1091 + 26834994 + + + + Aedes + Zika + dengue + drug discovery + ebola + flavivirus + microcephaly + yellow fever + +
+ + + + 2016 + 02 + 08 + + + 2016 + 5 + 3 + 6 + 0 + + + 2016 + 5 + 3 + 6 + 0 + + + 2016 + 5 + 3 + 6 + 1 + + + epublish + + 27134728 + 10.12688/f1000research.8013.1 + PMC4841202 + + +
+ + + + + 27124623 + + 2017 + 08 + 03 + + + 2018 + 01 + 09 + +
+ + 1096-9071 + + 88 + 8 + + 2016 + 08 + + + Journal of medical virology + J. Med. Virol. + + Zika virus: An update on epidemiology, pathology, molecular biology, and animal model. + + 1291-6 + + 10.1002/jmv.24563 + + Zika virus (ZIKV) was first described in 1947, and became a health emergency problem in 2016 when its association with fetal microcephaly cases was confirmed by Centers for Disease Control and Prevention (CDC) in the United States. To date, ZIKV infection has been documented in 66 countries. ZIKV is recognized as a neurotropic virus and numerous diseases manifested in multiple neurological disorders have been described, mainly in countries that have been exposed to ZIKV after the 2007 outbreak in the Federated States of Micronesia. The most dramatic consequence of ZIKV infection documented is the abrupt increase in fetal microcephaly cases in Brazil. Here, we present an update of the published research progress in the past few months. J. Med. Virol. 88:1291-1296, 2016. © 2016 Wiley Periodicals, Inc. + © 2016 Wiley Periodicals, Inc. + + + + Ramos da Silva + Suzane + S + + Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California. + + + + Gao + Shou-Jiang + SJ + + Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California. + + + + eng + + + R01 CA096512 + CA + NCI NIH HHS + United States + + + + Journal Article + Review + + + 2016 + 05 + 05 + +
+ + United States + J Med Virol + 7705876 + 0146-6615 + + IM + + + PLoS Negl Trop Dis. 2016 Apr 12;10(4):e0004636 + 27070912 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Lancet. 2016 Apr 30;387(10030):1811-2 + 27103126 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Arq Neuropsiquiatr. 2016 Mar;74(3):253-5 + 27050856 + + + Cell Stem Cell. 2016 May 5;18(5):591-6 + 27038591 + + + Nat Rev Neurol. 2016 Apr;12(4):187 + 26988905 + + + Clin Microbiol Rev. 2016 Jul;29(3):487-524 + 27029595 + + + Cell. 2016 May 19;165(5):1238-54 + 27118425 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Emerg Infect Dis. 2015 Feb;21(2):381-2 + 25625687 + + + Science. 2016 May 13;352(6287):816-8 + 27064148 + + + Travel Med Infect Dis. 2016 May-Jun;14 (3):286-8 + 27063653 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Lancet. 2016 Feb 20;387(10020):719-21 + 26876373 + + + J Immunol. 1952 Aug;69(2):223-34 + 14946416 + + + Cell Host Microbe. 2016 May 11;19(5):705-12 + 27066743 + + + J Immunol. 1954 Apr;72(4):248-57 + 13163397 + + + PLoS Negl Trop Dis. 2016 Mar 03;10(3):e0004543 + 26938868 + + + Infect Genet Evol. 2016 Jul;41:142-5 + 27071531 + + + Medicine (Baltimore). 2016 Mar;95(12):e3201 + 27015222 + + + Emerg Infect Dis. 2016 May;22(5):927-9 + 27089253 + + + Clin Perinatol. 2015 Mar;42(1):77-103, viii + 25677998 + + + Cell Host Microbe. 2016 May 11;19(5):561-5 + 27091703 + + + Cell Host Microbe. 2016 May 11;19(5):720-30 + 27066744 + + + Trans R Soc Trop Med Hyg. 1953 Jan;47(1):13-48 + 13077697 + + + Genome Announc. 2016 Mar 03;4(2):null + 26941134 + + + Lancet. 2016 Aug 13;388(10045):717-27 + 26948435 + + + J Virol. 2005 Jul;79(13):8339-47 + 15956579 + + + Virology. 1994 Sep;203(2):241-9 + 8053148 + + + J Clin Virol. 2016 Jan;74:1-3 + 26615388 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Medicine (Baltimore). 2016 Apr;95(14):e3257 + 27057874 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Genome Announc. 2014 Jun 05;2(3):null + 24903869 + + + Adv Virus Res. 2003;59:23-61 + 14696326 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Nature. 2016 Apr 19;533(7603):425-8 + 27093288 + + + J Virol. 2016 Apr 29;90(10 ):4864-75 + 26962217 + + + J Virol. 2007 Jul;81(13):7136-48 + 17459925 + + + Am J Trop Med Hyg. 1954 Jan;3(1):9-18 + 13114587 + + + Antiviral Res. 2013 May;98(2):192-208 + 23523765 + + + PLoS Negl Trop Dis. 2016 Apr 19;10(4):e0004682 + 27093158 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Antiviral Res. 2016 Jun;130:69-80 + 26996139 + + + N Engl J Med. 2016 Apr 21;374(16):1552-63 + 27028561 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 04;65(8):215-6 + 26937739 + + + Elife. 2016 Apr 19;5:null + 27090089 + + + Science. 2016 Apr 22;352(6284):467-70 + 27033547 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + N Engl J Med. 2016 Apr 21;374(16):1506-9 + 26959308 + + + Euro Surveill. 2016;21(9):null + 26967758 + + + Emerg Infect Dis. 2015 Dec;21(12):2274-6 + 26584464 + + + Euro Surveill. 2016;21(8):null + 26939607 + + + Emerg Infect Dis. 2016 May;22(5):925-7 + 27089120 + + + Nat Struct Mol Biol. 2016 May;23(5):456-8 + 27088990 + + + Science. 2016 Apr 15;352(6283):345-9 + 27013429 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Am J Hyg. 1954 Mar;59(2):157-63 + 13138582 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + BMJ. 2016 Feb 04;352:i720 + 26848011 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Aedes + virology + + + Animals + + + Brazil + epidemiology + + + Disease Models, Animal + + + Disease Outbreaks + + + Humans + + + Insect Vectors + virology + + + Mice + + + Microcephaly + virology + + + Micronesia + epidemiology + + + Nervous System Diseases + virology + + + Primates + + + Zika Virus + genetics + + + Zika Virus Infection + epidemiology + physiopathology + virology + + + + Zika virus + animal model + epidemiology + pathology + transmission + +
+ + + + 2016 + 04 + 27 + + + 2016 + 4 + 29 + 6 + 0 + + + 2016 + 4 + 29 + 6 + 0 + + + 2017 + 8 + 5 + 6 + 0 + + + ppublish + + 27124623 + 10.1002/jmv.24563 + PMC5235365 + NIHMS841574 + + +
+ + + + + 27114968 + + 2016 + 04 + 26 + + + 2017 + 02 + 20 + +
+ + 2250-1541 + + 8 + 3 + + 2016 + Mar + + + North American journal of medical sciences + N Am J Med Sci + + Zika Virus: A Global Threat to Humanity: A Comprehensive Review and Current Developments. + + 123-8 + + 10.4103/1947-2714.179112 + + At present, one of greatest concerns of medical personnel is Zika virus (ZIKV). Though it has been reported for quite a long time, its rapid emergence, new modes of transmission, and more importantly, the congenital anomalies associated with it have made the situation worse. It was first detected in 1947. After that, this infection was found in the countries of Africa as well as Asia. At present, interestingly it has been reported from Brazil. Microcephaly and intracranial calcification have been postulated to be related to maternal infection with this virus. Though it is asymptomatic in maximum number of cases, the serious complications of the infection should be prevented at the earliest. No specific treatment and vaccine are available till now. But research continues and hopefully, success is not far off. The right information about this infection should reach patients as well as physicians. It will prevent unnecessary panic. In August, Brazil is going to organize the Olympic and Paralympic Games and all eyes are now focused on this. In this review article, the authors have tried to focus on the important points about this infection. The data were gathered after searching for relevant articles published in PubMed, the World Health Organization's (WHO) website, Centers for Disease Control and Prevention's (CDC) website, and some other related websites on the Internet. + + + + Hajra + Adrija + A + + Department of Internal Medicine, Institute of Post Graduate Medical Education and Research (IPGMER), Kolkata, West Bengal, India. + + + + Bandyopadhyay + Dhrubajyoti + D + + Department of Accident and Emergency, Lady Hardinge Medical College, New Delhi, India. + + + + Hajra + Shyamal Kumar + SK + + Consultant Physician, NMB Diagnostics, Serampore, Hooghly, West Bengal, India. + + + + eng + + Journal Article + Review + +
+ + India + N Am J Med Sci + 101521411 + 1947-2714 + + + + J Gen Virol. 1988 Aug;69 ( Pt 8):1913-20 + 2841406 + + + BMJ. 2016 Feb 11;352:i875 + 26868672 + + + J Gen Virol. 2016 Feb;97(2):269-73 + 26684466 + + + Int J Infect Dis. 2016 Mar;44:11-5 + 26854199 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):120-1 + 26866485 + + + Arch Virol. 2016 Mar;161(3):665-8 + 26611910 + + + Blood Transfus. 2016 Mar;14 (2):95-100 + 26674815 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):63-7 + 26820387 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3 + 26796813 + + + J Glob Infect Dis. 2016 Jan-Mar;8(1):3-15 + 27013839 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Virol J. 2013 Oct 22;10:311 + 24148652 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + J Clin Virol. 2015 Jul;68:53-5 + 26071336 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865476 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Lancet. 2016 Feb 6;387(10018):521-4 + 26852261 + + + Swiss Med Wkly. 2016 Feb 09;146:w14296 + 26859285 + + + Am J Trop Med Hyg. 2015 Aug;93(2):380-3 + 26101272 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + Aedes mosquitoes + Zika virus (ZIKV) + microcephaly + pregnancy + +
+ + + + 2016 + 4 + 27 + 6 + 0 + + + 2016 + 4 + 27 + 6 + 0 + + + 2016 + 4 + 27 + 6 + 1 + + + ppublish + + 27114968 + 10.4103/1947-2714.179112 + NAJMS-8-123 + PMC4821090 + + +
+ + + + + 27111294 + + 2016 + 08 + 29 + + + 2017 + 02 + 20 + +
+ + 1935-2735 + + 10 + 4 + + 2016 + Apr + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + Zika Virus Outbreak in Haiti in 2014: Molecular and Clinical Data. + + e0004687 + + 10.1371/journal.pntd.0004687 + + Zika virus (ZIKV), first isolated in Uganda in 1947, is currently spreading rapidly through South America and the Caribbean. In Brazil, infection has been linked with microcephaly and other serious complications, leading to declaration of a public health emergency of international concern; however, there currently are only limited data on the virus (and its possible sources and manifestations) in the Caribbean. + From May, 2014-February, 2015, in conjunction with studies of chikungunya (CHIKV) and dengue (DENV) virus infections, blood samples were collected from children in the Gressier/Leogane region of Haiti who presented to a school clinic with undifferentiated febrile illness. Samples were initially screened by RT-PCR for CHIKV and DENV, with samples negative in these assays further screened by viral culture. + Of 177 samples screened, three were positive for ZIKV, confirmed by viral sequencing; DENV-1 was also identified in culture from one of the three positive case patients. Patients were from two different schools and 3 different towns, with all three cases occurring within a single week, consistent with the occurrence of an outbreak in the region. Phylogenetic analysis of known full genome viral sequences demonstrated a close relationship with ZIKV from Brazil; additional analysis of the NS5 gene, for which more sequences are currently available, showed the Haitian strains clustering within a monophyletic clade distinct from Brazilian, Puerto Rican and Guatemalan sequences, with all part of a larger clade including isolates from Easter Island. Phylogeography also clarified that at least three major African sub-lineages exist, and confirmed that the South American epidemic is most likely to have originated from an initial ZIKV introduction from French Polynesia into Easter Island, and then to the remainder of the Americas. + ZIKV epidemics in South America, as well as in Africa, show complex dissemination patterns. The virus appears to have been circulating in Haiti prior to the first reported cases in Brazil. Factors contributing to transmission and the possible linkage of this early Haitian outbreak with microcephaly remain to be determined. + + + + Lednicky + John + J + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States of America. + + + + Beau De Rochars + Valery Madsen + VM + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Department of Health Services Research, Management, and Policy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States of America. + + + + El Badry + Maha + M + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States of America. + + + + Loeb + Julia + J + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States of America. + + + + Telisma + Taina + T + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Christianville Foundation School Clinic, Gressier, Haiti. + + + + Chavannes + Sonese + S + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Christianville Foundation School Clinic, Gressier, Haiti. + + + + Anilis + Gina + G + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Christianville Foundation School Clinic, Gressier, Haiti. + + + + Cella + Eleonora + E + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Department of Pathology, Immunology, and Laboratory Sciences, College of Medicine, University of Florida, Gainesville, Florida, United States of America. + + + Department of Infectious Parasitic and Immunomediated Diseases, Reference Centre on Phylogeny, Molecular Epidemiology and Microbial Evolution (FEMEM)/Epidemiology Unit, Istituto Superiore di Sanita, Rome, Italy. + + + + Ciccozzi + Massimo + M + + Department of Infectious Parasitic and Immunomediated Diseases, Reference Centre on Phylogeny, Molecular Epidemiology and Microbial Evolution (FEMEM)/Epidemiology Unit, Istituto Superiore di Sanita, Rome, Italy. + + + + Rashid + Mohammed + M + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + + Okech + Bernard + B + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States of America. + + + + Salemi + Marco + M + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Department of Pathology, Immunology, and Laboratory Sciences, College of Medicine, University of Florida, Gainesville, Florida, United States of America. + + + + Morris + J Glenn + JG + Jr + + Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America. + + + Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 04 + 25 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + + + 0 + NS5 protein, flavivirus + + + 0 + RNA, Viral + + + 0 + Viral Nonstructural Proteins + + + IM + + + PLoS Negl Trop Dis. 2014;8(1):e2636 + 24421913 + + + Am J Trop Med Hyg. 2015 Apr;92(4):752-7 + 25732684 + + + N Engl J Med. 2016 Mar 10;374(10):951-8 + 26862926 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):242-7 + 26963593 + + + N Engl J Med. 2016 Jun 2;374(22):2142-51 + 27028667 + + + Arch Virol. 2016 Mar;161(3):665-8 + 26611910 + + + MMWR Morb Mortal Wkly Rep. 2016;65(3):55-8 + 26820163 + + + PLoS Negl Trop Dis. 2013;7(7):e2311 + 23875046 + + + J Med Virol. 2012 Sep;84(9):1501-5 + 22825831 + + + Virol J. 2008;5:16 + 18218114 + + + Emerg Infect Dis. 2007 May;13(5):764-7 + 17553261 + + + Virol J. 2013;10:311 + 24148652 + + + MMWR Morb Mortal Wkly Rep. 2016;65(3):59-62 + 26820244 + + + Mol Biol Evol. 2012 Aug;29(8):1969-73 + 22367748 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Genome Announc. 2014 Jun 05;2(3):null + 24903869 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Wkly Epidemiol Rec. 2015 Nov 6;90(45):609-10 + 26552108 + + + Syst Biol. 2004 Oct;53(5):793-808 + 15545256 + + + Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6815-9 + 9192648 + + + Emerg Infect Dis. 2016 May;22(5):933-5 + 27088323 + + + Int J Infect Dis. 2015 Dec;41:11-2 + 26482390 + + + Nucleic Acids Res. 1994 Nov 11;22(22):4673-80 + 7984417 + + + Lancet. 2015 Jul 18;386(9990):243-4 + 26194519 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Adolescent + + + Child + + + Child, Preschool + + + Cluster Analysis + + + Disease Outbreaks + + + Haiti + epidemiology + + + Humans + + + Infant + + + Molecular Sequence Data + + + Phylogeography + + + RNA, Viral + genetics + + + Reverse Transcriptase Polymerase Chain Reaction + + + Sequence Analysis, DNA + + + Sequence Homology + + + Viral Nonstructural Proteins + genetics + + + Virus Cultivation + + + Zika Virus + classification + genetics + isolation & purification + + + Zika Virus Infection + epidemiology + virology + + +
+ + + + 2016 + 03 + 02 + + + 2016 + 04 + 13 + + + 2016 + 4 + 26 + 6 + 0 + + + 2016 + 4 + 26 + 6 + 0 + + + 2016 + 8 + 30 + 6 + 0 + + + epublish + + 27111294 + 10.1371/journal.pntd.0004687 + PNTD-D-16-00366 + PMC4844159 + + +
+ + + + + 27105931 + + 2017 + 06 + 16 + + + 2018 + 03 + 03 + +
+ + 1471-5007 + + 32 + 7 + + 2016 + 07 + + + Trends in parasitology + Trends Parasitol. + + Zika Virus and Microcephaly: Challenges for a Long-Term Agenda. + + 508-511 + + S1471-4922(16)30002-2 + 10.1016/j.pt.2016.03.008 + + Since its introduction in Brazil in 2015, Zika virus (ZIKV) has begun to spread worldwide. One of the major infection outcomes is related to congenital malformations, but little is known about the pathogenicity of ZIKV. Here we discuss concerns about the ongoing ZIKV epidemic in the context of academic research, politics, and society. + Copyright © 2016 Elsevier Ltd. All rights reserved. + + + + Duarte Dos Santos + Claudia Nunes + CN + + Laboratório de Virologia Molecular, Instituto Carlos Chagas, Fiocruz PR, Curitiba, PR, Brasil. Electronic address: clsantos@fiocruz.br. + + + + Goldenberg + Samuel + S + + Laboratório de Regulação da Expressão Gênica(,) Instituto Carlos Chagas, Fiocruz PR, Curitiba, PR, Brasil. + + + + eng + + Journal Article + + + 2016 + 04 + 19 + +
+ + England + Trends Parasitol + 100966034 + 1471-4922 + + IM + + + Biomedical Research + trends + + + Female + + + Humans + + + Microcephaly + etiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + etiology + pathology + virology + + + Zika Virus + pathogenicity + + + Zika Virus Infection + complications + + +
+ + + + 2016 + 03 + 17 + + + 2016 + 03 + 23 + + + 2016 + 4 + 24 + 6 + 0 + + + 2016 + 4 + 24 + 6 + 0 + + + 2017 + 6 + 18 + 6 + 0 + + + ppublish + + 27105931 + S1471-4922(16)30002-2 + 10.1016/j.pt.2016.03.008 + + +
+ + + + + 27103126 + + 2016 + 06 + 01 + + + 2016 + 05 + 21 + +
+ + 1474-547X + + 387 + 10030 + + 2016 + Apr + 30 + + + Lancet (London, England) + Lancet + + Positive IgM for Zika virus in the cerebrospinal fluid of 30 neonates with microcephaly in Brazil. + + 1811-2 + + 10.1016/S0140-6736(16)30253-7 + S0140-6736(16)30253-7 + + + Cordeiro + Marli Tenorio + MT + + Department of Virology, Centro de Pesquisas Aggeu Magalhães-CPqAM, Fiocruz, Recife, PE 50670-420, Brazil. Electronic address: marli@cpqam.fiocruz.br. + + + + Pena + Lindomar J + LJ + + Department of Virology, Centro de Pesquisas Aggeu Magalhães-CPqAM, Fiocruz, Recife, PE 50670-420, Brazil. + + + + Brito + Carlos A + CA + + Department of Clinical Medicine, Federal University of Pernambuco, Recife, Brazil. + + + + Gil + Laura H + LH + + Department of Virology, Centro de Pesquisas Aggeu Magalhães-CPqAM, Fiocruz, Recife, PE 50670-420, Brazil. + + + + Marques + Ernesto T + ET + + Department of Virology, Centro de Pesquisas Aggeu Magalhães-CPqAM, Fiocruz, Recife, PE 50670-420, Brazil; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA. + + + + eng + + Letter + + + 2016 + 04 + 18 + +
+ + England + Lancet + 2985213R + 0140-6736 + + + + 0 + Immunoglobulin M + + + AIM + IM + + + Brazil + + + Enzyme-Linked Immunosorbent Assay + + + Humans + + + Immunoglobulin M + cerebrospinal fluid + + + Infant + + + Infant, Newborn + + + Microcephaly + cerebrospinal fluid + + + Real-Time Polymerase Chain Reaction + + + Reverse Transcriptase Polymerase Chain Reaction + + + Zika Virus + isolation & purification + + + Zika Virus Infection + cerebrospinal fluid + + +
+ + + + 2016 + 4 + 23 + 6 + 0 + + + 2016 + 4 + 23 + 6 + 0 + + + 2016 + 6 + 2 + 6 + 0 + + + ppublish + + 27103126 + S0140-6736(16)30253-7 + 10.1016/S0140-6736(16)30253-7 + + +
+ + + + + 27102780 + + 2017 + 03 + 01 + + + 2017 + 03 + 02 + +
+ + 1678-4391 + + 20 + 3 + + 2016 May-Jun + + + The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases + Braz J Infect Dis + + Zika virus infection during pregnancy and microcephaly occurrence: a review of literature and Brazilian data. + + 282-9 + + 10.1016/j.bjid.2016.02.006 + S1413-8670(16)30049-6 + + In November of 2015, the Ministry of Health of Brazil published an announcement confirming the relationship between Zika virus and the microcephaly outbreak in the Northeast, suggesting that infected pregnant women might have transmitted the virus to their fetuses. The objectives of this study were to conduct a literature review about Zika virus infection and microcephaly, evaluate national and international epidemiological data, as well as the current recommendations for the health teams. Zika virus is an arbovirus, whose main vector is the Aedes sp. The main symptoms of the infection are maculopapular rash, fever, non-purulent conjunctivitis, and arthralgia. Transmission of this pathogen occurs mainly by mosquito bite, but there are also reports via the placenta. Microcephaly is defined as a measure of occipto-frontal circumference being more than two standard deviations below the mean for age and gender. The presence of microcephaly demands evaluation of the patient, in order to diagnose the etiology. Health authorities issued protocols, reports and notes concerning the management of microcephaly caused by Zika virus, but there is still controversy about managing the cases. The Ministry of Health advises notifying any suspected or confirmed cases of children with microcephaly related to the pathogen, which is confirmed by a positive specific laboratory test for the virus. The first choice for imaging exam in children with this malformation is transfontanellar ultrasound. The most effective way to control this outbreak of microcephaly probably caused by this virus is to combat the vector. Since there is still uncertainty about the period of vulnerability of transmission via placenta, the use of repellents is crucial throughout pregnancy. More investigations studying the consequences of this viral infection on the body of newborns and in their development are required. + Copyright © 2016 Elsevier Editora Ltda. All rights reserved. + + + + De Carvalho + Newton Sérgio + NS + + Department of Gynecology and Obstetrics, Universidade Federal do Paraná (UFPR), Infectious Diseases in Gynecology and Obstetrics Sector, Clinics Hospital and Postgraduate Education Program in Obstetrics and Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil. Electronic address: newtonsdc@gmail.com. + + + + De Carvalho + Beatriz Freitas + BF + + Pontifícia Universidade Católica do Paraná (PUC-PR), Curitiba, PR, Brazil. + + + + Fugaça + Cyllian Arias + CA + + Pontifícia Universidade Católica do Paraná (PUC-PR), Curitiba, PR, Brazil. + + + + Dóris + Bruna + B + + Pontifícia Universidade Católica do Paraná (PUC-PR), Curitiba, PR, Brazil. + + + + Biscaia + Evellyn Silverio + ES + + Pontifícia Universidade Católica do Paraná (PUC-PR), Curitiba, PR, Brazil. + + + + eng + + Journal Article + Review + + + 2016 + 04 + 18 + +
+ + Brazil + Braz J Infect Dis + 9812937 + 1413-8670 + + IM + + + Aedes + virology + + + Animals + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Prevalence + + + Zika Virus Infection + complications + epidemiology + transmission + + + + Aedes mosquitoes + Microcephaly + Pregnancy + Zika virus + +
+ + + + 2015 + 12 + 29 + + + 2016 + 02 + 06 + + + 2016 + 02 + 23 + + + 2016 + 4 + 23 + 6 + 0 + + + 2016 + 4 + 23 + 6 + 0 + + + 2017 + 3 + 3 + 6 + 0 + + + ppublish + + 27102780 + S1413-8670(16)30049-6 + 10.1016/j.bjid.2016.02.006 + + +
+ + + + + 27093860 + + 2016 + 10 + 21 + + + 2016 + 12 + 30 + +
+ + 2049-9957 + + 5 + + 2016 + Apr + 19 + + + Infectious diseases of poverty + Infect Dis Poverty + + The global spread of Zika virus: is public and media concern justified in regions currently unaffected? + + 37 + + 10.1186/s40249-016-0132-y + + Zika virus, an Aedes mosquito-borne flavivirus, is fast becoming a worldwide public health concern following its suspected association with over 4000 recent cases of microcephaly among newborn infants in Brazil. + Prior to its emergence in Latin America in 2015-2016, Zika was known to exist at a relatively low prevalence in parts of Africa, Asia and the Pacific islands. An extension of its apparent global dispersion may be enabled by climate conditions suitable to support the population growth of A. aegypti and A. albopictus mosquitoes over an expanding geographical range. In addition, increased globalisation continues to pose a risk for the spread of infection. Further, suspicions of alternative modes of virus transmission (sexual and vertical), if proven, provide a platform for outbreaks in mosquito non-endemic regions as well. Since a vaccine or anti-viral therapy is not yet available, current means of disease prevention involve protection from mosquito bites, excluding pregnant females from travelling to Zika-endemic territories, and practicing safe sex in those countries. Importantly, in countries where Zika is reported as endemic, caution is advised in planning to conceive a baby until such time as the apparent association between infection with the virus and microcephaly is either confirmed or refuted. The question arises as to what advice is appropriate to give in more economically developed countries distant to the current epidemic and in which Zika has not yet been reported. Despite understandable concern among the general public that has been fuelled by the media, in regions where Zika is not present, such as North America, Europe and Australia, at this time any outbreak (initiated by an infected traveler returning from an endemic area) would very probably be contained locally. Since Aedes spp. has very limited spatial dispersal, overlapping high population densities of mosquitoes and humans would be needed to sustain a focus of infection. However, as A. aegypti is distinctly anthropophilic, future control strategies for Zika should be considered in tandem with the continuing threat to human wellbeing that is presented by dengue, yellow fever and Japanese encephalitis, all of which are transmitted by the same vector species. + + + + Gyawali + Narayan + N + + Infectious Diseases Research Group, School of Medical & Applied Sciences, Central Queensland University, Rockhampton, 4702, QLD, Australia. + + + + Bradbury + Richard S + RS + + Infectious Diseases Research Group, School of Medical & Applied Sciences, Central Queensland University, Rockhampton, 4702, QLD, Australia. + + + + Taylor-Robinson + Andrew W + AW + + Infectious Diseases Research Group, School of Medical & Applied Sciences, Central Queensland University, Rockhampton, 4702, QLD, Australia. a.taylor-robinson@cqu.edu.au. + + + + eng + + Journal Article + + + 2016 + 04 + 19 + +
+ + England + Infect Dis Poverty + 101606645 + 2049-9957 + + IM + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + Bull World Health Organ. 1970;43(2):319-25 + 5312528 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + MMWR Morb Mortal Wkly Rep. 2016;65(5):120-1 + 26866485 + + + Lancet. 2016 Jan 23;387(10016):335-6 + 26777915 + + + MMWR Morb Mortal Wkly Rep. 2016;65(2):30-3 + 26796813 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Blood Transfus. 2016 Mar;14(2):95-100 + 26674815 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + Ann Trop Med Parasitol. 1983 Apr;77(2):131-7 + 6309104 + + + Am J Trop Med Hyg. 1998 Mar;58(3):277-82 + 9546403 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Arch Virol. 2007;152(4):687-96 + 17195954 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + PLoS Negl Trop Dis. 2012;6(8):e1792 + 22953014 + + + Virulence. 2013 May 15;4(4):295-306 + 23552814 + + + PLoS Negl Trop Dis. 2013;7(8):e2348 + 23936579 + + + PLoS Negl Trop Dis. 2014;8(1):e2636 + 24421913 + + + Euro Surveill. 2014;19(4). pii: 20685 + 24507467 + + + Vaccine. 2014 Mar 10;32(12):1326-37 + 24486372 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Parasit Vectors. 2014;7:379 + 25138897 + + + PLoS One. 2014;9(10):e109442 + 25310102 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Emerg Infect Dis. 2015 Apr;21(4):722-4 + 25811410 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Antiviral Res. 2015 Aug;120:32-9 + 25979669 + + + BMC Infect Dis. 2015;15:492 + 26527535 + + + Int J Infect Dis. 2015 Dec;41:11-2 + 26482390 + + + + + Aedes + virology + + + Animals + + + Female + + + Global Health + + + Humans + + + Insect Vectors + virology + + + Male + + + Pregnancy + + + Zika Virus + physiology + + + Zika Virus Infection + epidemiology + prevention & control + transmission + virology + + + + Aedes + Arbovirus + Diagnosis + Epidemic + Flavivirus + Mosquito + Transmission + Treatment + Vector control + Zika + +
+ + + + 2016 + 02 + 18 + + + 2016 + 04 + 15 + + + 2016 + 4 + 21 + 6 + 0 + + + 2016 + 4 + 21 + 6 + 0 + + + 2016 + 10 + 22 + 6 + 0 + + + epublish + + 27093860 + 10.1186/s40249-016-0132-y + 10.1186/s40249-016-0132-y + PMC4837632 + + +
+ + + + + 27090438 + + 2017 + 04 + 28 + + + 2017 + 04 + 28 + +
+ + 1532-6535 + + 100 + 1 + + 2016 + Jul + + + Clinical pharmacology and therapeutics + Clin. Pharmacol. Ther. + + Zika virus: A new human teratogen? Implications for women of reproductive age. + + 28-30 + + 10.1002/cpt.386 + + In 2015 an unprecedented increase of reports of newborns with microcephaly in Brazil made news headlines around the world. A possible etiological association with prenatal maternal infection by Zika virus (ZIKV) was suggested based on temporal and geographic distribution of ZIKV infection and the subsequent increase in the reports of microcephaly cases. Here we discuss ZIKV as a new human teratogen, with comments on potential treatment options. + © 2016 ASCPT. + + + + Schuler-Faccini + L + L + + SIAT, Brazilian Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil. + + + Post-Graduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Brazil. + + + + Sanseverino + Mtv + M + + SIAT, Brazilian Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil. + + + Post-Graduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Brazil. + + + + Vianna + Fsl + F + + SIAT, Brazilian Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil. + + + Post-Graduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Brazil. + + + + da Silva + A A + AA + + SIAT, Brazilian Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil. + + + UNIVATES University, Brazil. + + + + Larrandaburu + M + M + + SIAT, Brazilian Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil. + + + Post-Graduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Brazil. + + + + Marcolongo-Pereira + C + C + + Veterinary Sciences Faculty, UniRitter Laureate International Universities, Brazil. + + + + Abeche + A M + AM + + SIAT, Brazilian Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil. + + + Obstetrics and Gynecology Department, Federal University of Rio Grande do Sul, Brazil. + + + + eng + + Journal Article + + + 2016 + 05 + 13 + +
+ + United States + Clin Pharmacol Ther + 0372741 + 0009-9236 + + AIM + IM + + + Animals + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Zika Virus Infection + complications + epidemiology + therapy + + +
+ + + + 2016 + 04 + 04 + + + 2016 + 04 + 14 + + + 2016 + 04 + 15 + + + 2016 + 4 + 20 + 6 + 0 + + + 2016 + 4 + 20 + 6 + 0 + + + 2017 + 4 + 30 + 6 + 0 + + + ppublish + + 27090438 + 10.1002/cpt.386 + + +
+ + + + + 27090089 + + 2017 + 11 + 27 + + + 2017 + 12 + 23 + +
+ + 2050-084X + + 5 + + 2016 + 04 + 19 + + + eLife + Elife + + Mapping global environmental suitability for Zika virus. + 10.7554/eLife.15272 + e15272 + + Zika virus was discovered in Uganda in 1947 and is transmitted by Aedes mosquitoes, which also act as vectors for dengue and chikungunya viruses throughout much of the tropical world. In 2007, an outbreak in the Federated States of Micronesia sparked public health concern. In 2013, the virus began to spread across other parts of Oceania and in 2015, a large outbreak in Latin America began in Brazil. Possible associations with microcephaly and Guillain-Barré syndrome observed in this outbreak have raised concerns about continued global spread of Zika virus, prompting its declaration as a Public Health Emergency of International Concern by the World Health Organization. We conducted species distribution modelling to map environmental suitability for Zika. We show a large portion of tropical and sub-tropical regions globally have suitable environmental conditions with over 2.17 billion people inhabiting these areas. + + + + Messina + Jane P + JP + 0000-0001-7829-1272 + + Department of Zoology, University of Oxford, Oxford, United Kingdom. + + + + Kraemer + Moritz Ug + MU + 0000-0001-8838-7147 + + Department of Zoology, University of Oxford, Oxford, United Kingdom. + + + + Brady + Oliver J + OJ + + Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. + + + + Pigott + David M + DM + + Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. + + + Institute for Health Metrics and Evaluation, University of Washington, Seattle, United States. + + + + Shearer + Freya M + FM + + Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. + + + + Weiss + Daniel J + DJ + + Department of Zoology, University of Oxford, Oxford, United Kingdom. + + + + Golding + Nick + N + + Department of BioSciences, University of Melbourne, Parkville, United Kingdom. + + + + Ruktanonchai + Corrine W + CW + + WorldPop project, Department of Geography and Environment, University of Southampton, Southampton, United Kingdom. + + + + Gething + Peter W + PW + + Department of Zoology, University of Oxford, Oxford, United Kingdom. + + + + Cohn + Emily + E + + Boston Children's Hospital, Harvard Medical School, Boston, United Kingdom. + + + + Brownstein + John S + JS + + Boston Children's Hospital, Harvard Medical School, Boston, United Kingdom. + + + + Khan + Kamran + K + + Department of Medicine, Division of Infectious Diseases, University of Toronto, Toronto, Canada. + + + Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Canada. + + + + Tatem + Andrew J + AJ + + WorldPop project, Department of Geography and Environment, University of Southampton, Southampton, United Kingdom. + + + Flowminder Foundation, Stockholm, Sweden. + + + + Jaenisch + Thomas + T + + Section Clinical Tropical Medicine, Department for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany. + + + German Centre for Infection Research (DZIF), Heidelberg partner site, Heidelberg, Germany. + + + + Murray + Christopher Jl + CJ + + Institute for Health Metrics and Evaluation, University of Washington, Seattle, United States. + + + + Marinho + Fatima + F + + Secretariat of Health Surveillance, Ministry of Health Brazil, Brasilia, Brazil. + + + + Scott + Thomas W + TW + + Department of Entomology and Nematology, University of California Davis, Davis, United States. + + + + Hay + Simon I + SI + 0000-0002-0611-7272 + + Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. + + + Institute for Health Metrics and Evaluation, University of Washington, Seattle, United States. + + + + eng + + + 095066 + Wellcome Trust + United Kingdom + + + P01 AI098670 + AI + NIAID NIH HHS + United States + + + R01 LM010812 + LM + NLM NIH HHS + United States + + + + Journal Article + Research Support, Non-U.S. Gov't + Research Support, N.I.H., Extramural + + + 2016 + 04 + 19 + +
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1;30(2):265-282 + 20161131 + + + Adv Parasitol. 2006;62:37-77 + 16647967 + + + Parasit Vectors. 2013;6:351 + 24330720 + + + Bull World Health Organ. 1972;47(3):433-7 + 4539825 + + + Proc Natl Acad Sci U S A. 2011 May 3;108(18):7460-5 + 21502510 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Rev Panam Salud Publica. 2006 Jun;19(6):379-84 + 16968592 + + + J Med Entomol. 2001 May;38(3):441-5 + 11372971 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Ecol Appl. 2009 Jan;19(1):181-97 + 19323182 + + + Indian J Med Res. 2012 Oct;136(4):649-55 + 23168706 + + + ISPRS J Photogramm Remote Sens. 2014 Dec;98:106-118 + 25642100 + + + Sci Data. 2015;2:150045 + 26347245 + + + Int J Health Geogr. 2012;11:7 + 22433126 + + + Proc Biol Sci. 2011 Aug 22;278(1717):2446-54 + 21227970 + + + Sci Data. 2015;2:150035 + 26175912 + + + Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):994-9 + 23277539 + + + J Infect Dis. 2016 Feb 15;213(4):604-10 + 26410592 + + + PLoS Med. 2008 Mar 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13138582 + + + Trop Med Int Health. 2014 Jul;19(7):863-71 + 24862214 + + + Sex Transm Infect. 2015 Aug;91(5):359 + 26113729 + + + + + Animals + + + Environment + + + Global Health + + + Humans + + + Mosquito Vectors + growth & development + + + Tropical Climate + + + Zika Virus + physiology + + + Zika Virus Infection + epidemiology + transmission + + + + Zika virus + disease mapping + epidemiology + global health + human + infectious disease + microbiology + vector-borne disease + virus + +
+ + + + 2016 + 02 + 15 + + + 2016 + 04 + 10 + + + 2016 + 4 + 20 + 6 + 0 + + + 2016 + 4 + 20 + 6 + 0 + + + 2017 + 11 + 29 + 6 + 0 + + + epublish + + 27090089 + 10.7554/eLife.15272 + PMC4889326 + + +
+ + + + + 27088494 + + 2016 + 12 + 30 + + + 2016 + 12 + 31 + +
+ + 1080-6059 + + 22 + 5 + + 2016 + May + + + Emerging infectious diseases + Emerging Infect. Dis. + + Projecting Month of Birth for At-Risk Infants after Zika Virus Disease Outbreaks. + + 828-32 + + 10.3201/eid2205.160290 + + The marked increase in infants born with microcephaly in Brazil after a 2015 outbreak of Zika virus (Zika virus) disease suggests an association between maternal Zika virus infection and congenital microcephaly. To project the timing of delivery of infants born to mothers infected during early pregnancy in 1 city in Bahia State, Brazil, we incorporated data on reported Zika virus disease cases and microcephaly cases into a graphical schematic of weekly birth cohorts. We projected that these births would occur through February 2016. Applying similar projections to a hypothetical location at which Zika virus transmission started in November, we projected that full-term infants at risk for Zika virus infection would be born during April-September 2016. We also developed a modifiable spreadsheet tool that public health officials and researchers can use for their countries to plan for deliveries of infants to women who were infected with Zika virus during different pregnancy trimesters. + + + + Reefhuis + Jennita + J + + + Gilboa + Suzanne M + SM + + + Johansson + Michael A + MA + + + Valencia + Diana + D + + + Simeone + Regina M + RM + + + Hills + Susan L + SL + + + Polen + Kara + K + + + Jamieson + Denise J + DJ + + + Petersen + Lyle R + LR + + + Honein + Margaret A + MA + + + eng + + Journal Article + +
+ + United States + Emerg Infect Dis + 9508155 + 1080-6040 + + IM + + + Emerg Infect Dis. 2016 May;22(5):925-7 + 27089120 + + + Lancet. 1982 Oct 9;2(8302):781-4 + 6126663 + + + J Clin Virol. 2006 Feb;35(2):216-20 + 16368262 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + J Clin Virol. 2010 Feb;47(2):201-2 + 20006542 + + + Euro Surveill. 2014;19(13). pii: 20751 + 24721538 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 26;65(7):182-7 + 26914500 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + MMWR Morb Mortal Wkly Rep. 2016;65(3):55-8 + 26820163 + + + MMWR Morb Mortal Wkly Rep. 2016;65(3):59-62 + 26820244 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):122-7 + 26866840 + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Emerg Infect Dis. 2015 Dec;21(12):2274-6 + 26584464 + + + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Humans + + + Incidence + + + Infant + + + Microcephaly + epidemiology + etiology + + + Pregnancy + + + Pregnancy Complications, Infectious + virology + + + Public Health Surveillance + + + Risk + + + Zika Virus + + + Zika Virus Infection + complications + transmission + virology + + + + Brazil + ZIKAV + Zika virus + birth defects + flavivirus + microcephaly + pregnancy + vector-borne infections + viruses + +
+ + + + 2016 + 4 + 19 + 6 + 0 + + + 2016 + 4 + 19 + 6 + 0 + + + 2016 + 12 + 31 + 6 + 0 + + + ppublish + + 27088494 + 10.3201/eid2205.160290 + PMC4861542 + + +
+ + + + + 27080092 + + 2017 + 02 + 17 + + + 2017 + 08 + 17 + +
+ + 1433-0350 + + 32 + 6 + + 2016 + Jun + + + Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery + Childs Nerv Syst + + Microcephaly and Zika virus: neonatal neuroradiological aspects. + + 1057-60 + + 10.1007/s00381-016-3074-6 + + The aim of this study is to describe some radiological features in the newborns with microcephaly caused by Zika virus infection during pregnancy. + We radiologically analyzed 13 cases of newborns with microcephaly born to mothers who were infected by the Zika virus in the early stage of pregnancy. + The most frequently observed radiological findings were microcephaly and decreased brain parenchymal volume associated with lissencephaly, ventriculomegaly secondary to the lack of brain tissue (not hypertensive), and coarse and anarchic calcifications mainly involving the subcortical cortical transition, and the basal ganglia. + Although it cannot be concluded that there is a definitive pathognomonic radiographic pattern of microcephaly caused by Zika virus, gross calcifications and anarchic distribution involving the subcortical cortical transition and the basal ganglia, in association with lissencephaly and in the absence of hypertensive ventriculomegaly, are characteristic of this type of infection. + + + + Cavalheiro + Sergio + S + + Department of Neurosurgery, Federal University of Sao Paulo, Rua Botucatu, 591, conj 41, Sao Paulo, SP, 04023-062, Brazil. sergiocavalheironeuro@gmail.com. + + + + Lopez + Amanda + A + + Neurosurgery Service of Hospital da Restauração, Recife, Pernambuco, Brazil. + + + + Serra + Suzana + S + + Neurosurgery Service of Hospital da Restauração, Recife, Pernambuco, Brazil. + + + + Da Cunha + Arthur + A + + Neurosurgery Service of Hospital da Restauração, Recife, Pernambuco, Brazil. + + + + da Costa + Marcos Devanir S + MD + + Department of Neurosurgery, Federal University of Sao Paulo, Rua Botucatu, 591, conj 41, Sao Paulo, SP, 04023-062, Brazil. + + + + Moron + Antonio + A + + Department of Obstetrics, Federal University of Sao Paulo, Sao Paulo, SP, Brazil. + + + + Lederman + Henrique M + HM + + Department of Diagnostic Imaging, Federal University of Sao Paulo, Sao Paulo, SP, Brazil. + + + + eng + + Journal Article + + + 2016 + 04 + 14 + +
+ + Germany + Childs Nerv Syst + 8503227 + 0256-7040 + + IM + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Lancet. 2016 Apr 9;387(10027):1587-90 + 26952548 + + + AJNR Am J Neuroradiol. 1994 Apr;15(4):703-15 + 8010273 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Arq Neuropsiquiatr. 1964 Sep;22:166-94 + 14222495 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Brain + diagnostic imaging + virology + + + Female + + + Humans + + + Infant + + + Infant, Newborn + + + Magnetic Resonance Imaging + + + Microcephaly + diagnostic imaging + etiology + virology + + + Pregnancy + + + Retrospective Studies + + + Zika Virus + pathogenicity + + + Zika Virus Infection + complications + diagnostic imaging + + + + Aedes aegypti + Intracranial calcifications + Lissencephaly + Microcephaly + Ventriculomegaly + Zika virus + +
+ + + + 2016 + 03 + 21 + + + 2016 + 03 + 27 + + + 2016 + 4 + 16 + 6 + 0 + + + 2016 + 4 + 16 + 6 + 0 + + + 2017 + 2 + 18 + 6 + 0 + + + ppublish + + 27080092 + 10.1007/s00381-016-3074-6 + 10.1007/s00381-016-3074-6 + PMC4882355 + + +
+ + + + + 27075009 + + 2016 + 08 + 15 + + + 2016 + 11 + 26 + +
+ + 1756-1833 + + 353 + + 2016 + Apr + 13 + + + BMJ (Clinical research ed.) + BMJ + + Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study. + + i1901 + + 10.1136/bmj.i1901 + + To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. + Retrospective study with a case series. + Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. + 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. + Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. + Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus--the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. + Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical development, often with a simplified gyral pattern and predominance of pachygyria or polymicrogyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem. + Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. + + + + de Fatima Vasco Aragao + Maria + M + + Centro Diagnostico Multimagem, Rua Frei Matias Tevis, 194, Ilha do Leite Recife Pernambuco 52010-450, Brazil; Medical School, Mauricio de Nassau University, Recife, Pernambuco, Brazil fatima.vascoaragao@gmail.com. + + + + van der Linden + Vanessa + V + + Association for Assistance of Disabled Children, Recife, Brazil; Barão de Lucena Hospital, Recife, Brazil. + + + + Brainer-Lima + Alessandra Mertens + AM + + PROCAPE, University of Pernambuco, Recife, Brazil. + + + + Coeli + Regina Ramos + RR + + Oswaldo Cruz University Hospital, Recife, Brazil. + + + + Rocha + Maria Angela + MA + + Oswaldo Cruz University Hospital, Recife, Brazil. + + + + Sobral da Silva + Paula + P + + Oswaldo Cruz University Hospital, Recife, Brazil. + + + + Durce Costa Gomes de Carvalho + Maria + M + + Oswaldo Cruz University Hospital, Recife, Brazil. + + + + van der Linden + Ana + A + + Prof Fernando Figueira Integral Medicine Institute, Recife, Brazil. + + + + Cesario de Holanda + Arthur + A + + Medical School, Federal University of Pernambuco, Recife, Brazil. + + + + Valenca + Marcelo Moraes + MM + + Neurology and Neurosurgery, Federal University of Pernambuco, Recife, Brazil. + + + + eng + + Journal Article + Video-Audio Media + + + 2016 + 04 + 13 + +
+ + England + BMJ + 8900488 + 0959-535X + + + + 0 + Immunoglobulin M + + + AIM + IM + + + AJNR Am J Neuroradiol. 2003 Jan;24(1):28-32 + 12533323 + + + Nature. 2004 Jul 8;430(6996):242-9 + 15241422 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Nat Med. 2004 Dec;10(12 Suppl):S98-109 + 15577938 + + + AJNR Am J Neuroradiol. 2009 Jan;30(1):19-30 + 19039041 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Fetal Diagn Ther. 2011;30(2):141-9 + 21952353 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + J Clin Microbiol. 2000 May;38(5):1823-6 + 10790107 + + + Rev Med Virol. 2012 Mar;22(2):69-87 + 22086854 + + + Euro Surveill. 2014;19(13). pii: 20751 + 24721538 + + + Dev Med Child Neurol. 2014 Jul;56(7):612-26 + 24372060 + + + Radiographics. 2015 Jan-Feb;35(1):200-20 + 25590398 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + MMWR Morb Mortal Wkly Rep. 2016;65(3):59-62 + 26820244 + + + N Engl J Med. 2016 Mar 10;374(10):951-8 + 26862926 + + + BMJ. 2016;353:i2194 + 27083981 + + + + + Adult + + + Agenesis of Corpus Callosum + complications + diagnosis + + + Brain + diagnostic imaging + pathology + + + Brazil + + + Calcinosis + complications + diagnosis + + + Cisterna Magna + diagnostic imaging + pathology + + + Corpus Callosum + diagnostic imaging + pathology + + + Female + + + Humans + + + Hydrocephalus + complications + diagnosis + + + Immunoglobulin M + cerebrospinal fluid + + + Infant + + + Infant, Newborn + + + Magnetic Resonance Imaging + + + Male + + + Malformations of Cortical Development + complications + diagnosis + + + Microcephaly + complications + diagnosis + + + Nerve Fibers, Myelinated + diagnostic imaging + pathology + + + Organ Size + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Retrospective Studies + + + Tomography, X-Ray Computed + + + White Matter + diagnostic imaging + pathology + + + Young Adult + + + Zika Virus + immunology + + + Zika Virus Infection + complications + congenital + diagnosis + + +
+ + + + 2016 + 4 + 15 + 6 + 0 + + + 2016 + 4 + 15 + 6 + 0 + + + 2016 + 8 + 16 + 6 + 0 + + + epublish + + 27075009 + PMC4830901 + + +
+ + + + + 27074377 + + 2016 + 06 + 03 + + + 2016 + 05 + 19 + +
+ + 1533-4406 + + 374 + 20 + + 2016 + May + 19 + + + The New England journal of medicine + N. Engl. J. Med. + + Zika Virus and Birth Defects--Reviewing the Evidence for Causality. + + 1981-7 + + 10.1056/NEJMsr1604338 + + + Rasmussen + Sonja A + SA + + From the Division of Public Health Information Dissemination, Center for Surveillance, Epidemiology, and Laboratory Services (S.A.R.), Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion (D.J.J.), and Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities (M.A.H.), Centers for Disease Control and Prevention, Atlanta; and the Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO (L.R.P.). + + + + Jamieson + Denise J + DJ + + From the Division of Public Health Information Dissemination, Center for Surveillance, Epidemiology, and Laboratory Services (S.A.R.), Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion (D.J.J.), and Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities (M.A.H.), Centers for Disease Control and Prevention, Atlanta; and the Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO (L.R.P.). + + + + Honein + Margaret A + MA + + From the Division of Public Health Information Dissemination, Center for Surveillance, Epidemiology, and Laboratory Services (S.A.R.), Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion (D.J.J.), and Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities (M.A.H.), Centers for Disease Control and Prevention, Atlanta; and the Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO (L.R.P.). + + + + Petersen + Lyle R + LR + + From the Division of Public Health Information Dissemination, Center for Surveillance, Epidemiology, and Laboratory Services (S.A.R.), Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion (D.J.J.), and Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities (M.A.H.), Centers for Disease Control and Prevention, Atlanta; and the Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO (L.R.P.). + + + + eng + + Journal Article + + + 2016 + 04 + 13 + +
+ + United States + N Engl J Med + 0255562 + 0028-4793 + + AIM + IM + + + Brazil + epidemiology + + + Causality + + + Humans + + + Microcephaly + epidemiology + virology + + + Zika Virus + + + Zika Virus Infection + complications + + +
+ + + + 2016 + 4 + 14 + 6 + 0 + + + 2016 + 4 + 14 + 6 + 0 + + + 2016 + 6 + 4 + 6 + 0 + + + ppublish + + 27074377 + 10.1056/NEJMsr1604338 + + +
+ + + + + 27071041 + + 2018 + 01 + 12 + + + 2018 + 01 + 12 + +
+ + 1080-6059 + + 22 + 6 + + 2016 + 06 + + + Emerging infectious diseases + Emerging Infect. Dis. + + Microcephaly in Infants, Pernambuco State, Brazil, 2015. + + 1090-1093 + + 10.3201/eid2206.160062 + + We studied the clinical characteristics for 104 infants born with microcephaly in the delivery hospitals of Pernambuco State, Brazil, during 2015. Testing is ongoing to exclude known infectious causes. However, microcephaly peaked in October and demonstrated central nervous system abnormalities with brain dysgenesis and intracranial calcifications consistent with an intrauterine infection. + + + + Microcephaly Epidemic Research Group + + + eng + + Historical Article + Journal Article + + + 2016 + 06 + 15 + +
+ + United States + Emerg Infect Dis + 9508155 + 1080-6040 + + IM + + + MMWR Morb Mortal Wkly Rep. 2016;65(9):242-7 + 26963593 + + + N Engl J Med. 2016 Mar 10;374(10):951-8 + 26862926 + + + BMC Pediatr. 2013;13:59 + 23601190 + + + Am J Public Health. 2016 Apr;106(4):598-600 + 26959258 + + + Clin Perinatol. 2015 Mar;42(1):77-103, viii + 25677998 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Cad Saude Publica. 2014 Aug;30 Suppl 1:S1-12 + 25167191 + + + + + Adolescent + + + Adult + + + Brazil + epidemiology + + + Female + + + History, 21st Century + + + Humans + + + Infant + + + Infant, Newborn + + + Male + + + Microcephaly + diagnosis + epidemiology + etiology + history + + + Population Surveillance + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Seasons + + + Tomography, X-Ray Computed + + + Young Adult + + + Zika Virus + + + Zika Virus Infection + complications + + + + Brazil + Microcephaly + Zika virus + disease outbreaks + infants + vector-borne infections + viruses + + + + Albuquerque + Maria + M + + + Araújo + Thalia + T + + + Barkokebas + Andreza + A + + + Bezerra + Luciana + L + + + Braga + Cynthia + C + + + Brandão-Filho + Sinval + S + + + Brito + Carlos + C + + + Cabral + Renata + R + + + Carneiro + Adriana + A + + + Carvalho + Maria + M + + + Cordeiro + Marli + M + + + Costa-Jr + Iran + I + + + Cunha + Adriana + A + + + Cruz + Danielle + D + + + Dhalia + Rafael + R + + + Hazin + Adriano + A + + + Katz + Leticia + L + + + Marques + Ernesto + E + + + Martelli + Celina + C + + + Miranda-Filho + Demócrito + D + + + Moraes + Monica + M + + + Mota + Cristina + C + + + Van Der Linden + Vanessa + V + + + Ramos + Regina + R + + + Rocha + Maria + M + + + Silva + Paula + P + + + Souza + Wayner + W + + + Van Der Linden + Ana + A + + + Ximenes + Ricardo + R + + + Batista + Joanna d'Arc + JD + + + Vazquez + Enrique + E + + + Coelho + Giovanini + G + + + Cortez-Escalante + Juan + J + + + Duarte + Elisete + E + + + Henriques + Cláudio + C + + + Melo + Carlos + C + + + Oliveira + Wanderson + W + + + Schüler-Faccini + Lavínia + L + + + Aldighieri + Sylvain + S + + + Almiron + Maria + M + + + Mendez-Rico + Jairo + J + + + Ramon-Pardo + Pilar + P + + + Rodrigues + Laura + L + + +
+ + + + 2016 + 4 + 13 + 6 + 0 + + + 2016 + 4 + 14 + 6 + 0 + + + 2018 + 1 + 13 + 6 + 0 + + + ppublish + + 27071041 + 10.3201/eid2206.160062 + PMC4880105 + + +
+ + + + + 27070380 + + 2018 + 01 + 10 + + + 2018 + 01 + 10 + +
+ + 1080-6059 + + 22 + 7 + + 2016 + 07 + + + Emerging infectious diseases + Emerging Infect. Dis. + + A Literature Review of Zika Virus. + + 1185-92 + + 10.3201/eid2207.151990 + + Zika virus is a mosquitoborne flavivirus that is the focus of an ongoing pandemic and public health emergency. Previously limited to sporadic cases in Africa and Asia, the emergence of Zika virus in Brazil in 2015 heralded rapid spread throughout the Americas. Although most Zika virus infections are characterized by subclinical or mild influenza-like illness, severe manifestations have been described, including Guillain-Barre syndrome in adults and microcephaly in babies born to infected mothers. Neither an effective treatment nor a vaccine is available for Zika virus; therefore, the public health response primarily focuses on preventing infection, particularly in pregnant women. Despite growing knowledge about this virus, questions remain regarding the virus's vectors and reservoirs, pathogenesis, genetic diversity, and potential synergistic effects of co-infection with other circulating viruses. These questions highlight the need for research to optimize surveillance, patient management, and public health intervention in the current Zika virus epidemic. + + + + Plourde + Anna R + AR + + + Bloch + Evan M + EM + + + eng + + Journal Article + Review + + + 2016 + 07 + 15 + +
+ + United States + Emerg Infect Dis + 9508155 + 1080-6040 + + IM + + + J Gen Virol. 1988 Aug;69 ( Pt 8):1913-20 + 2841406 + + + Sci Data. 2015 Jul 07;2:150035 + 26175912 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Arch Virol. 2007;152(4):687-96 + 17195954 + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + J Gen Virol. 2016 Feb;97(2):269-73 + 26684466 + + + PLoS One. 2014 Oct 13;9(10):e109442 + 25310102 + + + PLoS Negl Trop Dis. 2014 Feb 06;8(2):e2681 + 24516683 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + Emerg Infect Dis. 2015 Feb;21(2):381-2 + 25625687 + + + Arch Virol. 2016 Mar;161(3):665-8 + 26611910 + + + Euro Surveill. 2016;21(2):null + 26794427 + + + J Virol. 2015 Sep;89(17 ):8880-96 + 26085147 + + + Euro Surveill. 2014 Oct 16;19(41):null + 25345518 + + + Trans R Soc Trop Med Hyg. 1964 Jul;58:335-8 + 14175744 + + + Southeast Asian J Trop Med Public Health. 2015 May;46(3):460-4 + 26521519 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + PLoS Negl Trop Dis. 2014 Oct 09;8(10):e3188 + 25299181 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):55-8 + 26820163 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Trans R Soc Trop Med Hyg. 1956 May;50(3):238-42 + 13337908 + + + Comp Immunol Microbiol Infect Dis. 1999 Jan;22(1):71-9 + 10099030 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Humans + + + Zika Virus + genetics + physiology + + + Zika Virus Infection + epidemiology + transmission + virology + + + + Aedes + Zika virus + arbovirus + craniofacial abnormalities + emerging infectious diseases + flavivirus + microcephaly + mosquitoes + review literature as topic + viruses + zoonoses + +
+ + + + 2016 + 4 + 13 + 6 + 0 + + + 2016 + 4 + 14 + 6 + 0 + + + 2018 + 1 + 11 + 6 + 0 + + + ppublish + + 27070380 + 10.3201/eid2207.151990 + PMC4918175 + + +
+ + + + + 27069825 + + 2016 + 04 + 12 + + + 2017 + 02 + 20 + +
+ + 2167-8359 + + 4 + + 2016 + + + PeerJ + PeerJ + + Estimating risks of importation and local transmission of Zika virus infection. + + e1904 + + 10.7717/peerj.1904 + + Background. An international spread of Zika virus (ZIKV) infection has attracted global attention. ZIKV is conveyed by a mosquito vector, Aedes species, which also acts as the vector species of dengue and chikungunya viruses. Methods. Arrival time of ZIKV importation (i.e., the time at which the first imported case was diagnosed) in each imported country was collected from publicly available data sources. Employing a survival analysis model in which the hazard is an inverse function of the effective distance as informed by the airline transportation network data, and using dengue and chikungunya virus transmission data, risks of importation and local transmission were estimated. Results. A total of 78 countries with imported case(s) have been identified, with the arrival time ranging from 1 to 44 weeks since the first ZIKV was identified in Brazil, 2015. Whereas the risk of importation was well explained by the airline transportation network data, the risk of local transmission appeared to be best captured by additionally accounting for the presence of dengue and chikungunya viruses. Discussion. The risk of importation may be high given continued global travel of mildly infected travelers but, considering that the public health concerns over ZIKV infection stems from microcephaly, it is more important to focus on the risk of local and widespread transmission that could involve pregnant women. The predicted risk of local transmission was frequently seen in tropical and subtropical countries with dengue or chikungunya epidemic experience. + + + + Nah + Kyeongah + K + + Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency, Saitama, Japan; Graduate School of Medicine, Hokkaido University, Sapporo, Japan. + + + + Mizumoto + Kenji + K + + Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan. + + + + Miyamatsu + Yuichiro + Y + + Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency, Saitama, Japan; Graduate School of Medicine, Hokkaido University, Sapporo, Japan. + + + + Yasuda + Yohei + Y + + Graduate School of Medicine, The University of Tokyo , Tokyo , Japan. + + + + Kinoshita + Ryo + R + + Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency, Saitama, Japan; Graduate School of Medicine, Hokkaido University, Sapporo, Japan. + + + + Nishiura + Hiroshi + H + + Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency, Saitama, Japan; Graduate School of Medicine, Hokkaido University, Sapporo, Japan. + + + + eng + + Journal Article + + + 2016 + 04 + 05 + +
+ + United States + PeerJ + 101603425 + + + + Sci Data. 2015 Jul 07;2:150035 + 26175912 + + + Euro Surveill. 2014 Jan 30;19(4):null + 24507466 + + + J Gen Virol. 2016 Feb;97(2):269-73 + 26684466 + + + N Engl J Med. 2016 Dec 15;375(24):2321-2334 + 26943629 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + Stat Methods Med Res. 2008 Apr;17(2):207-21 + 18426855 + + + Int J Infect Dis. 2016 Mar;44:11-5 + 26854199 + + + Int J Infect Dis. 2016 Apr;45:95-7 + 26923081 + + + Euro Surveill. 2016;21(2):null + 26794427 + + + Lancet. 2016 Jan 23;387(10016):335-6 + 26777915 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):63-7 + 26820387 + + + Trends Parasitol. 2016 Mar;32(3):219-29 + 26897660 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + Prev Vet Med. 2000 May 30;45(1-2):23-41 + 10802332 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Science. 2013 Dec 13;342(6164):1337-42 + 24337289 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Lancet. 2015 Jul 18;386(9990):243-4 + 26194519 + + + Euro Surveill. 2014 Jan 30;19(4):null + 24507467 + + + Parasitol Res. 2016 May;115(5):1747-54 + 26932263 + + + Parasitol Res. 2016 Jan;115(1):23-34 + 26541154 + + + Am J Trop Med Hyg. 2013 Sep;89(3):516-7 + 23878182 + + + + Epidemiology + Importation + Mathematical model + Network + Risk + Statistical estimation + Transmission + Zika virus + +
+ + + + 2016 + 02 + 11 + + + 2016 + 03 + 16 + + + 2016 + 4 + 13 + 6 + 0 + + + 2016 + 4 + 14 + 6 + 0 + + + 2016 + 4 + 14 + 6 + 1 + + + epublish + + 27069825 + 10.7717/peerj.1904 + 1904 + PMC4824915 + + +
+ + + + + 27066743 + + 2017 + 09 + 21 + + + 2017 + 10 + 26 + +
+ + 1934-6069 + + 19 + 5 + + 2016 + May + 11 + + + Cell host & microbe + Cell Host Microbe + + Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection. + + 705-12 + + 10.1016/j.chom.2016.03.008 + S1931-3128(16)30100-7 + + During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHTs), which are the barrier cells of the placenta. We discovered that PHT cells from full-term placentas are refractory to ZIKV infection. In addition, medium from uninfected PHT cells protects non-placental cells from ZIKV infection. PHT cells constitutively release the type III interferon (IFN) IFNλ1, which functions in both a paracrine and autocrine manner to protect trophoblast and non-trophoblast cells from ZIKV infection. Our data suggest that for ZIKV to access the fetal compartment, it must evade restriction by trophoblast-derived IFNλ1 and other trophoblast-specific antiviral factors and/or use alternative strategies to cross the placental barrier. + Copyright © 2016 Elsevier Inc. All rights reserved. + + + + Bayer + Avraham + A + + Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Obstetrics, Gynecology, and Reproductive Science, University of Pittsburgh, Pittsburgh, PA 15213, USA. + + + + Lennemann + Nicholas J + NJ + + Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. + + + + Ouyang + Yingshi + Y + + Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Obstetrics, Gynecology, and Reproductive Science, University of Pittsburgh, Pittsburgh, PA 15213, USA. + + + + Bramley + John C + JC + + Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. + + + + Morosky + Stefanie + S + + Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. + + + + Marques + Ernesto Torres De Azeved + ET + Jr + + Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Fundação Osvaldo Cruz - FIOCRUZ, Recife, Pernambuco 50670-420, Brazil. + + + + Cherry + Sara + S + + Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA. + + + + Sadovsky + Yoel + Y + + Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Obstetrics, Gynecology, and Reproductive Science, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: ysadovsky@mwri.magee.edu. + + + + Coyne + Carolyn B + CB + + Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Obstetrics, Gynecology, and Reproductive Science, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: coynec2@pitt.edu. + + + + eng + + + R01 AI074951 + AI + NIAID NIH HHS + United States + + + R01 AI081759 + AI + NIAID NIH HHS + United States + + + R01 HD075665 + HD + NICHD NIH HHS + United States + + + R01 AI095500 + AI + NIAID NIH HHS + United States + + + T32 AI049820 + AI + NIAID NIH HHS + United States + + + + Journal Article + + + 2016 + 04 + 05 + +
+ + United States + Cell Host Microbe + 101302316 + 1931-3128 + + + + 0 + IL29 protein, human + + + 0 + Interleukins + + + 9008-11-1 + Interferons + + + IM + + + PLoS One. 2012;7(6):e39080 + 22720036 + + + J Clin Invest. 2010 Apr;120(4):1016-25 + 20364099 + + + Nat Immunol. 2003 Jan;4(1):63-8 + 12469119 + + + Sci Transl Med. 2015 Apr 22;7(284):284ra59 + 25904743 + + + Endocrinology. 1986 Apr;118(4):1567-82 + 3512258 + + + J Clin Endocrinol Metab. 1987 Dec;65(6):1282-90 + 3500181 + + + J Biol Chem. 1993 Sep 15;268(26):19760-8 + 7690039 + + + Microb Pathog. 2001 Jan;30(1):19-28 + 11162182 + + + J Virol Methods. 2006 Jun;134(1-2):183-9 + 16510196 + + + Am J Obstet Gynecol. 2015 Jan;212(1):71.e1-8 + 25108145 + + + MMWR Morb Mortal Wkly Rep. 2016;65(3):59-62 + 26820244 + + + Virology. 2008 Nov 10;381(1):67-74 + 18801552 + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + Am J Reprod Immunol. 1996 Apr;35(4):297-308 + 8739445 + + + J Cell Biochem. 1997 Jun 15;65(4):460-8 + 9178096 + + + Emerg Infect Dis. 2008 Mar;14(3):502-4 + 18325274 + + + Exp Cell Res. 1993 Jun;206(2):204-11 + 7684692 + + + Nat Immunol. 2003 Jan;4(1):69-77 + 12483210 + + + J Biol Chem. 2009 Jul 31;284(31):20869-75 + 19457860 + + + Sci Adv. 2016 Mar;2(3):e1501462 + 26973875 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Immunity. 2015 Jul 21;43(1):15-28 + 26200010 + + + PLoS Pathog. 2015 Sep;11(9):e1005150 + 26372645 + + + Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11455-9 + 1837150 + + + Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12048-53 + 23818581 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Nature. 2011 Apr 28;472(7344):481-5 + 21478870 + + + MMWR Morb Mortal Wkly Rep. 2016;65(6):159-60 + 26890059 + + + Arq Bras Oftalmol. 2016 Feb;79(1):1-3 + 26840156 + + + Annu Rev Immunol. 2014;32:513-45 + 24555472 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + PLoS Pathog. 2008 Mar;4(3):e1000017 + 18369468 + + + Exp Cell Res. 1990 Feb;186(2):306-16 + 2153559 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Genome Biol. 2014;15(12):550 + 25516281 + + + Cell Host Microbe. 2016 May 11;19(5):566-7 + 27173920 + + + + + Animals + + + Cell Line, Tumor + + + Cells, Cultured + + + Cercopithecus aethiops + + + Female + + + Fetal Diseases + immunology + prevention & control + virology + + + Humans + + + Interferons + biosynthesis + immunology + pharmacology + + + Interleukins + genetics + metabolism + pharmacology + + + Microcephaly + immunology + prevention & control + virology + + + Placenta + cytology + immunology + metabolism + + + Pregnancy + + + Pregnancy Complications, Infectious + immunology + prevention & control + virology + + + Trophoblasts + cytology + immunology + metabolism + + + Vero Cells + + + Zika Virus + drug effects + immunology + + + Zika Virus Infection + immunology + prevention & control + + + + IFNλ + Zika virus + placenta + trophoblasts + type III interferon + virus + +
+ + + + 2016 + 03 + 08 + + + 2016 + 03 + 23 + + + 2016 + 03 + 25 + + + 2016 + 4 + 13 + 6 + 0 + + + 2016 + 4 + 14 + 6 + 0 + + + 2017 + 9 + 22 + 6 + 0 + + + ppublish + + 27066743 + S1931-3128(16)30100-7 + 10.1016/j.chom.2016.03.008 + PMC4866896 + NIHMS776613 + + +
+ + + + + 27064148 + + 2016 + 06 + 01 + + + 2016 + 05 + 13 + +
+ + 1095-9203 + + 352 + 6287 + + 2016 + May + 13 + + + Science (New York, N.Y.) + Science + + Zika virus impairs growth in human neurospheres and brain organoids. + + 816-8 + + 10.1126/science.aaf6116 + + Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased considerably in Brazil; however, causality between the viral epidemic and malformations in fetal brains needs further confirmation. We examined the effects of ZIKV infection in human neural stem cells growing as neurospheres and brain organoids. Using immunocytochemistry and electron microscopy, we showed that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and brain organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development. + Copyright © 2016, American Association for the Advancement of Science. + + + + Garcez + Patricia P + PP + + Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + + Loiola + Erick Correia + EC + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + + Madeiro da Costa + Rodrigo + R + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + + Higa + Luiza M + LM + + Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Trindade + Pablo + P + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. + + + + Delvecchio + Rodrigo + R + + Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Nascimento + Juliana Minardi + JM + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. Institute of Biology, State University of Campinas, Campinas, Brazil. + + + + Brindeiro + Rodrigo + R + + Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Tanuri + Amilcar + A + + Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Rehen + Stevens K + SK + + D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 04 + 10 + +
+ + United States + Science + 0404511 + 0036-8075 + + IM + + + Brain + abnormalities + virology + + + Brazil + + + Cell Death + + + Cells, Cultured + + + Humans + + + Microcephaly + pathology + virology + + + Neural Stem Cells + pathology + virology + + + Neurogenesis + + + Organoids + abnormalities + virology + + + Zika Virus + pathogenicity + + + Zika Virus Infection + complications + pathology + + +
+ + + + 2016 + 03 + 02 + + + 2016 + 04 + 04 + + + 2016 + 4 + 12 + 6 + 0 + + + 2016 + 4 + 12 + 6 + 0 + + + 2016 + 6 + 2 + 6 + 0 + + + ppublish + + 27064148 + science.aaf6116 + 10.1126/science.aaf6116 + + +
+ + + + + 27060396 + + 2017 + 01 + 30 + + + 2017 + 01 + 30 + +
+ + 1532-3099 + + 35 + + 2016 + Apr + + + Midwifery + Midwifery + + Zika virus and pregnancy: A perspective from Brazil. + + 22-3 + + 10.1016/j.midw.2016.02.011 + S0266-6138(16)00049-8 + + + Diniz + Simone Grilo + SG + + Department of Maternal and Child Health, School of Public Health, University of São Paulo, Av. Dr. Arnaldo, 715 sala 203,CEP 01246-904 São Paulo, SP, Brazil. Electronic address: sidiniz@usp.br. + + + + eng + + Editorial + + + 2016 + 02 + 18 + +
+ + Scotland + Midwifery + 8510930 + 0266-6138 + + N + + + Brazil + epidemiology + + + Communicable Disease Control + + + Female + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + etiology + prevention & control + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + epidemiology + physiopathology + prevention & control + + + Public Health + + + Zika Virus Infection + diagnosis + epidemiology + physiopathology + prevention & control + + +
+ + + + 2016 + 4 + 10 + 6 + 0 + + + 2016 + 4 + 10 + 6 + 0 + + + 2017 + 1 + 31 + 6 + 0 + + + ppublish + + 27060396 + S0266-6138(16)00049-8 + 10.1016/j.midw.2016.02.011 + + +
+ + + + + 27058990 + + 2017 + 04 + 24 + + + 2017 + 04 + 24 + +
+ + 1879-3479 + + 133 + 2 + + 2016 + May + + + International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics + Int J Gynaecol Obstet + + New threat on the horizon: The Zika virus. + + 137-8 + + 10.1016/j.ijgo.2016.03.006 + S0020-7292(16)30042-X + + + Granato + Celso + C + + Discipline of Infectious Disease, São Paulo Federal University, São Paulo, Brazil; Fleury Medical Group, São Paulo, Brazil. + + + + Lázari + Carolina + C + + Fleury Medical Group, São Paulo, Brazil; Department of Infectious Diseases, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. + + + + Serafini + Paulo C + PC + + Department of Obstetrics and Gynecology, Discipline of Gynecology, University of São Paulo, São Paulo, Brazil; Reproductive Endocrinology, Huntington Reproductive Medicine, São Paulo, Brazil; Human Reproductive Service, University of Sao Paulo, São Paulo, Brazil. Electronic address: pauloivf@aol.com. + + + + eng + + Historical Article + Journal Article + + + 2016 + 03 + 24 + +
+ + United States + Int J Gynaecol Obstet + 0210174 + 0020-7292 + + IM + + + Disease Outbreaks + history + + + Female + + + History, 20th Century + + + History, 21st Century + + + Humans + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + transmission + + +
+ + + + 2016 + 03 + 11 + + + 2016 + 4 + 10 + 6 + 0 + + + 2016 + 4 + 10 + 6 + 0 + + + 2017 + 4 + 25 + 6 + 0 + + + ppublish + + 27058990 + S0020-7292(16)30042-X + 10.1016/j.ijgo.2016.03.006 + + +
+ + + + + 27052792 + + 2017 + 02 + 24 + + + 2017 + 02 + 24 + +
+ + 1728-7731 + + 79 + 4 + + 2016 + Apr + + + Journal of the Chinese Medical Association : JCMA + J Chin Med Assoc + + Why Zika virus infection has become a public health concern? + + 174-8 + + 10.1016/j.jcma.2016.03.001 + S1726-4901(16)30006-5 + + Prior to 2015, Zika Virus (ZIKV) outbreaks had occurred in areas of Africa, Southeast Asia, and the Pacific Islands. Although a causal relationship between Zika infection during pregnancy and microcephaly is strongly suspected, such a connection has not yet been scientifically proven. In May 2015, the outbreak of ZIKV infection in Brazil led to reports of syndrome and pregnant women giving birth to babies with birth defects and poor pregnancy outcomes; the Pan American Health Organization (PAHO) issued an alert regarding the first confirmed ZIKV infection in Brazil. Currently, ZIKV outbreaks are ongoing and it will be difficult to predict how the virus will spread over time. ZIKV is transmitted to humans primarily through the bite of infected mosquitos, Aedes aegypti and Aedes albopictus. These mosquitoes are the principle vectors of dengue, and ZIKV disease generally is reported to include symptoms associated with acute febrile illnesses that clinically resembles dengue fever. The laboratory diagnosis can be performed by using reverse-transcriptase polymerase chain reaction (RT-PCR) on serum, viral nucleic acid and virus-specific immunoglobulin M. There is currently no vaccine and antiviral treatment available for ZIKV infection, and the only way to prevent congenital ZIKV infection is to prevent maternal infection. In February 2016, the Taiwan Centers for Disease Control (Taiwan CDC) activated ZIKV as a Category V Notifiable Infectious Disease similar to Ebola virus disease and MERS. + Copyright © 2016. Published by Elsevier Taiwan LLC. + + + + Chen + Hui-Lan + HL + + Department of Pediatrics, Keelung Hospital, Ministry of Health and Welfare, Keelung, Taiwan, ROC. + + + + Tang + Ren-Bin + RB + + Division of Pediatrics, Cheng Hsin General Hospital, Taipei, Taiwan, ROC. Electronic address: ch9406@chgh.org.com.tw. + + + + eng + + Journal Article + Review + + + 2016 + 03 + 24 + +
+ + China (Republic : 1949- ) + J Chin Med Assoc + 101174817 + 1726-4901 + + IM + + + Female + + + Humans + + + Microcephaly + etiology + + + Pregnancy + + + Public Health + + + Zika Virus Infection + complications + diagnosis + prevention & control + transmission + + + + Zika virus + microcephaly + transmission + +
+ + + + 2016 + 02 + 17 + + + 2016 + 03 + 03 + + + 2016 + 4 + 8 + 6 + 0 + + + 2016 + 4 + 8 + 6 + 0 + + + 2017 + 2 + 25 + 6 + 0 + + + ppublish + + 27052792 + S1726-4901(16)30006-5 + 10.1016/j.jcma.2016.03.001 + + +
+ + + + + 27050112 + + 2016 + 06 + 10 + + + 2017 + 04 + 06 + +
+ + 1533-4406 + + 374 + 22 + + 2016 + 06 + 02 + + + The New England journal of medicine + N. Engl. J. Med. + + Computed Tomographic Findings in Microcephaly Associated with Zika Virus. + + 2193-5 + + 10.1056/NEJMc1603617 + + + Hazin + Adriano N + AN + + Instituto de Medicina Integral Professor Fernando Figueira, Recife, Brazil. + + + + Poretti + Andrea + A + + Johns Hopkins University School of Medicine, Baltimore, MD aporett1@jhmi.edu. + + + + Di Cavalcanti Souza Cruz + Danielle + D + + Instituto de Medicina Integral Professor Fernando Figueira, Recife, Brazil. + + + + Tenorio + Marli + M + + Research Center Aggeu Magalhães, Recife, Brazil. + + + + van der Linden + Ana + A + + Instituto de Medicina Integral Professor Fernando Figueira, Recife, Brazil. + + + + Pena + Lindomar Jose + LJ + + Research Center Aggeu Magalhães, Recife, Brazil. + + + + Brito + Carlos + C + + Research Center Aggeu Magalhães, Recife, Brazil. + + + + Gil + Laura H Vega + LH + + Research Center Aggeu Magalhães, Recife, Brazil. + + + + de Barros Miranda-Filho + Demócrito + D + + Oswaldo Cruz University Hospital, Recife, Brazil. + + + + Marques + Ernesto Torres de Azevedo + ET + + Research Center Aggeu Magalhães, Recife, Brazil. + + + + Turchi Martelli + Celina M + CM + + Research Center Aggeu Magalhães, Recife, Brazil. + + + + Alves + João G Bezerra + JG + + Instituto de Medicina Integral Professor Fernando Figueira, Recife, Brazil. + + + + Huisman + Thierry A + TA + + Johns Hopkins University School of Medicine, Baltimore, MD. + + + + Microcephaly Epidemic Research Group + + + eng + + Letter + + + 2016 + 04 + 06 + +
+ + United States + N Engl J Med + 0255562 + 0028-4793 + + AIM + IM + + + Brain + diagnostic imaging + + + Female + + + Humans + + + Infant + + + Infant, Newborn + + + Male + + + Microcephaly + diagnostic imaging + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Tomography, X-Ray Computed + + + Zika Virus Infection + complications + diagnostic imaging + + + + + Rodrigues + Laura Cunha + LC + + + de Araújo + Thália Velho Barreto + TV + + + Ximenes + Ricardo Arraes de Alencar + RA + + + Braga + Maria Cynthia + MC + + + de Albuquerque + Maria de Fatima P Militão + Mde F + + + Souza + Wayner Vieira + WV + + +
+ + + + 2016 + 4 + 7 + 6 + 0 + + + 2016 + 4 + 7 + 6 + 0 + + + 2016 + 6 + 11 + 6 + 0 + + + ppublish + + 27050112 + 10.1056/NEJMc1603617 + + +
+ + + + + 27049675 + + 2017 + 02 + 01 + + + 2017 + 02 + 01 + +
+ + 1678-4782 + + 92 + 3 + + 2016 May-Jun + + + Jornal de pediatria + J Pediatr (Rio J) + + Microcephaly and Zika virus: a clinical and epidemiological analysis of the current outbreak in Brazil. + + 230-40 + + 10.1016/j.jped.2016.02.009 + S0021-7557(16)30001-8 + + This study aimed to critically review the literature available regarding the Zika virus outbreak in Brazil and its possible association with microcephaly cases. + Experts from Instituto do Cérebro do Rio Grande do Sul performed a critical (nonsystematic) literature review regarding different aspects of the Zika virus outbreak in Brazil, such as transmission, epidemiology, diagnostic criteria, and its possible association with the increase of microcephaly reports. The PubMed search using the key word "Zika virus" in February 2016 yielded 151 articles. The manuscripts were reviewed, as well as all publications/guidelines from the Brazilian Ministry of Health, World Health Organization and Centers for Disease Control and Prevention (CDC - United States). + Epidemiological data suggest a temporal association between the increased number of microcephaly notifications in Brazil and outbreak of Zika virus, primarily in the Brazil's Northeast. It has been previously documented that many different viruses might cause congenital acquired microcephaly. Still there is no consensus on the best curve to measure cephalic circumference, specifically in preterm neonates. Conflicting opinions regarding the diagnosis of microcephaly (below 2 or 3 standard deviations) that should be used for the notifications were also found in the literature. + The development of diagnostic techniques that confirm a cause-effect association and studies regarding the physiopathology of the central nervous system impairment should be prioritized. It is also necessary to strictly define the criteria for the diagnosis of microcephaly to identify cases that should undergo an etiological investigation. + Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved. + + + + Nunes + Magda Lahorgue + ML + + School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Zika-Team, Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil. Electronic address: nunes@pucrs.br. + + + + Carlini + Celia Regina + CR + + Zika-Team, Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil; Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil. + + + + Marinowic + Daniel + D + + Zika-Team, Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil; Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil. + + + + Neto + Felipe Kalil + FK + + Zika-Team, Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil; Post-Graduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil. + + + + Fiori + Humberto Holmer + HH + + School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Zika-Team, Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil. + + + + Scotta + Marcelo Comerlato + MC + + Zika-Team, Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil; Department of Pediatrics, School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil. + + + + Zanella + Pedro Luis Ávila + PL + + School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Zika-Team, Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil. + + + + Soder + Ricardo Bernardi + RB + + Zika-Team, Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil; Department of Diagnostic Methods, School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil. + + + + da Costa + Jaderson Costa + JC + + School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Zika-Team, Instituto do Cérebro do Rio Grande do Sul (Inscer), Porto Alegre, RS, Brazil. + + + + eng + + Journal Article + Review + + + 2016 + 04 + 15 + +
+ + Brazil + J Pediatr (Rio J) + 2985188R + 0021-7557 + + IM + + + Aedes + + + Animals + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Humans + + + Infant, Newborn + + + Insect Vectors + + + Microcephaly + diagnosis + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + epidemiology + virology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + epidemiology + + + + Cortical development + Desenvolvimento cortical + Gestação + Microcefalia + Microcephaly + Neuroimagem + Neuroimaging + Pregnancy + Vírus Zika + Zika virus + +
+ + + + 2016 + 02 + 19 + + + 2016 + 02 + 22 + + + 2016 + 4 + 7 + 6 + 0 + + + 2016 + 4 + 7 + 6 + 0 + + + 2017 + 2 + 2 + 6 + 0 + + + ppublish + + 27049675 + S0021-7557(16)30001-8 + 10.1016/j.jped.2016.02.009 + + +
+ + + + + 27046524 + + 2016 + 08 + 15 + + + 2016 + 04 + 06 + +
+ + 1942-5546 + + 91 + 4 + + 2016 + Apr + + + Mayo Clinic proceedings + Mayo Clin. Proc. + + Zika Virus in the Americas: A Review for Clinicians. + + 514-21 + + 10.1016/j.mayocp.2016.02.017 + S0025-6196(16)00148-8 + + Zika virus has recently emerged as a new public health threat. An arthropod-borne virus named after the Zika forest in Uganda, it was first discovered in 1947. The virus caused only sporadic cases of Zika infection in Africa and Southeast Asia until 2007, when the first large outbreak occurred in the Yap State in the Federated States of Micronesia. Another outbreak in French Polynesia in 2013 was notable for being associated temporally with an increase in cases of Guillain-Barré syndrome. In 2015, the virus was first reported in Brazil and since then has spread explosively through several additional countries in South and Central America and the Caribbean. Simultaneously, several of these countries have seen a dramatic increase in the incidence of infants born with microcephaly. The rapid spread of Zika virus through the Americas, together with the association of infection with microcephaly and Guillain-Barré syndrome, has resulted in the World Health Organization declaring a public health emergency. Zika virus has the potential to spread to new areas where the Aedes mosquito vector is present and therefore presents a risk to the United States. This concise review describes the clinical features of Zika virus infection and provides advice for clinicians on counseling travelers and others about the disease. + Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved. + + + + Sampathkumar + Priya + P + + Division of Infectious Diseases, Mayo Clinic, Rochester, MN. Electronic address: sampathkumar.priya@mayo.edu. + + + + Sanchez + Joyce L + JL + + Division of Infectious Diseases, Mayo Clinic, Rochester, MN. + + + + eng + + Historical Article + Journal Article + Review + +
+ + England + Mayo Clin Proc + 0405543 + 0025-6196 + + AIM + IM + + + Americas + epidemiology + + + Animals + + + Asia, Southeastern + epidemiology + + + Brazil + epidemiology + + + Disease Outbreaks + history + statistics & numerical data + + + Female + + + Guillain-Barre Syndrome + epidemiology + + + History, 20th Century + + + History, 21st Century + + + Humans + + + Incidence + + + Infant, Newborn + + + Male + + + Microcephaly + epidemiology + virology + + + Micronesia + epidemiology + + + Polynesia + epidemiology + + + Uganda + epidemiology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + history + transmission + + +
+ + + + 2016 + 02 + 09 + + + 2016 + 02 + 23 + + + 2016 + 02 + 23 + + + 2016 + 4 + 6 + 6 + 0 + + + 2016 + 4 + 6 + 6 + 0 + + + 2016 + 8 + 16 + 6 + 0 + + + ppublish + + 27046524 + S0025-6196(16)00148-8 + 10.1016/j.mayocp.2016.02.017 + + +
+ + + + + 27038591 + + 2017 + 07 + 19 + + + 2017 + 08 + 07 + +
+ + 1875-9777 + + 18 + 5 + + 2016 + May + 05 + + + Cell stem cell + Cell Stem Cell + + Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells. + + 591-6 + + 10.1016/j.stem.2016.03.012 + S1934-5909(16)00118-1 + + The recent outbreak of Zika virus (ZIKV) in Brazil has been linked to substantial increases in fetal abnormalities and microcephaly. However, information about the underlying molecular and cellular mechanisms connecting viral infection to these defects remains limited. In this study we have examined the expression of receptors implicated in cell entry of several enveloped viruses including ZIKV across diverse cell types in the developing brain. Using single-cell RNA-seq and immunohistochemistry, we found that the candidate viral entry receptor AXL is highly expressed by human radial glial cells, astrocytes, endothelial cells, and microglia in developing human cortex and by progenitor cells in developing retina. We also show that AXL expression in radial glia is conserved in developing mouse and ferret cortex and in human stem cell-derived cerebral organoids, highlighting multiple experimental systems that could be applied to study mechanisms of ZIKV infectivity and effects on brain development. + Copyright © 2016 Elsevier Inc. All rights reserved. + + + + Nowakowski + Tomasz J + TJ + + Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. + + + + Pollen + Alex A + AA + + Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. + + + + Di Lullo + Elizabeth + E + + Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. + + + + Sandoval-Espinosa + Carmen + C + + Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. + + + + Bershteyn + Marina + M + + Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. + + + + Kriegstein + Arnold R + AR + + Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: kriegsteina@stemcell.ucsf.edu. + + + + eng + + + R01 NS035710 + NS + NINDS NIH HHS + United States + + + R01 NS075998 + NS + NINDS NIH HHS + United States + + + R37 NS035710 + NS + NINDS NIH HHS + United States + + + U01 MH105989 + MH + NIMH NIH HHS + United States + + + + Journal Article + + + 2016 + 03 + 30 + +
+ + United States + Cell Stem Cell + 101311472 + 1875-9777 + + + + 0 + Proto-Oncogene Proteins + + + 0 + Receptors, Virus + + + EC 2.7.10.1 + Receptor Protein-Tyrosine Kinases + + + EC 2.7.10.1 + axl receptor tyrosine kinase + + + IM + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + Nat Commun. 2015;6:8896 + 26573335 + + + Lancet. 2016 Feb 20;387(10020):719-21 + 26876373 + + + PLoS Negl Trop Dis. 2014 Jul;8(7):e2996 + 25033077 + + + Nat Med. 2015 Dec;21(12):1464-72 + 26523970 + + + J Immunol. 2013 Dec 15;191(12):6165-77 + 24244024 + + + Brain. 2012 May;135(Pt 5):1348-69 + 22427329 + + + Cell. 2007 Dec 14;131(6):1124-36 + 18083102 + + + J Ment Defic Res. 1972 Jun;16(2):90-6 + 4369315 + + + MMWR Morb Mortal Wkly Rep. 2016;65(3):59-62 + 26820244 + + + Pediatrics. 2006 Mar;117(3):e537-45 + 16510632 + + + J Neuropathol Exp Neurol. 2014 Feb;73(2):143-58 + 24423639 + + + Pediatrics. 1986 Dec;78(6):1058-63 + 3024098 + + + Development. 2010 Jun;137(11):1907-17 + 20460369 + + + Nat Cell Biol. 2011 Nov;13(11):1325-34 + 21947081 + + + Pediatrics. 1970 Sep;46(3):483-4 + 4318344 + + + Cell. 2015 Sep 24;163(1):55-67 + 26406371 + + + Nature. 2001 Feb 8;409(6821):714-20 + 11217860 + + + Cell Host Microbe. 2012 Oct 18;12(4):544-57 + 23084921 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + N Engl J Med. 1992 Mar 5;326(10):663-7 + 1310525 + + + Lancet. 2016 Apr 2;387(10026):1481 + 26946926 + + + Dev Med Child Neurol. 2014 Aug;56(8):732-41 + 24617602 + + + Cell Rep. 2014 Aug 7;8(3):656-64 + 25088420 + + + Stem Cells. 2011 Oct;29(10):1589-600 + 21805534 + + + Viruses. 2014 Jan;6(1):69-88 + 24381034 + + + Nature. 2010 Mar 25;464(7288):554-561 + 20154730 + + + Neuron. 2005 Aug 4;47(3):353-64 + 16055060 + + + MMWR Morb Mortal Wkly Rep. 2016;65(6):159-60 + 26890059 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + J Virol. 2015 Sep;89(17):8880-96 + 26085147 + + + Am J Pathol. 2015 May;185(5):1304-23 + 25797647 + + + Nat Neurosci. 2010 Jun;13(6):690-9 + 20436478 + + + Am J Hum Genet. 2005 May;76(5):717-28 + 15806441 + + + Ann N Y Acad Sci. 2010 Oct;1209:23-9 + 20958312 + + + PLoS One. 2014;9(12):e115140 + 25514676 + + + Pediatrics. 1986 Jun;77(6):801-6 + 3012452 + + + Early Hum Dev. 2012 May;88 Suppl 2:S3-5 + 22633509 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + Cell Stem Cell. 2016 May 5;18(5):559-60 + 27152436 + + + + + Animals + + + Blood Vessels + metabolism + + + Cerebral Cortex + embryology + metabolism + + + Disease Models, Animal + + + Ferrets + + + Mice + + + Neural Stem Cells + metabolism + virology + + + Neurogenesis + + + Neuroglia + metabolism + + + Pluripotent Stem Cells + cytology + + + Proto-Oncogene Proteins + metabolism + + + Receptor Protein-Tyrosine Kinases + metabolism + + + Receptors, Virus + metabolism + + + Virus Internalization + + + Zika Virus + physiology + + +
+ + + + 2016 + 03 + 07 + + + 2016 + 03 + 18 + + + 2016 + 03 + 21 + + + 2016 + 4 + 4 + 6 + 0 + + + 2016 + 4 + 4 + 6 + 0 + + + 2017 + 7 + 20 + 6 + 0 + + + ppublish + + 27038591 + S1934-5909(16)00118-1 + 10.1016/j.stem.2016.03.012 + PMC4860115 + NIHMS773793 + + +
+ + + + + 27036749 + + 2016 + 12 + 13 + + + 2016 + 12 + 30 + +
+ + 1678-4782 + + 92 + 2 + + 2016 Mar-Apr + + + Jornal de pediatria + J Pediatr (Rio J) + + Microcephaly and Zika virus. + + 103-5 + + 10.1016/j.jped.2016.02.003 + S0021-7557(16)00039-5 + + + de Oliveira + Consuelo Silva + CS + + Section of Arbovirology and Hemorrhagic Fevers, Instituto Evandro Chagas (IEC), Secretaria de Vigilância em Saúde (SVS), Ministério da Saúde (MS), Ananindeua, PA, Brazil; Universidade do Estado do Pará, Belém, PA, Brazil. Electronic address: consuelooliveira@iec.pa.gov.br. + + + + da Costa Vasconcelos + Pedro Fernando + PF + + Section of Arbovirology and Hemorrhagic Fevers, Instituto Evandro Chagas (IEC), Secretaria de Vigilância em Saúde (SVS), Ministério da Saúde (MS), Ananindeua, PA, Brazil; Universidade do Estado do Pará, Belém, PA, Brazil; Research and Reference in Arbovirus, World Health Organization (WHO) Collaborating Center, Organização Pan-Americana da Saúde (OPAS), Brasília, DF, Brazil. + + + + eng + + Editorial + Introductory Journal Article + +
+ + Brazil + J Pediatr (Rio J) + 2985188R + 0021-7557 + + IM + + + Brazil + + + Female + + + Humans + + + Infant, Newborn + + + Microcephaly + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + virology + + + Zika Virus Infection + complications + + +
+ + + + 2016 + 4 + 3 + 6 + 0 + + + 2016 + 4 + 3 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + ppublish + + 27036749 + S0021-7557(16)00039-5 + 10.1016/j.jped.2016.02.003 + + +
+ + + + + 27031450 + + 2016 + 12 + 14 + + + 2016 + 12 + 30 + +
+ + 1972-2680 + + 10 + 3 + + 2016 + Mar + 31 + + + Journal of infection in developing countries + J Infect Dev Ctries + + Zika virus: a new pandemic threat. + + 201-7 + + 10.3855/jidc.8350 + + Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family and is related to dengue, Chikungunya, West Nile, yellow fever, and Japanese encephalitis viruses. ZIKV was first discovered in Uganda in 1947. Different species of mosquito from the Aedes genus, mainly A. aegypti and A. albopictus are the vectors responsible for ZIKV infection in humans. It is also reported that ZIKV is transmitted congenitally, sexually, and through blood donation. Until recently, ZIKV outbreaks were sporadic and self-limiting. The first large epidemic was reported from Yap Island in 2007 followed by an outbreak of Zika fever in French Polynesia in 2013. Brazil is the epicenter of the current ZIKV epidemic which is rapidly spreading across the Americas. ZIKV infection remained relatively less studied in view of its low case numbers, and low clinical impact relative to other arboviruses. However, all this is set to change with its rapid spread in the Western hemisphere and suspected complications particularly microcephaly in newborn babies with ZIKV infected mothers. ZIKV is expected to substantially add to both short-term and long-term economic burden of the effected countries. Due to the large number of people travelling across the borders and some reported cases of transmission of ZIKV via contaminated blood, screening and identification of asymptomatic infected individuals are important. + + + + Al-Qahtani + Ahmed Ali + AA + + King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. aqahtani@kfshrc.edu.sa. + + + + Nazir + Nyla + N + + + Al-Anazi + Mashael R + MR + + + Rubino + Salvatore + S + + + Al-Ahdal + Mohammed N + MN + + + eng + + Journal Article + Review + + + 2016 + 03 + 31 + +
+ + Italy + J Infect Dev Ctries + 101305410 + 1972-2680 + + IM + + + Aedes + + + Animals + + + Humans + + + Insect Vectors + + + Microcephaly + epidemiology + + + Pandemics + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + epidemiology + transmission + + +
+ + + + 2016 + 03 + 08 + + + 2016 + 03 + 22 + + + 2016 + 03 + 22 + + + 2016 + 4 + 1 + 6 + 0 + + + 2016 + 4 + 1 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + epublish + + 27031450 + + +
+ + + + + 27029927 + + 2017 + 01 + 03 + + + 2017 + 01 + 04 + +
+ + 2081-3252 + + 67 + 1 + + 2016 + + + International maritime health + Int Marit Health + + Zika - another threat on the epidemiological map of the world. + + 31-7 + + 10.5603/IMH.2016.0007 + + Zika fever is an acute infectious disease caused by the Zika virus (ZIKV) of the Flaviviridae family and Flavivirus genus. It is transmitted by day-time active Aedes mosquitoes, and potentially by sexual contacts, blood transfusion, and from mother to foetus (resulting in microcephaly in a child). ZIKV was first isolated from a macaque monkey in the Zika forest in Uganda in 1947. The first case of the Zika fever in a human was recorded in Nigeria in 1954. Until 2007 only 14 cases of the disease were confirmed worldwide. In 2007, there was an outbreak of the Zika fever in Micronesia (Yap Island) with an estimated 5,000 cases. Between 2013 and 2015 a further outbreak of the disease occurred in the Pacific islands: in French Polynesia, New Caledonia, Cook Islands, Easter Island, and Solomon Islands. In 2015, the Zika fever spread to Brazil and more than 20 other countries in the South and Central America. Until March 2016, an estimated 1.6 million autochthonous cases of Zika have been reported globally, with approximately 1.5 million cases recorded in Brazil. Typically, 80% of Zika infections are asymptomatic. The most common symptoms of the disease include fever, maculopapular rash, muscle and joint pain, conjunctivitis. Zika fever can be diagnosed on the basis of clinical signs (it must be differentiated from dengue, chikungunya), ZIKV identification is also possible by the application of polymerase chain reaction in acutely ill patients and the detection of specific IgM and IgG antibodies to ZIKV. Until today, there is no effective antiviral treatment or an effective vaccine against Zika fever (in case of an infection only symptomatic treatment is applied). In August 2016 in Rio de Janeiro (Brazil) Summer Olympic Games will take place, attracting thousands of athletes and spectators. The fight against the Zika fever and the race against time have gained momentum. + + + + Korzeniewski + Krzysztof + K + + Department of Epidemiology and Tropical Medicine; Military Institute of Medicine, Warsaw, Poland. kktropmed@wp.pl. + + + + Juszczak + Dariusz + D + + + Zwolińska + Ewa + E + + + eng + + Journal Article + Review + +
+ + Poland + Int Marit Health + 100958373 + 1641-9251 + + IM + + + Africa + epidemiology + + + Central America + epidemiology + + + Humans + + + Pacific Islands + epidemiology + + + Pandemics + prevention & control + statistics & numerical data + + + South America + epidemiology + + + Zika Virus Infection + complications + diagnosis + epidemiology + therapy + + + + Zika virus + clinical symptoms + epidemiology + prevention + +
+ + + + 2016 + 03 + 11 + + + 2016 + 03 + 15 + + + 2016 + 03 + 14 + + + 2016 + 4 + 1 + 6 + 0 + + + 2016 + 4 + 1 + 6 + 0 + + + 2017 + 1 + 4 + 6 + 0 + + + ppublish + + 27029927 + VM/OJS/J/44968 + 10.5603/IMH.2016.0007 + + +
+ + + + + 27029595 + + 2016 + 12 + 13 + + + 2017 + 07 + 14 + +
+ + 1098-6618 + + 29 + 3 + + 2016 + Jul + + + Clinical microbiology reviews + Clin. Microbiol. Rev. + + Zika Virus. + + 487-524 + + 10.1128/CMR.00072-15 + + Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the family Flaviviridae. ZIKV was first isolated from a nonhuman primate in 1947 and from mosquitoes in 1948 in Africa, and ZIKV infections in humans were sporadic for half a century before emerging in the Pacific and the Americas. ZIKV is usually transmitted by the bite of infected mosquitoes. The clinical presentation of Zika fever is nonspecific and can be misdiagnosed as other infectious diseases, especially those due to arboviruses such as dengue and chikungunya. ZIKV infection was associated with only mild illness prior to the large French Polynesian outbreak in 2013 and 2014, when severe neurological complications were reported, and the emergence in Brazil of a dramatic increase in severe congenital malformations (microcephaly) suspected to be associated with ZIKV. Laboratory diagnosis of Zika fever relies on virus isolation or detection of ZIKV-specific RNA. Serological diagnosis is complicated by cross-reactivity among members of the Flavivirus genus. The adaptation of ZIKV to an urban cycle involving humans and domestic mosquito vectors in tropical areas where dengue is endemic suggests that the incidence of ZIKV infections may be underestimated. There is a high potential for ZIKV emergence in urban centers in the tropics that are infested with competent mosquito vectors such as Aedes aegypti and Aedes albopictus. + Copyright © 2016, American Society for Microbiology. All Rights Reserved. + + + + Musso + Didier + D + + Unit of Emerging Infectious Diseases, Institut Louis Malardé, Tahiti, French Polynesia dmusso@ilm.pf duane.gubler@duke-nus.edu.sg. + + + + Gubler + Duane J + DJ + + Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore Partnership for Dengue Control, Lyon, France dmusso@ilm.pf duane.gubler@duke-nus.edu.sg. + + + + eng + + Journal Article + Review + +
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+ + + + 2016 + 4 + 1 + 6 + 0 + + + 2016 + 4 + 1 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + ppublish + + 27029595 + 29/3/487 + 10.1128/CMR.00072-15 + PMC4861986 + + +
+ + + + + 27015734 + + 2016 + 10 + 17 + + + 2016 + 12 + 30 + +
+ + 1873-2518 + + 34 + 20 + + 2016 + Apr + 29 + + + Vaccine + Vaccine + + Another emerging arbovirus, another emerging vaccine: Targeting Zika virus. + + 2291-3 + + 10.1016/j.vaccine.2016.03.059 + S0264-410X(16)30055-X + + + Palacios + Ricardo + R + + Instituto Butantan, São Paulo, Brazil. + + + + Poland + Gregory A + GA + + Mayo Vaccine Research Group, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA. + + + + Kalil + Jorge + J + + Instituto Butantan, São Paulo, Brazil; Clinical Immunology and Allergy Division, University of São Paulo, São Paulo, Brazil. Electronic address: jorge.kalil@butantan.gov.br. + + + + eng + + Editorial + + + 2016 + 03 + 23 + +
+ + Netherlands + Vaccine + 8406899 + 0264-410X + + + + 0 + Viral Vaccines + + + IM + + + Communicable Diseases, Emerging + epidemiology + prevention & control + + + Global Health + + + Humans + + + Microcephaly + etiology + + + Viral Vaccines + therapeutic use + + + Zika Virus + + + Zika Virus Infection + epidemiology + prevention & control + + +
+ + + + 2016 + 03 + 18 + + + 2016 + 3 + 27 + 6 + 0 + + + 2016 + 3 + 27 + 6 + 0 + + + 2016 + 10 + 19 + 6 + 0 + + + ppublish + + 27015734 + S0264-410X(16)30055-X + 10.1016/j.vaccine.2016.03.059 + + +
+ + + + + 27013429 + + 2016 + 04 + 28 + + + 2017 + 09 + 22 + +
+ + 1095-9203 + + 352 + 6283 + + 2016 + Apr + 15 + + + Science (New York, N.Y.) + Science + + Zika virus in the Americas: Early epidemiological and genetic findings. + + 345-349 + + 10.1126/science.aaf5036 + + Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas. + Copyright © 2016, American Association for the Advancement of Science. + + + + Faria + Nuno Rodrigues + NR + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK. + + + + Azevedo + Raimunda do Socorro da Silva + RDSDS + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Kraemer + Moritz U G + MUG + + Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK. + + + + Souza + Renato + R + + Instituto Adolfo Lutz, University of São Paulo, Brazil. + + + + Cunha + Mariana Sequetin + MS + + Instituto Adolfo Lutz, University of São Paulo, Brazil. + + + + Hill + Sarah C + SC + + Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK. + + + + Thézé + Julien + J + + Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK. + + + + Bonsall + Michael B + MB + + Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK. + + + + Bowden + Thomas A + TA + + Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. + + + + Rissanen + Ilona + I + + Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. + + + + Rocco + Iray Maria + IM + + Instituto Adolfo Lutz, University of São Paulo, Brazil. + + + + Nogueira + Juliana Silva + JS + + Instituto Adolfo Lutz, University of São Paulo, Brazil. + + + + Maeda + Adriana Yurika + AY + + Instituto Adolfo Lutz, University of São Paulo, Brazil. + + + + Vasami + Fernanda Giseli da Silva + FGDS + + Instituto Adolfo Lutz, University of São Paulo, Brazil. + + + + Macedo + Fernando Luiz de Lima + FLL + + Instituto Adolfo Lutz, University of São Paulo, Brazil. + + + + Suzuki + Akemi + A + + Instituto Adolfo Lutz, University of São Paulo, Brazil. + + + + Rodrigues + Sueli Guerreiro + SG + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Cruz + Ana Cecilia Ribeiro + ACR + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Nunes + Bruno Tardeli + BT + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Medeiros + Daniele Barbosa de Almeida + DBA + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Rodrigues + Daniela Sueli Guerreiro + DSG + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Queiroz + Alice Louize Nunes + ALN + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + da Silva + Eliana Vieira Pinto + EVP + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Henriques + Daniele Freitas + DF + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + da Rosa + Elisabeth Salbe Travassos + EST + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + de Oliveira + Consuelo Silva + CS + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Martins + Livia Caricio + LC + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Vasconcelos + Helena Baldez + HB + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Casseb + Livia Medeiros Neves + LMN + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Simith + Darlene de Brito + DB + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + Messina + Jane P + JP + + Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK. + + + Metabiota, San Francisco, California 94104, USA. + + + + Abade + Leandro + L + + Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK. + + + + Lourenço + José + J + + Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK. + + + + Alcantara + Luiz Carlos Junior + LCJ + + Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil. + + + + de Lima + Maricélia Maia + MM + + Centre of Post Graduation in Collective Health, Department of Health, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil. + + + + Giovanetti + Marta + M + + Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil. + + + + Hay + Simon I + SI + + Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA. + + + Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. + + + + de Oliveira + Rodrigo Santos + RS + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + + Lemos + Poliana da Silva + PDS + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + + de Oliveira + Layanna Freitas + LF + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + + de Lima + Clayton Pereira Silva + CPS + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + + da Silva + Sandro Patroca + SP + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + + de Vasconcelos + Janaina Mota + JM + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + + Franco + Luciano + L + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + + Cardoso + Jedson Ferreira + JF + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + + Vianez-Júnior + João Lídio da Silva Gonçalves + JLDSG + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + + Mir + Daiana + D + + Laboratório de AIDS and Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. + + + + Bello + Gonzalo + G + + Laboratório de AIDS and Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. + + + + Delatorre + Edson + E + + Laboratório de AIDS and Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. + + + + Khan + Kamran + K + + Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada. + + + Department of Medicine, Division of Infectious Diseases, University of Toronto, Canada. + + + + Creatore + Marisa + M + + Dalla Lana School of Public Health, University of Toronto, Canada. + + + + Coelho + Giovanini Evelim + GE + + Brazilian Ministry of Health, Brasília, Brazil. + + + + de Oliveira + Wanderson Kleber + WK + + Brazilian Ministry of Health, Brasília, Brazil. + + + + Tesh + Robert + R + + Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. + + + + Pybus + Oliver G + OG + + Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK. + + + Metabiota, San Francisco, California 94104, USA. + + + + Nunes + Marcio R T + MRT + + Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. + + + Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. + + + + Vasconcelos + Pedro F C + PFC + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil. + + + + eng + + + GENBANK + + KU321639 + KU365777 + KU365778 + KU365779 + KU365780 + KU729217 + KU729218 + + + + + + 090532/Z/09/Z + Wellcome Trust + United Kingdom + + + 095066 + Wellcome Trust + United Kingdom + + + 102427 + Wellcome Trust + United Kingdom + + + MR/L009528/1 + Medical Research Council + United Kingdom + + + 268904 + European Research Council + International + + + R24 AI120942 + AI + NIAID NIH HHS + United States + + + R24 AT 120942 + AT + NCCIH NIH HHS + United States + + + + Journal Article + Research Support, N.I.H., Extramural + Research Support, Non-U.S. Gov't + Research Support, U.S. Gov't, Non-P.H.S. + + + 2016 + 03 + 24 + +
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+ + 1806-9282 + + 62 + 1 + + 2016 Jan-Feb + + + Revista da Associacao Medica Brasileira (1992) + Rev Assoc Med Bras (1992) + + Zika virus. + + 4-9 + + 10.1590/1806-9282.62.01.4 + S0104-42302016000100004 + + + Lopes + Marta Heloisa + MH + + Department of Infectious and Parasitic Diseases, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. + + + + Miyaji + Karina Takesaki + KT + + Hospital das Clínicas, FM, USP, São Paulo, SP, Brazil. + + + + Infante + Vanessa + V + + Hospital das Clínicas, FM, USP, São Paulo, SP, Brazil. + + + + eng + + Journal Article + +
+ + Brazil + Rev Assoc Med Bras (1992) + 9308586 + 0104-4230 + + IM + + + Brazil + epidemiology + + + Chikungunya Fever + diagnosis + + + Dengue + diagnosis + + + Diagnosis, Differential + + + Disease Outbreaks + + + Humans + + + Microcephaly + virology + + + Zika Virus + + + Zika Virus Infection + diagnosis + epidemiology + therapy + + +
+ + + + 2016 + 01 + 15 + + + 2016 + 3 + 24 + 6 + 0 + + + 2016 + 3 + 24 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + ppublish + + 27008481 + S0104-42302016000100004 + 10.1590/1806-9282.62.01.4 + + +
+ + + + + 27004142 + + 2016 + 03 + 23 + + + 2017 + 02 + 20 + +
+ + 1043-3155 + + 30 + 1 + + 2016 + Jan + + + Pediatric neurology briefs + Pediatr Neurol Briefs + + Zika Virus Infection and Microcephaly. + + 8 + + 10.15844/pedneurbriefs-30-1-7 + + A Task Force established by the Brazil Ministry of Health investigated the possible association of microcephaly with Zika virus infection during pregnancy and a registry for microcephaly cases among women suspected to have had Zika virus infection during pregnancy. + + + + Millichap + J Gordon + JG + 0000-0002-0173-7931 + + Division of Neurology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL. + + + + eng + + Journal Article + +
+ + United States + Pediatr Neurol Briefs + 9889575 + 1043-3155 + + + + Pediatr Neurol Briefs. 2017 Jan;31(1):1 + 28070150 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3 + 26796813 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Pediatrics. 1968 Jan;41(1):106-14 + 5635472 + + + + Aedes mosquitoes + Brazil + Microcephaly + Zika virus + +
+ + + + 2016 + 3 + 23 + 6 + 0 + + + 2016 + 3 + 24 + 6 + 0 + + + 2016 + 3 + 24 + 6 + 1 + + + ppublish + + 27004142 + 10.15844/pedneurbriefs-30-1-7 + PNB-30-08 + PMC4798858 + + +
+ + + + + 26998633 + + 2017 + 02 + 20 + +
+ + 1468-2044 + + 101 + 7 + + 2016 + Jul + + + Archives of disease in childhood + Arch. Dis. Child. + + Outbreak of Zika virus disease in the Americas and the association with microcephaly, congenital malformations and Guillain-Barré syndrome. + + 600-2 + + 10.1136/archdischild-2016-310590 + + + Ladhani + Shamez N + SN + + National Infection Service, Public Health England, London, UK Paediatric Infectious Diseases Research Group, St. George's University of London, London, UK. + + + + O'Connor + Catherine + C + + National Infection Service, Public Health England, London, UK. + + + + Kirkbride + Hilary + H + + National Infection Service, Public Health England, London, UK. + + + + Brooks + Tim + T + + Rare and Imported Pathogens Laboratory, Public Health England, Salisbury, UK. + + + + Morgan + Dilys + D + + National Infection Service, Public Health England, London, UK. + + + + eng + + Journal Article + + + 2016 + 03 + 14 + +
+ + England + Arch Dis Child + 0372434 + 0003-9888 + + AIM + IM + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Emerg Infect Dis. 2016 May;22(5):925-7 + 27089120 + + + + Brazil + Guillain-Barre syndrome + Zika virus + microcephaly + trave + +
+ + + + 2016 + 02 + 01 + + + 2016 + 02 + 14 + + + 2016 + 3 + 22 + 6 + 0 + + + 2016 + 3 + 22 + 6 + 0 + + + 2016 + 3 + 22 + 6 + 0 + + + ppublish + + 26998633 + archdischild-2016-310590 + 10.1136/archdischild-2016-310590 + PMC4941169 + + +
+ + + + + 26996139 + + 2017 + 11 + 16 + + + 2018 + 02 + 12 + +
+ + 1872-9096 + + 130 + + 2016 + 06 + + + Antiviral research + Antiviral Res. + + Zika virus: History, emergence, biology, and prospects for control. + + 69-80 + + 10.1016/j.antiviral.2016.03.010 + S0166-3542(16)30120-6 + + Zika virus (ZIKV), a previously obscure flavivirus closely related to dengue, West Nile, Japanese encephalitis and yellow fever viruses, has emerged explosively since 2007 to cause a series of epidemics in Micronesia, the South Pacific, and most recently the Americas. After its putative evolution in sub-Saharan Africa, ZIKV spread in the distant past to Asia and has probably emerged on multiple occasions into urban transmission cycles involving Aedes (Stegomyia) spp. mosquitoes and human amplification hosts, accompanied by a relatively mild dengue-like illness. The unprecedented numbers of people infected during recent outbreaks in the South Pacific and the Americas may have resulted in enough ZIKV infections to notice relatively rare congenital microcephaly and Guillain-Barré syndromes. Another hypothesis is that phenotypic changes in Asian lineage ZIKV strains led to these disease outcomes. Here, we review potential strategies to control the ongoing outbreak through vector-centric approaches as well as the prospects for the development of vaccines and therapeutics. + Copyright © 2016 Elsevier B.V. All rights reserved. + + + + Weaver + Scott C + SC + + Institute for Human Infections and Immunity, Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston TX, USA; Institute for Human Infections and Immunity, Department of Pathology, University of Texas Medical Branch, Galveston TX, USA. Electronic address: sweaver@utmb.edu. + + + + Costa + Federico + F + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, BA, Brazil; Instituto da Saúde Coletiva, Universidade Federal da Bahia, Salvador, BA, Brazil. + + + + Garcia-Blanco + Mariano A + MA + + Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore. + + + + Ko + Albert I + AI + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, BA, Brazil; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA. + + + + Ribeiro + Guilherme S + GS + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, BA, Brazil; Instituto da Saúde Coletiva, Universidade Federal da Bahia, Salvador, BA, Brazil. + + + + Saade + George + G + + Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA. + + + + Shi + Pei-Yong + PY + + Department of Biochemistry & Molecular Biology, and Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA; Department of Pharmacology & Toxicology, and Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA. + + + + Vasilakis + Nikos + N + + Institute for Human Infections and Immunity, Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston TX, USA; Institute for Human Infections and Immunity, Department of Pathology, University of Texas Medical Branch, Galveston TX, USA. + + + + eng + + + R01 AI093491 + AI + NIAID NIH HHS + United States + + + R01 AI121207 + AI + NIAID NIH HHS + United States + + + R24 AI120942 + AI + NIAID NIH HHS + United States + + + + Historical Article + Journal Article + Review + Research Support, N.I.H., Extramural + + + 2016 + 03 + 18 + +
+ + Netherlands + Antiviral Res + 8109699 + 0166-3542 + + IM + + + Am J Obstet Gynecol. 2016 Jun;214(6):B2-4 + 26901275 + + + Lancet. 2016 Apr 9;387(10027):1531-9 + 26948433 + + + Nature. 2009 Apr 23;458(7241):1047-50 + 19396146 + + + Acta Trop. 2016 Feb;154:139-44 + 26571068 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Vector Borne Zoonotic Dis. 2014 Dec;14(12):862-5 + 25514122 + + + PLoS Negl Trop Dis. 2014;8(1):e2636 + 24421913 + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + J Virol. 2010 Jan;84(1):599-611 + 19864381 + + + Western Pac Surveill Response J. 2013 Apr-Jun;4(2):8-10 + 24015365 + + + PLoS Negl Trop Dis. 2014 Oct;8(10):e3188 + 25299181 + + + Int J Infect Dis. 2016 Mar;44:11-5 + 26854199 + + + PLoS Negl Trop Dis. 2014 Feb;8(2):e2681 + 24516683 + + + MMWR Morb Mortal Wkly Rep. 2016;65(6):154-8 + 26890470 + + + Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4772-5 + 21383140 + + + Methods Mol Biol. 2014;1138:285-99 + 24696344 + + + N Engl J Med. 2012 Jun 14;366(24):2294-304 + 22694000 + + + Nat Commun. 2014;5:4084 + 24933611 + + + PLoS Negl Trop Dis. 2015 May;9(5):e0003764 + 25951202 + + + Ann Intern Med. 2016 May 17;164(10):689-91 + 26914810 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + PLoS Negl Trop Dis. 2012;6(9):e1820 + 23029581 + + + Neurol India. 2015 Jul-Aug;63(4):497-516 + 26238884 + + + PLoS One. 2011;6(8):e23247 + 21826243 + + + PLoS Negl Trop Dis. 2016 Feb;10(2):e0004517 + 26914330 + + + Bull Soc Pathol Exot. 2001 Aug;94(3):227-30 + 11681215 + + + Trans R Soc Trop Med Hyg. 1982;76(4):552-62 + 6304948 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Antiviral Res. 2013 Nov;100(2):500-19 + 24076358 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + J Virol. 2000 Apr;74(7):3227-34 + 10708439 + + + J Clin Virol. 2016 Apr;77:29-31 + 26895226 + + + Nat Rev Microbiol. 2011 Jul;9(7):532-41 + 21666708 + + + PLoS Negl Trop Dis. 2012;6(8):e1792 + 22953014 + + + PLoS One. 2014;9(10):e109442 + 25310102 + + + Emerg Infect Dis. 2012 Feb;18(2):349-51 + 22305269 + + + Science. 2015 Oct 9;350(6257):217-21 + 26138103 + + + Viruses. 2011 Sep;3(9):1562-608 + 21994796 + + + Trans R Soc Trop Med Hyg. 1956 Sep;50(5):442-8 + 13380987 + + + PLoS Negl Trop Dis. 2013;7(8):e2348 + 23936579 + + + J Med Entomol. 2014 Jan;51(1):145-54 + 24605464 + + + PLoS Negl Trop Dis. 2015;9(7):e0003930 + 26204449 + + + Euro Surveill. 2014;19(9). pii: 20720 + 24626205 + + + Emerg Infect Dis. 2016 May;22(5):940 + 27088817 + + + Trop Med Health. 2011 Dec;39(4 Suppl):3-11 + 22500131 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + Lancet. 2016 Jan 16;387(10015):227-8 + 26775124 + + + Cell Rep. 2015 Jul 28;12(4):673-83 + 26190106 + + + Antiviral Res. 2015 Dec;124:30-42 + 26518229 + + + Handb Clin Neurol. 2013;111:129-41 + 23622158 + + + MMWR Morb Mortal Wkly Rep. 2016;65(6):159-60 + 26890059 + + + J Hyg (Lond). 1979 Oct;83(2):213-9 + 489960 + + + J Virol. 2015 Sep;89(17):8880-96 + 26085147 + + + RNA. 2015 Apr;21(4):525-6 + 25780123 + + + Infect Genet Evol. 2013 Oct;19:292-311 + 23523817 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + Nature. 2008 Sep 11;455(7210):242-5 + 18690214 + + + Nature. 2010 Nov 18;468(7322):452-6 + 21085181 + + + Am J Trop Med Hyg. 2002 Oct;67(4):363-70 + 12452490 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Trans R Soc Trop Med Hyg. 1956 May;50(3):238-42 + 13337908 + + + Cell Stem Cell. 2016 May 5;18(5):587-90 + 26952870 + + + P R Health Sci J. 1987 Aug;6(2):107-11 + 3313490 + + + Biochem J. 2014 Sep 1;462(2):215-30 + 25102029 + + + Neurology. 2007 Nov 27;69(22):2105-7 + 18040016 + + + Am J Perinatol. 2016 Jun;33(7):625-39 + 26939047 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Animals + + + Biological Evolution + + + Disease Outbreaks + history + + + Disease Vectors + + + Flavivirus + classification + physiology + + + History, 21st Century + + + Host-Pathogen Interactions + + + Humans + + + Patient Outcome Assessment + + + Phylogeny + + + Phylogeography + + + Zika Virus + classification + physiology + + + Zika Virus Infection + epidemiology + prevention & control + transmission + virology + + +
+ + + + 2016 + 02 + 29 + + + 2016 + 03 + 09 + + + 2016 + 03 + 12 + + + 2016 + 3 + 22 + 6 + 0 + + + 2016 + 3 + 22 + 6 + 0 + + + 2017 + 11 + 29 + 6 + 0 + + + ppublish + + 26996139 + S0166-3542(16)30120-6 + 10.1016/j.antiviral.2016.03.010 + PMC4851879 + NIHMS776231 + + +
+ + + + + 26994509 + + 2017 + 05 + 08 + + + 2017 + 11 + 28 + +
+ + 1555-7162 + + 129 + 8 + + 2016 + Aug + + + The American journal of medicine + Am. J. Med. + + Re-Emergence of Zika Virus: A Review on Pathogenesis, Clinical Manifestations, Diagnosis, Treatment, and Prevention. + + 879.e7-879.e12 + + 10.1016/j.amjmed.2016.02.027 + S0002-9343(16)30245-5 + + Zika virus (ZKV) is an arbovirus of the Flaviviridae family, which includes West Nile, dengue fever, yellow fever, and Japanese encephalitis virus. It is transmitted by the Aedes genus of mosquitoes. Before 2015, ZKV outbreaks occurred in areas of Africa, the Pacific Islands, and Southeast Asia. The current large outbreak, which began in Brazil, has also emerged throughout a large part of South/Central America, a number of islands in the Caribbean, including Puerto Rico, the Virgin Islands, and Mexico. A sudden rise in the numbers of infants reported born with microcephaly in Brazil, and the detection of the single-stranded positive RNA virus in the amniotic fluid of affected newborns, has captured medical, mainstream media, and global political attention, causing considerable concern in a post-Ebola global community considerably more focused on the threat of internationally transmissible diseases. The goal of this article is to provide an overview of ZKV for clinicians, with the emphasis on pathogenesis, clinical manifestations, diagnosis, and treatment/preventive measures. + Copyright © 2016 Elsevier Inc. All rights reserved. + + + + Shuaib + Waqas + W + + Department of Medicine, Auburn Community Hospital, NY. Electronic address: waqas1184@hotmail.com. + + + + Stanazai + Hashim + H + + Wichita Falls Family Practice Residency Program, Witchita Falls, TX. + + + + Abazid + Ahmad G + AG + + Wichita Falls Family Practice Residency Program, Witchita Falls, TX. + + + + Mattar + Ahmed A + AA + + Wichita Falls Family Practice Residency Program, Witchita Falls, TX. + + + + eng + + Journal Article + Review + + + 2016 + 03 + 17 + +
+ + United States + Am J Med + 0267200 + 0002-9343 + + AIM + IM + + + Am J Med. 2016 Dec;129(12 ):e351 + 27866593 + + + + + Aedes + + + Animals + + + Disease Outbreaks + + + Global Health + + + Humans + + + Zika Virus Infection + diagnosis + epidemiology + prevention & control + therapy + + + + Brazil + Chikungunya + Dengue + Microcephaly + Zika + +
+ + + + 2016 + 02 + 13 + + + 2016 + 02 + 17 + + + 2016 + 02 + 18 + + + 2016 + 3 + 21 + 6 + 0 + + + 2016 + 3 + 21 + 6 + 0 + + + 2017 + 5 + 10 + 6 + 0 + + + ppublish + + 26994509 + S0002-9343(16)30245-5 + 10.1016/j.amjmed.2016.02.027 + + +
+ + + + + 26993880 + + 2016 + 07 + 07 + + + 2017 + 07 + 12 + +
+ + 1474-547X + + 387 + 10033 + + 2016 + May + 21 + + + Lancet (London, England) + Lancet + + Microcephaly and Zika virus infection. + + 2070-2072 + + S0140-6736(16)00742-X + 10.1016/S0140-6736(16)00742-X + + + Rodrigues + Laura C + LC + + London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK; Microcephaly Epidemic Research Group (MERG), Recife, Brazil. Electronic address: laura.rodrigues@lshtm.ac.uk. + + + + eng + + Comment + Journal Article + + + 2016 + 03 + 16 + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Lancet. 2016 May 21;387(10033):2125-32 + 26993883 + + + + + Female + + + Humans + + + Male + + + Microcephaly + epidemiology + + + Pregnancy + + + Zika Virus + + + Zika Virus Infection + epidemiology + + +
+ + + + 2016 + 3 + 20 + 6 + 0 + + + 2016 + 3 + 20 + 6 + 0 + + + 2016 + 7 + 9 + 6 + 0 + + + ppublish + + 26993880 + S0140-6736(16)00742-X + 10.1016/S0140-6736(16)00742-X + + +
+ + + + + 26988170 + + 2017 + 01 + 05 + + + 2017 + 11 + 16 + +
+ + 1576-6578 + + 62 + 7 + + 2016 + Apr + 01 + + + Revista de neurologia + Rev Neurol + + Epidemiology and neurological complications of infection by the Zika virus: a new emerging neurotropic virus. + + 317-28 + + + The current epidemic outbreak due to Zika virus began in 2015 and since then it has been reported in 31 countries and territories in America. The epidemiological and clinical aspects related to infection by Zika virus are reviewed. + Since 2007, 55 countries in America, Asia, Africa and Oceania have detected local transmission of the virus. This epidemic has affected almost 1.5 million people in Brazil. 80% of the cases are asymptomatic. The symptoms of Zika virus disease include fever, maculopapular rash, arthralgia and non-purulent conjunctivitis. The symptoms are usually self-limiting and last one week. An increase in the incidence of cases of microcephaly, retinal lesions and Guillain-Barre syndrome associated with the Zika virus has been reported. Zika-associated Guillain-Barre syndrome in Polynesia is a pure motor axonal variant. The RNA of the Zika virus has been identified in samples of brain tissue, placenta and amniotic liquid of children with microcephaly and in the still-born infants of women infected by Zika during pregnancy. The reverse transcription polymerase chain reaction test is recommended to detect viral RNA, and serological tests (IgM ELISA and neutralising antibodies) should be conducted to confirm infection by Zika. The differential diagnosis includes infection by the dengue and chikungunya viruses. + Knowledge about the pathogenic mechanisms involved in infection due to Zika virus and its long-term consequences in adults and newborn infants is still limited. + + + + Carod-Artal + Francisco J + FJ + + Raigmore Hospital, Inverness, Reino Unido. + + + + eng + spa + + Journal Article + Review + +
+ + Spain + Rev Neurol + 7706841 + 0210-0010 + + IM + + + Adult + + + Aedes + virology + + + Animals + + + Chikungunya Fever + diagnosis + + + Communicable Diseases, Emerging + epidemiology + + + Dengue + diagnosis + + + Disease Outbreaks + + + Female + + + Global Health + + + Guillain-Barre Syndrome + epidemiology + etiology + + + Humans + + + Incidence + + + Infant, Newborn + + + Infectious Disease Transmission, Vertical + + + Insect Vectors + virology + + + Male + + + Microcephaly + epidemiology + etiology + + + Nervous System Diseases + epidemiology + etiology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Retinal Diseases + epidemiology + etiology + + + Sexually Transmitted Diseases, Viral + epidemiology + + + Stillbirth + + + Transfusion Reaction + + + Zika Virus + genetics + isolation & purification + + + Zika Virus Infection + complications + epidemiology + transmission + + + + Epidemiologia y complicaciones neurologicas de la infeccion por el virus del Zika: un nuevo virus neurotropo emergente. + Introduccion. El actual brote epidemico por virus Zika se inicio en 2015 y en la actualidad afecta a 31 paises y territorios en America. Se revisan los aspectos epidemiologicos y clinicos asociados con la infeccion por virus Zika. Desarrollo. Desde 2007, 55 paises de America, Asia, Africa y Oceania han detectado transmision local del virus. La actual epidemia ha afectado a casi 1,5 millones de personas en Brasil. El 80% de los casos son asintomaticos. La enfermedad por virus Zika cursa con fiebre, exantema maculopapular, artralgias y conjuntivitis no purulenta. Los sintomas suelen ser autolimitados y duran una semana. Se ha descrito un aumento de la incidencia de los casos de microcefalia, lesiones retinianas y sindrome de Guillain-Barre asociados con el virus Zika. El sindrome de Guillain-Barre asociado al Zika en la Polinesia es una variante axonal motora pura. El ARN del virus Zika se ha identificado en muestras de tejido cerebral, placenta y liquido amniotico de niños con microcefalia y en perdidas fetales de mujeres infectadas por Zika durante el embarazo. Se recomienda realizar la prueba de reaccion en cadena de la polimerasa mediante transcriptasa inversa para detectar ARN virico y pruebas serologicas (IgM ELISA y anticuerpos neutralizantes) para confirmar una infeccion por Zika. El diagnostico diferencial incluye la infeccion por virus dengue y chikungunya. Conclusiones. Existe un conocimiento limitado sobre los mecanismos patogenicos implicados y las consecuencias a largo plazo de la infeccion por virus Zika en adultos y recien nacidos. + +
+ + + + 2016 + 3 + 19 + 6 + 0 + + + 2016 + 3 + 19 + 6 + 0 + + + 2017 + 1 + 6 + 6 + 0 + + + ppublish + + 26988170 + rn2016152 + + +
+ + + + + 26985965 + + 2016 + 07 + 22 + + + 2016 + 03 + 18 + +
+ + 1545-861X + + 65 + 10 + + 2016 + Mar + 18 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Revision to CDC's Zika Travel Notices: Minimal Likelihood for Mosquito-Borne Zika Virus Transmission at Elevations Above 2,000 Meters. + + 267-8 + + 10.15585/mmwr.mm6510e1 + + Since May 2015, when Zika virus, a flavivirus transmitted primarily by Aedes aegypti mosquitoes, was reported in Brazil, the virus has rapidly spread across the Region of the Americas and the Caribbean. The association between maternal Zika virus infection and adverse fetal and reproductive outcomes, including microcephaly, prompted CDC to issue a Level 2 alert travel notice* for the 37 countries and U.S. territories (at the national and territorial level) that have reported recent Zika virus transmission as of March 11, 2016. In addition to mosquito bite precautions for all travelers, CDC advises that pregnant women postpone travel to affected countries and U.S. territories. Within a nation's borders, ecologic characteristics, which determine the distribution of mosquito vectors, can vary considerably. CDC conducted a spatial analysis, focusing on the probability of occurrence of Ae. aegypti, to support the demarcation for subnational travel alerts. Based on results of this analysis, travel that is limited to elevations higher than 2,000 m (6,562 ft) above sea level is considered to have minimal (approximately 1%) likelihood for mosquito-borne Zika virus transmission, even within countries reporting active transmission. Women who are pregnant should avoid travel to elevations <2,000 m in countries with active Zika virus transmission. + + + + Cetron + Martin + M + + Division of Global Migration and Quarantine, National Center for Emerging and Zoonotic Infectious Diseases, CDC. + + + + eng + + Journal Article + + + 2016 + 03 + 18 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + Altitude + + + Animals + + + Centers for Disease Control and Prevention (U.S.) + + + Culicidae + virology + + + Female + + + Guidelines as Topic + + + Humans + + + Likelihood Functions + + + Pregnancy + + + Pregnancy Complications, Infectious + prevention & control + + + Travel + + + United States + + + Zika Virus + isolation & purification + + + Zika Virus Infection + prevention & control + transmission + + +
+ + + + 2016 + 3 + 18 + 6 + 0 + + + 2016 + 3 + 18 + 6 + 0 + + + 2016 + 7 + 23 + 6 + 0 + + + epublish + + 26985965 + 10.15585/mmwr.mm6510e1 + + +
+ + + + + 26981761 + + 2016 + 05 + 02 + + + 2016 + 03 + 17 + +
+ + 1807-3107 + + 30 + + 2016 + + + Brazilian oral research + Braz Oral Res + + Zika virus infection spread through saliva--a truth or myth? + 10.1590/1807-3107BOR-2016.vol30.0046 + S1806-83242016000100801 + + In this Point-of-view article we highlighted some features related to saliva and virus infection, in special for zika virus. In addition, we pointed out the potential oral problems caused by a microcephaly originated by a zika virus infection. In the end the, we demonstrated the importance of a more comprehensive exploration of saliva and their components as a fluid for diagnostic and therapeutic approaches on oral and systemic diseases. + + + + Siqueira + Walter Luiz + WL + + Department of Dentistry and Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada. + + + + Moffa + Eduardo Buozi + EB + + Department of Dentistry and Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada. + + + + Mussi + Maria Carolina Martins + MC + + Department of Oral Pathology, School of Dentistry, Universidade de São Paulo, São Paulo, SP, Brazil. + + + + Machado + Maria Aparecida de Andrade Moreira + MA + + Department of Pediatric Dentistry, Orthodontics and Public Health, Bauru Dental School, Universidade de São Paulo, Bauru, SP, Brazil. + + + + eng + + + 106657 + Canadian Institutes of Health Research + Canada + + + 113166 + Canadian Institutes of Health Research + Canada + + + 97577 + Canadian Institutes of Health Research + Canada + + + + Journal Article + Research Support, Non-U.S. Gov't + + + 2016 + 03 + 15 + +
+ + Brazil + Braz Oral Res + 101307187 + 1806-8324 + + D + IM + + + HIV Infections + + + Humans + + + Microcephaly + virology + + + Saliva + virology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + diagnosis + transmission + + +
+ + + + 2016 + 02 + 13 + + + 2016 + 02 + 22 + + + 2016 + 3 + 17 + 6 + 0 + + + 2016 + 3 + 18 + 6 + 0 + + + 2016 + 5 + 3 + 6 + 0 + + + ppublish + + 26981761 + S1806-83242016000100801 + 10.1590/1807-3107BOR-2016.vol30.0046 + + +
+ + + + + 26978815 + + 2017 + 01 + 30 + + + 2017 + 01 + 30 + +
+ + 1652-7518 + + 113 + + 2016 + 03 + 10 + + + Lakartidningen + Lakartidningen + + [Zika virus - ancient virus gets new life in a new ecosystem. Microcephaly and Guillain-Barre syndrome are possible consequences when there is no background herd immunity in the population]. + DX9X + + Zika virus is a mosquito-borne flavivirus transmitted by Aedes mosquitos. The virus was discovered in 1947 in the Zika forest in Uganda. Symptomatic disease is usually mild and is characterized by maculopapular rash, headache, fever, arthralgia and conjunctivitis. Fatalities are rare. There is neither vaccine nor curative treatment available. In May 2015, the first observation of local virus transmission was reported from Brazil. During the expanding outbreak in the Americas, Zika virus infection has been associated with microcephaly in newborn and fetal losses in women infected with Zika virus during pregnancy. The main reason for the current epidemic in the Americas is the introduction of an Old World virus into a new ecosystem, with no background herd immunity in the population. It is likely that the spread of Zika virus will continue, affecting all countries in the Americas except for Chile and Canada. + + + + Olsen + Björn + B + + Institutionen för medicinska vetenskaper, infektionssjukdomar - Uppsala universitet Uppsala, Sweden Institutionen för medicinska vetenskaper - Uppsala universitet Uppsala, Sweden. + + + + Lundkvist + Åke + Å + + Uppsala universitetet Institutionen for medicinsk biokemi och mikrobiologi - Uppsala, Sweden Uppsala universitetet Institutionen for medicinsk biokemi och mikrobiologi - Uppsala, Sweden. + + + + swe + + Journal Article + + Zikavirus--gammalt virus får nytt liv i nytt ecosystem. Mikrocefali och Guillain-Barrés syndrom möjliga följder när bakgrundsimmunitet saknas hos befolkningen. + + 2016 + 03 + 10 + +
+ + Sweden + Lakartidningen + 0027707 + 0023-7205 + + IM + + + Communicable Diseases, Emerging + + + Female + + + Guillain-Barre Syndrome + virology + + + Humans + + + Immunity, Herd + + + Microcephaly + virology + + + Pregnancy + + + Zika Virus + immunology + + + Zika Virus Infection + complications + immunology + transmission + + +
+ + + + 2016 + 3 + 16 + 6 + 0 + + + 2016 + 3 + 16 + 6 + 0 + + + 2017 + 1 + 31 + 6 + 0 + + + epublish + + 26978815 + DX9X + + +
+ + + + + 26976611 + + 2018 + 02 + 15 + + + 2018 + 02 + 15 + +
+ + 1757-4684 + + 8 + 4 + + 2016 + 04 + 01 + + + EMBO molecular medicine + EMBO Mol Med + + Causal or not: applying the Bradford Hill aspects of evidence to the association between Zika virus and microcephaly. + + 305-7 + + 10.15252/emmm.201506058 + + + Frank + Christina + C + 0000-0001-6776-8450 + + Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany. + + + + Faber + Mirko + M + + Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany. + + + + Stark + Klaus + K + + Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany. + + + + eng + + Journal Article + +
+ + England + EMBO Mol Med + 101487380 + 1757-4676 + + IM + + + Am J Ophthalmol. 2003 Oct;136(4):733-5 + 14516816 + + + Clin Pediatr (Phila). 1968 Jun;7(6):323-30 + 4869853 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Microbes Infect. 2016 Mar;18(3):167-8 + 26774330 + + + Pediatrics. 2006 Mar;117(3):936-9 + 16510678 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + MMWR Morb Mortal Wkly Rep. 2016;65(6):159-60 + 26890059 + + + N Engl J Med. 2016 Mar 10;374(10):951-8 + 26862926 + + + Proc R Soc Med. 1965 May;58:295-300 + 14283879 + + + + + Brazil + epidemiology + + + Female + + + Humans + + + Microcephaly + epidemiology + virology + + + Polynesia + epidemiology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + epidemiology + + +
+ + + + 2016 + 3 + 16 + 6 + 0 + + + 2016 + 3 + 16 + 6 + 0 + + + 2018 + 2 + 16 + 6 + 0 + + + ppublish + + 26976611 + emmm.201506058 + 10.15252/emmm.201506058 + PMC4818755 + + +
+ + + + + 28515967 + + 2017 + 05 + 21 + +
+ + 2157-3999 + + 8 + + 2016 + Mar + 16 + + + PLoS currents + PLoS Curr + + Unintended Pregnancies in Brazil - A Challenge for the Recommendation to Delay Pregnancy Due to Zika. + ecurrents.outbreaks.7038a6813f734c1db547240c2a0ba291 + 10.1371/currents.outbreaks.7038a6813f734c1db547240c2a0ba291 + + Because of the potential link between the ongoing Zika virus outbreak and a surge in the number of cases of congenital microcephaly, officials in Latin America have recommended that women postpone pregnancy until this association is firmly established or the outbreak subsides. However, in all these countries a large proportion of babies are still born out of unplanned pregnancies. Teenage girls are particularly at high risk, as they often lack access to preventive contraception methods, or the knowledge to use them appropriately. To gauge the magnitude of the barriers preventing the implementation of such a recommendation in Brazil, the country so far most affected by the Zika epidemic, we evaluated pregnancy rates in teenage girls, and their spatial heterogeneity in the country, in recent years (2012-2014). Nearly 20% of children born in Brazil today (~560,000 live births) are by teenage mothers. Birth incidence is far higher in the tropical and poorer northern states. However, in absolute terms most births occur in the populous southeastern states, matching to a large extent the geographic distribution of dengue (an indicator of suitable climatic and sociodemographic conditions for the circulation of Aedes mosquitoes). These findings indicate that recommendation to delay pregnancy will leave over half a million pregnant adolescents in Brazil vulnerable to infection every year if not accompanied by effective education and real access to prevention. + + + + Schuck-Paim + Cynthia + C + + Wolfson College, Oxford University, Oxford, Oxfordshire, United Kingdom. + + + + López + Daniel + D + + National Institute of Pure and Applied Mathematics (IMPA), Rio de Janeiro, Brazil. + + + + Simonsen + Lone + L + + Department of Global Health, George Washington University, Milken Insittute School of Public Health, Washington DC, Maryland, USA. + + + + Alonso + Wladimir + W + + Laboratory for Human Evolution Studies, Genetics and Evolutionary Biology, University of São Paulo, São Paulo, Brazil. + + + + eng + + Journal Article + + + 2016 + 03 + 16 + +
+ + United States + PLoS Curr + 101515638 + 2157-3999 + + + + BMC Public Health. 2012 Nov 15;12:982 + 23153033 + + + Sci Data. 2015 Jul 07;2:150035 + 26175912 + + + PLoS Negl Trop Dis. 2014 Feb 06;8(2):e2681 + 24516683 + + + JAMA. 2016 Mar 22-29;315(12):1227-8 + 26914692 + + + Nature. 2016 Feb 4;530(7588):13-4 + 26842033 + + + Lancet. 2016 Feb 6;387(10018):521-4 + 26852261 + + + + Aedes + Brazil + Zika + microcephaly + pregancy + teenagers + +
+ + + + 2017 + 5 + 19 + 6 + 0 + + + 2016 + 3 + 16 + 0 + 0 + + + 2016 + 3 + 16 + 0 + 0 + + + epublish + + 28515967 + 10.1371/currents.outbreaks.7038a6813f734c1db547240c2a0ba291 + PMC4866532 + + +
+ + + + + 26973301 + + 2016 + 07 + 29 + + + 2018 + 03 + 07 + +
+ + 1474-4457 + + 16 + 3 + + 2016 + Mar + + + The Lancet. Infectious diseases + Lancet Infect Dis + + Zika virus in the dock. + + 265 + + 10.1016/S1473-3099(16)00085-2 + S1473-3099(16)00085-2 + + + Lancet Infectious Diseases + + + eng + + Editorial + +
+ + United States + Lancet Infect Dis + 101130150 + 1473-3099 + + IM + + + Lancet Infect Dis. 2016 Jul;16(7):772 + 27352749 + + + + + Aedes + physiology + virology + + + Animals + + + Brazil + epidemiology + + + Global Health + + + Humans + + + Infant, Newborn + + + Insect Vectors + physiology + virology + + + Microcephaly + epidemiology + etiology + + + Risk Factors + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + epidemiology + + +
+ + + + 2016 + 3 + 15 + 6 + 0 + + + 2016 + 3 + 15 + 6 + 0 + + + 2016 + 7 + 30 + 6 + 0 + + + ppublish + + 26973301 + S1473-3099(16)00085-2 + 10.1016/S1473-3099(16)00085-2 + + +
+ + + + + 26969497 + + 2018 + 01 + 08 + + + 2018 + 01 + 08 + +
+ + 1573-3610 + + 41 + 3 + + 2016 + Jun + + + Journal of community health + J Community Health + + The Convergence of a Virus, Mosquitoes, and Human Travel in Globalizing the Zika Epidemic. + + 674-9 + + 10.1007/s10900-016-0177-7 + + The Zika virus was first identified in 1947 in the Zika Forest of Uganda. It was discovered in a rhesus monkey that had been placed in a cage on a sentinel platform in the forest by the Virus Research Institute. When this writer visited the institute and the Zika Forest in 1961, work was underway to identify mosquito species at various levels of the tree canopy. This was done through the placement of traps at various levels of a 120-foot-high steel tower which this writer climbed. At that time, researchers isolated 12 strains of Zika virus from traps on the tower. Over the next six decades, the virus spread slowly to other parts of Africa, and eventually appeared in Southeast Asia, transmitted by Aedes aegypti and other Aedes mosquito species. By 1981, only 14 cases of illness had been reported as due to the Zika virus. Since most infections with this virus are either mild or asymptomatic, its true geographic spread was not fully appreciated. The current globalization of the Zika epidemic began on the Pacific island of Yap in the Federated States of Polynesia in 2007. This was the first known presence of the Zika virus outside of Africa and Southeast Asia. It was estimated that 73 % of the island's population had been infected. In 2013, the virus spread to French Polynesia where an estimated 28,000 cases occurred in a population of 270,000. During that year and afterwards, microcephaly and other congenital abnormalities were observed in the infants of women who were pregnant when they contracted the virus. It is currently not known if cases of microcephaly have resulted from infection of pregnant women or from infection plus some other co-factor. The epidemic rapidly spread to the Cook Islands and Easter Island. In 2015, Zika virus infection was diagnosed in Brazil where it was associated with microcephaly in the infants of some women who were pregnant when they contracted the disease. Cases of the Guillain-Barré syndrome were also found to be associated with Zika virus infection. How the disease entered Brazil is a matter of conjecture. However, the strain responsible for the epidemic in Brazil and elsewhere in South and Central America is phylogenetically identical to that which caused the epidemic in French Polynesia. The wide distribution of Aedes aegypti, a principal vector of the virus, and other Aedes species has greatly facilitated the spread of the disease. Aedes aegypti is an invasive species of mosquito in the Western Hemisphere that has adapted well to densely-populated urban environments. In addition, male-to-female human sexual transmission has increasingly been demonstrated in the US and elsewhere. In February 2016, the World Health Organization (WHO) declared the current Zika outbreak a Public Health Emergency of international concern. On the recommendation of its Emergency Committee on Zika Virus and Observed Increase in Neurological Disorders and Neonatal Malformations, WHO issued a group of recommendations to contain the epidemic. The globalization of the Zika virus was made possible by the widespread presence in various parts of the world of Aedes vectors and increased human travel that facilitated geographic spread. This globalization of Zika follows upon that of West Nile, Ebola, Dengue, and Chikungunya. Its ultimate spread is difficult to predict, but will hopefully be restricted through vigorous preventive measures. + + + + Imperato + Pascal James + PJ + + Downstate Medical Center, School of Public Health, State University of New York, 450 Clarkson Avenue, MSC 43, Brooklyn, NY, 11203, USA. pascal.imperato@downstate.edu. + + + + eng + + Historical Article + Journal Article + Review + +
+ + Netherlands + J Community Health + 7600747 + 0094-5145 + + IM + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Ann Trop Med Parasitol. 1975 Mar;69(1):49-64 + 1124969 + + + Euro Surveill. 2014 Apr 10;19(14):null + 24739982 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):120-1 + 26866485 + + + Antiviral Res. 2010 Feb;85(2):328-45 + 19857523 + + + Trans R Soc Trop Med Hyg. 1964 Jul;58:335-8 + 14175744 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + Lancet Infect Dis. 2016 Feb;16(2):156-7 + 26723756 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + J Hyg (Lond). 1979 Oct;83(2):213-9 + 489960 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Aedes + virology + + + Animals + + + Epidemics + + + Global Health + + + History, 20th Century + + + History, 21st Century + + + Humans + + + Mosquito Vectors + + + Travel + + + Uganda + + + Zika Virus + + + Zika Virus Infection + epidemiology + history + transmission + + + + Aedes aegypti + Guillain-Barré syndrome + Kisubi Catholic Mission + Microcephaly + Zika Forest and Pascal James Imperato + Zika virus + Zika virus and travel + Zika virus infection + +
+ + + + 2016 + 3 + 13 + 6 + 0 + + + 2016 + 3 + 13 + 6 + 0 + + + 2018 + 1 + 9 + 6 + 0 + + + ppublish + + 26969497 + 10.1007/s10900-016-0177-7 + 10.1007/s10900-016-0177-7 + + +
+ + + + + 26966326 + + 2017 + 02 + 24 + + + 2017 + 02 + 24 + +
+ + 1564-0604 + + 94 + 3 + + 2016 + Mar + 01 + + + Bulletin of the World Health Organization + Bull. World Health Organ. + + Brazil's scientists scramble to solve the Zika puzzle. + + 165-6 + + 10.2471/BLT.16.030316 + + The World Health Organization has declared the recent leap in the number of microcephaly cases and their suspected association with Zika virus a public health emergency of international concern. Ana Bispo tells Andréia Azevedo Soares why Brazil should have some scientific answers in coming months. + + + + Bispo + Ana + A + + + eng + + Interview + +
+ + Switzerland + Bull World Health Organ + 7507052 + 0042-9686 + + IM + + + Brazil + + + Humans + + + Public Health + + + Research + + + World Health Organization + + + Zika Virus + isolation & purification + + + Zika Virus Infection + prevention & control + + +
+ + + + 2016 + 3 + 12 + 6 + 0 + + + 2016 + 3 + 12 + 6 + 0 + + + 2017 + 2 + 25 + 6 + 0 + + + ppublish + + 26966326 + 10.2471/BLT.16.030316 + BLT.16.030316 + PMC4773940 + + +
+ + + + + 26965962 + + 2017 + 01 + 17 + + + 2017 + 08 + 22 + +
+ + 0929-6646 + + 115 + 4 + + 2016 + Apr + + + Journal of the Formosan Medical Association = Taiwan yi zhi + J. Formos. Med. Assoc. + + Zika virus infection-the next wave after dengue? + + 226-42 + + 10.1016/j.jfma.2016.02.002 + S0929-6646(16)00077-2 + + Zika virus was initially discovered in east Africa about 70 years ago and remained a neglected arboviral disease in Africa and Southeast Asia. The virus first came into the limelight in 2007 when it caused an outbreak in Micronesia. In the ensuing decade, it spread widely in other Pacific islands, after which its incursion into Brazil in 2015 led to a widespread epidemic in Latin America. In most infected patients the disease is relatively benign. Serious complications include Guillain-Barré syndrome and congenital infection which may lead to microcephaly and maculopathy. Aedes mosquitoes are the main vectors, in particular, Ae. aegypti. Ae. albopictus is another potential vector. Since the competent mosquito vectors are highly prevalent in most tropical and subtropical countries, introduction of the virus to these areas could readily result in endemic transmission of the disease. The priorities of control include reinforcing education of travellers to and residents of endemic areas, preventing further local transmission by vectors, and an integrated vector management programme. The container habitats of Ae. aegypti and Ae. albopictus means engagement of the community and citizens is of utmost importance to the success of vector control. + Copyright © 2016. Published by Elsevier B.V. + + + + Wong + Samson Sai-Yin + SS + + Department of Microbiology, Research Centre for Infection and Immunology, Faculty of Medicine, The University of Hong Kong, Hong Kong. Electronic address: samsonsy@hku.hk. + + + + Poon + Rosana Wing-Shan + RW + + Department of Microbiology, Queen Mary Hospital, Hong Kong. + + + + Wong + Sally Cheuk-Ying + SC + + Department of Microbiology, Queen Mary Hospital, Hong Kong. + + + + eng + + Historical Article + Journal Article + Review + + + 2016 + 03 + 07 + +
+ + Singapore + J Formos Med Assoc + 9214933 + 0929-6646 + + IM + + + J Formos Med Assoc. 2016 Aug;115(8):684 + 27265325 + + + + + Aedes + virology + + + Animals + + + Disease Outbreaks + history + + + Guillain-Barre Syndrome + etiology + + + History, 20th Century + + + History, 21st Century + + + Humans + + + Infant, Newborn + + + Macular Degeneration + etiology + + + Microcephaly + etiology + + + Travel Medicine + + + Zika Virus + + + Zika Virus Infection + complications + epidemiology + transmission + + + + Aedes + Flavivirus + Zika virus + congenital abnormalities + travel medicine + +
+ + + + 2016 + 02 + 16 + + + 2016 + 02 + 17 + + + 2016 + 3 + 12 + 6 + 0 + + + 2016 + 3 + 12 + 6 + 0 + + + 2017 + 1 + 18 + 6 + 0 + + + ppublish + + 26965962 + S0929-6646(16)00077-2 + 10.1016/j.jfma.2016.02.002 + + +
+ + + + + 26963593 + + 2016 + 07 + 15 + + + 2016 + 03 + 11 + +
+ + 1545-861X + + 65 + 9 + + 2016 + Mar + 11 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Increase in Reported Prevalence of Microcephaly in Infants Born to Women Living in Areas with Confirmed Zika Virus Transmission During the First Trimester of Pregnancy - Brazil, 2015. + + 242-7 + + 10.15585/mmwr.mm6509e2 + + Widespread transmission of Zika virus by Aedes mosquitoes has been recognized in Brazil since late 2014, and in October 2015, an increase in the number of reported cases of microcephaly was reported to the Brazil Ministry of Health.* By January 2016, a total of 3,530 suspected microcephaly cases had been reported, many of which occurred in infants born to women who lived in or had visited areas where Zika virus transmission was occurring. Microcephaly surveillance was enhanced in late 2015 by implementing a more sensitive case definition. Based on the peak number of reported cases of microcephaly, and assuming an average estimated pregnancy duration of 38 weeks in Brazil (1), the first trimester of pregnancy coincided with reports of cases of febrile rash illness compatible with Zika virus disease in pregnant women in Bahia, Paraíba, and Pernambuco states, supporting an association between Zika virus infection during early pregnancy and the occurrence of microcephaly. Pregnant women in areas where Zika virus transmission is occurring should take steps to avoid mosquito bites. Additional studies are needed to further elucidate the relationship between Zika virus infection in pregnancy and microcephaly. + + + + Kleber de Oliveira + Wanderson + W + + + Cortez-Escalante + Juan + J + + + De Oliveira + Wanessa Tenório Gonçalves Holanda + WT + + + do Carmo + Greice Madeleine Ikeda + GM + + + Henriques + Cláudio Maierovitch Pessanha + CM + + + Coelho + Giovanini Evelim + GE + + + Araújo de França + Giovanny Vinícius + GV + + + eng + + Journal Article + + + 2016 + 03 + 11 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant + + + Infant, Newborn + + + Male + + + Microcephaly + epidemiology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Pregnancy Trimester, First + + + Prevalence + + + Residence Characteristics + statistics & numerical data + + + Zika Virus Infection + epidemiology + transmission + + +
+ + + + 2016 + 3 + 11 + 6 + 0 + + + 2016 + 3 + 11 + 6 + 0 + + + 2016 + 7 + 16 + 6 + 0 + + + epublish + + 26963593 + 10.15585/mmwr.mm6509e2 + + +
+ + + + + 26961637 + + 2016 + 04 + 05 + + + 2016 + 03 + 10 + +
+ + 1476-4687 + + 531 + 7593 + + 2016 + Mar + 10 + + + Nature + Nature + + First Zika-linked birth defects detected in Colombia. + + 153 + + 10.1038/nature.2016.19502 + + + Butler + Declan + D + + + eng + + News + +
+ + England + Nature + 0410462 + 0028-0836 + + IM + + + Brazil + epidemiology + + + Colombia + epidemiology + + + Epidemiological Monitoring + + + Female + + + Humans + + + Infant, Newborn + + + Infant, Newborn, Diseases + diagnosis + epidemiology + virology + + + Microcephaly + diagnosis + epidemiology + virology + + + Pregnancy + + + Zika Virus + pathogenicity + + + Zika Virus Infection + complications + diagnosis + epidemiology + virology + + +
+ + + + 2016 + 3 + 11 + 6 + 0 + + + 2016 + 3 + 11 + 6 + 0 + + + 2016 + 4 + 6 + 6 + 0 + + + ppublish + + 26961637 + nature.2016.19502 + 10.1038/nature.2016.19502 + + +
+ + + + + 26959260 + + 2016 + 07 + 26 + + + 2017 + 02 + 20 + +
+ + 1541-0048 + + 106 + 4 + + 2016 + Apr + + + American journal of public health + Am J Public Health + + History, Epidemiology, and Clinical Manifestations of Zika: A Systematic Review. + + 606-12 + + 10.2105/AJPH.2016.303112 + + To describe salient epidemiological characteristics of Zika virus outbreaks across the world and to examine the clinical presentations, complications, and atypical manifestations related to their occurrence in recent history. + We conducted a systematic review of the literature by searching through MEDLINE, Embase, and Global Health Library, as well as the epidemiological bulletins and alerts from the World Health Organization, the Pan American Health Organization, and the European Centre for Disease Prevention and Control over the period 1954 to 2016. + The search yielded 547 records. We retained 333 for further analysis, to which we added 11 epidemiological bulletins from various sources. Of these, we systematically reviewed 52 articles and reports, revealing some epidemiological features and patterns of spread of the Zika virus worldwide, as well as pathological outcomes suspected to be linked to Zika outbreaks. Neurologic disorders among zika patients were similar in Brazil and French Polynesia but a causal link is not established. Incidence of zika infection in pregnant women is not known. In Brazil, during the zika outbreak the incidence of microcephaly increased more than 20 times. Among 35 infants with microcephaly, born from women suspected to have Zika infection during pregnancy in northeast Brazil, 74% of the mothers reported rash during the first and second trimester. + On February 1, 2016, The World Health Organization declared the ongoing Zika crisis an emergency and that, although not yet scientifically proven, the link between the virus and growing numbers of microcephaly cases was "strongly suspected." However, the causal relationship between zika and microcephaly is not universally accepted. Public Health Implications. The current situation with regard to Zika is not encouraging, because there is no vaccine, no treatment, and no good serological test, and vector control remains a challenge. + + + + Paixão + Enny S + ES + + Enny S. Paixão and Laura C. Rodrigues are with the London School of Hygiene and Tropical Medicine, London, England. Florisneide Barreto, Maria da Glória Teixeira, and Maria da Conceição N. Costa are with the Instituto de Saúde Coletiva-Universidade Federal da Bahia, Salvador, Brazil. + + + + Barreto + Florisneide + F + + Enny S. Paixão and Laura C. Rodrigues are with the London School of Hygiene and Tropical Medicine, London, England. Florisneide Barreto, Maria da Glória Teixeira, and Maria da Conceição N. Costa are with the Instituto de Saúde Coletiva-Universidade Federal da Bahia, Salvador, Brazil. + + + + Teixeira + Maria da Glória + Mda G + + Enny S. Paixão and Laura C. Rodrigues are with the London School of Hygiene and Tropical Medicine, London, England. Florisneide Barreto, Maria da Glória Teixeira, and Maria da Conceição N. Costa are with the Instituto de Saúde Coletiva-Universidade Federal da Bahia, Salvador, Brazil. + + + + Costa + Maria da Conceição N + Mda C + + Enny S. Paixão and Laura C. Rodrigues are with the London School of Hygiene and Tropical Medicine, London, England. Florisneide Barreto, Maria da Glória Teixeira, and Maria da Conceição N. Costa are with the Instituto de Saúde Coletiva-Universidade Federal da Bahia, Salvador, Brazil. + + + + Rodrigues + Laura C + LC + + Enny S. Paixão and Laura C. Rodrigues are with the London School of Hygiene and Tropical Medicine, London, England. Florisneide Barreto, Maria da Glória Teixeira, and Maria da Conceição N. Costa are with the Instituto de Saúde Coletiva-Universidade Federal da Bahia, Salvador, Brazil. + + + + eng + + Historical Article + Journal Article + Research Support, Non-U.S. Gov't + Review + +
+ + United States + Am J Public Health + 1254074 + 0090-0036 + + AIM + IM + + + J Travel Med. 2016 Jan;23(1). pii: tav011. doi: 10.1093/jtm/tav011 + 26782128 + + + PLoS Curr. 2014 Jun 02;6:null + 24944843 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + J Virol. 1998 Jan;72(1):73-83 + 9420202 + + + Euro Surveill. 2014;19(41). pii: 20929 + 25345518 + + + Euro Surveill. 2014;19(4). pii: 20685 + 24507467 + + + Emerg Infect Dis. 2015 Feb;21(2):381-2 + 25625687 + + + PLoS Negl Trop Dis. 2014 Oct;8(10):e3188 + 25299181 + + + Emerg Infect Dis. 2014 Aug;20(8):1412-4 + 25062427 + + + BMC Infect Dis. 2015;15:492 + 26527535 + + + Arch Virol. 2016 Mar;161(3):665-8 + 26611910 + + + PLoS Negl Trop Dis. 2014 Feb;8(2):e2681 + 24516683 + + + J Travel Med. 2015 Sep-Oct;22(5):338-40 + 25996909 + + + Trans R Soc Trop Med Hyg. 1964 Jul;58:335-8 + 14175744 + + + Lancet. 2016 Jan 23;387(10016):335-6 + 26777915 + + + Am J Trop Med Hyg. 2014 Nov;91(5):1035-8 + 25294619 + + + MMWR Morb Mortal Wkly Rep. 2016;65(3):59-62 + 26820244 + + + Bull World Health Organ. 1964;31:57-69 + 14230895 + + + J Clin Virol. 2016 Jan;74:1-3 + 26615388 + + + Southeast Asian J Trop Med Public Health. 2015 May;46(3):460-4 + 26521519 + + + Curr Neurol Neurosci Rep. 2015 Jun;15(6):29 + 25877545 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Trans R Soc Trop Med Hyg. 1981;75(3):389-93 + 6275577 + + + East Afr Med J. 2010 Jun;87(6):262-8 + 23057269 + + + Euro Surveill. 2014;19(4). pii: 20683 + 24507466 + + + J Clin Virol. 2015 Feb;63:32-5 + 25600600 + + + Euro Surveill. 2014;19(13). pii: 20751 + 24721538 + + + Euro Surveill. 2015;20(23). pii: 21153 + 26084316 + + + BMJ. 2016;352:i212 + 26762624 + + + Euro Surveill. 2014;19(14). pii: 20761 + 24739982 + + + Euro Surveill. 2016;21(2). doi: 10.2807/1560-7917.ES.2016.21.2.30107 + 26794427 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + PLoS One. 2014;9(10):e109442 + 25310102 + + + Emerg Infect Dis. 2012 Feb;18(2):349-51 + 22305269 + + + PLoS Negl Trop Dis. 2013;7(8):e2348 + 23936579 + + + BMC Infect Dis. 2014;14:248 + 24884681 + + + IDCases. 2014 Nov 03;1(4):95-6 + 26839785 + + + Euro Surveill. 2014;19(9). pii: 20720 + 24626205 + + + Emerg Infect Dis. 2015 Apr;21(4):722-4 + 25811410 + + + Lancet. 2001 Jul 28;358(9278):261-4 + 11498211 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + J Clin Virol. 2015 Jul;68:53-5 + 26071336 + + + Emerg Infect Dis. 2015 May;21(5):911-3 + 25898277 + + + Emerg Infect Dis. 2015 Feb;21(2):359-61 + 25625872 + + + Front Immunol. 2014 Jun 11;5:280 + 24966859 + + + J Hyg (Lond). 1979 Oct;83(2):213-9 + 489960 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Emerg Infect Dis. 2015 Dec;21(12):2274-6 + 26584464 + + + Int J Environ Res Public Health. 2014 Mar;11(3):3360-74 + 24658412 + + + Am J Trop Med Hyg. 1969 May;18(3):411-5 + 4976739 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45 + 13157159 + + + Am J Trop Med Hyg. 2015 Aug;93(2):380-3 + 26101272 + + + Bull Soc Pathol Exot Filiales. 1954;47(2):223-7 + 13182499 + + + Am J Trop Med Hyg. 2013 Sep;89(3):516-7 + 23878182 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Adult + + + Animals + + + Brazil + epidemiology + + + Disease Outbreaks + history + + + Female + + + Global Health + + + History, 20th Century + + + History, 21st Century + + + Humans + + + Infant + + + Microcephaly + complications + etiology + + + Nervous System Diseases + complications + etiology + + + Pregnancy + + + World Health Organization + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + epidemiology + history + virology + + +
+ + + + 2016 + 3 + 10 + 6 + 0 + + + 2016 + 3 + 10 + 6 + 0 + + + 2016 + 7 + 28 + 6 + 0 + + + ppublish + + 26959260 + 10.2105/AJPH.2016.303112 + PMC4816002 + + +
+ + + + + 26959259 + + 2016 + 07 + 26 + + + 2017 + 12 + 20 + +
+ + 1541-0048 + + 106 + 4 + + 2016 + Apr + + + American journal of public health + Am J Public Health + + The Epidemic of Zika Virus-Related Microcephaly in Brazil: Detection, Control, Etiology, and Future Scenarios. + + 601-5 + + 10.2105/AJPH.2016.303113 + + We describe the epidemic of microcephaly in Brazil, its detection and attempts to control it, the suspected causal link with Zika virus infection during pregnancy, and possible scenarios for the future. In October 2015, in Pernambuco, Brazil, an increase in the number of newborns with microcephaly was reported. Mothers of the affected newborns reported rashes during pregnancy and no exposure to other potentially teratogenic agents. Women delivering in October would have been in the first trimester of pregnancy during the peak of a Zika epidemic in March. By the end of 2015, 4180 cases of suspected microcephaly had been reported. Zika spread to other American countries and, in February 2016, the World Health Organization declared the Zika epidemic a public health emergency of international concern. This unprecedented situation underscores the urgent need to establish the evidence of congenital infection risk by gestational week and accrue knowledge. There is an urgent call for a Zika vaccine, better diagnostic tests, effective treatment, and improved mosquito-control methods. + + + + Teixeira + Maria G + MG + + Maria G. Teixeira and Maria da Conceição N. Costa are with Instituto de Saúde Coletiva-Universidade Federal da Bahia, Salvador, Brazil. Wanderson Kleber de Oliveira and Marilia Lavocat Nunes are with Ministry of Health, Brasilia, Brazil. Laura C. Rodrigues is with London School of Hygiene and Tropical Medicine, London, England. + + + + Costa + Maria da Conceição N + Mda C + + Maria G. Teixeira and Maria da Conceição N. Costa are with Instituto de Saúde Coletiva-Universidade Federal da Bahia, Salvador, Brazil. Wanderson Kleber de Oliveira and Marilia Lavocat Nunes are with Ministry of Health, Brasilia, Brazil. Laura C. Rodrigues is with London School of Hygiene and Tropical Medicine, London, England. + + + + de Oliveira + Wanderson K + WK + + Maria G. Teixeira and Maria da Conceição N. Costa are with Instituto de Saúde Coletiva-Universidade Federal da Bahia, Salvador, Brazil. Wanderson Kleber de Oliveira and Marilia Lavocat Nunes are with Ministry of Health, Brasilia, Brazil. Laura C. Rodrigues is with London School of Hygiene and Tropical Medicine, London, England. + + + + Nunes + Marilia Lavocat + ML + + Maria G. Teixeira and Maria da Conceição N. Costa are with Instituto de Saúde Coletiva-Universidade Federal da Bahia, Salvador, Brazil. Wanderson Kleber de Oliveira and Marilia Lavocat Nunes are with Ministry of Health, Brasilia, Brazil. Laura C. Rodrigues is with London School of Hygiene and Tropical Medicine, London, England. + + + + Rodrigues + Laura C + LC + + Maria G. Teixeira and Maria da Conceição N. Costa are with Instituto de Saúde Coletiva-Universidade Federal da Bahia, Salvador, Brazil. Wanderson Kleber de Oliveira and Marilia Lavocat Nunes are with Ministry of Health, Brasilia, Brazil. Laura C. Rodrigues is with London School of Hygiene and Tropical Medicine, London, England. + + + + eng + + Journal Article + +
+ + United States + Am J Public Health + 1254074 + 0090-0036 + + AIM + IM + + + Am J Public Health. 2016 Aug;106(8):e9 + 27400363 + + + Am J Public Health. 2016 Aug;106(8):e9 + 27400362 + + + + + Brazil + epidemiology + + + Epidemics + prevention & control + + + Female + + + Humans + + + Infant, Newborn + + + Infectious Disease Transmission, Vertical + + + Microcephaly + epidemiology + etiology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + virology + + + Pregnancy Trimester, First + + + Public Health + + + World Health Organization + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + epidemiology + transmission + + +
+ + + + 2016 + 3 + 10 + 6 + 0 + + + 2016 + 3 + 10 + 6 + 0 + + + 2016 + 7 + 28 + 6 + 0 + + + ppublish + + 26959259 + 10.2105/AJPH.2016.303113 + + +
+ + + + + 26959258 + + 2016 + 07 + 26 + + + 2016 + 03 + 10 + +
+ + 1541-0048 + + 106 + 4 + + 2016 + Apr + + + American journal of public health + Am J Public Health + + Initial Description of the Presumed Congenital Zika Syndrome. + + 598-600 + + 10.2105/AJPH.2016.303115 + + To provide an initial description of the congenital syndrome presumably associated with infection by Zika virus compared with other syndromes including congenital infections of established etiologies. + We provide an overview of a published case series of 35 cases, a clinical series of 104 cases, and published and unpublished reports of clinical and laboratory findings describing cases diagnosed since the beginning of the epidemic of microcephaly in Brazil. + About 60% to 70% of mothers report rash during pregnancy; mainly in the first trimester. Principal features are microcephaly, facial disproportionality, cutis girata, hypertonia/spasticity, hyperreflexia, and irritability; abnormal neuroimages include calcifications, ventriculomegaly, and lissencephaly. Hearing and visual abnormalities may be present. + Preliminary data suggest that severe congenital abnormalities are linked to Zika virus infection. Cases have severe abnormalities, and although sharing many characteristics with congenital abnormalities associated with other viral infections, abnormalities presumably linked to the Zika virus may have distinguishing characteristics. These severe neurologic abnormalities may result in marked mental retardation and motor disabilities for many surviving offspring. + Affected nations need to prepare to provide complex and costly multidisciplinary care that children diagnosed with this new congenital syndrome will require. + + + + Miranda-Filho + Demócrito de Barros + Dde B + + Demócrito de Barros Miranda-Filho, Ricardo Arraes de Alencar Ximenes, Maria Angela Wanderley Rocha, and Regina Coeli Ferreira Ramos are with the University of Pernambuco, Recife, Brazil. Celina Maria Turchi Martelli, Rafael Dhalia, Rafael Freitas de Oliveira França, and Ernesto T. A. Marques Júnior are with The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife. Thalia Velho Barreto Araújo and Ricardo Arraes de Alencar Ximenes are with the Federal University of Pernambuco, Recife. Laura Cunha Rodrigues is with the London School of Hygiene and Tropical Medicine, London, UK. + + + + Martelli + Celina Maria Turchi + CM + + Demócrito de Barros Miranda-Filho, Ricardo Arraes de Alencar Ximenes, Maria Angela Wanderley Rocha, and Regina Coeli Ferreira Ramos are with the University of Pernambuco, Recife, Brazil. Celina Maria Turchi Martelli, Rafael Dhalia, Rafael Freitas de Oliveira França, and Ernesto T. A. Marques Júnior are with The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife. Thalia Velho Barreto Araújo and Ricardo Arraes de Alencar Ximenes are with the Federal University of Pernambuco, Recife. Laura Cunha Rodrigues is with the London School of Hygiene and Tropical Medicine, London, UK. + + + + Ximenes + Ricardo Arraes de Alencar + RA + + Demócrito de Barros Miranda-Filho, Ricardo Arraes de Alencar Ximenes, Maria Angela Wanderley Rocha, and Regina Coeli Ferreira Ramos are with the University of Pernambuco, Recife, Brazil. Celina Maria Turchi Martelli, Rafael Dhalia, Rafael Freitas de Oliveira França, and Ernesto T. A. Marques Júnior are with The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife. Thalia Velho Barreto Araújo and Ricardo Arraes de Alencar Ximenes are with the Federal University of Pernambuco, Recife. Laura Cunha Rodrigues is with the London School of Hygiene and Tropical Medicine, London, UK. + + + + Araújo + Thalia Velho Barreto + TV + + Demócrito de Barros Miranda-Filho, Ricardo Arraes de Alencar Ximenes, Maria Angela Wanderley Rocha, and Regina Coeli Ferreira Ramos are with the University of Pernambuco, Recife, Brazil. Celina Maria Turchi Martelli, Rafael Dhalia, Rafael Freitas de Oliveira França, and Ernesto T. A. Marques Júnior are with The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife. Thalia Velho Barreto Araújo and Ricardo Arraes de Alencar Ximenes are with the Federal University of Pernambuco, Recife. Laura Cunha Rodrigues is with the London School of Hygiene and Tropical Medicine, London, UK. + + + + Rocha + Maria Angela Wanderley + MA + + Demócrito de Barros Miranda-Filho, Ricardo Arraes de Alencar Ximenes, Maria Angela Wanderley Rocha, and Regina Coeli Ferreira Ramos are with the University of Pernambuco, Recife, Brazil. Celina Maria Turchi Martelli, Rafael Dhalia, Rafael Freitas de Oliveira França, and Ernesto T. A. Marques Júnior are with The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife. Thalia Velho Barreto Araújo and Ricardo Arraes de Alencar Ximenes are with the Federal University of Pernambuco, Recife. Laura Cunha Rodrigues is with the London School of Hygiene and Tropical Medicine, London, UK. + + + + Ramos + Regina Coeli Ferreira + RC + + Demócrito de Barros Miranda-Filho, Ricardo Arraes de Alencar Ximenes, Maria Angela Wanderley Rocha, and Regina Coeli Ferreira Ramos are with the University of Pernambuco, Recife, Brazil. Celina Maria Turchi Martelli, Rafael Dhalia, Rafael Freitas de Oliveira França, and Ernesto T. A. Marques Júnior are with The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife. Thalia Velho Barreto Araújo and Ricardo Arraes de Alencar Ximenes are with the Federal University of Pernambuco, Recife. Laura Cunha Rodrigues is with the London School of Hygiene and Tropical Medicine, London, UK. + + + + Dhalia + Rafael + R + + Demócrito de Barros Miranda-Filho, Ricardo Arraes de Alencar Ximenes, Maria Angela Wanderley Rocha, and Regina Coeli Ferreira Ramos are with the University of Pernambuco, Recife, Brazil. Celina Maria Turchi Martelli, Rafael Dhalia, Rafael Freitas de Oliveira França, and Ernesto T. A. Marques Júnior are with The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife. Thalia Velho Barreto Araújo and Ricardo Arraes de Alencar Ximenes are with the Federal University of Pernambuco, Recife. Laura Cunha Rodrigues is with the London School of Hygiene and Tropical Medicine, London, UK. + + + + França + Rafael Freitas de Oliveira + RF + + Demócrito de Barros Miranda-Filho, Ricardo Arraes de Alencar Ximenes, Maria Angela Wanderley Rocha, and Regina Coeli Ferreira Ramos are with the University of Pernambuco, Recife, Brazil. Celina Maria Turchi Martelli, Rafael Dhalia, Rafael Freitas de Oliveira França, and Ernesto T. A. Marques Júnior are with The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife. Thalia Velho Barreto Araújo and Ricardo Arraes de Alencar Ximenes are with the Federal University of Pernambuco, Recife. Laura Cunha Rodrigues is with the London School of Hygiene and Tropical Medicine, London, UK. + + + + Marques Júnior + Ernesto Torres de Azevedo + ET + + Demócrito de Barros Miranda-Filho, Ricardo Arraes de Alencar Ximenes, Maria Angela Wanderley Rocha, and Regina Coeli Ferreira Ramos are with the University of Pernambuco, Recife, Brazil. Celina Maria Turchi Martelli, Rafael Dhalia, Rafael Freitas de Oliveira França, and Ernesto T. A. Marques Júnior are with The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife. Thalia Velho Barreto Araújo and Ricardo Arraes de Alencar Ximenes are with the Federal University of Pernambuco, Recife. Laura Cunha Rodrigues is with the London School of Hygiene and Tropical Medicine, London, UK. + + + + Rodrigues + Laura Cunha + LC + + Demócrito de Barros Miranda-Filho, Ricardo Arraes de Alencar Ximenes, Maria Angela Wanderley Rocha, and Regina Coeli Ferreira Ramos are with the University of Pernambuco, Recife, Brazil. Celina Maria Turchi Martelli, Rafael Dhalia, Rafael Freitas de Oliveira França, and Ernesto T. A. Marques Júnior are with The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife. Thalia Velho Barreto Araújo and Ricardo Arraes de Alencar Ximenes are with the Federal University of Pernambuco, Recife. Laura Cunha Rodrigues is with the London School of Hygiene and Tropical Medicine, London, UK. + + + + eng + + Case Reports + Journal Article + Research Support, Non-U.S. Gov't + +
+ + United States + Am J Public Health + 1254074 + 0090-0036 + + AIM + IM + + + Brazil + + + Exanthema + + + Female + + + Humans + + + Infant, Newborn + + + Infectious Disease Transmission, Vertical + + + Intellectual Disability + etiology + + + Microcephaly + etiology + + + Neuroimaging + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Syndrome + + + Zika Virus + isolation & purification + + + Zika Virus Infection + congenital + transmission + + +
+ + + + 2016 + 3 + 10 + 6 + 0 + + + 2016 + 3 + 10 + 6 + 0 + + + 2016 + 7 + 28 + 6 + 0 + + + ppublish + + 26959258 + 10.2105/AJPH.2016.303115 + + +
+ + + + + 26956448 + + 2016 + 12 + 13 + + + 2017 + 02 + 20 + +
+ + 2222-1751 + + 5 + + 2016 + Mar + 09 + + + Emerging microbes & infections + Emerg Microbes Infect + + Zika virus outbreak: 'a perfect storm'. + + e21 + + 10.1038/emi.2016.42 + + + Ai + Jing-Wen + JW + + Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. + + + + Zhang + Ying + Y + + Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. + + + Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. + + + + Zhang + Wenhong + W + + Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. + + + MOH and MOE Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, China. + + + + eng + + News + + + 2016 + 03 + 09 + +
+ + United States + Emerg Microbes Infect + 101594885 + 2222-1751 + + IM + + + PLoS Curr. 2014 Jun 02;6:null + 24944843 + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Clin Microbiol Infect. 2014 Oct;20(10):O595-6 + 24909208 + + + J Gen Virol. 2016 Feb;97(2):269-73 + 26684466 + + + Emerg Infect Dis. 2015 Feb;21(2):381-2 + 25625687 + + + Lancet. 2016 Jan 23;387(10016):335-6 + 26777915 + + + Wkly Epidemiol Rec. 2015 Nov 6;90(45):609-10 + 26552108 + + + Euro Surveill. 2014;19(9). pii: 20720 + 24626205 + + + Am J Trop Med Hyg. 2015 Aug;93(2):380-3 + 26101272 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Brazil + epidemiology + + + Disease Outbreaks + + + Humans + + + Microcephaly + etiology + virology + + + Zika Virus Infection + epidemiology + + +
+ + + + 2016 + 02 + 13 + + + 2016 + 02 + 23 + + + 2016 + 02 + 23 + + + 2016 + 3 + 10 + 6 + 0 + + + 2016 + 3 + 10 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + epublish + + 26956448 + emi201642 + 10.1038/emi.2016.42 + PMC4820676 + + +
+ + + + + 26953673 + + 2017 + 01 + 24 + + + 2017 + 01 + 24 + +
+ + 1547-1896 + + 29 + 4 + + 2016 + Apr + + + JAAPA : official journal of the American Academy of Physician Assistants + JAAPA + + Zika virus: A rapidly emerging infectious disease. + + 48-50 + + 10.1097/01.JAA.0000481413.11539.b1 + + Zika virus is a flavivirus transmitted to humans via the bite of infected mosquitoes. A recent outbreak in Brazil has spread to several surrounding countries, and the virus also has been reported in the United States. The virus is associated with microcephaly among newborns whose mothers were infected. Because no vaccine or treatment is available, efforts have focused on preventing mosquito bites and advising pregnant women and women trying to get pregnant to avoid active areas of Zika virus transmission. Clinicians should understand the infection, its diagnosis and testing, and monitor pregnant women for travel history to outbreak regions and for the presence of clinical symptoms. Patient education on preventive measures offers the best option to avoid Zika virus infection. + + + + Borchardt + Roy A + RA + + Roy A. Borchardt is supervisor of advanced practice providers in the Department of Infectious Diseases, Infection Control, and Employee Health at MD Anderson Cancer Center in Houston, Tex. The author has disclosed no potential conflicts of interest, financial or otherwise. + + + + eng + + Journal Article + +
+ + United States + JAAPA + 9513102 + 0893-7400 + + T + + + Adult + + + Centers for Disease Control and Prevention (U.S.) + + + Communicable Diseases, Emerging + + + Female + + + Humans + + + Hydrocephalus + virology + + + Infant, Newborn + + + Male + + + Pregnancy + + + Travel + + + United States + + + Zika Virus + + + Zika Virus Infection + + +
+ + + + 2016 + 3 + 9 + 6 + 0 + + + 2016 + 3 + 10 + 6 + 0 + + + 2017 + 1 + 25 + 6 + 0 + + + ppublish + + 26953673 + 10.1097/01.JAA.0000481413.11539.b1 + + +
+ + + + + 26952548 + + 2016 + 05 + 09 + + + 2017 + 03 + 20 + +
+ + 1474-547X + + 387 + 10027 + + 2016 + Apr + 09 + + + Lancet (London, England) + Lancet + + Teratogenic effects of the Zika virus and the role of the placenta. + + 1587-90 + + 10.1016/S0140-6736(16)00650-4 + S0140-6736(16)00650-4 + + The mechanism by which the Zika virus can cause fetal microcephaly is not known. Reports indicate that Zika is able to evade the normal immunoprotective responses of the placenta. Microcephaly has genetic causes, some associated with maternal exposures including radiation, tobacco smoke, alcohol, and viruses. Two hypotheses regarding the role of the placenta are possible: one is that the placenta directly conveys the Zika virus to the early embryo or fetus. Alternatively, the placenta itself might be mounting a response to the exposure; this response might be contributing to or causing the brain defect. This distinction is crucial to the diagnosis of fetuses at risk and the design of therapeutic strategies to prevent Zika-induced teratogenesis. + Copyright © 2016 Elsevier Ltd. All rights reserved. + + + + Adibi + Jennifer J + JJ + + Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Obstetrics and Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: adibij@pitt.edu. + + + + Marques + Ernesto T A + ET + Jr + + Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA; The Research Center Aggeu Magalhães (CPqAM)/Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil. + + + + Cartus + Abigail + A + + Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Sciences Center, Houston, TX, USA. + + + + Beigi + Richard H + RH + + Department of Obstetrics and Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA. + + + + eng + + Journal Article + + + 2016 + 03 + 04 + +
+ + England + Lancet + 2985213R + 0140-6736 + + + + 0 + Teratogens + + + AIM + IM + + + Front Cell Infect Microbiol. 2017 Mar 03;7:62 + 28316955 + + + + + Female + + + Fetus + virology + + + Humans + + + Microcephaly + prevention & control + virology + + + Placenta + immunology + virology + + + Pregnancy + + + Teratogens + + + Zika Virus + pathogenicity + + +
+ + + + 2016 + 3 + 9 + 6 + 0 + + + 2016 + 3 + 10 + 6 + 0 + + + 2016 + 5 + 10 + 6 + 0 + + + ppublish + + 26952548 + S0140-6736(16)00650-4 + 10.1016/S0140-6736(16)00650-4 + + +
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+ + + + + 26950736 + + 2018 + 01 + 16 + + + 2018 + 01 + 16 + +
+ + 0034-8376 + + 67 + 6 + + 2015 Nov-Dec + + + Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion + Rev. Invest. Clin. + + Zika Virus: A New Epidemic on Our Doorstep. + + 329-32 + + + Zika virus, a flavivirus transmitted to humans by mosquitoes of the genus Aedes, was first described in humans as isolated cases in Africa. Outbreaks have been reported outside that region since 2007, followed by its gradual introduction to different geographical areas. In 2015, Zika virus was detected in Brazil, from where it is rapidly expanding in the continent; the first case in Mexico was detected in October 2015. Initially deemed as a cause of mild illness, confirmation of microcephaly cases associated with this infection in Brazil have resulted in the World Health Organization declaration of Zika virus infection as a Public Health Emergency of International Concern. The US Centers for Disease Control and Prevention issued travel alerts for countries with declared cases. The vector is widely distributed in Mexico and control measures are the most effective means for prevention, not only of Zika virus, but also dengue and chikungunya. + + + + Galindo-Fraga + Arturo + A + + Department of Hospital Epidemiology and Health Care Quality Control, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. + + + + Ochoa-Hein + Eric + E + + Department of Hospital Epidemiology and Health Care Quality Control, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. + + + + Sifuentes-Osornio + José + J + + Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. + + + + Ruiz-Palacios + Guillermo + G + + Commissioner, Mexican National Institutes of Health, Mexico City, Mexico. + + + + eng + + Journal Article + +
+ + Mexico + Rev Invest Clin + 9421552 + 0034-8376 + + IM + + + Aedes + + + Animals + + + Centers for Disease Control and Prevention (U.S.) + + + Disease Outbreaks + prevention & control + statistics & numerical data + + + Humans + + + Insect Vectors + virology + + + Mexico + epidemiology + + + United States + + + World Health Organization + + + Zika Virus Infection + epidemiology + prevention & control + transmission + + +
+ + + + 2016 + 3 + 8 + 6 + 0 + + + 2016 + 3 + 8 + 6 + 0 + + + 2016 + 3 + 8 + 6 + 1 + + + ppublish + + 26950736 + + +
+ + + + + 26943629 + + 2017 + 01 + 03 + + + 2018 + 01 + 16 + +
+ + 1533-4406 + + 375 + 24 + + 2016 + 12 + 15 + + + The New England journal of medicine + N. Engl. J. Med. + + Zika Virus Infection in Pregnant Women in Rio de Janeiro. + + 2321-2334 + + + Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. + We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. + A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester). + Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.). + + + + Brasil + Patrícia + P + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Pereira + José P + JP + Jr + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Moreira + M Elisabeth + ME + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Ribeiro Nogueira + Rita M + RM + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Damasceno + Luana + L + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Wakimoto + Mayumi + M + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Rabello + Renata S + RS + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Valderramos + Stephanie G + SG + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Halai + Umme-Aiman + UA + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Salles + Tania S + TS + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Zin + Andrea A + AA + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Horovitz + Dafne + D + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Daltro + Pedro + P + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Boechat + Marcia + M + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Raja Gabaglia + Claudia + C + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Carvalho de Sequeira + Patrícia + P + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Pilotto + José H + JH + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Medialdea-Carrera + Raquel + R + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Cotrim da Cunha + Denise + D + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Abreu de Carvalho + Liege M + LM + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Pone + Marcos + M + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Machado Siqueira + André + A + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Calvet + Guilherme A + GA + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Rodrigues Baião + Ana E + AE + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Neves + Elizabeth S + ES + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Nassar de Carvalho + Paulo R + PR + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Hasue + Renata H + RH + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Marschik + Peter B + PB + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Einspieler + Christa + C + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Janzen + Carla + C + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Cherry + James D + JD + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Bispo de Filippis + Ana M + AM + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + Nielsen-Saines + Karin + K + + From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.). + + + + eng + + + P30 AI028697 + AI + NIAID NIH HHS + United States + + + R21 AI129534 + AI + NIAID NIH HHS + United States + + + + Journal Article + + + 2016 + 03 + 04 + +
+ + United States + N Engl J Med + 0255562 + 0028-4793 + + AIM + IM + + + N Engl J Med. 2016 Dec 15;375(24):2393-2394 + 27960068 + + + Obstet Gynecol. 1964 Feb;23:153-9 + 14117317 + + + Pediatr Radiol. 2009 Aug;39(8):772-80; quiz 888-9 + 19437006 + + + Lancet. 1992 Feb 1;339(8788):283-7 + 1346292 + + + J Clin Virol. 2016 Jan;74:1-3 + 26615388 + + + N Engl J Med. 2016 Mar 10;374(10 ):951-8 + 26862926 + + + PLoS Negl Trop Dis. 2013 Jul 11;7(7):e2311 + 23875046 + + + Emerg Infect Dis. 2015 Jan;21(1):84-6 + 25530324 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Lancet. 2014 Sep 6;384(9946):857-68 + 25209487 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2015 Oct;21(10):1887 + 26403318 + + + MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):59-62 + 26820244 + + + Emerg Infect Dis. 2016 Nov;22(11):1894-1899 + 27603576 + + + Am J Epidemiol. 1965 Jan;81:71-85 + 14246083 + + + Ultrasound Obstet Gynecol. 2007 Sep;30(3):287-96 + 17721916 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + N Engl J Med. 2016 May 19;374(20):1981-7 + 27074377 + + + Lancet. 2016 Jan 16;387(10015):228 + 26775125 + + + Epidemiol Infect. 2013 May;141(5):1080-8 + 22800513 + + + Nature. 2016 Feb 4;530(7588):13-4 + 26842033 + + + Radiology. 2016 Oct;281(1):203-18 + 27552432 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + J Trop Pediatr. 2015 Oct;61(5):386-92 + 26246086 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + N Engl J Med. 2016 Jun 15;:null + 27305043 + + + JAMA. 1965 Dec 20;194(12):1277-83 + 5898080 + + + Evid Based Med. 2016 Oct;21(5):193 + 27495823 + + + + + Adolescent + + + Adult + + + Brain + abnormalities + + + Brazil + epidemiology + + + Central Nervous System + abnormalities + embryology + + + Female + + + Fetal Death + etiology + + + Fetal Growth Retardation + epidemiology + virology + + + Fetus + abnormalities + + + Gestational Age + + + Humans + + + Microcephaly + virology + + + Middle Aged + + + Pregnancy + + + Pregnancy Complications, Infectious + + + Premature Birth + epidemiology + + + Ultrasonography, Prenatal + + + Young Adult + + + Zika Virus + isolation & purification + + + Zika Virus Infection + complications + + +
+ + + + 2016 + 3 + 5 + 6 + 0 + + + 2017 + 1 + 4 + 6 + 0 + + + 2016 + 3 + 5 + 6 + 0 + + + ppublish + + 26943629 + 10.1056/NEJMoa1602412 + PMC5323261 + NIHMS848289 + + +
+ + + + + 26940218 + + 2017 + 04 + 25 + + + 2017 + 04 + 25 + +
+ + 1945-1938 + + 31 + 2 + + 2016 + Apr + + + Prehospital and disaster medicine + Prehosp Disaster Med + + Zika Virus Association with Microcephaly: The Power for Population Statistics to Identify Public Health Emergencies. + + 119-20 + + 10.1017/S1049023X16000170 + + + Stratton + Samuel J + SJ + + + eng + + Editorial + + + 2016 + 03 + 04 + +
+ + United States + Prehosp Disaster Med + 8918173 + 1049-023X + + T + + + Brazil + epidemiology + + + Disaster Medicine + + + Emergencies + + + Humans + + + Incidence + + + Microcephaly + epidemiology + virology + + + Prevalence + + + Public Health + + + Zika Virus + + + Zika Virus Infection + epidemiology + virology + + +
+ + + + 2016 + 3 + 5 + 6 + 0 + + + 2016 + 3 + 5 + 6 + 0 + + + 2017 + 4 + 26 + 6 + 0 + + + ppublish + + 26940218 + S1049023X16000170 + 10.1017/S1049023X16000170 + + +
+ + + + + 26938703 + + 2016 + 07 + 08 + + + 2016 + 03 + 04 + +
+ + 1545-861X + + 65 + 8 + + 2016 + Mar + 04 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Zika Virus Infection Among U.S. Pregnant Travelers - August 2015-February 2016. + + 211-4 + + 10.15585/mmwr.mm6508e1 + + After reports of microcephaly and other adverse pregnancy outcomes in infants of mothers infected with Zika virus during pregnancy, CDC issued a travel alert on January 15, 2016, advising pregnant women to consider postponing travel to areas with active transmission of Zika virus. On January 19, CDC released interim guidelines for U.S. health care providers caring for pregnant women with travel to an affected area, and an update was released on February 5. As of February 17, CDC had received reports of nine pregnant travelers with laboratory-confirmed Zika virus disease; 10 additional reports of Zika virus disease among pregnant women are currently under investigation. No Zika virus-related hospitalizations or deaths among pregnant women were reported. Pregnancy outcomes among the nine confirmed cases included two early pregnancy losses, two elective terminations, and three live births (two apparently healthy infants and one infant with severe microcephaly); two pregnancies (approximately 18 weeks' and 34 weeks' gestation) are continuing without known complications. Confirmed cases of Zika virus infection were reported among women who had traveled to one or more of the following nine areas with ongoing local transmission of Zika virus: American Samoa, Brazil, El Salvador, Guatemala, Haiti, Honduras, Mexico, Puerto Rico, and Samoa. This report summarizes findings from the nine women with confirmed Zika virus infection during pregnancy, including case reports for four women with various clinical outcomes. U.S. health care providers caring for pregnant women with possible Zika virus exposure during pregnancy should follow CDC guidelines for patient evaluation and management. Zika virus disease is a nationally notifiable condition. CDC has developed a voluntary registry to collect information about U.S. pregnant women with confirmed Zika virus infection and their infants. Information about the registry is in preparation and will be available on the CDC website. + + + + Meaney-Delman + Dana + D + + + Hills + Susan L + SL + + + Williams + Charnetta + C + + + Galang + Romeo R + RR + + + Iyengar + Preetha + P + + + Hennenfent + Andrew K + AK + + + Rabe + Ingrid B + IB + + + Panella + Amanda + A + + + Oduyebo + Titilope + T + + + Honein + Margaret A + MA + + + Zaki + Sherif + S + + + Lindsey + Nicole + N + + + Lehman + Jennifer A + JA + + + Kwit + Natalie + N + + + Bertolli + Jeanne + J + + + Ellington + Sascha + S + + + Igbinosa + Irogue + I + + + Minta + Anna A + AA + + + Petersen + Emily E + EE + + + Mead + Paul + P + + + Rasmussen + Sonja A + SA + + + Jamieson + Denise J + DJ + + + eng + + Case Reports + Journal Article + + + 2016 + 03 + 04 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + Adult + + + Centers for Disease Control and Prevention (U.S.) + + + Female + + + Guidelines as Topic + + + Humans + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + + + Travel + + + United States + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + epidemiology + + +
+ + + + 2016 + 3 + 4 + 6 + 0 + + + 2016 + 3 + 5 + 6 + 0 + + + 2016 + 7 + 9 + 6 + 0 + + + epublish + + 26938703 + 10.15585/mmwr.mm6508e1 + + +
+ + + + + 26937612 + + 2016 + 07 + 19 + + + 2017 + 02 + 20 + +
+ + 1546-170X + + 22 + 3 + + 2016 + Mar + + + Nature medicine + Nat. Med. + + Missing link: Animal models to study whether Zika causes birth defects. + + 225-7 + + 10.1038/nm0316-225 + + + Becker + Rachel + R + + + eng + + News + +
+ + United States + Nat Med + 9502015 + 1078-8956 + + IM + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Emerg Infect Dis. 2014 Jun;20(6):1085-6 + 24856001 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + Acta Med Port. 2015 Nov-Dec;28(6):679-80 + 26849748 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + Nature. 2013 Sep 19;501(7467):373-9 + 23995685 + + + PLoS Negl Trop Dis. 2012;6(2):e1477 + 22389730 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + Arch Gesamte Virusforsch. 1971;35(2):183-93 + 5002906 + + + J Virol. 1999 Jan;73(1):783-6 + 9847388 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636 + 24421913 + + + Acta Neuropathol. 2016 Feb;131(2):159-84 + 26659576 + + + Trans R Soc Trop Med Hyg. 1956 May;50(3):238-42 + 13337908 + + + Curr Opin Neurobiol. 2012 Oct;22(5):747-53 + 22487088 + + + + + Animals + + + Brazil + epidemiology + + + Causality + + + Disease Models, Animal + + + Epidemics + + + Female + + + Humans + + + Infectious Disease Transmission, Vertical + + + Mice + + + Microcephaly + embryology + epidemiology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Zika Virus Infection + embryology + epidemiology + + +
+ + + + 2016 + 3 + 4 + 6 + 0 + + + 2016 + 3 + 5 + 6 + 0 + + + 2016 + 7 + 20 + 6 + 0 + + + ppublish + + 26937612 + nm0316-225 + 10.1038/nm0316-225 + + +
+ + + + + 26935676 + + 2016 + 03 + 21 + + + 2016 + 03 + 03 + +
+ + 1476-4687 + + 531 + 7592 + + 2016 + Mar + 03 + + + Nature + Nature + + Spectre of Ebola haunts Zika response. + + 19 + + 10.1038/531019a + + + Check Hayden + Erika + E + + + eng + + News + +
+ + England + Nature + 0410462 + 0028-0836 + + IM + + + Africa, Western + epidemiology + + + Brazil + epidemiology + + + Disease Outbreaks + statistics & numerical data + + + Epidemiological Monitoring + + + Global Health + + + Hemorrhagic Fever, Ebola + epidemiology + + + Humans + + + Influenza A Virus, H1N1 Subtype + + + Influenza, Human + epidemiology + + + Information Dissemination + + + Microcephaly + complications + epidemiology + + + Public Health + + + World Health Organization + organization & administration + + + Zika Virus + + + Zika Virus Infection + epidemiology + virology + + +
+ + + + 2016 + 3 + 4 + 6 + 0 + + + 2016 + 3 + 5 + 6 + 0 + + + 2016 + 3 + 22 + 6 + 0 + + + ppublish + + 26935676 + 531019a + 10.1038/531019a + + +
+ + + + + 26934531 + + 2016 + 08 + 02 + + + 2017 + 02 + 20 + +
+ + 1935-2735 + + 10 + 3 + + 2016 + Mar + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + Zika Virus: Medical Countermeasure Development Challenges. + + e0004530 + + 10.1371/journal.pntd.0004530 + + Reports of high rates of primary microcephaly and Guillain-Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment. + Multiple information sources were employed to support the review. These included publically available literature, patents, official communications, English and Lusophone lay press. Online surveys were distributed to physicians in the US, Mexico and Argentina and responses analyzed. Computational epitope analysis as well as infectious disease outbreak modeling and forecasting were implemented. Field observations in Brazil were compiled and interviews conducted with public health officials. + + + + Malone + Robert W + RW + + RW Malone MD LLC, Scottsville, Virginia, United States of America. + + + Class of 2016, Harvard Medical School Global Clinical Scholars Research Training Program, Boston, Massachusetts, United States of America. + + + + Homan + Jane + J + + ioGenetics, Madison, Wisconsin, United States of America. + + + + Callahan + Michael V + MV + + Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America. + + + + Glasspool-Malone + Jill + J + + RW Malone MD LLC, Scottsville, Virginia, United States of America. + + + Class of 2016, Harvard Medical School Global Clinical Scholars Research Training Program, Boston, Massachusetts, United States of America. + + + + Damodaran + Lambodhar + L + + Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, North Carolina, United States of America. + + + + Schneider + Adriano De Bernardi + Ade B + + Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, North Carolina, United States of America. + + + + Zimler + Rebecca + R + + University of Florida, Department of Entomology and Nematology, Florida Medical Entomology Laboratory, Vero Beach, Florida, United States of America. + + + + Talton + James + J + + Nanotherapeutics, NANO-ADM Advanced Development and Manufacturing Center, Alachua, Florida, United States of America. + + + + Cobb + Ronald R + RR + + Nanotherapeutics, NANO-ADM Advanced Development and Manufacturing Center, Alachua, Florida, United States of America. + + + + Ruzic + Ivan + I + + Analytical Outcomes, Washington Crossing, Pennsylvania, United States of America. + + + + Smith-Gagen + Julie + J + + School of Community Health Sciences, University of Nevada, Reno, Nevada, United States of America. + + + + Janies + Daniel + D + + Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, North Carolina, United States of America. + + + + Wilson + James + J + + Nevada Center for Infectious Disease Forecasting, University of Nevada, Reno, Nevada, United States of America. + + + + Zika Response Working Group + + + eng + + Journal Article + Research Support, U.S. Gov't, Non-P.H.S. + Review + + + 2016 + 03 + 02 + +
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+ 4976739 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + Vet Res. 2009 Mar-Apr;40(2):43 + 19406093 + + + Lancet Infect Dis. 2016 Jun;16(6):653-60 + 26897108 + + + PLoS Negl Trop Dis. 2015;9(6):e0003749 + 26065421 + + + Am J Hyg. 1954 Mar;59(2):157-63 + 13138582 + + + Cochrane Database Syst Rev. 2011;(3):CD008630 + 21412923 + + + Vaccine. 2010 Jan 8;28(3):632-49 + 19808029 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Aedes + growth & development + virology + + + Americas + epidemiology + + + Animals + + + Communicable Disease Control + methods + + + Disease Transmission, Infectious + prevention & control + + + Humans + + + Pandemics + + + Polynesia + epidemiology + + + Zika Virus Infection + epidemiology + pathology + prevention & control + transmission + + +
+ + + + 2016 + 3 + 3 + 6 + 0 + + + 2016 + 3 + 5 + 6 + 0 + + + 2016 + 8 + 3 + 6 + 0 + + + epublish + + 26934531 + 10.1371/journal.pntd.0004530 + PNTD-D-16-00150 + PMC4774925 + + +
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+ + 1972-2680 + + 10 + 2 + + 2016 + Feb + 28 + + + Journal of infection in developing countries + J Infect Dev Ctries + + Zika virus outbreak in Brazil. + + 116-20 + + 10.3855/jidc.8217 + + Zika virus (ZIKV) infection is spreading rapidly within the Americas after originating from an outbreak in Brazil. We describe the current ZIKV infection epidemic in Brazil and the neurological symptoms arising. First cases of an acute exanthematic disease were reported in Brazil's Northeast region at the end of 2014. In March 2015, autochthonous ZIKV was determined to be the causative agent of the exanthematic disease. As cases of neurological syndromes in regions where ZIKV, dengue and/or Chikungunya viruses co-circulate were reported, ZIKV was also identified in the cerebrospinal fluid of patients with acute neurological syndromes and previous exanthematic disease. By the end of September 2015, an increasing number of infants with small head circumference or microcephaly were noted in Brazil's Northeast which was estimated to be 29 cases between August and October. ZIKV was identified in blood and tissue samples of a newborn and in mothers who had given birth to infants with microcephaly and ophthalmological anomalies. In 2015, there were an estimated 440,000 - 1,300,000 Zika cases in Brazil. There have been 4,783 suspected cases of microcephaly, most of them in the Northeast of Brazil associated with 76 deaths. The Ministry of Health is intensifying control measures against the mosquito Aedes aegypti and implemented intensive surveillance actions. Further studies are needed to confirm the suspected association between ZIKV infection and microcephaly; to identify antiviral, immunotherapy, or prophylactic vaccine; to introduce diagnostic ELISA testing. Clinical and epidemiological studies must be performed to describe viral dynamics and expansion of the outbreak. + + + + Heukelbach + Jorg + J + + School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. heukelbach@web.de. + + + + Alencar + Carlos Henrique + CH + + + Kelvin + Alyson Ann + AA + + + de Oliveira + Wanderson Kleber + WK + + + Pamplona de Góes Cavalcanti + Luciano + L + + + eng + + Journal Article + + + 2016 + 02 + 28 + +
+ + Italy + J Infect Dev Ctries + 101305410 + 1972-2680 + + IM + + + Aedes + + + Animals + + + Blood + virology + + + Brazil + epidemiology + + + Cerebrospinal Fluid + virology + + + Disease Outbreaks + + + Epidemiological Monitoring + + + Humans + + + Insect Vectors + + + Microcephaly + epidemiology + + + Mosquito Control + organization & administration + + + Zika Virus + isolation & purification + + + Zika Virus Infection + epidemiology + pathology + + +
+ + + + 2016 + 02 + 05 + + + 2016 + 02 + 16 + + + 2016 + 02 + 15 + + + 2016 + 3 + 2 + 6 + 0 + + + 2016 + 3 + 2 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + epublish + + 26927450 + + +
+ + + + + 26925496 + + 2016 + 12 + 13 + + + 2016 + 12 + 30 + +
+ + 1095-9157 + + 68 + + 2016 + Apr + + + Journal of autoimmunity + J. Autoimmun. + + The Zika outbreak of the 21st century. + + 1-13 + + 10.1016/j.jaut.2016.02.006 + S0896-8411(16)30008-7 + + The Zika virus outbreak has captivated the attention of the global audience and information has spread rapidly and wildly through the internet and other media channels. This virus was first identified in 1947, when it was isolated from a sentinel rhesus monkey placed by British scientists working at the Yellow Fever Research Laboratory located in the Zika forest area of Uganda, hence its name, and is transmitted primarily by the mosquito vector, Aedes aegypti. The fact that the rhesus macaque is an Asian species being placed in an African forest brings to mind the possibility of rapid adaptation of the virus from an African to Asian species, an issue that has not been considered. Whether such adaptation has played any role in acquiring pathogenicity due to cross species transmission remains to be identified. The first human infection was described in Nigeria in 1954, with only scattered reports of about a dozen human infections identified over a 50-year period. It was not until 2007 that Zika virus raised its ugly head with infections noted in three-quarters of the population on the tiny island of Yap located between the Philippines and Papua New Guinea in the western Pacific Ocean, followed by a major outbreak in French Polynesia in 2013. The virus remained confined to a narrow equatorial band in Africa and Asia until 2014 when it began to spread eastward, first toward Oceania and then to South America. Since then, millions of infected individuals have been identified in Brazil, Colombia, Venezuela, including 25 additional countries in the Americas. While the symptoms associated with Zika virus infection are generally mild, consisting of fever, maculopapular rash, arthralgia and conjunctivitis, there have been reports of more severe reactions that are associated with neurological complications. In pregnant women, fetal neurological complications include brain damage and microcephaly, while in adults there have been several cases of virus-associated Guillain-Barre syndrome. The virus was until recently believed to only be transmitted via mosquitoes. But when the Zika virus was isolated from the semen specimens from a patient in Texas, this provided the basis for the recent report of possible sexual transmission of the Zika virus. Due to the neurological complications, various vectors for infection as well as the rapid spread throughout the globe, it has prompted the World Health Organization to issue a global health emergency. Various governmental organizations have recommended that pregnant women do not travel to countries where the virus is epidemic, and within the countries affected by the virus, recommendations were provided for women of childbearing age to delay pregnancy. The overall public health impact of these above findings highlights the need for a rapid but specific diagnostic test for blood banks worldwide to identify those infected and for the counseling of women who are pregnant or contemplating pregnancy. As of this date, there are neither commercially licensed diagnostic tests nor a vaccine. Because cross-reactivity of the Zika virus with dengue and Chikungunya virus is common, it may pose difficulty in being able to quickly develop such tests and vaccines. So far the most effective public health measures include controlling the mosquito populations via insecticides and preventing humans from direct exposure to mosquitoes. + Copyright © 2016 Elsevier Ltd. All rights reserved. + + + + Chang + Christopher + C + + Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA. + + + + Ortiz + Kristina + K + + Departmenty of Pathology, Emory University School of Medicine, Atlanta, GA, USA. + + + + Ansari + Aftab + A + + Departmenty of Pathology, Emory University School of Medicine, Atlanta, GA, USA. + + + + Gershwin + M Eric + ME + + Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA. Electronic address: megershwin@ucdavis.edu. + + + + eng + + Historical Article + Journal Article + + + 2016 + 02 + 28 + +
+ + England + J Autoimmun + 8812164 + 0896-8411 + + IM + + + Animals + + + Communicable Disease Control + + + Disease Management + + + Disease Outbreaks + + + Global Health + + + History, 21st Century + + + Humans + + + Population Surveillance + + + Zika Virus + classification + physiology + + + Zika Virus Infection + diagnosis + epidemiology + history + transmission + + + + Aedes aegypti + Arborvirus + Autophagy + Centrosome + Dengue + Flavivirus + Glycosylation + Guillain-Barre + Microcephaly + Mosquitoes + Pandemic + Sexual transmission + Zika fever + +
+ + + + 2016 + 02 + 16 + + + 2016 + 02 + 16 + + + 2016 + 02 + 16 + + + 2016 + 3 + 2 + 6 + 0 + + + 2016 + 3 + 2 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + ppublish + + 26925496 + S0896-8411(16)30008-7 + 10.1016/j.jaut.2016.02.006 + + +
+ + + + + 26923098 + + 2017 + 05 + 16 + + + 2017 + 08 + 17 + +
+ + 1469-0705 + + 47 + 5 + + 2016 + May + + + Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology + Ultrasound Obstet Gynecol + + Intrauterine Zika virus infection and microcephaly: correlation of perinatal imaging and three-dimensional virtual physical models. + + 657-60 + + 10.1002/uog.15901 + + + Werner + H + H + + Department of Radiology, Clínica de Diagnóstico por Imagem (CPDI), Rio de Janeiro, Brazil. + + + + Fazecas + T + T + + Department of Radiology, Clínica de Diagnóstico por Imagem (CPDI), Rio de Janeiro, Brazil. + + + + Guedes + B + B + + Department of Radiology, Clínica de Diagnóstico por Imagem (CPDI), Rio de Janeiro, Brazil. + + + + Lopes Dos Santos + J + J + + Department of Arts and Design, Pontifícia Universidade Católica (PUC Rio), Rio de Janeiro, Brazil. + + + + Daltro + P + P + + Department of Radiology, Clínica de Diagnóstico por Imagem (CPDI), Rio de Janeiro, Brazil. + + + + Tonni + G + G + + Department of Obstetrics and Gynecology, Guastalla Civil Hospital, AUSL Reggio Emilia, Reggio Emilia, Italy. + + + + Campbell + S + S + + Create Health Clinic, London, UK. + + + + Araujo Júnior + E + E + + Department of Obstetrics, Paulista School of Medicine, Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil. + + + + eng + + Case Reports + Journal Article + + + 2016 + 04 + 05 + +
+ + England + Ultrasound Obstet Gynecol + 9108340 + 0960-7692 + + IM + + + Female + + + Humans + + + Magnetic Resonance Imaging + methods + + + Microcephaly + diagnostic imaging + virology + + + Middle Aged + + + Pregnancy + + + Pregnancy Complications, Infectious + virology + + + Prenatal Diagnosis + methods + + + Ultrasonography, Prenatal + methods + + + Zika Virus Infection + diagnosis + + +
+ + + + 2016 + 02 + 06 + + + 2016 + 02 + 22 + + + 2016 + 02 + 24 + + + 2016 + 3 + 1 + 6 + 0 + + + 2016 + 3 + 1 + 6 + 0 + + + 2017 + 5 + 17 + 6 + 0 + + + ppublish + + 26923098 + 10.1002/uog.15901 + + +
+ + + + + 26921913 + + 2016 + 03 + 18 + + + 2017 + 08 + 23 + +
+ + 1474-547X + + 387 + 10022 + + 2016 + Mar + 05 + + + Lancet (London, England) + Lancet + + Zika virus and microcephaly in Brazil: a scientific agenda. + + 919-921 + + S0140-6736(16)00545-6 + 10.1016/S0140-6736(16)00545-6 + + + Barreto + Mauricio L + ML + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, 40296-710 Salvador-Bahia, Brazil. Electronic address: mauricio.barreto@bahia.fiocruz.br. + + + + Barral-Netto + Manoel + M + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, 40296-710 Salvador-Bahia, Brazil. + + + + Stabeli + Rodrigo + R + + Office of the Presidency, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Almeida-Filho + Naomar + N + + Universidade Federal do Sul da Bahia, Itabuna, Brazil. + + + + Vasconcelos + Pedro F C + PFC + + Department of Arbovirology and Hemorrhagic Fevers, Instituto Evandro Chagas, Ananindeua, Brazil. + + + + Teixeira + Mauro + M + + Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Minas Gerais, Brazil. + + + + Buss + Paulo + P + + Center for International Relations in Health, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Gadelha + Paulo E + PE + + Office of the Presidency, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + eng + + Journal Article + + + 2016 + 02 + 24 + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Biomedical Research + + + Brazil + epidemiology + + + Health Policy + + + Humans + + + Microcephaly + epidemiology + prevention & control + virology + + + Zika Virus + + + Zika Virus Infection + epidemiology + prevention & control + + +
+ + + + 2016 + 2 + 29 + 6 + 0 + + + 2016 + 2 + 29 + 6 + 0 + + + 2016 + 3 + 19 + 6 + 0 + + + ppublish + + 26921913 + S0140-6736(16)00545-6 + 10.1016/S0140-6736(16)00545-6 + + +
+ + + + + 26921912 + + 2016 + 03 + 18 + + + 2017 + 08 + 23 + +
+ + 1474-547X + + 387 + 10022 + + 2016 + Mar + 05 + + + Lancet (London, England) + Lancet + + Utilising additional sources of information on microcephaly. + + 940-941 + + S0140-6736(16)00519-5 + 10.1016/S0140-6736(16)00519-5 + + + Byass + Peter + P + + WHO Collaborating Centre for Verbal Autopsy, Epidemiology and Global Health, Umeå University, Umeå 90187, Sweden. Electronic address: peter.byass@umu.se. + + + + Wilder-Smith + Annelies + A + + WHO Collaborating Centre for Verbal Autopsy, Epidemiology and Global Health, Umeå University, Umeå 90187, Sweden; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. + + + + eng + + Letter + + + 2016 + 02 + 25 + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Brazil + epidemiology + + + Disease Outbreaks + + + Humans + + + Microcephaly + diagnosis + epidemiology + virology + + + Zika Virus Infection + diagnosis + epidemiology + + +
+ + + + 2016 + 2 + 29 + 6 + 0 + + + 2016 + 2 + 29 + 6 + 0 + + + 2016 + 3 + 19 + 6 + 0 + + + ppublish + + 26921912 + S0140-6736(16)00519-5 + 10.1016/S0140-6736(16)00519-5 + + +
+ + + + + 26914810 + + 2017 + 12 + 19 + + + 2017 + 12 + 19 + +
+ + 1539-3704 + + 164 + 10 + + 2016 + May + 17 + + + Annals of internal medicine + Ann. Intern. Med. + + Emergence of Congenital Zika Syndrome: Viewpoint From the Front Lines. + + 689-91 + + 10.7326/M16-0332 + + + Costa + Federico + F + + + Sarno + Manoel + M + + + Khouri + Ricardo + R + + + de Paula Freitas + Bruno + B + + + Siqueira + Isadora + I + + + Ribeiro + Guilherme S + GS + + + Ribeiro + Hugo C + HC + + + Campos + Gubio S + GS + + + Alcântara + Luiz C + LC + + + Reis + Mitermayer G + MG + + + Weaver + Scott C + SC + + + Vasilakis + Nikos + N + + + Ko + Albert I + AI + + + Almeida + Antonio Raimundo + AR + + + eng + + + R01 AI121207 + AI + NIAID NIH HHS + United States + + + + Journal Article + + + 2016 + 02 + 24 + +
+ + United States + Ann Intern Med + 0372351 + 0003-4819 + + AIM + IM + + + Lancet. 2016 Feb 13;387(10019):621-4 + 26864961 + + + Euro Surveill. 2014 Mar 06;19(9):null + 24626205 + + + JAMA Ophthalmol. 2016 Feb 9;: + 26865554 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Emerg Infect Dis. 2015 Dec;21(12):2274-6 + 26584464 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + Lancet. 2015 Jul 18;386(9990):243-4 + 26194519 + + + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant, Newborn + + + Infectious Disease Transmission, Vertical + prevention & control + + + Microcephaly + diagnostic imaging + epidemiology + virology + + + Pregnancy + + + Syndrome + + + Tomography, X-Ray Computed + + + Zika Virus Infection + congenital + epidemiology + prevention & control + transmission + + +
+ + + + 2016 + 2 + 26 + 6 + 0 + + + 2016 + 2 + 26 + 6 + 0 + + + 2017 + 12 + 20 + 6 + 0 + + + ppublish + + 26914810 + 2498549 + 10.7326/M16-0332 + PMC5444536 + NIHMS858509 + + +
+ + + + + 26914596 + + 2016 + 03 + 22 + + + 2016 + 10 + 17 + +
+ + 1538-3598 + + 315 + 11 + + 2016 + Mar + 15 + + + JAMA + JAMA + + Researchers Focus on Solving the Zika Riddles. + + 1097-9 + + 10.1001/jama.2016.1219 + + + Jacob + Julie A + JA + + + eng + + News + +
+ + United States + JAMA + 7501160 + 0098-7484 + + + + 0 + Viral Vaccines + + + AIM + IM + + + Brazil + epidemiology + + + Causality + + + Humans + + + Microcephaly + epidemiology + immunology + virology + + + Sexually Transmitted Diseases, Viral + complications + prevention & control + virology + + + Viral Vaccines + + + Zika Virus + immunology + pathogenicity + + + Zika Virus Infection + complications + prevention & control + transmission + + +
+ + + + 2016 + 2 + 26 + 6 + 0 + + + 2016 + 2 + 26 + 6 + 0 + + + 2016 + 3 + 24 + 6 + 0 + + + ppublish + + 26914596 + 2498483 + 10.1001/jama.2016.1219 + + +
+ + + + + 26914330 + + 2016 + 07 + 20 + + + 2017 + 02 + 20 + +
+ + 1935-2735 + + 10 + 2 + + 2016 + Feb + + + PLoS neglected tropical diseases + PLoS Negl Trop Dis + + Zika Virus Infection and Stillbirths: A Case of Hydrops Fetalis, Hydranencephaly and Fetal Demise. + + e0004517 + + 10.1371/journal.pntd.0004517 + + The rapid spread of Zika virus in the Americas and current outbreak of microcephaly in Brazil has raised attention to the possible deleterious effects that the virus may have on fetuses. + We report a case of a 20-year-old pregnant woman who was referred to our service after a large Zika virus outbreak in the city of Salvador, Brazil with an ultrasound examination that showed intrauterine growth retardation of the fetus at the 18th gestational week. Ultrasound examinations in the 2nd and 3rd trimesters demonstrated severe microcephaly, hydranencephaly, intracranial calcifications and destructive lesions of posterior fossa, in addition to hydrothorax, ascites and subcutaneous edema. An induced labor was performed at the 32nd gestational week due to fetal demise and delivered a female fetus. ZIKV-specific real-time polymerase chain reaction amplification products were obtained from extracts of cerebral cortex, medulla oblongata and cerebrospinal and amniotic fluid, while extracts of heart, lung, liver, vitreous body of the eye and placenta did not yield detectable products. + This case report provides evidence that in addition to microcephaly, there may be a link between Zika virus infection and hydrops fetalis and fetal demise. Given the recent spread of the virus, systematic investigation of spontaneous abortions and stillbirths may be warranted to evaluate the risk that ZIKV infection imparts on these outcomes. + + + + Sarno + Manoel + M + + Hospital Geral Roberto Santos, Secretaria Estadual da Saúde da Bahia, Salvador, Bahia, Brazil. + + + Faculdade de Medicina da Bahia and Instituto da Saúde Coletiva, Universidade Federal da Bahia, Salvador, Bahia, Brazil. + + + + Sacramento + Gielson A + GA + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Sáude, Salvador, Bahia, Brazil. + + + + Khouri + Ricardo + R + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Sáude, Salvador, Bahia, Brazil. + + + + do Rosário + Mateus S + MS + + Hospital Geral Roberto Santos, Secretaria Estadual da Saúde da Bahia, Salvador, Bahia, Brazil. + + + + Costa + Federico + F + + Faculdade de Medicina da Bahia and Instituto da Saúde Coletiva, Universidade Federal da Bahia, Salvador, Bahia, Brazil. + + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Sáude, Salvador, Bahia, Brazil. + + + Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America. + + + + Archanjo + Gracinda + G + + Hospital Geral Roberto Santos, Secretaria Estadual da Saúde da Bahia, Salvador, Bahia, Brazil. + + + + Santos + Luciane A + LA + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Sáude, Salvador, Bahia, Brazil. + + + + Nery + Nivison + N + Jr + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Sáude, Salvador, Bahia, Brazil. + + + + Vasilakis + Nikos + N + + Department of Pathology and Center of Biodefense and Emerging Infectious Diseases, Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America. + + + + Ko + Albert I + AI + + Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Sáude, Salvador, Bahia, Brazil. + + + Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America. + + + + de Almeida + Antonio R P + AR + + Hospital Geral Roberto Santos, Secretaria Estadual da Saúde da Bahia, Salvador, Bahia, Brazil. + + + Faculdade de Medicina da Bahia and Instituto da Saúde Coletiva, Universidade Federal da Bahia, Salvador, Bahia, Brazil. + + + + eng + + + R01 AI121207 + AI + NIAID NIH HHS + United States + + + + Case Reports + Journal Article + + + 2016 + 02 + 25 + +
+ + United States + PLoS Negl Trop Dis + 101291488 + 1935-2727 + + IM + + + J Med Virol. 2012 Sep;84(9):1501-5 + 22825831 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + MMWR Morb Mortal Wkly Rep. 2016 Feb 19;65(6):159-60 + 26890059 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + JAMA Ophthalmol. 2016 Feb 9;:null + 26865554 + + + Lancet. 2016 Jan 16;387(10015):227-8 + 26775124 + + + N Engl J Med. 2016 Feb 18;374(7):601-4 + 26761185 + + + Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7 + 26731034 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + + + + Female + + + Humans + + + Hydranencephaly + mortality + virology + + + Hydrops Fetalis + mortality + virology + + + Pregnancy + + + Stillbirth + + + Young Adult + + + Zika Virus + genetics + isolation & purification + physiology + + + Zika Virus Infection + mortality + virology + + +
+ + + + 2016 + 02 + 16 + + + 2016 + 02 + 16 + + + 2016 + 2 + 26 + 6 + 0 + + + 2016 + 2 + 26 + 6 + 0 + + + 2016 + 7 + 21 + 6 + 0 + + + epublish + + 26914330 + 10.1371/journal.pntd.0004517 + PNTD-D-16-00248 + PMC4767410 + + +
+ + + + + 26911164 + + 2016 + 05 + 03 + + + 2016 + 11 + 26 + +
+ + 0966-0461 + + 25 + 4 + + 2016 Feb 25-Mar 9 + + + British journal of nursing (Mark Allen Publishing) + Br J Nurs + + Zika virus disease: a public health emergency of international concern. + + 198, 200-2 + + 10.12968/bjon.2016.25.4.198 + + The emergence of Zika virus disease (ZIKV) in the Americas, mainly Brazil, has required the World Health Organization to take action to halt the spread of the virus by implementing preventive measures. This has resulted in increased surveillance of the virus and its potential complications. In the UK, cases of ZIKV have been reported in returning travellers. With the importance of this disease increasing, it is vital that nurses and other health professionals take the time to learn about ZIKV in order to pass on this knowledge to patients, enabling them to make informed choices about travel to affected areas. This article will discuss the ZIKV, its complications and what to advise travellers, including pregnant women, to prevent transmission and spread. + + + + Lupton + Kelly + K + + Registered Nurse, Queen Alexandra Hospital, Portsmouth Hospitals Trust. + + + + eng + + Journal Article + +
+ + England + Br J Nurs + 9212059 + 0966-0461 + + N + + + Adult + + + Brazil + epidemiology + + + Disease Outbreaks + prevention & control + + + Female + + + Global Health + + + Humans + + + Microcephaly + virology + + + Pregnancy + + + Pregnant Women + + + Public Health + methods + + + Risk Factors + + + Travel + + + United Kingdom + epidemiology + + + World Health Organization + + + Young Adult + + + Zika Virus + pathogenicity + + + Zika Virus Infection + epidemiology + pathology + + + + Blood safety + Global health + Pregnant women + Public health + World Health Organization + Zika virus + +
+ + + + 2016 + 2 + 26 + 6 + 0 + + + 2016 + 2 + 26 + 6 + 0 + + + 2016 + 5 + 4 + 6 + 0 + + + ppublish + + 26911164 + 10.12968/bjon.2016.25.4.198 + + +
+ + + + + 26897108 + + 2017 + 06 + 05 + + + 2018 + 03 + 07 + +
+ + 1474-4457 + + 16 + 6 + + 2016 + Jun + + + The Lancet. Infectious diseases + Lancet Infect Dis + + Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. + + 653-660 + + S1473-3099(16)00095-5 + 10.1016/S1473-3099(16)00095-5 + + The incidence of microcephaly in Brazil in 2015 was 20 times higher than in previous years. Congenital microcephaly is associated with genetic factors and several causative agents. Epidemiological data suggest that microcephaly cases in Brazil might be associated with the introduction of Zika virus. We aimed to detect and sequence the Zika virus genome in amniotic fluid samples of two pregnant women in Brazil whose fetuses were diagnosed with microcephaly. + In this case study, amniotic fluid samples from two pregnant women from the state of Paraíba in Brazil whose fetuses had been diagnosed with microcephaly were obtained, on the recommendation of the Brazilian health authorities, by ultrasound-guided transabdominal amniocentesis at 28 weeks' gestation. The women had presented at 18 weeks' and 10 weeks' gestation, respectively, with clinical manifestations that could have been symptoms of Zika virus infection, including fever, myalgia, and rash. After the amniotic fluid samples were centrifuged, DNA and RNA were extracted from the purified virus particles before the viral genome was identified by quantitative reverse transcription PCR and viral metagenomic next-generation sequencing. Phylogenetic reconstruction and investigation of recombination events were done by comparing the Brazilian Zika virus genome with sequences from other Zika strains and from flaviviruses that occur in similar regions in Brazil. + We detected the Zika virus genome in the amniotic fluid of both pregnant women. The virus was not detected in their urine or serum. Tests for dengue virus, chikungunya virus, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, HIV, Treponema pallidum, and parvovirus B19 were all negative. After sequencing of the complete genome of the Brazilian Zika virus isolated from patient 1, phylogenetic analyses showed that the virus shares 97-100% of its genomic identity with lineages isolated during an outbreak in French Polynesia in 2013, and that in both envelope and NS5 genomic regions, it clustered with sequences from North and South America, southeast Asia, and the Pacific. After assessing the possibility of recombination events between the Zika virus and other flaviviruses, we ruled out the hypothesis that the Brazilian Zika virus genome is a recombinant strain with other mosquito-borne flaviviruses. + These findings strengthen the putative association between Zika virus and cases of microcephaly in neonates in Brazil. Moreover, our results suggest that the virus can cross the placental barrier. As a result, Zika virus should be considered as a potential infectious agent for human fetuses. Pathogenesis studies that confirm the tropism of Zika virus for neuronal cells are warranted. + Consellho Nacional de Desenvolvimento e Pesquisa (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ). + Copyright © 2016 Elsevier Ltd. All rights reserved. + + + + Calvet + Guilherme + G + + Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica em Doenças Febris Agudas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Aguiar + Renato S + RS + + Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Melo + Adriana S O + ASO + + Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ), Campina Grande, Brazil. + + + + Sampaio + Simone A + SA + + Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + de Filippis + Ivano + I + + Instituto Nacional de Controle e Qualidade, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Fabri + Allison + A + + Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Araujo + Eliane S M + ESM + + Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + de Sequeira + Patricia C + PC + + Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + de Mendonça + Marcos C L + MCL + + Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + de Oliveira + Louisi + L + + Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Tschoeke + Diogo A + DA + + Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Schrago + Carlos G + CG + + Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + Thompson + Fabiano L + FL + + Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Laboratório de Sistemas Avançados de Gestão de Produção-SAGE-COPPE, Centro de Gestão Tecnológica-CT2, UFRJ, Rio de Janeiro, Brazil. + + + + Brasil + Patricia + P + + Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica em Doenças Febris Agudas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Dos Santos + Flavia B + FB + + Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Nogueira + Rita M R + RMR + + Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. + + + + Tanuri + Amilcar + A + + Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. + + + + de Filippis + Ana M B + AMB + + Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Electronic address: abispo@ioc.fiocruz.br. + + + + eng + + Case Reports + Journal Article + + + 2016 + 02 + 18 + +
+ + United States + Lancet Infect Dis + 101130150 + 1473-3099 + + + + 0 + RNA, Viral + + + IM + + + Lancet Infect Dis. 2016 Jun;16(6):620-621 + 26897106 + + + Lancet Infect Dis. 2016 Jul;16(7):771-772 + 27352748 + + + + + Amniotic Fluid + virology + + + Brazil + epidemiology + + + Disease Outbreaks + + + Female + + + Genome, Viral + genetics + + + Gestational Age + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + genetics + + + Phylogeny + + + Placenta + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + virology + + + RNA, Viral + isolation & purification + + + Zika Virus + isolation & purification + + + Zika Virus Infection + diagnosis + virology + + +
+ + + + 2016 + 02 + 02 + + + 2016 + 02 + 06 + + + 2016 + 02 + 08 + + + 2016 + 2 + 22 + 6 + 0 + + + 2016 + 2 + 22 + 6 + 0 + + + 2017 + 6 + 6 + 6 + 0 + + + ppublish + + 26897108 + S1473-3099(16)00095-5 + 10.1016/S1473-3099(16)00095-5 + + +
+ + + + + 26890059 + + 2016 + 06 + 22 + + + 2016 + 02 + 19 + +
+ + 1545-861X + + 65 + 6 + + 2016 + Feb + 19 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses--Brazil, 2015. + + 159-60 + + 10.15585/mmwr.mm6506e1 + + Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3). + + + + Martines + Roosecelis Brasil + RB + + + Bhatnagar + Julu + J + + + Keating + M Kelly + MK + + + Silva-Flannery + Luciana + L + + + Muehlenbachs + Atis + A + + + Gary + Joy + J + + + Goldsmith + Cynthia + C + + + Hale + Gillian + G + + + Ritter + Jana + J + + + Rollin + Dominique + D + + + Shieh + Wun-Ju + WJ + + + Luz + Kleber G + KG + + + Ramos + Ana Maria de Oliveira + AM + + + Davi + Helaine Pompeia Freire + HP + + + Kleber de Oliveria + Wanderson + W + + + Lanciotti + Robert + R + + + Lambert + Amy + A + + + Zaki + Sherif + S + + + eng + + Case Reports + Journal Article + + + 2016 + 02 + 19 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + + + 0 + Antigens, Viral + + + 0 + RNA, Viral + + + IM + + + Abortion, Spontaneous + virology + + + Antigens, Viral + isolation & purification + + + Brain + virology + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant, Newborn + + + Placenta + virology + + + Pregnancy + + + RNA, Viral + isolation & purification + + + Zika Virus + immunology + isolation & purification + + + Zika Virus Infection + congenital + diagnosis + + +
+ + + + 2016 + 2 + 19 + 6 + 0 + + + 2016 + 2 + 20 + 6 + 0 + + + 2016 + 6 + 23 + 6 + 0 + + + epublish + + 26890059 + 10.15585/mmwr.mm6506e1 + + +
+ + + + + 26889662 + + 2016 + 08 + 08 + + + 2018 + 01 + 12 + +
+ + 1873-233X + + 127 + 4 + + 2016 + Apr + + + Obstetrics and gynecology + Obstet Gynecol + + Zika Virus and Pregnancy: What Obstetric Health Care Providers Need to Know. + + 642-8 + + 10.1097/AOG.0000000000001378 + + Zika virus is a flavivirus transmitted by Aedes (Stegomyia) species of mosquitoes. In May 2015, the World Health Organization confirmed the first local transmission of Zika virus in the Americas in Brazil. The virus has spread rapidly to other countries in the Americas; as of January 29, 2016, local transmission has been detected in at least 22 countries or territories, including the Commonwealth of Puerto Rico and the U.S. Virgin Islands. Zika virus can infect pregnant women in all three trimesters. Although pregnant women do not appear to be more susceptible to or more severely affected by Zika virus infection, maternal-fetal transmission has been documented. Several pieces of evidence suggest that maternal Zika virus infection is associated with adverse neonatal outcomes, most notably microcephaly. Because of the number of countries and territories with local Zika virus transmission, it is likely that obstetric health care providers will care for pregnant women who live in or have traveled to an area of local Zika virus transmission. We review information on Zika virus, its clinical presentation, modes of transmission, laboratory testing, effects during pregnancy, and methods of prevention to assist obstetric health care providers in caring for pregnant women considering travel or with a history of travel to areas with ongoing Zika virus transmission and pregnant women residing in areas with ongoing Zika virus transmission. + + + + Meaney-Delman + Dana + D + + Centers for Disease Control and Prevention, Atlanta, Georgia. + + + + Rasmussen + Sonja A + SA + + + Staples + J Erin + JE + + + Oduyebo + Titilope + T + + + Ellington + Sascha R + SR + + + Petersen + Emily E + EE + + + Fischer + Marc + M + + + Jamieson + Denise J + DJ + + + eng + + Journal Article + Review + +
+ + United States + Obstet Gynecol + 0401101 + 0029-7844 + + AIM + IM + + + Obstet Gynecol. 2016 Aug;128(2):405 + 27454712 + + + + + Brazil + + + Female + + + Humans + + + Infant, Newborn + + + Infectious Disease Transmission, Vertical + prevention & control + + + Microcephaly + prevention & control + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + prevention & control + virology + + + Puerto Rico + + + Travel + + + United States Virgin Islands + + + Zika Virus + + + Zika Virus Infection + complications + transmission + + +
+ + + + 2016 + 2 + 19 + 6 + 0 + + + 2016 + 2 + 19 + 6 + 0 + + + 2016 + 8 + 9 + 6 + 0 + + + ppublish + + 26889662 + 10.1097/AOG.0000000000001378 + + +
+ + + + + 26876373 + + 2016 + 03 + 07 + + + 2016 + 02 + 24 + +
+ + 1474-547X + + 387 + 10020 + + 2016 + Feb + 20 + + + Lancet (London, England) + Lancet + + Zika virus and microcephaly: why is this situation a PHEIC? + + 719-21 + + 10.1016/S0140-6736(16)00320-2 + S0140-6736(16)00320-2 + + + Heymann + David L + DL + + Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK; Centre on Global Health Security, Chatham House, The Royal Institute of International Affairs, London SW1Y 4LE, UK. Electronic address: david.heymann@phe.gov.uk. + + + + Hodgson + Abraham + A + + Research and Development Division, Ghana Health Service, Accra, Ghana. + + + + Sall + Amadou Alpha + AA + + WHO Collaborating Centre for Arboviruses and Viral Haemorrhagic Fevers, Senegal Institut Pasteur de Dakar, Dakar, Senegal. + + + + Freedman + David O + DO + + Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA. + + + + Staples + J Erin + JE + + Division of Vector-borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, USA. + + + + Althabe + Fernando + F + + Department of Maternal and Child Health Research, Institute for Clinical Effectiveness and Health Policy, Buenos Aires, Argentina. + + + + Baruah + Kalpana + K + + National Vector Borne Disease Control Programme, Ministry of Health and Family Welfare, Government of India, New Delhi, India. + + + + Mahmud + Ghazala + G + + Faculty of Medicine, Quaid i Azam University, Quaid i Azam Post Graduate Medical College, Pakistan Institute of Medical Sciences, Islamabad, Pakistan. + + + + Kandun + Nyoman + N + + Field Epidemiology Training Program, Ministry of Health, Jakarta, Indonesia. + + + + Vasconcelos + Pedro F C + PF + + Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ananindeua, Brazil. + + + + Bino + Silvia + S + + Control of Infectious Diseases Department, Institute of Public Health, Tirana, Albania. + + + + Menon + K U + KU + + Ministry of Communications and Information, Singapore. + + + + eng + + Journal Article + + + 2016 + 02 + 11 + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Emergencies + + + Global Health + + + Humans + + + Microcephaly + epidemiology + virology + + + Public Health + + + World Health Organization + + + Zika Virus Infection + complications + epidemiology + + +
+ + + + 2016 + 2 + 16 + 6 + 0 + + + 2016 + 2 + 16 + 6 + 0 + + + 2016 + 3 + 8 + 6 + 0 + + + ppublish + + 26876373 + S0140-6736(16)00320-2 + 10.1016/S0140-6736(16)00320-2 + + +
+ + + + + 26868672 + + 2016 + 06 + 16 + + + 2016 + 11 + 26 + +
+ + 1756-1833 + + 352 + + 2016 + Feb + 11 + + + BMJ (Clinical research ed.) + BMJ + + UK records four cases of Zika virus in past six weeks. + + i875 + + 10.1136/bmj.i875 + + + O'Dowd + Adrian + A + + London. + + + + eng + + News + + + 2016 + 02 + 11 + +
+ + England + BMJ + 8900488 + 0959-535X + + + + 0 + Viral Vaccines + + + AIM + IM + + + Brazil + epidemiology + + + Humans + + + Microcephaly + virology + + + Travel + + + United Kingdom + epidemiology + + + Viral Vaccines + + + Zika Virus Infection + complications + epidemiology + prevention & control + + +
+ + + + 2016 + 2 + 13 + 6 + 0 + + + 2016 + 2 + 13 + 6 + 0 + + + 2016 + 6 + 17 + 6 + 0 + + + epublish + + 26868672 + + +
+ + + + + 26865554 + + 2017 + 08 + 09 + +
+ + 2168-6173 + + + 2016 + Feb + 09 + + + JAMA ophthalmology + JAMA Ophthalmol + + Ocular Findings in Infants With Microcephaly Associated With Presumed Zika Virus Congenital Infection in Salvador, Brazil. + 10.1001/jamaophthalmol.2016.0267 + + The Zika virus (ZIKV) has rapidly reached epidemic proportions, especially in northeastern Brazil, and has rapidly spread to other parts of the Americas. A recent increase in the prevalence of microcephaly in newborn infants and vision-threatening findings in these infants is likely associated with the rapid spread of ZIKV. + To evaluate the ocular findings in infants with microcephaly associated with presumed intrauterine ZIKV infection in Salvador, Bahia, Brazil. + Case series at a tertiary hospital. Twenty-nine infants with microcephaly (defined by a cephalic circumference of ≤32 cm) with a presumed diagnosis of congenital ZIKV were recruited through an active search and referrals from other hospitals and health unities. The study was conducted between December 1 and December 21, 2015. + All infants and mothers underwent systemic and ophthalmic examinations from December 1 through December 21, 2015, in the Roberto Santos General Hospital, Salvador, Brazil. Anterior segment and retinal, choroidal, and optic nerve abnormalities were documented using a wide-field digital imaging system. The differential diagnosis included toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis, and human immunodeficiency virus, which were ruled out through serologic and clinical examinations. + Ocular abnormalities associated with ZIKV. + Twenty-three of 29 mothers (79.3%) reported suspected ZIKV infection signs and symptoms during pregnancy, 18 in the first trimester, 4 in the second trimester, and 1 in the third trimester. Of the 29 infants (58 eyes) examined (18 [62.1%] female), ocular abnormalities were present in 17 eyes (29.3%) of 10 children (34.5%). Bilateral findings were found in 7 of 10 patients presenting with ocular lesions, the most common of which were focal pigment mottling of the retina and chorioretinal atrophy in 11 of the 17 eyes with abnormalities (64.7%), followed by optic nerve abnormalities in 8 eyes (47.1%), bilateral iris coloboma in 1 patient (2 eyes [11.8%]), and lens subluxation in 1 eye (5.9%). + Congenital infection due to presumed ZIKV exposure is associated with vision-threatening findings, which include bilateral macular and perimacular lesions as well as optic nerve abnormalities in most cases. + + + + de Paula Freitas + Bruno + B + + Department of Ophthalmology, Hospital Geral Roberto Santos, Salvador, Brazil. + + + + de Oliveira Dias + João Rafael + JR + + Vision Institute, Department of Ophthalmology, Paulista Medical School, Federal University of São Paulo, São Paulo, Brazil. + + + + Prazeres + Juliana + J + + Vision Institute, Department of Ophthalmology, Paulista Medical School, Federal University of São Paulo, São Paulo, Brazil. + + + + Sacramento + Gielson Almeida + GA + + Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Salvador, Brazil. + + + + Ko + Albert Icksang + AI + + Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Salvador, Brazil4Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut. + + + + Maia + Maurício + M + + Vision Institute, Department of Ophthalmology, Paulista Medical School, Federal University of São Paulo, São Paulo, Brazil. + + + + Belfort + Rubens + R + Jr + + Vision Institute, Department of Ophthalmology, Paulista Medical School, Federal University of São Paulo, São Paulo, Brazil. + + + + eng + + + R01 AI121207 + AI + NIAID NIH HHS + United States + + + + Journal Article + + + 2016 + 02 + 09 + +
+ + United States + JAMA Ophthalmol + 101589539 + 2168-6165 + + + + Euro Surveill. 2014 Jan 30;19(4):null + 24507466 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20 + 12995440 + + + Arch Virol. 2007;152(4):687-96 + 17195954 + + + Obstet Gynecol. 2008 May;111(5):1111-7 + 18448743 + + + Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34 + 12995441 + + + Emerg Infect Dis. 2015 Feb;21(2):381-2 + 25625687 + + + PLoS Med. 2008 Mar 18;5(3):e60 + 18351797 + + + Emerg Infect Dis. 2010 Mar;16(3):418-25 + 20202416 + + + MMWR Morb Mortal Wkly Rep. 2002 Oct 4;51(39):877-8 + 12375687 + + + Obstet Gynecol Surv. 2010 Feb;65(2):107-18 + 20100360 + + + Am J Ophthalmol. 2003 Oct;136(4):733-5 + 14516816 + + + Emerg Infect Dis. 2015 Oct;21(10):1885-6 + 26401719 + + + Case Rep Infect Dis. 2013;2013:351872 + 23533851 + + + Emerg Infect Dis. 2008 Aug;14(8):1232-9 + 18680646 + + + Emerg Infect Dis. 2011 May;17(5):880-2 + 21529401 + + + Euro Surveill. 2014 Apr 03;19(13):null + 24721538 + + + Virol J. 2010 Jul 13;7:153 + 20626851 + + + Mem Inst Oswaldo Cruz. 2015 Jun;110(4):569-72 + 26061233 + + + JAMA. 2013 Nov 27;310(20):2191-4 + 24141714 + + + Emerg Infect Dis. 2011 Sep;17(9):1779-80 + 21888828 + + + Med Mal Infect. 2014 Jul;44(7):302-7 + 25001879 + + + Clin Infect Dis. 2013 Aug;57(3):415-7 + 23575200 + + + Emerg Infect Dis. 2009 Sep;15(9):1347-50 + 19788800 + + + N Engl J Med. 2009 Jun 11;360(24):2536-43 + 19516034 + + +
+ + + + 2016 + 2 + 12 + 6 + 0 + + + 2016 + 2 + 13 + 6 + 0 + + + 2016 + 2 + 13 + 6 + 0 + + + aheadofprint + + 26865554 + 2491896 + 10.1001/jamaophthalmol.2016.0267 + PMC5444996 + NIHMS858515 + + +
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+ + 1474-547X + + 387 + 10019 + + 2016 + Feb + 13 + + + Lancet (London, England) + Lancet + + A crucial time for public health preparedness: Zika virus and the 2016 Olympics, Umrah, and Hajj. + + 630-2 + + 10.1016/S0140-6736(16)00274-9 + S0140-6736(16)00274-9 + + + Elachola + Habida + H + + Atlanta, Georgia, USA. + + + + Gozzer + Ernesto + E + + Instituto Nacional de Salud, Lima, Peru. + + + + Zhuo + Jiatong + J + + Guangxi Centers for Disease Control and Prevention, Guangxi, China. + + + + Memish + Ziad A + ZA + + Ministry of Health, Riyadh, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh 11514, Saudi Arabia. Electronic address: zmemish@yahoo.com. + + + + eng + + Journal Article + + + 2016 + 02 + 07 + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Americas + epidemiology + + + Brazil + epidemiology + + + Central Nervous System Viral Diseases + epidemiology + prevention & control + + + Ceremonial Behavior + + + Disease Outbreaks + + + Female + + + Humans + + + Islam + + + Microcephaly + epidemiology + prevention & control + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + prevention & control + + + Public Health + + + Saudi Arabia + + + Sports + + + Travel + + + Zika Virus Infection + epidemiology + prevention & control + + +
+ + + + 2016 + 2 + 12 + 6 + 0 + + + 2016 + 2 + 13 + 6 + 0 + + + 2016 + 3 + 8 + 6 + 0 + + + ppublish + + 26864962 + S0140-6736(16)00274-9 + 10.1016/S0140-6736(16)00274-9 + + +
+ + + + + 26864344 + + 2016 + 06 + 09 + + + 2016 + 02 + 11 + +
+ + 1756-1833 + + 352 + + 2016 + Feb + 10 + + + BMJ (Clinical research ed.) + BMJ + + Severe eye damage in infants with microcephaly is presumed to be due to Zika virus. + + i855 + + 10.1136/bmj.i855 + + + McCarthy + Michael + M + + Seattle. + + + + eng + + News + + + 2016 + 02 + 10 + +
+ + England + BMJ + 8900488 + 0959-535X + + AIM + IM + + + Brazil + epidemiology + + + Eye Diseases + diagnosis + etiology + virology + + + Female + + + Humans + + + Infant, Newborn + + + Male + + + Zika Virus Infection + complications + + +
+ + + + 2016 + 2 + 12 + 6 + 0 + + + 2016 + 2 + 13 + 6 + 0 + + + 2016 + 6 + 10 + 6 + 0 + + + epublish + + 26864344 + + +
+ + + + + 26863963 + + 2016 + 02 + 24 + + + 2016 + 02 + 25 + +
+ + 1476-4687 + + 530 + 7589 + + 2016 + Feb + 11 + + + Nature + Nature + + Proving Zika link to birth defects poses huge challenge. + + 142-3 + + 10.1038/530142a + + + Check Hayden + Erika + E + + + eng + + News + +
+ + England + Nature + 0410462 + 0028-0836 + + + + 0 + Antibodies, Viral + + + IM + + + Nature. 2016 Feb 25;530(7591):395 + 26911761 + + + + + Animals + + + Antibodies, Viral + analysis + immunology + + + Biomedical Research + trends + + + Brazil + epidemiology + + + Case-Control Studies + + + Disease Models, Animal + + + Evidence-Based Medicine + + + Female + + + Fetal Diseases + epidemiology + etiology + virology + + + Humans + + + Infant, Newborn + + + Infant, Newborn, Diseases + epidemiology + etiology + virology + + + Infectious Disease Transmission, Vertical + + + Microcephaly + epidemiology + etiology + pathology + virology + + + Pregnancy + + + Time Factors + + + Zika Virus + genetics + immunology + isolation & purification + pathogenicity + + + Zika Virus Infection + complications + diagnosis + epidemiology + virology + + +
+ + + + 2016 + 2 + 12 + 6 + 0 + + + 2016 + 2 + 13 + 6 + 0 + + + 2016 + 2 + 26 + 6 + 0 + + + ppublish + + 26863963 + 530142a + 10.1038/530142a + + +
+ + + + + 26863943 + + 2016 + 02 + 24 + + + 2016 + 02 + 11 + +
+ + 1476-4687 + + 530 + 7589 + + 2016 + Feb + 11 + + + Nature + Nature + + Benefits of sharing. + + 129 + + 10.1038/530129a + eng + + Editorial + +
+ + England + Nature + 0410462 + 0028-0836 + + IM + + + Brazil + epidemiology + + + Databases, Factual + utilization + + + Disease Outbreaks + statistics & numerical data + + + Evidence-Based Medicine + + + Humans + + + Information Dissemination + + + Microcephaly + epidemiology + etiology + virology + + + Open Access Publishing + + + Sequence Analysis, DNA + + + Time Factors + + + World Health Organization + + + Zika Virus + genetics + pathogenicity + + + Zika Virus Infection + epidemiology + virology + + +
+ + + + 2016 + 2 + 12 + 6 + 0 + + + 2016 + 2 + 13 + 6 + 0 + + + 2016 + 2 + 26 + 6 + 0 + + + ppublish + + 26863943 + 530129a + 10.1038/530129a + + +
+ + + + + 26862926 + + 2016 + 03 + 15 + + + 2016 + 11 + 26 + +
+ + 1533-4406 + + 374 + 10 + + 2016 + Mar + 10 + + + The New England journal of medicine + N. Engl. J. Med. + + Zika Virus Associated with Microcephaly. + + 951-8 + + 10.1056/NEJMoa1600651 + + A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain. + + + + Mlakar + Jernej + J + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Korva + Misa + M + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Tul + Nataša + N + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Popović + Mara + M + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Poljšak-Prijatelj + Mateja + M + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Mraz + Jerica + J + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Kolenc + Marko + M + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Resman Rus + Katarina + K + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Vesnaver Vipotnik + Tina + T + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Fabjan Vodušek + Vesna + V + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Vizjak + Alenka + A + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Pižem + Jože + J + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Petrovec + Miroslav + M + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + Avšič Županc + Tatjana + T + + From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia. + + + + eng + + Case Reports + Journal Article + + + 2016 + 02 + 10 + +
+ + United States + N Engl J Med + 0255562 + 0028-4793 + + AIM + IM + + + N Engl J Med. 2016 Mar 10;374(10):984-5 + 26862812 + + + + + Abortion, Therapeutic + + + Adult + + + Brain + embryology + pathology + virology + + + Female + + + Fetal Diseases + diagnostic imaging + pathology + virology + + + Genome, Viral + + + Humans + + + Infectious Disease Transmission, Vertical + + + Microcephaly + diagnostic imaging + pathology + virology + + + Phylogeny + + + Pregnancy + + + Pregnancy Trimester, Third + + + Reverse Transcriptase Polymerase Chain Reaction + + + Ultrasonography, Prenatal + + + Zika Virus + genetics + isolation & purification + + + Zika Virus Infection + complications + pathology + transmission + + +
+ + + + 2016 + 2 + 11 + 6 + 0 + + + 2016 + 2 + 11 + 6 + 0 + + + 2016 + 3 + 16 + 6 + 0 + + + ppublish + + 26862926 + 10.1056/NEJMoa1600651 + + +
+ + + + + 26854199 + + 2016 + 10 + 28 + + + 2016 + 12 + 30 + +
+ + 1878-3511 + + 44 + + 2016 + Mar + + + International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases + Int. J. Infect. Dis. + + Rapid Spread of Zika Virus in The Americas--Implications for Public Health Preparedness for Mass Gatherings at the 2016 Brazil Olympic Games. + + 11-5 + + 10.1016/j.ijid.2016.02.001 + S1201-9712(16)00021-7 + + Mass gatherings at major international sporting events put millions of international travelers and local host-country residents at risk of acquiring infectious diseases, including locally endemic infectious diseases. The mosquito-borne Zika virus (ZIKV) has recently aroused global attention due to its rapid spread since its first detection in May 2015 in Brazil to 22 other countries and other territories in the Americas. The ZIKV outbreak in Brazil, has also been associated with a significant rise in the number of babies born with microcephaly and neurological disorders, and has been declared a 'Global Emergency by the World Health Organization. This explosive spread of ZIKV in Brazil poses challenges for public health preparedness and surveillance for the Olympics and Paralympics which are due to be held in Rio De Janeiro in August, 2016. We review the epidemiology and clinical features of the current ZIKV outbreak in Brazil, highlight knowledge gaps, and review the public health implications of the current ZIKV outbreak in the Americas. We highlight the urgent need for a coordinated collaborative response for prevention and spread of infectious diseases with epidemic potential at mass gatherings events. + Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved. + + + + Petersen + Eskild + E + + The Royal Hospital, Muscat, Oman, and Insititute of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: eskildp@dadlnet.dk. + + + + Wilson + Mary E + ME + + School of Medicine, University of California, San Francisco, USA; Harvard T.H. Chan School of Public Health, Boston, MA, USA. + + + + Touch + Sok + S + + Communicable Disease Control Department, Ministry of Health, Cambodia. + + + + McCloskey + Brian + B + + Global Health Department, Public Health England, London, United Kingdom. + + + + Mwaba + Peter + P + + UNZA-UCLMS Project, University Teaching Hospital, and Ministry of Health, Lusaka, Zambia. + + + + Bates + Matthew + M + + UNZA-UCLMS Project, University Teaching Hospital, and Ministry of Health, Lusaka, Zambia. + + + + Dar + Osman + O + + Global Health Department, Public Health England, London, United Kingdom. + + + + Mattes + Frank + F + + Dept of Virology, University College London Hospitals NHS Foundation Trust, London, UK. + + + + Kidd + Mike + M + + Dept of Virology, University College London Hospitals NHS Foundation Trust, London, UK. + + + + Ippolito + Giuseppe + G + + National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy. + + + + Azhar + Esam I + EI + + Special Infectious Agents Unit, King Fahd Medical Research Centre, and Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. + + + + Zumla + Alimuddin + A + + Special Infectious Agents Unit, King Fahd Medical Research Centre, and Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, United Kingdom. + + + + eng + + Journal Article + Review + + + 2016 + 02 + 04 + +
+ + Canada + Int J Infect Dis + 9610933 + 1201-9712 + + IM + + + Brazil + epidemiology + + + Disease Outbreaks + prevention & control + + + Humans + + + Infant + + + Microcephaly + epidemiology + virology + + + Public Health + + + Sports + + + World Health Organization + + + Zika Virus + + + Zika Virus Infection + complications + epidemiology + + + + Arboviruses + Brazil + Mass Gatherings + Olympics + Sporting events + Zika virus + +
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+ + 1476-4687 + + 530 + 7588 + + 2016 + Feb + 04 + + + Nature + Nature + + Zika virus: Brazil's surge in small-headed babies questioned by report. + + 13-4 + + 10.1038/nature.2016.19259 + + + Butler + Declan + D + + + eng + + News + +
+ + England + Nature + 0410462 + 0028-0836 + + IM + + + Nature. 2016 Feb 11;530(7589):143 + 26863964 + + + + + Brazil + epidemiology + + + Diagnostic Errors + statistics & numerical data + + + Female + + + Humans + + + Infectious Disease Transmission, Vertical + statistics & numerical data + + + Microcephaly + diagnosis + epidemiology + etiology + virology + + + Pregnancy + + + Uncertainty + + + Zika Virus + isolation & purification + pathogenicity + + + Zika Virus Infection + epidemiology + transmission + virology + + +
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+ + 1476-4687 + + 530 + 7588 + + 2016 + Feb + 04 + + + Nature + Nature + + The next steps on Zika. + + 5 + + 10.1038/530005a + eng + + Editorial + +
+ + England + Nature + 0410462 + 0028-0836 + + IM + + + Nature. 2016 Mar 10;531(7593):173 + 26961646 + + + + + Aedes + virology + + + Animals + + + Brazil + epidemiology + + + Female + + + Humans + + + Infectious Disease Transmission, Vertical + prevention & control + statistics & numerical data + + + Microcephaly + epidemiology + etiology + virology + + + Mosquito Control + methods + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + prevention & control + virology + + + Rubella + epidemiology + + + Tropical Climate + + + Virology + trends + + + Zika Virus + isolation & purification + pathogenicity + + + Zika Virus Infection + epidemiology + prevention & control + virology + + +
+ + + + 2016 + 2 + 5 + 6 + 0 + + + 2016 + 2 + 6 + 6 + 0 + + + 2016 + 2 + 26 + 6 + 0 + + + ppublish + + 26842018 + 530005a + 10.1038/530005a + + +
+ + + + + 26840156 + + 2016 + 10 + 31 + + + 2016 + 12 + 30 + +
+ + 1678-2925 + + 79 + 1 + + 2016 + Feb + + + Arquivos brasileiros de oftalmologia + Arq Bras Oftalmol + + Ophthalmological findings in infants with microcephaly and presumable intra-uterus Zika virus infection. + + 1-3 + + 10.5935/0004-2749.20160002 + S0004-27492016000100002 + + In 2015, a twenty-fold increase in the prevalence of microcephaly in Brazil was reported, and the Ministry of Health associated this abnormal prevalence with the maternal-fetal Zika virus (ZIKV) transmission. + We assessed the ophthalmological findings of ten mothers and their infants that had been clinically diagnosed with ZIKV-related microcephaly and presented ocular abnormalities, born from May to December 2015. + Seven mothers (70.0%) referred symptoms during pregnancy (malaise, rash and arthralgia), of which six (85.7%) were in the first trimester. At the time of exam, no ophthalmological abnormalities were identified in the mothers and they did not report ocular symptoms during pregnancy. Serology was negative in all infants for Toxoplasmosis, Rubella, Cytomegalovirus, Syphilis and Human Immunodeficiency Viruses. Ocular findings included macular alterations (gross pigment mottling and/or chorioretinal atrophy) in fifteen eyes (75.0%), and optic nerve abnormalities (hypoplasia with double-ring sign, pallor, and/or increased cup-to-disk ratio) in nine eyes (45.0%). + Patients presented normal anterior segment and important macular and optic nerve abnormalities. Further studies will assess the visual significance of these alterations. + + + + Ventura + Camila V + CV + + Fundação Altino Ventura, Recife, PE, Brazil. + + + + Maia + Mauricio + M + + Department of Ophthalmology and Visual Sciences, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. + + + + Ventura + Bruna V + BV + + Fundação Altino Ventura, Recife, PE, Brazil. + + + + Linden + Vanessa Van Der + VV + + Hospital Barão de Lucena, Recife, PE, Brazil. + + + + Araújo + Eveline B + EB + + Fundação Altino Ventura, Recife, PE, Brazil. + + + + Ramos + Regina C + RC + + Hospital Universitário Oswaldo Cruz, Recife, PE, Brazil. + + + + Rocha + Maria Angela W + MA + + Hospital Universitário Oswaldo Cruz, Recife, PE, Brazil. + + + + Carvalho + Maria Durce C G + MD + + Hospital Universitário Oswaldo Cruz, Recife, PE, Brazil. + + + + Belfort + Rubens + R + Jr + + Department of Ophthalmology and Visual Sciences, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. + + + + Ventura + Liana O + LO + + Fundação Altino Ventura, Recife, PE, Brazil. + + + + eng + + Journal Article + +
+ + Brazil + Arq Bras Oftalmol + 0400645 + 0004-2749 + + IM + + + Adult + + + Brazil + + + Eye Abnormalities + pathology + virology + + + Female + + + Fundus Oculi + + + Humans + + + Infant, Newborn + + + Macula Lutea + abnormalities + + + Male + + + Microcephaly + virology + + + Ophthalmoscopy + methods + + + Optic Nerve + abnormalities + + + Pregnancy + + + Pregnancy Complications, Infectious + virology + + + Zika Virus Infection + complications + + +
+ + + + 2016 + 01 + 15 + + + 2016 + 01 + 17 + + + 2016 + 2 + 4 + 6 + 0 + + + 2016 + 2 + 4 + 6 + 0 + + + 2016 + 11 + 1 + 6 + 0 + + + ppublish + + 26840156 + S0004-27492016000100002 + 10.5935/0004-2749.20160002 + + +
+ + + + + 26820244 + + 2016 + 05 + 31 + + + 2016 + 01 + 29 + +
+ + 1545-861X + + 65 + 3 + + 2016 + Jan + 29 + + + MMWR. Morbidity and mortality weekly report + MMWR Morb. Mortal. Wkly. Rep. + + Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015. + + 59-62 + + 10.15585/mmwr.mm6503e2 + + In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear, and using insect repellents when outdoors. Pregnant and lactating women can use all U.S. Environmental Protection Agency (EPA)-registered insect repellents according to the product label. + + + + Schuler-Faccini + Lavinia + L + + + Ribeiro + Erlane M + EM + + + Feitosa + Ian M L + IM + + + Horovitz + Dafne D G + DD + + + Cavalcanti + Denise P + DP + + + Pessoa + André + A + + + Doriqui + Maria Juliana R + MJ + + + Neri + Joao Ivanildo + JI + + + Neto + Joao Monteiro de Pina + JM + + + Wanderley + Hector Y C + HY + + + Cernach + Mirlene + M + + + El-Husny + Antonette S + AS + + + Pone + Marcos V S + MV + + + Serao + Cassio L C + CL + + + Sanseverino + Maria Teresa V + MT + + + Brazilian Medical Genetics Society–Zika Embryopathy Task Force + + + eng + + Journal Article + + + 2016 + 01 + 29 + +
+ + United States + MMWR Morb Mortal Wkly Rep + 7802429 + 0149-2195 + + IM + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant, Newborn + + + Microcephaly + epidemiology + virology + + + Pregnancy + + + Pregnancy Complications, Infectious + epidemiology + + + Zika Virus Infection + epidemiology + + +
+ + + + 2016 + 1 + 29 + 6 + 0 + + + 2016 + 1 + 29 + 6 + 0 + + + 2016 + 6 + 1 + 6 + 0 + + + epublish + + 26820244 + 10.15585/mmwr.mm6503e2 + + +
+ + + + + 26775125 + + 2016 + 04 + 01 + + + 2016 + 02 + 04 + +
+ + 1474-547X + + 387 + 10015 + + 2016 + Jan + 16 + + + Lancet (London, England) + Lancet + + Zika virus in Brazil and macular atrophy in a child with microcephaly. + + 228 + + 10.1016/S0140-6736(16)00006-4 + S0140-6736(16)00006-4 + + + Ventura + Camila V + CV + + Altino Ventura Foundation, Recife, Brazil; Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil. + + + + Maia + Mauricio + M + + Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil. + + + + Bravo-Filho + Vasco + V + + Altino Ventura Foundation, Recife, Brazil; HOPE Eye Hospital, Recife, Brazil. + + + + Góis + Adriana L + AL + + Altino Ventura Foundation, Recife, Brazil; HOPE Eye Hospital, Recife, Brazil. + + + + Belfort + Rubens + R + Jr + + Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil. Electronic address: clinbelf@uol.com.br. + + + + eng + + Letter + + + 2016 + 01 + 08 + +
+ + England + Lancet + 2985213R + 0140-6736 + + AIM + IM + + + Atrophy + + + Brazil + epidemiology + + + Female + + + Humans + + + Infant + + + Macula Lutea + pathology + + + Male + + + Microcephaly + diagnosis + etiology + virology + + + Retinal Diseases + diagnosis + etiology + virology + + + Zika Virus + + + Zika Virus Infection + complications + diagnosis + + +
+ + + + 2016 + 1 + 18 + 6 + 0 + + + 2016 + 1 + 18 + 6 + 0 + + + 2016 + 4 + 2 + 6 + 0 + + + ppublish + + 26775125 + S0140-6736(16)00006-4 + 10.1016/S0140-6736(16)00006-4 + + +
+ + + + + 26774331 + + 2016 + 12 + 13 + + + 2016 + 12 + 30 + +
+ + 1769-714X + + 18 + 3 + + 2016 + Mar + + + Microbes and infection + Microbes Infect. + + Autophagy and viral diseases transmitted by Aedes aegypti and Aedes albopictus. + + 169-71 + + 10.1016/j.micinf.2015.12.006 + S1286-4579(16)00004-6 + + Despite a long battle that was started by Oswaldo Cruz more than a century ago, in 1903, Brazil still struggles to fight Aedes aegypti and Aedes albopictus, the mosquito vectors of dengue virus (DENV), Chikungynya virus (CHIKV) and Zika virus (ZIKV). Dengue fever has been a serious public health problem in Brazil for decades, with recurrent epidemic outbreaks occurring during summers. In 2015, until November, 1,534,932 possible cases were reported to the Ministry of Healthv. More recently, the less studied CHIKV and ZIKV have gained attention because of a dramatic increase in their incidence (around 400% for CHIKV) and the association of ZIKV infection with a 11-fold increase in the number of cases of microcephaly from 2014 to 2015 in northeast Brazil (1761 cases until December 2015). The symptoms of these three infections are very similar, which complicates the diagnosis. These include fever, headache, nausea, fatigue, and joint pain. In some cases, DENV infection develops into dengue hemorrhagic fever, a life threatening condition characterized by bleeding and decreases in platelet numbers in the blood. As for CHIKV, the most important complication is joint pain, which can last for months. + Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. + + + + Carneiro + Leticia A M + LA + + Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: leticiac@micro.ufrj.br. + + + + Travassos + Leonardo H + LH + + Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: leo.travassos@biof.ufrj.br. + + + + eng + + Editorial + Research Support, Non-U.S. Gov't + + + 2016 + 01 + 14 + +
+ + France + Microbes Infect + 100883508 + 1286-4579 + + IM + + + Aedes + virology + + + Animals + + + Autophagy + + + Brazil + epidemiology + + + Chikungunya Fever + epidemiology + transmission + + + Dengue + epidemiology + transmission + + + Disease Transmission, Infectious + prevention & control + + + Host-Pathogen Interactions + + + Humans + + + Incidence + + + Insect Vectors + + + Zika Virus Infection + epidemiology + transmission + + + + Aedes aegypti + Autophagy + Chikungynya virus + Dengue virus + Zika virus + +
+ + + + 2015 + 12 + 22 + + + 2015 + 12 + 24 + + + 2016 + 1 + 18 + 6 + 0 + + + 2016 + 1 + 18 + 6 + 0 + + + 2016 + 12 + 15 + 6 + 0 + + + ppublish + + 26774331 + S1286-4579(16)00004-6 + 10.1016/j.micinf.2015.12.006 + + +
+ + + + + 26731034 + + 2016 + 10 + 05 + + + 2017 + 01 + 03 + +
+ + 1469-0705 + + 47 + 1 + + 2016 + Jan + + + Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology + Ultrasound Obstet Gynecol + + Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? + + 6-7 + + 10.1002/uog.15831 + + + Oliveira Melo + A S + AS + + Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ), Instituto de Saúde Elpidio de Almeida (ISEA), Campina Grande, Brazil. + + + + Malinger + G + G + + Division of Ultrasound in Obstetrics & Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. + + + + Ximenes + R + R + + Fetal Medicine Foundation Latinamerica - FMFLA, Centrus - Fetal Medicine, Campinas, Brazil. + + + + Szejnfeld + P O + PO + + FIDI - Fundação Instituto de Ensino e Pesquisa em Diagnóstico por Imagem, Departamento de Diagnóstico por Imagem -DDI- UNIFESP, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil. + + + + Alves Sampaio + S + S + + Laboratório de Flavivírus, Instituto Oswaldo Cruz - FIOCRUZ, Rio de Janeiro, Brazil. + + + + Bispo de Filippis + A M + AM + + Laboratório de Flavivírus, Instituto Oswaldo Cruz - FIOCRUZ, Rio de Janeiro, Brazil. + + + + eng + + Case Reports + Journal Article + +
+ + England + Ultrasound Obstet Gynecol + 9108340 + 0960-7692 + + IM + + + Ultrasound Obstet Gynecol. 2016 Apr;47(4):525-6 + 26947268 + + + + + Brain + abnormalities + + + Brazil + + + Calcinosis + diagnostic imaging + + + Female + + + Humans + + + Microcephaly + diagnostic imaging + + + Nervous System Malformations + diagnostic imaging + + + Pregnancy + + + Pregnancy Complications, Infectious + diagnosis + diagnostic imaging + + + Ultrasonography, Prenatal + + + Zika Virus Infection + diagnosis + diagnostic imaging + + +
+ + + + 2016 + 1 + 6 + 6 + 0 + + + 2016 + 1 + 6 + 6 + 0 + + + 2016 + 10 + 7 + 6 + 0 + + + ppublish + + 26731034 + 10.1002/uog.15831 + + +
+ + + + + 26723756 + + 2016 + 07 + 06 + + + 2016 + 02 + 12 + +
+ + 1474-4457 + + 16 + 2 + + 2016 + Feb + + + The Lancet. Infectious diseases + Lancet Infect Dis + + A new mosquito-borne threat to pregnant women in Brazil. + + 156-7 + + 10.1016/S1473-3099(15)00548-4 + S1473-3099(15)00548-4 + + + Triunfol + Marcia + M + + + eng + + Journal Article + + + 2015 + 12 + 24 + +
+ + United States + Lancet Infect Dis + 101130150 + 1473-3099 + + IM + + + Animals + + + Brazil + + + Culicidae + virology + + + Female + + + Humans + + + Insect Vectors + virology + + + Microcephaly + virology + + + Pregnancy + + + Pregnant Women + + + Zika Virus + + + Zika Virus Infection + transmission + + +
+ + + + 2016 + 1 + 3 + 6 + 0 + + + 2016 + 1 + 3 + 6 + 0 + + + 2016 + 7 + 7 + 6 + 0 + + + ppublish + + 26723756 + S1473-3099(15)00548-4 + 10.1016/S1473-3099(15)00548-4 + + +
+ +
\ No newline at end of file diff --git a/easyPM_example01.xml b/easyPM_example01.xml new file mode 100644 index 0000000..5d4dd3f --- /dev/null +++ b/easyPM_example01.xml @@ -0,0 +1,3 @@ + + +279148572017021620171225
1873-64242212017FebEnvironmental pollution (Barking, Essex : 1987)Environ. Pollut.Imidacloprid induces various toxicological effects related to the expression of 3β-HSD, NR5A1, and OGG1 genes in mature and immature rats.15-25S0269-7491(16)31055-710.1016/j.envpol.2016.08.082This study aimed to evaluate the adverse effects of the insecticide imidacloprid (IMI) on male spermatogenesis, steroidogenesis, and DNA damage in sexually mature and immature rats. Forty male rats (mature and immature) were equally divided into four groups: two mature and two immature groups. IMI groups of both ages were orally administered IMI in corn oil at a concentration of 1 mg/mL for kg BW/day, whereas their respective controls were orally administered corn oil only (1 mL/kg of body weight) daily for 65 days. On day 66, the rats were lightly anesthetized and then euthanized by cervical dislocation. Whole blood was collected for hemogram, serum for hormonal profile, semen for sperm profile, and testes for gene expression and histopathological, and immunohistochemical examinations. The obtained results revealed that both sexually mature and immature rats orally exposed to IMI showed serious abnormalities in sperm morphology and concentrations, with an imbalance of sexual hormones. There were increases in the level of serum 8-hydroxy-2'-deoxyguanosine and in the percentage of comet (tailed) sperm DNA in the IMI-treated groups. The results exhibited the upregulation of a DNA damage tolerance gene (8-oxoguanine glycosylase 1) and downregulation of the activity of steroidogenic genes (nuclear receptor subfamily 5, group A, member 1 and 3β-hydroxysteroid dehydrogenase). Immunohistochemical examination of the B-cell lymphoma 2-associated X apoptotic protein in testicular sections showed various degrees of apoptosis in the spermatogonial cells of the IMI-treated rats compared to the control groups. These damaging effects of IMI were more pronounced in the sexually mature rats than in the immature rats. In conclusion, despite using a low dose of IMI in the present study, there were noticeable harmful consequences on the reproductive system at different stages of sexual maturity in male rats.Copyright © 2016 Elsevier Ltd. All rights reserved.Abdel-Rahman MohamedAmanyADepartment of Forensic Medicine and Toxicology, Clinical Pathology and Biochemistry, Faculty of Veterinary Medicine, Zagazig University, 44511 Zagazig, Egypt. Electronic address: amanyrahman292@yahoo.com.MohamedWafaa A MWAMDepartment of Forensic Medicine and Toxicology, Clinical Pathology and Biochemistry, Faculty of Veterinary Medicine, Zagazig University, 44511 Zagazig, Egypt.KhaterSafaa ISIDepartment of Forensic Medicine and Toxicology, Clinical Pathology and Biochemistry, Faculty of Veterinary Medicine, Zagazig University, 44511 Zagazig, Egypt.engJournal Article20161201
EnglandEnviron Pollut88044760269-74910Imidazoles0Insecticides0Neonicotinoids0Nitro Compounds0Steroidogenic Factor 10steroidogenic factor 1, rat3BN7M937V8imidacloprid3XMK78S47OTestosterone5614-64-28-hydroxyguanine5Z93L87A1RGuanine88847-89-68-oxo-7-hydrodeoxyguanosineEC 1.1.-3-Hydroxysteroid DehydrogenasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-OGG1 protein, ratG9481N71RODeoxyguanosineIM3-Hydroxysteroid DehydrogenasesgeneticsAnimalsBody WeightDNA GlycosylasesgeneticsDeoxyguanosineanalogs & derivativesmetabolismGuanineanalogs & derivativesImidazolestoxicityInsecticidestoxicityMaleNeonicotinoidsNitro CompoundstoxicityRatsSpermatogenesisdrug effectsSpermatozoadrug effectsSteroidogenic Factor 1geneticsTestisdrug effectsTestosteroneblood8-OHdGBaxCometNeonicotinoidSpermatogenesis
201602212016081520160830201612560201721760201612560ppublish27914857S0269-7491(16)31055-710.1016/j.envpol.2016.08.082
279034532018020620180320
1873-4596107201706Free radical biology & medicineFree Radic. Biol. Med.Repair of 8-oxo-7,8-dihydroguanine in prokaryotic and eukaryotic cells: Properties and biological roles of the Fpg and OGG1 DNA N-glycosylases.179-201S0891-5849(16)31078-410.1016/j.freeradbiomed.2016.11.042Oxidatively damaged DNA results from the attack of sugar and base moieties by reactive oxygen species (ROS), which are formed as byproducts of normal cell metabolism and during exposure to endogenous or exogenous chemical or physical agents. Guanine, having the lowest redox potential, is the DNA base the most susceptible to oxidation, yielding products such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2-6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). In DNA, 8-oxoG was shown to be mutagenic yielding GC to TA transversions upon incorporation of dAMP opposite this lesion by replicative DNA polymerases. In prokaryotic and eukaryotic cells, 8-oxoG is primarily repaired by the base excision repair pathway (BER) initiated by a DNA N-glycosylase, Fpg and OGG1, respectively. In Escherichia coli, Fpg cooperates with MutY and MutT to prevent 8-oxoG-induced mutations, the "GO-repair system". In Saccharomyces cerevisiae, OGG1 cooperates with nucleotide excision repair (NER), mismatch repair (MMR), post-replication repair (PRR) and DNA polymerase η to prevent mutagenesis. Human and mouse cells mobilize all these pathways using OGG1, MUTYH (MutY-homolog also known as MYH), MTH1 (MutT-homolog also known as NUDT1), NER, MMR, NEILs and DNA polymerases η and λ, to prevent 8-oxoG-induced mutations. In fact, mice deficient in both OGG1 and MUTYH develop cancer in different organs at adult age, which points to the critical impact of 8-oxoG repair on genetic stability in mammals. In this review, we will focus on Fpg and OGG1 proteins, their biochemical and structural properties as well as their biological roles. Other DNA N-glycosylases able to release 8-oxoG from damaged DNA in various organisms will be discussed. Finally, we will report on the role of OGG1 in human disease and the possible use of 8-oxoG DNA N-glycosylases as therapeutic targets.Copyright © 2017 Elsevier Inc. All rights reserved.BoiteuxSergeSCentre de Biophysique Moléculaire, CNRS, UPR4301, rue Charles Sadron, 45072 Orléans, France. Electronic address: serge.boiteux@cnrs-orleans.fr.CosteFranckFCentre de Biophysique Moléculaire, CNRS, UPR4301, rue Charles Sadron, 45072 Orléans, France.CastaingBertrandBCentre de Biophysique Moléculaire, CNRS, UPR4301, rue Charles Sadron, 45072 Orléans, France. Electronic address: bertrand.castaing@cnrs-orleans.fr.engJournal ArticleReviewResearch Support, Non-U.S. Gov't20161127
United StatesFree Radic Biol Med87091590891-58490Escherichia coli Proteins5614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.2.2.23DNA-Formamidopyrimidine GlycosylaseEC 3.2.2.23DNA-formamidopyrimidine glycosylase, E coliIMAnimalsCarcinogenesisDNA GlycosylasesgeneticsmetabolismDNA RepairDNA-Formamidopyrimidine GlycosylasemetabolismEscherichia coliphysiologyEscherichia coli ProteinsmetabolismGenomic InstabilityGuanineanalogs & derivativesmetabolismHumansMiceMice, KnockoutOxidative StressSaccharomyces cerevisiaephysiology8-oxoguanine8-oxoguanine-DNA glycosylasesBase excision repairFpgGO repair networkOGG1Spontaneous mutationsTherapeutic targets cancer
20160905201611222016112520161236020182760201612260ppublish27903453S0891-5849(16)31078-410.1016/j.freeradbiomed.2016.11.042
278643322017082520180109
1464-3804321201701MutagenesisMutagenesisWeak silica nanomaterial-induced genotoxicity can be explained by indirect DNA damage as shown by the OGG1-modified comet assay and genomic analysis.5-1210.1093/mutage/gew064In a previous study, 15-nm silica nanoparticles (NPs) caused small increases in DNA damage in liver as measured in the in vivo comet and micronucleus assays after intravenous administration to rats at their maximum tolerated dose, a worst-case exposure scenario. Histopathological examination supported a particle-induced, tissue damage-mediated inflammatory response. This study used a targeted approach to provide insight into the mode of action (MoA) by examining transcriptional regulation of genes in liver in a time and dose-dependent manner at 1, 2, 4, 8 and 24 h after intravenous administration of 15-nm silica NPs. DNA damage was assessed using the standard comet assay and hOGG1 glycosylase-modified comet assay that also measures oxidative DNA damage. Potassium bromate, an IARC Class 2B carcinogen that specifically operates via an oxidative stress MoA, was used as a positive control for the hOGG1 comet assay and gave a strong signal in its main target organ, the kidney, while showing less activity in liver. Treatment of rats with silica NPs at 50 mg/kg body weight (bw) caused small, statistically insignificant increases in DNA damage in liver measured by the standard comet assay, while a statistically significant increase was observed at 4 h with the hOGG1 comet assay, consistent with a MoA involving reactive oxygen species. Histopathology showed liver damage and neutrophil involvement while genomic analysis and response pattern of key genes involved in inflammation and oxidative stress supported a tissue damage-mediated inflammatory response involving the complement system for removing/phagocytising damaged cells. No changes were observed for histopathology or gene array for the low-dose (5 mg/kg bw) silica NPs. The results of this study confirm our hypothesis that the weak DNA damage observed by silica NPs occurs secondary to inflammation/immune response, indicating that a threshold can be applied in the risk assessment of these materials.© The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.PfuhlerStefanSDownsThomas RTRAllemangAshley JAJShanYuchingYCrosbyMeredith EMEPresent address: AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.engJournal ArticleResearch Support, Non-U.S. Gov't20161117
EnglandMutagenesis87078120267-83577631-86-9Silicon Dioxide9007-49-2DNAEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdministration, IntravenousAnimalsComet AssayDNAdrug effectsDNA DamageDNA GlycosylasesGene Expression ProfilingInflammationLiverdrug effectsmetabolismMaleNanoparticlesadministration & dosagechemistrytoxicityOxidative Stressdrug effectsRatsSilicon Dioxideadministration & dosagepharmacologytoxicity
20161120602017826602016112060ppublish27864332gew06410.1093/mutage/gew064
278169392017052920171216
1083-351X291512016Dec16The Journal of biological chemistryJ. Biol. Chem.O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts.26515-26528mtDNA damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which can cause mutations when not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). Although the mtDNA repair machinery has been described in cardiac myocytes, the regulation of this repair has been incompletely investigated. Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice. In diabetic hearts, we further observed increased levels of 8-OHdG and an increased amount of mtDNA damage. Interestingly, Ogg1 was found to be highly O-GlcNAcylated in diabetic mice compared with controls. In vitro experiments demonstrated that O-GlcNAcylation inhibits Ogg1 activity, which could explain the mtDNA lesion accumulation observed in vivo Reducing Ogg1 O-GlcNAcylation in vivo by introducing a dominant negative O-GlcNAc transferase mutant (F460A) restored Ogg1 enzymatic activity and, consequently, reduced 8-OHdG and mtDNA damage despite the adverse hyperglycemic milieu. Taken together, our results implicate hyperglycemia-induced O-GlcNAcylation of Ogg1 in increased mtDNA damage and, therefore, provide a new plausible biochemical mechanism for diabetic cardiomyopathy.© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.CividiniFedericoFFrom the Department of Medicine, University of California, San Diego, La Jolla, California 92093-0671 and fcividini@ucsd.edu.ScottBrian TBTFrom the Department of Medicine, University of California, San Diego, La Jolla, California 92093-0671 and.DaiAnzhiAFrom the Department of Medicine, University of California, San Diego, La Jolla, California 92093-0671 and.HanWenlongWFrom the Department of Medicine, University of California, San Diego, La Jolla, California 92093-0671 and.SuarezJorgeJFrom the Department of Medicine, University of California, San Diego, La Jolla, California 92093-0671 and.Diaz-JuarezJulietaJthe Department of Pharmacology, Instituto Nacional de Cardiología, Juan Badiano 41, Barrio Belisario Domínguez Secc XVI, 14080 Tlalpan, DF, Mexico.DiemerTanjaTFrom the Department of Medicine, University of California, San Diego, La Jolla, California 92093-0671 and.CasteelDarren EDEFrom the Department of Medicine, University of California, San Diego, La Jolla, California 92093-0671 and.DillmannWolfgang HWHFrom the Department of Medicine, University of California, San Diego, La Jolla, California 92093-0671 and wdillmann@ucsd.edu.engP01 HL066941HLNHLBI NIH HHSUnited StatesP30 NS047101NSNINDS NIH HHSUnited StatesJournal Article20161105
United StatesJ Biol Chem2985121R0021-92580DNA, MitochondrialEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMLife Sci. 2013 Mar 28;92(11):657-6323000101FASEB J. 2000 Feb;14(2):355-6010657991Annu Rev Biochem. 2007;76:679-9917408359Amino Acids. 2011 Mar;40(3):819-2820676904Proc Natl Acad Sci U S A. 2000 May 23;97(11):5735-910801981J Biol Chem. 1994 Jul 29;269(30):19321-308034696J Biol Chem. 2004 Jul 16;279(29):30133-4215138254J Biol Chem. 2001 Mar 30;276(13):9838-4511148210FASEB J. 2003 Jul;17(10):1195-21412832285Biol Rev Camb Philos Soc. 2004 May;79(2):235-5115191224Life Sci. 2013 Mar 28;92(11):648-5622728715DNA Repair (Amst). 2010 Feb 4;9(2):144-5220042377Aging Cell. 2012 Jun;11(3):439-4822314054J Biol Chem. 2014 Dec 12;289(50):34449-5625336635J Biol Chem. 2003 Nov 7;278(45):44230-712941958J Bioenerg Biomembr. 2011 Feb;43(1):25-921286795Nucleic Acids Res. 2005 Jun 07;33(10):3271-8215942030Toxicol Appl Pharmacol. 2006 Apr 15;212(2):167-7816490224Circ Res. 2005 May 13;96(9):1006-1315817886Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2227-3617208994Am J Physiol Regul Integr Comp Physiol. 2012 Oct 1;303(7):R689-9922874425Biochim Biophys Acta. 2016 Dec;1863(12 ):2977-299227646922Circ Res. 2000 May 12;86(9):960-610807868Curr Protoc Hum Genet. 2009 Jul;Chapter 19:Unit 19.119582765Proc Natl Acad Sci U S A. 1988 Sep;85(17):6465-73413108Exp Gerontol. 2010 Aug;45(7-8):478-8820096766Ann N Y Acad Sci. 2004 Apr;1011:101-1115126288Free Radic Biol Med. 2002 Jun 1;32(11):1102-1512031895Trends Pharmacol Sci. 2011 Mar;32(3):125-3021216018Circ Res. 2007 May 25;100(10):1415-2717525381Mol Cell Biol. 2006 Mar;26(5):1654-6516478987Circ Res. 2010 Jul 23;107(2):171-8520651294J Biol Chem. 2005 Oct 21;280(42):35537-4416105839Proc Natl Acad Sci U S A. 2015 May 12;112(19):6050-525918408J Biol Chem. 1997 Apr 4;272(14):9308-159083067J Biol Chem. 2012 Aug 24;287(35):30024-3422745122Biochem Biophys Res Commun. 2007 Apr 6;355(2):431-717303074BMC Endocr Disord. 2002 Apr 25;2(1):212003641J Biol Chem. 2012 Aug 17;287(34):28882-9722692202Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-99012815J Biol Chem. 1997 Apr 4;272(14):9316-249083068Biochim Biophys Acta. 1999 Feb 9;1410(2):103-2310076021Trends Genet. 1993 Jul;9(7):246-98379000Am J Physiol Cell Physiol. 2014 May 1;306(9):C794-80424553187Proc Natl Acad Sci U S A. 1977 Apr;74(4):1348-52266177J Biol Chem. 1984 Mar 10;259(5):3308-176421821Arch Biochem Biophys. 1995 Feb 1;316(2):909-167864650J Biol Chem. 2009 Jan 2;284(1):547-5519004814Amino Acid SubstitutionAnimalsDNA DamageDNA GlycosylasesgeneticsmetabolismDNA, MitochondrialgeneticsmetabolismDiabetes Mellitus, ExperimentalgeneticsmetabolismpathologyDiabetic CardiomyopathiesgeneticsmetabolismpathologyHyperglycemiageneticsmetabolismpathologyMaleMiceMitochondria, HeartgeneticsmetabolismMutation, MissenseMyocytes, Cardiacmetabolism8-oxoguanine glycosylase (OGG1)cardiomyopathymtDNA; O-linked N-acetylglucosamine (O-GlcNAc)oxidative stresstype 1 diabetes
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1949-25537472016Nov22OncotargetOncotargetSerum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients.77482-7749410.18632/oncotarget.13030To define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy.Our investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue (r2 = 0.639, p < 0.001). The elevated APE1 level in both tissue and serum of patients prior to chemotherapy was associated with worse progression-free survival (HR: 2.165, p < 0.001, HR: 1.421, p = 0.012), but not with overall survival. After 6 cycles of chemotherapy, a low APE1 serum level was associated with better overall survival (HR: 0.497, p = 0.010).We measured APE1 protein levels in biopsy tissue from 172 NSCLC patients and sera of 412 NSCLC patients receiving platinum-based chemotherapy by immunohistochemistry and a newly established sensitive and specific enzyme-linked immunosorbent assay, respectively. APE1 levels in sera of 523 healthy donors were also determined as control.Our studies indicate that APE1 is a biomarker for predicting prognosis and therapeutic efficacy in NSCLC. The chemotherapy-naïve serum APE1 level, which correlated with its tissue level inversely associated with progression-free survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival.ZhangShihengSCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.HeLeLCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.DaiNanNCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.GuanWeiWCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.ShanJinluJCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.YangXueqinXCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.ZhongZhaoyangZCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.QingYiYCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.JinFengFCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.ChenChuanCCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.YangYuxinYCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.WangHongyiHDepartment of Pathology, Baylor University Medical Center, Dallas, TX 75246, USA.BaughLauraLDepartment of Pathology, Baylor University Medical Center, Dallas, TX 75246, USA.TellGianlucaGLaboratory of Molecular Biology and DNA repair, Department of Medical and Biological Sciences, University of Udine, Udine 33100, Italy.WilsonDavid MDM3rdLaboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.LiMengxiaMCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.WangDongDCancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.engJournal Article
United StatesOncotarget1015329651949-25530Biomarkers, Tumor49DFR088MYPlatinumEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMOncotarget. 2015 May 10;6(13):11575-8425865228Mol Cell Proteomics. 2011 Jun;10(6):M110.00533021474795Curr Med Chem. 2012;19(22):3689-70022680928Int J Cancer. 2005 Oct 10;116(6):925-3315856462Biochem Biophys Res Commun. 2013 Jun 7;435(3):403-723665318Nucleic Acids Res. 1998 Jun 1;26(11):2771-89592167Anticancer Res. 2014 Jan;34(1):493-50124403507Lung Cancer. 2009 Dec;66(3):298-30419324449Cancer Chemother Pharmacol. 2014 Oct;74(4):777-8625107571Nat Rev Clin Oncol. 2012 Feb 14;9(3):144-5522330686Gut. 1995 Mar;36(3):455-87698709Cancer Lett. 2005 Dec 18;230(2):187-9816297705PLoS One. 2014 Sep 04;9(9):e10648525188410Cancer Res. 1992 Aug 1;52(15):4168-741322237Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463N Engl J Med. 2013 Mar 21;368(12):1101-1023514287Nature. 2013 Oct 17;502(7471):333-924132290Int J Oncol. 2006 Apr;28(4):995-100216525651Clin Cancer Res. 2002 Mar;8(3):752-811895905PLoS One. 2013;8(3):e5800123472128Cancer Res. 2015 Jun 1;75(11):2133-825931285Oncotarget. 2015 Sep 15;6(27):23383-9826125438Korean Circ J. 2015 Sep;45(5):364-7126413103Cancer Res Treat. 2015 Oct;47(4):823-3325672588Clin Cancer Res. 2011 Nov 15;17(22):6973-8421908578AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy Protocolsadverse effectstherapeutic useBiomarkers, TumorCarcinoma, Non-Small-Cell Lungblooddiagnosisdrug therapymortalityDNA-(Apurinic or Apyrimidinic Site) LyasebloodEnzyme-Linked Immunosorbent AssayFemaleGene ExpressionHumansLung Neoplasmsblooddiagnosisdrug therapymortalityMaleMiddle AgedNeoplasm StagingPlatinumadministration & dosagePrognosisProportional Hazards ModelsROC CurveTreatment OutcomeAPE1NSCLCbiomarkerchemotherapy
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1538-85141511201611Molecular cancer therapeuticsMol. Cancer Ther.Regulation of HIF1α under Hypoxia by APE1/Ref-1 Impacts CA9 Expression: Dual Targeting in Patient-Derived 3D Pancreatic Cancer Models.2722-2732Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality in the United States. Aggressive treatment regimens have not changed the disease course, and the median survival has just recently reached a year. Several mechanisms are proposed to play a role in PDAC therapeutic resistance, including hypoxia, which creates a more aggressive phenotype with increased metastatic potential and impaired therapeutic efficacy. AP Endonuclease-1/Redox Effector Factor 1 (APE1/Ref-1) is a multifunctional protein possessing a DNA repair function in base excision repair and the ability to reduce oxidized transcription factors, enabling them to bind to their DNA target sequences. APE1/Ref-1 regulates several transcription factors involved in survival mechanisms, tumor growth, and hypoxia signaling. Here, we explore the mechanisms underlying PDAC cell responses to hypoxia and modulation of APE1/Ref-1 redox signaling activity, which regulates the transcriptional activation of hypoxia-inducible factor 1 alpha (HIF1α). Carbonic anhydrase IX (CA9) is regulated by HIF1α and functions as a part of the cellular response to hypoxia to regulate intracellular pH, thereby promoting cell survival. We hypothesized that modulating APE1/Ref-1 function will block activation of downstream transcription factors, STAT3 and HIF1α, interfering with the hypoxia-induced gene expression. We demonstrate APE1/Ref-1 inhibition in patient-derived and established PDAC cells results in decreased HIF1α-mediated induction of CA9. Furthermore, an ex vivo three-dimensional tumor coculture model demonstrates dramatic enhancement of APE1/Ref-1-induced cell killing upon dual targeting of APE1/Ref-1 and CA9. Both APE1/Ref-1 and CA9 are under clinical development; therefore, these studies have the potential to direct novel PDAC therapeutic treatment. Mol Cancer Ther; 15(11); 2722-32. ©2016 AACR.©2016 American Association for Cancer Research.LogsdonDerek PDPDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana.GrimardMichelleMDepartment of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.LuoMeihuaMDepartment of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.ShahdaSafiSDivision of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.Pancreatic Cancer Signature Center, Indianapolis, Indiana.JiangYanlinYDepartment of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.TongYanYDepartment of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana.YuZhangshengZDepartment of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana.ZyromskiNicholasNPancreatic Cancer Signature Center, Indianapolis, Indiana.Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana.SchipaniErnestinaEDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan.CartaFabrizioFNeurofarba Department, Section of Medicinal Chemistry, University of Florence, Florence, Italy.SupuranClaudiu TCTNeurofarba Department, Section of Medicinal Chemistry, University of Florence, Florence, Italy.KorcMurrayMPancreatic Cancer Signature Center, Indianapolis, Indiana.Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.IvanMirceaMDivision of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.Pancreatic Cancer Signature Center, Indianapolis, Indiana.Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana.KelleyMark RMRDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana.Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.Pancreatic Cancer Signature Center, Indianapolis, Indiana.Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.FishelMelissa LMLDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana. mfishel@iu.edu.Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.Pancreatic Cancer Signature Center, Indianapolis, Indiana.engR21 CA122298CANCI NIH HHSUnited StatesR37 CA075059CANCI NIH HHSUnited StatesUL1 TR001108TRNCATS NIH HHSUnited StatesR01 CA075059CANCI NIH HHSUnited StatesR01 AR065403ARNIAMS NIH HHSUnited StatesR01 CA167291CANCI NIH HHSUnited StatesR21 NS091667NSNINDS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20160817
United StatesMol Cancer Ther1011325351535-71630Antigens, Neoplasm0Hypoxia-Inducible Factor 1, alpha Subunit0STAT3 Transcription FactorEC 4.2.1.1CA9 protein, humanEC 4.2.1.1Carbonic Anhydrase IXEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCancer Cell. 2009 Sep 8;16(3):259-6619732725Antioxid Redox Signal. 2008 Nov;10(11):1853-6718627350Biochemistry. 2013 Apr 30;52(17):2955-6623597102Oncology (Williston Park). 2014 Jan;28(1):70-424683721Clin Cancer Res. 2012 Jun 1;18(11):3100-1122498007Vision Res. 2011 Jan;51(1):93-10020937296DNA Repair (Amst). 2011 Sep 5;10(9):942-5221741887Biochemistry. 2011 Jan 11;50(1):82-9221117647Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Methods. 2001 Dec;25(4):402-811846609Crit Rev Oncol Hematol. 2015 Sep;95(3):318-3625921418Front Pharmacol. 2013 Apr 30;4:5623641216Exp Hematol. 2010 Dec;38(12 ):1178-8820826193Mol Cancer Ther. 2011 Sep;10(9):1698-70821700832Cancer Res. 2015 Jan 1;75(1):111-925385028Acta Pharm Sin B. 2015 Sep;5(5):378-8926579469Cancer Cell. 2014 Jun 16;25(6):735-4724856585J Enzyme Inhib Med Chem. 2016;31(3):345-6026619898Redox Biol. 2014 Feb 21;2:485-9424624338Aliment Pharmacol Ther. 2003 Oct 15;18(8):837-4614535878Mutat Res. 2015 Sep;779:96-10426164266Front Nutr. 2015 Mar 27;2:1025988138Cancer Invest. 2010 Nov;28(9):885-9520919954J Biol Chem. 2008 Jul 18;283(29):20473-8318482982Semin Oncol. 2015 Feb;42(1):19-2725726049Front Physiol. 2014 Jan 08;4:40024409151Biochemistry. 2012 Jan 17;51(2):695-70522148505Biochem Pharmacol. 2010 Aug 15;80(4):455-6220488164Sci Signal. 2013 Apr 02;6(269):pl123550210Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Histochem Cell Biol. 2000 Sep;114(3):197-20411083462Toxicol Pathol. 2012;40(1):18-3222131108Cancer Biol Ther. 2011 Aug 1;12(3):198-20721613822World J Gastroenterol. 2014 Aug 28;20(32):11216-2925170206Mol Cancer Ther. 2008 Jul;7(7):2012-2118645011Molecules. 2015 Nov 19;20(11):20551-6826610437Biochim Biophys Acta. 2014 Aug;1846(1):152-6024821201Oncotarget. 2014 Nov 30;5(22):10969-7525473891BMC Bioinformatics. 2006 Feb 22;7:8516504059Oncotarget. 2012 Jan;3(1):84-9722289741Cancer Biol Ther. 2008 Jun;7(6):882-818344687Cancer Metastasis Rev. 2015 Mar;34(1):97-11425566685Cell. 2012 Mar 30;149(1):63-7422464323Science. 2008 Sep 26;321(5897):1801-618772397Nat Cell Biol. 2000 Jul;2(7):423-710878807Mol Carcinog. 2016 May;55(5):688-70425865359PLoS One. 2013;8(2):e5531323418439Clin Cancer Res. 2012 Aug 15;18(16):4266-7622896693J Biol Chem. 2013 Jul 19;288(29):21197-20723740244Oncogene. 2014 Mar 27;33(13):1670-923604114Biochim Biophys Acta. 2009 Apr;1795(2):162-7219344680Clin Exp Metastasis. 2012 Aug;29(6):615-2422484976Cancer Discov. 2012 May;2(5):401-422588877Cancer Res. 2003 May 15;63(10):2649-5712750293DNA Repair (Amst). 2009 Nov 2;8(11):1273-8219726241Future Oncol. 2014 May;10(7):1215-3724947262Expert Opin Drug Discov. 2015 Jun;10 (6):591-725891195J Biol Chem. 2015 Jan 30;290(5):3057-6825492865Subcell Biochem. 2014;75:181-9824146380Cell Death Dis. 2014 Feb 20;5:e106524556680Front Physiol. 2014 Apr 09;5:14124782785Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463Mol Cancer Ther. 2016 May;15(5):794-80526873728ACS Chem Biol. 2016 Feb 19;11(2):308-1826730496Cancer Res. 2015 Jul 15;75(14):2800-1025979873PLoS One. 2012;7(10):e4746223094050Antigens, NeoplasmgeneticsCarbonic Anhydrase IXgeneticsCarcinoma, Pancreatic Ductaldrug therapygeneticsmetabolismpathologyCell Line, TumorCell Proliferationdrug effectsCell Survivaldrug effectsgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismGene Expression Regulation, Neoplasticdrug effectsHumansHypoxiageneticsmetabolismHypoxia-Inducible Factor 1, alpha SubunitgeneticsmetabolismOxidation-ReductionPancreatic Neoplasmsdrug therapygeneticsmetabolismpathologyProtein BindingSTAT3 Transcription FactormetabolismSignal Transductiondrug effectsSpheroids, CellularTranscription, GeneticTumor Cells, CulturedMark R. Kelley has licensed APX3330 though Indiana University Research & Technology Corporation to ApeX Therapeutics.
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278022072017011820170118
1875-85921732016Sep26Cancer biomarkers : section A of Disease markersCancer BiomarkAPE1 overexpression promotes the progression of ovarian cancer and serves as a potential therapeutic target.313-322Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme that is involved in DNA repair and the redox regulation of transcription factors. Blocking these functions leads to cell-growth inhibition, apoptosis and other effects. Previous studies have demonstrated that high expression levels of the APE1 protein are associated with the progression and chemoresistance of cancers. We hypothesized that APE1 silencing in ovarian cancer cells might have anticancer effects mediated by cell-growth inhibition and an increase in drug-sensitivity.In this study, we explored the consequences of APE1 silencing in ovarian cancer cells.Immunohistochemistry (IHC) was used to detect the APE1 protein levels in tissue samples from twelve ovarian cancer (OC) patients and eleven non-OC patients. APE1 knockdown was achieved via the stable transfection of SKOV3 and A2780 cells with a construct encoding a short hairpin DNA directed against the APE1 gene. Then, cell proliferation, colony formation, cell cycle and apoptosis assays were performed to reveal the consequences of APE1 silencing in ovarian cancer cells. Additionally, the SKOV3 and A2780 cells were subjected to the treatment with camptothecin (CPT) and ultraviolet rays (UV) to assess the possible link between the APE1 protein and drug-resistance.Our results revealed that the APE1 protein was overexpressed in OC tissues. APE1 knockdown in A2780 and SKOV3 cells reduced cell proliferation, arrested cell cycle progression, repressed colony formation and weakly promoted cell apoptosis through the BAX and BCL-2 apoptotic pathways. Additionally, the down-regulation of APE1 significantly enhanced the sensitivity of ovarian cancer cells to the CPT/UV treatment.Our study suggested that the APE1 protein is important for the proliferation and growth of ovarian cancer cells. APE1 silencing might enhance drug-sensitivity, and thus APE1 might serve as a novel anti-OC therapeutic target.WenXuemeiXDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.LuRenquanRDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.XieSuhongSDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.ZhengHuiHDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.WangHonglingHDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.WangYanchunYDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.SunJiajunJDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.GaoXiangXDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.GuoLinLDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.engJournal Article
NetherlandsCancer Biomark1012565091574-01530Histones0RNA, Messenger0RNA, Small InterferingEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMApoptosisgeneticsCell CyclegeneticsCell Line, TumorCell ProliferationDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsgeneticsmetabolismDisease ProgressionFemaleGene ExpressionGene Knockdown TechniquesHistonesmetabolismHumansOvarian NeoplasmsgeneticspathologyRNA InterferenceRNA, MessengergeneticsRNA, Small InterferinggeneticsApurinic/apyrimidinic endonuclease 1apoptosisovarian cancerproliferation
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1551-400515222016Nov16Cell cycle (Georgetown, Tex.)Cell CycleNovel protective mechanism of reducing renal cell damage in diabetes: Activation AMPK by AICAR increased NRF2/OGG1 proteins and reduced oxidative DNA damage.3048-3059Exposure of renal cells to high glucose (HG) during diabetes has been recently proposed to be involved in renal injury. In the present study, we investigated a potential mechanism by which AICAR treatment regulates the DNA repair enzyme, 8-oxoG-DNA glycosylase (OGG1) in renal proximal tubular mouse cells exposed to HG and in kidney of db/db mice. Cells treated with HG for 2 days show inhibition in OGG1 promoter activity as well as OGG1 and Nrf2 protein expression. In addition, activation of AMPK by AICAR resulted in an increase raptor phosphorylation at Ser792 and leads to increase the promoter activity of OGG1 through upregulation of Nrf2. Downregulation of AMPK by DN-AMPK and raptor and Nrf2 by siRNA resulted in significant decease in promoter activity and protein expression of OGG1. On the other hand, downregulation of Akt by DN-Akt and rictor by siRNA resulted in significant increase in promoter activity and protein expression of Nrf2 and OGG1. Moreover, gel shift analysis shows reduction of Nrf2 binding to OGG1 promoter in cells treated with HG while cells treated with AICAR reversed the effect of HG. Furthermore, db/db mice treated with AICAR show significant increased in AMPK and raptor phosphroylation as well as OGG1 and Nrf2 protein expression that associated with significant decrease in oxidative DNA damage (8-oxodG) compared to non-treated mice. In summary, our data provide a novel protective mechanism by which AICAR prevents renal cell damage in diabetes and the consequence complications of hyperglycemia with a specific focus on nephropathy.HabibSamy LSLa Department of Cellular and Structural Biology , University of Texas Health Science Center , San Antonio , TX , USA.b Geriatric Research, Education and Clinical Department , South Texas Veterans Health Care System , San Antonio , TX , USA.YadavAnamikaAa Department of Cellular and Structural Biology , University of Texas Health Science Center , San Antonio , TX , USA.KidaneDawitDc Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute , Austin , TX , USA.WeissRobert HRHd Division of Nephrology and Cancer Center, University of California at Davis , Davis , CA , USA.LiangSitaiSa Department of Cellular and Structural Biology , University of Texas Health Science Center , San Antonio , TX , USA.engJournal Article20160909
United StatesCell Cycle1011378411551-40050Adaptor Proteins, Signal Transducing0Carrier Proteins0Multiprotein Complexes0NF-E2-Related Factor 20RNA, Messenger0Rapamycin-Insensitive Companion of mTOR Protein0Regulatory-Associated Protein of mTOR0Ribonucleotides0Rptor protein, mouse0rictor protein, mouse360-97-4Aminoimidazole CarboxamideEC 2.7.1.1TOR Serine-Threonine KinasesEC 2.7.11.1Mechanistic Target of Rapamycin Complex 1EC 2.7.11.1Proto-Oncogene Proteins c-aktEC 2.7.11.31AMP-Activated Protein KinasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseF0X88YW0YKAICA ribonucleotideIY9XDZ35W2GlucoseIMDNA Repair (Amst). 2006 Nov 8;5(11):1337-4516861056Am J Physiol Renal Physiol. 2008 Jan;294(1):F281-9017989114Curr Opin Clin Nutr Metab Care. 2002 Sep;5(5):561-812172481Am J Pathol. 2006 May;168(5):1443-5116651612Mol Cell Biol. 2005 Nov;25(21):9554-7516227605Biochem Biophys Res Commun. 1997 Jul 18;236(2):313-229240432Diabetologia. 2008 Oct;51(10):1761-418696044J Am Soc Nephrol. 2012 Oct;23(10):1652-6222904348Diabetologia. 2002 Jun;45(6):877-8212107732Diabetologia. 2002 Jan;45(1):85-9611845227Diabetes Care. 2003 May;26(5):1507-1212716813Carcinogenesis. 2003 Mar;24(3):573-8212663520Diabetes. 2010 Jun;59(6):1386-9620299472Diabetes. 2005 Jun;54(6):1615-2515919781Biochem Biophys Res Commun. 2002 Jun 21;294(4):798-80512061777Mol Cancer. 2008 Jan 24;7:1018218111Nature. 2001 Dec 13;414(6865):813-2011742414Eur J Cancer. 2010 Oct;46(15):2806-2020656472Mutat Res. 2000 Oct 16;461(2):109-1811018584J Am Soc Nephrol. 2003 Aug;14(8 Suppl 3):S241-512874439Am J Physiol Endocrinol Metab. 2013 Jan 1;304(1):E87-9923132297Diabetes. 2008 Oct;57(10):2626-3618599524Mol Cell Biol. 2010 Feb;30(4):908-2119995915Mutat Res. 2004 Sep;567(1):1-6115341901Diabetes Obes Metab. 2011 Dec;13(12):1097-10421733059Am J Physiol Renal Physiol. 2006 Jul;291(1):F162-7516467130Anal Biochem. 1976 May 7;72:248-54942051Mol Cell Biol. 2009 Jul;29(14):3991-400119451232Carcinogenesis. 2010 Nov;31(11):2022-3020837600J Biol Chem. 2005 Aug 12;280(32):29158-6815901726Cell Biochem Biophys. 2007;47(3):332-4717652779Mol Cell Biol. 2006 Jul;26(14 ):5336-4716809770Diabetologia. 2008 Oct;51(10):1893-90018709353Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12932-719625624AMP-Activated Protein KinasesmetabolismAdaptor Proteins, Signal TransducingmetabolismAminoimidazole Carboxamideanalogs & derivativespharmacologyAnimalsBase SequenceCarrier ProteinsmetabolismDNA DamageDNA GlycosylasesgeneticsmetabolismDiabetes MellituspathologyDown-Regulationdrug effectsEnzyme Activationdrug effectsGlucosepharmacologyHEK293 CellsHumansKidneypathologyKidney Tubules, Proximaldrug effectspathologyMechanistic Target of Rapamycin Complex 1MiceModels, BiologicalMultiprotein ComplexesmetabolismNF-E2-Related Factor 2metabolismOxidative Stressdrug effectsPromoter Regions, GeneticProtein Bindingdrug effectsProto-Oncogene Proteins c-aktmetabolismRNA, MessengergeneticsmetabolismRapamycin-Insensitive Companion of mTOR ProteinRegulatory-Associated Protein of mTORRibonucleotidespharmacologyTOR Serine-Threonine KinasesmetabolismUp-Regulationdrug effectsAICARAMPKNrf2OGG1diabetesmTOR
2016102160201762060201691060ppublish2761108510.1080/15384101.2016.1231259PMC5134712
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1471-24151612016Sep29BMC ophthalmologyBMC OphthalmolAssociation between polymorphisms of OGG1, EPHA2 and age-related cataract risk: a meta-analysis.168Evidences have identified the correlation of 8-oxoguanine DNA glycosylase-1 (OGG1) and eph-receptor tyrosine kinase-type A2 (EPHA2) polymorphisms in age-related cataract (ARC) risk. However, the results were not consistent. The objective of this study was to examine the role of these two gene polymorphisms in ARC susceptibility.Eligible case-control studies published between January 2000 and 2015 were searched and retrieved in the electronic databases. The odds ratio with 95 % confidence interval (CI) was employed to calculate the strength of the relationship.We totally screened out six articles, including 5971 cataract patients and 4189 matched controls. Three variants were contained (OGG1 rs1052133; EPHA2 rs7543472 and rs11260867). For OGG1 rs1052133, we detected a significant correlation between OGG1 polymorphism and ARC risk under the heterogenous model (CG vs. CC: OR = 1.34, 95 % CI = 1.06-1.70, P = 0.01) and dominant model (GG+CG vs. CC: OR = 1.45, 95 % CI = 1.16-1.81, P = 0.001), especially in patients with cortical cataract of subgroup analysis by phenotypes (P < 0.05). For EPHA2 rs7543472 and rs11260867, we did not find a positive association between these two mutations and ARC susceptibility in total cases. Subgroup analysis by phenotypes of cataract showed that only in cortical cataract, genotypes of rs7543472 under the allele model, homogenous model and recessive model; genotypes of rs11260867 under the heterogenous model and dominant model were associated with ARC risk.OGG1 rs1052133 (CG and CG+GG genotypes) might be risk factor for ARC, particularly in cortical cataract risk. EPHA2 rs7543472 (T allele and TT genotype) and rs11260867 (CG and GG+CG genotypes) might be associated with cortical cataract.ZhangHongxuHDepartment of Ophtalmology, Hangzhou First People's Hospital, Hangzhou Hospital Affiliated to Nanjing Medical University, Huansha Road No. 261, Hangzhou, 310006, Zhejiang, People's Republic of China.ZhongJianguangJDepartment of Ophtalmology, Hangzhou First People's Hospital, Hangzhou Hospital Affiliated to Nanjing Medical University, Huansha Road No. 261, Hangzhou, 310006, Zhejiang, People's Republic of China.BianZhenyuZDepartment of Orthopaedics, Hangzhou First People's Hospital, Hangzhou Hospital Affiliated to Nanjing Medical University, Hangzhou, 310006, Zhejiang, People's Republic of China.FangXiangXDepartment of Central Laboratory, Hangzhou First People's Hospital, Hangzhou Hospital Affiliated to Nanjing Medical University, Hangzhou, 310006, Zhejiang, People's Republic of China.PengYouYDepartment of Surgical Oncology, Hangzhou First People's Hospital, Hangzhou Hospital Affiliated to Nanjing Medical University, Hangzhou, 310006, Zhejiang, People's Republic of China.HuYongpingYDepartment of Ophtalmology, Hangzhou First People's Hospital, Hangzhou Hospital Affiliated to Nanjing Medical University, Huansha Road No. 261, Hangzhou, 310006, Zhejiang, People's Republic of China. huypkf@163.com.engJournal Article20160929
EnglandBMC Ophthalmol1009678021471-2415Antioxid Redox Signal. 2014 Feb 1;20(4):708-2623901781Br J Ophthalmol. 2012 May;96(5):614-822133988Mol Vis. 2014 May 21;20:661-924868140PLoS One. 2012;7(8):e4212022916121J Biol Chem. 2014 Jul 11;289(28):19694-70324825902Acta Ophthalmol. 2010 May;88(3):358-6619222399Mutagenesis. 2012 Jul;27(4):501-1022451681Annu Rev Pharmacol Toxicol. 2015;55:465-8725292427Mol Vis. 2010 Mar 24;16:511-720361013Age (Dordr). 2013 Dec;35(6):2435-4423334603PLoS Genet. 2009 Jul;5(7):e100058419649315ACS Chem Biol. 2015 Oct 16;10(10):2334-4326218629PLoS One. 2012;7(5):e3656422570727Mol Vis. 2009 Nov 24;15:2448-6319956408Curr Eye Res. 2015;40(8):815-2125310012Brain Res Mol Brain Res. 1995 Apr;29(2):325-357609620Ophthalmology. 2012 May;119(5):900-622306120Hum Mutat. 2009 May;30(5):E603-1119306328Mol Vis. 2008;14:2042-5519005574Free Radic Biol Med. 2013 Oct;63:401-923726996Exp Eye Res. 2015 Jun;135:102-825660075Cancer Res. 2016 Jan 1;76(1):30-426586787PLoS One. 2012;7(3):e3300122412971Cancer Res. 2015 Aug 15;75(16):3327-3926130649Curr Eye Res. 2015 Apr;40(4):378-8524911554J Cell Sci. 2013 Mar 15;126(Pt 6):1488-9723378024Annu Rev Public Health. 1996;17:159-778724222Sci China Life Sci. 2012 May;55(5):434-4322645087Invest Ophthalmol Vis Sci. 2013 Dec 13;54(14):ORSF5-ORSF1324335069Rev Prat. 2013 Jan;63(1):43-723457826Invest Ophthalmol Vis Sci. 2013 Feb 01;54(2):1201-723322570Ophthalmology. 2012 Dec;119(12):2463-7022921386Mol Vis. 2011;17:1553-821686326Oncogene. 1998 Jun 25;16(25):3219-259681819Invest Ophthalmol Vis Sci. 2013 Apr 26;54(4):3010-823572101Expert Opin Ther Targets. 2011 Jan;15(1):31-5121142802Ophthalmic Genet. 2016;37(1):14-824673449DNA Repair (Amst). 2013 Dec;12(12):1094-10424075420Ophthalmic Epidemiol. 2007 Jul-Aug;14(4):173-817896293Ophthalmology. 2015 Nov;122(11):2179-8526278859PLoS One. 2013 Aug 16;8(8):e7100323976972Invest Ophthalmol Vis Sci. 2013 Sep 05;54(9):5989-9423887802Antioxid Redox Signal. 2014 Aug 10;21(5):700-424527727Ophthalmology. 2015 Nov;122(11):2169-7826256834PLoS One. 2013 Aug 27;8(8):e7251824014202Dis Markers. 2015;2015:69087826089588Clin Genet. 2013 Aug;84(2):120-723647473Geriatrics. 2009 May;64(5):19-22, 25-619435391J Ophthalmol. 2015;2015:40189426664742Oftalmologia. 2006;50(2):3-916927750Arch Ophthalmol. 1993 Jun;111(6):831-68512486Age-related cataractEPHA2Meta-analysisOGG1Polymorphism
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1949-255374620161115OncotargetOncotargetElevated level of acetylation of APE1 in tumor cells modulates DNA damage repair.75197-7520910.18632/oncotarget.12113Apurinic/apyrimidinic (AP) sites are frequently generated in the genome by spontaneous depurination/depyrimidination or after removal of oxidized/modified bases by DNA glycosylases during the base excision repair (BER) pathway. Unrepaired AP sites are mutagenic and block DNA replication and transcription. The primary enzyme to repair AP sites in mammalian cells is AP endonuclease (APE1), which plays a key role in this repair pathway. Although overexpression of APE1 in diverse cancer types and its association with chemotherapeutic resistance are well documented, alteration of posttranslational modification of APE1 and modulation of its functions during tumorigenesis are largely unknown. Here, we show that both classical histone deacetylase HDAC1 and NAD+-dependent deacetylase SIRT1 regulate acetylation level of APE1 and acetylation of APE1 enhances its AP-endonuclease activity both in vitro and in cells. Modulation of APE1 acetylation level in cells alters AP site repair capacity of the cell extracts in vitro. Primary tumor tissues of diverse cancer types have higher level of acetylated APE1 (AcAPE1) compared to adjacent non-tumor tissue and exhibit enhanced AP site repair capacity. Importantly, in the absence of APE1 acetylation, cells accumulate AP sites in the genome and show increased sensitivity to DNA damaging agents. Together, our study demonstrates that elevation of acetylation level of APE1 in tumor could be a novel mechanism by which cells handle the elevated levels of DNA damages in response to genotoxic stress and maintain sustained proliferation.SenguptaShiladityaSDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030 , USA.ManthaAnil KAKDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.Center for Animal Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151001, Punjab, India.SongHeyuHDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.RoychoudhuryShrabastiSDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.NathSomsubhraSDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.Molecular Biology Research & Diagnostic Laboratory, Saroj Gupta Cancer Centre & Research Institute, Kolkata 700063, India.RaySutapaSDepartment of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE 68198, USA.BhakatKishor KKKDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.engR01 CA148941CANCI NIH HHSUnited StatesJournal Article
United StatesOncotarget1015329651949-25530U46U6E8UKNADEC 3.5.1.-Sirtuin 1EC 3.5.1.98Histone Deacetylase 1EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCurr Mol Pharmacol. 2012 Jan;5(1):14-3522122462Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Mutat Res. 2008 Aug 25;643(1-2):54-6318579163J Biol Chem. 1998 Nov 13;273(46):30360-59804799PLoS One. 2009 Jun 01;4(6):e574019484131J Biol Chem. 2005 Apr 29;280(17):17187-9515749705Mutat Res. 2009 Mar 31;674(1-2):131-618948225Cancer Treat Rev. 2010 Aug;36(5):425-3520056333Annu Rev Biochem. 1994;63:915-487979257Mutat Res. 1997 Nov;385(2):139-499447235Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):686-9110639140Nucleic Acids Res. 2011 Oct;39(18):8017-2821727086DNA Repair (Amst). 2008 Feb 1;7(2):177-8617974506Oncogene. 2011 Jan 27;30(4):482-9320856196Mutat Res. 2000 Oct 16;461(2):83-10811018583Mol Endocrinol. 2010 Feb;24(2):391-40120032196Biochim Biophys Acta. 2012 Jun;1820(6):730-521571039Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642J Pharmacol Exp Ther. 2010 Sep 1;334(3):988-9820504914Nucleic Acids Res. 2001 Jul 15;29(14):3116-2211452037DNA Repair (Amst). 2005 Dec 8;4(12):1442-916199212Nucleic Acids Res. 2010 Jan;38(3):832-4519934257J Biol Chem. 1990 Oct 5;265(28):17174-92211619Biochemistry. 1972 Sep 12;11(19):3618-234559796Chem Res Toxicol. 2006 Sep;19(9):1215-2016978026Mol Biol Cell. 2012 Oct;23(20):4079-9622918947EMBO J. 2003 Dec 1;22(23):6299-30914633989Free Radic Biol Med. 2002 Jul 1;33(1):15-2812086678Cancer Res. 1997 Dec 15;57(24):5457-99407949J Biol Chem. 2011 Feb 18;286(7):4968-7721081487Mol Cell Biol. 2008 Dec;28(23):7066-8018809583PLoS One. 2013 Jul 16;8(7):e6846723874636J Hypertens. 2012 May;30(5):917-2522441348Free Radic Res. 2008 Jan;42(1):20-918324520Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-69560228Nucleic Acids Res. 2004 Jun 02;32(10):3033-915175427Carcinogenesis. 1998 Mar;19(3):525-79525290Nature. 2000 Jan 27;403(6768):451-610667800Nat Cell Biol. 2010 Jun;12 (6):563-7120473298Free Radic Biol Med. 2010 Dec 1;49(11):1603-1620840865FASEB J. 2006 Dec;20(14):2612-417068113FEBS Lett. 1995 Jan 16;358(1):1-37821417Nucleic Acids Res. 2007;35(8):2522-3217403694Med Oncol. 2011 Sep;28(3):673-820354813Mutat Res. 1990 Sep-Nov;236(2-3):173-2011697933Biochemistry. 2012 Aug 7;51(31):6246-5922788932Oncotarget. 2016 Apr 19;7(16):22590-60426981776Mol Cancer Res. 2007 Jan;5(1):61-7017259346Chem Res Toxicol. 2010 Jan;23(1):99-10720017514Clin Cancer Res. 2001 Nov;7(11):3510-811705870Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143Cell Mol Life Sci. 2010 Nov;67(21):3609-2020711647Mol Cell Biol. 2006 Mar;26(5):1654-6516478987Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463J Cell Sci. 2001 Jul;114(Pt 13):2363-7311559745Annu Rev Genet. 1986;20:201-303545059Oncogene. 2014 May 29;33(22):2876-8723831574Lung Cancer. 2008 May;60(2):277-8418061304Drug Des Devel Ther. 2014 May 09;8:485-9624872679J Mol Biol. 2008 May 23;379(1):28-3718436236Mol Oncol. 2015 Jun;9(6):1071-8025681012DNA Repair (Amst). 2004 Jan 5;3(1):1-1214697754Free Radic Biol Med. 2003 Sep 1;35(5):495-50312927599Curr Opin Cell Biol. 2003 Apr;15(2):164-7112648672Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325J Biol Chem. 1998 Nov 13;273(46):30352-99804798Gastroenterology. 2009 Jun;136(7):2258-6919505426Oncogene. 2012 Mar 22;31(12 ):1546-5721841822Clin Cancer Res. 2005 Oct 15;11(20):7405-1416243814Oncogene. 1999 Jan 28;18(4):1033-4010023679BMC Cancer. 2014 Jan 08;14:1124400589Oncogene. 2009 Apr 2;28(13):1616-2519219073Antioxid Redox Signal. 2014 Feb 1;20(4):621-3923879289FASEB J. 2010 Oct;24(10):3674-8020511393Mol Cancer Res. 2009 Jun;7(6):897-90619470598AcetylationBinding SitesCell Line, TumorCell SurvivalgeneticsDNA DamageDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismHistone Deacetylase 1metabolismHumansNADmetabolismNeoplasmsgeneticsmetabolismpathologyProtein BindingSirtuin 1metabolismBERDNA damage repairacetylationapurinic/apyrimidinic endonuclease 1 (APE1)
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1083-351X291452016Nov04The Journal of biological chemistryJ. Biol. Chem.Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 (Ape1/Ref-1) Modulates Antigen Presenting Cell-mediated T Helper Cell Type 1 Responses.23672-23680Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1) is a multifunctional protein possessing DNA repair, redox control, and transcriptional regulatory activities. Although Ape1/Ref-1 plays multiple roles in the immune system, its functions in helper T (Th) cell activation and differentiation are largely unknown. In this study, the function of Ape1/Ref-1 in Th cell activation was analyzed using an Ape1/Ref-1 redox-specific inhibitor, E3330. When splenocytes from OT-II mice, which are ovalbumin (OVA)-specific T-cell receptor transgenic mice, were activated with OVA in the presence of E3330, the induction of IFN-γ-producing OT-II T cells was significantly increased. In contrast, E3330 did not enhance IFN-γ production from plate-bound anti-CD3 antibody-stimulated CD4+ T cells in the absence of antigen presenting cells (APCs). Furthermore, E3330-pretreated and OVA-pulsed APCs also enhanced the IFN-γ production from OT-II T cells. These results suggested that E3330 enhances Th1 responses by modifying APC function. E3330 did not alter the surface expression of MHC-II or the co-stimulatory molecules CD80 and CD86 on APCs. On the other hand, E3330 up-regulated the IL-12 p35 and p40 gene expression, and IL-12 surface retention, but decreased the IL-12 secretion from Toll-like receptor (TLR) ligand-stimulated APCs. These results were confirmed with Ape1/Ref-1 knockdown experiments. Taken together, our findings indicated that the suppression of Ape1/Ref-1 redox function leads to an increased cell surface retention of IL-12 and enhances Th1 responses. This is the first study to demonstrate that Ape1/Ref-1 modulates the IL-12 production and secretion from APCs and controls Th1 immune responses.© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.AkhterNasrinNFrom the Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585.TakedaYujiYFrom the Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585.NaraHidetoshiHFrom the Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585.ArakiAkemiAFrom the Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585.IshiiNaotoNthe Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai 980-8075, and.AsaoNaokiNWPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan.AsaoHironobuHFrom the Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, asao-h@med.id.yamagata-u.ac.jp.engJournal Article20160916
United StatesJ Biol Chem2985121R0021-92580Benzoquinones0Propionates136164-66-4E 3330187348-17-0Interleukin-1282115-62-6Interferon-gammaEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAntioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2008 Nov;10(11):1853-6718627350J Biol Chem. 2001 Oct 5;276(40):37692-911477091Immunol Cell Biol. 1998 Feb;76(1):34-409553774Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Antioxid Redox Signal. 2011 Apr 15;14(8):1387-40120874257Nucleic Acids Res. 1991 Oct 25;19(20):5519-231719477J Biol Chem. 2000 Jan 14;275(2):867-7410625620Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Int Immunol. 2007 Oct;19(10):1191-917698559J Biol Chem. 2004 Jan 16;279(3):1777-8614594818Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-41722334J Exp Med. 2000 Aug 21;192(4):507-1610952720Vaccine. 2004 Mar 12;22(9-10):1199-20515003648J Immunol. 2009 Nov 15;183(10):6839-4819846872Annu Rev Immunol. 1996;14:233-588717514Inflamm Res. 2013 Nov;62(11):951-923979690PLoS One. 2012;7(7):e4126022844448Biochem Biophys Res Commun. 1996 Aug 23;225(3):1063-78780734Eur J Biochem. 2000 May;267(9):2624-3110785383Mol Cell Biol. 2013 Apr;33(7):1468-7323382073J Biol Chem. 2003 Oct 3;278(40):38829-3912832423Cytokine. 2013 May;62(2):262-7123557800Cell. 1991 Jul 12;66(1):9-102070420Biochem Biophys Res Commun. 2012 Apr 13;420(3):628-3422450323Nat Biotechnol. 2000 Aug;18(8):877-8110932159J Gene Med. 2004 Jul;6(7):777-8515241785EMBO J. 1992 Feb;11(2):653-651537340J Immunol. 1999 Dec 15;163(12 ):6403-1210586030Blood. 2007 Mar 1;109(5):1917-2217053053Curr Immunol Rev. 2005 Jun;1(2):119-13721037949AnimalsAntigen-Presenting Cellscytologydrug effectsimmunologyBenzoquinonespharmacologyCells, CulturedDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsimmunologyImmunity, Cellulardrug effectsInterferon-gammaimmunologyInterleukin-12immunologyMice, Inbred C57BLOxidation-Reductiondrug effectsPropionatespharmacologyTh1 Cellscytologydrug effectsimmunologyApe1/Ref-1IL-12T helper cellsantigen presenting cellcytokinedendritic celldifferentiationredox regulation
20160608201691860201753160201691860ppublish27637330M116.74235310.1074/jbc.M116.742353PMC5095420
275396712017071320170713
1880-42332432017MayBreast cancer (Tokyo, Japan)Breast CancerGenetic polymorphisms in APE1 Asp148Glu(rs3136820) as a modifier of the background levels of abasic sites in human leukocytes derived from breast cancer patients and controls.420-42610.1007/s12282-016-0719-yApurinic/apyrimidinic (abasic/AP) sites are among the most common endogenous DNA lesions. AP sites, if not repaired, could result in genomic instability as well as chromosome aberrations. Information regarding the direct assay of the number of abasic sites in human leukocytes and its association with risk of breast cancer has not been reported.In this study, we investigated the association between certain risk factors for breast cancer and the background levels of AP sites in leukocytes derived from 148 Taiwanese women with breast cancer and 140 cancer-free controls. The risk factors studied include age, body mass index (BMI), and polymorphisms of apurinic/apyrimidinic endonuclease (APE1) [APE1 Asp148Glu(rs3136820)].Mean levels of AP sites were estimated to be 23.3 and 50.3 per 106 nucleotides in controls and breast cancer patients, respectively (~twofold, p < 0.001). In subjects with age <50 or BMI < 27 (kg/m2), the levels of AP sites in breast cancer patients were ~2-3-fold greater than those of controls (p < 0.05). Additionally, results from the AP site 3'-cleavage assay indicated that the AP sites detected in both controls and patients were likely to be oxidant-mediated 5'-cleaved AP sites (~61-64 %). The number of AP sites in breast cancer patients was ~twofold greater in subjects with Asp/Glu + Glu/Glugenotypes than those with Asp/Asp genotype (p < 0.001).We confirmed that cumulative body burden of AP sites is a significant predictor of the risk of developing breast cancer and that genetic predisposition and environment factors may modulate the induction of oxidative DNA lesions in breast cancer patients.HsiehWei-ChungWCDepartment of Laboratory Medicine, Da-Chien General Hospital, Miaoli, Taiwan.LinCheCComprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.ChenDar-RenDRComprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.YuWen-FaWFDepartment of Laboratory Medicine, Da-Chien General Hospital, Miaoli, Taiwan.ChenGuan-JieGJDepartment of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan.HuSuh-WoanSWCollege of Oral Medicine, Chung Shan Medical University, Taichung, Taiwan.LiuChin-ChenCCDepartment of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan.GeMao-HueiMHDepartment of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan.RuanChang-SinCSDepartment of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan.ChenCheng-YouCYDepartment of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan.LinChia-HuaCHDepartment of Biotechnology, National Formosa University, Yunlin, 63208, Taiwan.LinPo-HsiungPHDepartment of Environmental Engineering, National Chung Hsing University, Taichung, 402, Taiwan. pohsiunglin@yahoo.com.engJournal Article20160818
JapanBreast Cancer1008882011340-68689007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseV10TVZ52E4PutrescineIMAdultBreast NeoplasmsgeneticspathologyCase-Control StudiesDNAmetabolismDNA DamageDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleGene FrequencyGenetic Predisposition to DiseaseHumansLeukocytespathologyMiddle AgedPolymorphism, Single NucleotidePutrescinemetabolismAP sitesBiomarkerDNA repairOxidative stress
2016030920160808201682060201771460201682060ppublish2753967110.1007/s12282-016-0719-y10.1007/s12282-016-0719-y
275386222017051720170817
1878-58833682016Sep15Journal of the neurological sciencesJ. Neurol. Sci.The levels of 7,8-dihydrodeoxyguanosine (8-oxoG) and 8-oxoguanine DNA glycosylase 1 (OGG1) - A potential diagnostic biomarkers of Alzheimer's disease.155-910.1016/j.jns.2016.07.008S0022-510X(16)30421-XEvidence indicates that oxidative stress contributes to neuronal cell death in Alzheimer's disease (AD). Increased oxidative DNA damage l, as measured with 8-oxoguanine (8-oxoG), and reduced capacity of proteins responsible for removing of DNA damage, including 8-oxoguanine DNA glycosylase 1 (OGG1), were detected in brains of AD patients. In the present study we assessed peripheral blood biomarkers of oxidative DNA damage, i.e. 8- oxoG and OGG1, in AD diagnosis, by comparing their levels between the patients and the controls. Our study was performed on DNA and serum isolated from peripheral blood taken from 100 AD patients and 110 controls. For 8-oxoG ELISA was employed. The OGG1 level was determined using ELISA and Western blot technique. Levels of 8-oxoG were significantly higher in DNA of AD patients. Both ELISA and Western blot showed decreased levels of OGG1 in serum of AD patients. Our results show that oxidative DNA damage biomarkers detected in peripheral tissue could reflect the changes occurring in the brain of patients with AD. These results also suggest that peripheral blood samples may be useful to measure oxidative stress biomarkers in AD. Copyright © 2016 Elsevier B.V. All rights reserved.SliwinskaAgnieszkaADepartment of Internal Disease, Diabetology and Clinical Pharmacology, Medical University of Lodz, Lodz, Poland.KwiatkowskiDominikDUniversity of Lodz, Department of Molecular Genetics, Lodz, Poland.CzarnyPiotrPUniversity of Lodz, Department of Molecular Genetics, Lodz, Poland; Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.TomaMonikaMUniversity of Lodz, Department of Molecular Genetics, Lodz, Poland.WignerPaulinaPUniversity of Lodz, Department of Molecular Genetics, Lodz, Poland.DrzewoskiJozefJDepartment of Internal Disease, Diabetology and Clinical Pharmacology, Medical University of Lodz, Lodz, Poland.Fabianowska-MajewskaKrystynaKDepartment of Biomedical Chemistry, Medical University of Lodz, Lodz, Poland.SzemrajJanuszJDepartment of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.MaesMichaelMDeakin University IMPACT Strategic Research Centre, Deakin University, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand; Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Brazil.GaleckiPiotrPDepartment of Adult Psychiatry, Medical University of Lodz, Lodz, Poland.SliwinskiTomaszTUniversity of Lodz, Department of Molecular Genetics, Lodz, Poland. Electronic address: tomsliw@biol.uni.lodz.pl.engJournal Article20160709
NetherlandsJ Neurol Sci03754030022-510X07,8-dihydro-8-oxoguanine0Biomarkers5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAgedAlzheimer DiseasebloodArea Under CurveBiomarkersbloodBlood Chemical AnalysisBlotting, WesternDNA GlycosylasesbloodEnzyme-Linked Immunosorbent AssayFemaleGuanineanalogs & derivativesbloodHumansMaleROC Curve7,8-dihydrodeoxyguanosine (8-oxoG)8-oxoguanine DNA glycosylase 1 (OGG1)Alzheimer's diseaseDNA base excision repairOxidative DNA damageOxidative stress
201603302016060220160707201682060201682060201751860ppublish27538622S0022-510X(16)30421-X10.1016/j.jns.2016.07.008
275137502017020220170202
1421-97783932016Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacologyCell. Physiol. Biochem.Cadmium Exposure Enhances Bisphenol A-Induced Genotoxicity through 8-Oxoguanine-DNA Glycosylase-1 OGG1 Inhibition in NIH3T3 Fibroblast Cells.961-7410.1159/000447804Both cadmium (Cd) and bisphenol A (BPA) are commonly encountered in humans' daily activities, but their combined genotoxic effects remain unclear.In the present study, we exposed a mouse embryonic fibroblast cell line (NIH3T3) to Cd for 24 h, followed by a 24 h BPA exposure to evaluate toxicity. The cytotoxicity was evaluated by viability with CCK-8 assay and lactate dehydrogenase (LDH) release. Reactive oxygen species (ROS) production was measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA). And DNA damage was measured by 8-hydroxydeoxyguanosine (8-OHdG), phosphorylated H2AX (γH2AX) and the comet assay. The flow cytometry was used to detect cell cycle distribution, and apoptosis was determined by TUNEL assay and western blot against poly-ADP-ribose polymerase (PARP).The results showed that Cd or BPA treatments alone (with the exception of BPA exposure at 50 μM) did not alter cell viability. However, pre-treatment with Cd aggravated the BPA-induced reduction in cell viability; increased BPA-induced LDH release, ROS production, DNA damage and G2 phase arrest; and elevated BPA-induced TUNEL-positive cells and the expression levels of cleaved PARP. Cd exposure concurrently decreased the expression of 8-oxoguanine-DNA glycosylase-1 (OGG1), whereas OGG1 over-expression abolished the enhancement of Cd on BPA-induced genotoxicity and cytotoxicity.These findings indicate that Cd exposure aggravates BPA-induced genotoxicity and cytotoxicity through OGG1 inhibition.© 2016 The Author(s) Published by S. Karger AG, Basel.ChenZhi-YuZYDepartment of Occupational Health, Third Military Medical University, Chongqing, People's Republic of China.LiuChuanCLuYong-HuiYHYangLing-LingLLLiMinMHeMin-DiMDChenChun-HaiCHZhangLeiLYuZheng-PingZPZhouZhouZengJournal Article20160812
SwitzerlandCell Physiol Biochem91132211015-89870Air Pollutants, Occupational0Benzhydryl Compounds0Drug Combinations0Estrogens, Non-Steroidal0H2AFX protein, human0Histones0Phenols0Reactive Oxygen SpeciesEC 1.1.1.27L-Lactate DehydrogenaseEC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanJ6K4F9V3BACadmium ChlorideMLT3645I99bisphenol AIMAir Pollutants, OccupationalpharmacologyAnimalsBenzhydryl CompoundspharmacologyCadmium ChloridepharmacologyCell Survivaldrug effectsComet AssayDNA DamageDNA Glycosylasesantagonists & inhibitorsgeneticsmetabolismDrug CombinationsEstrogens, Non-SteroidalpharmacologyG2 Phase Cell Cycle Checkpointsdrug effectsGene Expression RegulationHistonesgeneticsmetabolismL-Lactate DehydrogenasesecretionMiceNIH 3T3 CellsPhenolspharmacologyPhosphorylationdrug effectsPoly(ADP-ribose) PolymerasesgeneticsmetabolismReactive Oxygen Speciesagonistsmetabolism
2016070720168126020168126020172660ppublish2751375000044780410.1159/000447804
274637242017080420171212
1660-460113820160725International journal of environmental research and public healthInt J Environ Res Public HealthGenetic Variations in the Promoter of the APE1 Gene Are Associated with DMF-Induced Abnormal Liver Function: A Case-Control Study in a Chinese Population.10.3390/ijerph13080752E752Acute or long-term exposure to N,N-dimethylformamide (DMF) can induce abnormal liver function. It is well known that DMF is mainly metabolized in the liver and thereby produces reactive oxygen species (ROS). The base excision repair (BER) pathway is regarded as a very important pathway involved in repairing ROS-induced DNA damage. Several studies have explored the associations between GSTM1, GSTT1, CYP2E1 polymorphisms and DMF-induced abnormal liver function; however, little is known about how common hOGG1, XRCC1 and APE1 polymorphisms and DMF induce abnormal liver function. The purpose of this study was to investigate whether the polymorphisms in the hOGG1 (rs159153 and rs2072668), XRCC1 (rs25487, rs25489, and rs1799782), APE1 (rs1130409 and 1760944) genes in the human BER pathway were associated with the susceptibility to DMF-induced abnormal liver function in a Chinese population. These polymorphisms were genotyped in 123 workers with DMF-induced abnormal liver function and 123 workers with normal liver function. We found that workers with the APE1 rs1760944 TG/GG genotypes had a reduced risk of abnormal liver function, which was more pronounced in the subgroups that were exposed to DMF for <10 years, exposed to ≥10 mg/m³ DMF, never smoked and never drank. In summary, our study supported the hypothesis that the APE1 rs1760944 T > G polymorphism may be associated with DMF-induced abnormal liver function in the Chinese Han population.TongZhiminZKunshan Municipal Center for Disease Prevention and Control, Kunshan 215301, China. 79972002tzm@163.com.ShenHuanxiHKunshan Municipal Center for Disease Prevention and Control, Kunshan 215301, China. shenhuanxi@163.com.Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing 211166, China. shenhuanxi@163.com.YangDandanDDepartment of Integrated Management &amp; Emergency Preparedness and Response, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing 210009, China. Yangdan1997@163.com.ZhangFengFInstitute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, No.172 Jiangsu Road, Nanjing 210009, China. zhangfeng0401@163.com.BaiYingYInstitute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, No.172 Jiangsu Road, Nanjing 210009, China. baiy@jscdc.cn.LiQianQThe First People's Hospital of Kunshan, Kunshan 215300, China. qianyingbingfeng@163.com.ShiJianJKunshan Municipal Center for Disease Prevention and Control, Kunshan 215301, China. sjian@163.com.ZhangHengdongHInstitute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, No.172 Jiangsu Road, Nanjing 210009, China. hd-zhang@263.net.ZhuBaoliBDepartment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing 211166, China. zhubl@jscdc.cn.Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, No.172 Jiangsu Road, Nanjing 210009, China. zhubl@jscdc.cn.engJournal ArticleResearch Support, Non-U.S. Gov't20160725
SwitzerlandInt J Environ Res Public Health1012384551660-46018696NH0Y2XDimethylformamideEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMMol Biol Rep. 2011 Oct;38(7):4565-7321499756Toxicology. 1987 Mar;43(3):231-83824392Biomarkers. 2005 Nov-Dec;10 (6):464-7416308270Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Mol Cell Biochem. 2014 Jun;391(1-2):127-3624557852Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2007 Feb;25(2):80-317456397Nature. 2000 Feb 24;403(6772):859-6610706276Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2009 Jun;27(6):333-719927646Prog Nucleic Acid Res Mol Biol. 2001;68:129-3811554292DNA Repair (Amst). 2003 Sep 18;2(9):955-6912967653Int Arch Occup Environ Health. 1999 Jan;72(1):19-2510029226Mutagenesis. 2008 Jan;23(1):35-4117971348Int Arch Occup Environ Health. 2001 Sep;74(7):519-2211697456Int Arch Occup Environ Health. 1992;63(7):461-81577525Mol Carcinog. 2005 Mar;42(3):127-4115584022Toxicology. 2003 Jul 15;189(1-2):21-3912821280Carcinogenesis. 2004 Sep;25(9):1689-9415073047Arch Toxicol. 2001 Feb;74(12):755-911305777Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Carcinogenesis. 2004 May;25(5):757-6314729591Mutat Res. 2008 Mar-Apr;658(3):215-3318037339Nature. 1991 Jan 31;349(6308):431-41992344Mutagenesis. 2009 Nov;24(6):507-1219762350Arch Environ Health. 1991 May-Jun;46(3):161-62039271Int J Occup Med Environ Health. 2015 ;28(2):395-826182934J Occup Health. 2004 Nov;46(6):429-3915613765Ann Intern Med. 1988 May;108(5):680-63358569Carcinogenesis. 2007 Jul;28(7):1520-517374727Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2014 Apr;32(4):285-624754947PLoS One. 2014 Mar 05;9(3):e8966224599382Toxicol Sci. 2003 Apr;72(2):347-5812655034FASEB J. 2009 Oct;23(10):3459-6919541747Saf Health Work. 2011 Jun;2(2):97-10422953193J Natl Cancer Inst. 2009 Jan 7;101(1):24-3619116388Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Exp Mol Med. 2014 Jul 18;46:e10625033834Carcinogenesis. 2000 Mar;21(3):453-6010688865Int J Radiat Oncol Biol Phys. 2006 Oct 1;66(2):537-4516965996Nature. 2001 May 17;411(6835):366-7411357144Asian Continental Ancestry GroupCase-Control StudiesChemical and Drug Induced Liver InjuryepidemiologyDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismDimethylformamideadministration & dosagetoxicityDose-Response Relationship, DrugFemaleGenotypeHumansLiverdrug effectsmetabolismMalePolymorphism, GeneticAPE1N,N-dimethylformamideXRCC1hOGG1polymorphism
20160330201606292016072020167286020167286020178560epublish27463724ijerph1308075210.3390/ijerph13080752PMC4997438
274478002017121420171214
1874-996872201612UltrasonicsUltrasonicsSuppression of human 8-oxoguanine DNA glycosylase (OGG1) augments ultrasound-induced apoptosis in cervical cancer cells.1-1410.1016/j.ultras.2016.07.005S0041-624X(16)30111-1Human 8-oxoguanine DNA glycosylase (OGG1) is a major base excision repair enzyme, and it was reported to suppress the activation of intrinsic apoptotic signaling pathway in response to oxidative stress. In this study, our aim was to investigate the effects of OGG1 downregulation on ultrasound-induced apoptosis in cervical cancer cells.OGG1 expression was silenced by shRNA in the cervical cancer SW756 and CaSki cells. Cell viability was evaluated by MTT assay after OGG1 knockdown following ultrasound treatment. Ultrasound-induced apoptosis was measured by Annexin V-FITC/propidium iodide. Intracellular reactive oxygen species (ROS) production and Ca(2+) concentration were detected using a fluorescent probe, 2',7'-dichlorofluorescin diacetate (DCFH-DA) and a green fluorescent dye fluo-4AM, respectively. Western blotting was used to analyze the expression of Bcl-2, Bax, cleaved caspase-3, and nuclear factor-κB p65 (NF-κB p65).The results indicated that OGG1 knockdown did not suppress cell proliferation, but significantly augmented ultrasound-induced inhibitory effects on the cell viability, and increased ultrasound-induced early apoptosis and late apoptosis and necrosis in the SW756 and CaSki cells when exposure to ultrasound (1MHz) at 1.5W/cm(2) for 30 and 60s. OGG1 knockdown significantly increased intracellular ROS production and Ca(2+) concentration after incubation of 6, 24, and 48h post-ultrasound treatment. The downregulation of Bcl-2 protein and the upregulation of Bax, cleaved caspase-3, and NF-κB p65 protein levels were observed in the shRNA-OGG1 cells and mock-shRNA cells, but no significant change of these protein levels was found between of them.These results indicate that downregulation of OGG1 expression can augment ultrasound-induced apoptosis in cervical cancer cells, which suggests that OGG1 suppression might provide a new insight for ultrasound-induced therapeutic effects on cervical cancer treatment.Copyright © 2016 Elsevier B.V. All rights reserved.XuTaoTDepartment of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.NieYongliYDepartment of Oncology, Han Jiang Group Co. Ltd-Han Jiang Hospital, DanJiangKou 442700, Hubei Province, China.BaiJiaoJDepartment of Ultrasound, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.LiLinjunLDepartment of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.YangBoBDepartment of Ultrasound, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.ZhengGuangmeiGDepartment of Ultrasound, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.ZhangJunJDepartment of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.YuJianyunJDepartment of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.ChengXiongfeiXDepartment of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.JiaoJiaoJDepartment of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.JingHongxiaHDepartment of Ultrasound, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China. Electronic address: hongxiajing@sina.com.engJournal Article20160711
NetherlandsUltrasonics00504520041-624X0Aniline Compounds0Annexin A50FITC-annexin A50Fluo 40Fluoresceins0NF-kappa B0Proto-Oncogene Proteins c-bcl-20RNA, Small Interfering0Reactive Oxygen Species0Xanthenes0bcl-2-Associated X Protein2044-85-1diacetyldichlorofluoresceinEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.4.22.-CASP3 protein, humanEC 3.4.22.-Caspase 3I223NX31W9Fluorescein-5-isothiocyanateSY7Q814VUPCalciumIMAniline CompoundsAnnexin A5metabolismApoptosisBlotting, WesternCalciummetabolismCaspase 3metabolismCell Line, TumorCell ProliferationCell SurvivalDNA GlycosylasesmetabolismDown-RegulationFemaleFluorescein-5-isothiocyanateanalogs & derivativesmetabolismFluoresceinsHumansNF-kappa BmetabolismOxidative StressProto-Oncogene Proteins c-bcl-2metabolismRNA, Small InterferingmetabolismReactive Oxygen SpeciesmetabolismSignal TransductionUltrasonic TherapyUterine Cervical NeoplasmsmetabolismtherapyXanthenesbcl-2-Associated X ProteinmetabolismApoptosisCervical cancer cellsOGG1Reactive oxygen speciesUltrasound
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273934512016090620171116
1011-601X2942016JulPakistan journal of pharmaceutical sciencesPak J Pharm SciPolymorphisms in DNA repair genes XRCC1 and OGG1 lead to the progression of rheumatoid arthritis in Pakistani patients.1189-95This study points at the elucidation of a possible association of Rheumatoid arthritis (RA) with Ser326Cys in OGG1 Arg194Trp and Arg399Gln polymorphisms of XRCC1 using a sample size of 100 patients and 100 controls from a Pakistani population. This association was determined using Random Fragment Length Polymorphism Analysis as well as the DAS scoring system. In RA, oxidative damage due to free radical production leads to destructive proliferative synovitis showing cellular transformations of synoviocytes into a tumorigenic state. XRCC1 and OGG1 genes, which are part of the DNA Break Excision Repair pathway, manifest various polymorphisms which may cause a variation in the response to inflammation by changing DNA repair potential. Our results showed a significant association between the DAS28 score values as well as the genotypic state of the RA patients. It was seen that the score was significantly higher in GG genotypes thereby corroborating the role of the polymorphism XRCC1 Arg399Gln. Using a Pearson's correlation test it was found to be <0.000003. It has been shown by the results in this research that an increased risk of DNA damage exists when the polymorphic genotypes studied, exist in a RA patient. QadirMirza Muhammad FahdMMAtta-ur-Rahman School of Applied Biosciences (ASAB). National University of Sciences and Technology (NUST). Sector H-12, Islamabad, Pakistan.BhattiAttyaAAtta-ur-Rahman School of Applied Biosciences (ASAB). National University of Sciences and Technology (NUST). Sector H-12, Islamabad, Pakistan.KhurshidRabiaRAtta-ur-Rahman School of Applied Biosciences (ASAB). National University of Sciences and Technology (NUST). Sector H-12, Islamabad, Pakistan.AshrafMuhammad UsmanMUAtta-ur-Rahman School of Applied Biosciences (ASAB). National University of Sciences and Technology (NUST). Sector H-12, Islamabad, Pakistan.AnjumSidrahSAtta-ur-Rahman School of Applied Biosciences (ASAB). National University of Sciences and Technology (NUST). Sector H-12, Islamabad, Pakistan.JohnPeterPAtta-ur-Rahman School of Applied Biosciences (ASAB). National University of Sciences and Technology (NUST). Sector H-12, Islamabad, Pakistan.engJournal Article
PakistanPak J Pharm Sci94263561011-601X0DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMArthritis, RheumatoidgeneticsDNA GlycosylasesgeneticsDNA-Binding ProteinsgeneticsDisease ProgressionGenetic Predisposition to DiseaseGenotypeHumansPolymorphism, Single NucleotideX-ray Repair Cross Complementing Protein 1
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1837-96647102016Journal of CancerJ CancerAssociation between the OGG1 Ser326Cys Polymorphism and Cancer Risk: Evidence from 152 Case-Control Studies.1273-8010.7150/jca.15035Although it has been suggested that the 8-oxoguanine DNA glycosylase (OGG1) gene Ser326Cys polymorphism may be a risk factor for cancer, the conclusions from previous studies are inconsistent. Thus, we conducted an updated meta-analysis to estimate the effect of OGG1 variant genotypes on cancer susceptibility. We searched the PubMed for all eligible studies published in English for the period ending September 2014. We found the association between OGG1 Ser326Cys polymorphism and cancer susceptibility based on 152 case-control studies in different genetic model comparisons (dominant model: OR = 1.053, P = 0.018; recessive model: OR = 1.108, P < 0.001; homozygote: OR = 1.135, P < 0.001; additive model: OR = 1.059, P < 0.001). However, the results from the subgroup analyses based on types of cancer, health population as controls or studies with relatively large sample size did not support the conclusion. Although the overall results of this meta-analysis showed a positive association between OGG1 variant genotypes and cancer susceptibility, the subgroup analyses by cancer type, sample size, and source of controls presented inconsistent results. Therefore, the current evidence from the meta-analysis did not support the hypothesis of OGG1 Ser326Cys polymorphism as a risk factor of cancer. ZouHuaH1. Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China;LiQingQ1. Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China;XiaWeiW1. Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China;LiuYongY3. Intensive care unit, Suining Central Hospital, Deshengxi Road 127, Chuanshan District, Suining, Sichuan 629000, China.WeiXiX2. Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China;WangDongD1. Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China;engJournal Article20160623
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2045-2322620160708Scientific reportsSci RepPeroxiredoxin 1 interacts with and blocks the redox factor APE1 from activating interleukin-8 expression.2938910.1038/srep29389APE1 is an essential DNA repair protein that also possesses the ability to regulate transcription. It has a unique cysteine residue C65, which maintains the reduce state of several transcriptional activators such as NF-κB. How APE1 is being recruited to execute the various biological functions remains unknown. Herein, we show that APE1 interacts with a novel partner PRDX1, a peroxidase that can also prevent oxidative damage to proteins by serving as a chaperone. PRDX1 knockdown did not interfere with APE1 expression level or its DNA repair activities. However, PRDX1 knockdown greatly facilitates APE1 detection within the nucleus by indirect immunofluorescence analysis, even though APE1 level was unchanged. The loss of APE1 interaction with PRDX1 promotes APE1 redox function to activate binding of the transcription factor NF-κB onto the promoter of a target gene, the proinflammatory chemokine IL-8 involved in cancer invasion and metastasis, resulting in its upregulation. Depletion of APE1 blocked the upregulation of IL-8 in the PRDX1 knockdown cells. Our findings suggest that the interaction of PRDX1 with APE1 represents a novel anti-inflammatory function of PRDX1, whereby the association safeguards APE1 from reducing transcription factors and activating superfluous gene expression, which otherwise could trigger cancer invasion and metastasis.NassourHassanHMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.WangZhiqiangZMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.SaadAmineASegal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montréal, Québec, H3T 1E2, Canada.PapalucaArturoAMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.BrosseauNicolasNMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.AffarEl Bachirel BMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.Alaoui-JamaliMoulay AMASegal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montréal, Québec, H3T 1E2, Canada.RamotarDindialDMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.engMOP-93573 CIHRCanadaJournal ArticleResearch Support, Non-U.S. Gov't20160708
EnglandSci Rep1015632882045-23220IL8 protein, human0Interleukin-80NF-kappa BBBX060AN9VHydrogen PeroxideEC 1.11.1.15PRDX1 protein, humanEC 1.11.1.15PeroxiredoxinsEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMMethods Enzymol. 2003;370:430-4414712665Infect Immun. 2003 Oct;71(10):5523-3014500470J Leukoc Biol. 2002 Nov;72(5):847-5512429706Breast Cancer Res. 2013;15(4):21024041156Biochem J. 2002 Jul 15;365(Pt 2):547-5311966472Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116J Biol Chem. 2002 Jun 28;277(26):23573-8111950839Annu Rev Biochem. 1994;63:915-487979257Elife. 2015 Jun 01;4:null26030852J Immunol. 2013 Apr 15;190(8):4349-5923509368Biochem J. 2001 Jul 1;357(Pt 1):241-711415455Trends Biochem Sci. 2003 Jan;28(1):32-4012517450Oncogene. 2005 Dec 1;24(54):8038-5016170382Mutat Res. 2000 Oct 16;461(2):83-10811018583Neurochem Int. 2009 Nov;55(6):362-819375465Nat Chem Biol. 2015 Jan;11(1):64-7025402766J Biol Chem. 2002 Apr 26;277(17):14564-7411834746Nucleic Acids Res. 2001 Jul 15;29(14):3116-2211452037J Clin Biochem Nutr. 2012 Mar;50(2):91-10522448089Mol Biol Cell. 2011 Oct;22(20):3887-90121865600J Biol Chem. 2002 Jun 7;277(23 ):20336-4211916965Nature. 2008 Jul 24;454(7203):428-3518650913Pharmaceuticals (Basel). 2013 Aug 06;6(8):929-5924276377EMBO J. 2003 Dec 1;22(23):6299-30914633989EMBO J. 2009 May 20;28(10 ):1505-1719369943Proc Natl Acad Sci U S A. 2001 Jul 17;98 (15):8774-911438700Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):E3071-8023898172Biochem Biophys Res Commun. 2010 Feb 12;392(3):363-820074557Nat Immunol. 2003 Feb;4(2):145-5312524539FEBS Lett. 2006 Jan 9;580(1):351-516376335Free Radic Biol Med. 2012 Oct 1;53(7):1522-3022902630Nature. 2003 Jul 31;424(6948):561-512891360Biochemistry. 2012 Jan 17;51(2):695-70522148505J Biol Chem. 1996 Dec 13;271(50):32253-98943284Sci Rep. 2013;3:245623949117Am J Transl Res. 2016 Feb 15;8(2):842-5927158373Nature. 2011 Jun 29;474(7353):609-1521720365Biol Chem. 2002 Mar-Apr;383(3-4):347-6412033427Cell. 2004 Jun 25;117(7):859-7215210108Mol Cancer Res. 2009 Sep;7(9):1543-5219737972Breast Cancer Res. 2014 Jul 10;16(4):R7925011585J Biol Chem. 2002 Nov 8;277(45):43175-8412196529Antioxid Redox Signal. 2011 Aug 1;15(3):781-9420919930Int J Mol Sci. 2013 Feb 06;14(2):3467-8623389043J Biol Chem. 2012 Feb 10;287(7):4403-1022147704EMBO J. 1999 Oct 15;18(20):5609-2110523305Nucleic Acids Res. 2001 Mar 15;29(6):1285-9211238994J Biol Chem. 1995 Nov 24;270(47):28006-97499282Mol Cell Biol. 2009 Apr;29(7):1834-5419188445PLoS One. 2013 Aug 15;8(8):e7090923967134Mol Cells. 2013 Nov;36(5):439-4524213673Proteomics. 2009 Feb;9(4):1058-7419180539Apoptosis. 2007 Jul;12(7):1243-5517333320EMBO J. 1992 Sep;11(9):3323-351380454Immunol Rev. 2012 Mar;246(1):311-2622435563Nucleic Acids Res. 2013 Jan;41(Database issue):D808-1523203871Endocr Relat Cancer. 2012 Apr 10;19(2):197-20822277193J Biol Chem. 2015 Jan 30;290(5):3057-6825492865Mutat Res. 2012 Jul 1;735(1-2):39-4522583657Nature. 2002 Jan 10;415(6868):183-711805838Antioxid Redox Signal. 2001 Aug;3(4):671-8311554453J Biol Chem. 2002 Nov 15;277(46):44548-5612213807EMBO J. 1992 Feb;11(2):653-651537340Toxicology. 2003 Nov 15;193(1-2):43-6514599767Am J Pathol. 2001 Feb;158(2):639-4611159200Free Radic Biol Med. 2007 Jul 15;43(2):282-817603937Oncogene. 2009 Apr 2;28(13):1616-2519219073Antioxid Redox Signal. 2012 Mar 15;16(6):506-2322114845Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766Breast Cancer Res Treat. 2010 Oct;123(3):725-3120020197Cell NucleusmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismGene Expression Regulation, NeoplasticHEK293 CellsHeLa CellsHep G2 CellsHumansHydrogen PeroxidepharmacologyInterleukin-8geneticsNF-kappa BmetabolismNeoplasm InvasivenessNeoplasm MetastasisOxidative StressPeroxiredoxinsgeneticsmetabolismPromoter Regions, GeneticStomach NeoplasmsgeneticsmetabolismTranscriptional Activation
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1524-457111962016Sep02Circulation researchCirc. Res.Ogg1-Dependent DNA Repair Regulates NLRP3 Inflammasome and Prevents Atherosclerosis.e76-9010.1161/CIRCRESAHA.116.308362Activation of NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome-mediating interleukin (IL)-1β secretion has emerged as an important component of inflammatory processes in atherosclerosis. Mitochondrial DNA (mtDNA) damage is detrimental in atherosclerosis, and mitochondria are central regulators of the nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 inflammasome. Human atherosclerotic plaques express increased mtDNA damage. The major DNA glycosylase, 8-oxoguanine glycosylase (OGG1), is responsible for removing the most abundant form of oxidative DNA damage.To test the role of OGG1 in the development of atherosclerosis in mouse.We observed that Ogg1 expression decreases over time in atherosclerotic lesion macrophages of low-density lipoprotein receptor (Ldlr) knockout mice fed a Western diet. Ogg1(-/-)Ldlr(-/-) mice fed a Western diet resulted in an increase in plaque size and lipid content. We found increased oxidized mtDNA, inflammasome activation, and apoptosis in atherosclerotic lesions and also higher serum IL-1β and IL-18 in Ogg1(-/-)Ldlr(-/-) mice than in Ldlr(-/-). Transplantation with Ogg1(-/-) bone marrow into Ldlr(-/-) mice led to larger atherosclerotic lesions and increased IL-1β production. However, transplantation of Ogg1(-/-)Nlrp3(-/-) bone marrow reversed the Ogg1(-/-) phenotype of increased plaque size. Ogg1(-/-) macrophages showed increased oxidized mtDNA and had greater amounts of cytosolic mtDNA and cytochrome c, increased apoptosis, and more IL-1β secretion. Finally, we found that proatherogenic miR-33 can directly inhibit human OGG1 expression and indirectly suppress both mouse and human OGG1 via AMP-activated protein kinase.OGG1 plays a protective role in atherogenesis by preventing excessive inflammasome activation. Our study provides insight into a new target for therapeutic intervention based on a link between oxidative mtDNA damage, OGG1, and atherosclerosis via NLRP3 inflammasome.© 2016 American Heart Association, Inc.TumurkhuuGantsetsegGFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).ShimadaKenichiKFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).DagvadorjJargalsaikhanJFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).CrotherTimothy RTRFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).ZhangWenxuanWFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).LuthringerDanielDFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).GottliebRoberta ARAFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).ChenShuangSFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).ArditiMosheMFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.). moshe.arditi@cshs.org.engR01 HL111483HLNHLBI NIH HHSUnited StatesR21 AI105845AINIAID NIH HHSUnited StatesP01 HL112730HLNHLBI NIH HHSUnited StatesR01 HL132075HLNHLBI NIH HHSUnited StatesR01 HL066436HLNHLBI NIH HHSUnited StatesR01 HL130353HLNHLBI NIH HHSUnited StatesJournal Article20160706
United StatesCirc Res00471030009-73300DNA, Mitochondrial0Inflammasomes0NLR Family, Pyrin Domain-Containing 3 Protein0Nlrp3 protein, mouseEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMArterioscler Thromb Vasc Biol. 2005 Nov;25(11):2255-6416141399J Clin Invest. 2011 Jul;121(7):2921-3121646721Nat Rev Immunol. 2010 Jan;10(1):36-4619960040PLoS One. 2012;7(12):e5169723284747Free Radic Biol Med. 2002 May 1;32(9):804-1211978482Int J Mol Sci. 2015 Feb 09;16(2):3757-6825671815Can J Cardiol. 2012 Mar-Apr;28(2):222-922265992FEBS Lett. 1997 Dec 15;419(2-3):276-809428650J Biol Chem. 2004 Mar 12;279(11):9857-6614688259Circ Res. 2014 Jan 31;114(3):421-3324297735Cancer Res. 2001 Jul 15;61(14):5378-8111454679Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2234-911842210Am J Physiol Cell Physiol. 2014 Feb 1;306(3):C221-924304833Physiol Rev. 2006 Apr;86(2):515-8116601268Cardiovasc Res. 2008 Aug 1;79(3):360-7618487233Am J Physiol Lung Cell Mol Physiol. 2013 Feb 15;304(4):L287-9723241530Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15093-817846428Acta Pharmacol Sin. 2010 Sep;31(9):1075-8420711221Clin Exp Immunol. 2014 Apr;176(1):66-7724345202Cell Metab. 2012 Apr 4;15(4):545-5322445600Circ Res. 2015 Feb 27;116(5):816-2625524056Cancer Res. 2004 Jul 1;64(13):4411-415231648Nat Rev Cardiol. 2010 Feb;7(2):77-8620065951Am J Physiol Cell Physiol. 2008 Feb;294(2):C413-2218077603Nat Med. 2015 Jun;21(6):549-5126046571Mutat Res. 2011 May 10;709-710:21-3121376741Mol Cell Biol. 2013 Aug;33(15):2891-90223716591Circ Res. 2014 May 23;114(11):1757-7124855200Sci Rep. 2015 Mar 16;5:914425775051PLoS One. 2014 Jan 27;9(1):e8755224475307Circulation. 2002 Aug 20;106(8):927-3212186795Thromb Haemost. 2012 Apr;107(4):642-722274626J Atheroscler Thromb. 2012;19(4):316-2522277767J Biol Chem. 1998 Dec 11;273(50):33811-69837971J Immunol. 2010 Nov 1;185(9):5619-2720935201Free Radic Biol Med. 2011 May 1;50(9):1107-1320969951Diabetes. 2006 Aug;55(8):2180-9116873680Am J Respir Crit Care Med. 2011 Jan 15;183(2):226-3320732986Immunity. 2012 Mar 23;36(3):401-1422342844Nat Med. 2011 Feb;17 (2):179-8821217695PLoS One. 2013 Jun 25;8(6):e6753223825667EMBO Mol Med. 2014 Jul 18;6(9):1133-4125038053Eur J Cancer. 2010 Oct;46(15):2806-2020656472Mech Ageing Dev. 2007 Nov-Dec;128(11-12):637-4918006041Nat Rev Immunol. 2013 Oct;13(10):709-2123995626Circ Res. 2015 Jul 17;117(3):266-7826002865Curr Opin Lipidol. 2011 Apr;22(2):86-9221178770Ageing Res Rev. 2012 Apr;11(2):230-4122186033J Am Heart Assoc. 2012 Dec;1(6):e00337623316322Curr Pharm Des. 2014;20(1):108-2423944376Free Radic Biol Med. 2005 Mar 15;38(6):737-4515721984J Inflamm Res. 2015 Jan 16;8:15-2725653548Nature. 2011 Oct 19;478(7369):404-722012398Circ Res. 2014 Oct 10;115(9):759-6925201910Circ Res. 2015 Jul 17;117(3):225-826185207Circulation. 2010 Feb 16;121(6):792-80320124121Trends Endocrinol Metab. 2010 Dec;21(12):699-70620880716J Clin Invest. 2015 Oct 26;125(12):4334-4826517695Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):1973-723702658Exp Mol Med. 2015 Mar 13;47:e15025766619Nat Immunol. 2011 May;12 (5):408-1521478880Circ Res. 2007 Mar 2;100(4):460-7317332437J Atheroscler Thromb. 2014;21(5):381-9024717761Nature. 2002 Dec 19-26;420(6917):868-7412490960Nat Immunol. 2010 Oct;11(10 ):897-90420835230J Biol Chem. 2012 Jun 15;287(25):20769-7322568941Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-99012815Circulation. 2002 Jul 30;106(5):544-912147534Mutat Res. 1992 Sep;275(3-6):169-801383759Trends Mol Med. 2015 Mar;21(3):193-20125500014J Biol Chem. 1997 Oct 10;272(41):25409-129325246Cell. 2011 Apr 29;145(3):341-5521529710Cardiovasc Res. 2000 Feb;45(3):736-4610728396Biochim Biophys Acta. 2010 Feb;1797(2):113-2819761752Nature. 2010 Apr 29;464(7293):1357-6120428172Circulation. 2013 Aug 13;128(7):702-1223841983Arterioscler Thromb Vasc Biol. 2003 Apr 1;23(4):656-6012615675Mutat Res. 2001 Jun 27;493(1-2):23-3011516712Cell Metab. 2011 Apr 6;13(4):376-8821459323Coron Artery Dis. 2015 Jun;26(4):322-725768243J Am Heart Assoc. 2014 Dec;3(6):e00120225527624Curr Atheroscler Rep. 2013 May;15(5):32223512606Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L530-515563690Circ Res. 2016 Sep 2;119(6):698-70027587405AnimalsAtherosclerosisgeneticsmetabolismprevention & controlDNA GlycosylasesdeficiencygeneticsmetabolismDNA RepairphysiologyDNA, MitochondrialgeneticsmetabolismDiet, Westernadverse effectsHumansInflammasomesgeneticsmetabolismMiceMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteingeneticsmetabolismDNA repairatherosclerosisinflammasomesmacrophagesmitochondria
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2008-2398912016FebIranian journal of cancer preventionIran J Cancer PrevXRCC1 and OGG1 Gene Polymorphisms and Breast Cancer: A Systematic Review of Literature.e346710.17795/ijcp-3467Known polymorphisms of DNA repair genes can be associated with the risk of many types of cancer. There is no consensus regarding association between XRCC1 and OGG1 with breast cancer (BC).The aim of this study is to collect relevant published studies systematically.Sixty-two publications were identified through searching PubMed, PubMed Central, ISI web of knowledge, and reference list of related articles.We performed a systematic review according MOOSE guideline criteria. All longitudinal cohort and case-control studies investigating association of any type and grade of breast cancer with XRCC1 and OGG1 gene and their polymorphisms were eligible for initial inclusion.Two authors screened titles and abstracts and extracted all needed information from eligible studies. Four research methodological components causing bias for the association between gene polymorphisms and breast cancer risk, including source of controls sampling, population ethnicity, sample size of studies and menopausal status of cases and controls was used for assessment of quality of studies.A total of 14,793 breast cancer cases and 15,409 controls were included in assessment of XRCC1 Arg194Trp. Four studies showed significant association and one study showed protective effect of XRCC1 Arg194Trp and BC. A total of 7,716 cases and 7,370 controls were included for XRCC1 Arg280His. Only one study showed significant association of XRCC1 Arg280His and breast cancer (OR = 1.82 (1.06 - 3.15). A total of 27,167 cases and 31,998 controls were included to estimate association between XRCC1 Arg399Gln polymorphism and breast cancer. Seven studies showed significant association and one showed protective effect of XRCC1 Arg399Gln and BC. A total of 9,417 cases and 11,087 controls were included for OGG1 Ser326Cys. Among studies focused on OGG1 Ser326Cys, none showed significant association with breast cancer.Systematic search of major databases identify many studies addressing the relationship between BC and susceptible alleles in the base excision repair genes and the fact that there are many variations in the magnitude of association depending on inheritance model and the population of the study.Sanjari MoghaddamAliASchool of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.NazarzadehMiladMIranian Research Center on Healthy Aging, Sabzevar University of Medical Sciences, Sabzevar, IR Iran.NorooziRezvanRDepartment of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.DarvishHosseinHDepartment of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.Mosavi JarrahiAlirezaASchool of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran; Iranian Research Center on Healthy Aging, Sabzevar University of Medical Sciences, Sabzevar, IR Iran; Faculty of Health Sciences, Simon Fraser University, BC., Canada.engJournal ArticleReview20160223
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1091-64901132520160621Proceedings of the National Academy of Sciences of the United States of AmericaProc. Natl. Acad. Sci. U.S.A.APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury.E3558-6710.1073/pnas.1606226113A major hallmark of oxidative DNA damage after stroke is the induction of apurinic/apyrimidinic (AP) sites and strand breaks. To mitigate cell loss after oxidative DNA damage, ischemic cells rapidly engage the base excision-repair proteins, such as the AP site-repairing enzyme AP endonuclease-1 (APE1), also named redox effector factor-1 (Ref-1). Although forced overexpression of APE1 is known to protect against oxidative stress-induced neurodegeneration, there is no concrete evidence demonstrating a role for endogenous APE1 in the long-term recovery of gray and white matter following ischemic injury. To address this gap, we generated, to our knowledge, the first APE1 conditional knockout (cKO) mouse line under control of tamoxifen-dependent Cre recombinase. Using a well-established model of transient focal cerebral ischemia (tFCI), we show that induced deletion of APE1 dramatically enlarged infarct volume and impaired the recovery of sensorimotor and cognitive deficits. APE1 cKO markedly increased postischemic neuronal and oligodendrocyte degeneration, demonstrating that endogenous APE1 preserves both gray and white matter after tFCI. Because white matter repair is instrumental in behavioral recovery after stroke, we also examined the impact of APE1 cKO on demyelination and axonal conduction and discovered that APE1 cKO aggravated myelin loss and impaired neuronal communication following tFCI. Furthermore, APE1 cKO increased AP sites and activated the prodeath signaling proteins, PUMA and PARP1, after tFCI in topographically distinct manners. Our findings provide evidence that endogenous APE1 protects against ischemic infarction in both gray and white matter and facilitates the functional recovery of the central nervous system after mild stroke injury.StetlerR AnneRAState Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; Pittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261;GaoYanqinYState Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; Pittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213;LeakRehana KRKDivision of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282;WengZhongfangZPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261;ShiYejieY0000-0001-7502-9201Pittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261;ZhangLiliLPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261;PuHongjianHPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213;ZhangFengFState Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; Pittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261;HuXiaomingXState Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; Pittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261;HassanSulaimanSPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261;FergusonCarolynCDepartment of Anesthesiology, University of Pittsburgh, Pittsburgh, PA 15261; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261;HomanicsGregg EGEDepartment of Anesthesiology, University of Pittsburgh, Pittsburgh, PA 15261; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261;CaoGuodongGState Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; Pittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261;BennettMichael V LMVState Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461 michael.bennett@einstein.yu.edu chenj2@upmc.edu.ChenJunJState Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; Pittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261; michael.bennett@einstein.yu.edu chenj2@upmc.edu.engR37 AA010422AANIAAA NIH HHSUnited StatesR01 NS095029NSNINDS NIH HHSUnited StatesR01 NS045287NSNINDS NIH HHSUnited StatesR01 NS089534NSNINDS NIH HHSUnited StatesR01 NS036736NSNINDS NIH HHSUnited StatesR01 NS045048NSNINDS NIH HHSUnited StatesR01 AA010422AANIAAA NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20160606
United StatesProc Natl Acad Sci U S A75058760027-8424EC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMProc Natl Acad Sci U S A. 2006 Nov 28;103(48):18308-1317116882Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8424-88378314Brain Res. 2009 Jun 5;1274:1-1019374886Clin Biochem. 2009 Oct;42(15):1493-919631633J Cereb Blood Flow Metab. 2003 Nov;23(11):1324-3914600440Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2853-825691750EMBO J. 2002 Jun 3;21(11):2833-4112032096DNA Repair (Amst). 2005 Mar 2;4(3):367-7915661660Mol Cell. 2001 Mar;7(3):683-9411463392J Biol Chem. 1974 Mar 10;249(5):1530-54206354J Biol Chem. 1998 Aug 14;273(33):21203-99694877Stroke. 1996 Sep;27(9):1641-6; discussion 16478784142J Neurosci Methods. 2002 Jun 30;117(2):207-1412100987J Neurochem. 2000 Apr;74(4):1636-4510737622J Cereb Blood Flow Metab. 2006 Feb;26(2):181-9816001017J Biol Chem. 1974 Mar 10;249(5):1536-404361739Genomics. 1995 Mar 1;26(1):63-97782087Neurotherapeutics. 2013 Jan;10 (1):124-4223132328J Neurosci. 2008 Dec 3;28(49):13038-5519052195Stroke. 2013 Dec;44(12):3509-1524092548J Neurochem. 1997 Jul;69(1):232-459202315J Neurosci. 2007 Aug 29;27(35):9278-9317728442Free Radic Biol Med. 2012 Nov 1;53(9):1782-9022841870Dev Biol. 2002 Apr 15;244(2):305-1811944939J Neurocytol. 1996 Jan;25(1):1-78852934Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3204-920133634Neuroscience. 1999;93(4):1465-7310501471Stroke. 2009 Jun;40(6):2244-5019246690Mutat Res. 1998 Oct 21;409(1):17-299806499Nat Neurosci. 2014 Apr;17 (4):506-1224609463Antioxid Redox Signal. 2011 May 15;14(10):1905-1820677909N Engl J Med. 1998 Jan 29;338(5):278-859445407J Cereb Blood Flow Metab. 2001 Apr;21(4):321-3311323518Stroke. 1999 Feb;30(2):441-8; discussion 4499933285Antioxid Redox Signal. 2015 Jan 10;22(2):135-4824180454Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Stroke. 2009 Feb;40(2):530-619109548BMC Neurosci. 2007 Oct 10;8:8517927825Antioxid Redox Signal. 2012 Sep 1;17(5):719-3222356734EMBO J. 1992 Feb;11(2):653-651537340Stroke. 1998 Nov;29(11):2268-769804633CNS Neurol Disord Drug Targets. 2013 May 1;12(3):325-3723469858Curr Biol. 2000 Jul 27-Aug 10;10(15):886-9510959836Stroke. 2012 May;43(5):1390-722461332Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128AnimalsBehavior, AnimalDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsphysiologyGray MatterphysiopathologyMiceMice, Inbred C57BLMice, KnockoutStrokephysiopathologyWhite Matterphysiopathologybase excision repairischemianeurodegenerationoxidative DNA damagewhite matter injury
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1873-3913289201609Cellular signallingCell. Signal.OGG1 is essential in oxidative stress induced DNA demethylation.1163-7110.1016/j.cellsig.2016.05.021S0898-6568(16)30128-0DNA demethylation is an essential cellular activity to regulate gene expression; however, the mechanism that triggers DNA demethylation remains unknown. Furthermore, DNA demethylation was recently demonstrated to be induced by oxidative stress without a clear molecular mechanism. In this manuscript, we demonstrated that 8-oxoguanine DNA glycosylase-1 (OGG1) is the essential protein involved in oxidative stress-induced DNA demethylation. Oxidative stress induced the formation of 8-oxoguanine (8-oxoG). We found that OGG1, the 8-oxoG binding protein, promotes DNA demethylation by interacting and recruiting TET1 to the 8-oxoG lesion. Downregulation of OGG1 makes cells resistant to oxidative stress-induced DNA demethylation, while over-expression of OGG1 renders cells susceptible to DNA demethylation by oxidative stress. These data not only illustrate the importance of base excision repair (BER) in DNA demethylation but also reveal how the DNA demethylation signal is transferred to downstream DNA demethylation enzymes.Copyright © 2016 Elsevier Inc. All rights reserved.ZhouXiaolongXJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.ZhuangZihengZChangzhou No. 7 People's Hospital, Changzhou 213011, China; School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou 213011, China.WangWentaoWJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.HeLingfengLJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.WuHuanHJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.CaoYanYJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.PanFeiyanFJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.ZhaoJingJJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.HuZhigangZJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.SekharChandraCJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.GuoZhigangZJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China. Electronic address: guozgang@gmail.com.engJournal ArticleResearch Support, Non-U.S. Gov't20160529
EnglandCell Signal89046830898-65680Proto-Oncogene Proteins0RNA, Small InterferingBBX060AN9VHydrogen PeroxideEC 1.-Mixed Function OxygenasesEC 1.-TET1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.4.-Amyloid Precursor Protein SecretasesEC 3.4.23.-Aspartic Acid EndopeptidasesEC 3.4.23.46BACE1 protein, humanIMAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesCpG IslandsDNA Demethylationdrug effectsDNA GlycosylasesmetabolismGene Knockdown TechniquesGenome, HumanHeLa CellsHumansHydrogen PeroxidepharmacologyMCF-7 CellsMiceMixed Function OxygenasesmetabolismModels, BiologicalOxidative Stressdrug effectsPromoter Regions, GeneticgeneticsProtein Bindingdrug effectsProto-Oncogene ProteinsmetabolismRNA, Small Interferingmetabolism8-OxoGDNA demethylationOGG1Oxidative stressTET1
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0973-71384122016JunJournal of biosciencesJ. Biosci.Accelerated processing of solitary and clustered abasic site DNA damage lesions by APE1 in the presence of aqueous extract of Ganoderma lucidum.265-75The stimulatory effect of the aqueous extract of G. lucidum, a basidiomycetes class fungus in the APE1-enzyme-mediated processing of solitary and bistranded clustered abasic sites DNA damages is presented. Abasic sites are considered the most common type of DNA damage lesions. Our study shows enhanced activity of APE1 in the processing of abasic sites in the presence of the polysaccharides fraction of G. lucidum. Remarkable increase in the amount of single-strand breaks (SSBs) and double-strand breaks (DSBs) from solitary and bistranded clustered abasic sites respectively with APE1 in the presence of the extract was found. This trend is maintained when abasic sites in DNA oligomers are exposed to fibroblast cell extracts in the presence of the extract. While DNA conformational alteration is negligible, APE1 enzyme shows characteristic changes in the alpha helix and beta strand ratio after incubation with G. lucidum extract. The enhanced reactivity of APE1 at the molecular level in the presence of G. lucidium is attributed to this effect. This study potentially amplifies the scope of the use of G. lucidum, which was earlier shown to have only reactive oxygen species (ROS) scavenging properties with regards to DNA damage inhibition. KumariBhaviniBDepartment of Chemistry, IIT Patna, Patna, India.DASProlayPKumariRekhaRengJournal Article
IndiaJ Biosci81008090250-59910Fungal Polysaccharides0Reactive Oxygen SpeciesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Hematol Oncol. 2009 Jun 10;2:2519515245Leuk Res. 2006 Jul;30(7):841-816423392EMBO J. 2001 Nov 15;20(22):6530-911707423Glycobiology. 2004 Apr;14(4):17R-30R14718374Mutat Res. 2001 May 10;485(4):283-30711585362Biochemistry. 2000 Jul 11;39(27):8026-3110891084Nucleic Acids Res. 2004 Oct 19;32(18):5609-2015494449Carbohydr Res. 2012 May 15;353:100-522486826Phytochemistry. 2006 Sep;67(18):1985-200116905165J Biol Chem. 1998 Aug 14;273(33):21203-99694877Int J Mol Med. 1999 Sep;4(3):273-710425278Molecules. 2008 Aug 08;13(8):1599-61618794775Nutr Cancer. 2008;60(1):109-1918444142Mol Cell Biochem. 2012 Mar;362(1-2):195-20122042551Phytomedicine. 2005 Apr;12(4):255-6315898702Nucleic Acids Res. 2005 Feb 24;33(4):1222-915731342J Mol Biol. 2008 May 23;379(1):17-2718439621Int J Cancer. 2002 Nov 20;102(3):250-312397644Anal Biochem. 1989 May 15;179(1):209-152757197Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):103-810618378Am J Chin Med. 2011;39(1):15-2721213395Biofactors. 2004;21(1-4):109-1215630179Nucleic Acids Res. 2008 May;36(8):2717-2718353858World J Gastroenterol. 2002 Aug;8(4):728-3312174387J Agric Food Chem. 2009 Nov 25;57(22):10565-7219863048Nucleic Acids Res. 2005 Jan 12;33(1):260-7115647508PLoS One. 2011;6(9):e2367921935361J Med Food. 2005 Summer;8(2):159-6816117607Int J Mol Sci. 2014 May 22;15(5):9103-1624857920FEBS Lett. 2000 Jun 30;476(1-2):73-710878254J Biosci. 2011 Mar;36(1):105-1621451252Nature. 1993 Apr 22;362(6422):709-158469282Food Chem. 2012 Dec 1;135(3):1097-10322953830DNA Repair (Amst). 2004 Jan 5;3(1):1-1214697754Food Chem. 2014 Jul 15;155:50-624594153Fitoterapia. 2014 Oct;98:254-925111010BMC Genomics. 2007 Nov 09;8:41117996095Eur Rev Med Pharmacol Sci. 2012 Feb;16(2):166-7522428467J Acupunct Meridian Stud. 2010 Mar;3(1):24-31206335123 Biotech. 2012 Mar;2(1):1-1522582152J Biol Chem. 1997 Jun 20;272(25):15650-59188454DNA Breaks, Double-Strandeddrug effectsDNA Breaks, Single-Strandeddrug effectsDNA Damagedrug effectsDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) Lyasedrug effectsgeneticsFibroblastsdrug effectsFungal Polysaccharidesadministration & dosagechemistryHumansNucleic Acid Conformationdrug effectsReactive Oxygen SpeciesmetabolismReishichemistry
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2233-73855222016MayChonnam medical journalChonnam Med JDynamic Regulation of APE1/Ref-1 as a Therapeutic Target Protein.75-8010.4068/cmj.2016.52.2.75Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that plays a central role in the cellular response to DNA damage and redox regulation against oxidative stress. APE1/Ref-1 functions in the DNA base excision repair pathway, the redox regulation of several transcription factors, and the control of intracellular redox status through the inhibition of reactive oxygen species (ROS) production. APE1/Ref-1 is predominantly localized in the nucleus; however, its subcellular localization is dynamically regulated and it may be found in the mitochondria or elsewhere in the cytoplasm. Studies have identified a nuclear localization signal and a mitochondrial target sequence in APE1/Ref-1, as well as the involvement of the nuclear export system, as determinants of APE1/Ref-1 subcellular distribution. Recently, it was shown that APE1/Ref-1 is secreted in response to hyperacetylation at specific lysine residues. Additionally, post-translational modifications such as phosphorylation, S-nitrosation, and ubiquitination appear to play a role in fine-tuning the activities and subcellular localization of APE1/Ref-1. In this review, we will introduce the multifunctional role of APE1/Ref-1 and its potential usefulness as a therapeutic target in cancer and cardiovascular disease. ChoiSungaSResearch Institute of Medical Sciences, Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea.JooHee KyoungHKResearch Institute of Medical Sciences, Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea.JeonByeong HwaBHResearch Institute of Medical Sciences, Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea.engJournal ArticleReview20160520
Korea (South)Chonnam Med J1015646592233-7393Hum Mol Genet. 1992 Dec;1(9):677-801284593Anticancer Res. 2011 Feb;31(2):379-8521378315Mutat Res. 2001 Mar 7;485(2):143-5211182545Mutat Res. 2008 Aug 25;643(1-2):54-6318579163Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Am J Hypertens. 2010 Feb;23(2):186-9120010699Nucleic Acids Res. 2012 Jan;40(2):701-1121933813Vision Res. 2011 Jan;51(1):93-10020937296Circ Res. 2004 Oct 29;95(9):902-1015472121Biochem Biophys Res Commun. 2013 Jun 14;435(4):621-623685156Cardiovasc Res. 2006 Feb 1;69(2):520-616325162Sci Rep. 2016 Mar 11;6:2301526964514Biochemistry. 2011 Jan 11;50(1):82-9221117647Brain Res Mol Brain Res. 1997 Feb;44(1):167-709030714Biochem Biophys Res Commun. 2008 Mar 28;368(1):68-7318206643J Pharmacol Exp Ther. 2010 Sep 1;334(3):988-9820504914Nucleic Acids Res. 2001 Jul 15;29(14):3116-2211452037Nucleic Acids Res. 2010 Jan;38(3):832-4519934257Cardiovasc Res. 2011 Aug 1;91(3):502-921467074Antioxid Redox Signal. 2009 Mar;11(3):571-418715142EMBO J. 2003 Dec 1;22(23):6299-30914633989Biochem Biophys Res Commun. 2013 Jun 7;435(3):403-723665318Cancer Res. 1997 Dec 15;57(24):5457-99407949J Hypertens. 2012 May;30(5):917-2522441348Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Curr Opin Cell Biol. 1998 Jun;10(3):392-99640541Biochemistry. 2012 Jan 17;51(2):695-70522148505Mitochondrion. 2014 Jul;17:42-924861944Ann Surg Oncol. 2013 Dec;20 Suppl 3:S336-4722688662Circ Res. 2012 Jul 6;111(2):212-922652909Cell Death Differ. 2002 Jul;9(7):717-2512058277FASEB J. 2002 Jun;16(8):889-9012039869Histopathology. 1998 Dec;33(6):561-99870152Cancer Res. 1995 Dec 15;55(24):6097-1028521399Nucleic Acids Res. 2005 Jun 07;33(10 ):3303-1215942031Nucleic Acids Res. 2007;35(8):2522-3217403694Cancer Sci. 2015 Oct;106(10):1394-40126250694J Hypertens. 2003 Feb;21(2):327-3512569263Int J Biochem. 1993 Jan;25(1):53-97679358Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463J Biol Chem. 2010 May 14;285(20):14871-8120231292Mol Cells. 2013 Nov;36(5):439-4524213673J Cell Physiol. 2009 Apr;219(1):209-1819097035Nucleic Acids Res. 2005 Aug 02;33(14):4379-9416077024Lung Cancer. 2008 May;60(2):277-8418061304FASEB J. 2004 Jun;18(9):986-815084519J Biol Chem. 1997 Aug 8;272(32):19633-69289489Nucleic Acids Res. 1994 Nov 25;22(23):4884-97800476Cancer Sci. 2014 Feb;105(2):186-9424329908Cancer Sci. 2012 May;103(5):882-822329793PLoS One. 2013;8(3):e5800123472128Stroke. 1999 Feb;30(2):441-8; discussion 4499933285Nucleic Acids Res. 2008 Mar;36(5):1555-6618208837Oncogene. 1999 Jan 28;18(4):1033-4010023679Oncotarget. 2015 Sep 15;6(27):23383-9826125438Oncogene. 2009 Apr 2;28(13):1616-2519219073Dis Markers. 2016;2016:727650227057081Korean Circ J. 2015 Sep;45(5):364-7126413103Cancer Res Treat. 2015 Oct;47(4):823-3325672588Nucleic Acids Res. 2015 Jun 23;43(11):5451-6425956655BiomarkersDNA-(apurinic or apyrimidinic site) lyaseOxidation-reductionProtein processing, post-translational
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2093-477720Suppl 12016MayInternational neurourology journalInt Neurourol JAltered Secretory Activity of APE1/Ref-1 D148E Variants Identified in Human Patients With Bladder Cancer.S30-3710.5213/inj.1632600.300Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA repair and redox modulation. Recently, serum and urinary APE1/Ref-1 levels were reported to be increased in patients with bladder cancer. Genetic variations of APE/Ref-1 are associated with the risk of cancer. However, the effect of APE1/Ref-1 variants on its secretory activity is yet unknown.APE1/Ref-1 variants were evaluated by DNA sequencing analysis of reverse transcription polymerase chain reaction products in coding DNA sequences (CDS) of APE1/Ref-1 in bladder tissue samples from patients with bladder cancer (n=10). Secretory activity of APE1/Ref-1 variants was evaluated with immunoblot and enzyme-linked immunosorbent assay of the culture medium supernatants.Four different substitution mutants (D148E, I64V/D148E, W67R/D148E, and E86G/D148E) of APE1/Ref-1 were identified in bladder cancer specimens. However, deletion mutants of APE1/Ref-1 CDS were not found. The secretory activity of the APE1/Ref-1 variants (D148E, I64V/D148E, and E86G/D148E) was increased compared to that of wild type APE1/Ref-1. Furthermore, the secretory activity in basal or hyperacetylated conditions was much higher than that in APE1/Ref-1 D148E-transfected HEK293 cells.Taken together, our data suggest that the increased secretory activity of D148E might contribute to increased serum levels of APE1/Ref-1 in patients with bladder cancer.LeeYu RanYR0000-0002-1902-8818Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.Department of Medical Science, Chungnam National University, Daejeon, Korea.LimJae SungJS0000-0003-4324-8148Department of Urology, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea.ShinJu HyunJH0000-0001-5996-5876Department of Urology, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea.ChoiSungaS0000-0002-3358-7923Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.JooHee KyoungHK0000-0002-2860-6448Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.JeonByeong HwaBH0000-0002-3347-2739Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.Department of Medical Science, Chungnam National University, Daejeon, Korea.engJournal Article20160526
Korea (South)Int Neurourol J1015345132093-4777Hum Mol Genet. 1992 Dec;1(9):677-801284593Dis Markers. 2015;2015:86951226257461Sci Rep. 2016 Mar 11;6:2301526964514DNA Cell Biol. 2010 Jun;29(6):303-1120218899Nucleic Acids Res. 2010 Jan;38(3):832-4519934257Antioxid Redox Signal. 2009 Mar;11(3):571-418715142EMBO J. 2003 Dec 1;22(23):6299-30914633989Biochem Biophys Res Commun. 2013 Jun 7;435(3):403-723665318Curr Opin Genet Dev. 2004 Feb;14(1):5-1015108798Nucleic Acids Res. 2005 Jun 07;33(10 ):3303-1215942031Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):84-9117220334Nucleic Acids Res. 2007;35(8):2522-3217403694Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12754-79398071Mol Cells. 2013 Nov;36(5):439-4524213673PLoS One. 2013 Jun 03;8(6):e6541523755229Oxid Med Cell Longev. 2014;2014:73030125243052Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165J Epidemiol. 2012;22(6):537-4223038158PLoS One. 2013 Dec 12;8(12):e8352724349526Curr Med Res Opin. 2011 Jul;27(7):1295-30221561390Oncotarget. 2015 Sep 15;6(27):23383-9826125438Dis Markers. 2016;2016:727650227057081Korean Circ J. 2015 Sep;45(5):364-7126413103Cancer Res Treat. 2011 Mar;43(1):1-1121509157Cancer Res Treat. 2015 Oct;47(4):823-3325672588Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 (APE1/Ref-1)Bladder CancerEnzyme-Linked Immunosorbent AssayPoint MutationSecretion
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1949-25537192016May10OncotargetOncotargetPrediction of survival prognosis of non-small cell lung cancer by APE1 through regulation of Epithelial-Mesenchymal Transition.28523-3910.18632/oncotarget.8660The DNA base excision repair gene APE1 involves in DNA damage repair pathway and overexpression in a variety of human cancers. Analyses of patients with non-small cell lung cancer (NSCLC) suggested that multiple factors associated with prognosis of NSCLC patients. Further investigation showed that APE1 expression was able to predict the progression-free survival and overall survival in patients with NSCLC and correlated with lymph node metastasis. Intriguingly, as a stratification of APE1-141 SNPs in APE1 positive expression, we also found APE1-141 GT/GG was identified as a marker for prediction of poor survival in NSCLC patients. In the in vitro experiments, the results showed that when APE1 expression was inhibited by siRNA or AT101 (an APE1 inhibitor), the migration and invasion of NSCLC cells were suppressed. Furthermore, Epithelial-Mesenchymal Transition (EMT) markers was tested to provide evidence that APE1 promoted NSCLC EMT through interaction with SirT1. Using NSCLC xenograft models, we confirmed that AT101 shrank tumor volumes and inhibited lymph node metastasis. In conclusion, APE1 could be a potential target for patients with NSCLC metastasis and AT101 is a potent inhibitor in further treatment of NSCLC patients. WeiXiXDepartment of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.LiQingQCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China.LiYingYThe Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.DuanWeiWCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China.HuangChongbiaoCDepartment of Senior Ward, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.ZhengXiangqianXDepartment of Thyroid and Cervical Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.SunLeiLDepartment of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.LuoJingtaoJThe Department of Otorhinolaryngology and Maxillofacial Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin, China.WangDongDCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China.ZhangShengSDepartment of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.XinXiaojieXDepartment of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.GaoMingMDepartment of Thyroid and Cervical Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.engJournal Article
United StatesOncotarget1015329651949-25530Antineoplastic Agents, PhytogenicEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseKAV15B369OGossypolS7RL72610Rgossypol acetic acidIMHealth Technol Assess. 2013 Jul;17(31):1-27823886301Asian Pac J Cancer Prev. 2013;14(9):5145-5124175791Nat Rev Cancer. 2009 Apr;9(4):265-7319262571Mutat Res. 2001 May 10;485(4):283-30711585362Nucleic Acids Res. 2010 Jan;38(3):832-4519934257Int J Cancer. 2014 Dec 1;135(11):2687-9624729390Mol Biol Cell. 2012 Oct;23(20):4079-9622918947Cancer Sci. 2007 Dec;98(12):1993-200117892509Curr Opin Pulm Med. 2005 Jul;11(4):287-9115928493Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):1893-90720647400Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Drug Des Devel Ther. 2015 Jun 08;9:2887-91026089640J Biol Chem. 2003 Sep 26;278(39):37768-7612842873CA Cancer J Clin. 2008 Mar-Apr;58(2):71-9618287387Tumour Biol. 2014 Sep;35(9):8559-6424863948Anticancer Res. 2013 Oct;33(10):4631-724123041Mol Biol Cell. 2014 Feb;25(4):532-4724356447EMBO J. 1992 Feb;11(2):653-651537340Transl Oncol. 2014 Apr;7(2):284-9124685547A549 CellsAnimalsAntineoplastic Agents, PhytogenicpharmacologyCarcinoma, Non-Small-Cell Lungdrug therapygeneticsmetabolismCell Line, TumorCell Movementdrug effectsgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismEpithelial-Mesenchymal Transitiondrug effectsgeneticsFemaleGene Expression Regulation, Neoplasticdrug effectsgeneticsGossypolanalogs & derivativespharmacologyHumansKaplan-Meier EstimateLung Neoplasmsdrug therapygeneticsmetabolismMaleMice, Inbred BALB CMice, NudeMiddle AgedPrognosisXenograft Model Antitumor AssaysAPE1Epithelial-Mesenchymal Transition (EMT)lymph node metastasisnon-small cell lung cancer (NSCLC)The authors declare no conflicts of interest.
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1875-863020162016Disease markersDis. MarkersUrinary APE1/Ref-1: A Potential Bladder Cancer Biomarker.727650210.1155/2016/7276502Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were significantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. The receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 μL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa. ChoiSungaSResearch Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.ShinJu HyunJHDepartment of Urology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea.LeeYu RanYRResearch Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.JooHee KyoungHKResearch Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.SongKi HakKHDepartment of Urology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea.NaYong GilYGDepartment of Urology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea.ChangSeok JongSJDepartment of Physiology, College of Medicine, Seonam University, Namwon 55724, Republic of Korea.LimJae SungJSDepartment of Urology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea.JeonByeong HwaBHResearch Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.engJournal ArticleResearch Support, Non-U.S. Gov't20160121
United StatesDis Markers86041270278-02400Biomarkers, TumorEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnticancer Res. 2004 Jul-Aug;24(4):2127-3415330152Br J Cancer. 2014 Feb 4;110(3):679-8524292452CA Cancer J Clin. 2012 Jul-Aug;62(4):220-4122700443Mol Cell Proteomics. 2011 Jun;10(6):M110.00533021474795Mol Diagn Ther. 2013 Apr;17(2):71-8423479428CA Cancer J Clin. 2010 Sep-Oct;60(5):277-30020610543CMAJ. 2007 Aug 14;177(4):361-817698825Biochem Biophys Res Commun. 2013 Jun 7;435(3):403-723665318Proteomics. 2004 Nov;4(11):3485-9715529407Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Acta Oncol. 2010 Nov;49(8):1283-720843171J Urol. 2002 Feb;167(2 Pt 1):555-811792917Clin Cancer Res. 2001 Nov;7(11):3510-811705870Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463J Urol. 2002 Mar;167(3):1318-9; discussion 1319-2011832722Biom J. 2005 Aug;47(4):458-7216161804Lung Cancer. 2008 May;60(2):277-8418061304Can Urol Assoc J. 2008 Jun;2(3):212-2118682775PLoS One. 2013;8(3):e5800123472128BMC Urol. 2012;12:1222559832Oncotarget. 2015 Sep 15;6(27):23383-9826125438J Urol. 2000 Sep;164(3 Pt 1):680-410954628Cancer Res Treat. 2011 Mar;43(1):1-1121509157Cancer Res Treat. 2015 Oct;47(4):823-3325672588AgedBiomarkers, TumorurineCase-Control StudiesDNA-(Apurinic or Apyrimidinic Site) LyaseurineEarly Detection of CancerFemaleHumansMaleMiddle AgedROC CurveSensitivity and SpecificityUp-RegulationUrinary Bladder Neoplasmsdiagnosismetabolismurine
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1949-25537182016May03OncotargetOncotargetAPE1 polymorphic variants cause persistent genomic stress and affect cancer cell proliferation.26293-30610.18632/oncotarget.8477Apurinic/apyrimidinic endonuclease 1 (APE1) is the main mammalian AP-endonuclease responsible for the repair of endogenous DNA damage through the base excision repair (BER) pathway. Molecular epidemiological studies have identified several genetic variants associated with human diseases, but a well-defined functional connection between mutations in APE1 and disease development is lacking. In order to understand the biological consequences of APE1 genetic mutations, we examined the molecular and cellular consequences of the selective expression of four non-synonymous APE1 variants (L104R, R237C, D148E and D283G) in human cells. We found that D283G, L104R and R237C variants have reduced endonuclease activity and impaired ability to associate with XRCC1 and DNA polymerase β, which are enzymes acting downstream of APE1 in the BER pathway. Complementation experiments performed in cells, where endogenous APE1 had been silenced by shRNA, showed that the expression of these variants resulted in increased phosphorylation of histone H2Ax and augmented levels of poly(ADP-ribosyl)ated (PAR) proteins. Persistent activation of DNA damage response markers was accompanied by growth defects likely due to combined apoptotic and autophagic processes. These phenotypes were observed in the absence of exogenous stressors, suggesting that chronic replication stress elicited by the BER defect may lead to a chronic activation of the DNA damage response. Hence, our data reinforce the concept that non-synonymous APE1 variants present in the human population may act as cancer susceptibility alleles. LirussiLisaLLaboratory of Molecular Biology and DNA Repair, Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1474 Nordbyhagen, Norway.AntonialiGiuliaGLaboratory of Molecular Biology and DNA Repair, Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.D'AmbrosioChiaraCProteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, 80147 Naples, Italy.ScaloniAndreaAProteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, 80147 Naples, Italy.NilsenHildeHDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1474 Nordbyhagen, Norway.TellGianlucaGLaboratory of Molecular Biology and DNA Repair, Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.engJournal Article
United StatesOncotarget1015329651949-2553EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCell Mol Life Sci. 2014 Jul;71(13):2451-6524496644Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W239-4216845001Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22090-521127267Mutat Res. 2011 Jun 3;711(1-2):100-1221167187J Mol Biol. 2015 Jan 30;427(2):298-31125498387J Cell Sci. 2007 Sep 15;120(Pt 18):3219-2717878236Methods Mol Med. 1999;28:17-2321374023PLoS One. 2013 Jun 11;8(6):e6592223776569Mol Biol Cell. 2012 Oct;23(20):4079-9622918947EMBO J. 2003 Dec 1;22(23):6299-30914633989Annu Rev Pathol. 2015;10:425-4825621662Mol Oncol. 2015 Jan;9(1):204-1725205036Nat Commun. 2013;4:267424154628Mutat Res. 2015 Sep;779:96-10426164266Mol Cell. 2013 Jan 24;49(2):339-4523246433PLoS One. 2012;7(10):e4668823056405Mol Biol Cell. 2014 May;25(10 ):1641-5224648491Trends Biochem Sci. 2010 May;35(5):247-5220172733Nature. 2014 Aug 14;512(7513):198-20225079315Nat Methods. 2010 Apr;7(4):248-920354512Mutat Res. 2001 Jan;432(3-4):53-911465542Exp Gerontol. 2010 Oct;45(10):772-820117203J Natl Cancer Inst. 2000 Jun 7;92(11):874-9710841823J Biol Chem. 2011 Apr 22;286(16):14564-7421357694Mutat Res. 2013 Mar-Apr;743-744:44-5223219605Mutat Res. 2011 Jun 3;711(1-2):193-20121216256Mol Cell Biol. 2013 Apr;33(7):1468-7323382073PLoS One. 2014 Sep 04;9(9):e10648525188410Int J Biomed Sci. 2011 Sep;7(3):158-7123675233PLoS One. 2014 Mar 04;9(3):e9083724595156Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Nature. 2011 Mar 3;471(7336):74-921368826Cells. 2012 Oct 15;1(4):774-9824710530Proteomics. 2009 Feb;9(4):1058-7419180539Nature. 2007 Jun 7;447(7145):730-417554310Oncogene. 2014 May 29;33(22):2876-8723831574Biochem Pharmacol. 2012 Jul 15;84(2):137-4622469522J Biol Chem. 2015 Aug 21;290(34):21067-7526134573Nucleic Acids Res. 2010 Dec;38(22):8239-5620699270Nature. 1993 Apr 22;362(6422):709-158469282Nat Protoc. 2009;4(7):1073-8119561590Autophagy. 2005 Jul;1(2):84-9116874052Nucleic Acids Res. 2009 Jun;37(11):3723-3819372272Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Prog Nucleic Acid Res Mol Biol. 2001;68:41-5411554312Mol Cell. 2010 Oct 22;40(2):216-2720965417J Biol Chem. 1998 Nov 13;273(46):30352-99804798Mol Aspects Med. 2013 Dec;34(6):1153-6723416893Antioxid Redox Signal. 2014 Feb 1;20(4):621-3923879289Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766Methods Mol Biol. 2012;809:519-3322113298Cell ProliferationgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGenetic Predisposition to DiseasegeneticsGenotypeHeLa CellsHumansNeoplasmsgeneticsPolymorphism, Single NucleotideAPE1/Ref-1genetic variantsgenotoxic damagereplication stressAuthors declare they have no conflicts of interest pending.
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1178-693092016OncoTargets and therapyOnco Targets TherAssociation between APE1 Asp148Glu polymorphism and the risk of urinary cancers: a meta-analysis of 18 case-control studies.1499-51010.2147/OTT.S101456Several observational studies suggested that APE1 Asp148Glu was significantly associated with urinary cancers; however, the results of published studies are inconsistent.The PubMed and EMBASE were searched for case-control studies regarding the association between Asp148Glu and the risk of urinary cancers with a time limit of September 12, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between Asp148Glu and the risk of developing prostate cancer, kidney cancer, bladder cancer, as well as all urinary cancers combined.A total of 18 case-control studies were included in the analysis. Our meta-analysis revealed that the inheritance of at least one APE1 148Glu among Asian men was associated with a 1.26-fold increase in the risk of developing urinary cancers. Meanwhile, APE1 Asp148Glu was significantly associated with the risk of prostate cancer. However, there were no significant relationships between the APE1 SNP (single nucleotide polymorphism) and all urinary cancers combined and bladder cancer and kidney cancer among the men of Caucasian/Asian/African descent or all racial/ethnic groups combined. When stratified by the quality score, no significant association was found in high-quality studies (score ≥7), but a significant increased risk of urinary cancers was observed in lower quality studies (score <7) (dominant model: OR=1.27, 95% CI=1.11-1.45).Our meta-analysis suggests that APE1 Asp148Glu was not associated with the risk of urinary cancers but might increase the risk of urinary cancers among Asians. Stratification by cancer type identified a significant association of Asp148Glu with prostate cancer.ZhongJie-HuiJHDepartment of Clinical Medicine, The First Clinical Medical College, Southern Medical University, Guangzhou, People's Republic of China; Institute of Genetic Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China.ZhaoZhenZDepartment of Urinary Surgery, Southern Medical University, Guangzhou, People's Republic of China.LiuJieJDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.YuHai-LangHLInstitute of Genetic Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China.ZhouJue-YuJYInstitute of Genetic Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China.ShiRongRInstitute of Genetic Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China.engJournal Article20160315
New ZealandOnco Targets Ther1015143221178-6930Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Biochimie. 2003 Nov;85(11):1053-7114726013Indian J Med Res. 2012;135:64-7122382185Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Carcinogenesis. 2011 Jul;32(7):945-5421459759Carcinogenesis. 2005 Jul;26(7):1263-7115746160Mutat Res. 2000 Oct 16;461(2):83-10811018583DNA Cell Biol. 2010 Jun;29(6):303-1120218899Environ Mol Mutagen. 1999;33(1):3-2010037319J Urol. 2006 Jan;175(1):108-12; discussion 11216406883Mol Carcinog. 2011 Nov;50(11):863-7021538578Genet Med. 2002 Mar-Apr;4(2):45-6111882781Control Clin Trials. 1986 Sep;7(3):177-883802833Tumour Biol. 2014 Oct;35(10):10111-925023401Mol Biol Rep. 2011 Mar;38(3):1585-9120852942JAMA. 1990 Mar 9;263(10 ):1385-92406472Carcinogenesis. 2006 May;27(5):997-100716308313Prostate. 2010 Feb 1;70(2):113-919760636Curr Opin Genet Dev. 2004 Feb;14(1):5-1015108798Genome Med. 2010 Jul 29;2(7):4520667146Int J Cancer. 2006 Jun 15;118(12):3170-316425270Hum Hered. 2008;65(2):105-1817898541BMJ. 2003 Sep 6;327(7414):557-6012958120Carcinogenesis. 2001 Jun;22(6):917-2211375899Carcinogenesis. 2009 May;30(5):763-819237606Carcinogenesis. 2006 May;27(5):1030-716311243Carcinogenesis. 2000 Jul;21(7):1329-3410874010Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):84-9117220334Hum Genet. 2007 Apr;121(2):233-4217203305Bioessays. 1995 Aug;17(8):713-97661852Genomics. 2004 Jun;83(6):970-915177551Urology. 2009 Mar;73(3):675-8019041121CA Cancer J Clin. 2015 Jan-Feb;65(1):5-2925559415Am J Epidemiol. 2005 Aug 1;162(3):201-1115987731J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060DNA Repair (Amst). 2010 Feb 4;9(2):191-20020061190Am J Hum Genet. 2006 Mar;78(3):464-7916465622Carcinogenesis. 2012 Jul;33(7):1259-6922523086BMJ. 1997 Sep 13;315(7109):629-349310563J Cancer Res Clin Oncol. 2014 Feb;140(2):179-8824077840CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Cancer Res. 2004 Mar 15;64(6):2251-715026370Clin Lab. 2013;59(1-2):163-823505922Mol Genet Genomics. 2015 Feb;290(1):281-825234162Methods Mol Biol. 2009;471:361-8519109789Nucleic Acids Res. 1992 Sep 11;20(17):4417-211383925Anticancer Res. 2009 Apr;29(4):1389-9319414392Cell Mol Biol (Noisy-le-grand). 2015 Aug 05;61(4):21-426255264Mech Ageing Dev. 2012 Apr;133(4):127-3222019847Curr Opin Genet Dev. 2010 Jun;20(3):201-920418093Environ Health Perspect. 2003 Nov;111(15):1843-5014630517Mol Biol Rep. 2013 Jan;40(1):171-623143180APE1cancermeta-analysispolymorphism
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2193-180152016SpringerPlusSpringerplusAssociation between OGG1 Ser326Cys polymorphism and risk of upper aero-digestive tract and gastrointestinal cancers: a meta-analysis.22710.1186/s40064-016-1858-5Cancers of the upper aero-digestive and gastrointestinal tract are one of the major causes of mortality around the world. DNA repair genes play a vital role in preventing carcinogenesis by maintaining genomic integrity. Polymorphisms in the nucleotide sequence of DNA repair genes are often reported to be associated with an increased risk for different cancers. The OGG1 gene encodes the enzyme 8-oxoguanine DNA glycosylase which removes oxidatively damaged bases of DNA. Several studies report that the OGG1 Ser326Cys polymorphism increases the risk for cancers of the upper aero-digestive and gastrointestinal tract. However, other studies provide evidence that such an association does not exist. A meta-analysis to assess the role of OGG1 Ser326Cys polymorphism in the cancers of the upper aero-digestive and gastrointestinal tract was therefore undertaken in order to resolve this ambiguity. Seventeen studies were recruited for this meta-analysis after screening 58 articles with a total of 5533 cases and 6834 controls for which the odds ratio with 95 % confidence interval was calculated. Begg's funnel test and Egger's test were performed for calculating publication bias. Our study reveals an association between OGG1 Ser326Cys polymorphism and cancer susceptibility of the upper aero-digestive and gastrointestinal tract (CG + GG vs CC; odds ratio, OR 1.22; 95 % CI 1.05-1.41; GG vs CG + CC; OR 1.36; 95 % CI 1.09-1.70; GG vs CC; OR 1.46; 95 % CI 1.12-1.92). Subgroup analysis based on cancer types and ethnicity also revealed the association of OGG1 Ser326Cys polymorphism to the risk for upper aero-digestive and gastrointestinal tract cancers among both the Asian and the Caucasian populations. No risk was however observed for smoking habits and OGG1 Ser326Cys polymorphism. In conclusion, OGG1 Ser326Cys polymorphism may be associated with the increased risk for aero-digestive tract and gastro-intestinal cancers in both Asian and Caucasian populations. DasSambuddhaSDepartment of Biotechnology, Assam University, Silchar, 788011 India.NathSayantanSDepartment of Biotechnology, Assam University, Silchar, 788011 India.BhowmikAditiADepartment of Biotechnology, Assam University, Silchar, 788011 India.GhoshSankar KumarSKDepartment of Biotechnology, Assam University, Silchar, 788011 India.ChoudhuryYashminYDepartment of Biotechnology, Assam University, Silchar, 788011 India.engJournal ArticleReview20160229
SwitzerlandSpringerplus1015979672193-1801Genet Test Mol Biomarkers. 2013 Oct;17(10):780-523909557Mutat Res. 2011 Dec 24;726(2):227-3321986195Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Mol Carcinog. 2011 Sep;50(9):732-721520294Med Oncol. 2015 Feb;32(2):47225588927Indian J Med Res. 2010 Aug;132:129-4920716813Mutat Res. 2013 May-Jun;745-746:6-1523618615N Engl J Med. 2009 Oct 8;361(15):1475-8519812404Tumour Biol. 2015 Sep;36(10):7569-7925916209Nature. 2004 Nov 18;432(7015):294-715549090Free Radic Res. 2006 Aug;40(8):885-9117015267Asian Pac J Cancer Prev. 2013;14(9):5145-5124175791Anticancer Res. 2010 Apr;30(4):1359-6420530453Gastroenterol Hepatol Bed Bench. 2015 Winter;8(1):19-2725584172Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12 ):3384-819959686Carcinogenesis. 2014 Jul;35(7):1523-724658182BMJ. 1998 Feb 7;316(7129):469; author reply 470-19492685Biometrika. 1950 Dec;37(3-4):256-6614801052Asian Pac J Cancer Prev. 2015 ;16(14 ):5767-7226320449Control Clin Trials. 1986 Sep;7(3):177-883802833J Gastrointest Cancer. 2010 Jun;41(2):110-520069464Ann Surg Oncol. 2009 Jun;16(6):1695-70319266243Oral Oncol. 2007 Sep;43(8):791-517207658Mutat Res. 2010 Apr-Jun;704(1-3):152-920060490Mutat Res. 2008 Feb 1;638(1-2):146-5317991492DNA Cell Biol. 2012 Apr;31(4):541-621899442Int J Colorectal Dis. 2011 Dec;26(12):1525-3021695387Tumour Biol. 2014 Mar;35(3):2397-40224186001Mol Biol Rep. 2011 Feb;38(2):1251-6120571908Mutagenesis. 2010 Nov;25(6):569-7520817763Tumour Biol. 2014 Jan;35(1):513-723975367Cancer Res. 2009 Apr 15;69(8):3642-919351836Mol Biol Rep. 2011 Nov;38(8):5379-8621390502J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060Cancer. 2010 Jul 1;116(13):3160-920564624Carcinogenesis. 2002 Jul;23(7):1229-3412117782BMJ. 1997 Sep 13;315(7109):629-349310563Clin Cancer Res. 2009 Jan 15;15(2):740-619147782Asian Pac J Cancer Prev. 2011;12(12):3427-3122471492Curr Med Res Opin. 2011 Jul;27(7):1295-30221561390GastrointestinalMeta-analysisOGG1Upper aero-digestive tract
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2219-284022122016Mar28World journal of gastroenterologyWorld J. Gastroenterol.Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan.3372-8010.3748/wjg.v22.i12.3372To evaluate the effects of OGG1 (Ser326Cys, 11657A/G, and Arg154His) and APE1 (Asp148Glu, and T-656G) polymorphisms on colorectal cancer (CRC) risk.We enrolled 727 cases newly diagnosed with colorectal adenocarcinoma and 736 age- and sex-matched healthy controls from a medical center in Taiwan. Genomic DNA isolated from the buffy coat was used for genotyping through polymerase chain reaction. Unconditional logistic regressions were used for calculating ORs and 95%CIs to determine the association between the genetic polymorphisms and CRC risk. Haplotype frequencies were estimated using PHASE software. Moreover, stratification analyses on the basis of sex, age at diagnosis, and tumor subsite and stage were performed.The CRC risk was higher in patients with the OGG1 326Ser/Cys + Cys/Cys genotype (OR = 1.38, 95%CI: 1.03-1.85, P = 0.030), particularly high in patients with stage III + IV cancer (OR = 1.48, 95%CI: 1.03-2.13) compared with patients with the Ser/Ser genotype. In addition, OGG1 11657G allele carriers had a 41% reduced CRC risk among stage 0-II patients (OR = 0.59, 95%CI: 0.35-0.98). The CRC risk was significantly higher among females with the APE1 Glu allele (OR = 1.41, 95%CI: 1.02-1.96). The APE1 148Glu/-656G haplotype was also associated with a significant CRC risk in females (OR = 1.36, 95%CI: 1.03-1.78).OGG1 and APE1 polymorphisms are associated with stage- and sex-specific risk of CRC in the Taiwanese population.LaiChing-YuCYChing-Yu Lai, Chih-Ching Yeh, School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan.HsiehLing-LingLLChing-Yu Lai, Chih-Ching Yeh, School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan.TangReipingRChing-Yu Lai, Chih-Ching Yeh, School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan.SantellaRegina MRMChing-Yu Lai, Chih-Ching Yeh, School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan.Chang-ChiehChung RongCRChing-Yu Lai, Chih-Ching Yeh, School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan.YehChih-ChingCCChing-Yu Lai, Chih-Ching Yeh, School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan.engP30 ES009089ESNIEHS NIH HHSUnited StatesComparative StudyJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't
United StatesWorld J Gastroenterol1008834481007-9327EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMInt J Cancer. 2009 Apr 1;124(7):1565-7119115208Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Mutagenesis. 2009 Nov;24(6):507-1219762350Mutagenesis. 2010 Sep;25(5):463-7120534734Clin Cancer Res. 2011 Apr 1;17(7):1701-1221355073Int J Colorectal Dis. 2011 Dec;26(12):1525-3021695387BMC Cancer. 2011;11:52122176746J Cancer Res Clin Oncol. 2012 Sep;138(9):1443-822526153Mol Carcinog. 2012 Oct;51 Suppl 1:E94-10322213390Hum Exp Toxicol. 2012 Oct;31(10):981-100523023028Med Oncol. 2013 Jun;30(2):50523430444World J Gastroenterol. 2014 Jul 14;20(26):8700-825024628Int J Biochem Cell Biol. 2000 Feb;32(2):157-7010687951Clin Cancer Res. 2000 Apr;6(4):1394-40010778969Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Carcinogenesis. 2001 Jun;22(6):917-2211375899Cancer Res. 2002 Apr 15;62(8):2253-711956079World J Gastroenterol. 2003 May;9(5):956-6012717837J Formos Med Assoc. 2003 May;102(5):305-1212874668Genomics. 2004 Jun;83(6):970-915177551IARC Sci Publ. 1980;(32):5-3387216345J Mol Med (Berl). 1996 Jun;74(6):297-3128862511Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-99207062Jpn J Cancer Res. 1998 Aug;89(8):825-89765618Genome Res. 1999 May;9(5):492-810330129BMC Cancer. 2005 Jan 28;5:1215679883World J Gastroenterol. 2005 Mar 14;11(10):1473-8015770723Nucleic Acids Res. 2006;34(5):1620-3216549874Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2101-816609022Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):811-516614128J Radiat Res. 2006;47 Suppl B:B13-717019047J Biomed Sci. 2007 Mar;14(2):183-9317191090Mol Aspects Med. 2007 Jun-Aug;28(3-4):258-7517628657J Epidemiol. 2007 Sep;17(5):156-6017827862Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2363-7218006925Mutat Res. 2008 Feb 1;638(1-2):146-5317991492J Exp Clin Cancer Res. 2008;27:4918823566FASEB J. 2009 Oct;23(10):3459-6919541747AdenocarcinomaenzymologygeneticspathologyAgedCase-Control StudiesChi-Square DistributionColorectal NeoplasmsenzymologygeneticspathologyDNA GlycosylasesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseHaplotypesHumansLogistic ModelsMaleMiddle AgedNeoplasm StagingOdds RatioPhenotypePolymorphism, Single NucleotideRisk FactorsSex FactorsTaiwanAPE1Colorectal cancerOGG1PolymorphismsTaiwan
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1949-25537182016May03OncotargetOncotargetMolecular insights into the OGG1 gene, a cancer risk modifier in BRCA1 and BRCA2 mutations carriers.25815-2510.18632/oncotarget.8272We have recently shown that rs2304277 variant in the OGG1 glycosidase gene of the Base Excision Repair pathway can increase ovarian cancer risk in BRCA1 mutation carriers. In the present study, we aimed to explore the role of this genetic variant on different genome instability hallmarks to explain its association with cancer risk.We have evaluated the effect of this polymorphism on OGG1 transcriptional regulation and its contribution to telomere shortening and DNA damage accumulation. For that, we have used a series of 89 BRCA1 and BRCA2 mutation carriers, 74 BRCAX cases, 60 non-carrier controls and 23 lymphoblastoid cell lines (LCL) derived from BRCA1 mutation carriers and non-carriers.We have identified that this SNP is associated to a significant OGG1 transcriptional down regulation independently of the BRCA mutational status and that the variant may exert a synergistic effect together with BRCA1 or BRCA2 mutations on DNA damage and telomere shortening.These results suggest that this variant, could be associated to a higher cancer risk in BRCA1 mutation carriers, due to an OGG1 transcriptional down regulation and its effect on genome instability. Benitez-BuelgaCarlosCHuman Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.VaclováTerezaTHuman Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.FerreiraSofiaSHuman Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.UriosteMiguelMFamilial Cancer Clinical Unit, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.Spanish Network on Rare Diseases (CIBERER), Madrid 28029, Spain.Inglada-PerezLuciaLEndocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.Spanish Network on Rare Diseases (CIBERER), Madrid 28029, Spain.SoberónNoraNTelomere and Telomerase Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.BlascoMaria AMATelomere and Telomerase Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.OsorioAnaAHuman Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.Spanish Network on Rare Diseases (CIBERER), Madrid 28029, Spain.BenitezJavierJHuman Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.Spanish Network on Rare Diseases (CIBERER), Madrid 28029, Spain.engR01 DA006227DANIDA NIH HHSUnited StatesR01 MH101782MHNIMH NIH HHSUnited StatesR01 MH101810MHNIMH NIH HHSUnited StatesR01 MH101819MHNIMH NIH HHSUnited StatesR01 DA033684DANIDA NIH HHSUnited StatesR01 MH090936MHNIMH NIH HHSUnited StatesR01 MH090951MHNIMH NIH HHSUnited StatesR01 MH101820MHNIMH NIH HHSUnited StatesR01 MH101825MHNIMH NIH HHSUnited StatesR01 MH090948MHNIMH NIH HHSUnited StatesR01 MH090941MHNIMH NIH HHSUnited StatesR01 MH101822MHNIMH NIH HHSUnited StatesHHSN261200800001CRCCCR NIH HHSUnited StatesR01 MH090937MHNIMH NIH HHSUnited States232854European Research CouncilInternationalHHSN268201000029CHLNHLBI NIH HHSUnited StatesHHSN261200800001ECANCI NIH HHSUnited StatesR01 MH101814MHNIMH NIH HHSUnited StatesJournal Article
United StatesOncotarget1015329651949-25530BRCA1 Protein0BRCA1 protein, human0BRCA2 Protein0BRCA2 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMHum Mol Genet. 2013 Dec 15;22(24):5056-6423900074Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5300-517369361PLoS Genet. 2014 Apr 03;10(4):e100425624698998PLoS Genet. 2010 May 13;6(5):e100095120485567J Mol Cell Cardiol. 2015 Jan;78:9-2225446179Breast Cancer Res Treat. 2010 Aug;122(3):835-4220058067EMBO J. 2010 Jan 20;29(2):398-40919942858Mutat Res. 2013 Aug 15;755(2):115-923830927Am J Hum Genet. 2007 Dec;81(6):1186-20017999359Carcinogenesis. 2014 Jun;35(6):1426-3324632493Cancer Res. 2016 Jan 1;76(1):30-426586787Dig Dis Sci. 2012 Sep;57(9):2451-722565339Nucleic Acids Res. 2015 Apr 30;43(8):4039-5425813041Hum Mutat. 2012 Dec;33(12):1665-7522753153PLoS One. 2011;6(11):e2754522114677PLoS One. 2014 Oct 29;9(10):e11096325354277Nat Genet. 2006 Jul;38(7):813-816751773Nature. 2003 Jan 23;421(6921):436-4012540918Acta Chim Slov. 2010 Mar;57(1):182-824061671Cancer Res. 2001 Feb 1;61(3):912-511221881Cell Res. 2008 Jan;18(1):27-4718166975Mutat Res. 2013 Jul-Sep;753(1):24-4023416207BMC Cancer. 2012 May 15;12:17722587342Carcinogenesis. 2014 Dec;35(12):2643-5225355293Nat Genet. 2001 Mar;27(3):247-5411242102Cancer Res. 2003 Mar 1;63(5):902-512615700Breast Cancer Res Treat. 2015 Jan;149(2):385-9425528024Breast Cancer Res Treat. 2015 Jul;152(2):271-8226071757Br J Cancer. 2011 Apr 12;104(8):1356-6121427728Nature. 2005 Apr 14;434(7035):917-2115829967Clin Cancer Res. 2008 May 1;14(9):2861-918451254Free Radic Biol Med. 2000 Jan 1;28(1):64-7410656292Mol Biol Rep. 2011 Feb;38(2):1163-7020602259Nat Rev Genet. 2008 Aug;9(8):619-3118626472Am J Hum Genet. 2003 May;72(5):1117-3012677558BRCA1 ProteingeneticsBRCA2 ProteingeneticsDNA GlycosylasesgeneticsFemaleGene Expression Regulation, NeoplasticgeneticsGenetic Predisposition to DiseasegeneticsGenotypeHumansMutationOvarian NeoplasmsgeneticsPolymorphism, Single NucleotideRisk FactorsBRCA1 and BRCA2DNA damageOGG1 polymorfismcancer risk modifiertelomere shorteningThe authors declare no conflicts of interest.
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1949-25537162016Apr19OncotargetOncotargetRegulation of limited N-terminal proteolysis of APE1 in tumor via acetylation and its role in cell proliferation.22590-60410.18632/oncotarget.8026Mammalian apurinic/apyrimidinic (AP) endonuclease 1 (APE1), a ubiquitous and multifunctional protein, plays an essential role in the repair of both endogenous and drug-induced DNA damages in the genome. Unlike its E.coli counterpart Xth, mammalian APE1 has a unique N-terminal domain and possesses both DNA damage repair and transcriptional regulatory functions. Although the overexpression of APE1 in diverse cancer types and the association of APE1 expression with chemotherapy resistance and poor prognosis are well documented, the cellular and molecular mechanisms that alter APE1 functions during tumorigenesis are largely unknown. Here, we show the presence of full-length APE1 and N-terminal truncated isoforms of APE1 in tumor tissue samples of various cancer types. However, primary tumor tissue has higher levels of acetylated APE1 (AcAPE1) as well as full-length APE1 compared to adjacent non-tumor tissue. We found that APE1 is proteolytically cleaved by an unknown serine protease at its N-terminus following residue lysine (Lys) Lys6 and/or Lys7 and after Lys27 and Lys31 or Lys32. Acetylation of these Lys residues in APE1 prevents this proteolysis. The N-terminal domain of APE1 and its acetylation are required for modulation of the expression of hundreds of genes. Importantly, we found that AcAPE1 is essential for sustained cell proliferation. Together, our study demonstrates that increased acetylation levels of APE1 in tumor cells inhibit the limited N-terminal proteolysis of APE1 and thereby maintain the functions of APE1 to promote tumor cells' sustained proliferation and survival. BhakatKishor KKKDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE-68198, USA.Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE-68198, USA.Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX-77555, USA.SenguptaShiladityaSDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX-77555, USA.Current Affiliation: Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX-77030, USA.AdeniyiVictor FVFDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX-77555, USA.RoychoudhuryShrabastiSDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE-68198, USA.NathSomsubhraSDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE-68198, USA.Current Affiliation: Molecular Biology Research and Diagnostic Laboratory, Saroj Gupta Cancer Centre and Research Institute (SGCC & RI), Kolkata-63, India.BellotLarry JLJDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX-77555, USA.FengDanDDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE-68198, USA.ManthaAnil KAKCenter for Animal Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab 151001, India.SinhaMalaMDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX-77555, USA.Bioinformatics Program, University of Texas Medical Branch, Galveston, TX-77555, USA.QiuSuiminSDepartment of Pathology, University of Texas Medical Branch, Galveston, TX-77555, USA.LuxonBruce ABADepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX-77555, USA.Bioinformatics Program, University of Texas Medical Branch, Galveston, TX-77555, USA.engR01 CA148941CANCI NIH HHSUnited StatesJournal Article
United StatesOncotarget1015329651949-2553EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAntioxid Redox Signal. 2009 Mar;11(3):621-3818715144Mutat Res. 2008 Aug 25;643(1-2):54-6318579163Cancer Treat Rev. 2010 Aug;36(5):425-3520056333DNA Repair (Amst). 2011 Sep 5;10(9):942-5221741887Oncogene. 2011 Jan 27;30(4):482-9320856196Antioxid Redox Signal. 2011 Apr 15;14(8):1387-40120874257Subcell Biochem. 2013;61:37-5523150245DNA Repair (Amst). 2005 Dec 8;4(12):1442-916199212Mol Biol Cell. 2011 Oct;22(20):3887-90121865600Nucleic Acids Res. 2010 Jan;38(3):832-4519934257J Biol Chem. 1994 Nov 11;269(45):27855-627961715Mol Biol Cell. 2012 Oct;23(20):4079-9622918947EMBO J. 2003 Dec 1;22(23):6299-30914633989Free Radic Biol Med. 2002 Jul 1;33(1):15-2812086678Mol Cell Biol. 2008 Dec;28(23):7066-8018809583Mutat Res. 2015 Sep;779:96-10426164266PLoS One. 2013 Jul 16;8(7):e6846723874636J Hypertens. 2012 May;30(5):917-2522441348Nat Immunol. 2003 Feb;4(2):145-5312524539Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Free Radic Res. 2008 Jan;42(1):20-918324520Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-69560228Carcinogenesis. 1998 Mar;19(3):525-79525290Genome Biol. 2004;5(10):R8015461798Biochemistry. 2012 Jan 17;51(2):695-70522148505Mol Endocrinol. 2009 Sep;23(9):1346-5919460860Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3523-811904416Nucleic Acids Res. 2005 Jun 07;33(10 ):3303-1215942031J Biol Chem. 2003 Sep 26;278(39):37768-7612842873Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Cell Mol Life Sci. 2010 Nov;67(21):3621-3120809131Mol Cell. 2005 Feb 4;17(3):463-7015694346J Mol Biol. 2013 Jul 10;425(13):2359-7123542007Nucleic Acids Res. 2010 Dec;38(22):8239-5620699270J Mol Biol. 2008 May 23;379(1):28-3718436236J Pathol. 1999 Nov;189(3):351-710547596Cancer Res. 2013 Aug 15;73(16):4965-7723913938Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Gastroenterology. 2009 Jun;136(7):2258-6919505426Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463Oncogene. 2009 Apr 2;28(13):1616-2519219073Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766Int J Radiat Oncol Biol Phys. 2001 May 1;50(1):27-3611316543Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128AcetylationCell ProliferationphysiologyDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismGene Expression Regulation, NeoplasticphysiologyHumansNeoplasmsmetabolismpathologyProteolysisTumor Cells, CulturedAPE1acetylationbase excision repairproliferationproteolysisThe authors disclose no potential conflicts of interest.
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1362-4962441120160620Nucleic acids researchNucleic Acids Res.Oxidized dNTPs and the OGG1 and MUTYH DNA glycosylases combine to induce CAG/CTG repeat instability.5190-20310.1093/nar/gkw170DNA trinucleotide repeat (TNR) expansion underlies several neurodegenerative disorders including Huntington's disease (HD). Accumulation of oxidized DNA bases and their inefficient processing by base excision repair (BER) are among the factors suggested to contribute to TNR expansion. In this study, we have examined whether oxidation of the purine dNTPs in the dNTP pool provides a source of DNA damage that promotes TNR expansion. We demonstrate that during BER of 8-oxoguanine (8-oxodG) in TNR sequences, DNA polymerase β (POL β) can incorporate 8-oxodGMP with the formation of 8-oxodG:C and 8-oxodG:A mispairs. Their processing by the OGG1 and MUTYH DNA glycosylases generates closely spaced incisions on opposite DNA strands that are permissive for TNR expansion. Evidence in HD model R6/2 mice indicates that these DNA glycosylases are present in brain areas affected by neurodegeneration. Consistent with prevailing oxidative stress, the same brain areas contained increased DNA 8-oxodG levels and expression of the p53-inducible ribonucleotide reductase. Our in vitro and in vivo data support a model where an oxidized dNTPs pool together with aberrant BER processing contribute to TNR expansion in non-replicating cells.© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.CilliPieraPDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, 00161 Roma, Italy Department of Science, University Roma Tre, 00154 Roma, Italy.VenturaIleniaIDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, 00161 Roma, Italy.MinoprioAnnaADepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, 00161 Roma, Italy.MecciaEttoreEDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, 00161 Roma, Italy.MartireAlbertoADepartment of Drug Safety and Evaluation, Istituto Superiore di Sanità, 00161 Roma, Italy.WilsonSamuel HSHGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.BignamiMargheritaMDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, 00161 Roma, Italy Margherita.bignami@gmail.com.MazzeiFilomenaFDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, 00161 Roma, Italy filomena.mazzei@iss.it.engZ01 ES050158ESNIEHS NIH HHSUnited StatesZ01 ES050159ESNIEHS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., IntramuralResearch Support, Non-U.S. Gov't20160314
EnglandNucleic Acids Res04110110305-104888847-89-68-oxo-7-hydrodeoxyguanosine9007-49-2DNAEC 2.7.7.-DNA Polymerase betaEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanG9481N71RODeoxyguanosineIMProc Natl Acad Sci U S A. 2012 Aug 14;109(33):13302-722847445Nat Struct Mol Biol. 2010 Jul;17(7):889-9020526335J Biol Chem. 2015 Oct 23;290(43):26259-6926338705Methods Enzymol. 1995;262:98-1078594388Biochemistry. 2000 Feb 8;39(5):1029-3310653647PLoS Genet. 2015 Apr 17;11(4):e100518125886163Neurobiol Dis. 2009 Jan;33(1):37-4718930147Cell. 1996 Nov 1;87(3):493-5068898202Nucleic Acids Res. 2008 Apr;36(7):2174-8118276636J Biol Chem. 1998 Jan 9;273(2):898-9029422747Nature. 2006 Oct 19;443(7113):787-9517051205Neurobiol Dis. 2013 Jan;49:148-5822974734Hum Mol Genet. 2002 Jan 15;11(2):191-811809728Trends Biochem Sci. 2012 Apr;37(4):162-7222285516Hum Mol Genet. 2003 Sep 15;12(18):2301-912915485Nucleic Acids Res. 2013 Apr;41(7):4093-10323460202PLoS Genet. 2009 Dec;5(12):e100074919997493J Clin Invest. 2012 Dec;122(12 ):4344-6123143307Prog Neurobiol. 1999 Dec;59(5):427-6810515664Free Radic Biol Med. 2006 Aug 15;41(4):620-616863995Nature. 2007 May 24;447(7143):447-5217450122Hum Mol Genet. 1999 Jan;8(1):115-229887339Nat Rev Genet. 2010 Nov;11(11):786-9920953213Neurosci Lett. 1999 Sep 3;272(1):53-610507541Nat Genet. 1999 Dec;23(4):471-310581038Hum Mol Genet. 2003 Feb 1;12 (3):273-8112554681Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12277-8223840062J Biol Chem. 2009 Oct 9;284(41):28352-6619674974Biochemistry. 2012 May 8;51(18):3919-3222497302FASEB J. 2006 Jul;20(9):1300-1416816105PLoS Genet. 2008 Nov;4(11):e100026619023407J Biol Chem. 2000 Jun 2;275(22):16420-710748145Am J Pathol. 2012 Oct;181(4):1378-8622841817J Mol Biol. 2007 Apr 13;367(5):1258-6917321545Hum Mutat. 2010 Feb;31(2):159-6619953527Mutat Res. 2013 Mar-Apr;743-744:33-4323507534PLoS Genet. 2010 Dec 09;6(12 ):e100124221170307Biochemistry. 2007 Jun 5;46(22):6639-4617497830Mutat Res. 2010 Nov 28;703(1):18-2320696268Nat Genet. 1993 Aug;4(4):387-928401587Biochemistry. 1994 Apr 19;33(15):4695-7018161527J Biol Chem. 1998 May 1;273(18):11069-749556591J Neurosci. 2006 Feb 8;26(6):1688-9816467516J Biol Chem. 1993 Nov 5;268(31):23524-308226881EMBO Rep. 2003 Mar;4(3):269-7312634844Nature. 2015 Jan 29;517(7536):635-925409153DNA Repair (Amst). 2008 Jul 1;7(7):1121-3418472310J Neurochem. 2001 Dec;79(6):1246-911752065Mol Cell. 1999 Dec;4(6):1079-8510635332Biochemistry. 2000 Aug 8;39(31):9508-1310924147Hum Mol Genet. 2012 Nov 15;21(22):4939-4722914735Nucleic Acids Res. 2005 Sep 20;33(16):5094-10516174844Nature. 2000 Mar 2;404(6773):42-910716435Nat Struct Mol Biol. 2005 Aug;12(8):663-7016025128Biochemistry. 1999 Mar 23;38(12):3610-410090747Cell Death Differ. 2006 Apr;13(4):551-6316273081PLoS Genet. 2015 Aug 06;11(8):e100526726247199J Biol Chem. 2006 Mar 24;281(12 ):7834-4116436374AnimalsDNAgeneticsmetabolismDNA GlycosylasesmetabolismDNA Polymerase betametabolismDNA RepairDeoxyguanosineanalogs & derivativesFemaleGenomic InstabilityHumansMaleMiceMice, TransgenicModels, BiologicalOxidation-ReductionOxidative StressTrinucleotide Repeat ExpansionTrinucleotide Repeats
2016030320151204201631760201631760201752760ppublish26980281gkw17010.1093/nar/gkw170PMC4914090
269800512017081520180113
1532-839252201606Human pathologyHum. Pathol.Reduced MUTYH, MTH1, and OGG1 expression and TP53 mutation in diffuse-type adenocarcinoma of gastric cardia.145-5210.1016/j.humpath.2016.01.006S0046-8177(16)00038-1The effects of oxidative stress in adenocarcinomas of gastric cardia (AGCs) have not been fully elucidated. With a strict definition of AGC, we examined the immunohistochemical expressions of inducible nitric oxide synthase; 8-hydroxy-deoxyguanosine; and the base excision repair enzymes such as MUTYH, MTH1, and OGG1, and TP53 mutational status. Sixty-three cases of AGC were characterized by younger patient age (P = .0227) and more frequent venous invasion (P = .0106) compared with the adenocarcinomas of pylorus (APs). 8-hydroxy-deoxyguanosine was accumulated (P = .0011), whereas MUTYH (P = .0325) and OGG1 (P = .0007) were decreased, in the AGCs compared with the adjacent mucosa, but these differences were not detected in the APs. Among the AGCs, lower expressions of MUTYH (P = .0013) and MTH1 (P = .0059) were each significantly associated with diffuse-type histology. A lower expression of OGG1 was correlated with higher T-stage (P = .0011), lymphatic invasion (P = .004), and lymph node metastasis (P = .0094). In addition, the presence of TP53 mutation was associated with diffuse-type histology (P = .0153) and a lower level of MUTYH (P = .0221). The AGCs also showed a relatively high rate of a transversion-type mutation of TP53 (50%), whereas all TP53 mutations in the APs were transition type. Age 62years or older (P = .0073), diffuse-type histology (P = .0020), and TP53 mutation (P = .0066) were each associated with worse survival in the AGC patients. Our results indicate that oxidative stress accumulation and a downregulation of base excision repair enzymes may play an important role in the pathogenesis of AGC, in particular diffuse-type AGCs. Diffuse-type AGC might involve molecular pathways different from those of other subsets of gastric cancer.Copyright © 2016 Elsevier Inc. All rights reserved.KohnoYukikoYDepartment of Anatomic Pathology, Graduate of School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.YamamotoHidetakaHDepartment of Anatomic Pathology, Graduate of School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.HirahashiMinakoMDepartment of Anatomic Pathology, Graduate of School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.KumagaeYoshiteruYDepartment of Anatomic Pathology, Graduate of School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.NakamuraMasafumiMDepartment of Surgery and Oncology, Graduate of School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.OkiEijiEDepartment of Surgery and Science, Graduate of School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.OdaYoshinaoYDepartment of Anatomic Pathology, Graduate of School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: oda@surgpath.med.kyushu-u.ac.jp.engJournal Article20160204
United StatesHum Pathol94215470046-81770Biomarkers, Tumor0TP53 protein, human0Tumor Suppressor Protein p5388847-89-68-oxo-7-hydrodeoxyguanosineEC 1.14.13.39NOS2 protein, humanEC 1.14.13.39Nitric Oxide Synthase Type IIEC 3.1.3.2Phosphoric Monoester HydrolasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.1.558-oxodGTPaseEC 6.5.1.-DNA Repair EnzymesG9481N71RODeoxyguanosineIMAdenocarcinomaenzymologygeneticsmortalitysecondaryAdultAgedAged, 80 and overBiomarkers, TumoranalysisgeneticsCardiaenzymologypathologyDNA GlycosylasesanalysisDNA Mutational AnalysisDNA RepairDNA Repair EnzymesanalysisDeoxyguanosineanalogs & derivativesanalysisDisease-Free SurvivalDown-RegulationFemaleGenetic Predisposition to DiseaseHumansImmunohistochemistryKaplan-Meier EstimateLymphatic MetastasisMaleMiddle AgedMutationNeoplasm StagingNitric Oxide Synthase Type IIanalysisOxidative StressPhenotypePhosphoric Monoester HydrolasesanalysisRetrospective StudiesStomach NeoplasmsenzymologygeneticsmortalitypathologyTumor Suppressor Protein p53geneticsAdenocarcinomaBase excision repair enzymesCardiaOxidative stressStomach
201511252016010720160114201631760201631760201781660ppublish26980051S0046-8177(16)00038-110.1016/j.humpath.2016.01.006
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2045-232262016Mar11Scientific reportsSci RepSecreted APE1/Ref-1 inhibits TNF-α-stimulated endothelial inflammation via thiol-disulfide exchange in TNF receptor.2301510.1038/srep23015Apurinic apyrimidinic endonuclease 1/Redox factor-1 (APE1/Ref-1) is a multifunctional protein with redox activity and is proved to be secreted from stimulated cells. The aim of this study was to evaluate the functions of extracellular APE1/Ref-1 with respect to leading anti-inflammatory signaling in TNF-α-stimulated endothelial cells in response to acetylation. Treatment of TNF-α-stimulated endothelial cells with an inhibitor of deacetylase that causes intracellular acetylation, considerably suppressed vascular cell adhesion molecule-1 (VCAM-1). During TSA-mediated acetylation in culture, a time-dependent increase in secreted APE1/Ref-1 was confirmed. The acetyl moiety of acetylated-APE1/Ref-1 was rapidly removed based on the removal kinetics. Additionally, recombinant human (rh) APE1/Ref-1 with reducing activity induced a conformational change in rh TNF-α receptor 1 (TNFR1) by thiol-disulfide exchange. Following treatment with the neutralizing anti-APE1/Ref-1 antibody, inflammatory signals via the binding of TNF-α to TNFR1 were remarkably recovered, leading to up-regulation of reactive oxygen species generation and VCAM-1, in accordance with the activation of p66(shc) and p38 MAPK. These results strongly indicate that anti-inflammatory effects in TNF-α-stimulated endothelial cells by acetylation are tightly linked to secreted APE1/Ref-1, which inhibits TNF-α binding to TNFR1 by reductive conformational change, with suggestion as an endogenous inhibitor of vascular inflammation. ParkMyoung SooMSInfectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of KOREA.ChoiSungaSInfectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of KOREA.LeeYu RanYRInfectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of KOREA.JooHee KyoungHKInfectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of KOREA.KangGunGInfectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of KOREA.KimCuk-SeongCSInfectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of KOREA.KimSoo JinSJInfectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of KOREA.LeeSang DoSDInfectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of KOREA.JeonByeong HwaBHInfectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of KOREA.engJournal ArticleResearch Support, Non-U.S. Gov't20160311
EnglandSci Rep1015632882045-23220Anti-Inflammatory Agents0Histone Deacetylase Inhibitors0Receptors, Tumor Necrosis Factor, Type I0Repressor Proteins0Tumor Necrosis Factor-alpha0Vascular Cell Adhesion Molecule-10p66alpha protein, humanEC 2.7.11.24p38 Mitogen-Activated Protein KinasesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMFEBS Lett. 2012 May 7;586(9):1349-5522616995Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2404-916141407Antioxid Redox Signal. 2008 Nov;10(11):1853-6718627350PLoS One. 2013;8(8):e7215623977237FASEB J. 2000 Sep;14(12):1705-1410973919Biochem Biophys Res Commun. 2013 Jun 14;435(4):621-623685156Mol Cell Proteomics. 2011 Jun;10(6):M110.00533021474795J Immunol. 2014 Sep 1;193(5):2427-3725063869Blood Cancer J. 2013 Dec 13;3:e16924335889J Mol Endocrinol. 2000 Jun;24(3):383-9010828831Nat Med. 2001 Apr;7(4):437-4311283670Nat Rev Immunol. 2011 Feb;11(2):98-10721233852J Biol Chem. 2006 Mar 31;281(13):8559-6416452475EMBO J. 2003 Dec 1;22(23):6299-30914633989Biochem Biophys Res Commun. 2013 Jun 7;435(3):403-723665318Cancer Res. 2008 Jun 15;68(12):4833-4218559531Circ Res. 2003 Nov 28;93(11):1029-3314645133J Biol Chem. 2010 Dec 17;285(51):39888-9720937823Nat Rev Drug Discov. 2003 Sep;2(9):736-4612951580Clin Cancer Res. 2001 Apr;7(4):971-611309348Cell Death Differ. 2002 Jul;9(7):717-2512058277Biochemistry. 2012 Aug 21;51(33):6545-5522799488Nat Rev Immunol. 2011 Nov;11(11):762-7421984070Gene. 2005 Dec 19;363:15-2316289629Circ Res. 2001 Sep 14;89(6):477-911557733J Biol Chem. 2013 Apr 12;288(15):10914-2223463508FEBS Lett. 2014 Jan 31;588(3):401-724374337Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2652-917008592Clin Exp Immunol. 1997 Sep;109(3):458-639328122Nature. 2002 Dec 19-26;420(6917):868-7412490960Mol Cell Biol. 2003 Jun;23(12):4257-6612773568PLoS One. 2013;8(3):e5800123472128Curr Drug Targets. 2015;16(4):393-40825706111Nucleic Acids Res. 2005;33(14):4379-9416077024Cell Signal. 2010 Mar;22(3):404-1419879354Immunol Rev. 2012 Mar;246(1):379-40022435567Cancer Res Treat. 2015 Oct;47(4):823-3325672588EMBO J. 2007 Jul 11;26(13):3086-9717557078AcetylationAnti-Inflammatory Agentsadministration & dosageCytoplasmdrug effectsgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasechemistrygeneticsmetabolismEndothelial Cellsdrug effectsHistone Deacetylase Inhibitorsadministration & dosageHumansInflammationchemically induceddrug therapygeneticspathologyOxidation-ReductionProtein BindingProtein Conformationdrug effectsReceptors, Tumor Necrosis Factor, Type IchemistrygeneticsmetabolismRepressor ProteinsgeneticsTumor Necrosis Factor-alphaadministration & dosagemetabolismVascular Cell Adhesion Molecule-1geneticsp38 Mitogen-Activated Protein Kinasesgenetics
2015081220160225201631260201631260201731160epublish26964514srep2301510.1038/srep23015PMC4786854
269346472017120620171206
1949-25537132016Mar29OncotargetOncotargetAPE1-mediated DNA damage repair provides survival advantage for esophageal adenocarcinoma cells in response to acidic bile salts.16688-70210.18632/oncotarget.7696Chronic Gastroesophageal Reflux Disease (GERD) is the main risk factor for the development of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Accordingly, EAC cells are subjected to high levels of oxidative stress and subsequent DNA damage. In this study, we investigated the expression and role of Apurinic/apyrimidinic endonuclease 1 (APE1) protein in promoting cancer cell survival by counteracting the lethal effects of acidic bile salts (ABS)-induced DNA damage. Immunohistochemistry analysis of human tissue samples demonstrated overexpression of APE1 in more than half of EACs (70 of 130), as compared to normal esophagus and non-dysplastic BE samples (P < 0.01). To mimic in vivo conditions, we treated in vitro cell models with a cocktail of ABS. The knockdown of endogenous APE1 in EAC FLO-1 cells significantly increased oxidative DNA damage (P < 0.01) and DNA single- and double-strand breaks (P < 0.01), whereas overexpression of APE1 in EAC OE33 cells reversed these effects. Annexin V/PI staining indicated that the APE1 expression in OE33 cells protects against ABS-induced apoptosis. In contrast, knockdown of endogenous APE1 in FLO-1 cells increased apoptosis under the same conditions. Mechanistic investigations indicated that the pro-survival function of APE1 was associated with the regulation of stress response c-Jun N-terminal protein kinase (JNK) and p38 kinases. Pharmacological inhibition of APE1 base excision repair (BER) function decreased cell survival and enhanced activation of JNK and p38 kinases by ABS. Our findings suggest that constitutive overexpression of APE1 in EAC may be an adaptive pro-survival mechanism that protects against the genotoxic lethal effects of bile reflux episodes. HongJunJDepartment of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.ChenZhengZDepartment of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.PengDunfaDDepartment of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.ZaikaAlexanderADepartment of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.RevettaFrankFDepartment of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.WashingtonM KayMKDepartment of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.BelkhiriAbbesADepartment of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.El-RifaiWaelWDepartment of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.engP50 CA095103CANCI NIH HHSUnited StatesR01 CA206564CANCI NIH HHSUnited StatesP30 DK058404DKNIDDK NIH HHSUnited StatesP30 CA068485CANCI NIH HHSUnited StatesI01 BX002115BXBLRD VAUnited StatesR01 CA206563CANCI NIH HHSUnited StatesJournal Article
United StatesOncotarget1015329651949-25530Bile Acids and SaltsEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseAdenocarcinoma Of EsophagusIMAnn Oncol. 2012 Dec;23(12):3155-6222847812Arch Surg. 2005 Dec;140(12):1204-9; discussion 120916365243Cell Cycle. 2009 May 15;8(10):1630-219372763Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Cancer Treat Rev. 2010 Aug;36(5):425-3520056333J Surg Oncol. 2005 Dec 1;92(3):151-916299786FEBS J. 2006 Apr;273(8):1620-916623699Cancer Res. 2009 Sep 15;69(18):7285-9319723658Mutat Res. 2000 Oct 16;461(2):83-10811018583Gut. 2009 Jan;58(1):5-1518664505Carcinogenesis. 2002 Aug;23(8):1281-812151345Cancer Res. 2013 Jan 1;73(1):331-4023117882Mol Cell Biol. 2003 May;23(9):3052-6612697808Biochim Biophys Acta. 2012 Dec;1823(12):2201-922917577Gut. 2007 Jun;56(6):763-7117145738CA Cancer J Clin. 2010 Sep-Oct;60(5):277-30020610543Mutagenesis. 2004 Jul;19(4):319-2415215332Carcinogenesis. 2002 May;23(5):687-9612016139J Biol Chem. 2011 Feb 18;286(7):4968-7721081487Toxicol Lett. 2013 Apr 26;218(3):235-4523416140World J Gastroenterol. 2005 Nov 7;11(41):6466-7116425417Mol Cancer Ther. 2012 Mar;11(3):763-7422302096Nature. 2001 Mar 1;410(6824):37-4011242034Surgery. 1997 Nov;122(5):874-819369886Am J Physiol Gastrointest Liver Physiol. 2011 Aug;301(2):G278-8621636532Hepatogastroenterology. 2007 Apr-May;54(75):761-517591057J Exp Clin Cancer Res. 2014 May 16;33:4224887205Cell Death Dis. 2014 Jul 10;5:e131825010984Scand J Gastroenterol Suppl. 2006;(243):11-716782617Cell Death Dis. 2011 May 19;2:e16021593792Mol Cancer Ther. 2004 Jun;3(6):679-8615210853J Hepatol. 2003 Aug;39(2):153-6112873810FASEB J. 2006 Dec;20(14):2612-417068113Mol Cancer Ther. 2008 Jul;7(7):2012-2118645011J Biol Chem. 2003 May 23;278(21):19245-5612637505Mol Cell Biol. 2009 Apr;29(8):2243-5319223463DNA Repair (Amst). 2006 Sep 8;5(9-10):1021-916807135Surgery. 2010 Aug;148(2):354-6320580047Br J Surg. 1993 Apr;80(4):467-708495313Nucleic Acids Res. 2005 Aug 19;33(15):4711-2416113242Carcinogenesis. 2000 Aug;21(8):1491-50010910949Carcinogenesis. 2003 Jan;24(1):25-912538345Mol Cell. 2005 Feb 4;17(3):463-7015694346Drug Des Devel Ther. 2014 May 09;8:485-9624872679World J Gastroenterol. 2009 Jul 21;15(27):3329-4019610133Cell. 2000 Oct 13;103(2):239-5211057897Blood. 2003 Apr 1;101(7):2454-6012446453Free Radic Biol Med. 1991;10(3-4):225-421650738Gut. 1999 May;44(5):598-60210205192Gastrointest Cancer Res. 2012 Mar;5(2):49-5722690258Mutagenesis. 2008 Sep;23(5):399-40518515815J Biol Chem. 2008 Mar 7;283(10 ):6572-8318162465FASEB J. 2010 Oct;24(10):3674-8020511393Cancer Res. 2009 Dec 1;69(23):9083-919920191AdenocarcinomaetiologymetabolismpathologyBarrett EsophagusetiologymetabolismBile Acids and Saltsadverse effectsCell Line, TumorCell SurvivalDNA Damagedrug effectsDNA RepairphysiologyDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismEsophageal NeoplasmsetiologymetabolismpathologyGastroesophageal RefluxcomplicationsmetabolismHumansAPE1JNKacidic bile saltsbase excision repairp38
20160108201602112016336020163560201712760ppublish26934647769610.18632/oncotarget.7696PMC4941344
268848802016121320171116
1936-26258122015International journal of clinical and experimental pathologyInt J Clin Exp PatholSenile cataract and genetic polymorphisms of APE1, XRCC1 and OGG1.16036-45Polymorphisms of DNA repair enzymes which may influence their repair efficiency lead to diseases, for example, senile cataract. In this study, we aimed to analyze the association of single nucleotide polymorphisms in AP endonuclease-1 (APE1), 8-oxoguanine glycosylase-1 (OGG1) and X-ray repair cross-complementing-1 (XRCC1) genes with the risk of age-related cataract in a Chinese population. Genotyping was carried out by the polymerase chain reaction and DNA sequencing on 402 cataract patients and 813 controls in this study. Differences in the frequencies were estimated by the chi-square test, and risk was estimated using unconditional logistic regression after adjusting for age and gender. Our results demonstrated there was a significant difference between the case and control groups in the APE1-141 G/G genotype (P=0.002). This difference still existed after adjusting for age and gender (P*=0.003). The APE1-141 T/T genotype and T allele frequencies were significantly higher in cataract patients, while the G/G genotype and G allele frequencies in patients were significantly lower than in controls (P < 0.05). The APE1-141 G/G genotype (OR, 0.49; 95% CI, 0.31-0.77) seems to have a protective role against cataract, and the T allele seems to have a deleterious role in the development of cataract. In OGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls. WangChenCCenter for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430030, China; Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430030, China.LaiQiaohongQCenter for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430030, China; Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430030, China.ZhangShuSCenter for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.HuJunJCenter for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430030, China; Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430030, China.engJournal ArticleResearch Support, Non-U.S. Gov't20151201
United StatesInt J Clin Exp Pathol1014805651936-26250DNA-Binding Proteins0Genetic Markers0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMMutat Res. 2013 Apr 30;753(1):12-2223499241Ophthalmic Res. 2014;51(3):124-824457594Exp Eye Res. 2007 Sep;85(3):328-3417637462Mutat Res. 2003 Oct 29;531(1-2):157-6314637252BMC Cancer. 2011;11:10421429202J Cell Biol. 1995 Jul;130(1):169-817790371Invest Ophthalmol Vis Sci. 2013 Oct;54(10):6789-9724022010Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4661-7016303963Nippon Ganka Gakkai Zasshi. 1995 Dec;99(12):1303-418571853Acta Ophthalmol. 2010 Dec;88(8):891-519706013Photochem Photobiol. 2014 Jul-Aug;90(4):853-924483628Int J Cancer. 2014 Dec 1;135(11):2687-9624729390Mol Vis. 2011;17:127-3321245954Mutat Res. 2013 Aug 15;755(2):115-923830927Mech Ageing Dev. 2003 Jan;124(1):27-3212618003Front Physiol. 2013 Dec 16;4:36624379787Mol Vis. 2010;16:698-70420431719Invest Ophthalmol Vis Sci. 2012 Oct;53(11):7276-8523010639Antioxid Redox Signal. 2001 Aug;3(4):597-60911554447Toxicology. 2009 Jan 8;255(1-2):1-518852014Gene. 2012 Aug 15;505(1):121-722652274J Cancer. 2014 Mar 13;5(3):253-924665350Science. 2001 Feb 16;291(5507):1284-911181991J Huazhong Univ Sci Technolog Med Sci. 2014 Jun;34(3):408-1424939308Lancet. 2005 Feb 12-18;365(9459):599-60915708105J Toxicol Environ Health. 1993 Oct-Nov;40(2-3):391-4048230310Curr Eye Res. 2011 Jul;36(7):632-621599457Mol Cell. 2005 Feb 4;17(3):463-7015694346Front Biosci (Elite Ed). 2012;4:141-5522201860Acta Ophthalmol. 2013 Nov;91(7):652-622994213Hum Exp Toxicol. 2012 Oct;31(10):981-100523023028Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4732-720375340FASEB J. 2009 Oct;23(10):3459-6919541747Biochim Biophys Acta. 2012 Aug;1822(8):1308-1522587838Curr Top Dev Biol. 2014;108:217-4624512711Clin Lab. 2013;59(1-2):163-823505922Cancer Lett. 2012 Dec 31;327(1-2):26-4722293091DNA Repair (Amst). 2014 Jun;18:52-6224794400Age FactorsAgedAsian Continental Ancestry GroupgeneticsBase SequenceCase-Control StudiesCataractdiagnosisenzymologyethnologygeneticsChi-Square DistributionChinaDNA GlycosylasesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGene FrequencyGenetic Association StudiesGenetic MarkersGenetic Predisposition to DiseaseHeterozygoteHomozygoteHumansLogistic ModelsMaleMiddle AgedMolecular Sequence DataPhenotypePolymerase Chain ReactionPolymorphism, Single NucleotideProtective FactorsRisk FactorsX-ray Repair Cross Complementing Protein 1APE1 geneGenetic polymorphismsOGG1 geneXRCC1 genesenile cataract
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1873-135X784-7852016 Feb-MarMutation researchMutat. Res.XPC deficiency is related to APE1 and OGG1 expression and function.25-3310.1016/j.mrfmmm.2016.01.004S0027-5107(16)30003-3Oxidative DNA damage is considered to be a major cause of neurodegeneration and internal tumors observed in syndromes that result from nucleotide excision repair (NER) deficiencies, such as Xeroderma Pigmentosum (XP) and Cockayne Syndrome (CS). Recent evidence has shown that NER aids in removing oxidized DNA damage and may interact with base excision repair (BER) enzymes. Here, we investigated APE1 and OGG1 expression, localization and activity after oxidative stress in XPC-deficient cells. The endogenous APE1 and OGG1 mRNA levels were lower in XPC-deficient fibroblasts. However, XPC-deficient cells did not show hypersensitivity to oxidative stress compared with NER-proficient cells. To confirm the impact of an XPC deficiency in regulating APE1 and OGG1 expression and activity, we established an XPC-complemented cell line. Although the XPC complementation was only partial and transient, the transfected cells exhibited greater OGG1 expression and activity compared with XPC-deficient cells. However, the APE1 expression and activity did not significantly change. Furthermore, we observed a physical interaction between the XPC and APE1 proteins. Together, the results indicate that the responses of XPC-deficient cells under oxidative stress may not only be associated with NER deficiency per se but may also include new XPC functions in regulating BER proteins. Copyright © 2016 Elsevier B.V. All rights reserved.de MeloJulliane Tamara AraújoJTLaboratório de Biologia Molecular e Genômica, Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.de Souza TimoteoAna RafaelaARLaboratório de Biologia Molecular e Genômica, Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.LajusTirzah Braz PettaTBLaboratório de Biologia Molecular e Genômica, Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.BrandãoJuliana AlvesJALaboratório de Biologia Molecular e Genômica, Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.de Souza-PintoNadja CristhinaNCLaboratório de Genética Mitocondrial, Departamento de Química, Instituto de Química, Universidade de São Paulo-USP, São Paulo, Brazil.MenckCarlos Frederico MartinsCFLaboratório de Reparo de DNA, Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo-USP, São Paulo, Brazil.CampalansAnnaACEA, Institut de Radiobiologie Cellulaire et Moléculaire, 18 Route du Panorama, F-92265 Fontenay aux Roses, France.RadicellaJ PabloJPCEA, Institut de Radiobiologie Cellulaire et Moléculaire, 18 Route du Panorama, F-92265 Fontenay aux Roses, France.VessoniAlexandre TeixeiraATLaboratório de Reparo de DNA, Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo-USP, São Paulo, Brazil; Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, CA, USA.MuotriAlysson RenatoARDepartment of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, CA, USA.Agnez-LimaLucymara FassarellaLFLaboratório de Biologia Molecular e Genômica, Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. Electronic address: lfagnez@ufrnet.br.engJournal ArticleResearch Support, Non-U.S. Gov't20160116
NetherlandsMutat Res04007630027-51070DNA-Binding Proteins0Oxidants0RNA, Messenger156533-34-5XPC protein, humanBBX060AN9VHydrogen PeroxideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCells, CulturedDNA GlycosylasesgeneticsmetabolismDNA RepairphysiologyDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismDNA-Binding ProteinsdeficiencygeneticsmetabolismFibroblastsdrug effectspathologyGene Expression RegulationHumansHydrogen PeroxidepharmacologyImmunoprecipitationOxidantspharmacologyOxidative StressRNA, MessengermetabolismXeroderma PigmentosumgeneticspathologyAPE1DNA damageDNA repairOGG1Oxidative stressXPC
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1364-68933642016MayJournal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and GynaecologyJ Obstet GynaecolThe association of -656T > G and 1349T > G polymorphisms of ApE1 gene and the risk of female infertility.544-710.3109/01443615.2015.1127903Despite enormous progress in the understanding of human reproductive physiology, the underlying cause of male infertility remains undefined in about 50.0% of cases, which are referred to as idiopathic infertility. Human apurinic/apyrimidinic endonuclease 1 (ApE1) is a multifunctional protein that has an important role in the base excision repair pathway. The present study aimed to evaluate whether two functional ApE1 polymorphisms (-656T > G and 1349T > G) are associated with the susceptibility of female infertility. Blood samples were collected from 100 patients diagnosed with female infertility and 100 control subjects and genotyped by tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR). The results indicated that individuals with the variant TG genotypes had a significantly increased risk of female infertility (p = 0.035, OR = 1.98, 95% CI = 1.04-3.74). Whereas, a significant association between 1349T > G polymorphism and female infertility risk was not observed (p = 0.1). Larger studies with more patients and controls are required to confirm the results. MashayekhiFarhadFa Department of Biology, Faculty of Sciences , University of Guilan , Rasht , Iran.YousefiMostafaMa Department of Biology, Faculty of Sciences , University of Guilan , Rasht , Iran.SalehiZivarZa Department of Biology, Faculty of Sciences , University of Guilan , Rasht , Iran.PournouraliMostafaMa Department of Biology, Faculty of Sciences , University of Guilan , Rasht , Iran.engJournal Article20160120
EnglandJ Obstet Gynaecol83091400144-3615EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdultCase-Control StudiesDNA-(Apurinic or Apyrimidinic Site) LyasebloodgeneticsFemaleGenetic Predisposition to DiseaseGenotypeHumansInfertility, FemalebloodgeneticsPolymorphism, GeneticRisk FactorsApE1BERfemale infertilitygene polymorphism
20161226020161236020176960ppublish2679061610.3109/01443615.2015.1127903
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2211-124713122015Dec29Cell reportsCell RepSynergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice.2671-810.1016/j.celrep.2015.12.001S2211-1247(15)01413-8Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic DNA lesion associated with cognitive decline. We have examined behavior and cognitive function in mice deficient of these glycosylases. Ogg1(-/-)Mutyh(-/-) mice were more active and less anxious, with impaired learning ability. In contrast, Mutyh(-/-) mice showed moderately improved memory. We observed no apparent change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutants belong to pathways known to be involved in anxiety and cognition. Esr1 targets were upregulated, suggesting a role of Ogg1 and Mutyh in repression of Esr1 signaling. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh regulate hippocampal gene expression related to cognition and behavior, suggesting a role for the glycosylases in regulating adaptive behavior. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.BjørgeMonica DMDDepartment of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.HildrestrandGunn AGADepartment of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.SchefflerKatjaKDepartment of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.SuganthanRajikalaRDepartment of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.RolsethVeslemøyVDepartment of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.KuśnierczykAnnaAProteomics and Metabolomics Core Facility PROMEC, Norwegian University of Science and Technology, 7491 Trondheim, Norway.RoweAlexander DADDepartment of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.VågbøCathrine BCBProteomics and Metabolomics Core Facility PROMEC, Norwegian University of Science and Technology, 7491 Trondheim, Norway.VetlesenSusanneSDepartment of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.EideLarsLDepartment of Medical Biochemistry, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.SlupphaugGeirGProteomics and Metabolomics Core Facility PROMEC, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.NakabeppuYusakuYDivision of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, and Research Center for Nucleotide Pool, Kyushu University, Fukuoka 812-8582, Japan.BredyTimothy WTWQueensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.KlunglandArneADepartment of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.BjøråsMagnarMDepartment of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. Electronic address: magnar.bjoras@rr-research.no.engJournal ArticleResearch Support, Non-U.S. Gov't20151217
United StatesCell Rep1015736910Reactive Oxygen SpeciesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 3.2.2.-mutY adenine glycosylaseIMAnimalsAnxietyenzymologygeneticsmetabolismDNA GlycosylasesdeficiencygeneticsmetabolismDisease Models, AnimalMaleMiceMice, Inbred C57BLMice, KnockoutReactive Oxygen Speciesmetabolism
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1879-003857812016Mar01GeneGeneAssociation of XRCC1 and OGG1 DNA repair gene polymorphisms with rheumatoid arthritis in Egyptian patients.112-610.1016/j.gene.2015.12.021S0378-1119(15)01493-6Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. Previous studies indicated that the DNA repair system was involved in the pathology of RA. In this study, we investigated the association of two XRCC1 (X-ray repair cross-complementing group 1) (rs25487 and rs25489) gene polymorphisms and two OGG1 (8-oxoguanine glycosylase 1) gene polymorphisms (rs159153 and rs3219008) with the susceptibility to RA in 320 Egyptians individuals (160 RA patients and 160 controls). Genotyping was performed using restriction fragment length polymorphism polymerase chain reaction. We found an association between variant XRCC1 (rs25487 and rs25489) genotype polymorphisms, OGG1 (rs3219008) genotype polymorphism, and RA disease susceptibility. Moreover, the presence of the Gln/Gln, Arg/His, and His/His genotypes of XRCC1 was significantly more likely to have bone erosion and extra-articular features in RA patients. Further, patient's carrying the OGG1 A/G and G/G genotypes more likely to have bone erosion. However, the AA genotype and A allele were significantly more likely to have extra-articular features. Also, there were no significant associations between C/T OGG1 gene polymorphism and RA susceptibility, bone erosion, and extra-articular features occurrence in RA patients. We concluded that the XRCC1-Arg/Gln, XRCC1-Arg/His, and OGG1 A/G polymorphism have a role in the development of rheumatoid arthritis disease. Also, these variant are associated with the severity of RA.Copyright © 2015 Elsevier B.V. All rights reserved.MohamedRanda HRHMedical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Electronic address: randahussiny@yahoo.com.El-ShalAmal SASMedical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.El-ShahawyEman EEERheumatology and rehabilitation Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.Abdel GalilSahar MSMRheumatology and rehabilitation Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.engJournal Article20151209
NetherlandsGene77067610378-11190DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultAgedArthritis, RheumatoidgeneticspathologyDNA GlycosylasesgeneticsDNA-Binding ProteinsgeneticsEgyptEuropean Continental Ancestry GroupgeneticsFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansMiddle AgedPolymorphism, Single NucleotideX-ray Repair Cross Complementing Protein 1OGG1PolymorphismRheumatoid arthritisXRCC1
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2045-232252015Dec07Scientific reportsSci RepInhibition of Ape1 Redox Activity Promotes Odonto/osteogenic Differentiation of Dental Papilla Cells.1748310.1038/srep17483Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth, and this process is performed by odontoblasts. Dental papilla cells (DPCs), as the progenitor cells of odontoblasts, undergo the odontogenic differentiation regulated by multiple cytokines and paracrine signal molecules. Ape1 is a perfect paradigm of the function complexity of a biological macromolecule with two major functional regions for DNA repair and redox regulation, respectively. To date, it remains unclear whether Ape1 can regulate the dentinogenesis in DPCs. In the present study, we firstly examed the spatio-temporal expression of Ape1 during tooth germ developmental process, and found the Ape1 expression was initially high and then gradually reduced along with the tooth development. Secondly, the osteo/odontogenic differentiation capacity of DPCs was up-regulated when treated with either Ape1-shRNA or E3330 (a specific inhibitor of the Ape1 redox function), respectively. Moreover, we found that the canonical Wnt signaling pathway was activated in this process, and E3330 reinforced-osteo/odontogenic differentiation capacity was suppressed by Dickkopf1 (DKK1), a potent antagonist of canonical Wnt signaling pathway. Taken together, we for the first time showed that inhibition of Ape1 redox regulation could promote the osteo/odontogenic differentiation capacity of DPCs via canonical Wnt signaling pathway. ChenTianTNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.LiuZhiZNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.SunWenhuaWNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.LiJingyuJNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.LiangYanYNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.YangXianruiXNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.XuYangYNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.YuMeiMNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.TianWeidongWNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.ChenGuoqingGNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.BaiDingDNational Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R. China.Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, P.R. China.engJournal ArticleResearch Support, Non-U.S. Gov't20151207
EnglandSci Rep1015632882045-23220Benzoquinones0Propionates0RNA, Small Interfering136164-66-4E 3330EC 4.2.99.18Apex1 protein, ratEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Dent Res. 1958 Sep-Oct;37(5):767-7913587798Pediatr Dent. 2013 Sep-Oct;35(5):E179-8424290548J Endod. 2010 May;36(5):781-920416419Semin Cell Dev Biol. 2014 Jan-Feb;25-26:61-7024355560Cell Biol Int. 2015 Jan;39(1):94-10325077982Toxicology. 2013 Mar 8;305:120-923370007J Dent Res. 2009 Jan;88(1):51-519131317Genes Dev. 1997 Mar 1;11(5):558-709119221Free Radic Biol Med. 2013 Jan;54:26-3923085514Arch Histol Cytol. 2008 Sep;71(2):131-4618974605Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Nucleic Acids Res. 2008 Aug;36(13):4327-3618586825J Endod. 2014 Nov;40(11):1771-725258338J Clin Diagn Res. 2015 Jan;9(1):ZE07-1025738099Neural Regen Res. 2013 May 5;8(13):1190-20025206413Bone. 2014 Jun;63:158-6524657304Development. 2000 Apr;127(8):1671-910725243J Bone Miner Res. 2001 Apr;16(4):731-4111316001J Dent Res. 2009 Oct;88(10):904-919783797Stem Cells. 2009 Jun;27(6):1455-6219492297Arch Oral Biol. 2012 Sep;57(9):1165-7522534175J Biol Chem. 2014 Oct 3;289(40):27937-5125124032Free Radic Res. 2008 Jan;42(1):20-918324520Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-69560228Neoplasma. 2013;60(4):384-9423581410J Immunol. 2009 Nov 15;183(10):6839-4819846872PLoS One. 2014;9(2):e8923224586617J Biol Chem. 1997 Jun 6;272(23):14497-5009169404Development. 2012 Oct;139(19):3487-9722949612Dev Dyn. 2015 Apr;244(4):577-9025645398PLoS Comput Biol. 2015 Mar;11(3):e100410625793621Int J Dev Biol. 1995 Feb;39(1):51-687626422J Oral Maxillofac Surg. 2009 Mar;67(3):507-1419231773J Dent Res. 2015 Apr;94(4):608-1425694469Differentiation. 2008 May;76(5):495-50518093227J Cell Physiol. 2015 Nov;230(11):2588-9526037045Nature. 2014 Aug 7;512(7512):36-725079312Antioxid Redox Signal. 2009 Mar;11(3):589-60018717627Stem Cells. 2015 Mar;33(3):627-3825447379J Cell Physiol. 2009 Apr;219(1):209-1819097035PLoS One. 2014;9(9):e10648525188410Cell Res. 2008 Jan;18(1):27-4718166975EMBO J. 1992 Sep;11(9):3323-351380454Stem Cells Dev. 2014 Jun 15;23(12):1405-1624517722Mol Neurobiol. 2013 Feb;47(1):313-2423054678Cell Death Dis. 2013;4:e53723492768Dev Biol. 2009 Oct 1;334(1):174-8519631205J Endod. 2015 Jul;41(7):1091-925882137PLoS One. 2013;8(6):e6750423840726Int J Oncol. 2015 Aug;47(2):610-2026081414EMBO J. 1992 Feb;11(2):653-651537340Cell Physiol Biochem. 2015;35(3):1008-2225661467Cell Stem Cell. 2012 Sep 7;11(3):291-30122958928Biochim Biophys Acta. 2015 Aug;1850(8):1518-2625766871Blood. 2007 Mar 1;109(5):1917-2217053053DNA Repair (Amst). 2007 Apr 1;6(4):461-917166779AnimalsBenzoquinonespharmacologyCell Cycledrug effectsCell Differentiationdrug effectsCell Proliferationdrug effectsDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismDental PapillacytologyModels, BiologicalOdontogenesisdrug effectsOsteogenesisdrug effectsOxidation-Reductiondrug effectsPropionatespharmacologyRNA, Small InterferingmetabolismRatsTime FactorsToothenzymologyUp-Regulationdrug effectsWnt Signaling Pathwaydrug effects
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2284-072919222015NovEuropean review for medical and pharmacological sciencesEur Rev Med Pharmacol SciThe expression of PD-L1 APE1 and P53 in hepatocellular carcinoma and its relationship to clinical pathology.4207-99830BerrettaMMDepartment of Medical Oncology, National Cancer Institute, Aviano (PN) Italy. mberretta@cro.it.StanzioneBBDi FranciaRRTirelliUUengLetterComment
ItalyEur Rev Med Pharmacol Sci97173601128-36020B7-H1 Antigen0Biomarkers, Tumor0Tumor Suppressor Protein p53EC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMEur Rev Med Pharmacol Sci. 2015 Aug;19(16):3063-7126367730B7-H1 AntigenbiosynthesisBiomarkers, TumorbiosynthesisCarcinoma, HepatocellularmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisFemaleHumansLiver NeoplasmsmetabolismMaleTumor Suppressor Protein p53biosynthesis
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1932-620310122015PloS onePLoS ONETranscriptional Up-Regulation of APE1/Ref-1 in Hepatic Tumor: Role in Hepatocytes Resistance to Oxidative Stress and Apoptosis.e014328910.1371/journal.pone.0143289Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC.In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1.APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis significantly increased in HCC. The up-regulation was higher in the less differentiated cancers. In vitro, over-expression of APE1/Ref-1 in normal hepatocytes conferred cell protection against oxidative stress and it was associated with BAX inhibition and escape from apoptosis.APE1/Ref-1 is up-regulated in HCC and this over-expression correlates with cancer aggressiveness. The up-regulation occurs at the transcriptional level and it is present in the earliest phases of hepatocarcinogenesis. The APE-1/Ref-1 over-expression is associated with hepatocyte survival and inhibits BAX activation and apoptosis. These data suggest a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development calling attention to this molecule as a promising marker for HCC diagnosis and treatment.Di MasoVittorioVFIF- Fondazione Italiana Fegato Area Science Park Basovizza. Trieste, Italia.MediavillaMaría GabrielaMGFIF- Fondazione Italiana Fegato Area Science Park Basovizza. Trieste, Italia.VascottoCarloCDipartimento Scienze Mediche e Biologiche, Università di Udine. Udine, Itala.LupoFrancescoFChirurgia Generale 2 Centro Trapianto Fegato Universitá Torino. Torino, Italia.BaccaraniUmbertoUDipartimento Scienze Mediche e Biologiche, Università di Udine. Udine, Itala.AvelliniClaudioCDipartimento Scienze Mediche e Biologiche, Università di Udine. Udine, Itala.TellGianlucaGFIF- Fondazione Italiana Fegato Area Science Park Basovizza. Trieste, Italia.Dipartimento Scienze Mediche e Biologiche, Università di Udine. Udine, Itala.TiribelliClaudioCFIF- Fondazione Italiana Fegato Area Science Park Basovizza. Trieste, Italia.Dipartimento Scienze Mediche, Università di Trieste. Trieste, Italia.CrocèLory SaveriaLSFIF- Fondazione Italiana Fegato Area Science Park Basovizza. Trieste, Italia.Dipartimento Scienze Mediche, Università di Trieste. Trieste, Italia.engJournal ArticleResearch Support, Non-U.S. Gov't20151201
United StatesPLoS One1012850811932-62030RNA, Messenger0bcl-2-Associated X ProteinEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCarcinogenesis. 2007 Nov;28(11):2382-9017566060Cancer. 1954 May;7(3):462-50313160935Carcinogenesis. 1999 Mar;20(3):415-910190555Mol Cancer Ther. 2005 Dec;4(12):1923-3516373707Gastroenterology. 2004 Apr;126(4):1134-4615057752J Hepatol. 2005 Dec;43(6):1031-716169114Nucleic Acids Res. 2005;33(10):3303-1215942031Ann Hepatol. 2004 Jul-Sep;3(3):86-9215505592Nat Genet. 2002 Aug;31(4):339-4612149612Semin Liver Dis. 2005;25(2):143-5415918143J Gastroenterol Hepatol. 2000 Jul;15(7):718-2410937675Cancer Chemother Pharmacol. 2012 Jun;69(6):1545-5522481618Free Radic Biol Med. 2008 Sep 1;45(5):592-60118515104Mol Biol Cell. 2012 Oct;23(20):4079-9622918947J Hepatol. 2001 Nov;35(5):613-811690707Antioxid Redox Signal. 2006 May-Jun;8(5-6):1047-5816771694J Clin Biochem Nutr. 2013 Mar;52(2):112-923525727World J Hepatol. 2013 Apr 27;5(4):206-1323671725Br J Cancer. 1998 Apr;77(7):1169-739569057Oncogene. 2007 Apr 2;26(15):2166-7617401425Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Biosci Biotechnol Biochem. 2008 Dec;72(12):3206-1019060414Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-69560228Methods Cell Sci. 2000;22(4):313-811549944Hepatology. 2005 Oct;42(4):809-1816175600Methods Mol Biol. 2008;432:101-1618370013Nat Rev Cancer. 2006 Sep;6(9):674-8716929323Oncogene. 2010 Jul 29;29(30):4330-4020498636Mol Cancer Res. 2006 Apr;4(4):221-3316603636J Clin Invest. 2013 Jul 1;:null23863623J Hepatol. 2013 Feb;58(2):365-7423023012Cell. 2005 Jun 3;121(5):671-415935754Nucleic Acids Res. 2001 May 1;29(9):e4511328886Nucleic Acids Res. 2007;35(8):2522-3217403694Gastroenterology. 2007 Apr;132(4):1465-7517433324Br J Surg. 1973 Aug;60(8):646-94541913Oncogene. 2003 Jun 12;22(24):3813-2012802289Transplant Proc. 2010 May;42(4):1204-820534262PLoS One. 2013;8(2):e5531323418439Mol Med. 2007 Jan-Feb;13(1-2):89-9617515960Liver Int. 2007 Mar;27(2):155-6217311609Mol Cell Probes. 2004 Feb;18(1):45-5015036369Anal Biochem. 2003 Apr 1;315(1):90-412672416Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Proteomics. 2009 Feb;9(4):1058-7419180539Free Radic Biol Med. 2009 Jun 1;46(11):1488-9919268524Cancer Detect Prev. 2004;28(6):385-9115582261Nucleic Acids Res. 2000 Mar 1;28(5):1099-10510666449PLoS One. 2013;8(8):e7090923967134Hepatology. 1998 Sep;28(3):751-59731568Oncol Rep. 2002 Jan-Feb;9(1):11-711748448J Hepatol. 2000;32(1 Suppl):39-4710728793Best Pract Res Clin Gastroenterol. 2005 Feb;19(1):39-6215757804Gastroenterology. 2009 Jun;136(7):2258-6919505426Clin Cancer Res. 2001 Apr;7(4):824-3011309329DNA Repair (Amst). 2007 Apr 1;6(4):461-917166779Clin Liver Dis. 2005 May;9(2):191-211, v15831268ApoptosisgeneticsCarcinoma, HepatocellulargeneticsmetabolismpathologyCell Line, TumorDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleHepatocytesmetabolismpathologyHumansLiver NeoplasmsgeneticsmetabolismpathologyMaleMiddle AgedOxidative StressgeneticsRNA, MessengergeneticsmetabolismTranscription, GeneticUp-Regulationgeneticsbcl-2-Associated X Proteinmetabolism
2015081520151103201512260201512260201662460epublish2662499910.1371/journal.pone.0143289PONE-D-15-33947PMC4666459
266087912017062920180516
1522-1466310820160415American journal of physiology. Renal physiologyAm. J. Physiol. Renal Physiol.Unilateral ureteral obstruction induces DNA repair by APE1.F763-F77610.1152/ajprenal.00613.2014Ureteral obstruction is associated with oxidative stress and the development of fibrosis of the kidney parenchyma. Apurinic/apyrimidinic endonuclease (APE1) is an essential DNA repair enzyme for repair of oxidative DNA lesions and regulates several transcription factors. The aim of the present study was to investigate whether APE1 is regulated by acute (24 h) and chronic (7 days) unilateral ureteral obstruction (UUO). APE1 was expressed in essentially all kidney cells with the strongest expression in proximal tubuli. After 24 h of UUO, APE1 mRNA was induced in the cortex, inner stripe of the outer medulla (ISOM), and inner medulla (IM). In contrast, the APE1 protein level was not regulated in the IM and ISOM and only slightly increased in the cortex. APE1 DNA repair activity was not significantly changed. A different pattern of regulation was observed after 7 days of UUO, with an increase of the APE1 mRNA level in the cortex but not in the ISOM and IM. The APE1 protein level in the cortex, ISOM, and IM increased significantly. Importantly, we observed a significant increase in APE1 DNA repair activity in the cortex and IM. To confirm our model, we investigated heme oxygenase-1, collagen type I, fibronectin I, and α-smooth muscle actin levels. In vitro, we found the transcriptional regulatory activity of APE1 to be involved in the upregulation of the profibrotic factor connective tissue growth factor. In summary, APE1 is regulated at different levels after acute and chronic UUO. Thus, our results suggest that DNA repair activity is regulated in response to progressive (7 days) obstruction and that APE1 potentially could play a role in the development of fibrosis in kidney disease.Copyright © 2016 the American Physiological Society.AamannMaria DMDDepartment of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.NørregaardRikkeRDepartment of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.KristensenMarie Louise VindvadMLDepartment of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.StevnsnerTinnaTDanish Center for Molecular Gerontology and Danish Aging Research Center, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark; and.FrøkiærJørgenJDepartment of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; JF@clin.au.dk.Department of Clinical Physiology and Molecular Imaging, Aarhus University Hospital, Aarhus, Denmark.engJournal ArticleResearch Support, Non-U.S. Gov't20151125
United StatesAm J Physiol Renal Physiol1009019901522-14660Collagen Type I0FibronectinsEC 1.14.14.18Heme Oxygenase-1EC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsCollagen Type ImetabolismDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismDisease Models, AnimalFibronectinsmetabolismFibrosismetabolismpathologyGene Expression RegulationHeme Oxygenase-1metabolismKidneymetabolismpathologyMaleOxidative StressphysiologyRatsRats, WistarUreteral ObstructionmetabolismpathologyDNA repairapurinic/apyrimidinic endonuclease Ifibrosiskidneyobstructive nephropathyunilateral ureteral obstruction
20141110201511232015112760201771602015112760ppublish26608791ajprenal.00613.201410.1152/ajprenal.00613.2014
265867872016060620170101
1538-74457612016Jan01Cancer researchCancer Res.Mitochondrial DNA Repair through OGG1 Activity Attenuates Breast Cancer Progression and Metastasis.30-410.1158/0008-5472.CAN-15-0692Production of mitochondrial reactive oxygen species and integrity of mitochondrial DNA (mtDNA) are crucial in breast cancer progression and metastasis. Therefore, we evaluated the role of mtDNA damage in breast cancer by genetically modulating the DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1) in the PyMT transgenic mouse model of mammary tumorigenesis. We generated mice lacking OGG1 (KO), mice overexpressing human OGG1 subunit 1α in mitochondria (Tg), and mice simultaneously lacking OGG1 and overexpressing human OGG1 subunit 1α in mitochondria (KO/Tg). We found that Tg and KO/Tg mice developed significantly smaller tumors than KO and wild-type (WT) mice after 16 weeks. Histologic analysis revealed a roughly 2-fold decrease in the incidence of lung metastases in Tg mice (33.3%) compared to WT mice (62.5%). Furthermore, lungs from Tg mice exhibited nearly a 15-fold decrease in the average number of metastatic foci compared with WT mice (P ≤ 0.05). Primary tumors isolated from Tg mice also demonstrated reduced total and mitochondrial oxidative stress, diminished mtDNA damage, and increased mitochondrial function. Targeting hOGG1 to the mitochondria protected cells from mtDNA damage, resulting in downregulation of HIF1α and attenuated phosphorylation of Akt. Collectively, we demonstrate proof of concept that mtDNA damage results in breast cancer progression and metastasis in vivo. Moreover, our findings offer new therapeutic strategies for modulating the levels of mtDNA repair enzymes to delay or stall metastatic progression.©2015 American Association for Cancer Research.YuzefovychLarysa VLVDepartment of Pharmacology, College of Medicine, University of South Alabama, Mobile, Alabama.KahnAndrea GAGDepartment of Pathology, College of Medicine, University of South Alabama, Mobile, Alabama.SchulerMichele AMADepartment of Comparative Medicine, College of Medicine, University of South Alabama, Mobile, Alabama.EideLarsLDepartment of Medical Biochemistry, University of Oslo and Centre of Molecular Biology and Neuroscience, University of Oslo and Oslo University Hospital, Oslo, Norway.AroraRituRMitchell Cancer Institute, University of South Alabama, Mobile, Alabama.WilsonGlenn LGLDepartment of Physiology and Cell Biology, College of Medicine, University of South Alabama, Mobile, Alabama.TanMingMMitchell Cancer Institute, University of South Alabama, Mobile, Alabama.RachekLyudmila ILIDepartment of Pharmacology, College of Medicine, University of South Alabama, Mobile, Alabama. lrachek@southalabama.edu.engR01 CA149646CANCI NIH HHSUnited StatesR01CA149646CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20151119
United StatesCancer Res2984705R0008-54720DNA, MitochondrialEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMOsteoarthritis Cartilage. 2010 Mar;18(3):424-3219822235BMC Cancer. 2011;11:19121605372J Neurosci. 2011 Jun 29;31(26):9746-5121715639Endocrinology. 2012 Jan;153(1):92-10022128025Br J Cancer. 2012 Jan 17;106(2):344-722108520PLoS One. 2013;8(1):e5405923342074Endocrinology. 2013 Aug;154(8):2640-923748360Oncogene. 2000 Feb 21;19(8):968-8810713680J Biol Chem. 2002 Nov 22;277(47):44932-712244119Cancer Res. 2003 Mar 1;63(5):902-512615700Nucleic Acids Res. 2004;32(18):5596-60815494448Mol Cell Biol. 1992 Mar;12(3):954-611312220Cancer Metastasis Rev. 2006 Dec;25(4):695-70517160708Transgenic Res. 2007 Apr;16(2):193-20117206489Cancer Res. 2007 May 15;67(10):4687-9417510395Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Science. 2008 May 2;320(5876):661-418388260Carcinogenesis. 2007 Aug;28(8):1629-3717389610Cancer Lett. 2008 Jul 18;266(1):53-918362051Cancer Res. 2009 Mar 15;69(6):2375-8319276362AnimalsBreast NeoplasmsgeneticsDNA GlycosylasesgeneticsmetabolismDNA RepairDNA, MitochondrialgeneticsDisease Models, AnimalDisease ProgressionFemaleHumansMiceMice, KnockoutMice, TransgenicNeoplasm Metastasis
20150316201509112015112160201511216020166960ppublish265867870008-5472.CAN-15-069210.1158/0008-5472.CAN-15-0692PMC4703513NIHMS734184
265484922016091520151216
1742-20511212016JanMolecular bioSystemsMol BiosystNew oligonucleotide derivatives as unreactive substrate analogues and potential inhibitors of human apurinic/apyrimidinic endonuclease APE1.67-7510.1039/c5mb00692aHuman apurinic/apyrimidinic endonuclease APE1 is one of the key enzymes of the base excision DNA repair system. The main biological function of APE1 is the hydrolysis of the phosphodiester bond on the 5'-side of an apurinic/apyrimidinic site (AP-site) to give the 5'-phosphate and 3'-hydroxyl group. It has long been known that AP-sites have mutagenic and cytotoxic effects and their accumulation in DNA is a potential hazard to the cell lifecycle. The structural and biochemical studies of APE1 are complicated by its high catalytic activity towards the AP-site and its cyclic or acyclic analogues. This work has focussed on the design, synthesis and analysis of oligonucleotide derivatives as potentially unreactive APE1 substrates. We have shown that the replacement of oxygen atoms in the phosphate group on the 5'-side from the AP-site analogue tetrahydrofuran (F) considerably decreases the rate of enzymatic hydrolysis of modified oligonucleotides. We have calculated that a N3'-P5' phosphoramidate linkage is hydrolysed about 30 times slower than the native phosphodiester bond while phosphorothioate or primary phosphoramidate linkages are cleaved more than three orders of magnitude slower. The value of IC50 of the oligonucleotide duplex containing a primary phosphoramidate linkage is 2.5 × 10(-7) M, which is in accordance with the APE1 association constant of DNA duplexes containing AP-sites. Thus, it is demonstrated that oligonucleotide duplexes with chemical modifications could be used as unreactive substrates and potential competitive inhibitors of APE1. KuznetsovNikita ANAInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia. fedorova@niboch.nsc.ru and Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia.KupryushkinMaxim SMSInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia. fedorova@niboch.nsc.ru.AbramovaTatyana VTVInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia. fedorova@niboch.nsc.ru.KuznetsovaAlexandra AAAInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia. fedorova@niboch.nsc.ru.MiroshnikovaAnastasia DADInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia. fedorova@niboch.nsc.ru.StetsenkoDmitry ADAInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia. fedorova@niboch.nsc.ru and Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia.PyshnyiDmitrii VDVInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia. fedorova@niboch.nsc.ru and Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia.FedorovaOlga SOSInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia. fedorova@niboch.nsc.ru and Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia.engJournal ArticleResearch Support, Non-U.S. Gov't
EnglandMol Biosyst1012516201742-20510Enzyme Inhibitors0Oligonucleotides0Phosphates9007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCatalysisDNAchemistrymetabolismDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorschemistryDrug DesignEnzyme Inhibitorschemical synthesischemistrypharmacologyHumansHydrolysisMolecular StructureOligonucleotideschemical synthesischemistrypharmacologyPhosphateschemistryProtein Binding
20151110602015111060201691660ppublish2654849210.1039/c5mb00692a
265203692016020920161126
1879-35927932015NovMutation research. Genetic toxicology and environmental mutagenesisMutat Res Genet Toxicol Environ MutagenAPE1/REF-1 down-regulation enhances the cytotoxic effects of temozolomide in a resistant glioblastoma cell line.19-2910.1016/j.mrgentox.2015.06.001S1383-5718(15)00141-2Temozolomide (TMZ) is widely used for patients with glioblastoma (GBM); however, tumor cells frequently exhibit drug-resistance. Base excision repair (BER) has been identified as a possible mediator of TMZ resistance, and an attractive approach to sensitizing cells to chemotherapy. Human apurinic/apyrimidinic endonuclease/redox factor-1 (APE1) is an essential enzyme with a role in the BER pathway by repairing abasic sites, and it also acts as a reduction factor, maintaining transcription factors in an active reduced state. Thus, we aimed to investigate whether the down-regulation of APE1 expression by siRNA can interfere with the resistance of GBM to TMZ, being evaluated by several cellular and molecular parameters. We demonstrated that APE1 knockdown associated with TMZ treatment efficiently reduced cell proliferation and clonogenic survival of resistant cells (T98G), which appears to be a consequence of increased DNA damage, S-phase arrest, and H2AX phosphorylation, resulting in apoptosis induction. On the contrary, for those assays, the sensitization effects of APE1 silencing plus TMZ treatment did not occur in the TMZ-sensitive cell line (U87MG). Interestingly, TMZ-treatment and APE1 knockdown significantly reduced cell invasion in both cell lines, but TMZ alone did not reduce the invasion capacity of U87MG cells, as observed for T98G. We also found that VEGF expression was down-regulated by TMZ treatment in T98G cells, regardless of APE1 knockdown, but U87MG showed a different response, since APE1 silencing counteracted VEGF induction promoted by TMZ, suggesting that the APE1-redox function may play an indirect role, depending on the cell line. The present results support the contribution of BER in the GBM resistance to TMZ, with a greater effect in TMZ-resistant, compared with TMZ-sensitive cells, emphasizing that APE1 can be a promising target for modifying TMZ tolerance. Furthermore, genetic characteristics of tumor cells should be considered as critical information to select an appropriate therapeutic strategy. Copyright © 2015 Elsevier B.V. All rights reserved.MontaldiAna PAPDepartment of Genetics, Ribeirão Preto Medical School, University of São Paulo (USP), Brazil; Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto - University of São Paulo (USP), Ribeirão Preto, S.P., Brazil.GodoyPaulo R D VPRDepartment of Genetics, Ribeirão Preto Medical School, University of São Paulo (USP), Brazil; Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto - University of São Paulo (USP), Ribeirão Preto, S.P., Brazil.Sakamoto-HojoElza TETDepartment of Genetics, Ribeirão Preto Medical School, University of São Paulo (USP), Brazil; Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto - University of São Paulo (USP), Ribeirão Preto, S.P., Brazil. Electronic address: etshojo@usp.br.engJournal ArticleResearch Support, Non-U.S. Gov't20150605
NetherlandsMutat Res Genet Toxicol Environ Mutagen1016321491383-57180Antineoplastic Agents, Alkylating0RNA, Small Interfering7GR28W0FJIDacarbazineEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseYF1K15M17YtemozolomideIMAntineoplastic Agents, AlkylatingpharmacologyCell Line, TumorCell Movementdrug effectsCell Proliferationdrug effectsCell Survivaldrug effectsDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsgeneticsDacarbazineanalogs & derivativespharmacologyDown-RegulationDrug Resistance, Neoplasmdrug effectsGene Knockdown TechniquesGlioblastomadrug therapygeneticsHumansRNA, Small InterferingmetabolismAPE1 geneBase excision repairGlioblastomaTemozolomidesiRNA methodology
2015053020150602201511260201511260201621060ppublish26520369S1383-5718(15)00141-210.1016/j.mrgentox.2015.06.001
265075172017011120171005
1432-12468942016MayInternational archives of occupational and environmental healthInt Arch Occup Environ HealthGenetic variation in APE1 gene promoter is associated with noise-induced hearing loss in a Chinese population.621-810.1007/s00420-015-1100-8To investigate whether the apurinic/apyrimidinic endonuclease 1 (APE1) 1349 T>G and -656 T>G polymorphisms were associated with the risk of noise-induced hearing loss (NIHL) in a Chinese population.The two APE1 polymorphisms were analyzed among 613 NIHL workers and 613 normal hearing workers using the minor groove binder TaqMan probe assay.We found that the APE1 -656 TT genotype was associated with a increased risk of NIHL [adjusted odds ratio (OR) 1.46, 95% confidence interval (CI) 1.05-2.06]. This increased risk was more pronounced in the stratification analysis. Furthermore, we found that subjects with two risk genotypes (hOGG1 Cys/Cys, APE1 -656 TT) had a significantly increased risk of NIHL (adjusted OR 1.91, 95% CI 1.27-2.88).Our study identified that the APE1 -656 T>G polymorphism may contribute to the susceptibility of NIHL.ShenHuanxiHKunshan Municipal Center for Disease Prevention and Control, Kunshan, China.Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.DouJianruiJYangzhou Center for Disease Prevention and Control, Yangzhou, China.HanLeiLDepartment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, 172 Jiangsu Road, Nanjing, 210009, China.BaiYingYInstitute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, 172 Jiangsu Road, Nanjing, 210009, China.LiQianQThe First People's Hospital of Kunshan, Kunshan, China.HongZhiqiangZInstitute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, 172 Jiangsu Road, Nanjing, 210009, China.ShiJianJKunshan Municipal Center for Disease Prevention and Control, Kunshan, China.ZhangHengdongHInstitute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, 172 Jiangsu Road, Nanjing, 210009, China.ZhangFengFInstitute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, 172 Jiangsu Road, Nanjing, 210009, China.DuChengCKunshan Municipal Center for Disease Prevention and Control, Kunshan, China.TongZhiminZKunshan Municipal Center for Disease Prevention and Control, Kunshan, China.ZhuBaoliBDepartment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China. zhubl@jscdc.cn.Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, 172 Jiangsu Road, Nanjing, 210009, China. zhubl@jscdc.cn.engJournal ArticleResearch Support, Non-U.S. Gov't20151027
GermanyInt Arch Occup Environ Health75121340340-0131EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBiochimie. 2003 Nov;85(11):1053-7114726013Hum Mutat. 2006 Aug;27(8):786-9516823764Hear Res. 2002 Nov;173(1-2):164-7112372644Curr Opin Otolaryngol Head Neck Surg. 2014 Oct;22(5):388-9325188429Lancet. 2014 Apr 12;383(9925):1325-3224183105Ear Hear. 2009 Apr;30(2):151-919194285J Assoc Res Otolaryngol. 2000 Nov;1(3):243-5411545230Prog Nucleic Acid Res Mol Biol. 2001;68:129-3811554292J Occup Health. 2013;55(2):56-6523327886Audiol Neurootol. 1999 Sep-Oct;4(5):237-4610436316J Sch Health. 2007 May;77(5):225-3117430434DNA Repair (Amst). 2007 Apr 1;6(4):544-5917112792Br J Audiol. 2000 Feb;34(1):47-5510759077Am J Obstet Gynecol. 2013 Oct;209(4):360.e1-723871947Ear Hear. 2011 Feb;32(1):46-5220802338Hear Res. 2002 Feb;164(1-2):231-911950541Ann Hum Genet. 2009 Jul;73(Pt 4):411-2119523148Pharmacogenet Genomics. 2005 Aug;15(8):557-6416006999Carcinogenesis. 2004 Sep;25(9):1689-9415073047Clin Chem. 2004 Nov;50(11):2012-815345661Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Ann Epidemiol. 2010 Jun;20(6):452-920470972Mutagenesis. 2009 Nov;24(6):507-1219762350J Assoc Res Otolaryngol. 2004 Mar;5(1):66-7914648237Ann Hum Genet. 2009 Mar;73(2):215-2419183343PLoS One. 2014 Mar 05;9(3):e8966224599382Public Health. 2001 May;115(3):192-611429714FEBS Lett. 2000 Jun 30;476(1-2):73-710878254Ear Hear. 2006 Feb;27(1):1-1916446561Cell Stress Chaperones. 2006 Autumn;11(3):233-917009596J Occup Environ Med. 2012 Sep;54(9):1157-6222885711Brain. 2013 Jan;136(Pt 1):194-20823365097Int J Audiol. 2011 Mar;50 Suppl 1:S3-1021288065FASEB J. 2009 Oct;23(10):3459-6919541747BMC Cancer. 2011 Dec 18;11:52122176746J Natl Cancer Inst. 2009 Jan 7;101(1):24-3619116388J Occup Environ Med. 2004 Jan;46(1):30-814724476Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Exp Mol Med. 2014 Jul 18;46:e10625033834Hum Mol Genet. 2007 Aug 1;16(15):1872-8317567781Hear Res. 1998 Mar;117(1-2):31-89557976Nature. 2001 May 17;411(6835):366-7411357144Eur J Hum Genet. 2009 Mar;17(3):329-3518813331AdultCase-Control StudiesChinaepidemiologyDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleGene FrequencyGenetic Predisposition to DiseaseepidemiologygeneticsGenotypeHearing Loss, Noise-InducedepidemiologygeneticsHumansMaleMiddle AgedNoise, Occupationaladverse effectsOccupational DiseasesepidemiologygeneticsPolymorphism, Single NucleotidePromoter Regions, GeneticRisk FactorsAPE1Noise-induced hearing loss susceptibilityPolymorphisms
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1545-998522112015NovNature structural & molecular biologyNat. Struct. Mol. Biol.Capturing snapshots of APE1 processing DNA damage.924-3110.1038/nsmb.3105DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. We report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylated CpG dinucleotides. These structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. These snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage. FreudenthalBret DBDGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Research Triangle Park, USA.BeardWilliam AWAGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Research Triangle Park, USA.CuneoMatthew JMJNeutron Sciences Directorate, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA.DyrkheevaNadezhda SNSGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Research Triangle Park, USA.WilsonSamuel HSHGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Research Triangle Park, USA.engPDB5DFF5DFH5DFI5DFJ5DG0Z01 ES050158ESNIEHS NIH HHSUnited StatesZ01 ES050161ESNIEHS NIH HHSUnited StatesZIA ES050158-18NULLIntramural NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., IntramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.20151012
United StatesNat Struct Mol Biol1011863741545-99859007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMDNA Repair (Amst). 2014 Sep;21:43-5425038572Curr Mol Pharmacol. 2012 Jan;5(1):3-1322122461Cancer Treat Rev. 2010 Aug;36(5):425-3520056333J Am Chem Soc. 2008 Jul 23;130(29):9332-4118576638J Mol Biol. 1999 Jul 9;290(2):447-5710390343J Mol Biol. 2015 Jan 30;427(2):298-31125498387Nature. 2012 Jul 12;487(7406):196-20122785315Acta Crystallogr D Biol Crystallogr. 2013 Dec;69(Pt 12):2555-6224311596EMBO J. 1997 Nov 3;16(21):6548-589351835Cancer Res. 2001 Jul 15;61(14):5552-711454706Nat Struct Biol. 2000 Mar;7(3):176-810700268Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16852-723035246J Biol Chem. 2007 Oct 19;282(42):30577-8517724035J Biol Chem. 1997 Jan 10;272(2):1302-78995436Environ Mol Mutagen. 2015 Jan;56(1):1-2125111769DNA Repair (Amst). 2004 Nov 2;3(11):1447-5515380100Toxicology. 2006 Jul 5;224(1-2):44-5516730871Bioinformation. 2011;7(4):184-9822102776Biochemistry. 2004 Jan 27;43(3):684-914730972Nucleic Acids Res. 2004;32(1):73-8114704345Nature. 1970 Mar 7;225(5236):948-94391887Nucleic Acids Res. 1991 Nov 11;19(21):5907-141719484Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11995-97505451Free Radic Biol Med. 1995 Jun;18(6):1033-777628729Biochemistry. 2013 Oct 29;52(43):7669-7724079850Nat Struct Mol Biol. 2012 Dec;19(12):1363-7123104055Nature. 2000 Jan 27;403(6768):451-610667800PLoS One. 2013;8(6):e6592223776569Nature. 2015 Mar 19;519(7543):315-2025762137Cell. 2013 Jul 3;154(1):157-6823827680Mutagenesis. 2004 May;19(3):169-8515123782J Biol Chem. 1995 Jul 7;270(27):16002-77608159Biochemistry. 2009 Jan 13;48(1):19-2619123919J Biol Chem. 1995 Sep 15;270(37):21441-47665552Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17644-822006298Mol Cancer Res. 2007 Jan;5(1):61-7017259346Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-2120124702Anal Biochem. 2012 Feb 15;421(2):433-822230282Chem Res Toxicol. 2005 Aug;18(8):1187-9216097791Annu Rev Genet. 1986;20:201-303545059J Biol Chem. 2007 May 4;282(18):13532-4117355977Biochim Biophys Acta. 2013 Jan;1834(1):247-7123076011EMBO J. 1998 Apr 15;17(8):2426-359545253Biochemistry. 2014 Oct 21;53(41):6520-925251148J Mol Biol. 2011 Mar 18;407(1):149-7021262234J Mol Biol. 2001 Apr 6;307(4):1023-3411286553Chem Rev. 2006 Feb;106(2):361-8216464010J Biol Chem. 2013 Mar 22;288(12):8445-5523355472J Mol Biol. 2000 May 5;298(3):447-5910772862Nat Struct Mol Biol. 2015 Jan;22(1):65-7225486305Exp Mol Med. 2014;46:e10625033834Nucleic Acids Res. 1994 Mar 25;22(6):972-68152929J Biol Chem. 2014 May 16;289(20):13996-400824695738Nucleic Acids Res. 2009 Jul;37(12):3946-5819401441J Mol Biol. 1990 May 20;213(2):303-142342108Nucleic Acids Res. 2013 Apr 1;41(6):3483-9023408852J Biol Chem. 2012 Oct 26;287(44):36702-1022989888Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1862-721233421Proteins. 2007 Jul 1;68(1):313-2317427952Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Binding SitesCatalytic DomainCrystallography, X-RayDNAchemistrymetabolismDNA DamageDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasechemistrymetabolismHumansModels, MolecularProtein BindingProtein Conformation
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1568-7856352015NovDNA repairDNA Repair (Amst.)Efficient cleavage of single and clustered AP site lesions within mono-nucleosome templates by CHO-K1 nuclear extract contrasts with retardation of incision by purified APE1.27-3610.1016/j.dnarep.2015.08.003S1568-7864(15)30011-2Clustered DNA damage is a unique characteristic of radiation-induced DNA damage and the formation of these sites poses a serious challenge to the cell's repair machinery. Within a cell DNA is compacted, with nucleosomes being the first order of higher level structure. However, few data are reported on the efficiency of clustered-lesion processing within nucleosomal DNA templates. Here, we show retardation of cleavage of a single AP site by purified APE1 when contained in nucleosomal DNA, compared to cleavage of an AP site in non-nucleosomal DNA. This retardation seen in nucleosomal DNA was alleviated by incubation with CHO-K1 nuclear extract. When clustered DNA damage sites containing bistranded AP sites were present in nucleosomal DNA, efficient cleavage of the AP sites was observed after treatment with nuclear extract. The resultant DSB formation led to DNA dissociating from the histone core and nucleosomal dispersion. Clustered damaged sites containing bistranded AP site/8-oxoG residues showed no retardation of cleavage of the AP site but retardation of 8-oxoG excision, compared to isolated lesions, thus DSB formation was not seen. An increased understanding of processing of clustered DNA damage in a nucleosomal environment may lead to new strategies to enhance the cytotoxic effects of radiotherapeutics. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.EcclesLaura JLJCRUK-MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.MenoniHervéHUniversité de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, CNRS-UMR 5239, Ecole Normale Supérieure de Lyon, 69007, France.AngelovDimitarDUniversité de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, CNRS-UMR 5239, Ecole Normale Supérieure de Lyon, 69007, France.LomaxMartine EMECRUK-MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.O'NeillPeterPCRUK-MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. Electronic address: peter.oneill@oncology.ox.ac.uk.engMC_PC_12001Medical Research CouncilUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20150912
NetherlandsDNA Repair (Amst)1011391381568-78560Cell Extracts0Nucleosomes5614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Mol Biol. 1999 Jul 16;290(3):667-8410395822DNA Repair (Amst). 2015 Aug;32:113-925957487Mutat Res. 2009 Oct 2;669(1-2):162-819540248Nature. 1997 Sep 18;389(6648):251-609305837J Biol Chem. 2014 Jul 18;289(29):19881-9324891506Int J Radiat Biol. 1994 Jan;65(1):7-177905912Biochemistry. 2004 Aug 31;43(34):11017-2615323560Radiat Res. 2013 Jul;180(1):100-923682596Free Radic Biol Med. 2004 Aug 15;37(4):488-9915256220Biochemistry. 1999 Jul 20;38(29):9485-9410413526Nature. 2009 Dec 24;462(7276):1016-2120033039Mol Cell Biol. 2007 Dec;27(24):8442-5317923696J Biol Chem. 2009 Nov 27;284(48):33056-6119808662J Biol Chem. 2013 May 10;288(19):13863-7523543741DNA Repair (Amst). 2010 Feb 4;9(2):134-4320005182EMBO J. 2002 Dec 16;21(24):6865-7312486007EMBO J. 2000 Oct 16;19(20):5492-50111032816Front Genet. 2012 Sep 03;3:16922969794Subcell Biochem. 2007;41:29-4317484122J Biol Chem. 2000 Apr 21;275(16):11865-7310766813Mutat Res. 2011 Jun 3;711(1-2):134-4121130102Mutat Res. 2011 Jun 3;711(1-2):123-3321185841Mutat Res. 2014 Aug;766-767:19-2425083139Methods Mol Biol. 2001;148:275-9011357591Nucleic Acids Res. 2004;32(4):1602-915004247Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1877-8215671175Mol Biosyst. 2008 Jan;4(1):30-518075671Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7426-3011404468J Biol Chem. 2000 Aug 4;275(31):23729-3510821833Int J Radiat Biol. 2009 Jan;85(1):9-2519205982Radiat Res. 2002 Jun;157(6):611-612005538Nucleic Acids Res. 2002 Aug 1;30(15):3464-7212140332Radiat Res. 2007 Jul;168(1):87-9717723001Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):103-810618378Nucleic Acids Res. 2008 May;36(8):2717-2718353858Radiat Res. 2010 Mar;173(3):272-8220199212Biochemistry. 2001 Oct 2;40(39):11811-811570881Cell Mol Life Sci. 2008 May;65(10):1544-6518259689Biophys J. 1980 Oct;32(1):261-706264987Carcinogenesis. 1999 May;20(5):905-910334210DNA Repair (Amst). 2004 Mar 4;3(3):289-9915177044Nucleic Acids Res. 2009 Apr;37(6):1767-7719174565J Biol Chem. 2010 Jan 22;285(4):2876-8519933279Proc Natl Acad Sci U S A. 1990 Oct;87(19):7405-92170977J Mol Biol. 1998 Feb 13;276(1):19-429514715Mol Cell. 2001 Nov;8(5):1085-9211741543Mol Cell Biol. 2002 Oct;22(20):7147-5712242292EMBO J. 2002 Nov 1;21(21):5943-5212411511DNA Repair (Amst). 2013 Dec;12(12):1037-4224183900Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4646-5120176960Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7465-7012799467Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):119-3020123074Cell Res. 2008 Jan;18(1):27-4718166975Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6599-60411381129Nucleic Acids Res. 2012 Jan;40(2):692-70021930508DNA Repair (Amst). 2005 Feb 3;4(2):203-915590328Free Radic Biol Med. 2003 Sep 1;35(5):495-50312927599Mol Cell Biol. 2007 Sep;27(17):5949-5617591702Biochemistry. 2002 Jan 15;41(2):634-4211781104Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22475-8021149689Mol Cell Biol. 2002 Nov;22(21):7484-9012370295Nat Rev Mol Cell Biol. 2006 Jun;7(6):437-4716723979Biochemistry. 2008 Nov 18;47(46):11909-1918950195Nucleic Acids Res. 2010 Mar;38(4):1123-3419965771J Biol Chem. 1997 Jun 20;272(25):15650-59188454Mol Cell Biol. 2011 Nov;31(22):4623-3221930793J Mol Biol. 2001 Apr 27;308(2):341-5211327771AnimalsCHO CellsCell ExtractschemistryCell NucleusenzymologyCricetulusDNA CleavageDNA DamageDNA GlycosylaseschemistryDNA RepairDNA-(Apurinic or Apyrimidinic Site) Lyasechemistryisolation & purificationGuanineanalogs & derivativeschemistryHumansNucleosomeschemistryTemplates, Genetic8-oxoGAP siteBERClustered DNA damageNucleosome
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1179-20001962015DecMolecular diagnosis & therapyMol Diagn TherDNA Base-Excision Repair Genes OGG1 and NTH1 in Brazilian Lung Cancer Patients.389-9510.1007/s40291-015-0164-1Lung cancer is the leading global cause of cancer-related mortality and is associated with poor prognosis. To improve survival rates of lung cancer patients, better understanding of tumorigenic mechanisms is necessary, which may lead to development of new therapeutic strategies. The hOGG1 and NTH1 genes act in the DNA BER repair pathway and their involvement in lung cancer pathogenesis has been analyzed in several populations.We analyzed targeted regions of the hOGG1 and NTH1 genes in 96 Brazilian patients with non-small-cell lung cancer (NSCLC) and 89 cancer-free, ethnically matched controls.The NTH1 c.98G>T polymorphism rs2302172 (p = 0.02 and p = 0.02 for allele and genotype frequency between cases and controls, respectively) and the 140-17C> T variant (rs2233518) (p = 0.02 and p = 0.02 for allele and genotype frequency between cases and controls, respectively) were detected in four lung cancer cases (4 %) while the NTH1 Q131K (C391A) polymorphism was found in seven lung cancer cases (7 %) (p = 0.001 and p = 0.008, for allele and genotype frequency between cases and controls, respectively). None of these sequence variants were detected in controls. The Ser326Cys (C1245G, rs1052133) polymorphism in the OGG1 gene was detected in 42 % of analyzed NSCLC patients and in 34 % of the controls (p = 0.11 and p = 0.25 for allele and genotype frequency between cases and controls, respectively).Our study provides preliminary evidence that polymorphisms in OGG1 do not contribute to development of NSCLC in Brazilian patients and that NTH1 polymorphisms may be associated with NSCLC pathogenesis.CoutoPatricia GPGDepartment of Surgery, Universidade Federal de Minas Gerais, Av. Alfredo Balena 190, Room 114, Belo Horizonte, 30130-100, Brazil.Bastos-RodriguesLucianaLUniversidade Federal de Juiz de Fora, Campus Governador Valadares, Governador Valadares, Minas Gerais, Brazil.CarneiroJuliana GJGFaculty of Medical Science, Centro de Ensino Superior e Desenvolvimento, Campina Grande, Brazil.GuieiroFernandaFDepartment of Surgery, Universidade Federal de Minas Gerais, Av. Alfredo Balena 190, Room 114, Belo Horizonte, 30130-100, Brazil.BicalhoMaria AparecidaMADepartment of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.LeidenzFranciele BFBDepartment of Surgery, Universidade Federal de Minas Gerais, Av. Alfredo Balena 190, Room 114, Belo Horizonte, 30130-100, Brazil.BicalhoAna JAJDepartment of Surgery, Universidade Federal de Minas Gerais, Av. Alfredo Balena 190, Room 114, Belo Horizonte, 30130-100, Brazil.FriedmanEitanEThe Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, Israel.De MarcoLuizLDepartment of Surgery, Universidade Federal de Minas Gerais, Av. Alfredo Balena 190, Room 114, Belo Horizonte, 30130-100, Brazil. Ldemarco@ufmg.br.engJournal ArticleResearch Support, Non-U.S. Gov't
New ZealandMol Diagn Ther1012642601177-1062EC 3.1.25.1Deoxyribonuclease (Pyrimidine Dimer)EC 3.1.25.1NTHL1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMSci Rep. 2012;2:54822855704Carcinogenesis. 2009 Jan;30(1):78-8719029194Biochem Genet. 2004 Dec;42(11-12):453-6015587988Med Oncol. 2015 Feb;32(2):47225588927Cancer Sci. 2006 Aug;97(8):724-816800823Asian Pac J Cancer Prev. 2011;12(4):1067-7221790253Cell Mol Life Sci. 2009 Mar;66(6):981-9319153658Environ Mol Mutagen. 2014 Dec;55(9):689-70325044514Int J Cancer. 2012 Dec 15;131(12):2724-3222945513PLoS One. 2013 Dec 09;8(12):e8166724349107J Natl Cancer Inst. 2003 Sep 3;95(17):1312-912953085Mutat Res. 2011 May 10;709-710:21-3121376741Cancer Epidemiol Biomarkers Prev. 2008 Jul;17(7):1739-4518628426Cancer Lett. 2005 Mar 10;219(2):191-515723719Int J Cancer. 2014 Dec 1;135(11):2687-9624729390DNA Repair (Amst). 2014 Jul;19:14-2624780558Lung Cancer. 2011 Aug;73(2):138-4621195504Mutat Res. 2007 Jul 28;631(2):101-1017531525Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502Carcinogenesis. 2004 Sep;25(9):1689-9415073047J Clin Oncol. 2013 Mar 10;31(8):992-100123401443Cancer Res. 2013 Jan 1;73(1):256-6423108145Gene. 2013 Dec 15;532(2):192-624076439Nucleic Acids Res. 1991 Oct 11;19(19):54441681511Am J Respir Cell Mol Biol. 2010 Nov;43(5):576-8420008282CA Cancer J Clin. 2015 Mar;65(2):87-10825651787Cancer Prev Res (Phila). 2014 Apr;7(4):398-40624356339Cancer Res. 2009 Apr 15;69(8):3642-919351836Carcinogenesis. 2006 Mar;27(3):560-716195237Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14314-923940330Cancer Lett. 2012 Dec 31;327(1-2):73-8922252118Nat Rev Cancer. 2012 Dec;12(12):801-1723175119Mol Biol Rep. 2012 Dec;39(12):11249-6223065211J Natl Cancer Inst. 2012 Nov 21;104(22):1765-923104324Cancer Prev Res (Phila). 2014 Jan;7(1):1-824403288PLoS One. 2012;7(4):e3597022540013Carcinogenesis. 2012 May;33(5):1059-6422382497J Nucleic Acids. 2010 Oct 14;2010:70176020981350Cancer Res. 2014 Nov 1;74(21):6071-8125189529AdenocarcinomageneticsAdultAgedAged, 80 and overBrazilCarcinoma, Squamous CellgeneticsCase-Control StudiesDNA GlycosylasesgeneticsDNA RepairDeoxyribonuclease (Pyrimidine Dimer)geneticsFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseHumansLung NeoplasmsgeneticsMaleMiddle AgedPolymorphism, Single NucleotideSequence Analysis, DNA
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1940-5901872015International journal of clinical and experimental medicineInt J Clin Exp MedAssociation between polymorphisms in APE1 and XRCC1 and the risk of gastric cancer in Korean population.11484-9The DNA repair system plays a pivotal role in maintaining genomic integrity and protection against mutations that could lead to cancer development. The aim of this study was to explore the association between common polymorphisms of DNA repair genes, APE1 (rs1760944 and rs1130409) and XRCC1 (rs1799782, rs25487, and rs25489), and gastric cancer (GC) risk in the Korean population. We conducted a case-control study of 368 GC patients and 398 controls by using TaqMan genotyping assay. None of the polymorphisms was associated with the risk of GC. Further analysis showed a lack of association between APE1 and XRCC1 polymorphisms or haplotypes and the risk of GC and GC subgroups. The heterozygous CT genotype of XRCC1 rs25487 was related to 1.94 times increased risk of lymph node metastasis (LNM) in diffuse type GC compared to the XRCC1 rs25487 CC genotype (adjusted OR = 1.94, 95% CI = 1.06-3.53, P = 0.031) after adjusting for gender and age, whereas the remaining polymorphisms showed no association with GC or GC subgroups. This result suggests that genetic variation of XRCC1 rs25487 could be a risk factor for LNM in diffuse type of GC in the Korean population. JinEun-HeuiEHClinical Trials Center, Chungnam National University Hospital Daejeon, South Korea.KimJaeWooJClinical Trials Center, Chungnam National University Hospital Daejeon, South Korea.LeeSang-IlSIDepartment of Surgery, Chungnam National University Hospital Daejeon, South Korea.HongJang HeeJHClinical Trials Center, Chungnam National University Hospital Daejeon, South Korea ; Department of Pharmacology, College of Medicine, Chungnam National University Daejeon, South Korea.engJournal Article20150715
United StatesInt J Clin Exp Med1014710101940-5901Cancer Lett. 2002 Dec 10;187(1-2):53-6012359351Am J Surg Pathol. 1996;20 Suppl 1:S8-228694148Am J Epidemiol. 2011 Feb 15;173(4):363-7521216841Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Int J Cancer. 2000 Nov 15;88(4):601-611058877PLoS One. 2011;6(12):e2897122205985Int J Cancer. 2006 Jun 15;118(12):3030-4416404738Anticancer Res. 2010 Apr;30(4):1359-6420530453Environ Mol Mutagen. 1999;33(1):3-2010037319Cancer Res Treat. 2014 Apr;46(2):124-3024851103Acta Pathol Microbiol Scand. 1965;64:31-4914320675Arh Hig Rada Toksikol. 2011 Sep;62(3):207-1421971103Cancer Epidemiol. 2011 Apr;35(2):170-420863780Nat Rev Genet. 2004 Oct;5(10):764-7215510167Int J Cancer. 2009 Aug 1;125(3):666-7319382179Mol Aspects Med. 2007 Jun-Aug;28(3-4):258-7517628657Genet Mol Res. 2012 Nov 12;11(4):3852-6023212324Asian Pac J Cancer Prev. 2012;13(5):2139-4422901183Mutagenesis. 2010 Nov;25(6):569-7520817763Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808J Cancer. 2014 Mar 13;5(3):253-924665350Cancer Sci. 2011 Jul;102(7):1293-721615620Asian Pac J Cancer Prev. 2012;13(11):5637-4223317230Science. 2001 Feb 16;291(5507):1284-911181991Cancer Lett. 2004 Dec 28;216(2):157-6415533591Dis Esophagus. 2009;22(5):396-40119673050World J Gastroenterol. 2005 Nov 14;11(42):6593-60016425350Hum Exp Toxicol. 2012 Oct;31(10):981-100523023028Gastroenterology. 2006 Aug;131(2):420-716890595Mutat Res. 2000 Apr;462(2-3):129-3510767624J Natl Cancer Inst. 2000 Sep 20;92(18):1536-710995815APE1DNA repairGastric cancerXRCC1diffuse typelymph node metastasis
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1364-548X51882015Nov14Chemical communications (Cambridge, England)Chem. Commun. (Camb.)Efficient inhibition of human AP endonuclease 1 (APE1) via substrate masking by abasic site-binding macrocyclic ligands.15948-5110.1039/c5cc06084bBis-naphthalene macrocycles, which bind with high affinity and selectivity to abasic sites in DNA, efficiently inhibit their cleavage by APE1 (IC50 = 55-60 nM in the kinetic assay with a model THF substrate). These results demonstrate that substrate masking by non-covalent abasic-site ligands is an efficient strategy for inhibition of APE1. KoteraNaokoNCNRS UMR9187/INSERM U1196 "Chemistry, Modelling and Imaging for Biology", Centre de Recherche, Institut Curie, 91405 Orsay, France. anton.granzhan@curie.fr.PoyerFlorentFGranzhanAntonATeulade-FichouMarie-PauleMPengJournal Article20150917
EnglandChem Commun (Camb)96108381359-734507-nitro-1H-indole-2-carboxylic acid0Enzyme Inhibitors0Indoles0Intercalating Agents0Ligands0Macrocyclic Compounds0Naphthalenes4431-00-9Aurintricarboxylic Acid9007-49-2DNA91080-16-9calf thymus DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEN464416SIEthidiumIMAnimalsAurintricarboxylic AcidpharmacologyCattleDNAchemistryDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsmetabolismEnzyme InhibitorschemistrypharmacologyEthidiumpharmacologyHumansIndolespharmacologyIntercalating AgentschemistrypharmacologyKineticsLigandsMacrocyclic CompoundschemistrypharmacologyNaphthaleneschemistrypharmacology
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2284-072919162015AugEuropean review for medical and pharmacological sciencesEur Rev Med Pharmacol SciThe expression of PD-L1 APE1 and P53 in hepatocellular carcinoma and its relationship to clinical pathology.3063-719367To study the expression of programmed death-ligand1 (PD-L1) in hepatocellular carcinoma and its relationship with clinicopathological characteristics and, prognosis of hepatocellular carcinoma and APE1, P53 protein expression levels.A total of 128 patients with hepatocellular carcinoma were enrolled in this study. The expression of PD-L1, APE1 and P53 were detected by immunohistochemistry.Use immunohistochemical ABC staining method to detect the expression levels of PD-L1, APE1 and P53 protein in the hepatocellular carcinoma of 128 cases.Positive The positive expression rates levels of PD-L1, APE1, and P53 protein in hepatocellular carcinoma tissues are were 82.03%, 92.19%, and 60.94%. PD-L1 positive expression were significantly associated with clinical stage, The PD-L1 protein has a high expression in patients with I ~ II stage liver cancerHBV infection positive and nonportal vein thrombosis (p=0.041; p=0.030; p=0.014). It is inversely correlated with P53 and PD-L1 expression (correlation coefficient -0.227, p=0.010), and positively correlated with APE1 expression (correlation coefficient 0.189, p=0.032). The expression of PD-L1 is associated with the survival time of patients with hepatocellular carcinoma, and the median survival time of patients with high expression of PD-L1 is ten months. The median survival time of patients with low expression is five months (p=0.001). The relationship between the expression of APE1 and P53 protein and overall survival time of patients with hepatocellular carcinoma has not been found.The PD-L1 and APE1 expression in hepatocellular carcinoma are related to the level of the expression of P53 protein. The expression state of PD-L1 may be a prognostic factor in hepatocellular carcinoma.KanGGCancer Center of Research Institute of field surgery of the Third Military Medical University Daping Hospital, Chongqing, China. dongwang64@hotmail.com.DongWWengJournal Article
ItalyEur Rev Med Pharmacol Sci97173601128-36020B7-H1 Antigen0Biomarkers, Tumor0CD274 protein, human0TP53 protein, human0Tumor Suppressor Protein p53EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMEur Rev Med Pharmacol Sci. 2015 Nov;19(22):4207-926636502AdolescentAdultAgedB7-H1 AntigenbiosynthesisgeneticsBiomarkers, TumorbiosynthesisCarcinoma, HepatocellulargeneticsmetabolismpathologyDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisgeneticsFemaleHumansImmunohistochemistryLiver NeoplasmsmetabolismpathologyMaleMiddle AgedPrognosisTumor Suppressor Protein p53biosynthesisgeneticsYoung Adult
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1420-30492092015Sep02Molecules (Basel, Switzerland)MoleculesSynthetic Routes to N-9 Alkylated 8-Oxoguanines; Weak Inhibitors of the Human DNA Glycosylase OGG1.15944-6510.3390/molecules200915944The human 8-oxoguanine DNA glycosylase OGG1 is involved in base excision repair (BER), one of several DNA repair mechanisms that may counteract the effects of chemo- and radiation therapy for the treatment of cancer. We envisage that potent inhibitors of OGG1 may be found among the 9-alkyl-8-oxoguanines. Thus we explored synthetic routes to 8-oxoguanines and examined these as OGG1 inhibitors. The best reaction sequence started from 6-chloroguanine and involved N-9 alkylation, C-8 bromination, and finally simultaneous hydrolysis of both halides. Bromination before N-alkylation should only be considered when the N-substituent is not compatible with bromination conditions. The 8-oxoguanines were found to be weak inhibitors of OGG1. 6-Chloro-8-oxopurines, byproducts in the hydrolysis of 2,6-halopurines, turned out to be slightly better inhibitors than the corresponding 8-oxoguanines. MahajanTushar RTRDepartment of Chemistry, University of Oslo, P. O. Box 1033, Blindern, N-0315 Oslo, Norway. t.r.mahajan@kjemi.uio.no.Ytre-ArneMari EknesMEDepartment of Microbiology, Oslo University Hospital, P. O. Box 4950, Nydalen, N-0424 Oslo, Norway. pernille.strom-andersen@medisin.uio.no.Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, P. O. Box 4950, Nydalen, N-0424 Oslo, Norway. pernille.strom-andersen@medisin.uio.no.Strøm-AndersenPernillePDepartment of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, P. O. Box 4950, Nydalen, N-0424 Oslo, Norway. pernille.strom-andersen@medisin.uio.no.DalhusBjørnBDepartment of Microbiology, Oslo University Hospital, P. O. Box 4950, Nydalen, N-0424 Oslo, Norway. pernille.strom-andersen@medisin.uio.no.Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, P. O. Box 4950, Nydalen, N-0424 Oslo, Norway. pernille.strom-andersen@medisin.uio.no.GundersenLise-LotteLLDepartment of Chemistry, University of Oslo, P. O. Box 1033, Blindern, N-0315 Oslo, Norway. l.l.gundersen@kjemi.uio.no.engJournal ArticleResearch Support, Non-U.S. Gov't20150902
SwitzerlandMolecules1009640091420-30490Enzyme Inhibitors5614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAlkylationDNA Glycosylasesantagonists & inhibitorsmetabolismEnzyme Activationdrug effectsEnzyme Inhibitorschemical synthesischemistrypharmacologyGuanineanalogs & derivativeschemical synthesischemistrypharmacologyHumansSubstrate SpecificityDNAalkylationcancerenzyme inhibitorsguaninehalogenation
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1520-499554382015Sep29BiochemistryBiochemistryExtreme Expression of DNA Repair Protein Apurinic/Apyrimidinic Endonuclease 1 (APE1) in Human Breast Cancer As Measured by Liquid Chromatography and Isotope Dilution Tandem Mass Spectrometry.5787-9010.1021/acs.biochem.5b00928Apurinic/apyrimidinic endonuclease 1 (APE1) is a DNA repair protein and plays other important roles. Increased levels of APE1 in cancer have been reported. However, available methods for measuring APE1 levels are indirect and not quantitative. We previously developed an approach using liquid chromatography and tandem mass spectrometry with isotope dilution to accurately measure APE1 levels. Here, we applied this methodology to measure APE1 levels in normal and cancerous human breast tissues. Extreme expression of APE1 in malignant tumors was observed, suggesting that breast cancer cells may require APE1 for survival. Accurate measurement of APE1 may be essential for the development of novel treatment strategies and APE1 inhibitors as anticancer drugs. CoskunErdemEBiomolecular Measurement Division, National Institute of Standards and Technology , Gaithersburg, Maryland 20899, United States.Department of Toxicology, Faculty of Pharmacy, Gazi University , Ankara, Turkey.JarugaPawelPBiomolecular Measurement Division, National Institute of Standards and Technology , Gaithersburg, Maryland 20899, United States.ReddyPrasad TPTBiomolecular Measurement Division, National Institute of Standards and Technology , Gaithersburg, Maryland 20899, United States.DizdarogluMiralMBiomolecular Measurement Division, National Institute of Standards and Technology , Gaithersburg, Maryland 20899, United States.engJournal Article20150915
United StatesBiochemistry03706230006-2960EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAmino Acid SequenceBreastpathologyBreast NeoplasmschemistrypathologyCell Line, TumorChromatography, LiquidDNA-(Apurinic or Apyrimidinic Site) LyaseanalysisFemaleHumansModels, MolecularMolecular Sequence DataTandem Mass Spectrometry
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1165-158X6142015Aug28Cellular and molecular biology (Noisy-le-Grand, France)Cell. Mol. Biol. (Noisy-le-grand)The association of ApE1 -656T>G and 1349T>G polymorphisms with breast cancer susceptibility in northern Iran.70-4Breast cancer is the most common cancer and one of the main causes of cancer-related death in the world and has become a major public health concern. Many genes have been shown to be involved in the progress of the breast cancer. Human apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that has an important role in the base excision repair (BER) pathway. The aim of this study was to evaluate the association between ApE1 -656T>G and 1349T>G polymorphisms and the susceptibility to breast cancer in northern Iran population. Samples were obtained from 150 patients diagnosed with breast cancer and 150 control subjects and genotyped by tetra - primer amplification refractory mutation system PCR (T-ARMS-PCR). We observed a significant difference in genotype distributions of -656T>G polymorphism between patients and controls (P= 0.03). Findings indicated that individuals with the variant TG genotypes had a significant decreased risk of breast cancer (OR= 0.55, 95% CI= 0.33 - 0.91, P= 0.019). However, the significant association between 1349T>G polymorphism and breast cancer risk was not observed (P = 0.89). Larger studies are needed to confirm our results.MashayekhiFFUniversity of Guilan Department of Biology, Faculty of Sciences Rasht Iran mashayekhi&commat;guilan.ac.ir.YousefiMMUniversity of Guilan Department of Biology, Faculty of Sciences Rasht Iran.SalehiZZUniversity of Guilan Department of Biology, Faculty of Sciences Rasht Iran.SaediH SHSGuilan University of Medical Sciences Department of Radiotherapy, Faculty of Medicine Rasht Iran.PournouraliMMUniversity of Guilan Department of Biology, Faculty of Sciences Rasht Iran.engJournal ArticleResearch Support, Non-U.S. Gov't20150828
FranceCell Mol Biol (Noisy-le-grand)92167890145-5680EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdultAgedBreast NeoplasmsgeneticsCase-Control StudiesDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansIranMiddle AgedPolymorphism, Single Nucleotidegenetics
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1940-5901862015International journal of clinical and experimental medicineInt J Clin Exp MedEffect of APE1 and XRCC1 gene polymorphism on susceptibility to hepatocellular carcinoma and sensitivity to cisplatin.9931-6The relationship between APE1 and XRCC1 gene polymorphism and the susceptibility to hepatocellular carcinoma (HCC) was discussed, and the effect of APE1 and XRCC1 gene polymorphism on the sensitivity of HCC to cisplatin was investigated.From January 2010 to August 2014, 118 HCC patients were admitted to our hospital. 120 patients treated for non-tumor diseases during this period were recruited as controls. PCR-RFLP analyses were performed to determine the association between APE1 Asp148Glu and XRCC1 Arg194Trp polymorphism, risk of HCC, and sensitivity to cisplatin.The risk of HCC in patients with Glu/Glu genotype of APE1 gene was increased by 4.510 times (95% CI: 1.235~16.472, P<0.05). Compared with Asp/Asp, the risk of cisplatin resistance in patients with Glu/Glu genotype was increased by 10.500 times (95% CI: 1.800~61.241). Compared Arg/Arg genotype, the risk of cisplatin resistance in patients with Arp/Trp genotype of XRCC1 gene was increased by 6.701 times (95% CI: 1.464~30.732, P<0.05).APE1 Asp148Glu polymorphism is associated with the susceptibility to HCC. APE1 Asp148Glu and XRCC1 Arg194Trp polymorphism plays a part in the cisplatin resistance of HCC cells.YangZhihongZDepartment of Digestive, Yantaishan Hospital Yantai 264000, Shandong Province, China.ZhaoJuanJDepartment of Oncology, Xiangyang Central Hospital Xiangyang 441021, Hubei Province, China.engJournal Article20150615
United StatesInt J Clin Exp Med1014710101940-5901Iran J Med Sci. 2015 Jan;40(1):2-1225649829Tumour Biol. 2014 Mar;35(3):2529-3524254302Asian Pac J Cancer Prev. 2014 Jan;14(11):6613-824377576Clin Cancer Res. 1996 Apr;2(4):695-7069816220Cancer Lett. 2009 Jan 18;273(2):201-918824293Br J Cancer. 2012 Nov 6;107(10):1672-723059748Lung Cancer. 2009 Dec;66(3):298-30419324449World J Clin Oncol. 2014 Dec 10;5(5):874-8225493225Int J Clin Exp Med. 2015 Jan 15;8(1):145-5425784983Cancer Biomark. 2014;14(6):449-5625335737Cell Death Dis. 2014 Dec 04;5:e155125476899Hepat Mon. 2013 May 08;13(5):e761223922558Hum Vaccin Immunother. 2014;10(10):2983-9125483678Hepatobiliary Pancreat Dis Int. 2015 Apr;14(2):157-6325865688Genet Mol Res. 2014 Mar 06;13(1):1438-4624634242Biomed Res Int. 2015;2015:50921525710005Oncol Rep. 2014 May;31(5):2328-3424676454Mol Clin Oncol. 2013 May;1(3):403-41024649183Hum Exp Toxicol. 2012 Oct;31(10):981-100523023028Med J Aust. 1994 Oct 3;161(7):433-57935098Biochem Biophys Res Commun. 2012 Jul 13;423(4):826-3122713463Gene polymorphismcisplatin resistancehepatocellular carcinomasensitivity to cisplatinsusceptibility
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1096-09459922015OctExperimental and molecular pathologyExp. Mol. Pathol.Mitochondrial OGG1 protects against PM2.5-induced oxidative DNA damage in BEAS-2B cells.365-7310.1016/j.yexmp.2015.08.005S0014-4800(15)00167-7The enzyme 8-oxoguanine glycosylase 1 (OGG1) has been shown to be involved in the repair of oxidative DNA damage. However, the effect of OGG1 on oxidative DNA damage caused by particulate matter 2.5 (PM2.5) is unknown. Herein, we demonstrated that OGG1 could inhibit the generation of ROS and alleviate mitochondrial dysfunction and increased the expression of IL-1β caused by PM2.5. The dichlorodihydrofluorescein diacetate (DCFH-DA) staining and 5,5',6,6'-tetrachloro-1,1',3,3'-. tetraethylbenzi-midazolylcarbocyanine iodide (JC-1) staining using flow cytometry showed that PM2.5 induces the generation of ROS and leads to a reduction in mitochondrial membrane potential (MMP) in BEAS-2B cells. Overexpression of OGG1 inhibited the generation of ROS and the decline in MMP. Knockdown of OGG1 by RNA interference (RNAi) increased the generation of ROS and reduced the MMP. Real-time quantitative PCR (RT-qPCR) for the mitochondrial DNA copy number (mtDNAcn) and flow cytometry for apoptosis revealed that OGG1 inhibits the apoptosis and decreases mtDNAcn induced by PM2.5. Additionally, the results of the comet assay showed that OGG1 had a significant repair effect on DNA strand breaks caused by PM2.5. Overexpression of OGG1 also significantly suppressed the expression of IL-1β caused by PM2.5. Together, these data suggest that PM2.5 leads to mitochondrial dysfunction and the up-regulation of IL-1β could be reversed by overexpression of OGG1. The mitochondrial dysfunction caused by PM2.5 could be relieved by OGG1. Thus, the base excision repair enzyme OGG1 may alleviate mitochondrial dysfunction caused by PM2.5 involved in the expression of IL-1β. Copyright © 2015 Elsevier Inc. All rights reserved.YangLaweiLClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.WangYahongYClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.LinZiyingZClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.ZhouXuXClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.ChenTingTClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.HeHuijuanHClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.HuangHailiHClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.YangTengTClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.JiangYunYClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China; Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.XuWenyaWClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China; Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.YaoWeiminWDepartment of Respiratory Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.LiuTieTImmunology and Tumor Research Instituted, The First Affiliated Hospital, Health Science Center of Xi'an Jiaotong University, China.LiuGangGClinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China; Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China. Electronic address: gangliu11@gdmc.edu.cn.engJournal ArticleResearch Support, Non-U.S. Gov't20150819
NetherlandsExp Mol Pathol03707110014-48000Air Pollutants0DNA, Mitochondrial0Particulate Matter0RNA, Small InterferingEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAir Pollutantsadverse effectsApoptosisdrug effectsBlotting, WesternBronchidrug effectsmetabolismpathologyDNA Damagedrug effectsDNA Glycosylasesantagonists & inhibitorsgeneticsmetabolismDNA, MitochondrialEpithelial Cellsdrug effectsmetabolismpathologyFluorescent Antibody TechniqueHumansInflammationmetabolismpathologyprevention & controlMembrane Potential, Mitochondrialdrug effectsMitochondriametabolismOxidative Stressdrug effectsParticulate Matteradverse effectsRNA, Small InterferinggeneticsMMPOGG1PM2.5ROSmtDNAcn
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1643-3750212015Aug21Medical science monitor : international medical journal of experimental and clinical researchMed. Sci. Monit.Association of APE1 Gene Asp148Glu Variant with Digestive Cancer: A Meta-Analysis.2456-6610.12659/MSM.893954Apurinic/apyrimidinic endonuclease-1 (APE1) is a rate-limiting enzyme in DNA base excision repair and has been implicated in carcinogenesis. In this study, we summarize available data to examine the susceptibility of APE1 gene Asp148Glu variant to digestive cancer via a meta-analysis.Study selection and data abstraction were conducted independently by 2 authors. Random-effects model was utilized to pool effect estimates. Heterogeneity and publication bias were addressed.Sixteen articles involving 4916 digestive cancer patients and 7748 controls were qualified for this meta-analysis. Overall association showed an indicative association between Asp148Glu variant and digestive cancer under allelic (odds ratio or OR=1.11; 95% confidence interval or CI: 0.99-1.25; P=0.074) and dominant (OR=1.18; 95% CI: 1.00-1.40; P=0.056) models, with strong evidence of heterogeneity. Deviation from Hardy-Weinberg equilibrium was an obvious source of heterogeneity. In subgroup analyses by cancer sites, this variant was significantly associated with the increased risk for hepatocellular cancer under allelic (OR=1.50; 95% CI: 1.25-1.80; P<0.001) and homozygous genotypic (OR=1.55; 95% CI: 1.02-2.29; P=0.028) models. There were low probabilities of publication bias for the above comparisons.The results of this meta-analysis collectively suggest that APE1 gene Asp148Glu variant is not a risk-conferring factor for digestive cancer. Further large and well-designed studies are required.LiHeHDepartment of Gastric and Intestine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China (mainland).ZouJingJDepartment of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China (mainland).MiJiaJMedicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China (mainland).WeiXiaodanXMedicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China (mainland).ZhaoDongmeiDInstitute of Anatomy, Binzhou Medical University, Yantai, Shandong, China (mainland).ZhangShupingSInstitute of Pharmacology, Binzhou Medical University, Yantai, Shandong, China (mainland).TianGengGMedicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China (mainland).engJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov't20150821
United StatesMed Sci Monit96090631234-101030KYC7MIAIAspartic Acid3KX376GY7LGlutamic AcidEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCancer Res. 2007 Feb 1;67(3):1395-40417283177DNA Cell Biol. 2012 Aug;31(8):1384-9122691054J Oncol. 2012;2012:37048122997517Carcinogenesis. 2008 Jan;29(1):100-517984110PLoS One. 2011;6(12):e2897122205985Cancer Res. 2015 Feb 15;75(4):624-725634214Anticancer Res. 2010 Apr;30(4):1359-6420530453DNA Cell Biol. 2010 Jun;29(6):303-1120218899Trends Genet. 2004 Sep;20(9):439-4415313553Nucleic Acids Res. 2001 Jul 15;29(14):3116-2211452037BMC Med Res Methodol. 2011;11:4121473747Mol Cancer Ther. 2011 Sep;10(9):1698-70821700832Int J Mol Sci. 2012;13(2):1951-201122408433Int J Epidemiol. 2011 Oct;40(5):1329-4121729879Cancer Detect Prev. 2006;30(3):284-9116844323Med Sci Monit. 2011 Jun;17(6):CR329-3321629187Mutat Res. 2008 Feb 1;638(1-2):146-5317991492PLoS One. 2012;7(6):e3797022701590BMJ. 2003 Sep 6;327(7414):557-6012958120Nature. 2013 Sep 19;501(7467):338-4524048066PLoS One. 2012;7(7):e4013122792228Mutagenesis. 2010 Nov;25(6):569-7520817763J Clin Invest. 2013 Jul 1;:null23863623Mol Cell Biol. 2009 Apr;29(8):2264-7719188437J Epidemiol. 2012;22(6):477-8322850545Cancer Epidemiol Biomarkers Prev. 2010 Dec;19(12):3167-7321037106Mol Cell. 2005 Feb 4;17(3):463-7015694346Med Oncol. 2013 Jun;30(2):50523430444Asian Pac J Cancer Prev. 2012;13 Suppl:59-6423480773Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2101-816609022Am J Epidemiol. 2002 Aug 15;156(4):300-1012181099J Exp Clin Cancer Res. 2008;27:4918823566J Epidemiol. 2012;22(6):537-4223038158Curr Med Res Opin. 2011 Jul;27(7):1295-30221561390Cancer Causes Control. 2008 Dec;19(10):1077-8318478337J Appl Genet. 2010;51(3):343-5220720310Clin Chem. 2010 May;56(5):723-820224045Leuk Lymphoma. 2012 Oct;53(10):1934-4422475179Aspartic AcidgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDigestive System NeoplasmsgeneticsGenetic HeterogeneityGlutamic AcidgeneticsHumans
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1464-38043112016JanMutagenesisMutagenesisInfluence of Ogg1 repair on the genetic stability of ccc2 mutant of Saccharomyces cerevisiae chemically challenged with 4-nitroquinoline-1-oxide (4-NQO).107-1410.1093/mutage/gev062In Saccharomyces cerevisiae, disruption of genes by deletion allowed elucidation of the molecular mechanisms of a series of human diseases, such as in Wilson disease (WD). WD is a disorder of copper metabolism, due to inherited mutations in human copper-transporting ATPase (ATP7B). An orthologous gene is present in S. cerevisiae, CCC2 gene. Copper is required as a cofactor for a number of enzymes. In excess, however, it is toxic, potentially carcinogenic, leading to many pathological conditions via oxidatively generated DNA damage. Deficiency in ATP7B (human) or Ccc2 (yeast) causes accumulation of intracellular copper, favouring the generation of reactive oxygen species. Thus, it becomes important to study the relative importance of proteins involved in the repair of these lesions, such as Ogg1. Herein, we addressed the influence Ogg1 repair in a ccc2 deficient strain of S. cerevisiae. We constructed ccc2-disrupted strains from S. cerevisiae (ogg1ccc2 and ccc2), which were analysed in terms of viability and spontaneous mutator phenotype. We also investigated the impact of 4-nitroquinoline-1-oxide (4-NQO) on nuclear DNA damage and on the stability of mitochondrial DNA. The results indicated a synergistic effect on spontaneous mutagenesis upon OGG1 and CCC2 double inactivation, placing 8-oxoguanine as a strong lesion-candidate at the origin of spontaneous mutations. The ccc2 mutant was more sensitive to cell killing and to mutagenesis upon 4-NQO challenge than the other studied strains. However, Ogg1 repair of exogenous-induced DNA damage revealed to be toxic and mutagenic to ccc2 deficient cells, which can be due to a detrimental action of Ogg1 on DNA lesions induced in ccc2 cells. Altogether, our results point to a critical and ambivalent role of BER mediated by Ogg1 in the maintenance of genomic stability in eukaryotes deficient in CCC2 gene.© The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.da SilvaClaudia RCRLaboratório de Radio e Fotobiologia, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, UERJ, Rio de Janeiro CEP 20551-030, Brasil, Laboratório de Radiobiologia Molecular; Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro CEP 21.941-902, Brasil and.AlmeidaGabriella SGSLaboratório de Radio e Fotobiologia, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, UERJ, Rio de Janeiro CEP 20551-030, Brasil, Laboratório de Radiobiologia Molecular; Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro CEP 21.941-902, Brasil and Laboratório de Microbiologia e Avaliação Genotóxica, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, UFRJ, Rio de Janeiro CEP 21.941-902, Brasil.Caldeira-de-AraújoAdrianoALaboratório de Radio e Fotobiologia, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, UERJ, Rio de Janeiro CEP 20551-030, Brasil.LeitãoAlvaro CACLaboratório de Radiobiologia Molecular; Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro CEP 21.941-902, Brasil and.de PádulaMarceloMLaboratório de Radiobiologia Molecular; Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro CEP 21.941-902, Brasil and Laboratório de Microbiologia e Avaliação Genotóxica, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, UFRJ, Rio de Janeiro CEP 21.941-902, Brasil marcelo@pharma.ufrj.br.engJournal ArticleResearch Support, Non-U.S. Gov't20150814
EnglandMutagenesis87078120267-83570Cation Transport Proteins0DNA, Fungal0Saccharomyces cerevisiae Proteins56-57-54-Nitroquinoline-1-oxide5614-64-28-hydroxyguanine5Z93L87A1RGuanine789U1901C5CopperEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, S cerevisiaeEC 3.6.3.4CCC2 protein, S cerevisiaeIM4-Nitroquinoline-1-oxidetoxicityCation Transport ProteinsgeneticsCoppermetabolismDNA DamageDNA GlycosylasesmetabolismDNA RepairDNA, Fungaldrug effectsmetabolismGene DeletionGuanineanalogs & derivativesmetabolismSaccharomyces cerevisiaedrug effectsmetabolismSaccharomyces cerevisiae Proteinsgeneticsmetabolism
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1875-863020152015Disease markersDis. MarkersAssociation of DNA Repair Gene APE1 Asp148Glu Polymorphism with Breast Cancer Risk.86951210.1155/2015/869512The aim of this study was to investigate the role of APE1 Asp148Glu polymorphism in breast cancer progression in Saudi population.We examined the genetic variations (rs1130409) in the DNA base excision repair gene APE1 at codon 148 (Asp148Glu) and its association with breast cancer risk using genotypic assays and in silico structural as well as functional predictions. In silico structural analysis was performed with Asp148Glu allele and compared with the predicted native protein structure. The wild and mutant 3D structures of APE1 were compared and analyzed using solvent accessibility models for protein stability confirmation.Genotypic analysis of APE1 (rs1130409) showed statistically significant association of Asp148Glu with elevated susceptibility to breast cancer. The in silico analysis results indicated that the nsSNP Asp148Glu may cause changes in the protein structure and is associated with breast cancer risk.Taken together, this is the first report that established that Asp148Glu variant has structural and functional effect on the APE1 and may play an important role in breast cancer progression in Saudi population.AlMutairiFatimaFGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.PathanAkbar Ali KhanAAGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia ; Integrated Gulf Biosystems, Riyadh 11391, Saudi Arabia.AlanaziMohammedMGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.ShalabyManalMGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia ; Genetic Engineering and Biotechnology Research Institute (GEBRI), City for Scientific Research and Technology Applications, Alexandria 21934, Egypt.AlabdulkarimHuda AHAThe Comprehensive Cancer Center, King Fahad Medical City, Riyadh 11525, Saudi Arabia.AlamriAbdullahAGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.Al NaeemAbdulrahmanADepartment of Women's Imaging, King Fahad Medical City, Riyadh 11525, Saudi Arabia.ElrobhMoammadMGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.ShaikJilani PJPGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.KhanWajahatullahWDepartment of Basic Sciences, College of Science and Health Professions, King Saud Bin Abdul Aziz University for Health Sciences, Riyadh 11426, Saudi Arabia.KhanZahidZGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.ParineNarasimha ReddyNRGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.engJournal ArticleResearch Support, Non-U.S. Gov't20150716
United StatesDis Markers86041270278-0240EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBMC Bioinformatics. 2011;12:15121569468Arch Med Res. 2011 Apr;42(3):226-3421722819Biochemistry. 2011 Dec 6;50(48):10540-922032234Mech Ageing Dev. 2012 Apr;133(4):127-3222019847Mol Biol Rep. 2013 Jan;40(1):171-623143180PLoS One. 2013;8(3):e5955523516639Nucleic Acids Res. 2013 Apr 1;41(6):3483-9023408852Biol Res. 2013;46(2):161-723959014PLoS One. 2013;8(12):e8554124392019Tumour Biol. 2014 May;35(5):4727-3424414702Exp Mol Med. 2014;46:e10625033834Biomed Res Int. 2014;2014:29032525136576Crit Rev Biochem Mol Biol. 2008 Jul-Aug;43(4):239-7618756381J Bacteriol. 2000 Apr;182(8):2104-1210735851Carcinogenesis. 2000 Jul;21(7):1329-3410874010Science. 2001 Feb 16;291(5507):1284-911181991Mutat Res. 2001 Jan;432(3-4):53-911465542Free Radic Biol Med. 2002 Jul 1;33(1):15-2812086678Neuromolecular Med. 2002;2(1):47-6012230304Oncogene. 2002 Dec 16;21(58):8905-2512483508Mutat Res. 2003 May 15;526(1-2):93-12512714187Mutat Res. 1990 Sep-Nov;236(2-3):173-2011697933EMBO J. 1992 Sep;11(9):3323-351380454Annu Rev Biochem. 1994;63:915-487979257Bioessays. 1995 Aug;17(8):713-97661852J Med Genet. 1995 Aug;32(8):623-67473654Proteins. 1995 Nov;23(3):318-268710825Biochem Biophys Res Commun. 1998 Nov 9;252(1):178-839813166Genet Anal. 1999 Feb;14(5-6):143-910084106EMBO J. 1999 Apr 1;18(7):1905-1410202154EMBO J. 1999 Oct 15;18(20):5609-2110523305J Urol. 2006 Jan;175(1):108-12; discussion 11216406883Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W239-4216845001Breast Cancer Res Treat. 2006 Nov;100(1):121-616685588Breast Cancer Res Treat. 2007 Jun;103(2):161-617131038Mol Med. 2007 Jan-Feb;13(1-2):89-9617515960Nucleic Acids Res. 2007 Jul;35(Web Server issue):W407-1017517781Breast Cancer Res Treat. 2008 Sep;111(2):279-8817922186J Comput Chem. 2009 Jul 30;30(10):1545-61419444816Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Br J Cancer. 2010 Feb 16;102(4):704-920087352Nat Protoc. 2010 Apr;5(4):725-3820360767Anticancer Res. 2010 Apr;30(4):1359-6420530453BMC Bioinformatics. 2010;11:54821059217AdultBreast NeoplasmsgeneticsCase-Control StudiesDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleHumansMiddle AgedMutation, MissensePolymorphism, Single NucleotideSaudi Arabia
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1165-158X6142015Aug05Cellular and molecular biology (Noisy-le-Grand, France)Cell. Mol. Biol. (Noisy-le-grand)The association between 1349T>G polymorphism of ApE1 gene and the risk of prostate cancer in northern Iran.21-4Prostate cancer (PCa) is the most common malignancy in men and the fourth most common cause of death based on cancer all over the world. Many genes has been shown to be involved in the progress of the prostate cancer. Human apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that has an important role in the base excision repair (BER) pathway. The aim of this study was to evaluate the association of ApE1 1349T>G polymorphism and the susceptibility to prostate cancer in northern Iran population. Samples were collected from 100 patients diagnosed with prostate cancer patients and 100 controls subjects and genotyped by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). We observed a significant difference in genotype distributions of ApE1 1349T>G polymorphism between patients and controls (P= 0.039). Our findings revealed individuals with the variant TG and GG had a significant increased risk of prostate cancer (GG: OR= 2.50, 95%CI= 1.063-5.874, P= 0.035. TG: OR= 2.40, 95%CI= 1.16-4.95, P= 0.017). Also, more analyses were showed that G allele were associated with increased risk of prostate cancer (OR= 1.493, 95%CI= 1.007-2.21, P= 0.045). The data from this study indicates that the ApE1 1349T>G polymorphism is associated with increased risk of prostate cancer. Although more studies should be considered with larger number of patients and control subjects to confirm our results.PournouraliMMFaculty of Sciences, University of Guilan Department of Biology Rasht Iran mostafapournourali&commat;yahoo.com.TarangA RARAgriculture Biotechnology Research Institute of Iran (ABRII) Department of Genomics and Animal, Branches of north region of Iran Rasht Iran.YousefiMMFaculty of Sciences, University of Guilan Department of Biology Rasht Iran.engJournal Article20150805
FranceCell Mol Biol (Noisy-le-grand)92167890145-5680EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCase-Control StudiesDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansIranepidemiologyMaleMiddle AgedPolymerase Chain ReactionPolymorphism, Restriction Fragment LengthPolymorphism, Single NucleotidegeneticsProstatic Neoplasmsepidemiologygenetics
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1791-24313442015OctOncology reportsOncol. Rep.Impact of reduced levels of APE1 transcripts on the survival of patients with urothelial carcinoma of the bladder.1667-7410.3892/or.2015.4151Molecular evidence indicates that alterations in genes involved in the maintenance of genome stability may be related to susceptibility to bladder carcinoma. Our goal was to evaluate the prognostic role of base excision repair (BER) genes in a cohort of patients diagnosed with primary urothelial carcinoma of the bladder (UCB). The levels of all APE1, XRCC1 and POLB transcripts were detected by quantitative real-time PCR (qPCR) technique in tumor samples from 52 patients undergoing transurethral resection (TUR) for primary UCB at the Department of Urology, Brazilian National Cancer Institute, Rio de Janeiro. Increased levels of APE1, XRCC1 and POLB transcripts were significantly associated with high-grade tumors when compared to these levels in low-grade tumors (p<0.01) and could be attributed to different mechanisms of transcriptional regulation as a response to tumorigenesis and oxidative stress. By analyzing the collected data in the present study, regardless of pathological grade or stage, univariate analysis revealed that the reduced levels of APE1 transcripts were significantly associated with cancer-specific mortality (p=0.032). Furthermore, the variant genotype (TG/GG) of the APE1 T1349G polymorphism was observed in 75% of a subset of patients who concomitantly experienced reduced levels of the APE1 transcript and death and/or recurrence events. Taken together, our data reinforce the idea that human DNA repair mechanisms must be finely regulated in order to avoid instability leading to tumorigenesis and poor clinical outcomes in UCB patients.Chantre-JustinoMarianaMCarlos Chagas Filho Institute of Biophysics, Rio de Janeiro Federal University, Rio de Janeiro, Brazil.AlvesGildaGResearch Coordination, National Institute of Cancer (INCA), Rio de Janeiro, Brazil.BrittoConstançaCMolecular Biology and Endemic Diseases Laboratory, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.CardosoAngélicaAMolecular Biology and Endemic Diseases Laboratory, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.ScherrerLucianoLBrazilian Society of Clinical Oncology, Belo Horizonte, Minas Gerais, Brazil.MoreiraAline dos SantosAdos SDNA Sequencing Platform, PDTIS/FIOCRUZ, Rio de Janeiro, Brazil.QuirinoRaulRDepartment of Urology, National Institute of Cancer, Rio de Janeiro, Brazil.OrnellasAntonioADepartment of Urology, National Institute of Cancer, Rio de Janeiro, Brazil.LeitãoAlvaroACarlos Chagas Filho Institute of Biophysics, Rio de Janeiro Federal University, Rio de Janeiro, Brazil.LageClaudiaCCarlos Chagas Filho Institute of Biophysics, Rio de Janeiro Federal University, Rio de Janeiro, Brazil.engJournal ArticleResearch Support, Non-U.S. Gov't20150724
GreeceOncol Rep94227561021-335X0DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 2.7.7.-DNA Polymerase betaEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMClin Chem. 2009 Apr;55(4):611-2219246619Carcinogenesis. 2009 May;30(5):763-819237606Anticancer Res. 2009 Apr;29(4):1389-9319414392J Urol. 2009 Aug;182(2):741-819539325Int J Oncol. 2009 Nov;35(5):1069-7919787261Mutagenesis. 2009 Nov;24(6):507-1219762350J Urol. 2010 Jul;184(1):336-4320488473Urol Oncol. 2010 Jul-Aug;28(4):401-820610278PLoS One. 2011;6(12):e2897122205985J Surg Oncol. 2012 Mar 15;105(4):425-3022311819J Cancer Res Clin Oncol. 2012 May;138(5):739-4322258852Mol Biol Rep. 2013 Jan;40(1):171-623143180Eur Urol. 2013 Feb;63(2):234-4122877502CA Cancer J Clin. 2013 Jan;63(1):11-3023335087Exp Biol Med (Maywood). 2013 Jan;238(1):66-7623479765Urol Oncol. 2013 Aug;31(6):802-1121924649BMC Urol. 2013;13:5624156254Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165J Mol Biol. 2003 Aug 29;331(5):1017-2312927538Toxicology. 2003 Nov 15;193(1-2):3-3414599765Environ Health Perspect. 2003 Nov;111(15):1843-5014630517J Clin Oncol. 2004 Mar 15;22(6):1014-2414981102Cell Cycle. 2004 Aug;3(8):998-100115280658EMBO J. 1996 Dec 2;15(23):6662-708978692J Biol Chem. 1999 Feb 5;274(6):3642-509920913DNA Repair (Amst). 2005 May 2;4(5):583-9315811630Mol Cancer. 2005;4(1):1815882455DNA Repair (Amst). 2005 Jul 12;4(7):826-3515927541Mutat Res. 2005 Sep 4;577(1-2):275-8315922366Clin Cancer Res. 2005 Sep 1;11(17):6205-1116144922Cell Cycle. 2006 Feb;5(3):250-916418580Carcinogenesis. 2006 Mar;27(3):361-7316352616Cell Cycle. 2007 Feb 15;6(4):471-717329970Hum Genet. 2007 Apr;121(2):233-4217203305Cancer Res. 2008 Mar 15;68(6):1777-8518339858Clin Cancer Res. 2000 Feb;6(2):602-910690545Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):3110-524520177Int J Biochem Cell Biol. 2000 Sep;32(9):925-911084372Cancer Res. 2001 Mar 1;61(5):2220-511280790Clin Cancer Res. 2001 Apr;7(4):824-3011309329Nature. 2001 May 17;411(6835):366-7411357144Clin Cancer Res. 2001 Nov;7(11):3510-811705870EMBO J. 2001 Dec 3;20(23):6919-2611726527Cancer Res. 2002 Jun 15;62(12):3511-412067997Nat Genet. 2003 Jan;33(1):90-612469123Cancer Sci. 2008 Apr;99(4):646-5218377416J Mol Biol. 2008 May 23;379(1):17-2718439621Cell Mol Life Sci. 2008 May;65(10):1544-6518259689AgedAged, 80 and overBrazilDNA Polymerase betabiosynthesisgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisgeneticsDNA-Binding ProteinsbiosynthesisgeneticsFemaleGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseGenotypeHumansMaleMiddle AgedNeoplasm GradingNeoplasm Recurrence, LocalgeneticsmortalitypathologyPolymorphism, Single NucleotidePrognosisSurvival AnalysisUrinary Bladder NeoplasmsgeneticsmortalitypathologyX-ray Repair Cross Complementing Protein 1
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1554-893710102015Oct16ACS chemical biologyACS Chem. Biol.Small Molecule Inhibitors of 8-Oxoguanine DNA Glycosylase-1 (OGG1).2334-4310.1021/acschembio.5b00452The DNA base excision repair (BER) pathway, which utilizes DNA glycosylases to initiate repair of specific DNA lesions, is the major pathway for the repair of DNA damage induced by oxidation, alkylation, and deamination. Early results from clinical trials suggest that inhibiting certain enzymes in the BER pathway can be a useful anticancer strategy when combined with certain DNA-damaging agents or tumor-specific genetic deficiencies. Despite this general validation of BER enzymes as drug targets, there are many enzymes that function in the BER pathway that have few, if any, specific inhibitors. There is a growing body of evidence that suggests inhibition of 8-oxoguanine DNA glycosylase-1 (OGG1) could be useful as a monotherapy or in combination therapy to treat certain types of cancer. To identify inhibitors of OGG1, a fluorescence-based screen was developed to analyze OGG1 activity in a high-throughput manner. From a primary screen of ∼50,000 molecules, 13 inhibitors were identified, 12 of which were hydrazides or acyl hydrazones. Five inhibitors with an IC50 value of less than 1 μM were chosen for further experimentation and verified using two additional biochemical assays. None of the five OGG1 inhibitors reduced DNA binding of OGG1 to a 7,8-dihydro-8-oxoguanine (8-oxo-Gua)-containing substrate, but all five inhibited Schiff base formation during OGG1-mediated catalysis. All of these inhibitors displayed a >100-fold selectivity for OGG1 relative to several other DNA glycosylases involved in repair of oxidatively damaged bases. These inhibitors represent the most potent and selective OGG1 inhibitors identified to date.DonleyNathanNOregon Institute of Occupational Health Sciences, Oregon Health & Science University , Portland, Oregon 97239, United States.JarugaPawelPBiomolecular Measurement Division, National Institute of Standards and Technology , Gaithersburg, Maryland 20899, United States.CoskunErdemEBiomolecular Measurement Division, National Institute of Standards and Technology , Gaithersburg, Maryland 20899, United States.DizdarogluMiralMBiomolecular Measurement Division, National Institute of Standards and Technology , Gaithersburg, Maryland 20899, United States.McCulloughAmanda KAKOregon Institute of Occupational Health Sciences, Oregon Health & Science University , Portland, Oregon 97239, United States.LloydR StephenRSOregon Institute of Occupational Health Sciences, Oregon Health & Science University , Portland, Oregon 97239, United States.engP01 CA160032CANCI NIH HHSUnited StatesT32 ES007060ESNIEHS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20150807
United StatesACS Chem Biol1012829061554-89290Antineoplastic Agents0Enzyme Inhibitors0Hydrazines0Small Molecule Libraries27RFH0GB4RhydrazineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMDNA Repair (Amst). 2007 Apr 1;6(4):470-8017116430Structure. 2011 Jan 12;19(1):117-2721220122Mutat Res Rev Mutat Res. 2015 Jan-Mar;763:212-4525795122J Proteome Res. 2013 Feb 1;12(2):1049-6123268652Cell Cycle. 2010 Dec 15;9(24):4876-8321131780Mol Cancer Ther. 2009 Jul;8(7):2015-2619567822Chem Res Toxicol. 2014 Dec 15;27(12):2113-825405892Clin Chim Acta. 2006 Mar;365(1-2):30-4916214123DNA Repair (Amst). 2013 Oct;12(10):856-6323890570EMBO Mol Med. 2009 Sep;1(6-7):315-2220049735Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Curr Opin Allergy Clin Immunol. 2015 Feb;15(1):89-9725486379PLoS One. 2013 Dec 09;8(12):e8166724349107Nucleic Acids Res. 2006 Mar 20;34(5):1620-3216549874Nucleic Acids Res. 2014;42(16):10748-6125143530DNA Repair (Amst). 2013 Jan 1;12(1):18-2623127499Nature. 2014 Apr 10;508(7495):222-724695225Biochimie. 2002 Jan;84(1):27-4711900875PLoS One. 2014 Dec 19;9(12 ):e11555825526641Free Radic Biol Med. 2015 Apr;81:107-1825614460Nature. 2014 Apr 10;508(7495):215-2124695224Biochemistry. 2004 Dec 21;43(50):15909-1415595846J Biol Chem. 2011 Dec 30;286(52):44679-9022057269J Biol Chem. 2005 Dec 9;280(49):40544-5116221681FEBS Lett. 1994 Mar 14;341(1):59-648137923J Immunol. 2014 Nov 1;193(9):4643-5325267977Int J Cancer. 2012 Nov 15;131(10):2433-4422377908Lancet. 2010 Jul 24;376(9737):235-4420609467Free Radic Biol Med. 2013 Aug;61:384-9423612479Mol Cancer Res. 2009 Dec;7(12 ):1973-8319996303Biochemistry. 2002 Jun 4;41(22):7054-6412033939Cancer Res. 2009 Apr 15;69(8):3589-9619351835Free Radic Biol Med. 2014 Aug;73:430-824681335J Immunol. 2014 Mar 1;192(5):2384-9424489103Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3523-811904416Free Radic Biol Med. 2012 Jan 15;52(2):392-40122100973Environ Sci Pollut Res Int. 2014 Feb;21(3):1599-61324170504Oncogene. 2006 Apr 20;25(17):2425-3216369492J Biol Chem. 2007 May 25;282(21):15790-817389588Nucleic Acids Res. 1999 Oct 15;27(20):4001-710497264Free Radic Biol Med. 2008 Dec 15;45(12):1601-918926902Free Radic Biol Med. 2002 Feb 1;32(3):212-2011827746Mutat Res. 2010 Nov 28;703(1):18-2320696268Nat Rev Cancer. 2012 Dec;12(12):801-1723175119Biochim Biophys Acta. 2013 Jan;1834(1):247-7123076011Cancer Sci. 2014 Apr;105(4):370-8824484288Cell Res. 2008 Jan;18(1):27-4718166975Br J Pharmacol. 2013 Aug;169(8):1745-6523682925PLoS Biol. 2014 Mar 11;12(3):e100180724618719Cancer Cell. 2010 Mar 16;17 (3):235-4820227038Biochemistry. 1992 Jan 14;31(1):106-101731864Biochemistry. 1980 Sep 2;19(18):4299-3036158332Antineoplastic AgentschemistrypharmacologyDNA Glycosylasesantagonists & inhibitorsDrug Evaluation, PreclinicalEnzyme Activationdrug effectsEnzyme InhibitorschemistrypharmacologyHumansHydrazineschemistryInhibitory Concentration 50Small Molecule Librarieschemistrypharmacology
201572960201572960201651460ppublish2621862910.1021/acschembio.5b00452PMC4894821NIHMS790632
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1873-135X7792015SepMutation researchMutat. Res.Reduced cellular DNA repair capacity after environmentally relevant arsenic exposure. Influence of Ogg1 deficiency.144-5110.1016/j.mrfmmm.2015.07.004S0027-5107(15)30023-3Inorganic arsenic (i-As) is a genotoxic and carcinogenic environmental contaminant known to affect millions of people worldwide. Our previous work demonstrated that chronic sub-toxic i-As concentrations were able to induce biologically significant levels of genotoxic and oxidative DNA damage that were strongly influenced by the Ogg1 genotype. In order to study the nature of the observed levels of damage and the observed differences between MEF Ogg1(+/+) and Ogg1(-/-) genetic backgrounds, the genotoxic and oxidative DNA repair kinetics of 18-weeks exposed MEF cells were evaluated by the comet assay. Results indicate that MEF Ogg1(+/+) and Ogg1(-/-) cells chronically exposed to i-As repair the DNA damage induced by arsenite, potassium bromide and UVC radiation less efficiently than control cells, being that observation clearly more pronounced in MEF Ogg1(-/-) cells. Consequently, exposed cells accumulate a higher percentage of unrepaired DNA damage at the end of the repair period. As an attempt to eliminate i-As associated toxicity, chronically exposed MEF Ogg1(-/-) cells overexpress the arsenic metabolizing enzyme As3mt. This adaptive response confers cells a significant resistance to i-As-induced cell death, but at expenses of accumulating high levels of DNA damage due to their repair impairment. Overall, the work presented here evidences that i-As chronic exposure disrupts the normal cellular repair function, and that oxidative DNA damage-and Ogg1 deficiency-exacerbates this phenomenon. The observed cell death resistance under a chronic scenario of genotoxic and oxidative stress may in turn contribute to the carcinogenic effects of i-As. Copyright © 2015 Elsevier B.V. All rights reserved.BachJordiJGrup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain.PeremartíJanaJGrup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain.AnnangiBalasubramnayamBGrup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain.MarcosRicardRGrup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain; CIBER Epidemiología y Salud Pública, ISCIII, Madrid, Spain. Electronic address: ricard.marcos@uab.es.HernándezAlbaAGrup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain; CIBER Epidemiología y Salud Pública, ISCIII, Madrid, Spain. Electronic address: alba.hernandez@uab.es.engJournal ArticleResearch Support, Non-U.S. Gov't20150713
NetherlandsMutat Res04007630027-5107EC 2.1.1.-MethyltransferasesEC 2.1.1.137AS3MT protein, mouseEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseN712M78A8GArsenicIMAnimalsArsenictoxicityDNA DamagegeneticsDNA GlycosylasesgeneticsDNA Repairdrug effectsgeneticsEnvironmental ExposureFibroblastsGene Expression Regulationdrug effectsMethyltransferasesbiosynthesisgeneticsMiceOxidative StressgeneticsUltraviolet RaysArsenicAs3mtChronic exposureDNA repair kineticsOgg1Oxidative DNA damage
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1554-86351192015AutophagyAutophagyStructure of yeast Ape1 and its role in autophagic vesicle formation.1580-9310.1080/15548627.2015.1067363In Saccharomyces cerevisiae, a constitutive biosynthetic transport pathway, termed the cytoplasm-to-vacuole targeting (Cvt) pathway, sequesters precursor aminopeptidase I (prApe1) dodecamers in the form of a large complex into a Cvt vesicle using autophagic machinery, targeting it into the vacuole (the yeast lysosome) where it is proteolytically processed into its mature form, Ape1, by removal of an amino-terminal 45-amino acid propeptide. prApe1 is thought to serve as a scaffolding cargo critical for the assembly of the Cvt vesicle by presenting the propeptide to mediate higher-ordered complex formation and autophagic receptor recognition. Here we report the X-ray crystal structure of Ape1 at 2.5 Å resolution and reveal its dodecameric architecture consisting of dimeric and trimeric units, which associate to form a large tetrahedron. The propeptide of prApe1 exhibits concentration-dependent oligomerization and forms a stable tetramer. Structure-based mutagenesis demonstrates that disruption of the inter-subunit interface prevents dodecameric assembly and vacuolar targeting in vivo despite the presence of the propeptide. Furthermore, by examining the vacuolar import of propeptide-fused exogenous protein assemblies with different quaternary structures, we found that 3-dimensional spatial distribution of propeptides presented by a scaffolding cargo is essential for the assembly of the Cvt vesicle for vacuolar delivery. This study describes a molecular framework for understanding the mechanism of Cvt or autophagosomal biogenesis in selective macroautophagy. SuMing-YuanMYa Institute of Biological Chemistry; Academia Sinica ; Taipei , Taiwan.b Institute of Biochemical Sciences; College of Life Science; National Taiwan University ; Taipei , Taiwan.PengWen-HsinWHa Institute of Biological Chemistry; Academia Sinica ; Taipei , Taiwan.HoMeng-RuMRa Institute of Biological Chemistry; Academia Sinica ; Taipei , Taiwan.SuShih-ChiehSCa Institute of Biological Chemistry; Academia Sinica ; Taipei , Taiwan.b Institute of Biochemical Sciences; College of Life Science; National Taiwan University ; Taipei , Taiwan.ChangYuan-ChihYCc Institute of Cellular and Organismic Biology; Academia Sinica ; Taipei , Taiwan.ChenGuang-ChaoGCa Institute of Biological Chemistry; Academia Sinica ; Taipei , Taiwan.b Institute of Biochemical Sciences; College of Life Science; National Taiwan University ; Taipei , Taiwan.ChangChung-ICIa Institute of Biological Chemistry; Academia Sinica ; Taipei , Taiwan.b Institute of Biochemical Sciences; College of Life Science; National Taiwan University ; Taipei , Taiwan.engJournal ArticleResearch Support, Non-U.S. Gov't
United StatesAutophagy1012651881554-86270Peptides0Recombinant Fusion Proteins0Saccharomyces cerevisiae ProteinsEC 3.4.11.-AminopeptidasesEC 3.4.11.22APE1 protein, S cerevisiaeIMCancer Res. 2010 May 1;70(9):3431-420424122Autophagy. 2011 Apr;7(4):386-40021183797Mol Cell. 2001 Jun;7(6):1131-4111430817Chem Soc Rev. 2010 Sep;39(9):3541-7520676430J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-67419461840Curr Opin Cell Biol. 2002 Aug;14(4):468-7512383798J Biol Chem. 2012 Mar 23;287(13):10121-3322123825Autophagy. 2007 Mar-Apr;3(2):106-1617204848J Biol Chem. 2001 Jan 19;276(3):2083-711085977Z Naturforsch C. 1977 Nov-Dec;32(11-12):938-43146356Acta Crystallogr D Biol Crystallogr. 2006 Sep;62(Pt 9):1002-1116929101Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1395-40223897463Nat Cell Biol. 2014 Jun;16(6):495-50124875736Mol Biol Cell. 2005 Apr;16(4):1593-60515659643Science. 2012 May 25;336(6084):1030-322628654J Cell Biol. 1997 Jul 14;138(1):37-449214379Mol Cell. 2009 Feb 27;33(4):505-1619250911IEEE Trans Vis Comput Graph. 2006 Sep-Oct;12(5):1237-4417080857Ann Neurol. 2007 May;61(5):476-8317469125Nat Cell Biol. 2014 May;16(5):425-3324705553J Comput Chem. 2004 Oct;25(13):1605-1215264254PLoS One. 2013;8(7):e6784323861819EMBO J. 2001 Nov 1;20(21):5971-8111689437Int Immunol. 2013 Jan;25(1):1-1023042773Z Naturforsch C. 1977 Nov-Dec;32(11-12):929-37146355Anal Biochem. 2003 Sep 1;320(1):104-2412895474J Cell Biol. 1996 Mar;132(6):999-10108601598J Struct Biol. 2007 Jan;157(1):38-4616859925Biophys J. 2000 Mar;78(3):1606-1910692345J Cell Biol. 1997 Dec 29;139(7):1687-959412464Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-6721460454Nature. 2010 Jul 1;466(7302):68-7620562859Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-315299374Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-3215572765BMC Struct Biol. 2012;12:1422720794J Cell Biol. 1992 Oct;119(2):287-991400574Nat Cell Biol. 2010 Sep;12(9):814-2220811353Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Jan 1;67(Pt 1):17-2221206015J Cell Biol. 1997 May 5;137(3):609-189151668BMC Bioinformatics. 2008;9:4018215316Dev Cell. 2002 Dec;3(6):815-2412479807J Mol Biol. 2012 Sep 28;422(4):495-50722709581AminopeptidaseschemistrymetabolismAutophagyCrystallography, X-RayCytoplasmic VesiclesmetabolismultrastructureModels, MolecularMutationPeptideschemistryProtein MultimerizationRecombinant Fusion ProteinsmetabolismSaccharomyces cerevisiaecytologymetabolismultrastructureSaccharomyces cerevisiae ProteinschemistrymetabolismSubcellular FractionsmetabolismVacuolesmetabolismApe1Atg19CvtX-ray crystallographyautophagy
201572660201572660201662160ppublish2620868110.1080/15548627.2015.1067363PMC4590589
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1873-4596892015DecFree radical biology & medicineFree Radic. Biol. Med.Whole transcriptome analysis reveals a role for OGG1-initiated DNA repair signaling in airway remodeling.20-3310.1016/j.freeradbiomed.2015.07.007S0891-5849(15)00328-7Reactive oxygen species (ROS) generated by environmental exposures, and endogenously as by-products of respiration, oxidatively modify biomolecules including DNA. Accumulation of ROS-induced DNA damage has been implicated in various diseases that involve inflammatory processes, and efficient DNA repair is considered critical in preventing such diseases. One of the most abundant DNA base lesions is 7,8-dihydro-8-oxoguanine (8-oxoG), which is repaired by the 8-oxoguanine DNA glycosylase 1 (OGG1)-initiated base-excision repair (OGG1-BER) pathway. Recent studies have shown that the OGG1-BER by-product 8-oxoG base forms a complex with cytosolic OGG1, activating small GTPases and downstream cell signaling in cultured cells and lungs. This implies that persistent OGG1-BER could result in signaling leading to histological changes in airways. To test this, we mimicked OGG1-BER by repeatedly challenging airways with its repair product 8-oxoG base. Gene expression was analyzed by RNA sequencing (RNA-Seq) and qRT-PCR, and datasets were evaluated by gene ontology and statistical tools. RNA-Seq analysis identified 3252 differentially expressed transcripts (2435 up- and 817 downregulated, ≥ 3-fold change). Among the upregulated transcripts, 2080 mRNAs were identified whose encoded protein products were involved in modulation of the actin family cytoskeleton, extracellular matrix, cell adhesion, cadherin, and cell junctions, affecting biological processes such as tissue development, cell-to-cell adhesion, cell communication, and the immune system. These data are supported by histological observations showing epithelial alterations, subepithelial fibrosis, and collagen deposits in the lungs. These data imply that continuous challenge by the environment and consequent OGG1-BER-driven signaling trigger gene expression consistent with airway remodeling.Copyright © 2015. Published by Elsevier Inc.Aguilera-AguirreLeopoldoLDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.HosokiKoaKDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.BacsiAttilaADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.RadákZsoltZDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.SurSanjivSDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, and, University of Texas Medical Branch, Galveston, TX 77555, USA.HegdeMuralidhar LMLDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.TianBingBDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, and, University of Texas Medical Branch, Galveston, TX 77555, USA.Saavedra-MolinaAlfredoADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.BrasierAllan RARDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, and, University of Texas Medical Branch, Galveston, TX 77555, USA.BaXueqingXDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.BoldoghIstvanIDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, and, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: sboldogh@utmb.edu.engP01 AI062885AINIAID NIH HHSUnited StatesN01HV00245HVNHLBI NIH HHSUnited StatesR01 ES018948ESNIEHS NIH HHSUnited StatesR01 NS088645NSNINDS NIH HHSUnited StatesT32 ES007254ESNIEHS NIH HHSUnited StatesP30 ES006676ESNIEHS NIH HHSUnited StatesT32 ES007254-22ESNIEHS NIH HHSUnited StatesAI062885AINIAID NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20150715
United StatesFree Radic Biol Med87091590891-58490Biomarkers5614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMNature. 2007 May 31;447(7144):606-817507928Hypertension. 2010 Apr;55(4):939-4520177000Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-5016199517Curr Opin Allergy Clin Immunol. 2014 Feb;14(1):44-824322009PLoS One. 2012;7(12):e5169723284747DNA Repair (Amst). 2013 Oct;12(10):856-6323890570Annu Rev Cell Dev Biol. 2011;27:265-9021568710Methods Mol Biol. 2011;763:195-20621874453Methods Mol Biol. 2009;563:123-4019597783FASEB J. 2003 Jul;17(10):1195-21412832285Free Radic Biol Med. 2012 Feb 15;52(4):749-5622198182Mutat Res. 2003 Oct 29;531(1-2):109-2614637249Dev Biol. 2011 Jun 15;354(2):191-20721420400Methods. 2001 Dec;25(4):402-811846609Dev Biol. 2006 Jun 15;294(2):271-916643883Annu Rev Cell Dev Biol. 2004;20:61-8615473835J Clin Invest. 2005 Aug;115(8):2169-7916075057DNA Repair (Amst). 2013 Jan 1;12(1):18-2623127499Free Radic Biol Med. 2015 Apr;81:107-1825614460Mol Cell Biol. 2008 Jun;28(11):3623-3818362169Curr Opin Allergy Clin Immunol. 2015 Feb;15(1):21-625546326Int J Mol Med. 2006 Sep;18(3):523-816865240J Immunol. 2014 Nov 1;193(9):4643-5325267977Brief Bioinform. 2013 Nov;14(6):671-8322988256DNA Repair (Amst). 2004 Nov 2;3(11):1457-6815380101Free Radic Biol Med. 2013 Aug;61:384-9423612479Int J Mol Sci. 2014 Sep 23;15(9):16975-9725250913Free Radic Biol Med. 2014 Aug;73:430-824681335Nat Rev Cancer. 2014 Feb;14(2):121-3424442140J Immunol. 2014 Mar 1;192(5):2384-9424489103Biochim Biophys Acta. 2014 Mar;1839(3):169-7724345612World Allergy Organ J. 2014 Jun 02;7(1):1324982697J Cell Sci. 2010 Mar 1;123(Pt 5):637-4220164302J Immunol. 2009 Oct 15;183(8):5379-8719786549Biochim Biophys Acta. 2010 Feb;1803(2):191-20019171166Am J Respir Crit Care Med. 2000 May;161(5):1720-4510806180Genes Dev. 2006 Dec 1;20(23):3199-21417158740Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):5-1310708948Free Radic Biol Med. 2010 Aug 15;49(4):587-9620483371J Mol Cell Biol. 2011 Jun;3(3):159-6621502305Antioxid Redox Signal. 2006 May-Jun;8(5-6):985-9216771688DNA Repair (Amst). 2013 Dec;12(12):1094-10424075420FASEB J. 2013 Apr;27(4):1631-4323254341Mol Cells. 1997 Jun 30;7(3):305-129264015Mol Cancer Ther. 2012 Nov;11(11):2362-7222933707J Biol Chem. 2012 Jun 15;287(25):20769-7322568941Toxicol Sci. 2011 May;121(1):177-9021297082Nat Protoc. 2013 Aug;8(8):1551-6623868073Mutat Res. 2003 Oct 29;531(1-2):5-2314637244Nat Commun. 2012 Mar 13;3:73522415826Ann Allergy Asthma Immunol. 2009 Mar;102(3):238-4619354071FEBS Lett. 2006 May 22;580(12):2811-2016678165Clin Exp Allergy. 2009 Jul;39(7):1018-2619364333Eur Respir J. 2007 Jul;30(1):134-5517601971Nat Rev Mol Cell Biol. 2014 Jun;15(6):411-2124854789Cell Signal. 2007 Jul;19(7):1419-3317317104J Biol Chem. 2009 Nov 13;284(46):31658-6319758983Cancer Res. 2013 Aug 1;73(15):4909-2223761328Airway RemodelinggeneticsAnimalsBiomarkersmetabolismDNA Damagedrug effectsgeneticsDNA GlycosylasesgeneticsmetabolismDNA Repairdrug effectsgeneticsFemaleGene Expression ProfilingGene Expression Regulationdrug effectsGene OntologyGuanineanalogs & derivativespharmacologyHigh-Throughput Nucleotide SequencingmethodsLungcytologydrug effectsmetabolismMiceMice, Inbred BALB COxidative Stress8-OxoguanineAirway remodelingOGG1-BER
201504092015070320150707201571960201571960201692360ppublish26187872S0891-5849(15)00328-710.1016/j.freeradbiomed.2015.07.007PMC4924473NIHMS782672
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1873-135X7792015SepMutation researchMutat. Res.APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER.96-10410.1016/j.mrfmmm.2015.06.010S0027-5107(15)30016-6Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24h. In cultures where APE1 expression was reduced by ∼ 80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons.Copyright © 2015 Elsevier B.V. All rights reserved.KimHyun-SukHSDepartment of Biochemistry and Molecular Biology, Indianapolis, IN 46202, USA.GuoChunluCDepartment of Pharmacology and Toxicology, Indianapolis, IN 46202, USA.ThompsonEric LELDepartment of Pharmacology and Toxicology, Indianapolis, IN 46202, USA.JiangYanlinYDepartment of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.KelleyMark RMRDepartment of Biochemistry and Molecular Biology, Indianapolis, IN 46202, USA; Department of Pharmacology and Toxicology, Indianapolis, IN 46202, USA; Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.VaskoMichael RMRDepartment of Pharmacology and Toxicology, Indianapolis, IN 46202, USA.LeeSuk-HeeSHDepartment of Biochemistry and Molecular Biology, Indianapolis, IN 46202, USA. Electronic address: slee@iu.edu.engCA151367CANCI NIH HHSUnited StatesCA121168CANCI NIH HHSUnited StatesCA121168S1CANCI NIH HHSUnited StatesR01 CA151367CANCI NIH HHSUnited StatesCA167291CANCI NIH HHSUnited StatesR01 CA121168CANCI NIH HHSUnited StatesR01 CA167291CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20150626
NetherlandsMutat Res04007630027-5107EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseQ20Q21Q62JCisplatinIMCancer Chemother Pharmacol. 1989;25(1):62-42556219Metallomics. 2009;1(4):280-9120046924Cancer. 1990 Oct 15;66(8):1697-7022119878Cancer. 1992 Jan 1;69(1):203-71309303J Clin Oncol. 1992 May;10(5):795-8031569451Neurosci Lett. 1995 May 26;191(3):189-927644143Cancer Res. 1995 Dec 15;55(24):6097-1028521399Exp Neurol. 1996 Mar;138(1):93-1048593900Mutat Res. 1996 Apr 2;362(3):237-488637502Annu Rev Biochem. 1996;65:135-678811177J Clin Invest. 1998 Jun 15;101(12):2842-509637718Mol Cell. 2005 Feb 4;17(3):463-7015694346Neurobiol Dis. 2005 Mar;18(2):305-1315686959J Clin Oncol. 1999 Jan;17(1):409-2210458260J Biol Chem. 2006 Feb 17;281(7):3889-9816356936DNA Repair (Amst). 2011 Sep 5;10(9):942-5221741887Curr Mol Pharmacol. 2012 Jan;5(1):3-1322122461Neurotoxicology. 1999 Dec;20(6):883-710693969Biochemistry. 2000 May 30;39(21):6433-910828957Mol Cell Biol. 2001 Apr;21(7):2281-9111259578J Biol Chem. 2003 Feb 28;278(9):7476-8512486030Biochemistry. 2003 Jun 10;42(22):6747-5312779329DNA Repair (Amst). 2005 Mar 2;4(3):367-7915661660Biochemistry. 2011 Jan 11;50(1):82-9221117647Free Radic Biol Med. 2012 Nov 1;53(9):1782-9022841870Redox Biol. 2014;2:485-9424624338Rev Med Suisse. 2014 Apr 30;10(428):954, 956-724834616Mitochondrion. 2014 May;16:38-4924220222PLoS One. 2014;9(9):e10648525188410Exp Neurol. 2003 Jul;182(1):12-2012821373Methods Mol Med. 2004;99:189-20215131338Respir Res. 2004;5:1615450125Cancer. 1984 Oct 1;54(7):1269-756088023Cancer. 1985 May 15;55(10):2303-l63886121Cancer. 1988 Jun 1;61(11):2192-52835140Neurotoxicology. 2006 Dec;27(6):992-100216797073Mutat Res. 2007 Jan 3;614(1-2):24-3616879837Cell Cycle. 2007 Feb 1;6(3):318-2917297309Nucleic Acids Res. 2007;35(6):1812-2117329374J Neurosci. 2007 Aug 29;27(35):9451-717728458J Peripher Nerv Syst. 2008 Mar;13(1):27-4618346229Cancer Res. 2008 Aug 1;68(15):6425-3418676868Mutat Res. 2008 Aug 25;643(1-2):54-6318579163Brain Res. 2008 Sep 16;1230:91-818657527Mol Cancer Ther. 2009 Jan;8(1):10-619139108Eur J Cancer. 2009 Mar;45(4):656-6519091544Mol Pain. 2009;5:919245717Mol Cell Biol. 2009 Apr;29(8):2264-7719188437DNA Repair (Amst). 2009 Nov 2;8(11):1273-8219726241Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Antioxid Redox Signal. 2010 Jun 1;12(11):1247-6919764832J Pharmacol Exp Ther. 2010 Sep 1;334(3):988-9820504914Nat Rev Neurol. 2010 Dec;6(12):657-6621060341Cancer. 1990 Sep 15;66(6):1117-232169332AnimalsCisplatinadverse effectsDNA Damagedrug effectsDNA Repairdrug effectsgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisgeneticsGene Expression Regulationdrug effectsHumansPeripheral Nervous System Diseaseschemically inducedgeneticspathologyPrimary Cell CultureRatsSensory Receptor Cellsdrug effectsmetabolismAPE1Base excision repairCisplatin damageNucleotide excision repairReplication protein ASensory neuronal cultures
20150226201506222015713602015715602015121560ppublish26164266S0027-5107(15)30016-610.1016/j.mrfmmm.2015.06.010PMC4554977NIHMS709203
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1942-099420152015Oxidative medicine and cellular longevityOxid Med Cell LongevOGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells.68319710.1155/2015/683197Hyperglycemia can inhibit expression of the 8-oxoG-DNA glycosylase (OGG1) which is one of the key repair enzymes for DNA oxidative damage. The effect of hyperglycemia on OGG1 expression in response to local anesthetics-induced DNA damage is unknown. This study was designed to determine whether high glucose inhibits OGG1 expression and aggravates bupivacaine-induced DNA damage via reactive oxygen species (ROS). SH-SY5Y cells were cultured with or without 50 mM glucose for 8 days before they were treated with 1.5 mM bupivacaine for 24 h. OGG1 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. ROS was estimated using the redox-sensitive fluorescent dye DCFH-DA. DNA damage was investigated with immunostaining for 8-oxodG and comet assays. OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. Treatment with the antioxidant N-acetyl-L-cysteine (NAC) prevented high glucose and bupivacaine mediated increase in ROS production and restored functional expression of OGG1, which lead to attenuated high glucose-mediated exacerbation of bupivacaine neurotoxicity. Our findings indicate that subjects with diabetes may experience more detrimental effects following bupivacaine use.LiuZhong-JieZJDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.ZhaoWeiWDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.ZhangQing-GuoQGDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.LiLeLDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.LaiLu-YingLYDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.JiangShanSDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.XuShi-YuanSYDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.engJournal ArticleResearch Support, Non-U.S. Gov't20150616
United StatesOxid Med Cell Longev1014798261942-09940Reactive Oxygen Species88847-89-68-oxo-7-hydrodeoxyguanosineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanG9481N71RODeoxyguanosineIY9XDZ35W2GlucoseWYQ7N0BPYCAcetylcysteineY8335394ROBupivacaineIMMutat Res. 2003 Oct 29;531(1-2):5-2314637244J Am Soc Nephrol. 2003 Aug;14(8 Suppl 3):S241-512874439Diabetes. 2005 Jun;54(6):1615-2515919781J Dent Res. 2005 Sep;84(9):852-716109997Free Radic Biol Med. 2006 Mar 1;40(5):754-6216520228Diabetes Metab Res Rev. 2006 Jul-Aug;22(4):257-7316506271Anesth Analg. 2006 Nov;103(5):1294-917056972DNA Repair (Amst). 2006 Nov 8;5(11):1337-4516861056Mech Ageing Dev. 2007 Nov-Dec;128(11-12):637-4918006041Mutat Res. 2008 Feb 1;638(1-2):110-2117961607Nat Protoc. 2008;3(6):1101-818546601Diabetes. 2008 Oct;57(10):2626-3618599524Diabetes. 2009 Jun;58(6):1356-6419252136Pharmacology. 2011;87(3-4):121-921304223Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):1856-6122308447Mol Cells. 2013 Jun;35(6):489-9723677377Oxid Med Cell Longev. 2013;2013:15986424228138PLoS One. 2013;8(11):e7973924260294Ageing Res Rev. 2013 Sep;12(4):918-3024080227Antioxid Redox Signal. 2014 Feb 1;20(4):708-2623901781DNA Repair (Amst). 2014 Jul;19:143-5124767258Mutat Res. 2014 May-Jun;763-764:53-6324732344Reprod Sci. 2015 Jan;22(1):102-1224828139Cancer Biol Ther. 2014 Jul;15(7):906-1024755532Metabolism. 2000 Aug;49(8):1030-510954022Cancer Res. 2001 Jul 15;61(14):5378-8111454679Free Radic Biol Med. 2002 Jun 1;32(11):1102-1512031895Mutat Res. 2004 Sep;567(1):1-6115341901AcetylcysteinepharmacologyBupivacainetoxicityCell Line, TumorCell Proliferationdrug effectsCell Survivaldrug effectsComet AssayDNA Damagedrug effectsDNA GlycosylasesgeneticsmetabolismDeoxyguanosineanalogs & derivativesmetabolismGlucosepharmacologyHumansOxidative Stressdrug effectsReactive Oxygen SpeciesmetabolismReal-Time Polymerase Chain Reaction
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1083-351X290342015Aug21The Journal of biological chemistryJ. Biol. Chem.Reduced Nuclease Activity of Apurinic/Apyrimidinic Endonuclease (APE1) Variants on Nucleosomes: IDENTIFICATION OF ACCESS RESIDUES.21067-7510.1074/jbc.M115.665547Non-coding apurinic/apyrimidinic (AP) sites are generated at high frequency in genomic DNA via spontaneous hydrolytic, damage-induced or enzyme-mediated base release. AP endonuclease 1 (APE1) is the predominant mammalian enzyme responsible for initiating removal of mutagenic and cytotoxic abasic lesions as part of the base excision repair (BER) pathway. We have examined here the ability of wild-type (WT) and a collection of variant/mutant APE1 proteins to cleave at an AP site within a nucleosome core particle. Our studies indicate that, in comparison to the WT protein and other variant/mutant enzymes, the incision activity of the tumor-associated variant R237C and the rare population variant G241R are uniquely hypersensitive to nucleosome complexes in the vicinity of the AP site. This defect appears to stem from an abnormal interaction of R237C and G241R with abasic DNA substrates, but is not simply due to a DNA binding defect, as the site-specific APE1 mutant Y128A, which displays markedly reduced AP-DNA complex stability, did not exhibit a similar hypersensitivity to nucleosome structures. Notably, this incision defect of R237C and G241R was observed on a pre-assembled DNA glycosylase·AP-DNA complex as well. Our results suggest that the BER enzyme, APE1, has acquired distinct surface residues that permit efficient processing of AP sites within the context of protein-DNA complexes independent of classic chromatin remodeling mechanisms. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.HinzJohn MJMFrom the School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-7520 and jmhinz@wsu.edu.MaoPengPFrom the School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-7520 and.McNeillDaniel RDRthe Laboratory of Molecular Gerontology, National Institute on Aging, IRP, National Institutes of Health, Baltimore, Maryland 21224.WilsonDavid MDM3rdthe Laboratory of Molecular Gerontology, National Institute on Aging, IRP, National Institutes of Health, Baltimore, Maryland 21224.engPDB3LZ0R01 ES002614ESNIEHS NIH HHSUnited StatesIntramural NIH HHSUnited StatesR01 ES004106ESNIEHS NIH HHSUnited StatesES004106ESNIEHS NIH HHSUnited StatesES002614ESNIEHS NIH HHSUnited StatesR21 ES020955ESNIEHS NIH HHSUnited StatesR37 ES002614ESNIEHS NIH HHSUnited StatesES020955ESNIEHS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, N.I.H., Intramural20150701
United StatesJ Biol Chem2985121R0021-92580Isoenzymes0Nucleosomes0Recombinant Proteins9007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMNature. 1997 Sep 18;389(6648):251-609305837J Mol Biol. 2007 Aug 17;371(3):649-6817586522DNA Repair (Amst). 2007 Apr 1;6(4):454-6017123872Mol Cell Biol. 2007 Dec;27(24):8442-5317923696J Mol Biol. 2015 Jan 30;427(2):298-31125498387J Cell Physiol. 2013 Feb;228(2):258-6622718094J Biol Chem. 2013 May 10;288(19):13863-7523543741Cancer Res. 2001 Jul 15;61(14):5552-711454706Nat Struct Biol. 2000 Mar;7(3):176-810700268Cell Mol Life Sci. 2012 Mar;69(5):727-4021952828Mutat Res. 2014 Aug;766-767:19-2425083139Biochemistry. 2008 Nov 4;47(44):11434-4518839966Mutat Res. 2010 Mar 1;685(1-2):11-2019909758Nucleic Acids Res. 1998 Jun 1;26(11):2771-89592167EMBO J. 1998 Sep 1;17(17):5214-269724657Nature. 2000 Jan 27;403(6768):451-610667800PLoS One. 2013;8(6):e6592223776569PLoS One. 2014;9(3):e9083724595156J Biol Chem. 2010 Jan 22;285(4):2876-8519933279J Mol Biol. 1998 Feb 13;276(1):19-429514715Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463Annu Rev Genet. 1986;20:201-303545059EMBO J. 2002 Nov 1;21(21):5943-5212411511Mol Cell. 2005 Feb 4;17(3):463-7015694346Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4646-5120176960Biochim Biophys Acta. 2013 Jan;1834(1):247-7123076011Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7465-7012799467Nature. 1993 Apr 22;362(6422):709-158469282Biochemistry. 2010 Sep 14;49(36):7879-9120701268Mol Cell Biol. 1995 Aug;15(8):4375-847623832Biochemistry. 1998 Jan 13;37(2):580-99425080Carcinogenesis. 2014 Dec;35(12):2643-5225355293J Mol Biol. 2000 May 5;298(3):447-5910772862Nucleic Acids Res. 2012 Jan;40(2):692-70021930508Nucleic Acids Res. 1980 Aug 25;8(16):3517-347433098Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Biochemistry. 1999 Dec 14;38(50):16553-6010600117J Mol Biol. 2010 Oct 15;403(1):1-1020800598Mutat Res. 2000 Aug 30;460(3-4):183-9910946228Mol Cell Biol. 2011 Nov;31(22):4623-3221930793Nucleic Acids Res. 1993 Dec 11;21(24):5561-98284199Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Genes Dev. 1993 Dec;7(12A):2471-828253391DNAchemistrygeneticsmetabolismDNA DamageDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasechemistrygeneticsmetabolismEscherichia coligeneticsmetabolismGene ExpressionHumansIsoenzymeschemistrygeneticsmetabolismModels, MolecularMutationNucleosomeschemistryenzymologygeneticsProtein Interaction Domains and MotifsRecombinant ProteinschemistrygeneticsmetabolismAP endonuclease 1DNA damagebase excision repair (BER)genetic polymorphismnucleosomeprotein-DNA interaction
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1949-25536272015Sep15OncotargetOncotargetExtracellularly secreted APE1/Ref-1 triggers apoptosis in triple-negative breast cancer cells via RAGE binding, which is mediated through acetylation.23383-98The present study evaluated the mechanism of apoptosis caused by post-translational modification, hyperacetylation in triple-negative breast cancer (TNBC) cells. We previously showed that trichostatin A (TSA) induced secretion of acetylated apurinic apyrimidinic endonuclease 1/redox factor-1 (Ac-APE1/Ref-1). This is the first report showing that Ac-APE1/Ref-1 initiates apoptosis in TNBC cells by binding to the receptor for advanced glycation end products (RAGE). The functional significance of secreted Ac-APE1/Ref-1 was studied by induction of intracellular hyperacetylation through co-treatment with acetylsalicylic acid and TSA in MDA-MB-231 cells. In response to hyperacetylation, secretion of Ac-APE1/Ref-1 in vesicles was observed, resulting in significantly decreased cell viability and induction of apoptosis with increased expression of RAGE. The hyperacetylation-induced apoptosis was similar in two other TNBC cell lines: BT-459 and MDA-MB-468. Therefore, hyperacetylation may be a therapeutic target for treatment of TNBCs. This study introduces a novel paradigm whereby post-translational modification induces apoptotic cell death in breast cancer cells resistant to standard chemotherapeutic agents through secretion of auto- or paracrine molecules such as Ac-APE1/Ref-1. LeeYu RanYRResearch Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301747, Korea.KimKi MoKMCancer Research Team, Korean Medicine Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, (KIOM), Daejeon, 305811, Korea.JeonByeong HwaBHResearch Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301747, Korea.ChoiSungaSResearch Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301747, Korea.engJournal ArticleResearch Support, Non-U.S. Gov't
United StatesOncotarget1015329651949-25530Antigens, Neoplasm0Hydroxamic Acids0Receptor for Advanced Glycation End Products3X2S926L3Ztrichostatin AEC 2.7.11.24p38 Mitogen-Activated Protein KinasesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseR16CO5Y76EAspirinIMEMBO J. 2003 Oct 15;22(20):5551-6014532127Curr Pharm Des. 2014;20(7):1161-924552186Cell Death Dis. 2013;4:e51923449455Nat Methods. 2006 Dec;3(12):995-100017072308Annu Rev Biochem. 2006;75:93-10916756486FEBS Lett. 2007 Jul 31;581(19):3689-9417499247Anticancer Res. 2011 Jun;31(6):2017-2221737617EMBO Rep. 2009 Jul;10(7):783-919483673Biochem Biophys Res Commun. 2013 Jun 14;435(4):621-623685156Int J Inflam. 2013;2013:40346024102034Clin Cancer Res. 2008 Dec 15;14(24):8010-819088017Eur J Immunol. 2004 Jun;34(6):1503-1215162419J Neurochem. 2006 Apr;97(1):151-6116515552PLoS One. 2012;7(7):e4194522860037Mol Med Rep. 2009 Jul-Aug;2(4):533-721475861Toxicol Appl Pharmacol. 2011 Dec 1;257(2):165-7321933677Biochem Biophys Res Commun. 2013 Jun 7;435(3):403-723665318Toxicol Appl Pharmacol. 2013 Dec 15;273(3):659-7124161344Cancer Treat Rev. 2010 Nov;36 Suppl 3:S80-621129616Expert Rev Anticancer Ther. 2010 Jun;10(6):935-5420553216J Immunol. 2011 Mar 15;186(6):3517-2621300822J Clin Oncol. 2006 Dec 1;24(34):5381-717135639N Engl J Med. 1998 Nov 26;339(22):1609-189828250Am J Epidemiol. 2000 Apr 1;151(7):703-1410752798Br J Cancer. 2001 May 4;84(9):1188-9211336469EMBO Rep. 2002 Oct;3(10):995-100112231511Am J Clin Oncol. 2010 Dec;33(6):637-4520023571Mol Cancer Ther. 2001 Dec;1(2):85-9412467226Nucleic Acids Res. 2014 Mar;42(5):3089-10324335147Eur J Biochem. 2003 May;270(10):2109-1912752430N Engl J Med. 2005 Dec 29;353(26):2747-5716382061Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):768-7215824141Mol Cancer Ther. 2004 Oct;3(10):1215-2015486188Clin Ther. 2008 Aug;30(8):1426-4718803986Breast Cancer Res Treat. 2007 Jun;103(2):149-6017039263FASEB J. 2001 May;15(7):1273-511344111Carcinogenesis. 2001 Sep;22(9):1393-711532860Curr Mol Med. 2007 Dec;7(8):777-8918331236Breast Dis. 2005-2006;24:3-1516917136N Engl J Med. 2003 Jun 12;348(24):2431-4212802030PLoS One. 2014;9(3):e9161024626188Immunol Cell Biol. 2012 Jan;90(1):85-9422124371Neurotox Res. 2011 Aug;20(2):159-6921116767Eur J Cancer Clin Oncol. 1988 Jan;24(1):29-433276531Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4429-3417671126Breast Cancer Res. 2006;8(4):R3916846528Lancet. 1995 Sep 30;346(8979):883-77564675Indian J Exp Biol. 2003 Nov;41(11):1273-815332496AcetylationAntigens, NeoplasmgeneticsmetabolismApoptosisAspirinchemistryBreast NeoplasmsgeneticsmetabolismCell Line, TumorCell MembranemetabolismCell SurvivalDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismFemaleGene Expression Regulation, NeoplasticHumansHydroxamic AcidschemistryMCF-7 CellsMicroscopy, Electron, TransmissionPhosphorylationProtein Processing, Post-TranslationalReceptor for Advanced Glycation End ProductsgeneticsmetabolismTriple Negative Breast Neoplasmsgeneticsmetabolismp38 Mitogen-Activated Protein KinasesmetabolismAPE1/Ref-1RAGEacetylationapoptosistriple-negative breast cancer
20150414201506122015716020157160201681660ppublish26125438434510.18632/oncotarget.4345PMC4695125
261196622016032420150629
1880-57799012015Genes & genetic systemsGenes Genet. Syst.Drosophila Ogg1 is required to suppress 8-oxo-guanine accumulation following oxidative stress.11-2010.1266/ggs.90.11Reactive oxygen species (ROS) generated during energy production processes are a major cause of oxidative DNA damage. A DNA glycosylase encoded by the Ogg1 gene removes oxidized guanine bases and is widely conserved. However, the biological role of the gene in individual organisms has not yet been characterized in Drosophila, which is a suitable model to study the influence of oxidative damage on senescence. Here, we performed a genetic analysis to confirm that Ogg1 plays an essential role in the removal of 8-oxo-guanines from nuclei. We first confirmed by quantitative real-time PCR that Ogg1 mRNA expression was reduced by 30-55% in Ogg1 mutants and in flies expressing inducible Ogg1 dsRNA compared to control flies. We then showed that additional accumulation of 8-oxo-guanines occurred in the nuclei of epithelial midgut cells after paraquat feeding in flies with downregulated Ogg1 expression. We confirmed that a transposon possessing the UAS sequence was integrated in the 5'-UTR of the Ogg1 alleles and that it is oriented in the same transcriptional direction as the gene. Using the Gal4/UAS system, which enables us to induce ectopic expression in Drosophila, we induced overexpression of Ogg1 by 40-fold. We observed a lower amount of 8-oxo-guanine in the midgut epithelial cells of adults overexpressing Ogg1. These genetic data strongly suggest that the Drosophila Ogg1 ortholog CG1795 plays an essential role in the suppression of 8-oxo-guanines, consistent with its role in other organisms. Although adult flies with reduced Ogg1 expression failed to show elevated sensitivity to paraquat, those with Ogg1 overexpression showed resistance to oxidative stress by paraquat feeding and had a significantly longer lifespan in normal feeding conditions. These observations are consistent with the hypothesis that oxidative DNA damage by ROS accumulation is a major contributor to senescence. YasukawaTakashiTInsect Biomedical Research Center, Kyoto Institute of Technology.NakaharaYasuyukiYHiraiJunJInoueYoshihiro HYHengJournal ArticleResearch Support, Non-U.S. Gov't
JapanGenes Genet Syst96078221341-75680DNA Transposable Elements0Drosophila Proteins0GAL4 protein, Drosophila0RNA, Messenger0Reactive Oxygen Species0Transcription Factors5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, DrosophilaPLG39H7695ParaquatIMAnimalsDNA GlycosylasesgeneticsmetabolismDNA Transposable ElementsDrosophiladrug effectsgeneticsmetabolismDrosophila ProteinsgeneticsmetabolismDrug ResistancegeneticsGene Expression Regulationdrug effectsGuaninemetabolismMutationOxidative StressParaquatpharmacologyRNA, MessengergeneticsmetabolismReactive Oxygen SpeciesTranscription Factorsmetabolism
201563060201563060201632560ppublish2611966210.1266/ggs.90.11
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1177-888192015Drug design, development and therapyDrug Des Devel TherSmall-molecule BH3 mimetic and pan-Bcl-2 inhibitor AT-101 enhances the antitumor efficacy of cisplatin through inhibition of APE1 repair and redox activity in non-small-cell lung cancer.2887-91010.2147/DDDT.S82724AT-101 is a BH3 mimetic and pan-Bcl-2 inhibitor that has shown potent anticancer activity in non-small-cell lung cancer (NSCLC) in murine models, but failed to show clinical efficacy when used in combination with docetaxel in NSCLC patients. Our recent study has demonstrated that AT-101 enhanced the antitumor effect of cisplatin (CDDP) in a murine model of NSCLC via inhibition of the interleukin-6/signal transducer and activator of transcription 3 (STAT3) pathway. This study explored the underlying mechanisms for the enhanced anticancer activity of CDDP by AT-101. Our results show that, when compared with monotherapy, AT-101 significantly enhanced the inhibitory effects of CDDP on proliferation and migration of A549 cells and on tube formation and migration in human umbilical vein endothelial cells. AT-101 promoted the proapoptotic activity of CDDP in A549 cells. AT-101 also enhanced the inhibitory effect of CDDP on DNA repair and redox activities of apurinic/apyrimidinic endonuclease 1 (APE1) in A549 cells. In tumor tissues from nude mice treated with AT-101 plus CDDP or monotherapy, the combination therapy resulted in greater inhibition of angiogenesis and tumor cell proliferation than the monotherapy. These results suggest that AT-101 can enhance the antitumor activity of CDDP in NSCLC via inhibition of APE1 DNA repair and redox activities and by angiogenesis and induction of apoptosis, but other mechanisms cannot be excluded. We are now conducting a Phase II trial to examine the clinical efficacy and safety profile of combined use of AT-101 plus CDDP in advanced NSCLC patients. RenTaoTCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China ; Department of Oncology, The Affiliated Hospital, North Sichuan Medical College, Sichuan, People's Republic of China ; Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.ShanJinluJCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.LiMengxiaMCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.QingYiYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.QianChengyuanCDepartment of Oncology, The 97 Hospital of PLA, Jiangsu, People's Republic of China.WangGuangjieGCancer Diagnosis and Treatment Center, Military District General Hospital of Chengdu Military Region, Sichuan, People's Republic of China.LiQingQCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China ; Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.LuGuoshouGCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.LiChongyiCCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.PengYuYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.LuoHaoHCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.ZhangShihengSCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.YangYuxingYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.ChengYiYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.WangDongDCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.ZhouShu-FengSFDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.engComparative StudyJournal Article20150608
New ZealandDrug Des Devel Ther1014757451177-8881EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseKAV15B369OGossypolQ20Q21Q62JCisplatinS7RL72610Rgossypol acetic acidIMBreast Cancer Res Treat. 2001 Apr;66(3):239-4811510695Curr Mol Pharmacol. 2012 Jan;5(1):14-3522122462J Med Chem. 2003 Sep 25;46(20):4259-6413678404Lancet. 2015 Mar 14;385(9972):977-101025467588Leuk Lymphoma. 2013 Oct;54(10):2263-823398207Nat Rev Cancer. 2007 Aug;7(8):573-8417625587Cancer Treat Rev. 2010 Aug;36(5):425-3520056333Mutat Res. 2003 Oct 29;531(1-2):157-6314637252Br J Cancer. 2010 Feb 16;102(4):704-920087352Int J Androl. 1998 Feb;21(1):8-129639146Ann Oncol. 2012 Jul;23(7):1803-822112969Semin Oncol. 2014 Apr;41(2):235-5124787295Biochim Biophys Acta. 2014 Aug;1846(1):161-7924836679Clin Cancer Res. 2009 May 1;15(9):3172-619366825Cancer Lett. 2008 Jun 18;264(2):192-20018314260Cancer Res. 2012 Feb 1;72(3):716-2522158856Drug Des Devel Ther. 2014;8:2517-2925548514Cell. 2007 Aug 24;130(4):691-70317719546Angiogenesis. 2014 Jul;17(3):471-9424482243N Engl J Med. 2008 Sep 25;359(13):1367-8018815398Cancer Treat Rev. 2014 May;40(4):548-5724360358Life Sci. 2014 Apr 25;102(1):41-824625733Immunopharmacol Immunotoxicol. 2013 Oct;35(5):615-2123981004PLoS One. 2014;9(5):e9673324824755Semin Cancer Biol. 2003 Apr;13(2):159-6712654259Cancer Res. 2001 Mar 1;61(5):2183-811280784Lancet. 2013 Aug 24;382(9893):709-1923972814Free Radic Biol Med. 2008 Sep 1;45(5):592-60118515104PLoS One. 2014;9(6):e9952824914806Cancer Sci. 2007 Dec;98(12):1993-200117892509J Thorac Oncol. 2010 Oct;5(10):1637-4320808253Am J Pathol. 1999 Feb;154(2):375-8410027396Cancers (Basel). 2014 Sep 05;6(3):1769-9225198391Anticancer Res. 2014 Jan;34(1):493-50124403507Mol Cancer Ther. 2005 Jan;4(1):13-2115657349J Thorac Oncol. 2011 Oct;6(10):1757-6021918390Lung Cancer. 2009 Dec;66(3):298-30419324449Mol Cancer Res. 2010 Jul;8(7):1002-1620587533Nat Rev Clin Oncol. 2014 Jul;11(7):413-3124913374Eur J Pharmacol. 2014 Oct 5;740:364-7825058905Cancer Res. 2005 Jun 15;65(12):5063-915958549Nat Rev Cancer. 2005 Mar;5(3):231-715738985Int J Cancer. 2007 Oct 15;121(8):1670-917597109Cell Death Dis. 2014;5:e125724874729Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17844-924127576Invest New Drugs. 2014 Apr;32(2):295-30223860642FASEB J. 2006 Oct;20(12):2147-916935937Lancet. 2011 Nov 12;378(9804):1727-4021565398Cell. 2010 Jan 22;140(2):268-7920141840Oncol Lett. 2014 Apr;7(4):1078-108224944672Mol Cancer Ther. 2005 Jul;4(7):1096-10416020667Nat Rev Cancer. 2013 Oct;13(10):714-2624060863Mol Cancer Ther. 2005 Jan;4(1):23-3115657350Chin J Cancer. 2014 Aug;33(8):402-525011459Drug Des Devel Ther. 2014;8:485-9624872679Autophagy. 2010 Nov;6(8):1201-320930561CA Cancer J Clin. 2015 Mar;65(2):87-10825651787Mol Cancer Ther. 2013 Sep;12(9):1691-70023974697PLoS One. 2012;7(12):e5078623226540Redox Biol. 2014;2:485-9424624338Cell. 2012 Mar 16;148(6):1145-5922424226PLoS One. 2013;8(2):e5531323418439Cancer Invest. 2013 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May;10(5):795-80521372225Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463Clin Cancer Res. 2009 Feb 15;15(4):1126-3219228717J Thorac Oncol. 2011 Apr;6(4):781-521289522Cancer Discov. 2014 Jan;4(1):31-4124356098Clin Exp Metastasis. 2012 Feb;29(2):165-7822167622Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128PLoS One. 2012;7(10):e4746223094050Cell. 2002 Jan 25;108(2):153-6411832206Free Radic Biol Med. 2012 Jul 15;53(2):237-4822580151AnimalsAntineoplastic Combined Chemotherapy Protocolsadministration & dosagepharmacologyApoptosisdrug effectsCarcinoma, Non-Small-Cell Lungdrug therapypathologyCell Line, TumorCell Proliferationdrug effectsCisplatinadministration & dosagepharmacologyDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismGossypoladministration & dosageanalogs & derivativespharmacologyHuman Umbilical Vein Endothelial CellsHumansLung Neoplasmsdrug therapypathologyMiceMice, Inbred BALB CMice, NudeNeovascularization, Pathologicdrug therapyOxidation-Reductiondrug effectsXenograft Model Antitumor AssaysAT-101angiogenesisapurinic/apyrimidinic endonuclease 1cisplatinnon-small-cell lung cancertumor
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1875-863020152015Disease markersDis. MarkersOGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data.69087810.1155/2015/690878In first part of this study association between OGG1 polymorphisms and breast cancer susceptibility was explored by meta-analysis. Second part of the study involved 925 subjects, used for mutational analysis of OGG1 gene using PCR-SSCP and sequencing. Fifteen mutations were observed, which included five intronic mutations, four splice site mutations, two 3'UTR mutations, three missense mutations, and a nonsense mutation. Significantly (p < 0.001) increased (~29 fold) breast cancer risk was associated with a splice site variant g.9800972T>G and 3'UTR variant g.9798848G>A. Among intronic mutations, highest (~15 fold) increase in breast cancer risk was associated with g.9793680G>A (p < 0.009). Similarly ~14-fold increased risk was associated with Val159Gly (p < 0.01), ~17-fold with Gly221Arg (p < 0.005), and ~18-fold with Ser326Cys (p < 0.004) in breast cancer patients compared with controls, whereas analysis of nonsense mutation showed that ~13-fold (p < 0.01) increased breast cancer risk was associated with Trp375STOP in patients compared to controls. In conclusion, a significant association was observed between OGG1 germ line mutations and breast cancer risk. These findings provide evidence that OGG1 may prove to be a good candidate of better diagnosis, treatment, and prevention of breast cancer. AliKashifKCancer Genetics Laboratory, Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000, Pakistan.MahjabeenIshratICancer Genetics Laboratory, Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000, Pakistan.SabirMaimoonaMCancer Genetics Laboratory, Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000, Pakistan.MehmoodHumeraHNuclear Medicine Oncology & Radiotherapy Institute (NORI), Islamabad 44000, Pakistan.KayaniMahmood AkhtarMACancer Genetics Laboratory, Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000, Pakistan.engJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov't20150519
United StatesDis Markers86041270278-0240EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMMed Oncol. 2012 Dec;29(4):2949-5422271435Int J Cancer. 2013 Jan 1;132(1):55-6222684821Dis Markers. 2013;34(2):71-8023324580Gene. 2013 May 1;519(2):231-723454624Mutat Res. 2013 May-Jun;745-746:6-1523618615PLoS One. 2013;8(8):e7115723951099Mol Biol Rep. 2013 Sep;40(9):5261-7323673479Tumour Biol. 2013 Oct;34(5):2843-823700156Mutat Res. 2011 May 10;709-710:67-7221414327DNA Cell Biol. 2011 May;30(5):317-2121166493Breast Cancer Res Treat. 2011 Jun;127(3):795-80321153698Cancer Sci. 2011 Jun;102(6):1123-721401806Curr Med Res Opin. 2011 Jul;27(7):1295-30221561390Arch Med Res. 2011 Apr;42(3):226-3421722819Indian J Med Res. 2011 Jun;133:605-1221727658Mol Carcinog. 2011 Sep;50(9):732-721520294Asian Pac J Cancer Prev. 2011;12(4):1067-7221790253Pol J Pathol. 2011;62(2):89-9421866464Int J Cancer. 2001 May 20;95(3):140-311307145Biochemistry. 2003 Feb 18;42(6):1564-7212578369Cancer Res. 2003 Jul 15;63(14):4287-9212874039Carcinogenesis. 2004 Sep;25(9):1689-9415073047Nucleic Acids Res. 2004;32(18):5596-60815494448Cell. 1996 Jul 26;86(2):321-98706136Cancer Sci. 2004 Dec;95(12):977-8315596047Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):353-816492928Int J Cancer. 2007 Aug 1;121(3):501-517417784Mutat Res. 2007 Jul 28;631(2):101-1017531525J Epidemiol. 2007 Sep;17(5):156-6017827862Jpn J Clin Oncol. 2008 Mar;38(3):186-9118272472Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008 Apr;25(2):211-318393249Cancer Biol Ther. 2008 Jan;7(1):23-717932460Neoplasma. 2008;55(4):330-718505345Breast Cancer Res Treat. 2008 Sep;111(2):279-8817922186Arh Hig Rada Toksikol. 2008 Dec;59(4):241-5019064361J Natl Cancer Inst. 2009 Jan 7;101(1):24-3619116388Carcinogenesis. 2009 Jan;30(1):78-8719029194Pol J Pathol. 2008;59(4):201-419391486Ann Surg Oncol. 2009 Jun;16(6):1695-70319266243Anticancer Res. 2009 Apr;29(4):1389-9319414392Tohoku J Exp Med. 2009 Jul;218(3):185-9119561388Tohoku J Exp Med. 2009 Dec;219(4):269-7519966524Ann Surg Oncol. 2010 Mar;17(3):760-7120183911Mutat Res. 2009 Nov-Dec;680(1-2):56-6319815090Nat Methods. 2010 Apr;7(4):248-920354512Urology. 2010 Apr;75(4):779-8519914697J Coll Physicians Surg Pak. 2010 Mar;20(3):181-520392381J Gastrointest Cancer. 2010 Jun;41(2):110-520069464Anticancer Res. 2010 Apr;30(4):1359-6420530453Gene. 2013 Dec 15;532(2):192-624076439Asian Pac J Cancer Prev. 2013;14(9):5145-5124175791Asian Pac J Cancer Prev. 2014;15(3):1133-4024606430Tumour Biol. 2014 Mar;35(3):2397-40224186001Biomarkers. 2014 Sep;19(6):509-1625089939Mol Biol Rep. 2011 Feb;38(2):1251-6120571908Cancer. 2010 Jul 1;116(13):3160-920564624Mol Vis. 2010;16:991-620577654Asian Pac J Cancer Prev. 2010;11(1):165-820593951Nat Methods. 2010 Aug;7(8):575-620676075Genet Test Mol Biomarkers. 2010 Aug;14(4):559-6420649433World J Gastroenterol. 2010 Sep 21;16(35):4476-8220845517Anticancer Res. 2010 Oct;30(10):4141-521036733Mol Biol Rep. 2011 Jan;38(1):445-5120364408Mol Biol Rep. 2011 Nov;38(8):5379-8621390502Mutat Res. 2011 Dec 24;726(2):227-3321986195Urol Oncol. 2011 Nov-Dec;29(6):641-619914098Mol Biol Rep. 2012 Jan;39(1):527-3421559836Anticancer Res. 2011 Nov;31(11):3939-4422110223Ann Oncol. 2012 Feb;23(2):401-521515665Asian Pac J Cancer Prev. 2011;12(10):2779-8322320992Indian J Med Res. 2012;135:64-7122382185Cancer Epidemiol. 2012 Apr;36(2):183-921974800DNA Cell Biol. 2012 Apr;31(4):541-621899442PLoS One. 2012;7(4):e3597022540013Mech Ageing Dev. 2012 Apr;133(4):127-3222019847Clin Chim Acta. 2012 Oct 9;413(19-20):1519-2422687647J Cancer Res Clin Oncol. 2012 Sep;138(9):1443-822526153Asian Pac J Cancer Prev. 2012;13(5):1803-822901126Dig Dis Sci. 2012 Sep;57(9):2451-722565339Oncol Rep. 2012 Nov;28(5):1859-6822922830Pathol Oncol Res. 2012 Oct;18(4):1015-2022544315AdultBreast NeoplasmsgeneticsDNA GlycosylasesgeneticsDNA Mutational AnalysismethodsFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGerm-Line MutationHumansMiddle AgedPakistan
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1791-24234722015AugInternational journal of oncologyInt. J. Oncol.Ape1 regulates WNT/β-catenin signaling through its redox functional domain in pancreatic cancer cells.610-2010.3892/ijo.2015.3048Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1, Ape1) is a multifunctional protein that is upregulated in human pancreatic cancer. Ape1 redox domain plays an essential role in regulating the effects of reactive oxygen species (ROS) generated during physiological metabolism and pathological stress. In the present study, we explored whether Ape1 and ROS affect WNT/β-catenin signaling. We used E3330, a small molecule inhibitor of the redox activity of Ape1, and a siRNA approach to knock down Ape1, in two human pancreatic cancer cell lines. Inhibition of Ape1 resulted in growth suppression of pancreatic cancer cells, increased ROS levels, upregulation of β-catenin and c-myc and downregulation of cyclin D1. Consistent with these data, overexpression of Ape1 in pancreatic cancer cells reduced ROS and c-myc levels and increased cyclin D1 levels. Moreover, treatment of pancreatic cancer cells with H2O2 to induce oxidative stress resulted in upregulated ROS levels, decreased Ape1 at both the mRNA and protein level, and alterations in WNT/β-catenin pathway components. Finally, treatment of pancreatic cancer cells with the WNT/β-catenin inhibitor IWR-1 resulted in growth inhibition, which was greatly enhanced when combined with E3330 treatment. In summary, our results demonstrate that ROS is an important intracellular messenger that can modulate WNT/β‑catenin signaling. The present study provides interesting new insight into crosstalk between the redox function of Ape1 and WNT/β-catenin signaling in cancer cells. Furthermore, our data show that the combination of Ape1 and WNT inhibitors enhanced the inhibition of pancreatic cell proliferation. These results provide a promising novel therapeutic strategy for treating pancreatic cancer in future.JiangShaojieSDepartment of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.ZhuLinaLDepartment of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.TangHaimeiHBiomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.ZhangMiaofengMDepartment of Orthopaedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.ChenZhihuaZXin Hua Hospital, Shanghai Key Laboratory for Pediatrics Gastroenterology and Nutrition, Shanghai Institute for Pediatrics Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.FeiJianJDepartment of Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.HanBaosanBDepartment of Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.ZouGang-MingGMXin Hua Hospital, Shanghai Key Laboratory for Pediatrics Gastroenterology and Nutrition, Shanghai Institute for Pediatrics Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.engJournal ArticleResearch Support, Non-U.S. Gov't20150612
GreeceInt J Oncol93060421019-64390Benzoquinones0IWR-1 compound0Imides0Propionates0Quinolines0Reactive Oxygen Species136164-66-4E 3330BBX060AN9VHydrogen PeroxideEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBenzoquinonespharmacologyCell Line, TumorCell Proliferationdrug effectsDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsgeneticsmetabolismGene Expression Regulation, Neoplasticdrug effectsGene Knockdown TechniquesHumansHydrogen PeroxidepharmacologyImidespharmacologyPancreatic Neoplasmsdrug therapygeneticsmetabolismPropionatespharmacologyQuinolinespharmacologyReactive Oxygen SpeciesmetabolismWnt Signaling Pathwaydrug effects
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1471-2199162015Jun11BMC molecular biologyBMC Mol. Biol.SIRT6 protein deacetylase interacts with MYH DNA glycosylase, APE1 endonuclease, and Rad9-Rad1-Hus1 checkpoint clamp.1210.1186/s12867-015-0041-9SIRT6, a member of the NAD(+)-dependent histone/protein deacetylase family, regulates genomic stability, metabolism, and lifespan. MYH glycosylase and APE1 are two base excision repair (BER) enzymes involved in mutation avoidance from oxidative DNA damage. Rad9-Rad1-Hus1 (9-1-1) checkpoint clamp promotes cell cycle checkpoint signaling and DNA repair. BER is coordinated with the checkpoint machinery and requires chromatin remodeling for efficient repair. SIRT6 is involved in DNA double-strand break repair and has been implicated in BER. Here we investigate the direct physical and functional interactions between SIRT6 and BER enzymes.We show that SIRT6 interacts with and stimulates MYH glycosylase and APE1. In addition, SIRT6 interacts with the 9-1-1 checkpoint clamp. These interactions are enhanced following oxidative stress. The interdomain connector of MYH is important for interactions with SIRT6, APE1, and 9-1-1. Mutagenesis studies indicate that SIRT6, APE1, and Hus1 bind overlapping but different sequence motifs on MYH. However, there is no competition of APE1, Hus1, or SIRT6 binding to MYH. Rather, one MYH partner enhances the association of the other two partners to MYH. Moreover, APE1 and Hus1 act together to stabilize the MYH/SIRT6 complex. Within human cells, MYH and SIRT6 are efficiently recruited to confined oxidative DNA damage sites within transcriptionally active chromatin, but not within repressive chromatin. In addition, Myh foci induced by oxidative stress and Sirt6 depletion are frequently localized on mouse telomeres.Although SIRT6, APE1, and 9-1-1 bind to the interdomain connector of MYH, they do not compete for MYH association. Our findings indicate that SIRT6 forms a complex with MYH, APE1, and 9-1-1 to maintain genomic and telomeric integrity in mammalian cells.HwangBor-JangBJDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD, 21201, USA. BHwang@som.umaryland.edu.JinJinJDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD, 21201, USA. jinjin1681@yahoo.com.GaoYingYUniversity of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA. yig10@pitt.edu.School of Medicine, Tsinghua University, No.1 Tsinghua Yuan, Haidian District, Beijing, 100084, China. yig10@pitt.edu.ShiGuoliGDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD, 21201, USA. gshi001@son.umaryland.edu.University of Maryland School of Nursing, 655 West Lombard Street, Baltimore, MD, 21201, USA. gshi001@son.umaryland.edu.MadabushiAmritaADepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD, 21201, USA. amadabushi@bccc.edu.Department of Natural and Physical Sciences, Life Sciences Institute, Baltimore City Community College, 801 West Baltimore Street, Baltimore, MD, 21201, USA. amadabushi@bccc.edu.YanAustinADepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD, 21201, USA. ay.savethetigers@gmail.com.GuanXinXDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD, 21201, USA. xin0709@yahoo.com.ZalzmanMichalMDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD, 21201, USA. MZalzman@som.umaryland.edu.Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, 16 South Eutaw Street, Baltimore, MD, 21201, USA. MZalzman@som.umaryland.edu.NakajimaSatoshiSUniversity of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA. san48@pitt.edu.Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA. san48@pitt.edu.LanLiLUniversity of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA. lilyrisa2@gmail.com.Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA. lilyrisa2@gmail.com.LuA-LienALDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD, 21201, USA. alu-chang@som.umaryland.edu.Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD, 21201, USA. alu-chang@som.umaryland.edu.engS10 OD011969ODNIH HHSUnited StatesS10-OD011969ODNIH HHSUnited StatesR01 CA078391CANCI NIH HHSUnited StatesR21-AG045545AGNIA NIH HHSUnited StatesR01-CA78391CANCI NIH HHSUnited StatesR21 AG045545AGNIA NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20150611
EnglandBMC Mol Biol1009669831471-21990Cell Cycle Proteins0Chromatin139691-42-2rad9 protein9007-49-2DNAEC 2.4.2.31Sirt6 protein, mouseEC 3.1.-ExonucleasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.5.1.-SIRT6 protein, humanEC 3.5.1.-SirtuinsEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMNature. 2007 Jun 21;447(7147):941-5017581577Cell Cycle. 2009 Aug 15;8(16):2664-619625767Science. 2011 Jun 17;332(6036):1443-621680843Cell. 2006 Jan 27;124(2):315-2916439206Cancer Treat Rev. 2010 Aug;36(5):425-3520056333Biochemistry. 2009 Jun 30;48(25):6022-3319449863Annu Rev Biochem. 1994;63:915-487979257Nat Genet. 2002 Feb;30(2):227-3211818965Nature. 2008 Mar 27;452(7186):492-618337721J Biol Chem. 2003 Oct 3;278(40):38121-412917422Front Biosci. 2006;11:3062-8016720376Nat Struct Biol. 2000 Mar;7(3):176-810700268Nucleic Acids Res. 2001 Jun 15;29(12):2666-7411410677Biochem J. 2006 Nov 15;400(1):53-6216879101Science. 2010 Sep 10;329(5997):1348-5320829486DNA Repair (Amst). 2005 Dec 8;4(12):1442-916199212DNA Repair (Amst). 2007 Mar 1;6(3):317-2817126083PLoS One. 2012;7(12):e5155523240041Nat Commun. 2014;5:501125247314J Biol Chem. 2005 Jun 3;280(22):21313-2015795229Nucleic Acids Res. 2007;35(8):2596-60817426133Trends Biochem Sci. 2002 Jul;27(7):339-4412114022Mutat Res. 1993 May;299(3-4):277-877683095Nat Genet. 2007 Feb;39(2):243-5017237781Mol Cell. 2013 Aug 22;51(4):454-6823911928Nucleic Acids Res. 2013 Apr;41(7):4093-10323460202J Mol Biol. 2011 Jan 21;405(3):653-6521110984J Mol Biol. 2005 Mar 11;346(5):1259-7415713479Cancer Res. 2006 Jan 1;66(1):113-2416397223Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17844-924127576DNA Repair (Amst). 2005 Mar 2;4(3):315-2515661655J Biol Chem. 2008 Nov 21;283(47):32680-9018805789Trends Biochem Sci. 2014 Feb;39(2):72-8124438746Annu Rev Biochem. 2004;73:39-8515189136PLoS Genet. 2010 May;6(5):e100095120485567Front Genet. 2013 Feb 28;4:1823450852Cell Cycle. 2015;14(2):269-7625607651Nucleic Acids Res. 1997 Jun 15;25(12):2495-5009171104Aging (Albany NY). 2009 Jan;1(1):109-2120157594Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12754-79398071Biochem J. 2013 Nov 15;456(1):89-9823952905Nucleic Acids Res. 2014 Feb;42(4):2330-4524293652FEBS Lett. 2000 Jun 30;476(1-2):73-710878254J Biol Chem. 2001 Feb 23;276(8):5547-5511092888Nucleic Acids Res. 2001 Feb 1;29(3):743-5211160897DNA Repair (Amst). 2011 Jan 2;10(1):34-4420951653J Mol Biol. 2010 Oct 29;403(3):351-7020816984DNA Repair (Amst). 2013 Dec;12(12):1043-5224209961Mol Cell Biol. 1995 Feb;15(2):989-967823963Curr Biol. 2006 Aug 8;16(15):1551-816890531Nature. 2013 Apr 4;496(7443):110-323552949FEBS Lett. 1999 Jun 25;453(3):365-810405177DNA Repair (Amst). 2014 Jan;13:10-2124315136Amino Acid MotifsAnimalsCell Cycle CheckpointsCell Cycle ProteinschemistrymetabolismChromatingeneticsDNAmetabolismDNA GlycosylasesgeneticsmetabolismDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismExonucleasesmetabolismHEK293 CellsHeLa CellsHumansMiceSirtuinsgeneticsmetabolismTelomeremetabolism
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1460-21803692015SepCarcinogenesisCarcinogenesisDevelopment of APE1 enzymatic DNA repair assays: low APE1 activity is associated with increase lung cancer risk.982-9110.1093/carcin/bgv082The key role of DNA repair in removing DNA damage and minimizing mutations makes it an attractive target for cancer risk assessment and prevention. Here we describe the development of a robust assay for apurinic/apyrimidinic (AP) endonuclease 1 (APE1; APEX1), an essential enzyme involved in the repair of oxidative DNA damage. APE1 DNA repair enzymatic activity was measured in peripheral blood mononuclear cell protein extracts using a radioactivity-based assay, and its association with lung cancer was determined using conditional logistic regression with specimens from a population-based case-control study with 96 lung cancer cases and 96 matched control subjects. The mean APE1 enzyme activity in case patients was 691 [95% confidence interval (CI) = 655-727] units/ng protein, significantly lower than in control subjects (mean = 793, 95% CI = 751-834 units/ng protein, P = 0.0006). The adjusted odds ratio for lung cancer associated with 1 SD (211 units) decrease in APE1 activity was 2.0 (95% CI = 1.3-3.1; P = 0.002). Comparison of radioactivity- and fluorescence-based assays showed that the two are equivalent, indicating no interference by the fluorescent tag. The APE1Asp148Glu SNP was associated neither with APE1 enzyme activity nor with lung cancer risk. Taken together, our results indicate that low APE1 activity is associated with lung cancer risk, consistent with the hypothesis that 'bad DNA repair', rather than 'bad luck', is involved in cancer etiology. Such assays may be useful, along with additional DNA repair biomarkers, for risk assessment of lung cancer and perhaps other cancers, and for selecting individuals to undergo early detection techniques such as low-dose CT.© The Author 2015. Published by Oxford University Press.SevilyaZivZDepartment of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel, Department of Community Medicine and Epidemiology, Carmel Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, and Clalit Health Services National Cancer Control Center, Haifa, Israel, Department of General Thoracic Surgery, Rambam Health Care Campus, Haifa, Israel and Biostatistics Unit, Gertner Institute for Epidemiology and Public Health Policy Research, Sheba Medical Center, Tel Hashomer 52621, Israel.Leitner-DaganYaelYDepartment of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel, Department of Community Medicine and Epidemiology, Carmel Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, and Clalit Health Services National Cancer Control Center, Haifa, Israel, Department of General Thoracic Surgery, Rambam Health Care Campus, Haifa, Israel and Biostatistics Unit, Gertner Institute for Epidemiology and Public Health Policy Research, Sheba Medical Center, Tel Hashomer 52621, Israel.PinchevMilaMDepartment of Community Medicine and Epidemiology, Carmel Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, and Clalit Health Services National Cancer Control Center, Haifa, Israel.KremerRanRDepartment of General Thoracic Surgery, Rambam Health Care Campus, Haifa, Israel and.ElingerDaliaDDepartment of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel, Department of Community Medicine and Epidemiology, Carmel Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, and Clalit Health Services National Cancer Control Center, Haifa, Israel, Department of General Thoracic Surgery, Rambam Health Care Campus, Haifa, Israel and Biostatistics Unit, Gertner Institute for Epidemiology and Public Health Policy Research, Sheba Medical Center, Tel Hashomer 52621, Israel.LejbkowiczFlavioFDepartment of Community Medicine and Epidemiology, Carmel Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, and Clalit Health Services National Cancer Control Center, Haifa, Israel.RennertHedy SHSDepartment of Community Medicine and Epidemiology, Carmel Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, and Clalit Health Services National Cancer Control Center, Haifa, Israel.FreedmanLaurence SLSBiostatistics Unit, Gertner Institute for Epidemiology and Public Health Policy Research, Sheba Medical Center, Tel Hashomer 52621, Israel.RennertGadGDepartment of Community Medicine and Epidemiology, Carmel Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, and Clalit Health Services National Cancer Control Center, Haifa, Israel.Paz-ElizurTamarTDepartment of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel, Department of Community Medicine and Epidemiology, Carmel Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, and Clalit Health Services National Cancer Control Center, Haifa, Israel, Department of General Thoracic Surgery, Rambam Health Care Campus, Haifa, Israel and Biostatistics Unit, Gertner Institute for Epidemiology and Public Health Policy Research, Sheba Medical Center, Tel Hashomer 52621, Israel zvi.livneh@weizmann.ac.il tamar.paz-elizur@weizmann.ac.il.LivnehZviZDepartment of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel, Department of Community Medicine and Epidemiology, Carmel Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, and Clalit Health Services National Cancer Control Center, Haifa, Israel, Department of General Thoracic Surgery, Rambam Health Care Campus, Haifa, Israel and Biostatistics Unit, Gertner Institute for Epidemiology and Public Health Policy Research, Sheba Medical Center, Tel Hashomer 52621, Israel zvi.livneh@weizmann.ac.il.eng1 U01 CA111219CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20150604
EnglandCarcinogenesis80080550143-3334EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMMutat Res. 2012 Apr 1;732(1-2):43-622266085N Engl J Med. 2009 Dec 17;361(25):2449-6020018966Curr Mol Pharmacol. 2012 Jan;5(1):14-3522122462Mutat Res. 2010 Aug 7;690(1-2):3-1120223251Cell. 2011 Mar 4;144(5):646-7421376230Int J Cancer. 2011 May 1;128(9):1999-200921387284J Natl Cancer Inst. 2012 Nov 21;104(22):1765-923104324Cold Spring Harb Perspect Biol. 2013 Apr;5(4):a01258323545420Oxid Med Cell Longev. 2013;2013:38701424382987Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463Cancer Prev Res (Phila). 2014 Apr;7(4):398-40624356339Tumour Biol. 2014 Apr;35(4):3597-60324310503Science. 2015 Jan 2;347(6217):78-8125554788Carcinogenesis. 2014 Dec;35(12):2763-7025355292Cancer Chemother Pharmacol. 2014 Oct;74(4):777-8625107571Mol Carcinog. 2015 Jun;54 Suppl 1:E103-1125156607J Natl Cancer Inst. 2000 Nov 1;92(21):1764-7211058619Nucleic Acids Res. 2001 Jan 15;29(2):430-811139613Environ Mol Mutagen. 2000;36(4):312-2411152564Hum Mol Genet. 2001 Apr;10(7):705-1311257103Nature. 2001 May 17;411(6835):366-7411357144Nature. 2002 Jan 10;415(6868):183-711805838J Biol Chem. 2002 Jun 21;277(25):22605-1511960995Cancer Res. 2003 Aug 1;63(15):4351-712907604Cancer Res. 2003 Aug 15;63(16):4899-90212941813J Natl Cancer Inst. 2003 Sep 3;95(17):1312-912953085Nat Med. 2004 Aug;10(8):789-9915286780Nature. 1993 Apr 22;362(6422):709-158469282Science. 1994 Dec 23;266(5193):1959-607801122J Biol Chem. 1995 Jul 7;270(27):16002-77608159Carcinogenesis. 2004 Dec;25(12):2433-4115333465J Natl Cancer Inst. 2005 Jan 19;97(2):127-3215657342Nucleic Acids Res. 2005;33(7):2204-915831793Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1585-716030087Nucleic Acids Res. 2005;33(15):4711-2416113242Cancer Res. 2006 Dec 15;66(24):11683-917178863DNA Repair (Amst). 2007 Mar 1;6(3):274-917161978Cancer Res. 2007 Apr 15;67(8):3493-517440053Lung Cancer. 2008 May;60(2):277-8418061304Cancer Lett. 2008 Jul 18;266(1):60-7218374480Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3081-918990748J Natl Cancer Inst. 2009 Jan 7;101(1):24-3619116388Lung Cancer. 2009 Dec;66(3):298-30419324449Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Curr Mol Pharmacol. 2012 Jan;5(1):3-1322122461Case-Control StudiesDNA DamagegeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyaseanalysisgeneticsmetabolismFemaleFluorescenceGenetic Predisposition to DiseaseHumansLeukocytes, MononuclearcytologyLungenzymologypathologyLung NeoplasmsenzymologyepidemiologygeneticsMalePolymorphism, Single NucleotideRisk
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1873-4596862015SepFree radical biology & medicineFree Radic. Biol. Med.Genistein induces apoptosis by stabilizing intracellular p53 protein through an APE1-mediated pathway.209-1810.1016/j.freeradbiomed.2015.05.030S0891-5849(15)00253-1Genistein (GEN) has been previously shown to have a proapoptotic effect on cancer cells through a p53-dependent pathway, the mechanism of which remains unclear. One of its intracellular targets, APE1, protects against apoptosis under genotoxic stress and interacts with p53. In this current study, we explored the mechanism of the proapoptotic effect of GEN by examining the APE1-p53 protein-protein interaction. We initially showed that the p53 protein level was elevated in GEN-treated human non-small lung cancer A549 cells and cervical cancer HeLa cells. By examining both protein synthesis and degradation, we found that GEN enhances p53 intracellular stability by interfering with the interaction of APE1 and p53, which provided a plausible explanation for how GEN initiates apoptosis. Furthermore, we found that the interaction between APE1 and p53 is important for the degradation of p53 and is dependent on the redox domain of APE1 by utilizing the redox domain mutant APE1 C65A. Our data suggest that the degradation of wild-type p53 is blocked when the redox domain of APE1 is masked or interrupted. Based on this evidence, we hereby report a novel mechanism of p53 degradation through an APE1-mediated, redox-dependent pathway. Copyright © 2015 Elsevier Inc. All rights reserved.ZhuJianwuJCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China.ZhangChongCCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China.QingYiYCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China.ChengYiYCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China.JiangXiaolinXCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China.LiMengxiaMCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China. Electronic address: mengxia.li@outlook.com.YangZhenzhouZCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China. Electronic address: yangzz1970@163.com.WangDongDCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China.engJournal ArticleResearch Support, Non-U.S. Gov't20150530
United StatesFree Radic Biol Med87091590891-58490Antineoplastic Agents0TP53 protein, human0Tumor Suppressor Protein p53DH2M523P0HGenisteinEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAntineoplastic AgentspharmacologyApoptosisDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismGenisteinpharmacologyHeLa CellsHumansOxidation-ReductionProtein StabilityProteolysisSignal TransductionTumor Suppressor Protein p53APE1GenisteinStabilityWild-type p53
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1932-62031052015PloS onePLoS ONEMammalian Base Excision Repair: Functional Partnership between PARP-1 and APE1 in AP-Site Repair.e012426910.1371/journal.pone.0124269The apurinic/apyrimidinic- (AP-) site in genomic DNA arises through spontaneous base loss and base removal by DNA glycosylases and is considered an abundant DNA lesion in mammalian cells. The base excision repair (BER) pathway repairs the AP-site lesion by excising and replacing the site with a normal nucleotide via template directed gap-filling DNA synthesis. The BER pathway is mediated by a specialized group of proteins, some of which can be found in multiprotein complexes in cultured mouse fibroblasts. Using a DNA polymerase (pol) β immunoaffinity-capture technique to isolate such a complex, we identified five tightly associated and abundant BER factors in the complex: PARP-1, XRCC1, DNA ligase III, PNKP, and Tdp1. AP endonuclease 1 (APE1), however, was not present. Nevertheless, the complex was capable of BER activity, since repair was initiated by PARP-1's AP lyase strand incision activity. Addition of purified APE1 increased the BER activity of the pol β complex. Surprisingly, the pol β complex stimulated the strand incision activity of APE1. Our results suggested that PARP-1 was responsible for this effect, whereas other proteins in the complex had no effect on APE1 strand incision activity. Studies of purified PARP-1 and APE1 revealed that PARP-1 was able to stimulate APE1 strand incision activity. These results illustrate roles of PARP-1 in BER including a functional partnership with APE1. PrasadRajendraRGenome Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.DyrkheevaNadezhdaNGenome Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.WilliamsJasonJEpigenetics and Stem Cell Biology Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.WilsonSamuel HSHGenome Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.engZ01ES050158ESNIEHS NIH HHSUnited StatesZ01ES050159ESNIEHS NIH HHSUnited StatesIntramural NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., IntramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.20150528
United StatesPLoS One1012850811932-62039007-49-2DNAEC 2.4.2.30Parp1 protein, mouseEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 2.7.7.-DNA Polymerase betaEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCurr Pharm Des. 2009;15(25):2908-1419754367Nucleic Acids Res. 2010 Jan;38(2):510-2119910369J Biol Chem. 2010 Dec 24;285(52):40479-8820952393Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22090-521127267Environ Mol Mutagen. 2011 Oct;52(8):623-3521786338Mutat Res. 1998 Jun;407(3):203-159653447J Biol Chem. 1998 Aug 14;273(33):21203-99694877Cancer Res. 1999 Jun 1;59(11):2522-610363965Bioessays. 2001 May;23(5):447-5511340626Methods. 2001 Jul;24(3):218-2911403571J Biol Chem. 2001 Jul 6;276(27):25541-811340072J Biol Chem. 2002 Aug 23;277(34):31115-2312063248DNA Repair (Amst). 2003 Jan 2;2(1):27-4812509266Mol Cell. 2005 Feb 4;17(3):463-7015694346Cell. 1985 Mar;40(3):483-42982494Biochemistry. 1986 Apr 22;25(8):2212-202423122Biochem J. 1987 Mar 1;242(2):565-722439070Biochem J. 1989 Sep 1;262(2):581-92679549J Biol Chem. 1990 Feb 5;265(4):2124-312404980Mutat Res. 1990 Sep-Nov;236(2-3):173-2011697933Prog Nucleic Acid Res Mol Biol. 1994;48:315-707938553Biochemistry. 1995 Jan 10;34(1):128-387819187Science. 1995 Aug 4;269(5224):699-7027624801Trends Biochem Sci. 1995 Oct;20(10):391-78533150Methods Enzymol. 1995;262:98-1078594388Nucleic Acids Res. 1995 Dec 11;23(23):4836-438532526Nature. 1996 Jan 11;379(6561):183-68538772J Biol Chem. 1996 Apr 19;271(16):9573-88621631J Biol Chem. 1996 Jun 7;271(23):13816-208662731J Biol Chem. 1996 Jul 5;271(27):16000-78663274J Biol Chem. 1996 Jul 26;271(30):17811-58663612J Biol Chem. 1997 Jan 10;272(2):1302-78995436Oncogene. 1997 Apr 24;14(16):1911-219150358Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-99207062EMBO J. 1997 Jun 2;16(11):3341-89214649J Biol Chem. 1998 Jan 9;273(2):898-9029422747Biochemistry. 1998 Mar 17;37(11):3575-809530283Mol Cell Biol. 1998 Jun;18(6):3563-719584196Biochemistry. 1990 Aug 7;29(31):7156-92207097Nature. 1993 Apr 22;362(6422):709-158469282Curr Opin Cell Biol. 1993 Jun;5(3):424-338352959Mol Cell Biol. 1994 Jan;14(1):310-78264597Mol Cell Biol. 1994 Jan;14(1):68-768264637J Biol Chem. 2013 Mar 22;288(12):8445-5523355472J Vis Exp. 2013;(78):e5069523995844Biochemistry. 2013 Oct 29;52(43):7669-7724079850Mol Biol Cell. 2014 May;25(10):1641-5224648491Nucleic Acids Res. 2014 Jun;42(10):6337-5124771347Cell Mol Life Sci. 2014 Jul;71(13):2451-6524496644Nucleic Acids Res. 2001 Mar 15;29(6):1285-9211238994DNA Repair (Amst). 2005 Sep 28;4(10):1099-11016051529Mol Cell Proteomics. 2006 Jan;5(1):144-5616219938J Biol Chem. 2007 Feb 2;282(5):2976-8617148452Nucleic Acids Res. 2007;35(5):1569-7717289756J Biol Chem. 2007 May 4;282(18):13532-4117355977Nucleic Acids Res. 2007;35(8):2596-60817426133Mol Cell. 2007 Sep 7;27(5):829-4117803946Nucleic Acids Res. 2007;35(17):e11217720705J Biol Chem. 2007 Oct 19;282(42):30577-8517724035J Biol Chem. 2012 Nov 9;287(46):39233-4422992732Nucleic Acids Res. 2012 Dec;40(22):11571-8223042675DNA Repair (Amst). 2004 Jun 3;3(6):581-9115135726J Biol Chem. 2014 May 16;289(20):13996-400824695738Mol Cancer Res. 2014 Aug;12(8):1128-3924770870Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Science. 1999 Dec 3;286(5446):1897-90510583946Radiat Res. 2000 Feb;153(2):186-9510629618J Biol Chem. 2000 Jan 21;275(3):2211-810636928Nature. 2000 Jan 27;403(6768):451-610667800Mutat Res. 2000 Apr;462(2-3):129-3510767624Cell. 2001 Jan 12;104(1):107-1711163244Biochem Soc Trans. 2003 Feb;31(Pt 1):247-5112546695DNA Repair (Amst). 2003 Oct 7;2(10):1087-10013679147Mutat Res. 2003 Oct 29;531(1-2):231-5114637258DNA Repair (Amst). 2004 Jul 2;3(7):703-1015177179Mol Cell. 2004 Jul 23;15(2):209-2015260972Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13738-4315365186Biochemistry. 1972 Sep 12;11(19):3610-84626532Annu Rev Biochem. 1982;51:61-876287922AnimalsCells, CulturedDNAmetabolismDNA Polymerase betametabolismDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismFibroblastscytologyenzymologyHumansMicePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerasesmetabolism
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1460-208324162015Aug15Human molecular geneticsHum. Mol. Genet.Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway.4516-2910.1093/hmg/ddv183Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency has been identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized to mitochondria in neuroblastoma cells, where it enhances preservation of mitochondrial function. In this study, we show that aprataxin deficiency impairs mitochondrial function, independent of its role in mitochondrial DNA repair. The bioenergetics defect in AOA1-mutant fibroblasts and APTX-depleted Hela cells is caused by decreased expression of SDHA and genes encoding CoQ biosynthetic enzymes, in association with reductions of APE1, NRF1 and NRF2. The biochemical and molecular abnormalities in APTX-depleted cells are recapitulated by knockdown of APE1 in Hela cells and are rescued by overexpression of NRF1/2. Importantly, pharmacological upregulation of NRF1 alone by 5-aminoimidazone-4-carboxamide ribonucleotide does not rescue the phenotype, which, in contrast, is reversed by the upregulation of NRF2 by rosiglitazone. Accordingly, we propose that the lack of aprataxin causes reduction of the pathway APE1/NRF1/NRF2 and their target genes. Our findings demonstrate a critical role of APTX in transcription regulation of mitochondrial function and the pathogenesis of AOA1 via a novel pathomechanistic pathway, which may be relevant to other neurodegenerative diseases. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.Garcia-DiazBeatrizBDepartment of Neurology.BarcaEmanueleEDepartment of Neurology, UOC of Neurology and Neuromuscular Disorders, Department of Neuroscience, University of Messina, Messina 98100, Italy.BalreiraAndreaADepartment of Neurology.LopezLuis CLCDepartment of Neurology, Institute of Biotechnology, Biomedical Research Center (CIBM), Health Science Technological Park (PTS), University of Granada, Armilla, Granada 18100, Spain and.TadesseSabaSDepartment of Neurology.KrishnaSindhuSDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.NainiAliADepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.MariottiCaterinaCUnitâ di Genetica delle Malattie Neurodegenerative e Metaboliche, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan 20126, Italy.CastellottiBarbaraBUnitâ di Genetica delle Malattie Neurodegenerative e Metaboliche, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan 20126, Italy.QuinziiCatarina MCMDepartment of Neurology, cmq2101@cumc.columbia.edu.eng5K23 HD065871HDNICHD NIH HHSUnited StatesNIH P01 HD080642-01HDNICHD NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20150514
EnglandHum Mol Genet92089580964-69060APTX protein, human0DNA-Binding Proteins0NF-E2-Related Factor 20NFE2L2 protein, human0NRF1 protein, human0Nuclear Proteins0Nuclear Respiratory Factor 1EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Biol Chem. 2008 Apr 18;283(16):10967-7718252725J Biol Chem. 2007 Mar 30;282(13):9469-7417276982Am J Hum Genet. 2006 Dec;79(6):1125-917186472J Cell Biol. 2015 Feb 16;208(4):429-4225688136Cell. 2006 Oct 20;127(2):397-40817055439Neurogenetics. 2011 Aug;12(3):193-20121465257FASEB J. 2013 Feb;27(2):612-2123150520Hum Mol Genet. 2009 Nov 1;18(21):4102-1719643912Neurology. 2003 Mar 11;60(5):868-7012629250IUBMB Life. 2014 Feb;66(2):63-7024470391Brain. 2003 Dec;126(Pt 12):2761-7214506070Biochem J. 2011 Apr 15;435(2):297-31221726199Brain. 2011 May;134(Pt 5):1387-9921486904Nat Genet. 2001 Feb;27(2):181-611175786Mol Cell Biol. 2009 Mar;29(5):1354-6219103743Orphanet J Rare Dis. 2006;1:4717112370Hepatology. 2013 May;57(5):2037-4822961760J Biol Chem. 2006 May 19;281(20):13939-4816547001J Child Neurol. 2008 Aug;23(8):895-90018403580Gene. 2002 Mar 6;286(1):81-911943463Nat Genet. 2001 Oct;29(2):184-811586299Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463Cell Mol Life Sci. 2005 Feb;62(4):485-9115719174DNA Repair (Amst). 2004 Nov 2;3(11):1493-50215380105Cell. 2014 May 8;157(4):882-9624813611Am J Hum Genet. 2008 Mar;82(3):661-7218319074Proteomics. 2009 Feb;9(4):1058-7419180539Mol Syndromol. 2014 Jul;5(3-4):119-4025126045Nature. 2006 Oct 12;443(7112):713-616964241Hum Mol Genet. 2014 May 1;23(9):2400-1524334768Mol Neurobiol. 2010 Jun;41(2-3):187-9620411356Ann Neurol. 2007 Feb;61(2):162-7417315206Rinsho Shinkeigaku. 1992 Oct;32(10):1067-741297549Hum Mol Genet. 2006 Jul 15;15(14):2239-4916777843Neurology. 2007 Jan 23;68(4):295-717242337FASEB J. 2010 Oct;24(10):3733-4320495179Proc Natl Acad Sci U S A. 2011 May 3;108(18):7437-4221502511DNA Repair (Amst). 2009 Jun 4;8(6):760-619303373Ann Neurol. 2004 Feb;55(2):241-914755728Neurology. 2001 Apr 10;56(7):849-5511294920Nat Genet. 2001 Oct;29(2):189-9311586300Hum Mol Genet. 2013 Mar 15;22(6):1233-4823255162Cardiovasc Res. 2005 Jun 1;66(3):562-7315914121Am J Physiol. 1997 Dec;273(6 Pt 1):E1107-129435525Hum Mol Genet. 2004 May 15;13(10):1081-9315044383Ann N Y Acad Sci. 2008 Dec;1147:321-3419076454J Biol Chem. 2003 Jul 18;278(29):26597-60312734177Neurology. 2005 Feb 8;64(3):539-4115699391Am J Hum Genet. 2006 Feb;78(2):345-916400613Free Radic Biol Med. 2012 Jul 15;53(2):237-4822580151AtaxiageneticsmetabolismpathologyDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisgeneticsDNA-Binding ProteinsdeficiencygeneticsDown-RegulationFemaleFibroblastsmetabolismpathologyGenetic Diseases, InborngeneticsmetabolismpathologyHumansMaleMitochondriametabolismpathologyNF-E2-Related Factor 2biosynthesisgeneticsNuclear ProteinsdeficiencygeneticsNuclear Respiratory Factor 1biosynthesisgeneticsSignal Transduction
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1791-24313412015JulOncology reportsOncol. Rep.Lentiviral-mediated short hairpin RNA silencing of APE1 suppresses hepatocellular carcinoma proliferation and migration: A potential therapeutic target for hepatoma treatment.95-10210.3892/or.2015.3976Apurinic/apyrimidinic endonuclease-1 (APE1) is a protein involved in DNA repair and transcriptional regulation of gene expression. APE1 expression was reported to be correlated with poor prognosis in hepatocellular carcinoma (HCC) patients. Based on our previous study, we hypothesized that APE1 may be involved in the metastatic progression of HCC. Thus, the present study aimed to investigate the knockdown effect of APE1 using shRNA in HCC and demonstrate that silencing of APE1 in MHCC97-H cells can decrease the oncogenic transforming potential in vitro and reduce the growth of HCC tumor xenografts in vivo. Silencing of APE1 expression decreased the cell proliferation and survival, reduced the cell adhesion ability in Matrigel or fibronectin-coated plates and suppressed the cell migration and invasion in a Transwell assay of HCC cells. In the xenograft study, tumor growth was markedly inhibited in the APE1-silenced group. Silencing of APE1 in MHCC97-H cells decreased the oncogenic transforming potential in vitro and reduced the growth of HCC tumor xenografts in vivo. Inhibition of APE1 may present a novel therapeutic approach for the treatment of HCC.ZhengZhi-HuaZHDepartment of Pathology, Quanzhou Medical College, Quanzhou, Fujian 362100, P.R. China.DuWeiWDepartment of Pathology and Institute of Oncology, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.LiYan-JuYJDepartment of Pathology and Institute of Oncology, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.GaoMei-QinMQDepartment of Pathology and Institute of Oncology, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.HuangAi-MinAMDepartment of Pathology and Institute of Oncology, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.LiuJing-FengJFMengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China.engJournal ArticleResearch Support, Non-U.S. Gov't20150513
GreeceOncol Rep94227561021-335X0RNA, Small InterferingEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsCarcinoma, HepatocellulargeneticspathologytherapyCell Line, TumorCell MovementgeneticsCell ProliferationgeneticsDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsgeneticsGene SilencingGenetic TherapyHumansLiver NeoplasmsgeneticspathologytherapyMiceRNA, Small InterferinggeneticsXenograft Model Antitumor Assays
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1362-496243112015Jun23Nucleic acids researchNucleic Acids Res.Mitochondrial translocation of APE1 relies on the MIA pathway.5451-6410.1093/nar/gkv433APE1 is a multifunctional protein with a fundamental role in repairing nuclear and mitochondrial DNA lesions caused by oxidative and alkylating agents. Unfortunately, comprehensions of the mechanisms regulating APE1 intracellular trafficking are still fragmentary and contrasting. Recent data demonstrate that APE1 interacts with the mitochondrial import and assembly protein Mia40 suggesting the involvement of a redox-assisted mechanism, dependent on the disulfide transfer system, to be responsible of APE1 trafficking into the mitochondria. The MIA pathway is an import machinery that uses a redox system for cysteine enriched proteins to drive them in this compartment. It is composed by two main proteins: Mia40 is the oxidoreductase that catalyzes the formation of the disulfide bonds in the substrate, while ALR reoxidizes Mia40 after the import. In this study, we demonstrated that: (i) APE1 and Mia40 interact through disulfide bond formation; and (ii) Mia40 expression levels directly affect APE1's mitochondrial translocation and, consequently, play a role in the maintenance of mitochondrial DNA integrity. In summary, our data strongly support the hypothesis of a redox-assisted mechanism, dependent on Mia40, in controlling APE1 translocation into the mitochondrial inner membrane space and thus highlight the role of this protein transport pathway in the maintenance of mitochondrial DNA stability and cell survival. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.BarchiesiAriannaADepartment of Medical and Biological Sciences, University of Udine, Udine 33100, Italy.WasilewskiMichalMInternational Institute of Molecular and Cell Biology, Warsaw, 02-109, Poland.ChacinskaAgnieszkaAInternational Institute of Molecular and Cell Biology, Warsaw, 02-109, Poland.TellGianlucaGDepartment of Medical and Biological Sciences, University of Udine, Udine 33100, Italy.VascottoCarloCDepartment of Medical and Biological Sciences, University of Udine, Udine 33100, Italy carlo.vascotto@uniud.it.engJournal ArticleResearch Support, Non-U.S. Gov't20150508
EnglandNucleic Acids Res04110110305-10480DNA, Mitochondrial0Disulfides0MIA40 protein, human0Mitochondrial Membrane Transport ProteinsEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseK848JZ4886CysteineIMMol Microbiol. 2007 Sep;65(5):1360-7317680986Mutat Res. 2001 Mar 7;485(2):143-5211182545Mutat Res. 2008 Aug 25;643(1-2):54-6318579163Nucleic Acids Res. 2006;34(7):2067-7616617147Free Radic Biol Med. 2002 May 1;32(9):804-1211978482Anticancer Res. 2001 Nov-Dec;21(6A):4041-911911289Med Oncol. 2012 Jun;29(2):1265-7121479902J Clin Invest. 2012 Feb;122(2):600-1122214851J Biol Chem. 2005 Mar 11;280(10):8901-515632148Mech Ageing Dev. 2008 Jul-Aug;129(7-8):383-9018417187EMBO J. 1997 Nov 3;16(21):6548-589351835J Biol Chem. 2007 Dec 28;282(52):37461-7017959605Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414Mol Biol Cell. 2011 Oct;22(20):3887-90121865600Gene. 2002 Mar 6;286(1):127-3411943468FEBS Lett. 2014 Aug 1;588(15):2484-9524866464Dev Cell. 2014 Jan 13;28(1):30-4224360785Lung Cancer. 2009 Dec;66(3):298-30419324449Antioxid Redox Signal. 2010 Jun 1;12(11):1247-6919764832Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084EMBO J. 2004 Oct 1;23(19):3735-4615359280J Mol Biol. 2007 Jan 19;365(3):612-2017095012Mol Cell Biol. 1993 Sep;13(9):5370-68355688Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17356-6124101517Free Radic Biol Med. 1990;8(6):523-392193852Proc Natl Acad Sci U S A. 1988 Sep;85(17):6465-73413108Int J Cell Biol. 2013;2013:74292324348563Mol Biol Cell. 2012 Oct;23(20):3957-6922918950J Am Chem Soc. 2012 Jan 25;134(3):1442-522224850Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20190-521059946Mol Cell. 2010 Feb 26;37(4):516-2820188670Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143Mol Med. 2007 Jan-Feb;13(1-2):89-9617515960Int J Oncol. 2009 Nov;35(5):1069-7919787261BMC Cancer. 2014;14:1124400589J Biol Chem. 2010 May 14;285(20):14871-8120231292Mol Cell. 2005 Feb 4;17(3):463-7015694346Proteomics. 2009 Feb;9(4):1058-7419180539Br J Ophthalmol. 2014 Mar;98(3):402-724385289Cancer Sci. 2012 May;103(5):882-822329793Methods Mol Biol. 2012;920:111-3222941600Nucleic Acids Res. 2004;32(7):2181-9215107486J Mol Biol. 2005 Oct 28;353(3):517-2816185709Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4811-621383138Cell Line, TumorCysteinechemistryDNA DamageDNA RepairDNA, MitochondrialmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasechemistrymetabolismDisulfideschemistryHumansMitochondriametabolismMitochondrial Membrane Transport ProteinschemistrymetabolismMutationProtein StabilityProtein Transport
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1573-25844762015JunInternational urology and nephrologyInt Urol NephrolThe association of ApE1 -656T>G and 1349T>G polymorphisms and idiopathic male infertility risk.921-610.1007/s11255-015-0979-zIn spite of variety studies in understanding of human reproductive and fertility, the underlying causes of male infertility remains undefined in about 50 % of cases. The polymorphism studies have a crucial role in diseases recognizing. Human apurinic/apyrimidinic endonuclease 1 (ApE1) is a multifunctional protein that has an important role in the base excision repair pathway. The present study was aimed to evaluate whether two polymorphisms -656T>G and 1349T>G ApE1 are related with the susceptibility to idiopathic male infertility.Samples were collected from 180 patients diagnosed with idiopathic male infertility and 120 control subjects and genotyped by tetra-primer amplification refractory mutation system PCR.We observed a significant difference in genotype distributions of -656T>G ApE1 polymorphism between infertile patients and controls (P = 0.0001). Our findings indicated individuals with the variant TG genotypes had a significant increased risk of idiopathic male infertility (OR 1.84, 95 % CI 1.09-3.11, P = 0.021), whereas the significant association between the 1349T>G polymorphism and idiopathic male infertility risk was not observed (P = 0.2).Our data suggest that the -656T>G ApE1 polymorphism may be associated with increased risk of idiopathic male infertility. Larger studies with more patients and controls are needed to confirm the results.YousefiMostafaMDepartment of Biology, Faculty of Sciences, University of Guilan, P.O. Box 1914, Rasht, Iran.SalehiZivarZMashayekhiFarhadFBahadoriMohammad HadiMHengJournal ArticleResearch Support, Non-U.S. Gov't20150428
NetherlandsInt Urol Nephrol02625210301-1623EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Biol Chem. 2003 May 16;278(20):18289-9612624104PLoS One. 2011;6(12):e2897122205985Biochim Biophys Acta. 2006 Jan;1762(1):17-2816297602Reprod Toxicol. 2006 Aug;22(2):133-4116806807BMC Cancer. 2011 Mar 23;11:10421429202Am J Epidemiol. 2005 Jan 1;161(1):1-1415615908Fertil Steril. 2009 Nov;92(5):1520-419828144Carcinogenesis. 2001 Jun;22(6):917-2211375899Carcinogenesis. 2000 Jul;21(7):1329-3410874010Balkan J Med Genet. 2012 Dec;15(Suppl):31-424052740Science. 2001 Feb 16;291(5507):1284-911181991Genomics. 2004 Jun;83(6):970-915177551Hum Reprod. 2008 Dec;23(12):2663-818757447Med Oncol. 2013 Jun;30(2):50523430444Eur J Obstet Gynecol Reprod Biol. 2009 Oct;146(2):160-419592152Int J Androl. 2009 Feb;32(1):46-5619076252BMC Cancer. 2011 Dec 18;11:52122176746Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Clin Cancer Res. 2001 Apr;7(4):824-3011309329Cancer Res. 2001 Feb 15;61(4):1354-711245433Adv Urol. 2012;2012:38452022046184Gene. 2013 Nov 15;531(1):97-10023994194Science. 2006 May 26;312(5777):1215-716728641Mol Biol Rep. 2013 Jan;40(1):171-623143180AdultDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGenetic Predisposition to DiseaseHumansInfertility, MalegeneticsMalePolymorphism, GeneticRisk Assessment
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1423-038036102015SepTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.XPD, APE1, and MUTYH polymorphisms increase head and neck cancer risk: effect of gene-gene and gene-environment interactions.7569-7910.1007/s13277-015-3472-5In the present study, we investigated the effect of the DNA repair gene polymorphisms XPD Asp312Asn (G>A), APE1 Asp148Glu (T>G), and MUTYH Tyr165Cys (G>A) on the risk for head and neck cancer (HNC) in association with tobacco use in a population of Northeast India. The study subjects comprised of 80 HNC patients and 92 healthy controls. Genotyping was performed using amplification refractory mutation system-PCR (ARMS-PCR) for XPD Asp312Asn (G>A) and PCR using confronting two-pair primers (PCR-CTPP) for APE1 Asp148Glu (T>G) and MUTYH Tyr165Cys (G>A). The XPD Asp/Asn genotype increased the risk for HNC by 2-fold (odds ratio, OR = 2.072; 95 % CI, 1.025-4.190; p < 0.05). Interaction between APE1 Asp/Asp and XPD Asp/Asn as well as MUTYH Tyr/Tyr and XPD Asp/Asn genotypes further increased the risk by 2.9 (OR = 2.97; 95 % CI, 1.16-7.61; p < 0.05) and 2.3 (OR = 2.37; 95 % CI, 1.11-5.10; p < 0.05) folds, respectively. The risk was further increased in heavy smokers with the XPD Asp/Asn genotype and heavy tobacco chewers with XPD Asn/Asn genotype by 7.7-fold (OR = 7.749; 95 % CI, 2.53-23.70; p < 0.05) and 10-fold (OR = 10; 95 % CI, 1.26-79.13; p < 0.05), respectively. We thus conclude that the XPD Asp312Asn and APE1 Asp148Glu polymorphisms increase the risk for HNC in association with smoking and/or tobacco chewing in the population under study.DasSambuddhaSDepartment of Biotechnology, Assam University, Silchar, 788011, India.BhowmikAditiADepartment of Biotechnology, Assam University, Silchar, 788011, India.BhattacharjeeAbhinandanADepartment of ENT, Silchar Medical College and Hospital, Silchar, 788014, India.ChoudhuryBiswadeepBDepartment of Biochemistry, Silchar Medical College and Hospital, Silchar, 788014, India.NaidingMomotaMDepartment of Pathology, Silchar Medical College and Hospital, Silchar, 788014, India.LaskarAgniv KrAKDepartment of Biotechnology, Assam University, Silchar, 788011, India.GhoshSankar KumarSKDepartment of Biotechnology, Assam University, Silchar, 788011, India.ChoudhuryYashminYDepartment of Biotechnology, Assam University, Silchar, 788011, India. yashminchoudhury@gmail.com.engJournal ArticleResearch Support, Non-U.S. Gov't20150429
United StatesTumour Biol84099221010-4283EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 5.99.-ERCC2 protein, humanIMJ Clin Oncol. 2010 May 10;28(14):2445-5120385987Med Oncol. 2014 Aug;31(8):6724958516AdultCase-Control StudiesDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleGene-Environment InteractionGenetic Predisposition to DiseasegeneticsGenotypeHead and Neck NeoplasmsgeneticsHumansIndiaMaleMiddle AgedPolymorphism, GeneticgeneticsRiskRisk FactorsSmokinggeneticsXeroderma Pigmentosum Group D ProteingeneticsAPE1Head and neck cancerMUTYHPolymorphismXPD
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1098-27445552016MayMolecular carcinogenesisMol. Carcinog.Inhibitors of the apurinic/apyrimidinic endonuclease 1 (APE1)/nucleophosmin (NPM1) interaction that display anti-tumor properties.688-70410.1002/mc.22313The apurinic/apyrimidinic endonuclease 1 (APE1) is a protein central to the base excision DNA repair pathway and operates in the modulation of gene expression through redox-dependent and independent mechanisms. Aberrant expression and localization of APE1 in tumors are recurrent hallmarks of aggressiveness and resistance to therapy. We identified and characterized the molecular association between APE1 and nucleophosmin (NPM1), a multifunctional protein involved in the preservation of genome stability and rRNA maturation. This protein-protein interaction modulates subcellular localization and endonuclease activity of APE1. Moreover, we reported a correlation between APE1 and NPM1 expression levels in ovarian cancer, with NPM1 overexpression being a marker of poor prognosis. These observations suggest that tumors that display an augmented APE1/NPM1 association may exhibit increased aggressiveness and resistance. Therefore, targeting the APE1/NPM1 interaction might represent an innovative strategy for the development of anticancer drugs, as tumor cells relying on higher levels of APE1 and NPM1 for proliferation and survival may be more sensitive than untransformed cells. We set up a chemiluminescence-based high-throughput screening assay in order to find small molecules able to interfere with the APE1/NPM1 interaction. This screening led to the identification of a set of bioactive compounds that impair the APE1/NPM1 association in living cells. Interestingly, some of these molecules display anti-proliferative activity and sensitize cells to therapeutically relevant genotoxins. Given the prognostic significance of APE1 and NPM1, these compounds might prove effective in the treatment of tumors that show abundant levels of both proteins, such as ovarian or hepatic carcinomas.© 2015 Wiley Periodicals, Inc.PolettoMattiaMDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.MalfattiMatilde CMCDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.DorjsurenDorjbalDNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland.ScognamiglioPasqualina LPLDepartment of Pharmacy, CIRPEB (Centro Interuniversitario di Ricerca sui Peptidi Bioattivi), University of Naples 'Federico II', Naples, Italy.Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano di Tecnologia (IIT), Naples, Italy.MarascoDanielaDDepartment of Pharmacy, CIRPEB (Centro Interuniversitario di Ricerca sui Peptidi Bioattivi), University of Naples 'Federico II', Naples, Italy.VascottoCarloCDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.JadhavAjitANIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland.MaloneyDavid JDJNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland.WilsonDavid MDM3rdLaboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.SimeonovAntonANIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland.TellGianlucaGDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.engZ99 TR999999NULLIntramural NIH HHSUnited StatesU54MH08468MHNIMH NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20150411
United StatesMol Carcinog88111050899-19870Antineoplastic Agents0Nuclear Proteins0Small Molecule Libraries117896-08-9nucleophosminEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Med Chem. 2012 Apr 12;55(7):3101-1222455312JALA Charlottesv Va. 2008 Apr;13(2):79-8918496600Nucleic Acids Res. 2012 Jan;40(2):701-1121933813Am J Clin Pathol. 2014 Mar;141(3):404-1424515769Mol Pharmacol. 1989 Apr;35(4):428-322468077Med Oncol. 2012 Jun;29(2):1265-7121479902Cancer. 2002 Nov 15;95(10):2243-5112412180Nucleic Acids Res. 2005;33(10):3303-1215942031Chem Biol. 2014 Sep 18;21(9):1102-1425237857Nat Biotechnol. 2000 Mar;18(3):304-810700146Toxicol Appl Pharmacol. 2009 Nov 1;240(3):348-5419632256Clin Chem. 2008 Jul;54(7):1218-2518499900Nat Rev Cancer. 2008 Mar;8(3):193-20418256616Nucleic Acids Res. 2010 Jan;38(3):832-4519934257Mol Biol Cell. 2012 Oct;23(20):4079-9622918947Nucleic Acids Res. 2004;32(1):73-8114704345J Biol Chem. 2011 Feb 18;286(7):4968-7721081487Br J Cancer. 1998 Apr;77(7):1169-739569057Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Eur J Pharmacol. 2000 Nov 3;407(3):227-3511068018Exp Cell Res. 1988 Mar;175(1):184-913345800Annu Rev Pharmacol Toxicol. 2014;54:435-5624160698Proc Natl Acad Sci U S A. 1990 Dec;87(23):9373-71701259Biochem Biophys Res Commun. 2012 Jul 20;424(1):34-922713458Oncogene. 2011 Jun 9;30(23):2595-60921278791Mol Med. 2007 Jan-Feb;13(1-2):89-9617515960J Clin Endocrinol Metab. 2001 Jul;86(7):3250-611443197Curr Med Chem. 2012;19(23):3922-3622788768J Biol Chem. 2010 Apr 16;285(16):12416-2520159984Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Cell Mol Life Sci. 2010 Nov;67(21):3621-3120809131DNA Repair (Amst). 2013 Mar 1;12(3):188-9523276627Proteomics. 2009 Feb;9(4):1058-7419180539Oncogene. 2014 May 29;33(22):2876-8723831574Mutat Res. 1998 Oct 21;409(1):17-299806499Nucleic Acids Res. 2010 Dec;38(22):8239-5620699270Cancer Res. 2001 Mar 1;61(5):2220-511280790Mol Cancer Ther. 2007 Aug;6(8):2303-917699725Mol Cell Proteomics. 2010 Jan;9(1):178-8319864249PLoS One. 2009;4(6):e574019484131Biochem J. 2013 Jun 15;452(3):545-5723544830PLoS One. 2013;8(8):e7090923967134PLoS One. 2013;8(6):e6636223840452Prog Nucleic Acid Res Mol Biol. 2001;68:41-5411554312Nucleic Acids Res. 2005;33(15):4711-2416113242Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463Br J Cancer. 2007 Feb 12;96(3):477-8417245342Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766Nat Genet. 2011 May;43(5):470-521441929Blood. 2007 Feb 1;109(3):874-8517008539Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Antineoplastic AgentspharmacologyCell Line, TumorCell Proliferationdrug effectsCell Survivaldrug effectsDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsmetabolismFemaleHeLa CellsHigh-Throughput Screening AssaysHumansMCF-7 CellsNeoplasmsmetabolismpathologyNuclear Proteinsantagonists & inhibitorsmetabolismProtein Bindingdrug effectsSmall Molecule LibrariespharmacologyAPE1NPM1combination therapyprotein/protein interactionsmall molecule
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1873-135X766-7672014 Aug-SepMutation researchMutat. Res.Direct observation of preferential processing of clustered abasic DNA damages with APE1 in TATA box and CpG island by reaction kinetics and fluorescence dynamics.56-6510.1016/j.mrfmmm.2014.06.002S0027-5107(14)00110-9Sequences like the core element of TATA box and CpG island are frequently encountered in the genome and related to transcription. The fate of repair of clustered abasic sites in such sequences of genomic importance is largely unknown. This prompted us to investigate the sequence dependence of cleavage efficiency of APE1 enzyme at abasic sites within the core sequences of TATA box and CpG island using fluorescence dynamics and reaction kinetics. Simultaneous molecular dynamics study through steady state and time resolved fluorescence spectroscopy using unique ethidium bromide dye release assay confirmed an elevated amount of abasic site cleavage of the TATA box sequence as compared to the core CpG island. Reaction kinetics showed that catalytic efficiency of APE1 for abasic site cleavage of core CpG island sequence was ∼4 times lower as compared to that of the TATA box. Higher value of Km was obtained from the core CpG island sequence than the TATA box sequence. This suggests a greater binding effect of APE1 enzyme on TATA sequence that signifies a prominent role of the sequence context of the DNA substrate. Evidently, a faster response from APE1 was obtained for clustered abasic damage repair of TATA box core sequences than CpG island consensus sequences. The neighboring bases of the abasic sites in the complementary DNA strand were found to have significant contribution in addition to the flanking bases in modulating APE1 activity. The repair refractivity of the bistranded clustered abasic sites arise from the slow processing of the second abasic site, consequently resulting in decreased overall production of potentially lethal double strand breaks. Copyright © 2014 Elsevier B.V. All rights reserved.SinghVandanaVDepartment of Chemistry, Indian Institute of Technology Patna, Govt. Polytechnic Campus, Patliputra Colony, Patna 800013, Bihar, India.KumariBhaviniBDepartment of Chemistry, Indian Institute of Technology Patna, Govt. Polytechnic Campus, Patliputra Colony, Patna 800013, Bihar, India.MaityBanibrataBDepartment of Chemistry, Indian Institute of Technology Patna, Govt. Polytechnic Campus, Patliputra Colony, Patna 800013, Bihar, India.SethDebabrataDDepartment of Chemistry, Indian Institute of Technology Patna, Govt. Polytechnic Campus, Patliputra Colony, Patna 800013, Bihar, India.DasProlayPDepartment of Chemistry, Indian Institute of Technology Patna, Govt. Polytechnic Campus, Patliputra Colony, Patna 800013, Bihar, India. Electronic address: prolay@iitp.ac.in.engJournal ArticleResearch Support, Non-U.S. Gov't20140621
NetherlandsMutat Res04007630027-51079007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBase SequenceBinding SitesgeneticsCatalysisCpG IslandsDNAgeneticsmetabolismDNA DamageDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismHumansKineticsMolecular Sequence DataNucleic Acid ConformationProtein BindingSpectrometry, FluorescenceTATA BoxAPE1Abasic siteCpG islandDNA damageTATA boxTime resolved fluorescence spectroscopy
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1873-135X766-7672014 Aug-SepMutation researchMutat. Res.Impact of abasic site orientation within nucleosomes on human APE1 endonuclease activity.19-2410.1016/j.mrfmmm.2014.05.008S0027-5107(14)00103-1Glycosylases responsible for recognizing DNA lesions and initiating Base Excision Repair (BER) are impeded by the presence of histones, which are essential for compaction of the genetic material in the nucleus. Abasic sites are an abundant mutagenic lesion in the DNA, arising spontaneously and as the product of glycosylase activity, making it a common intermediate in BER. The apurinic/apyrimidinic endonuclease 1 (APE1) recognizes abasic sites and cleaves the DNA backbone adjacent to the lesion, creating the single-strand break essential for the subsequent steps of BER. In this study the endonuclease activity of human APE1 was measured on reconstituted nucleosome core particles (NCPs) with DNA containing enzymatically created abasic sites (AP) or the abasic site analog tetrahydrofuran (TF) at different rotational positions relative to the histone core surface. The presence of histones on the DNA reduced APE1 activity overall, and the magnitude was greatly influenced by differences in orientation of the lesions along the DNA gyre relative to the histone core. Abasic moieties oriented with their phosphate backbones adjacent to the underlying histones (In) were cleaved less efficiently than those oriented away from the histone core (Out) or between the In and Out orientations (Mid). The impact on APE1 at each orientation was very similar between the AP and TF lesions, highlighting the dependability of the TF abasic analog in APE1 activity measurements in nucleosomes. Measurement of APE1 binding to the NCP substrates reveals a substantial reduction in its interaction with nucleosomes compared to naked DNA, also in a lesion orientation-dependent manner, reinforcing the concept that reduction in APE1 activity on nucleosomes is due to occlusion from its abasic DNA substrate by the histones. These results suggest that APE1 activity in nucleosomes, like BER glycosylases, is primarily regulated by its chance interactions with transiently exposed lesions. Copyright © 2014 Elsevier B.V. All rights reserved.HinzJohn MJMSchool of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, United States. Electronic address: jmhinz@wsu.edu.engES004106ESNIEHS NIH HHSUnited StatesES02095ESNIEHS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20140606
NetherlandsMutat Res04007630027-51070Nucleosomes9007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsBase SequenceBinding SitesChickensDNAchemistrygeneticsDNA DamagephysiologyDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismHumansNucleic Acid ConformationNucleosomesgeneticsmetabolismProtein BindingSubstrate SpecificityAPE1 endonucleaseDNA damageHistoneNucleosomeTetrahydrofuran
201312202014052020140530201548602015486020157360ppublish25847267S0027-5107(14)00103-110.1016/j.mrfmmm.2014.05.008
257900582016010820150421
1099-08443332015AprCell biochemistry and functionCell Biochem. Funct.A review on protein-protein interaction network of APE1/Ref-1 and its associated biological functions.101-1210.1002/cbf.3100Apurinic/apyrimidinic endonuclease 1 (APE1) is a classic example of functionally variable protein. Besides its well-known role in (i) DNA repair of oxidative base damage, APE1 also plays a critical role in (ii) redox regulation of transcription factors controlling gene expression for cell survival pathways, for which it is also known as redox effector factor 1 (Ref-1), and recent evidences advocates for (iii) coordinated control of other non-canonical protein-protein interaction(s) responsible for significant biological functions in mammalian cells. The diverse functions of APE1 can be ascribed to its ability to interact with different protein partners, owing to the attainment of unfolded domains during evolution. Association of dysregulation of APE1 with various human pathologies, such as cancer, cardiovascular diseases and neurodegeneration, is attributable to its multifunctional nature, and this makes APE1 a potential therapeutic target. This review covers the important aspects of APE1 in terms of its significant protein-protein interaction(s), and this knowledge is required to understand the onset and development of human pathologies and to design or improve the strategies to target such interactions for treatment and management of various human diseases.Copyright © 2015 John Wiley & Sons, Ltd.ThakurSSCenter for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, India.DhimanMMTellGGManthaA KAKengJournal ArticleResearch Support, Non-U.S. Gov'tReview20150319
EnglandCell Biochem Funct83058740263-64840Nerve Tissue ProteinsEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 6.5.1.-DNA Repair EnzymesIMDNA Repair EnzymeschemistrymetabolismDNA-(Apurinic or Apyrimidinic Site) LyasechemistrymetabolismHumansNerve Tissue ProteinschemistrymetabolismOxidative StressProtein Interaction MapsProtein Processing, Post-TranslationalAPE1/Ref-1BER-pathwayDNA repairoxidative stressredox regulation
20141115201502102015022420153206020153206020161960ppublish2579005810.1002/cbf.3100
257338102016051720171116
1177-888192015Drug design, development and therapyDrug Des Devel TherUpregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer.901-910.2147/DDDT.S75152Gastric cancer is a fatal malignancy with a rising incidence rate. Effective methods for early diagnosis, monitoring metastasis, and prognosis are currently unavailable for gastric cancer. In this study, we examined the association of programmed death ligand-1 (PD-L1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with the prognosis of gastric cancer.The expressions of PD-L1 and APE1 were detected by immunohistochemistry in 107 cases of human gastric carcinoma. The correlation of PD-L1 and APE1 expression with the clinicopathologic features of gastric carcinoma was analyzed by SPSS version 19.0.The positive expression rates of PD-L1 and APE1 in gastric cancer tissues were 50.5% (54/107) and 86.9% (93/107), respectively. PD-L1 and APE1 positive expressions were significantly associated with depth of invasion, lymph node metastasis, pathological type, overall survival, and higher T stage. Furthermore, the expression of PD-L1 in highly differentiated gastric cancers was higher than that in poorly differentiated cancers (P=0.008). Moreover, the expression of APE1 and PD-L1 in gastric cancers was positively correlated (r=0.336, P<0.01). Multivariate analysis showed that the depth of invasion was a significant prognostic factor (risk ratio 19.91; P=0.000), but there was no significant relationship with PD-L1, APE1, prognosis, and other characteristics.The deregulation of PD-L1 and APE1 might contribute to the development and the poor prognosis of gastric cancer. Our findings suggest that high expression of PD-L1 and APE1 is a risk factor of gastric cancer and a new biomarker to predict the prognosis of gastric cancer. Furthermore, our findings suggest that targeting the PD-L1 and APE1 signaling pathways may be a new strategy for cancer immune therapy and targeted therapy for gastric cancer, especially in patients with deep invasion and lymph node metastasis.QingYiYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.LiQingQCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.RenTaoTCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.XiaWeiWCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.PengYuYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.LiuGao-LeiGLUrological Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.LuoHaoHCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.YangYu-XinYXCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.DaiXiao-YanXYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.ZhouShu-FengSFDepartment of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.WangDongDCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.engJournal ArticleResearch Support, Non-U.S. Gov't20150216
New ZealandDrug Des Devel Ther1014757451177-88810B7-H1 Antigen0CD274 protein, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBlood. 2007 Mar 1;109(5):1917-2217053053Nat Med. 1999 Dec;5(12):1365-910581077Arch Dermatol Res. 2014 Aug;306(6):511-924615548Am J Respir Cell Mol Biol. 2001 Dec;25(6):664-711726389Nat Rev Immunol. 2002 Feb;2(2):116-2611910893Nat Med. 2002 Aug;8(8):793-80012091876Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12293-712218188J Immunol. 2002 Nov 15;169(10):5538-4512421930J Immunol. 2003 Apr 1;170(7):3637-4412646628J Mol Med (Berl). 2003 May;81(5):281-712721664Gastric Cancer. 2002;5 Suppl 1:5-1112772880J Clin Invest. 2003 Oct;112(7):989-9814523036Cancer Res. 2003 Oct 1;63(19):6501-514559843Cancer Res. 2007 Mar 1;67(5):2141-917332344Int J Cancer. 2007 Aug 15;121(4):751-817415709Mol Immunol. 2008 Jan;45(1):76-8617599408Cancer Sci. 2007 Dec;98(12):1993-200117892509Mol Immunol. 2008 Mar;45(5):1470-617920123Cancer Lett. 2008 Sep 8;268(1):98-10918486325Blood. 2008 Sep 1;112(5):2149-5518577709Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Autoimmun Rev. 2010 Jun;9(8):583-720433954Environ Mol Mutagen. 2010 Jun;51(5):417-2620544882Dis Markers. 2010;29(1):47-5320826917Cancer Sci. 2011 Jul;102(7):1272-8021466615PLoS One. 2011;6(12):e2897122205985J Immunol. 2012 Jun 1;188(11):5227-3722508931PLoS One. 2012;7(10):e4746223094050World J Gastroenterol. 2014 Feb 21;20(7):1657-6624587645Cancer Treat Rev. 2014 Jul;40(6):770-8024656976J Cancer Res Clin Oncol. 2014 Jul;140(7):1117-2424752338J Chin Med Assoc. 2014 Jul;77(7):345-5324907022Oncology. 2000 Feb;58(2):126-3610705239Cancer Res. 2003 Nov 1;63(21):7462-714612546Clin Cancer Res. 2004 Aug 1;10(15):5094-10015297412EMBO J. 1992 Feb;11(2):653-651537340Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17174-915569934Clin Cancer Res. 2005 Apr 15;11(8):2947-5315837746Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Cancer Res. 2006 Apr 1;66(7):3381-516585157Neoplasia. 2006 Mar;8(3):190-816611412J Exp Med. 2006 Apr 17;203(4):883-9516606670Acta Histochem. 2006;108(1):19-2416530813AdultAgedAged, 80 and overB7-H1 AntigenbiosynthesismetabolismCarcinogenesismetabolismDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesismetabolismFemaleHumansImmunohistochemistryMaleMiddle AgedPrognosisStomach NeoplasmsdiagnosisgeneticsmetabolismpathologyUp-Regulationgastric carcinomaimmunohistochemistrypotential targetsprognostic
2015346020153460201651860epublish2573381010.2147/DDDT.S75152dddt-9-901PMC4338255
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1098-55493592015MayMolecular and cellular biologyMol. Cell. Biol.Interaction with OGG1 is required for efficient recruitment of XRCC1 to base excision repair and maintenance of genetic stability after exposure to oxidative stress.1648-5810.1128/MCB.00134-15XRCC1 is an essential protein required for the maintenance of genomic stability through its implication in DNA repair. The main function of XRCC1 is associated with its role in the single-strand break (SSB) and base excision repair (BER) pathways that share several enzymatic steps. We show here that the polymorphic XRCC1 variant R194W presents a defect in its interaction with the DNA glycosylase OGG1 after oxidative stress. While proficient for single-strand break repair (SSBR), this variant does not colocalize with OGG1, reflecting a defect in its involvement in BER. Consistent with a role of XRCC1 in the coordination of the BER pathway, induction of oxidative base damage in XRCC1-deficient cells complemented with the R194W variant results in increased genetic instability as revealed by the accumulation of micronuclei. These data identify a specific molecular role for the XRCC1-OGG1 interaction in BER and provide a model for the effects of the R194W variant identified in molecular cancer epidemiology studies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.CampalansAnnaACEA, Institute of Cellular and Molecular Radiobiology, Fontenay-aux-Roses, France INSERM, U967, Fontenay-aux-Roses, France Université Paris Diderot, U967, Fontenay-aux-Roses, France Université Paris Sud, U967, Fontenay-aux-Roses, France anna.campalans@cea.fr pablo.radicella@cea.fr.MoritzEvaEInstitute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany.KortulewskiThierryTCEA, Institute of Cellular and Molecular Radiobiology, Fontenay-aux-Roses, France INSERM, U967, Fontenay-aux-Roses, France Université Paris Diderot, U967, Fontenay-aux-Roses, France Université Paris Sud, U967, Fontenay-aux-Roses, France.BiardDenisDCEA, DSV, iMETI, SEPIA, Fontenay-aux-Roses, France.EpeBerndBInstitute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany.RadicellaJ PabloJPCEA, Institute of Cellular and Molecular Radiobiology, Fontenay-aux-Roses, France INSERM, U967, Fontenay-aux-Roses, France Université Paris Diderot, U967, Fontenay-aux-Roses, France Université Paris Sud, U967, Fontenay-aux-Roses, France anna.campalans@cea.fr pablo.radicella@cea.fr.engJournal ArticleResearch Support, Non-U.S. Gov't20150302
United StatesMol Cell Biol81090870270-73060DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMJ Microsc. 2006 Dec;224(Pt 3):213-3217210054Annu Rev Genet. 2004;38:445-7615568983Biochem Soc Trans. 2003 Feb;31(Pt 1):247-5112546695Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039EMBO J. 2001 Nov 15;20(22):6530-911707423DNA Repair (Amst). 2007 Feb 4;6(2):254-6417118717Nucleic Acids Res. 2004;32(8):2550-515141024Nucleic Acids Res. 2010 Aug;38(15):5023-3520385586Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-59223305Biochemistry. 1976 Oct 19;15(21):4629-379979Nucleic Acids Res. 2013 Mar 1;41(5):3115-2923355608J Biol Chem. 2000 Oct 20;275(42):32635-4110924509Nat Struct Biol. 2000 Mar;7(3):176-810700268J Cell Biol. 2005 Aug 1;170(3):341-716061690DNA Repair (Amst). 2003 Sep 18;2(9):955-6912967653Mutat Res. 2005 Apr 4;582(1-2):135-4515781218Dev Biol. 1999 Apr 15;208(2):513-2910191063Nucleic Acids Res. 1996 Nov 15;24(22):4387-948948628Mech Ageing Dev. 2003 Jan;124(1):27-3212618003Nucleic Acids Res. 2005;33(8):2512-2015867196Mol Cell Biol. 2003 Jun;23(11):3974-8112748298FEBS Lett. 1994 Mar 14;341(1):59-648137923J Cell Sci. 2007 Jan 1;120(Pt 1):23-3217148573Mutat Res. 2008 Mar-Apr;658(3):215-3318037339Curr Biol. 1998 Jul 16;8(15):877-809705932Trends Cell Biol. 2009 Nov;19(11):617-2919819145DNA Repair (Amst). 2005 Jul 12;4(7):826-3515927541FEBS Lett. 1995 Jan 16;358(1):1-37821417FEBS Lett. 1992 Sep 7;309(2):193-81324197Carcinogenesis. 2000 Jun;21(6):1135-4110837001Tumour Biol. 2014 Nov;35(11):10665-7625062722Mol Cell Biol. 1998 Jun;18(6):3563-719584196Nucleic Acids Res. 2011 Apr;39(8):3166-7521183466Nucleic Acids Res. 2005;33(1):298-30615647512Environ Mol Mutagen. 2007 Jul;48(6):491-50017603793BMC Mol Biol. 2007;8:8117880707Nucleic Acids Res. 2000 May 15;28(10):2049-5910773072Mutat Res. 2000 Feb 16;459(1):1-1810677679EMBO J. 1996 Dec 2;15(23):6662-708978692Tumour Biol. 2014 Nov;35(11):10677-9725064613Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13738-4315365186J Biol Chem. 1997 Sep 19;272(38):23970-59295348Mol Cell Biol. 1994 Jan;14(1):68-768264637Mol Cancer Res. 2005 Sep;3(9):519-2916179499Environ Mol Mutagen. 2011 Oct;52(8):623-3521786338Carcinogenesis. 1997 Nov;18(11):2225-319395225Nat Struct Biol. 2000 Dec;7(12):1087-911101884J Biol Chem. 2003 Nov 7;278(45):44068-7412933815Nucleic Acids Res. 1995 Dec 11;23(23):4836-438532526Biochemistry. 1997 Apr 29;36(17):5207-119136882Nucleic Acids Res. 2003 Oct 1;31(19):5526-3314500814Nucleic Acids Res. 2010 May;38(9):2878-9020071746Mol Cell. 2001 Jul;8(1):213-2411511374EMBO J. 2008 Dec 3;27(23):3140-5018971944J Cell Biol. 2014 Jul 7;206(1):29-4324982429Mol Cell Biol. 2000 Jan;20(2):735-4010611252Mutat Res. 1999 Mar 8;424(1-2):9-2110064846AnimalsCHO CellsCell LineCricetulusDNA GlycosylasesanalysismetabolismDNA RepairDNA-Binding ProteinsanalysisgeneticsmetabolismGene DeletionHumansOxidative StressPolymorphism, Single NucleotideProtein Interaction MapsX-ray Repair Cross Complementing Protein 1
2015020520150225201534602015346020157460ppublish25733688MCB.00134-1510.1128/MCB.00134-15PMC4387214
257310272015041720171116
0016-67585082014AugGenetikaGenetika[The polymorphism of DNA repair genes XPD, XRCC1, OGG1, and ERCC6, life expectancy, and the inclination to smoke].975-85The polymorphism of excision repair genes XPD Asp312Asn, XRCC1 Arg399Gln, OGG1 Ser326Cys, and ERCC6 Met1097Val was analyzed by PCR-RFLP in 370 representatives of the Belarusian population of average, old, and elderly ages. Correlation analysis showed that the frequencies of wild-type homozygous combinations significantly increase with age in the group of subjects over 70 years old in the case of the interaction of two genes, XPD 312 and XRCC1399, or three genes, XPD312, XRCC1399, and ERCC6 1097. In a subgroup of the long-lived, this relationship is manifested in case of a pairwise interaction of gene XPD 312 with XRCC1 399 or ERCC6 1097, as well as an interaction of three genes, XPD 312, XRCC1 399, and ERCC6 1097. The data suggest that the optimum activity of repair processes may favor longevity. It is shown that the frequency of the Asp/Asp genotype is reduced, and the frequency of the Asn allele of the XPD 312 gene is increased in the subgroup of smokers as compared with nonsmokers, which apparently indicates an association of this gene polymorphism with an inclination to smoke. The problem requires further study.RomaniukO POPNikitchenkoN VNVSavinaN VNVKuzhirT DTDGoncharovaR IRIrusJournal Article
Russia (Federation)Genetika00473540016-67580DNA-Binding Proteins0Poly-ADP-Ribose Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.-DNA HelicasesEC 3.6.4.12ERCC6 protein, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanEC 6.5.1.-DNA Repair EnzymesIMAdultAgedAged, 80 and overDNA GlycosylasesgeneticsDNA HelicasesgeneticsDNA RepairgeneticsDNA Repair EnzymesgeneticsDNA-Binding ProteinsgeneticsFemaleGenetic Predisposition to DiseaseHumansLongevitygeneticsMaleMiddle AgedPoly-ADP-Ribose Binding ProteinsPolymorphism, GeneticSmokinggeneticsX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
2015346020153460201541860ppublish25731027
257114992016030820150617
1464-38043042015JulMutagenesisMutagenesisWood dust exposure induces cell transformation through EGFR-mediated OGG1 inhibition.487-9710.1093/mutage/gev007A high risk of neoplastic transformation of nasal and paranasal sinuses mucosa is related to the occupational exposure to wood dust. However, the role of occupational exposures in the aetiology of the airway cancers remains largely unknown. Here, an in vitro model was performed to investigate the carcinogenic effect of wood dusts. Human bronchial epithelial cells were incubated with hard and soft wood dusts and the DNA damage and response to DNA damage evaluated. Wood dust exposure induced accumulation of oxidised DNA bases, which was associated with a delay in DNA repair activity. By exposing cells to wood dust at a prolonged time, wood dust-initiated cells were obtained. Initiated-cells were able to form colonies in soft agar, and to induce blood vessel formation. These cells showed extensive autophagy, reduced DNA repair, which was associated with reduced OGG1 expression and oxidised DNA base accumulation. These events were found related to the activation of EGFR/AKT/mTOR pathway, through phosphorylation and subsequent inactivation of tuberin. The persistence in the tissue of wood dusts, their repetitious binding with EGFR may continually trigger the activation switch, leading to chronic down-regulation of genes involved in DNA repair, leading to cell transformation and proliferation. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.StaffolaniSaraSDepartment of Clinical and Molecular Science.ManzellaNicolaNDepartment of Clinical and Molecular Science.StrafellaElisabettaEDepartment of Clinical and Molecular Science.NocchiLindaLDepartment of Clinical and Molecular Science.BracciMassimoMDepartment of Clinical and Molecular Science.CiarapicaVeronicaVDepartment of Clinical and Molecular Science.AmatiMonicaMDepartment of Clinical and Molecular Science.RubiniCorradoCDepartment of Biomedical Sciences and Public Health.ReMassimoMDepartment of Clinical Sciences, Polytechnic University of Marche, via Tronto, 10A, 60020 Ancona, Italy.PugnaloniArmandaADepartment of Clinical and Molecular Science.PasquiniErnestoEUOC-ORL Budrio-Metropolitan Hospital Via Benni, 44, Budrio 40054, Bologna, Italy and.TarchiniPaoloPDepartment of E.N.T. Polyclinic 'Sant'Orsola Malpighi' Otolaryngology Clinic, University of Bologna Via Pietro Albertoni, 15, 40138, Bologna, Italy.ValentinoMatteoMDepartment of Clinical and Molecular Science.TomasettiMarcoMDepartment of Clinical and Molecular Science, m.tomasetti@univpm.it.SantarelliLoryLDepartment of Clinical and Molecular Science.engJournal ArticleResearch Support, Non-U.S. Gov't20150223
EnglandMutagenesis87078120267-83570Dust0RNA, Messenger0Tumor Suppressor Proteins4JG2LF96VFtuberous sclerosis complex 2 proteinEC 2.7.1.1MTOR protein, humanEC 2.7.1.1TOR Serine-Threonine KinasesEC 2.7.10.1EGFR protein, humanEC 2.7.10.1Receptor, Epidermal Growth FactorEC 2.7.11.1AKT1 protein, humanEC 2.7.11.1Proto-Oncogene Proteins c-aktEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMApoptosisBlotting, WesternBronchimetabolismpathologyCell ProliferationCell Transformation, NeoplasticgeneticsmetabolismpathologyCells, CulturedDNA Glycosylasesantagonists & inhibitorsgeneticsmetabolismDustEpithelial CellsmetabolismpathologyHumansImmunoenzyme TechniquesNeovascularization, PhysiologicOccupational Exposureadverse effectsPhosphorylationProto-Oncogene Proteins c-aktgeneticsmetabolismRNA, MessengergeneticsReal-Time Polymerase Chain ReactionReceptor, Epidermal Growth FactorgeneticsmetabolismReverse Transcriptase Polymerase Chain ReactionTOR Serine-Threonine KinasesgeneticsmetabolismTumor Suppressor ProteinsgeneticsmetabolismWoodchemistry
201522660201522660201631060ppublish25711499gev00710.1093/mutage/gev007
256725882017011820170220
2005-92564742015OctCancer research and treatment : official journal of Korean Cancer AssociationCancer Res TreatAPE1/Ref-1 as a Serological Biomarker for the Detection of Bladder Cancer.823-3310.4143/crt.2014.074Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that shows elevated expression in a number of cancers. We attempted to determine whether serum APE1/Ref-1 is elevated in patients with bladder cancer.Serum APE1/Ref-1 levels were determined using enzyme-linked immunosorbent assay in serum from patients with bladder cancer who had not received chemotherapy or radiotherapy (n=51) and non-tumor controls (n=55). The area under the receiver operating characteristic area under the curve was applied to determine the correlation between clinical factors and the serum levels of APE1/Ref-1.Serum levels of APE1/Ref-1 in bladder cancer patients were significantly elevated compared to those of the control group (3.548 ± 0.333 ng/100 μL [n=51] for bladder cancer vs. 1.547 ± 0.319 ng/100 μL [n=55] for the control group), with a sensitivity and specificity of 93% and 59%, respectively. Serum APE1/Ref-1 levels are associated with tumor stage, grade, muscle invasion, and recurrence.Serum APE1/Ref-1 might be useful as a potential serologic biomarker for bladder cancer.ShinJu HyunJHDepartment of Urology, Chungnam National University Hospital, Daejeon, Korea.ChoiSungaSInfection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.LeeYu RanYRInfection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.ParkMyoung SooMSInfection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.NaYong GilYGDepartment of Urology, Chungnam National University Hospital, Daejeon, Korea.IraniKaikobadKDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.LeeSang DoSDInfection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.ParkJin BongJBInfection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.KimJin ManJMDepartment of Pathology, Chungnam National University School of Medicine, Daejeon, Korea.LimJae SungJSDepartment of Urology, Chungnam National University Hospital, Daejeon, Korea.JeonByeong HwaBHInfection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.engJournal ArticleResearch Support, Non-U.S. Gov't20150102
Korea (South)Cancer Res Treat1011551371598-29980Biomarkers, TumorEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBJU Int. 2012 Sep;110(5):699-70822313585CA Cancer J Clin. 2012 Jul-Aug;62(4):220-4122700443Biochem Biophys Res Commun. 2013 Jun 14;435(4):621-623685156JAMA. 2005 Feb 16;293(7):810-615713770Cell. 2010 Mar 19;140(6):883-9920303878Biochem Biophys Res Commun. 2013 Jun 7;435(3):403-723665318Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084J Urol. 2000 Apr;163(4):1124-910737480Verh Dtsch Ges Pathol. 2002;86:57-6612647352Cancer Epidemiol. 2011 Apr;35(2):126-3120952269Am J Clin Pathol. 2007 Jun;127(6):946-5317509992Nucleic Acids Res. 2007;35(8):2522-3217403694Acta Oncol. 2010 Nov;49(8):1283-720843171Int J Oncol. 2009 Nov;35(5):1069-7919787261Bull Am Coll Surg. 2002 Jul;87(7):13-517387902Am J Clin Pathol. 2009 Nov;132(5):785-9319846822Biom J. 2005 Aug;47(4):458-7216161804Int J Urol. 2009 Mar;16(3):234-4319298346PLoS One. 2013;8(3):e5800123472128Urology. 2010 Aug;76(2):514.e6-1120346489Oncol Rep. 2002 Jan-Feb;9(1):11-711748448Biosci Rep. 2012 Feb;32(1):1-1521981137Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766Cancer Res Treat. 2011 Mar;43(1):1-1121509157AgedBiomarkers, TumorbloodDNA-(Apurinic or Apyrimidinic Site) LyasebloodgeneticsmetabolismFemaleHumansMaleMiddle AgedSensitivity and SpecificitySerologic TestsUrinary Bladder NeoplasmsblooddiagnosisApurinic/apyrimidinic endonuclease 1/redox factor-1Biological markersEnzyme-linked immunosorbent assayUrinary bladder neoplasms
2014032020140731201521360201521360201711960ppublish2567258810.4143/crt.2014.074crt.2014.074PMC4614188
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1559-131X3222015FebMedical oncology (Northwood, London, England)Med. Oncol.A systematic review and meta-analysis of the association between OGG1 Ser326Cys polymorphism and cancers.47210.1007/s12032-014-0472-zThe oxyguanine glycosylase 1 (OGG1) gene has an important role in DNA repair, and the polymorphism of the gene may alter cancer susceptibility. This study aims to examine the association between the OGG1 Ser326Cys polymorphism and cancer risk based on meta-analysis. Relevant studies were identified through a search of PubMed and Weipu databases, and a total of 109 studies including 111 comparisons containing 34,041 cases and 42,730 controls were enrolled. Overall, significant association was observed between OGG1 Ser326Cys polymorphism and cancer risk in all genetic models except for heterozygote model (Cys/Cys + Cys/Ser vs Ser/Ser: OR 1.071, 95 % CI 1.019-1.125; Cys/Cys vs Cys/Ser + Ser/Ser: OR 1.159, 95 % CI 1.076-1.248; Cys/Cys vs Ser/Ser: OR 1.202, 95 % CI 1.105-1.308). In stratified analysis by cancer type, significantly increased cancer risk was observed in digestive system cancer, head and neck cancer and lung cancer. For gynecologic cancer, significantly increased cancer risk was also observed in homozygote model (OR 1.974, 95 % CI 1.254-3.107). In addition, in stratified analysis by ethnicities, increased cancer risk was found in Asians (Cys/Cys vs Cys/Ser + Ser/Ser: OR 1.195, 95 % CI 1.088-1.313; Cys/Cys + Cys/Ser vs Ser/Ser: OR 1.115, 95 % CI 1.045-1.190; Cys/Cys vs Ser/Ser: OR 1.273, 95 % CI 1.149-1.410). The OGG1 Ser326Cys polymorphism may be a risk factor for cancers of lung, digestive system and head and neck. ZhouPing-TingPTDepartment of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China.LiBoBJiJunJWangMeng-MengMMGaoChun-FangCFengJournal ArticleMeta-AnalysisReview20150115
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1):2471-414634453Mutat Res. 2009 Nov-Dec;680(1-2):56-6319815090Urology. 2005 Jan;65(1):70-515667866Mech Ageing Dev. 2012 Apr;133(4):127-3222019847Carcinogenesis. 2004 Nov;25(11):2177-8115284179Nature. 2001 May 17;411(6835):366-7411357144DNA GlycosylasesgeneticsGenetic Predisposition to DiseasegeneticsGenotypeHumansNeoplasmsgeneticsPolymorphism, Single Nucleotide
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1880-7046372015Genes and environment : the official journal of the Japanese Environmental Mutagen SocietyGenes EnvironAn active alternative splicing isoform of human mitochondrial 8-oxoguanine DNA glycosylase (OGG1).2110.1186/s41021-015-0021-9Eight alternatively spliced isoforms of human 8-oxoguanine DNA glycosylase (OGG1) (OGG1-1a, -1b, -1c, -2a, -2b, -2c, -2d and -2e) are registered at the National Center for Biotechnology Information (NCBI). OGG1-1a is present in the nucleus, whereas the other seven isoforms are present in the mitochondria. Recombinant OGG1-1a has been purified and enzyme kinetics determined. OGG1(s) in mitochondria have not been fully characterized biochemically until recently. The major mitochondrial OGG1 isoform, OGG1-2a (also named β-OGG1), has also been expressed and purified; however, its activity is unresolved. Recently, we purified recombinant mitochondrial OGG1-1b and found that it was an active OGG1 enzyme. We reported its enzyme kinetics and compared the results with those of OGG1-1a. The reaction rate constant of OGG1-1b 8-oxoG glycosylase activity (k g) was 8-oxoG:C > > 8-oxoG:T > > 8-oxoG:G > 8-oxoG:A and was similar to that of OGG1-1a under single-turnover conditions ([E] > [S]). Both OGG1-1b and OGG1-1a showed high specificity towards 8-oxoG:C. The reaction rate constant of OGG1-1b N-glycosylase/DNA lyase activity (k gl) was 8-oxoG:C > 8-oxoG:T ≃ 8-oxoG:G > > 8-oxoG:A and that of OGG1-1a was 8-oxoG:C > 8-oxoG:T, 8-oxoG:G and 8-oxoG:A. The k gl of OGG1-1b and OGG1-1a is one order of magnitude lower than the corresponding k g value. OGG1-1b showed an especially low k gl towards 8-oxoG:A. Comparable expression of OGG1-1a and OGG1-1b was detected by RT-PCR in normal human lung tissue and lung cell lines. These results suggest that OGG1-1b is associated with 8-oxoG cleavage in human lung mitochondria and that the mechanism of this repair is similar to that of nuclear OGG1-1a. Currently, the other five mitochondrial OGG1 isoforms have not been isolated. I summarize information on OGG1 isoform mRNAs, coding DNA sequences and amino acid sequences that are archived by the National Center for Biotechnology Information. FurihataChieCSchool of Science and Engineering, Aoyama Gakuin University, Sagamihara, Kanagawa 252-5258 Japan ; Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Setagayaku, Tokyo 158-8501 Japan.engJournal ArticleReview20151001
EnglandGenes Environ1012853471880-7046Nucleic Acids Res. 2004 Oct 19;32(18):5596-60815494448FEBS Lett. 2013 Sep 17;587(18):3129-3423954288Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8016-209223306Mutat Res. 2001 Aug 9;486(3):207-1611459633J Mol Biol. 2002 Mar 22;317(2):171-711902834Mol Biol Cell. 1999 May;10(5):1637-5210233168Nucleic Acids Res. 1998 Jun 15;26(12):2917-229611236J Am Chem Soc. 2009 Jul 15;131(27):9506-1519537786Oncogene. 1998 Jun 25;16(25):3219-259681819J Biol Chem. 2013 Oct 4;288(40):28936-4723955443DNA Cell Biol. 2009 Nov;28(11):579-8819630534Gan. 1984 Dec;75(12):1037-96526216J Biochem Mol Toxicol. 2015 Feb;29(2):49-5625196052Cancer Res. 1997 Jun 1;57(11):2151-69187114Environ Mol Mutagen. 2013 Jan;54(1):54-6423055259Free Radic Biol Med. 2009 Sep 15;47(6):750-919524665J Am Chem Soc. 2012 Jan 25;134(3):1653-6122175854Human 8-oxoguanine DNA glycosylaseMitochondrial OGG1OGG1OGG1-1aOGG1-1bOGG1-2a
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1568-7856262015FebDNA repairDNA Repair (Amst.)Inactivation of a common OGG1 variant by TNF-alpha in mammalian cells.15-2210.1016/j.dnarep.2014.11.007S1568-7864(14)00282-1Reactive oxygen species threaten genomic integrity by inducing oxidative DNA damage. One common form of oxidative DNA damage is the mutagenic lesion 8-oxoguanine (8-oxodG). One driver of oxidative stress that can induce 8-oxodG is inflammation, which can be initiated by the cytokine tumor necrosis factor alpha (TNF-α). Oxidative DNA damage is primarily repaired by the base excision repair pathway, initiated by glycosylases targeting specific DNA lesions. 8-oxodG is excised by 8-oxoguanine glycosylase 1 (OGG1). A common Ogg1 allelic variant is S326C-Ogg1, prevalent in Asian and Caucasian populations. S326C-Ogg1 is associated with various forms of cancer, and is inactivated by oxidation. However, whether oxidative stress caused by inflammatory cytokines compromises OGG1 variant repair activity remains unknown. We addressed whether TNF-α causes oxidative stress that both induces DNA damage and inactivates S326C-OGG1 via cysteine 326 oxidation. In mouse embryonic fibroblasts, we found that S326C-OGG1 was inactivated only after exposure to H2O2 or TNF-α. Treatment with the antioxidant N-acetylcysteine prior to oxidative stress rescued S326C-OGG1 activity, demonstrated by in vitro and cellular repair assays. In contrast, S326C-OGG1 activity was unaffected by potassium bromate, which induces oxidative DNA damage without causing oxidative stress, and presumably cysteine oxidation. This study reveals that Cys326 is vulnerable to oxidation that inactivates S326C-OGG1. Physiologically relevant levels of TNF-α simultaneously induce 8-oxodG and inactivate S326C-OGG1. These results suggest a mechanism that could contribute to increased risk of cancer among S326C-Ogg1 homozygous individuals. Copyright © 2014 Elsevier B.V. All rights reserved.MorreallJordanJDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA; Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA, 30322, USA.LimposeKristinKDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA; Graduate Program in Cancer Biology, Emory University, Atlanta, GA, 30322, USA.SheppardClaytonCDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA.KowYoke WahYWDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA.WernerEricaEDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.DoetschPaul WPWDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA; Emory Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA; Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA. Electronic address: medpwd@emory.edu.engR01 CA120288CANCI NIH HHSUnited StatesCA120288CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20141204
NetherlandsDNA Repair (Amst)1011391381568-78560Reactive Oxygen Species0Tumor Necrosis Factor-alphaBBX060AN9VHydrogen PeroxideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMBr J Cancer. 1997;76(2):206-109231920J Biol Chem. 1998 May 1;273(18):11069-749556591Free Radic Biol Med. 2013 Oct;63:401-923726996FEBS Lett. 2013 Sep 17;587(18):3129-3423954288J Biol Chem. 2009 Nov 27;284(48):33400-819679659J Cell Sci. 2010 Aug 15;123(Pt 16):2834-4320663918Cell Death Differ. 2010 Sep;17(9):1420-3420203691J Hepatol. 2010 Nov;53(5):797-80420801537Free Radic Biol Med. 2010 Dec 1;49(11):1603-1620840865Cell. 2011 Mar 4;144(5):646-7421376230Toxicol Sci. 2011 Oct;123(2):471-921778470Free Radic Biol Med. 2012 Jan 1;52(1):118-2522019439Antioxid Redox Signal. 2012 Apr 1;16(7):649-5721967570Blood. 2012 Feb 23;119(8):e45-5622096246Mutagenesis. 2012 Jul;27(4):501-1022451681Environ Toxicol. 2012 Oct;27(10):590-721254323Carcinogenesis. 2014 Jun;35(6):1426-3324632493Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Mol Carcinog. 1999 Dec;26(4):254-6010569802Nature. 2000 Feb 24;403(6772):859-6610706276Nucleic Acids Res. 2000 Jul 15;28(14):2672-810908322Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2698-70211226302Chem Res Toxicol. 2001 Jun;14(6):678-8511409938Carcinogenesis. 2002 Jul;23(7):1229-3412117782Eur J Immunol. 2003 Aug;33(8):2297-30612884305J Natl Cancer Inst. 2003 Sep 3;95(17):1312-912953085Cell. 2004 Jan 9;116(1):99-10714718170Mutagenesis. 2004 May;19(3):169-8515123782Environ Health Perspect. 1979 Jun;30:185-9446450J Immunol Methods. 1983 Dec 16;65(1-2):55-636606682Free Radic Biol Med. 1989;6(6):593-72546864Cancer Res. 1993 May 1;53(9):1982-58481899Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915-228367443Mutat Res. 1994 Mar 1;305(2):253-647510036Environ Health Perspect. 1994 Dec;102 Suppl 10:5-127705305Annu Rev Immunol. 1997;15:351-699143692Curr Biol. 1997 Jun 1;7(6):397-4079197244PLoS One. 2013;8(11):e8116224260552DNA Repair (Amst). 2014 Feb;14:17-2624382305Biochem Biophys Res Commun. 2014 Apr 25;447(1):12-824680828Oncogene. 1998 Jun 25;16(25):3219-259681819Nucleic Acids Res. 1999 Oct 15;27(20):4001-710497264Carcinogenesis. 2004 Nov;25(11):2177-8115284179Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W230-215980459Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Nucleic Acids Res. 2006;34(5):1620-3216549874Biol Chem. 2006 Apr;387(4):373-916606334Genome Res. 2006 May;16(5):567-7516651663Mutagenesis. 2006 May;21(3):185-9016597659FASEB J. 2006 Aug;20(10):1589-9816873882DNA Repair (Amst). 2006 Nov 8;5(11):1337-4516861056Cell Signal. 2007 Jul;19(7):1419-3317317104J Clin Invest. 2007 Nov;117(11):3283-9517960249Exp Gerontol. 2008 Apr;43(4):353-918289818Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3081-918990748Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18877-8219020090Cancer Res. 2009 Apr 15;69(8):3642-919351836J Agromedicine. 2009;14(2):206-1419437279N Engl J Med. 2009 Jun 25;360(26):2719-2919516027FEBS J. 2009 Sep;276(18):5149-6219674107J Clin Invest. 2009 Oct;119(10):3011-2319741298AnimalsCell Line, TransformedDNA GlycosylasesgeneticsmetabolismDNA Repairdrug effectsgeneticsGene Knockdown TechniquesGenetic Predisposition to DiseaseHomozygoteHumansHydrogen PeroxidepharmacologyMiceNeoplasmsgeneticsOxidation-ReductionOxidative StressPolymorphism, Single NucleotideReactive Oxygen SpeciesmetabolismTumor Necrosis Factor-alphapharmacology8-oxodGCys326-Ogg1H(2)O(2)ROSS326C-Ogg1TNF-α
20141013201411202014112520141224602014122460201571860ppublish25534136S1568-7864(14)00282-110.1016/j.dnarep.2014.11.007PMC4308426NIHMS651201
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1932-62039122014PloS onePLoS ONEPARP-1 expression is increased in colon adenoma and carcinoma and correlates with OGG1.e11555810.1371/journal.pone.0115558The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo) level in leukocyte DNA of healthy controls (138 individuals), patients with benign adenomas (AD, 137 individuals) and with malignant carcinomas (CRC, 169 individuals) revealed a significant increase in the level of 8-oxodGuo in leukocyte DNA of AD and CRC patients in comparison to controls. The counteracting mechanism is base excision repair, in which OGG1 and PARP-1 play a key role. We investigated the level of PARP-1 and OGG1 mRNA and protein in diseased and marginal, normal tissues taken from AD and CRC patients and in leukocytes taken from the patients as well as from healthy subjects. In colon tumors the PARP-1 mRNA level was higher than in unaffected colon tissue and in polyp tissues. A high positive correlation was found between PARP-1 and OGG1 mRNA levels in all investigated tissues. This suggests reciprocal influence of PARP-1 and OGG1 on their expression and stability, and may contribute to progression of colon cancer. PARP-1 and OGG1 proteins level was several fold higher in polyps and CRC in comparison to normal colon tissues. Individuals bearing the Cys326Cys genotype of OGG1 were characterized by higher PARP-1 protein level in diseased tissues than the Ser326Cys and Ser326Ser genotypes. Aforementioned result may suggest that the diseased cells with polymorphic OGG1 recruit more PARP protein, which is necessary to remove 8-oxodGuo. Thus, patients with decreased activity of OGG1/polymorphism of the OGG1 gene and higher 8-oxodGuo level may be more susceptible to treatment with PARP-1 inhibitors. DziamanTomaszTDepartment of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Karlowicza 24, PO-85-092 Bydgoszcz, Poland.LudwiczakHubertHInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, PO-02-106 Warsaw, Poland.CieslaJaroslaw MJMInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, PO-02-106 Warsaw, Poland.BanaszkiewiczZbigniewZDepartment of Surgery, Collegium Medicum, Nicolaus Copernicus University, Ujejskiego 75, Bydgoszcz, Poland.WinczuraAlicjaAInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, PO-02-106 Warsaw, Poland.ChmielarczykMateuszMInstitute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, PO-02-106 Warsaw, Poland; Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, PO-02-106 Warsaw, Poland.WisniewskaEwaEDepartment of Clinical Pathomorphology, Collegium Medicum, Nicolaus Copernicus University, Sklodowskiej-Curie 9, PO-85-092 Bydgoszcz, Poland.MarszalekAndrzejADepartment of Clinical Pathomorphology, Collegium Medicum, Nicolaus Copernicus University, Sklodowskiej-Curie 9, PO-85-092 Bydgoszcz, Poland.TudekBarbaraBInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, PO-02-106 Warsaw, Poland; Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, PO-02-106 Warsaw, Poland; Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, PO-02-106 Warsaw, Poland.OlinskiRyszardRDepartment of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Karlowicza 24, PO-85-092 Bydgoszcz, Poland.engJournal ArticleResearch Support, Non-U.S. Gov't20141219
United StatesPLoS One1012850811932-6203EC 2.4.2.30PARP1 protein, humanEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMNucleic Acids Res. 2003 Sep 15;31(18):5332-712954769Cancer Res. 2003 Apr 15;63(8):1727-3012702551J Urol. 2003 Dec;170(6 Pt 1):2471-414634453Mutat Res. 2003 Oct 29;531(1-2):177-9014637254Int J Cancer. 2004 Apr 10;109(3):317-2114961567FASEB J. 2004 Apr;18(6):690-214766804Oncol Rep. 2004 Oct;12(4):821-515375506Cancer Res. 1983 Jul;43(7):3441-66406058Pathologe. 1987 May;8(3):138-403303008Am J Hematol. 1991 Aug;37(4):223-71907096FEBS Lett. 1994 Mar 14;341(1):59-648137923Biochim Biophys Acta. 1997 Jun 7;1332(3):F127-479196022Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-59223305Clin Cancer Res. 1996 Jul;2(7):1163-79816283Biotechniques. 2005 Feb;38(2):287-9315727135Gastroenterology. 2005 Jun;128(7):1919-3615940627Apoptosis. 2006 Jan;11(1):131-916374543Clin Chim Acta. 2006 Mar;365(1-2):30-4916214123J Natl Cancer Inst. 2006 Apr 5;98(7):472-8216595783Eur J Cancer. 2006 Sep;42(14):2374-8116809031BMC Cancer. 2006;6:20816914027DNA Repair (Amst). 2007 Jan 4;6(1):45-6016982217Curr Med Chem. 2007;14(11):1179-8717504138Toxicol Sci. 2007 Sep;99(1):277-8817578862J Physiol. 2007 Dec 15;585(Pt 3):741-5817947304Cell Res. 2008 Jan;18(1):27-4718166975Cancer Causes Control. 2008 Dec;19(10):1051-6418543072Free Radic Biol Med. 2010 Sep 15;49(6):1064-7120600828Mutagenesis. 2010 Sep;25(5):463-7120534734Cell Cycle. 2010 Aug 1;9(15):3002-420714214Mutat Res. 2011 May 10;709-710:21-3121376741J Biol Chem. 2011 Jun 10;286(23):20335-4421518760Mutat Res. 2008 Mar 1;639(1-2):45-5418155253Int J Cancer. 2008 Nov 15;123(10):2460-418729200J Biol Chem. 2011 Dec 30;286(52):44679-9022057269Nature. 2012 Jan 19;481(7381):287-9422258607Curr Mol Pharmacol. 2012 Jan;5(1):88-10122122466PLoS One. 2012;7(8):e4269022880082FEBS Lett. 2012 Nov 2;586(21):3771-723022557Biochem Soc Trans. 2014 Feb;42(1):82-824450632Diagn Pathol. 2013;8:14423971971Nat Rev Cancer. 2012 Dec;12(12):801-1723175119Int J Cancer. 2014 Jan 15;134(2):376-8323832862Genomics. 2014 Feb-Mar;103(2-3):211-2124316131Curr Biol. 2002 Jun 4;12(11):912-812062055Free Radic Biol Med. 2002 Jul 15;33(2):192-20012106815Int J Cancer. 2002 Oct 1;101(4):395-712209966Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Mutat Res. 2001 Jun 2;477(1-2):7-2111376682Antioxid Redox Signal. 2001 Aug;3(4):597-60911554447Methods. 2001 Dec;25(4):402-811846609Cancer Epidemiol Biomarkers Prev. 2003 Oct;12(10):1100-414578150Adenomatous PolypsbloodgeneticspathologyAdultAgedCase-Control StudiesColonmetabolismpathologyColonic NeoplasmsbloodgeneticspathologyDNA GlycosylasesgeneticsmetabolismFemaleGene Expression Regulation, NeoplasticHeLa CellsHumansLeukocytesmetabolismMaleMiddle AgedOxidative StressPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesgeneticsmetabolismUp-Regulation
2014072120141124201412206020141220602015122260epublish2552664110.1371/journal.pone.0115558PONE-D-14-32536PMC4272268
254983872015031920161125
1089-863842722015Jan30Journal of molecular biologyJ. Mol. Biol.Human apurinic/apyrimidinic endonuclease 1 (APE1) has 3' RNA phosphatase and 3' exoribonuclease activities.298-31110.1016/j.jmb.2014.12.001S0022-2836(14)00617-2Apurinic/apyrimidinic endonuclease 1 (APE1) is the predominant mammalian enzyme in DNA base excision repair pathway that cleaves the DNA backbone immediately 5' to abasic sites. In addition to its abasic endonuclease activity, APE1 has 3' phosphatase and 3'-5' exonuclease activities against DNA. We recently identified APE1 as an endoribonuclease that preferentially cleaves at UA, UG, and CA sites in single-stranded regions of RNAs and can regulate c-myc mRNA level and half-life in cells. APE1 can also endonucleolytically cleave abasic single-stranded RNA. Here, we show for the first time that the human APE1 has 3' RNA phosphatase and 3' exoribonuclease activities. Using three distinct RNA substrates, we show that APE1, but not RNase A, can remove the phosphoryl group from the 3' end of RNA decay products. Studies using various site-directed APE1 mutant proteins (H309N, H309S, D283N, N68A, D210N, Y171F, D308A, F266A, and D70A) suggest that the 3' RNA phosphatase activity shares the same active center as its other known nuclease activities. A number of APE1 variants previously identified in the human population, including the most common D148E variant, have greater than 80% reduction in the 3' RNA phosphatase activity. APE1 can remove a ribonucleotide from the 3' overhang of RNA decay product, but its 3'-5' exoribonuclease activity against unstructured poly(A), poly(C), and poly(U) RNAs is relatively weak. This study further underscores the significance of understanding the role of APE1 in RNA metabolism in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.ChohanManbirMChemistry Program, University of Northern British Columbia, 3333 University Way, Prince George, British Columbia, V2N 4Z9, Canada.MackedenskiSebastianSChemistry Program, University of Northern British Columbia, 3333 University Way, Prince George, British Columbia, V2N 4Z9, Canada.LiWai-MingWMChemistry Program, University of Northern British Columbia, 3333 University Way, Prince George, British Columbia, V2N 4Z9, Canada.LeeChow HCHChemistry Program, University of Northern British Columbia, 3333 University Way, Prince George, British Columbia, V2N 4Z9, Canada. Electronic address: chow.lee@unbc.ca.engJournal ArticleResearch Support, Non-U.S. Gov't20141210
EnglandJ Mol Biol2985088R0022-28360Benzoquinones0Flavonoids0Hydroxylamines0Propionates136164-66-4E 333063231-63-0RNA76XC01FTOJmyricetin9TZH4WY30JmethoxyamineEC 3.1.-EndoribonucleasesEC 3.1.-ExoribonucleasesEC 3.1.3.2Phosphoric Monoester HydrolasesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBenzoquinonespharmacologyDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismEndoribonucleasesgeneticsmetabolismExoribonucleasesgeneticsmetabolismFlavonoidspharmacologyHalf-LifeHumansHydroxylaminespharmacologyPhosphoric Monoester HydrolasesgeneticsmetabolismPropionatespharmacologyRNAgeneticsmetabolismSubstrate Specificity3′ RNA phosphataseAPE1RNA
20140901201412022014120220141216602014121760201532060ppublish25498387S0022-2836(14)00617-210.1016/j.jmb.2014.12.001
254928652015041520161202
1083-351X29052015Jan30The Journal of biological chemistryJ. Biol. Chem.Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) redox function negatively regulates NRF2.3057-6810.1074/jbc.M114.621995Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) (henceforth referred to as Ref-1) is a multifunctional protein that in addition to its base excision DNA repair activity exerts redox control of multiple transcription factors, including nuclear factor κ-light chain enhancer of activated B cells (NF-κB), STAT3, activator protein-1 (AP-1), hypoxia-inducible factor-1 (HIF-1), and tumor protein 53 (p53). In recent years, Ref-1 has emerged as a promising therapeutic target in cancer, particularly in pancreatic ductal carcinoma. Although a significant amount of research has centered on Ref-1, no wide-ranging approach had been performed on the effects of Ref-1 inhibition and transcription factor activity perturbation. Starting with a broader approach, we identified a previously unsuspected effect on the nuclear factor erythroid-related factor 2 (NRF2), a critical regulator of cellular defenses against oxidative stress. Based on genetic and small molecule inhibitor-based methodologies, we demonstrated that repression of Ref-1 potently activates NRF2 and its downstream targets in a dose-dependent fashion, and that the redox, rather than the DNA repair function of Ref-1 is critical for this effect. Intriguingly, our results also indicate that this pathway does not involve reactive oxygen species. The link between Ref-1 and NRF2 appears to be present in all cells tested in vitro, noncancerous and cancerous, including patient-derived tumor samples. In particular, we focused on understanding the implications of the novel interaction between these two pathways in primary pancreatic ductal adenocarcinoma tumor cells and provide the first evidence that this mechanism has implications for overcoming the resistance against experimental drugs targeting Ref-1 activity, with clear translational implications. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.FishelMelissa LMLFrom the Departments of Pediatrics, Wells Center for Pediatric Research, Pharmacology and Toxicology, mfishel@iu.edu.WuXueXMicrobiology and Immunology.DevlinCecilia MCMMedicine.LogsdonDerek PDPPharmacology and Toxicology.JiangYanlinYFrom the Departments of Pediatrics, Wells Center for Pediatric Research.LuoMeihuaMFrom the Departments of Pediatrics, Wells Center for Pediatric Research, Pharmacology and Toxicology.HeYingYFrom the Departments of Pediatrics, Wells Center for Pediatric Research.YuZhangshengZBiostatistics, and.TongYanYBiostatistics, and.LipkingKelsey PKPPathology, Indiana University School of Medicine, Indianapolis, Indiana 46202 and.MaitraAnirbanAthe Departments of Oncology and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.RajeshkumarN VNVthe Departments of Oncology and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.ScanduraGlendaGMedicine.KelleyMark RMRFrom the Departments of Pediatrics, Wells Center for Pediatric Research, Pharmacology and Toxicology.IvanMirceaMMicrobiology and Immunology, Medicine, mivan@iu.edu.engCA121168CANCI NIH HHSUnited States1R01 CA155332-01CANCI NIH HHSUnited StatesCA121168S1CANCI NIH HHSUnited StatesCA167291CANCI NIH HHSUnited StatesR01 CA121168CANCI NIH HHSUnited StatesR01 CA167291CANCI NIH HHSUnited StatesR01 CA155332CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20141209
United StatesJ Biol Chem2985121R0021-92580NF-E2-Related Factor 20NFE2L2 protein, human0Reactive Oxygen SpeciesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMGastroenterology. 2008 Oct;135(4):1358-1368, 1368.e1-418692501Antioxid Redox Signal. 2008 Nov;10(11):1853-6718627350Mol Cancer. 2009;8:3719508729Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116J Med Chem. 2010 Feb 11;53(3):1200-1020067291Toxicol Appl Pharmacol. 2010 May 1;244(3):291-920083128Pancreas. 2010 May;39(4):463-7220118824Cancer Invest. 2010 Nov;28(9):885-9520919954Exp Hematol. 2010 Dec;38(12):1178-8820826193Antioxid Redox Signal. 2011 Apr 15;14(8):1387-40120874257Biochemistry (Mosc). 2011 Apr;76(4):407-2221585316Chem Biol Interact. 2011 Jun 30;192(1-2):37-4520932822Mol Cancer Ther. 2011 Sep;10(9):1698-70821700832Biochemistry. 2012 Jan 17;51(2):695-70522148505Biochemistry. 2011 Jan 11;50(1):82-9221117647PLoS One. 2012;7(10):e4746223094050PLoS One. 2012;7(11):e5052123209767Curr Pharm Des. 2013;19(15):2765-7023092325Biochemistry. 2013 Apr 30;52(17):2955-6623597102Proc Natl Acad Sci U S A. 2013 May 14;110(20):E1857-6623630282PLoS One. 2013;8(7):e6846723874636Science. 2008 Sep 26;321(5897):1801-618772397Bioorg Med Chem. 2013 Sep 1;21(17):5145-5323867390Curr Med Chem. 2013;20(30):3711-3223746277Oncogene. 2013 Oct;32(40):4825-3523108405J Biol Chem. 2000 Dec 22;275(51):40134-4111013233Crit Care Med. 2001 Oct;29(10):1962-7111588462Biochem Biophys Res Commun. 2002 Sep 20;297(2):346-5212237125Nat Immunol. 2003 Feb;4(2):145-5312524539Mol Cancer Ther. 2004 Jun;3(6):679-8615210853J Biol Chem. 1982 Jul 10;257(13):7778-856806282Mol Cell Biol. 2006 Apr;26(7):2845-5616537925BMC Bioinformatics. 2006;7:8516504059Clin Cancer Res. 2005 May 15;11(10):3790-815897578Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642DNA Repair (Amst). 2008 Feb 1;7(2):177-8617974506Nat Methods. 2008 Mar;5(3):253-6018297081Mol Cancer Ther. 2008 Jul;7(7):2012-2118645011Planta Med. 2008 Oct;74(13):1526-3918937164Cell Line, TumorDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismHumansNF-E2-Related Factor 2geneticsmetabolismOxidation-ReductionPancreatic NeoplasmsgeneticsmetabolismReactive Oxygen SpeciesmetabolismAPE1/Ref-1HMOX1HypoxiaNuclear Factor 2 (Erythroid-derived 2-like Factor) (NFE2L2) (Nrf2)Pancreatic AdenocarcinomaReactive Oxygen Species (ROS)Redox SignalingTranscription Factor
20141211602014121160201541660ppublish25492865M114.62199510.1074/jbc.M114.621995PMC4317024
254633922015070820141223
1568-7856252015JanDNA repairDNA Repair (Amst.)The repair of oxidized purines in the DNA of human lymphocytes requires an activation involving NF-YA-mediated upregulation of OGG1.1-810.1016/j.dnarep.2014.10.008S1568-7864(14)00262-68-Oxoguanine DNA glycosylase (OGG1), which initiates the repair of DNA purine modifications such as 8-oxo-7,8-dihydroguanine (8-oxoG), is often regarded as a house keeping protein ubiquitously active in mammalian cells. We have analysed the repair rates of oxidized purines generated by photosensitization in peripheral human lymphocytes and observed that the cells were virtually unable to remove these lesions (less than 10% removal within 24h). However, stimulation of the lymphocytes with phytohemagglutinin (PHA) strongly accelerated the repair so that ∼30% of the lesions were repaired within 4h. Within 24h following PHA stimulation and preceding the induction of cell proliferation, Western blots revealed an approximately 4-fold up-regulation of OGG1. The levels of OGG1 mRNA were 4-fold increased already after 6h. Chromatin immunoprecipitation analysis indicated that the up-regulation of OGG1 was associated with increased binding of the transcription factor NF-YA to the promoter of the OGG1 gene. The binding of NF-YA and subsequent induction of OGG1 was inhibited in the presence of an inhibitor of Jun kinase, indicating an activation of the corresponding signalling pathway as the mechanism underlying this transcriptional up-regulation. Our results reveal a strict control of base excision repair in cells of the human immune system. Copyright © 2014 Elsevier B.V. All rights reserved.von der LippenCarinaCInstitute of Pharmacy and Biochemistry, University of Mainz, Staudingerweg 5, D-55099 Mainz, Germany.SahuSanjeebSInstitute of Molecular Biology, D-55218 Mainz, Germany.SeifermannMarcoMInstitute of Pharmacy and Biochemistry, University of Mainz, Staudingerweg 5, D-55099 Mainz, Germany.TiwariVijay KVKInstitute of Molecular Biology, D-55218 Mainz, Germany.EpeBerndBInstitute of Pharmacy and Biochemistry, University of Mainz, Staudingerweg 5, D-55099 Mainz, Germany. Electronic address: epe@uni-mainz.de.engJournal ArticleResearch Support, Non-U.S. Gov't20141105
NetherlandsDNA Repair (Amst)1011391381568-78560CCAAT-Binding Factor0NFYA protein, human0Phytohemagglutinins0Purines9007-49-2DNAEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMCCAAT-Binding FactormetabolismCell Line, TransformedDNAmetabolismDNA DamageDNA GlycosylasesgeneticsmetabolismDNA Repairdrug effectsHumansLymphocytesdrug effectsenzymologymetabolismOxidation-ReductionPhytohemagglutininspharmacologyPurinesmetabolismTranscriptional ActivationUp-RegulationBase excision repairNF-YAOGG1Oxidatively generated DNA damagePhytohemagglutinin
201407282014101720141022201412360201412360201571560ppublish25463392S1568-7864(14)00262-610.1016/j.dnarep.2014.10.008
254521432015100220141229
1873-4596782015JanFree radical biology & medicineFree Radic. Biol. Med.APE1 promotes antioxidant capacity by regulating Nrf-2 function through a redox-dependent mechanism.11-2210.1016/j.freeradbiomed.2014.10.007S0891-5849(14)00455-9APE1 is a multifunctional protein that has recently been implicated in protecting cells from oxidative stress. In the current study, we confirmed that APE1׳s effect on cellular antioxidant capacity is related to its redox activity through the use of an APE1 functional mutant, and we investigated the mechanism through which this multifunctional protein affects the function of the transcription factor Nrf-2 in regulating oxidative stress-induced genes. Using a pair of mutants for both the redox activity and the acetylation-regulated activity of APE1, in vitro assays showed that the redox activity of APE1 is crucial for its nuclear association with Nrf-2 and subsequent activation of Nrf-2׳s transcription of several downstream genes during oxidative challenge. Important oxidative stress genes are affected by APE1 redox activity, including Hmox1, Gstm1, and Txnrd1. In addition, utilizing human non-small-cell lung cancer sample tissue as well as a nude mouse xenograft model, we determined that APE1 expression levels are inversely correlated to oxidative stress in vivo. These findings indicated that interference with these crucial functions of APE1 shows promise in preventing resistance to certain radiotherapies and that further research is necessary to understand APE1׳s complex roles in regulating both the basal redox status and the oxidative stress state of the cellular environment. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.ShanJin-LuJLCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.HeHai-TaoHTDepartment of Oral and Maxillofacial Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.LiMeng-XiaMXCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.ZhuJian-WuJWCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.ChengYiYCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.HuNanNCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.WangGeGCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.WangDongDCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.YangXue-QinXQCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.HeYongYDepartment of Respiration, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.XiaoHua-LiangHLDepartment of Pathology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.TongWei-DongWDDepartment of General surgery, Research Institute of Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China.YangZhen-ZhouZZCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People׳s Republic of China. Electronic address: yangzhenzhou@sohu.com.engJournal ArticleResearch Support, Non-U.S. Gov't20141014
United StatesFree Radic Biol Med87091590891-58490Antioxidants0NF-E2-Related Factor 20NFE2L2 protein, human0RNA, Messenger0Reactive Oxygen SpeciesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdultAgedAnimalsAntioxidantsmetabolismBlotting, WesternBone NeoplasmsgeneticsmetabolismpathologyCarcinoma, Non-Small-Cell LunggeneticsmetabolismpathologyCells, CulturedDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismFemaleFibroblastscytologymetabolismGene Expression RegulationHumansImmunoenzyme TechniquesLung NeoplasmsgeneticsmetabolismpathologyMaleMiceMice, NudeMiddle AgedNF-E2-Related Factor 2geneticsmetabolismNeoplasm StagingOsteosarcomageneticsmetabolismpathologyOxidation-ReductionOxidative StressRNA, MessengergeneticsReactive Oxygen SpeciesmetabolismReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionXenograft Model Antitumor AssaysAPE1Antioxidant capacityNrf-2Redox
201403042014093020141007201412360201412360201510360ppublish25452143S0891-5849(14)00455-910.1016/j.freeradbiomed.2014.10.007
254043482015042820171116
1091-6490111482014Dec02Proceedings of the National Academy of Sciences of the United States of AmericaProc. Natl. Acad. Sci. U.S.A.APE1 is dispensable for S-region cleavage but required for its repair in class switch recombination.17242-710.1073/pnas.1420221111Activation-induced cytidine deaminase (AID) is essential for antibody diversification, namely somatic hypermutation (SHM) and class switch recombination (CSR). The deficiency of apurinic/apyrimidinic endonuclease 1 (Ape1) in CH12F3-2A B cells reduces CSR to ∼20% of wild-type cells, whereas the effect of APE1 loss on SHM has not been examined. Here we show that, although APE1's endonuclease activity is important for CSR, it is dispensable for SHM as well as IgH/c-myc translocation. Importantly, APE1 deficiency did not show any defect in AID-induced S-region break formation, but blocked both the recruitment of repair protein Ku80 to the S region and the synapse formation between Sμ and Sα. Knockdown of end-processing factors such as meiotic recombination 11 homolog (MRE11) and carboxy-terminal binding protein (CtBP)-interacting protein (CtIP) further reduced the remaining CSR in Ape1-null CH12F3-2A cells. Together, our results show that APE1 is dispensable for SHM and AID-induced DNA breaks and may function as a DNA end-processing enzyme to facilitate the joining of broken ends during CSR. XuJianliangJDepartment of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.HusainAfzalADepartment of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.HuWenjunWDepartment of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.HonjoTasukuTDepartment of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan honjo@mfour.med.kyoto-u.ac.jp.KobayashiMakiMDepartment of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.engJournal ArticleResearch Support, Non-U.S. Gov't20141117
United StatesProc Natl Acad Sci U S A75058760027-84240Carrier Proteins0Cell Cycle Proteins0CtIP protein, mouse0DNA-Binding Proteins0Immunoglobulin Heavy Chains0Mre11a protein, mouse0Proto-Oncogene Proteins c-mycEC 3.1.-MRE11 Homologue ProteinEC 3.5.4.-AICDA (activation-induced cytidine deaminase)EC 3.5.4.5Cytidine DeaminaseEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 6.5.1.-DNA Repair EnzymesIMProc Natl Acad Sci U S A. 2005 Feb 8;102(6):2022-715684068Nat Immunol. 2002 Sep;3(9):815-2112145648Adv Immunol. 2007;94:1-3617560270Nature. 2006 Mar 2;440(7080):105-916400328J Mol Biol. 2003 Jul 25;330(5):1027-3712860125Cell. 2000 Sep 1;102(5):565-7511007475Annu Rev Biochem. 2007;76:1-2217328676Nat Genet. 2010 Mar;42(3):245-920118933Science. 2004 Aug 20;305(5687):1160-315326357Nat Neurosci. 2014 Jun;17(6):813-2124793032J Biol Chem. 2009 Oct 9;284(41):28084-9219666469J Exp Med. 2005 Jan 17;201(2):189-9415657289J Immunol. 2013 Jun 15;190(12):5949-6023667108Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11534-98876170Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2752-719202054Mutat Res. 2001 May 10;485(4):283-30711585362J Immunol. 2012 Apr 15;188(8):3559-6622492685J Biol Chem. 1999 Jun 25;274(26):18470-610373455EMBO J. 2003 Dec 1;22(23):6299-30914633989J Exp Med. 2007 Nov 26;204(12):3017-2618025127Nature. 2012 Apr 5;484(7392):69-7422314321Mech Ageing Dev. 2007 Mar;128(3):259-6617224176Adv Immunol. 2007;94:157-21417560275J Mol Biol. 2011 Sep 2;411(5):960-7121762700Mutat Res. 2003 Nov 27;532(1-2):173-20314643436J Immunol. 2012 Jun 1;188(11):5528-3722547703Mol Cell. 2009 Jan 16;33(1):117-2319150433J Biol Chem. 2012 Apr 13;287(16):12848-5722375014J Exp Med. 2002 Feb 18;195(4):529-3411854365Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):E1016-2424591630Nature. 2007 Nov 22;450(7169):509-1417965729Mol Cell. 2014 Jun 19;54(6):1012-2124837675Mol Cell Biol. 1993 Sep;13(9):5370-68355688Carcinogenesis. 2000 Jul;21(7):1329-3410874010EMBO J. 1998 Apr 15;17(8):2404-119545251Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19305-1022080610J Exp Med. 2012 Jun 4;209(6):1075-8122615128Nature. 2002 Jul 4;418(6893):99-10312097915Nucleic Acids Res. 2004;32(17):5134-4615459284Nature. 2001 Dec 6;414(6864):660-511740565ISRN Mol Biol. 2012;2012:null24236237Nucleic Acids Res. 2004;32(12):3531-615247342Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22375-8020018730Int Immunol. 2009 Aug;21(8):947-5519556307Mol Cell Biol. 2013 Apr;33(7):1468-7323382073Nat Genet. 2002 Oct;32(2):267-7212244316J Immunol. 2007 Nov 1;179(9):6064-7117947680Nature. 2007 Sep 27;449(7161):478-8217713479Annu Rev Immunol. 2008;26:261-9218370922Mol Cell. 2014 Jun 19;54(6):1022-3324837676Nat Rev Immunol. 2004 Jul;4(7):541-5215229473Mol Cell. 2014 Jul 3;55(1):97-11024954901Cell. 2000 Sep 1;102(5):553-6311007474Nature. 2009 Jul 9;460(7252):231-619587764Annu Rev Immunol. 2002;20:165-9611861601Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463Cell. 2008 Dec 12;135(6):1028-3819070574Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128AnimalsBlotting, WesternCarrier ProteinsgeneticsmetabolismCell Cycle ProteinsgeneticsmetabolismCell Line, TumorCytidine DeaminasegeneticsmetabolismDNA DamageDNA RepairDNA Repair EnzymesgeneticsmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismDNA-Binding ProteinsgeneticsmetabolismImmunoglobulin Class SwitchinggeneticsImmunoglobulin Heavy ChainsgeneticsmetabolismLymphoma, B-CellgeneticsmetabolismpathologyMRE11 Homologue ProteinMiceMutationProtein TransportProto-Oncogene Proteins c-mycgeneticsmetabolismRNA InterferenceRecombination, GeneticSomatic Hypermutation, ImmunoglobulingeneticsDNA cleavageDNA synapse formationclass switch recombinationend processingsomatic hypermutation
20141119602014111960201542960ppublish25404348142022111110.1073/pnas.1420221111PMC4260585
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1423-038035122014DecTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Letter regarding Shen et al. entitled "The APE1 Asp148Glu polymorphism and colorectal cancer susceptibility: a meta-analysis".12775-610.1007/s13277-014-2804-1LiuFeiFDepartment of liver surgery, West China Hospital of Sichuan University, 37 Guo Xue Road, Chengdu, 610041, Sichuan Province, China.WeiYong-GangYGWangWen-TaoWTLiBoBengCommentEditorial20141111
United StatesTumour Biol84099221010-4283EC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMTumour Biol. 2014 Mar;35(3):2529-3524254302Cancer Res. 2007 Feb 1;67(3):1395-40417283177J Exp Clin Cancer Res. 2008 Sep 30;27:4918823566Tumour Biol. 2014 Mar;35(3):2529-3524254302Colorectal NeoplasmsgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGenetic Predisposition to DiseasegeneticsHumansPolymorphism, Single Nucleotidegenetics
201410222014110320141112602014111260201531160ppublish2538451010.1007/s13277-014-2804-1
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1364-5528139242014Dec21The AnalystAnalystSignal-on electrochemical immunoassay for APE1 using ionic liquid doped Au nanoparticle/graphene as a nanocarrier and alkaline phosphatase as enhancer.6563-810.1039/c4an01712aIn this paper, the Au nanoparticles decorated graphene nanosheets (AuNPs/Gr) were prepared as nanocarriers using ionic liquid (IL) as linker reagent. Then the alkaline phosphatase (ALP) and the ferrocene tagged detection antibodies (Fc-Ab2) were loaded on the IL doped AuNPs/Gr as a trace label for ultrasensitive measurements of human apurinic/apyrimidinic endonuclease 1 (APE1), which is a multifunctional protein in the DNA base excision repair pathway relating to various types of cancer. Several labeling protocols were investigated for the determination of the APE1 protein concentration and improved analytical features were obtained with the proposed carriers of IL doped AuNPs/Gr which were labeled with Fc-Ab2 and ALP (ALP/Fc-Ab2/AuNPs/IL/Gr). The reason may be that the IL doped AuNPs/Gr carriers (AuNPs/IL/Gr) could not only enhance the immobilized amount of ALP and Fc-Ab2, but also promote the electron transfer rate. Thus, through the specific recognition of antigen-antibody, numerous ALP/Fc-Ab2/AuNPs/IL/Gr, which are captured onto every single immunocomplex, could further catalyze the ascorbic acid 2-phosphate (AA-p) reaction to amplify the electrochemical signal. Transmission electron microscopy (TEM) images of the AuNPs/IL/Gr nanocomposites revealed the formation of a functionalized surface network structure. The resulting immunosensor exhibited a linear response to APE1 in the concentration range of 0.1-80 pg mL(-1) with a detection limit of 0.04 pg mL(-1), indicating potential applications in clinical diagnostics. ZhongZhaoyangZDepartment of Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, P.R. China. dongwang64@hotmail.com zhongzhaoyang08@hotmail.com.LiMengxiaMQingYiYDaiNanNGuanWeiWLiangWeiWWangDongDengEvaluation StudiesJournal ArticleResearch Support, Non-U.S. Gov't
EnglandAnalyst03726520003-26540Antibodies, Immobilized0Enzymes, Immobilized7440-57-5Gold7782-42-5GraphiteEC 3.1.3.1Alkaline PhosphataseEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAlkaline PhosphatasechemistryAntibodies, ImmobilizedchemistryDNA-(Apurinic or Apyrimidinic Site) LyaseanalysisbloodElectrochemical TechniquesinstrumentationEnzyme AssaysinstrumentationEnzymes, ImmobilizedchemistryEquipment DesignGoldchemistryGraphitechemistryHumansImmunoassayinstrumentationLimit of DetectionMetal Nanoparticleschemistry
2014103160201410316020159160ppublish2535693410.1039/c4an01712a
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1432-07389022016FebArchives of toxicologyArch. Toxicol.Deficient DNA repair exacerbates ethanol-initiated DNA oxidation and embryopathies in ogg1 knockout mice: gender risk and protection by a free radical spin trapping agent.415-2510.1007/s00204-014-1397-1Reactive oxygen species (ROS) have been implicated in the teratogenicity of alcohol (ethanol, EtOH). To determine the involvement of embryonic oxidative DNA damage, DNA repair-deficient oxoguanine glycosylase 1 (ogg1) knockout embryos were exposed in culture to EtOH (2 or 4 mg/ml), with or without pretreatment with the free radical spin trap phenylbutylnitrone (PBN) (0.125 mM). Visceral yolk sacs were used to genotype embryos for DNA repair status and gender. EtOH caused a concentration-dependent decrease in anterior neuropore closure (ANPC), somite development, turning, crown-rump length (CRL), yolk sac diameter (YSD) and head length (HL) (p < 0.001) in all 3 ogg1 genotypes. There was a further ogg1 gene dose-dependent decrease from +/+ to -/- embryos in ANPC, somite development, turning, CRL and HL (p < 0.05), and a gene-dependent correlation between HL and ANPC (p < 0.01). Female embryos exhibited lesser ANPC and turning than males (p < 0.05), suggesting underlying gender-dependent target-specific determinants. PBN pretreatment increased ANPC, somite development, turning, CRL, YSD and HL (p < 0.001), although this protection against EtOH was slightly less effective in -/- embryos. Oxidatively damaged DNA determined as 8-oxo-2'-deoxyguanosine (8-oxodGuo), which is repaired by OGG1, was measured in single embryos in vivo after maternal EtOH treatment (4 g/kg i.p). EtOH increased embryonic 8-oxodGuo in an ogg1 gene-dependent fashion, with the highest levels in -/- embryos. These results show that embryonic DNA repair status and gender are determinants of risk. ROS-initiated embryonic DNA oxidation is involved in EtOH embryopathies. Miller-PinslerLutfiyaLDepartment of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.Southern Research Institute, 2000 9th Avenue South, Birmingham, AL, 35205, USA.WellsPeter GPGDepartment of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. pg.wells@utoronto.ca.Division of Biomolecular Sciences, Faculty of Pharmacy, University of Toronto, 144 College St., Toronto, ON, M5S 3M2, Canada. pg.wells@utoronto.ca.engCanadian Institutes of Health ResearchCanadaJournal ArticleResearch Support, Non-U.S. Gov't20141030
GermanyArch Toxicol04176150340-57610Phenylbutyrates0Reactive Oxygen Species3K9958V90MEthanol88847-89-68-oxo-7-hydrodeoxyguanosine90-26-6phenylbutyramide9007-49-2DNAEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseG9481N71RODeoxyguanosineIMAnimalsDNAmetabolismDNA GlycosylasesgeneticsmetabolismDNA Repairdrug effectsgeneticsDNA Repair-Deficiency Disorderschemically inducedgeneticsDeoxyguanosineanalogs & derivativesmetabolismEmbryo Culture TechniquesEmbryo, Mammaliandrug effectspathologyEthanoltoxicityFemaleMaleMice, KnockoutOxidation-ReductionPhenylbutyratespharmacologyReactive Oxygen SpeciespharmacologySex FactorsSpin TrappingDNA oxidationEmbryo cultureEthanolOgg1 micePBNReactive oxygen species
201408142014101620141031602014103160201782660ppublish2535479810.1007/s00204-014-1397-110.1007/s00204-014-1397-1
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1879-35927722014Sep15Mutation research. Genetic toxicology and environmental mutagenesisMutat Res Genet Toxicol Environ MutagenSingle cell gel electrophoresis (SCGE) and Pig-a mutation assay in vivo-tools for genotoxicity testing from a regulatory perspective: a study of benzo[a]pyrene in Ogg1(-/-) mice.34-4110.1016/j.mrgentox.2014.07.010S1383-5718(14)00214-9The OECD has developed test guidelines (TG) to identify agents with genotoxic effects. The in vivo alkaline single cell gel electrophoresis (SCGE) assay is currently being prepared to become such a TG. The performance of a combined SCGE/Pig-a gene mutation study was evaluated with the prototypical genotoxicant benzo[a]pyrene (BaP) at an exposure level known to induce germ cell mutation. We aimed to better understand (i) the strengths and weaknesses of the two methods applied in blood and their potential to predict germ cell mutagenicity, and (ii) the involvement of reactive oxygen species (ROS) following in vivo BaP-exposure. To explore the involvement of ROS on BaP genotoxicity, we utilised a mouse model deficient in a DNA glycosylase. Specifically, C57BL/6 mice (Ogg1(+/+) and Ogg1(-/-)) were treated for three consecutive days with 50 mg BaP/kg/day. DNA damage in nucleated blood cells was measured four hours after the last treatment with the SCGE assay, with and without formamidopyrimidine DNA glycosylase (Fpg). Pig-a mutant phenotype blood erythrocytes were analysed two and four weeks after treatment. BaP-induced DNA lesions were not significantly increased in either version of the SCGE assay. The phenotypic mutation frequencies for immature and mature erythrocytes were significantly increased after two weeks. These effects were not affected by genotype, suggesting oxidative damage may have a minor role in BaP genotoxicity, at least in the acute exposure situation studied here. While both assays are promising tools for risk assessment, these results highlight the necessity of understanding the limitations regarding each assay's ability to detect chemicals' genotoxic potential.Copyright © 2014 Elsevier B.V. All rights reserved.GraupnerAnneADepartment of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo 0403, Norway.InstanesChristineCDepartment of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo 0403, Norway.DertingerStephen DSDLitron Laboratories, Rochester, NY 14623, United States.AndersenJill MariJMDepartment of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo 0403, Norway.LindemanBirgitteBDepartment of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo 0403, Norway.RongvedTonje DanielsenTDDepartment of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo 0403, Norway.BrunborgGunnarGDepartment of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo 0403, Norway.OlsenAnn-KarinAKDepartment of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo 0403, Norway. Electronic address: ann.karin.olsen@fhi.no.engR44 ES018017ESNIEHS NIH HHSUnited StatesR44ES018017ESNIEHS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20140807
NetherlandsMutat Res Genet Toxicol Environ Mutagen1016321491383-57180Membrane Proteins0Mutagens0Reactive Oxygen Species0phosphatidylinositol glycan-class A protein3417WMA06DBenzo(a)pyreneEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMProc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Mutagenesis. 2013 May;28(3):333-4023462850Nucleic Acids Res. 2003 Feb 15;31(4):1351-6312582255J Biol Chem. 1988 Feb 5;263(4):1814-203276678Exp Cell Res. 1988 Mar;175(1):184-913345800J Biol Chem. 1990 Mar 5;265(7):3916-221689309Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4690-42052552Biochemistry. 1992 Jan 14;31(1):106-101731864Environ Mol Mutagen. 1996;27(1):19-298625944Chem Res Toxicol. 1996 Jan-Feb;9(1):84-928924621Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5209-1410220445Biol Chem. 2006 Apr;387(4):373-916606334Mutagenesis. 2008 May;23(3):143-5118283046Proc Natl Acad Sci U S A. 2008 May 13;105(19):6846-5118474869Mutat Res. 2008 Jul 31;654(2):114-3218585956Mutat Res. 2008 Dec 8;657(2):122-618790079Mutat Res. 2009 Feb 19;673(1):21-819073277Mutat Res. 2009 Jun-Jul;677(1-2):86-9219501187Mutat Res. 2010 Feb;696(1):55-6120026424Toxicol Sci. 2010 Jun;115(2):401-1120202993PLoS One. 2010;5(6):e1134920596530J Appl Toxicol. 2010 Jul;30(5):402-1020186696Toxicol Sci. 2010 Oct;117(2):381-9220624995Environ Mol Mutagen. 2010 Oct-Dec;51(8-9):825-3520857433Mutat Res. 2011 Apr 3;721(2):163-7021277384Mutat Res. 2011 May 18;722(1):7-1921356328Environ Mol Mutagen. 2011 Dec;52(9):784-9421826740Environ Mol Mutagen. 2011 Dec;52(9):690-821910140Environ Mol Mutagen. 2011 Dec;52(9):685-921976154Environ Mol Mutagen. 2011 Dec;52(9):756-6521976233Environ Mol Mutagen. 2011 Dec;52(9):731-722052432Environ Mol Mutagen. 2011 Dec;52(9):681-422167884Pharm Stat. 2011 Nov-Dec;10(6):485-9322127874Environ Mol Mutagen. 2012 Apr;53(3):166-7222351488Proteomics. 2012 Jun;12(11):1731-5522623321Toxicol Sci. 2012 Dec;130(2):328-4822923490Drug Metab Rev. 2001 Feb;33(1):1-3511270659AnimalsBenzo(a)pyreneadverse effectspharmacologyDNA DamageDNA GlycosylasesElectrophoresismethodsErythrocytes, AbnormalmetabolismpathologyMembrane ProteinsgeneticsmetabolismMiceMice, KnockoutMutagensadverse effectspharmacologyMutationOxidative Stressdrug effectsReactive Oxygen SpeciesmetabolismAlkaline single cell gel electrophoresis (SCGE)Benzo[a]pyrene (BaP)GenotoxicityHazard identificationPig-a mutation assayRisk assessment
201403062014072520140729201410146020141014602014121560ppublish25308545S1383-5718(14)00214-910.1016/j.mrgentox.2014.07.010PMC4196198NIHMS620047
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1520-480457242014Dec26Journal of medicinal chemistryJ. Med. Chem.DNA repair and redox activities and inhibitors of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1): a comparative analysis and their scope and limitations toward anticancer drug development.10241-5610.1021/jm500865uThe apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional enzyme involved in DNA repair and activation of transcription factors through its redox function. The evolutionarily conserved C- and N-termini are involved in these functions independently. It is also reported that the activity of APE1/Ref-1 abruptly increases several-fold in various human cancers. The control over the outcomes of these two functions is emerging as a new strategy to combine enhanced DNA damage and chemotherapy in order to tackle the major hurdle of increased cancer cell growth and proliferation. Studies have targeted these two domains individually for the design and development of inhibitors for APE1/Ref-1. Here, we have made, for the first time, an attempt at a comparative analysis of APE1/Ref-1 inhibitors that target both DNA repair and redox activities simultaneously. We further discuss their scope and limitations with respect to the development of potential anticancer agents. KaurGagandeepGLaboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, School of Basic and Applied Sciences, Central University of Punjab , Bathinda, 151001, Punjab, India.CholiaRavi PRPManthaAnil KAKKumarRajRengComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't20141015
United StatesJ Med Chem97165310022-26230Antineoplastic AgentsEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAntineoplastic AgentspharmacologyDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsDrug DesignHumansNeoplasmsdrug therapyOxidation-Reduction
201410460201410460201531160ppublish2528018210.1021/jm500865u
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1422-006715102014Sep29International journal of molecular sciencesInt J Mol SciEffect of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in patients with colorectal cancer.17333-4310.3390/ijms151017333It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV) showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1). In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis. SantosJuliana CJCLaboratory of Microbiology and Molecular Biology, Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Bragança Paulista, SP. 12916-900, Brazil. ju_carvalho_s@hotmail.com.FunckAlexandreALaboratory of Microbiology and Molecular Biology, Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Bragança Paulista, SP. 12916-900, Brazil. afunck1@gmail.com.Silva-FernandesIsabelle J LIJDepartment of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, CE. 60020-181, Brazil. isabellejoyce@gmail.com.RabenhorstSilvia H BSHDepartment of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, CE. 60020-181, Brazil. srabenhorst@hotmail.com.MartinezCarlos A RCALaboratory of Microbiology and Molecular Biology, Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Bragança Paulista, SP. 12916-900, Brazil. caomartinez@uol.com.br.RibeiroMarcelo LMLLaboratory of Microbiology and Molecular Biology, Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Bragança Paulista, SP. 12916-900, Brazil. marcelo.ribeiro@usf.edu.br.engJournal ArticleResearch Support, Non-U.S. Gov't20140929
SwitzerlandInt J Mol Sci1010927911422-00670DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 2.4.2.30PARP1 protein, humanEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855Mutagenesis. 2010 Sep;25(5):463-7120534734Curr Cancer Drug Targets. 2012 May;12(4):356-7122385513PLoS One. 2012;7(7):e4013122792228Mutat Res. 2012 Aug 1;736(1-2):82-9222561673Pol J Pathol. 2012 Jun;63(2):87-9222864776J Surg Oncol. 2012 Sep 15;106(4):448-5522374853Clin Cancer Res. 2012 Nov 1;18(21):5878-8722966016Med Oncol. 2013 Jun;30(2):50523430444Hum Pathol. 2014 Feb;45(2):268-7524289972Acta Chir Belg. 2013 Nov-Dec;113(6):385-9024494463Carcinogenesis. 1999 Nov;20(11):2125-910545415Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Semin Gastrointest Dis. 2000 Oct;11(4):229-3711057950Cell. 2001 Jan 12;104(1):107-1711163244J Dermatol Sci. 2001 Oct;27(2):121-911532376Cancer Res. 2002 Mar 1;62(5):1377-8111888908Genes Dev. 2004 Mar 15;18(6):602-1615075289Genomics. 2004 Jun;83(6):970-915177551Cell. 1990 Jun 1;61(5):759-672188735J Biol Chem. 1992 Jan 5;267(1):166-721730583EMBO J. 1992 Sep;11(9):3323-351380454Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11759-631465394J Natl Cancer Inst. 1999 Jun 2;91(11):916-3210359544Chromosome Res. 2006;14(1):27-3716506094Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2101-816609022Nat Rev Mol Cell Biol. 2006 Jul;7(7):517-2816829982Clin Cancer Res. 2006 Sep 1;12(17):5104-1116951227Eur J Cancer. 2006 Sep;42(14):2374-8116809031BMC Cancer. 2006;6:20816914027Mutat Res. 2008 Feb 1;638(1-2):146-5317991492Cancer Lett. 2008 Jul 18;266(1):60-7218374480J Exp Clin Cancer Res. 2008;27:4918823566Asian Pac J Cancer Prev. 2008 Jul-Sep;9(3):501-518990028Pathologe. 2009 Dec;30 Suppl 2:193-919960300J Appl Genet. 2010;51(3):343-5220720310Curr Med Res Opin. 2011 Jul;27(7):1295-30221561390AdenocarcinomageneticspathologyAdultAgedAged, 80 and overAllelesColorectal NeoplasmsgeneticspathologyDNA GlycosylasesgeneticsmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismDNA-Binding ProteinsgeneticsmetabolismDown-RegulationFemaleGenotypeHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesgeneticsmetabolismPolymorphism, Single NucleotideUp-RegulationX-ray Repair Cross Complementing Protein 1
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1617-462329012015FebMolecular genetics and genomics : MGGMol. Genet. GenomicsThe association between the APE1 Asp148Glu polymorphism and prostate cancer susceptibility: a meta-analysis based on case-control studies.281-810.1007/s00438-014-0916-3The apurinic/apyrimidinic endonuclease 1 (APE1) plays important roles in the repair of DNA damage and adducts. However, previous case-control studies on the association between the APE1 Asp148Glu polymorphism and prostate cancer susceptibility have shown contradictory results, this meta-analysis was performed to draw a more precise estimation of the relationship. A total of seven case-control studies including 1,294 cases and 1,762 controls were included for analysis. In overall, no significant associations were found in all genetic models (GG vs. TT: OR = 1.16, 95 % CI 0.89-1.52; TG vs. TT: OR = 1.04, 95 % CI 0.81-1.35; the dominant model GG + TG vs. TT: OR = 1.12, 95 % CI 0.96-1.30; the recessive model GG vs. TG + TT: OR = 0.90, 95 % CI 0.77-1.04); in the subgroup by source of control, we found a significant association for the dominant model in Hospital-based subgroup (OR = 1.34, 95 % CI 1.08-1.68), no significant associations were found in other models in the subgroups. This meta-analysis suggested that the APE1 Asp148Glu polymorphism was a risk factor for prostate cancer susceptibility in Hospital-based population. ZhouXueXDepartment of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.WeiLiLJiaoGuangjunGGaoWeiWYingMingzhenMWangNingNWangYajieYLiuChuanCengJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov't20140919
GermanyMol Genet Genomics1010933201617-4623EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMIndian J Med Res. 2012;135:64-7122382185Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Cancer Treat Rev. 2010 Aug;36(5):425-3520056333Biometrics. 1994 Dec;50(4):1088-1017786990J Urol. 2006 Jan;175(1):108-12; discussion 11216406883CA Cancer J Clin. 2010 Sep-Oct;60(5):277-30020610543Control Clin Trials. 1986 Sep;7(3):177-883802833J Cell Sci Suppl. 1995;19:73-78655650CA Cancer J Clin. 2005 Mar-Apr;55(2):74-10815761078Mol Biol Rep. 2011 Mar;38(3):1585-9120852942Int J Epidemiol. 2008 Feb;37(1):120-3217898028Prostate. 2010 Feb 1;70(2):113-919760636Asian Pac J Cancer Prev. 2012;13(8):3931-623098495Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Int J Epidemiol. 2008 Feb;37(1):136-4618037675Carcinogenesis. 2001 Jun;22(6):917-2211375899Carcinogenesis. 2000 Jul;21(7):1329-3410874010Environ Mol Mutagen. 2004;44(1):74-8215199549Genomics. 2004 Jun;83(6):970-915177551Tumour Biol. 2014 Jan;35(1):667-7323975370PLoS One. 2013 Jul 04;8(7):e6863423861929Med Decis Making. 2005 Nov-Dec;25(6):646-5416282215Nature. 1993 Apr 22;362(6422):709-158469282BMJ. 1997 Sep 13;315(7109):629-349310563Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165CA Cancer J Clin. 2011 Jul-Aug;61(4):212-3621685461Clin Lab. 2013;59(1-2):163-823505922Cancer. 2004 Nov 15;101(10 Suppl):2371-49015495199Nucleic Acids Res. 1992 Sep 11;20(17):4417-211383925Mech Ageing Dev. 2012 Apr;133(4):127-3222019847Eur J Epidemiol. 2010 Sep;25(9):603-520652370Case-Control StudiesConfidence IntervalsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsEthnic GroupsgeneticsGenetic Association StudiesGenetic HeterogeneityGenetic Predisposition to DiseaseHumansMaleOdds RatioPolymorphism, Single NucleotidegeneticsProstatic NeoplasmsgeneticsPublication Bias
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1676-56801332014Sep05Genetics and molecular research : GMRGenet. Mol. Res.Association of c.461G>A genetic variant of OGG1 gene with pancreatic cancer susceptibility in Chinese.7256-6110.4238/2014.September.5.10This study aimed to evaluate the potential association of single nucleotide polymorphisms of the 8-oxoguanine DNA glycosylase gene (OGG1) with susceptibility to pancreatic cancer (PC). A total of 764 Chinese Han subjects were recruited in this study. The polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods were used to detect the genotype of c.461G>A genetic variant of OGG1. The genotype and allele frequencies were statistically different in PC patients compared with cancer-free controls. The AA genotype was statistically associated with increased PC susceptibility compared to GG wild genotype (AA vs GG, OR=2.62, 95%CI=1.48-4.63, χ2=11.46, P=0.001). Allele A could contribute to the increased risk of PC (A vs G, OR=1.35, 95%CI=1.08-1.69, χ2=6.86, P=0.009). Our data indicated that the c.461G>A genetic variant of the OGG1 gene was associated with susceptibility to PC in a Chinese Han population.ZhaoZ MZMDepartment of Surgical Oncology, The Chinese PLA General Hospital, Beijing, China zhi_ming_zhao@sina.com.LiC GCGDepartment of Surgical Oncology, The Chinese PLA General Hospital, Beijing, China.HuM GMGDepartment of Surgical Oncology, The Chinese PLA General Hospital, Beijing, China.ZhaoG DGDDepartment of Surgical Oncology, The Chinese PLA General Hospital, Beijing, China.LiuRRDepartment of Surgical Oncology, The Chinese PLA General Hospital, Beijing, China.engJournal Article20140905
BrazilGenet Mol Res1011693871676-5680EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultAgedAllelesAsian Continental Ancestry GroupgeneticsCase-Control StudiesChinaDNA GlycosylasesgeneticsFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansMaleMiddle AgedPancreatic NeoplasmsgeneticsPolymorphism, Single NucleotideRisk Factors
201491660201491660201642660epublish25222230gmr358310.4238/2014.September.5.10
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1083-351X289442014Oct31The Journal of biological chemistryJ. Biol. Chem.Distinct roles of Ape1 protein, an enzyme involved in DNA repair, in high or low linear energy transfer ionizing radiation-induced cell killing.30635-4410.1074/jbc.M114.604959High linear energy transfer (LET) radiation from space heavy charged particles or a heavier ion radiotherapy machine kills more cells than low LET radiation, mainly because high LET radiation-induced DNA damage is more difficult to repair. Relative biological effectiveness (RBE) is the ratio of the effects generated by high LET radiation to low LET radiation. Previously, our group and others demonstrated that the cell-killing RBE is involved in the interference of high LET radiation with non-homologous end joining but not homologous recombination repair. This effect is attributable, in part, to the small DNA fragments (≤40 bp) directly produced by high LET radiation, the size of which prevents Ku protein from efficiently binding to the two ends of one fragment at the same time, thereby reducing non-homologous end joining efficiency. Here we demonstrate that Ape1, an enzyme required for processing apurinic/apyrimidinic (known as abasic) sites, is also involved in the generation of small DNA fragments during the repair of high LET radiation-induced base damage, which contributes to the higher RBE of high LET radiation-induced cell killing. This discovery opens a new direction to develop approaches for either protecting astronauts from exposure to space radiation or benefiting cancer patients by sensitizing tumor cells to high LET radiotherapy. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.WangHongyanHFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and.WangXiangXFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and.ChenGuangnanGFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and.ZhangXiangmingXFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and.TangXiaobingXFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and.ParkDongkyooDFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and.CucinottaFrancis AFAthe Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, Nevada 89154.YuDavid SDSFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and.DengXingmingXFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and.DynanWilliam SWSFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and.DoetschPaul WPWFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and.WangYaYFrom the Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia 30322 and ywang94@emory.edu.engP30 CA138292CANCI NIH HHSUnited StatesP30CA138292CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, U.S. Gov't, Non-P.H.S.20140910
United StatesJ Biol Chem2985121R0021-92580DNA-Binding Proteins0Mre11a protein, mouseEC 3.1.-MRE11 Homologue ProteinEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 6.5.1.-DNA Repair EnzymesIMGenes Dev. 1999 Oct 15;13(20):2633-810541549DNA Repair (Amst). 2009 Dec 3;8(12):1343-5419800300Nucleic Acids Res. 1999 Dec 15;27(24):4679-8610572166Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):103-810618378J Vis Exp. 2012;(66):e416822895410Science. 2013 May 31;340(6136):1080-423723233Mol Cell. 2014 Jan 9;53(1):7-1824316220Nature. 2000 Jan 27;403(6768):451-610667800Nat Genet. 2001 Mar;27(3):247-5411242102Nucleic Acids Res. 2001 Apr 15;29(8):1653-6011292837Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Radiat Res. 2010 Jan;173(1):27-3920041757Nucleic Acids Res. 2010 Jun;38(10):3245-5120150414J Biol Chem. 2011 Feb 18;286(7):4968-7721081487Proc Natl Acad Sci U S A. 2011 May 17;108(20):8293-821527720Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Nature. 2001 Aug 9;412(6847):607-1411493912Radiat Prot Dosimetry. 2001;97(1):25-3111763354Mol Cell Biol. 2003 Aug;23(16):5706-1512897142Radiat Res. 2003 Sep;160(3):366-7512926995Nucleic Acids Res. 2004;32(18):5609-2015494449Int J Radiat Biol Relat Stud Phys Chem Med. 1980 Feb;37(2):135-676966263Radiat Res. 1981 May;86(2):185-957015409Int J Radiat Biol Relat Stud Phys Chem Med. 1987 May;51(5):779-903496288EMBO J. 1992 Feb;11(2):653-651537340Int J Radiat Biol. 1992 Jun;61(6):737-481351522Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414Radiat Res. 1994 Aug;139(2):133-418052688Cancer Res. 1995 Mar 15;55(6):1232-47882314Nature. 1996 Aug 8;382(6591):551-58700231Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-69560228J Mol Biol. 1999 Jul 9;290(2):447-5710390343Curr Biol. 1999 Jul 1;9(13):699-70210395545J Cell Physiol. 2005 Feb;202(2):492-50215389585Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Radiat Res. 2006 Jan;165(1):59-6716392963Nat Struct Mol Biol. 2006 May;13(5):451-716622404DNA Repair (Amst). 2008 May 3;7(5):725-3318325854Cell. 2008 Oct 3;135(1):85-9618854157Cell. 2008 Oct 3;135(1):97-10918854158Int J Radiat Oncol Biol Phys. 2009 Jul 15;74(4):1236-4119545789Cancer Res. 2012 Mar 1;72(5):1221-822237628AnimalsCell DeathCell LineDNA Breaks, Double-StrandedDNA End-Joining RepairDNA FragmentationDNA Repair EnzymesmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasephysiologyDNA-Binding ProteinsmetabolismHumansLinear Energy TransferMRE11 Homologue ProteinMice, Inbred C57BLRadiation Injuries, ExperimentalgeneticsmetabolismUp-RegulationX-RaysApe1DNA DamageDNA Damage ResponseDNA EnzymeDNA RepairDNA-binding ProteinHigh LETRadiation BiologyRadiosensitivity
20149126020149126020151160ppublish25210033M114.60495910.1074/jbc.M114.604959PMC4215242
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1099-04612922015FebJournal of biochemical and molecular toxicologyJ. Biochem. Mol. Toxicol.Enzyme kinetics of an alternative splicing isoform of mitochondrial 8-oxoguanine DNA glycosylase, ogg1-1b, and compared with the nuclear ogg1-1a.49-5610.1002/jbt.21605Eight alternatively spliced isoforms of human 8-oxoguanine DNA glycosylase (OGG1) (OGG1-1a to -1c and -2a to -2e) are registered in the National Center for Biotechnology Information. OGG1(s) in mitochondria have not yet been fully characterized biochemically. In this study, we purified mitochondrial recombinant OGG1-1b protein and compared its activity with nuclear OGG1-1a protein. The reaction rate constant (kg ) of the 7,8-dihydro-8-oxoguanine (8-oxoG) glycosylase activity of OGG1-1b was 8-oxoG:C > 8-oxoG:T > 8-oxoG:G > 8-oxoG:A (7.96, 0.805, 0.070, and 0.015 min(-1) , respectively) and that of the N-glycosylase/DNA lyase activity (kgl ) of OGG1-1b was 8-oxoG:C > 8-oxoG:T ≃8-oxoG:G > 8-oxoG:A (0.286, 0.079, 0.040, and negligible min(-1) , respectively). These reaction rate constants were similar to those of OGG1-1a except for kgl against 8-oxoG:A. APEX nuclease 1 was required to promote DNA strand breakage by OGG1-1b. These results suggest that OGG1-1b is associated with 8-oxoG cleavage in human mitochondria and that the mechanism of this repair is similar to that of nuclear OGG1-1a. © 2014 Wiley Periodicals, Inc.OgawaAkiraAFunctional Genomics Laboratory, School of Science and Engineering, Aoyama Gakuin University, Sagamihara, Kanagawa, 252-5258, Japan. chiefurihata@gmail.com.WatanabeTakashiTShojiSayakaSFurihataChieCengComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't20140904
United StatesJ Biochem Mol Toxicol97172311095-66700Isoenzymes0Mitochondrial Proteins0Nuclear ProteinsEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAlternative SplicingphysiologyCell Line, TumorCell NucleusenzymologygeneticsDNA GlycosylasesgeneticsmetabolismHumansIsoenzymesgeneticsmetabolismKineticsMitochondriaenzymologygeneticsMitochondrial ProteinsgeneticsmetabolismNuclear ProteinsgeneticsmetabolismEnzyme ActivityMitochondrial OGG1-1bMultiple-turnover ConditionNuclear OGG1-1aSingle-turnover Condition
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1932-6203992014PloS onePLoS ONERole of the DNA base excision repair protein, APE1 in cisplatin, oxaliplatin, or carboplatin induced sensory neuropathy.e10648510.1371/journal.pone.0106485Although chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of platinum drugs, the mechanisms of this toxicity remain unknown. Previous work in our laboratory suggests that cisplatin-induced CIPN is secondary to DNA damage which is susceptible to base excision repair (BER). To further examine this hypothesis, we studied the effects of cisplatin, oxaliplatin, and carboplatin on cell survival, DNA damage, ROS production, and functional endpoints in rat sensory neurons in culture in the absence or presence of reduced expression of the BER protein AP endonuclease/redox factor-1 (APE1). Using an in situ model of peptidergic sensory neuron function, we examined the effects of the platinum drugs on hind limb capsaicin-evoked vasodilatation. Exposing sensory neurons in culture to the three platinum drugs caused a concentration-dependent increase in apoptosis and cell death, although the concentrations of carboplatin were 10 fold higher than cisplatin. As previously observed with cisplatin, oxaliplatin and carboplatin also increased DNA damage as indicated by an increase in phospho-H2AX and reduced the capsaicin-evoked release of CGRP from neuronal cultures. Both cisplatin and oxaliplatin increased the production of ROS as well as 8-oxoguanine DNA adduct levels, whereas carboplatin did not. Reducing levels of APE1 in neuronal cultures augmented the cisplatin and oxaliplatin induced toxicity, but did not alter the effects of carboplatin. Using an in vivo model, systemic injection of cisplatin (3 mg/kg), oxaliplatin (3 mg/kg), or carboplatin (30 mg/kg) once a week for three weeks caused a decrease in capsaicin-evoked vasodilatation, which was delayed in onset. The effects of cisplatin on capsaicin-evoked vasodilatation were attenuated by chronic administration of E3330, a redox inhibitor of APE1 that serendipitously enhances APE1 DNA repair activity in sensory neurons. These outcomes support the importance of the BER pathway, and particularly APE1, in sensory neuropathy caused by cisplatin and oxaliplatin, but not carboplatin and suggest that augmenting DNA repair could be a therapeutic target for CIPN. KelleyMark RMRDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, Indiana, United States of America; Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.JiangYanlinYDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, Indiana, United States of America.GuoChunluCDepartment of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.ReedAprilADepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, Indiana, United States of America.MengHongdiHDepartment of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.VaskoMichael RMRDepartment of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.engCA121168CANCI NIH HHSUnited StatesCA121168S1CANCI NIH HHSUnited StatesCA167291CANCI NIH HHSUnited StatesR01 CA121168CANCI NIH HHSUnited StatesR01 CA167291CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20140904
United StatesPLoS One1012850811932-62030Organoplatinum Compounds04ZR38536JoxaliplatinBG3F62OND5CarboplatinEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseQ20Q21Q62JCisplatinIMJ Peripher Nerv Syst. 2008 Mar;13(1):27-4618346229Neurotoxicology. 1999 Dec;20(6):883-710693969Nature. 2007 Jun 21;447(7147):941-5017581577Rejuvenation Res. 2011 Jun;14(3):293-30821595514Anticancer Res. 2004 Jul-Aug;24(4):2127-3415330152Biochemistry. 2013 Apr 30;52(17):2955-6623597102Carcinogenesis. 2002 Feb;23(2):341-911872643J Neurosci. 2010 Mar 17;30(11):3933-4620237264J Pharmacol Exp Ther. 2002 Sep;302(3):839-4512183638Neurotoxicology. 2011 Jan;32(1):140-920932997Curr Mol Pharmacol. 2012 Jan;5(1):3-1322122461Carcinogenesis. 2007 Aug;28(8):1629-3717389610Am J Otol. 1997 Sep;18(5):559-719303151Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Ann Oncol. 1998 Oct;9(10):1053-719834817Mol Pain. 2010;6:7621050491Cancer. 1985 May 15;55(10):2303-l63886121Semin Oncol. 2002 Oct;29(5 Suppl 15):21-3312422305DNA Repair (Amst). 2011 Sep 5;10(9):942-5221741887Neuroscience. 2007 Apr 14;145(4):1260-617045754Cancer Treat Rev. 2006 Aug;32(5):390-716781082Antioxid Redox Signal. 2011 Jun 15;14(12):2465-7720812782Biochemistry. 2011 Jan 11;50(1):82-9221117647DNA Repair (Amst). 2005 Mar 2;4(3):367-7915661660Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642J Pharmacol Exp Ther. 2010 Sep 1;334(3):988-9820504914DNA Repair (Amst). 2013 Aug;12(8):685-9023684797Nat Rev Drug Discov. 2005 Apr;4(4):307-2015789122Fundam Appl Toxicol. 1995 Jul;26(2):293-3007589918Exp Neurol. 2011 Dec;232(2):154-6121907196Neurobiol Dis. 2005 Mar;18(2):305-1315686959Mol Cancer Ther. 2011 Sep;10(9):1698-70821700832Laryngoscope. 2001 Jul;111(7):1147-5511568534J Inorg Biochem. 1999 Oct;77(1-2):105-1010626361Cancer Invest. 2010 Nov;28(9):885-9520919954J Neurol Neurosurg Psychiatry. 1998 May;64(5):667-99598687Curr Cancer Drug Targets. 2010 Nov;10(7):670-8220578989Cancer Res. 2008 Aug 1;68(15):6425-3418676868Mutat Res. 2007 Jan 3;614(1-2):24-3616879837Mol Cancer Ther. 2009 Jan;8(1):10-619139108Biochemistry. 2012 Jan 17;51(2):695-70522148505Clin Colorectal Cancer. 2011 Jun;10(2):126-3321859566Int J Cancer. 2012 Nov 15;131(10):2433-4422377908Neurotoxicology. 2006 Dec;27(6):992-100216797073J Med Chem. 2010 Feb 11;53(3):1200-1020067291Cancer Invest. 2011 Jan;29(1):21-821166495Cytokine. 2004 Feb 7;25(3):94-10214698135Nat Rev Neurol. 2010 Dec;6(12):657-6621060341Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Microvasc Res. 1998 Jan;55(1):3-139473405J Clin Oncol. 2014 Jun 20;32(18):1941-6724733808Br J Cancer. 2011 Feb 15;104(4):653-6321266972J Clin Oncol. 1992 May;10(5):795-8031569451Neuroscience. 1988 Mar;24(3):739-683288903Metallomics. 2009;1(4):280-9120046924Muscle Nerve. 1999 Mar;22(3):329-4010086893Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143Chemother Res Pract. 2011;2011:84301922312559J Clin Oncol. 1999 Jan;17(1):409-2210458260J Clin Invest. 1998 Jun 15;101(12):2842-509637718J Clin Oncol. 2002 Apr 1;20(7):1767-7411919233Mol Cell. 2005 Feb 4;17(3):463-7015694346DNA Repair (Amst). 2009 Nov 2;8(11):1273-8219726241J Exp Pathol. 1992;6(1-2):65-741625039Muscle Nerve. 2004 Mar;29(3):387-9214981738Neurobiol Dis. 2001 Dec;8(6):1027-3511741398Ann Oncol. 1998 Apr;9(4):443-79636837Nucleic Acids Res. 2005;33(15):4711-2416113242Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463Pain. 2011 Feb;152(2):308-1321145656Nucleic Acids Res. 2007;35(6):1812-2117329374Nucleic Acids Res. 2013 Aug;41(15):7332-4323761438Muscle Nerve. 2005 Jul;32(1):51-6015880395J Neurosci. 2007 Aug 29;27(35):9451-717728458AnimalsCarboplatinpharmacologyCells, CulturedCisplatinpharmacologyDNA DamagegeneticsDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismMaleOrganoplatinum CompoundspharmacologyPeripheral Nervous System Diseaseschemically inducedgeneticsRatsSensory Receptor Cellsdrug effectsmetabolism
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1001-93913252014MayZhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseasesZhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi[Effects of polymorphisms in XRCC1 and APE1 on vinyl chloride-induced chromosome damage].321-6To evaluate the effects of polymorphisms in XRCC1 and APE1 genes on vinyl chloride (VC)-induced chromosomal damage in peripheral lymphocytes.In this study, 317 workers occupationally exposed to VC were recruited from a factory in Shandong Province, China. The micronucleus (MN) frequency in peripheral lymphocytes was used as an indicator of chromosomal damage. Polymerase chain reaction-restriction fragment length polymorphism and created restriction site combined with restriction fragment length polymorphism were used to determine the five single nucleotide polymorphisms in XRCC1 and APE1 genes in the base excision repair pathway. The association of chromosomal damage with these polymorphisms and the haplotype of XRCC1 was analyzed using Poisson regression and PHASE 2.0.2.It was found that among the VC-exposed workers, individuals with XRCC1 polymorphisms (-77C/T, Arg194Trp, Arg280His, and Arg399Gln) had a significantly higher MN frequency than those with homozygous wild-type genotypes, with frequency ratios (FR) as follows, respectively: FR = 1.21, 95%CI: 1.05∼1.39 (P < 0.05); FR = 1.14, 95%CI: 1.00∼1.38 (P < 0.05); FR = 1.26, 95%CI: 1.11∼1.44 (P < 0.05); FR = 1.23, 95%CI: 1.08∼1.46 (P < 0.05). APE1 Asp148Glu was found of no significant relationship with MN frequency. Haplotype analysis of XRCC1 demonstrated that the MN frequencies in subjects with CTAA/CTAA and CCAA/CTAA were significantly higher than that in those with TCGG/TCGG (FR = 1.19, 95%CI: 1.02∼1.32, P < 0.05; FR = 1.41, 95%CI: 1.02∼1.87, P < 0.05). Furthermore, association was found between accumulated exposure to VC and XRCC1 polymorphisms (-77C/T, Arg194Trp, Arg280His, and Arg399Gln) after adjustment for age, sex, drinking, and smoking.VC can induce chromosomal damage even when the exposure level is lower than the national occupational health standard of China (PC-TWA: 10 mg/m(3)); the polymorphisms in XRCC1 and APE1 are associated with chromosomal damage induced by VC.WangJinweiJDepartment of Occupational Health and Toxicity, School of Pubic Health, Fudan University, Shanghai 200032, China.XuXiaowenXWangQiQZhangFangFSunYuanYTanHongshanHFengNannanNZhouLifangLYeYunjieYChengXuemeiXShaoHuaHXiaZhaolinZE-mail: zlxia@shmu.edu.cn.chiJournal ArticleResearch Support, Non-U.S. Gov't
ChinaZhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi84108401001-93910DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseWD06X94M2DVinyl ChlorideIMAdultDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleHaplotypesHumansMaleMicronuclei, Chromosome-DefectiveMiddle AgedOccupational Exposureadverse effectsPolymorphism, Restriction Fragment LengthVinyl ChloridepoisoningX-ray Repair Cross Complementing Protein 1Young Adult
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1568-7856222014OctDNA repairDNA Repair (Amst.)Functional variants of human APE1 rescue the DNA repair defects of the yeast AP endonuclease/3'-diesterase-deficient strain.53-6610.1016/j.dnarep.2014.07.010S1568-7864(14)00196-7Human APE1 is an essential enzyme performing functions in DNA repair and transcription. It possesses four distinct repair activities acting on a variety of base and sugar derived DNA lesions. APE1 has seven cysteine residues and Cys65, and to a lesser extent Cys93 and Cys99, is uniquely involved in maintaining a subset of transcription factors in the reduced and active state. Four of the cysteines Cys93, 99, 208 and 310 of APE1 are located proximal to its active site residues Glu96, Asp210 and His309 involved in processing damaged DNA, raising the possibility that missense mutation of these cysteines could alter the enzyme DNA repair functions. An earlier report documented that serine substitution of the individual cysteine residues did not affect APE1 ability to cleave an abasic site oligonucleotide substrate in vitro, except for Cys99Ser, although any consequences of these variants in the repair of in vivo DNA lesions were not tested. Herein, we mutated all seven cysteines of APE1, either singly or in combination, to alanine and show that none of the resulting variants interfered with the enzyme DNA repair functions. Cross-specie complementation analysis reveals that these APE1 cysteine variants fully rescued the yeast DNA repair deficient strain YW778, lacking AP endonucleases and 3'-diesterases, from toxicities caused by DNA damaging agents. Moreover, the elevated spontaneous mutations arising in strain YW778 from the lack of the DNA repair activities were completely suppressed by the APE1 cysteine variants. These findings suggest that the cysteine residues of APE1 are unlikely to play a role in the DNA repair functions of the enzyme in vivo. We also examine other APE1 missense mutations and provide the first evidence that the variant Asp308Ala with normal AP endonuclease, but devoid of 3'→5' exonuclease, displays hypersensitivity to the anticancer drug bleomycin, and not to other agents, suggesting that it has a defect in processing unique DNA lesions. Molecular modeling reveals that Asp308Ala cannot make proper contact with Mg(2+) and may alter the enzyme ability to cleave or disassociate from specific DNA lesions. Copyright © 2014 Elsevier B.V. All rights reserved.WangZhiqiangZMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal 5415 Boul. de l' Assomption, Montréal, Québec, Canada H1T 2M4.AyoubEmilyEMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal 5415 Boul. de l' Assomption, Montréal, Québec, Canada H1T 2M4.MazouziAbdelghaniAMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal 5415 Boul. de l' Assomption, Montréal, Québec, Canada H1T 2M4.GrinIngaIGroupe Réparation de l'ADN, Université Paris Sud, Laboratoire Stabilité Génétique et Oncogenèse CNRS, UMR 8200, Gustave-Roussy Cancer Center, F-94805 Villejuif Cedex, France; SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave. , Novosibirsk 630090, Russia.IshchenkoAlexander AAAGroupe Réparation de l'ADN, Université Paris Sud, Laboratoire Stabilité Génétique et Oncogenèse CNRS, UMR 8200, Gustave-Roussy Cancer Center, F-94805 Villejuif Cedex, France.FanJinjiangJResearch Institute of the McGill University Health Centre and Department of Medicine, McGill University, 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada.YangXiaomingXMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal 5415 Boul. de l' Assomption, Montréal, Québec, Canada H1T 2M4.HariharTaramattiTMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal 5415 Boul. de l' Assomption, Montréal, Québec, Canada H1T 2M4.SaparbaevMuratMGroupe Réparation de l'ADN, Université Paris Sud, Laboratoire Stabilité Génétique et Oncogenèse CNRS, UMR 8200, Gustave-Roussy Cancer Center, F-94805 Villejuif Cedex, France.RamotarDindialDMaisonneuve-Rosemont Hospital, Research Center, Université de Montréal 5415 Boul. de l' Assomption, Montréal, Québec, Canada H1T 2M4. Electronic address: dindial.ramotar@umontreal.ca.engCanadian Institutes of Health ResearchCanadaJournal ArticleResearch Support, Non-U.S. Gov't20140809
NetherlandsDNA Repair (Amst)1011391381568-7856EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseK848JZ4886CysteineIMCysteinegeneticsDNA DamageDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismHumansMutation, MissenseSaccharomyces cerevisiaegeneticsmetabolismBase-excision repairDNA repairHuman AP endonucleaseMutationsOxidative DNA damageYeast
201403242014070220140717201481160201481260201562560ppublish25108836S1568-7864(14)00196-710.1016/j.dnarep.2014.07.010
251075712015022020151119
1432-08437442014OctCancer chemotherapy and pharmacologyCancer Chemother. Pharmacol.Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-paclitaxel chemotherapy.777-8610.1007/s00280-014-2562-1Drug resistance is not only one of the major obstacles to treatment but also a poor prognosis in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study was to evaluate the predictive value of APE1, BRCA1, ERCC1 and TUBB3 in advanced NSCLC patients who received platinum-paclitaxel treatment.One hundred and thirty-six advanced NSCLC patients, who were treated with first-line platinum-paclitaxel chemotherapy, were enrolled in this study. The protein expression levels of APE1, BRCA1, ERCC1 and TUBB3 were assessed by immunohistochemistry and analyzed for the association with response to chemotherapy and progression-free survival (PFS) and overall survival (OS).Patients with negative expression of APE1, ERCC1 or TUBB3 benefited from platinum plus paclitaxel regimen chemotherapy. ERCC1-negative patients had better PFS (P = 0.016) and OS (P = 0.030) compared with positive patients. Similarly, the APE1-negative patients showed better PFS (P = 0.004) and longer OS though statistically insignificant. Multivariate analysis showed that APE1 and ERCC1 were independent predictor for PFS (HR 2.07; P = 0.004 and HR 1.66; P = 0.016) and OS (HR 1.99; P = 0.008 and HR 1.64; P = 0.040). Moreover, patients with both APE1- and ERCC1-negative or both APE1- and TUBB3-negative tumors had significantly higher response rate, longer median PFS and OS following treatment with platinum and paclitaxel (P < 0.05).The data indicate that APE1, ERCC1 and TUBB3 could be a useful biomarker to predict clinical outcome in patients with advanced NSCLC receiving first-line platinum-paclitaxel chemotherapy.LiZhengZCancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, No. 10 Changjiang Zhi Rd., Yuzhong District, Chongqing, 400042, China.QingYiYGuanWeiWLiMengxiaMPengYuYZhangShihengSXiongYanliYWangDongDengJournal ArticleResearch Support, Non-U.S. Gov't20140809
GermanyCancer Chemother Pharmacol78065190344-57040Antineoplastic Agents0BRCA1 Protein0Biomarkers, Tumor0DNA-Binding Proteins0TUBB3 protein, human0TubulinEC 3.1.-ERCC1 protein, humanEC 3.1.-EndonucleasesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseP88XT4IS4DPaclitaxelQ20Q21Q62JCisplatinIMAntineoplastic Agentsadministration & dosageadverse effectsAntineoplastic Combined Chemotherapy ProtocolsBRCA1 ProteingeneticsBiomarkers, TumorgeneticsCarcinoma, Non-Small-Cell Lungdrug therapymetabolismmortalitypathologyCisplatinadministration & dosageadverse effectsDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsDisease-Free SurvivalDrug Resistance, NeoplasmDrug Screening Assays, AntitumorEndonucleasesgeneticsFemaleGene Expression ProfilingmethodsHumansImmunohistochemistryLung Neoplasmsdrug therapymetabolismmortalitypathologyMaleMiddle AgedNeoplasm StagingPaclitaxeladministration & dosageadverse effectsPredictive Value of TestsPrognosisTreatment OutcomeTubulingenetics
2014052020140728201481060201481260201522460ppublish2510757110.1007/s00280-014-2562-1
250899392015042020171116
1366-58041962014SepBiomarkers : biochemical indicators of exposure, response, and susceptibility to chemicalsBiomarkersPolymorphism of DNA repair genes OGG1, XRCC1, XPD and ERCC6 in bladder cancer in Belarus.509-1610.3109/1354750X.2014.943291The study of DNA base and nucleotide excision repair gene polymorphisms in bladder cancer seems to have a predictive value because of the evident relationship between the DNA damage response induced by environmental mutagens and cancer predisposition.The objective was to determine OGG1 Ser326Cys, XRCC1 Arg399Gln, XPD Asp312Asn, and ERCC6 Met1097Val polymorphisms in bladder cancer patients as compared to controls.Both groups were predominantly represented by Belarusians and Eastern Slavs. DNA samples from 336 patients and 370 controls were genotyped using a PCR-RFLP method.The genotype distributions were in agreement with the Hardy-Weinberg equilibrium. The minor allele frequencies in the control population were in the range of those in Caucasians in contrast to Asians. The OGG1 326 Ser/Cys and XPD 312 Asp/Asn heterozygous genotypes were inversely associated with cancer risk (OR [95% CI] = 0.69 [0.50-0.95] and 1.35 [1.0-1.82], respectively). The contrasting effects of these genotypes were potentiated due to their interactions with smoking habit or age.Among four DNA repair gene polymorphisms, the OGG1 326 Ser/Cys and XPD 312 Asp/Asn heterozygous genotypes might be recognized as potential genetic markers modifying susceptibility to bladder cancer in Belarus.RamaniukVolha PVPInstitute of Genetics and Cytology, National Academy of Sciences of Belarus , Minsk , Republic of Belarus .NikitchenkoNataliya VNVSavinaNataliya VNVKuzhirTatyana DTDRolevichAlexander IAIKrasnySergei ASASushinskyVadim EVEGoncharovaRoza IRIengJournal Article20140804
EnglandBiomarkers96060001354-750X0DNA-Binding Proteins0Poly-ADP-Ribose Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.-DNA HelicasesEC 3.6.4.12ERCC6 protein, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanEC 6.5.1.-DNA Repair EnzymesIMAdultAgedAged, 80 and overCarcinoma, Transitional CellgeneticsCase-Control StudiesDNA GlycosylasesgeneticsDNA HelicasesgeneticsDNA RepairDNA Repair EnzymesgeneticsDNA-Binding ProteinsgeneticsFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseHumansMaleMiddle AgedPoly-ADP-Ribose Binding ProteinsPolymorphism, Single NucleotideRepublic of BelarusUrinary Bladder NeoplasmsgeneticsX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D ProteingeneticsBladder cancerDNA repair gene polymorphismsERCC6OGG1XPDXRCC1
2014856020148560201542260ppublish2508993910.3109/1354750X.2014.943291
250862532014101720161126
0006-30021840102014OctBiochimica et biophysica actaBiochim. Biophys. ActaPre-steady-state fluorescence analysis of damaged DNA transfer from human DNA glycosylases to AP endonuclease APE1.3042-5110.1016/j.bbagen.2014.07.016S0304-4165(14)00261-XDNA glycosylases remove the modified, damaged or mismatched bases from the DNA by hydrolyzing the N-glycosidic bonds. Some enzymes can further catalyze the incision of a resulting abasic (apurinic/apyrimidinic, AP) site through β- or β,δ-elimination mechanisms. In most cases, the incision reaction of the AP-site is catalyzed by special enzymes called AP-endonucleases.Here, we report the kinetic analysis of the mechanisms of modified DNA transfer from some DNA glycosylases to the AP endonuclease, APE1. The modified DNA contained the tetrahydrofurane residue (F), the analogue of the AP-site. DNA glycosylases AAG, OGG1, NEIL1, MBD4(cat) and UNG from different structural superfamilies were used.We found that all DNA glycosylases may utilise direct protein-protein interactions in the transient ternary complex for the transfer of the AP-containing DNA strand to APE1.We hypothesize a fast "flip-flop" exchange mechanism of damaged and undamaged DNA strands within this complex for monofunctional DNA glycosylases like MBD4(cat), AAG and UNG. Bifunctional DNA glycosylase NEIL1 creates tightly specific complex with DNA containing F-site thereby efficiently competing with APE1. Whereas APE1 fast displaces other bifunctional DNA glycosylase OGG1 on F-site thereby induces its shifts to undamaged DNA regions.Kinetic analysis of the transfer of DNA between human DNA glycosylases and APE1 allows us to elucidate the critical step in the base excision repair pathway.Copyright © 2014 Elsevier B.V. All rights reserved.KuznetsovaAlexandra AAAInstitute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia.KuznetsovNikita ANAInstitute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia; Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia. Electronic address: nikita.kuznetsov@niboch.nsc.ru.IshchenkoAlexander AAAGroupe «Réparation de l'ADN», Université Paris-Sud XI, UMR8200 CNRS, Institut Gustave Roussy, Villejuif Cedex F-94805, France.SaparbaevMurat KMKGroupe «Réparation de l'ADN», Université Paris-Sud XI, UMR8200 CNRS, Institut Gustave Roussy, Villejuif Cedex F-94805, France.FedorovaOlga SOSInstitute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia; Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia. Electronic address: fedorova@niboch.nsc.ru.engJournal ArticleResearch Support, Non-U.S. Gov't20140731
NetherlandsBiochim Biophys Acta02175130006-3002EC 3.2.2.-DNA GlycosylasesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMDNA DamageDNA GlycosylaseschemistryDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasechemistryFluorescenceHumansAP endonucleaseBase excision repairCoordination of DNA repair processDNA glycosylaseProtein–protein interaction
20140508201407082014072220148360201483602014101860ppublish25086253S0304-4165(14)00261-X10.1016/j.bbagen.2014.07.016
2508313920170810
1873-135X766-7672014AugMutation researchMutat. Res.Impact of abasic site orientation within nucleosomes on human APE1 endonuclease activity.19-24Glycosylases responsible for recognizing DNA lesions and initiating Base Excision Repair (BER) are impeded by the presence of histones, which are essential for compaction of the genetic material in the nucleus. Abasic sites are an abundant mutagenic lesion in the DNA, arising spontaneously and as the product of glycosylase activity, making it a common intermediate in BER. The apurinic/apyrimidinic endonuclease 1 (APE1) recognizes abasic sites and cleaves the DNA backbone adjacent to the lesion, creating the single-strand break essential for the subsequent steps of BER. In this study the endonuclease activity of human APE1 was measured on reconstituted nucleosome core particles (NCPs) with DNA containing enzymatically-created abasic sites (AP) or the abasic site analog tetrahydrofuran (TF) at different rotational positions relative to the histone core surface. The presence of histones on the DNA reduced APE1 activity overall, and the magnitude was greatly influenced by differences in orientation of the lesions along the DNA gyre relative to the histone core. Abasic moieties oriented with their phosphate backbones adjacent to the underlying histones (In) were cleaved less efficiently than those oriented away from the histone core (Out) or between the In and Out orientations (Mid). The impact on APE1 at each orientation was very similar between the AP and TF lesions, highlighting the dependability of the TF abasic analog in APE1 activity measurements in nucleosomes. Measurement of APE1 binding to the NCP substrates reveals a substantial reduction in its interaction with nucleosomes compared to naked DNA, also in a lesion orientation-dependent manner, reinforcing the concept that reduction in APE1 activity on nucleosomes is due to occlusion from its abasic DNA substrate by the histones. These results suggest that APE1 activity in nucleosomes, like BER glycosylases, is primarily regulated by its chance interactions with transiently exposed lesions.HinzJohn MJMSchool of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520.engR01 ES004106ESNIEHS NIH HHSUnited StatesR21 ES020955ESNIEHS NIH HHSUnited StatesJournal Article
NetherlandsMutat Res04007630027-5107J Biol Chem. 1987 Jul 25;262(21):10171-92440861J Mol Biol. 2007 Aug 17;371(3):649-6817586522Biochemistry. 1999 Jul 20;38(29):9485-9410413526Crit Rev Biochem Mol Biol. 2008 Jul-Aug;43(4):239-7618756381Mol Cell Biol. 2007 Dec;27(24):8442-5317923696Cell Mol Life Sci. 2009 Mar;66(6):981-9319153658J Cell Physiol. 2013 Feb;228(2):258-6622718094J Biol Chem. 2013 May 10;288(19):13863-7523543741DNA Repair (Amst). 2010 Feb 4;9(2):134-4320005182Basic Life Sci. 1986;38:341-73741336Cold Spring Harb Symp Quant Biol. 2000;65:127-3312760027Carcinogenesis. 2001 Jul;22(7):987-9811408341J Biol Chem. 2005 Dec 2;280(48):40051-716210312Nature. 2000 Jan 27;403(6768):451-610667800Adv Enzymol Relat Areas Mol Biol. 1987;60:1-342444076Proc Natl Acad Sci U S A. 1989 Oct;86(19):7418-222798415Annu Rev Biochem. 2002;71:17-5012045089J Mol Biol. 2008 May 23;379(1):17-2718439621Annu Rev Biochem. 2002;71:133-6312045093J Biol Chem. 2010 Jan 22;285(4):2876-8519933279Nature. 1996 Nov 7;384(6604):87-928900285J Mol Biol. 1998 Feb 13;276(1):19-429514715EMBO J. 2002 Nov 1;21(21):5943-5212411511Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4646-5120176960Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7465-7012799467Cell Res. 2008 Jan;18(1):27-4718166975Mol Cell Biol. 1995 Aug;15(8):4375-847623832Nucleic Acids Res. 2012 Jan;40(2):692-70021930508DNA Repair (Amst). 2005 Feb 3;4(2):203-915590328Nucleic Acids Res. 1980 Aug 25;8(16):3517-347433098J Mol Biol. 1990 Nov 5;216(1):69-842172553Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Biochemistry. 1991 Oct 15;30(41):9931-401911785EMBO J. 1999 Jul 1;18(13):3712-2310393186Mol Cell Biol. 2011 Nov;31(22):4623-3221930793DNA Repair (Amst). 2007 Apr 1;6(4):398-40917129767APE1 endonucleaseDNA damagehistonenucleosometetrahydrofuran
201482602014826020148260ppublish2508313910.1016/j.mrfmmm.2014.05.008PMC4112536NIHMS603296S0027-5107(14)00103-1
250489462014102220140722
1879-12981122014OctChemosphereChemosphereProcessing of abasic site damaged lesions by APE1 enzyme on DNA adsorbed over normal and organomodified clay.503-1010.1016/j.chemosphere.2014.05.022S0045-6535(14)00646-8The efficiency of the apurinic/apyrimidinic endonuclease (APE1) DNA repair enzyme in the processing of abasic site DNA damage lesions at precise location in DNA oligomer duplexes that are adsorbed on clay surfaces was evaluated. Three different forms of clay namely montmorillonite, quaternary ammonium salt modified montmorillonite and its boiled counterpart i.e. partially devoid of organic moiety were used for a comparative study of adsorption, desorption and DNA repair efficiency on their surfaces. The interaction between the DNA and the clay was analysed by X-ray diffraction, Atomic force microscopy, UV-Vis spectroscopy and Infrared spectroscopy. The abasic site cleavage efficiency of APE1 enzyme was quantitatively evaluated by polyacrylamide gel electrophoresis. Apart from the difference in the DNA adsorption or desorption capacity of the various forms of clay, substantial variation in the repair efficiency of abasic sites initiated by the APE1 enzyme on the clay surfaces was observed. The incision efficiency of APE1 enzyme at abasic sites was found to be greatly diminished, when the DNA was adsorbed over organomodified montmorillonite. The reduced repair activity indicates an important role of the pendant surfactant groups on the clay surfaces in directing APE1 mediated cleavage of abasic site DNA damage lesions. Copyright © 2014 Elsevier Ltd. All rights reserved.KumariBhaviniBDepartment of Chemistry, Indian Institute of Technology Patna, Patna 800013, Bihar, India.BanerjeeShib ShankarSSDepartment of Materials Science and Engineering, Indian Institute of Technology Patna, Patna 800013, Bihar, India.SinghVandanaVDepartment of Chemistry, Indian Institute of Technology Patna, Patna 800013, Bihar, India.DasProlayPDepartment of Chemistry, Indian Institute of Technology Patna, Patna 800013, Bihar, India. Electronic address: prolay@iitp.ac.in.BhowmickAnil KAKDepartment of Materials Science and Engineering, Indian Institute of Technology Patna, Patna 800013, Bihar, India.engJournal ArticleResearch Support, Non-U.S. Gov't20140607
EnglandChemosphere03206570045-65350Quaternary Ammonium Compounds1302-78-9Bentonite9007-49-2DNAEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdsorptionBentonitechemistrytoxicityDNAchemistrygeneticsmetabolismDNA CleavageDNA DamageDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismModels, MolecularMutagenesisNucleic Acid ConformationQuaternary Ammonium CompoundschemistrySurface PropertiesX-Ray DiffractionAPE1Abasic siteDNA damageMontmorilloniteOrganomodified montmorillonite
2014032420140509201405112014723602014723602014102360ppublish25048946S0045-6535(14)00646-810.1016/j.chemosphere.2014.05.022
250385722015042120140805
1568-7856212014SepDNA repairDNA Repair (Amst.)The role of Asn-212 in the catalytic mechanism of human endonuclease APE1: stopped-flow kinetic study of incision activity on a natural AP site and a tetrahydrofuran analogue.43-5410.1016/j.dnarep.2014.06.008S1568-7864(14)00186-4Mammalian AP endonuclease 1 is a pivotal enzyme of the base excision repair pathway acting on apurinic/apyrimidinic sites. Previous structural and biochemical studies showed that the conserved Asn-212 residue is important for the enzymatic activity of APE1. Here, we report a comprehensive pre-steady-state kinetic analysis of two APE1 mutants, each containing amino acid substitutions at position 212, to ascertain the role of Asn-212 in individual steps of the APE1 catalytic mechanism. We applied the stopped-flow technique for detection of conformational transitions in the mutant proteins and DNA substrates during the catalytic cycle, using fluorophores that are sensitive to the micro-environment. Our data indicate that Asn-212 substitution by Asp reduces the rate of the incision step by ∼550-fold, while Ala substitution results in ∼70,000-fold decrease. Analysis of the binding steps revealed that both mutants continued to rapidly and efficiently bind to abasic DNA containing the natural AP site or its tetrahydrofuran analogue (F). Moreover, transient kinetic analysis showed that N212A APE1 possessed a higher binding rate and a higher affinity for specific substrates compared to N212D APE1. Molecular dynamics (MD) simulation revealed a significant dislocation of the key catalytic residues of both mutant proteins relative to wild-type APE1. The analysis of the model structure of N212D APE1 provides evidence for alternate hydrogen bonding between Asn-212 and Asp-210 residues, whereas N212A possesses an extended active site pocket due to Asn removal. Taken together, these biochemical and MD simulation results indicate that Asn-212 is essential for abasic DNA incision, but is not crucial for effective recognition/binding. Copyright © 2014 Elsevier B.V. All rights reserved.KanazhevskayaLyubov YuLYInstitute of Chemical Biology & Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrentyev Ave., 8, Novosibirsk 630090, Russia; Novosibirsk State University, Pirogova St., 2, Novosibirsk 630090, Russia.KovalVladimir VVVInstitute of Chemical Biology & Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrentyev Ave., 8, Novosibirsk 630090, Russia; Novosibirsk State University, Pirogova St., 2, Novosibirsk 630090, Russia.LomzovAlexander AAAInstitute of Chemical Biology & Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrentyev Ave., 8, Novosibirsk 630090, Russia; Novosibirsk State University, Pirogova St., 2, Novosibirsk 630090, Russia.FedorovaOlga SOSInstitute of Chemical Biology & Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrentyev Ave., 8, Novosibirsk 630090, Russia; Novosibirsk State University, Pirogova St., 2, Novosibirsk 630090, Russia. Electronic address: fedorova@niboch.nsc.ru.engJournal ArticleResearch Support, Non-U.S. Gov't
NetherlandsDNA Repair (Amst)1011391381568-78560Furans3N8FZZ6PY4tetrahydrofuran7006-34-0Asparagine9007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAmino Acid SequenceAsparaginechemistrygeneticsmetabolismCatalytic DomainDNAchemistrymetabolismDNA-(Apurinic or Apyrimidinic Site) LyasechemistrygeneticsmetabolismFuranschemistryHumansMolecular Dynamics SimulationMolecular Sequence DataMutation2-AminopurineAPE1Abasic siteBase excision repairMD simulationsPre-steady-state kineticsStopped-flow method
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250338342015022020170220
2092-6413462014Jul18Experimental & molecular medicineExp. Mol. Med.APE1/Ref-1 as an emerging therapeutic target for various human diseases: phytochemical modulation of its functions.e10610.1038/emm.2014.42Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme involved in the base excision repair (BER) pathway, which repairs oxidative base damage caused by endogenous and exogenous agents. APE1 acts as a reductive activator of many transcription factors (TFs) and has also been named redox effector factor 1, Ref-1. For example, APE1 activates activator protein-1, nuclear factor kappa B, hypoxia-inducible factor 1α, paired box gene 8, signal transducer activator of transcription 3 and p53, which are involved in apoptosis, inflammation, angiogenesis and survival pathways. APE1/Ref-1 maintains cellular homeostasis (redox) via the activation of TFs that regulate various physiological processes and that crosstalk with redox balancing agents (for example, thioredoxin, catalase and superoxide dismutase) by controlling levels of reactive oxygen and nitrogen species. The efficiency of APE1/Ref-1's function(s) depends on pairwise interaction with participant protein(s), the functions regulated by APE1/Ref-1 include the BER pathway, TFs, energy metabolism, cytoskeletal elements and stress-dependent responses. Thus, APE1/Ref-1 acts as a 'hub-protein' that controls pathways that are important for cell survival. In this review, we will discuss APE1/Ref-1's versatile nature in various human etiologies, including neurodegeneration, cancer, cardiovascular and other diseases that have been linked with alterations in the expression, subcellular localization and activities of APE/Ref-1. APE1/Ref-1 can be targeted for therapeutic intervention using natural plant products that modulate the expression and functions of APE1/Ref-1. In addition, studies focusing on translational applications based on APE1/Ref-1-mediated therapeutic interventions are discussed. ThakurShwetaSCenter for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Punjab, India.SarkarBibekanandaBCenter for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Punjab, India.CholiaRavi PRPCenter for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Punjab, India.GautamNandiniNCenter for Environmental Science and Technology, School of Environment and Earth Sciences, Central University of Punjab, Punjab, India.DhimanMonishaMCenter for Genetic Diseases and Molecular Medicine, School of Emerging Life Science Technologies, Central University of Punjab, Punjab, India.ManthaAnil KAK1] Center for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Punjab, India [2] Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.engJournal ArticleResearch Support, Non-U.S. Gov'tReview20140718
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1009-35912062014JunZhonghua nan ke xue = National journal of andrologyZhonghua Nan Ke Xue[Association of 8-hydroxyguanine glycosidase OGG1 Ser326Cys polymorphism with male infertility].518-22To explore the association of 8-hydroxyguanine glycosidase OGG1 Ser326Cys polymorphism with semen quality and the risk of male infertility.This case-control study included 620 idiopathic infertile patients and 385 normal fertile controls. We determined their genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and analyzed their semen quality by computer-aided semen analysis (CASA).The individuals with OGG1 326 Cys/Cys showed significantly lower sperm motility and concentration ([52.1 +/- 26.7]% and (3.75 +/- 0.91) x 10(6)/ml, ln transformed value) than the Ser/Ser carriers ([59.0 +/- 21.8] % and (4.12 +/- 0.88) x 10(6)/ml, ln transformed value) (P < 0.05). The risk of male infertility increased 69% in the OGG1 326Cys allele carriers as compared with the Ser carriers (OR = 1.69, 95% CI: 1.24 -2.31).OGG1 326 Ser/Cys polymorphism might contribute to the risk of male infertility in the southern Chinese population.ChenJian-ZhongJZWuSheng-MinSMJiGui-XiangGXGuAi-HuaAHchiEnglish AbstractJournal Article
ChinaZhonghua Nan Ke Xue1010935921009-3591EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultCase-Control StudiesDNA GlycosylasesgeneticsGenotypeHumansInfertility, MalegeneticsMaleMiddle AgedPolymorphism, Single NucleotideSemen AnalysisYoung Adult
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2219-284020262014Jul14World journal of gastroenterologyWorld J. Gastroenterol.APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans.8700-810.3748/wjg.v20.i26.8700To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ(2) tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility.The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m(2) (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter polymorphism -141 T/G genotype was associated with a reduced risk of colorectal cancer among subjects with a BMI < 25 kg/m(2) (OR = 0.214, 95%CI: 0.069-0.660, P < 0.05 relative to T/T genotype). There were significant gene-behavior interactions between smoking status and XRCC1 Arg399Gln, as well as BMI and APE1 -141T/G polymorphism (all P < 0.05).APE1 Asp148Glu is associated with increased CRC risk and smoking alters the association between XRCC1 Arg399Gln and CRC risk in the Chinese Han population.ZhangShi-HengSHShi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.WangLin-AngLAShi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.LiZhengZShi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.PengYuYShi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.CunYan-PingYPShi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.DaiNanNShi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.ChengYiYShi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.XiaoHeHShi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.XiongYan-LiYLShi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.WangDongDShi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.engJournal ArticleResearch Support, Non-U.S. Gov't
United StatesWorld J Gastroenterol1008834481007-93270DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMMol Vis. 2010;16:991-620577654Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12):3384-819959686Mutat Res. 2011 Jun 3;711(1-2):100-1221167187Mutagenesis. 2012 Jul;27(4):501-1022451681BMC Cancer. 2011;11:10421429202Cancer Sci. 2010 May;101(5):1247-5420331623Tumour Biol. 2013 Feb;34(1):555-6323188703Cancer Epidemiol. 2011 Oct;35(5):e38-4121612998Oncol Lett. 2013 Mar;5(3):959-96323426866Carcinogenesis. 2009 Jan;30(1):2-1018978338Arh Hig Rada Toksikol. 2011 Sep;62(3):207-1421971103J Mol Diagn. 2002 May;4(2):103-711986401Mol Aspects Med. 2007 Jun-Aug;28(3-4):258-7517628657Carcinogenesis. 2004 Sep;25(9):1689-9415073047Mutat Res. 2008 Feb 1;638(1-2):146-5317991492Carcinogenesis. 2001 Jun;22(6):917-2211375899Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Int J Colorectal Dis. 2011 Dec;26(12):1525-3021695387Jpn J Cancer Res. 2000 Sep;91(9):865-811011111Mutagenesis. 2012 Mar;27(2):219-2322294770Asian Pac J Cancer Prev. 2012;13(2):665-922524842J Epidemiol. 2012;22(1):64-7122186158Arch Med Res. 2011 Apr;42(3):226-3421722819Cancer Epidemiol Biomarkers Prev. 2010 Dec;19(12):3167-7321037106Prog Mol Biol Transl Sci. 2012;110:123-5322749145Environ Mol Mutagen. 2002;39(2-3):208-1511921191Int J Cancer. 2010 Dec 15;127(12):2893-91721351269Hum Exp Toxicol. 2012 Oct;31(10):981-100523023028Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2101-816609022Mutagenesis. 2010 Sep;25(5):463-7120534734J Exp Clin Cancer Res. 2008;27:4918823566FASEB J. 2009 Oct;23(10):3459-6919541747CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855J Natl Cancer Inst. 2012 Oct 3;104(19):1433-5723019048Antioxid Redox Signal. 2001 Aug;3(4):671-8311554453Clin Lab. 2013;59(1-2):163-823505922Curr Med Res Opin. 2011 Jul;27(7):1295-30221561390Cancer Lett. 2005 Nov 8;229(1):85-9115946795J Appl Genet. 2010;51(3):343-5220720310Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766AdultAgedAged, 80 and overAlcohol Drinkingadverse effectsethnologyAsian Continental Ancestry GroupgeneticsBody Mass IndexCase-Control StudiesChi-Square DistributionChinaepidemiologyColorectal NeoplasmsenzymologyethnologygeneticsDNA GlycosylasesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGene-Environment InteractionGenetic Association StudiesGenetic Predisposition to DiseaseHumansLogistic ModelsMaleMiddle AgedMultivariate AnalysisOdds RatioPhenotypePolymorphism, Single NucleotideProspective StudiesRisk FactorsSmokingadverse effectsethnologyX-ray Repair Cross Complementing Protein 1Young AdultApurinic endonuclease 1Base excision repairColorectal cancerSingle nucleotide polymorphismsX-ray repair cross-complementing groups
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1423-038035102014OctTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Association between APE1 T1349G polymorphism and prostate cancer risk: evidence from a meta-analysis.10111-910.1007/s13277-014-2115-6APE1 T1349G polymorphism was considered to be associated with risk of cancer, but studies on the association between APE1 T1349G polymorphism and risk of prostate cancer remained inconclusive. A meta-analysis of published studies was performed to precisely assess the association between APE1 Asp148Glu polymorphism and prostate cancer risk. PubMed, Embase, and Wanfang databases were searched for published case-control studies investigating the association between APE1 T1349G polymorphism and prostate cancer risk. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to assess the strength of the association. Overall, seven studies with a total of 3,063 individuals were finally included into the meta-analysis. The heterogeneity analysis did not find obvious heterogeneity among those included studies. Meta-analysis of total seven studies did not find an obvious association between APE1 T1349G polymorphism and prostate cancer risk (G vs T OR (95 % CI) = 1.11 (0.99-1.24); GG vs TT OR (95 % CI) = 1.25 (0.96-1.62); TG vs TT OR (95 % CI) = 1.11 (0.95-1.30); GG/TG vs T OR (95 % CI) = 1.13 (0.97-1.32); GG vs TT/TG OR (95 % CI) = 1.16 (0.91-1.48)). Subgroup analyses by ethnicity showed that APE1 T1349G polymorphism was associated with increased risk of prostate cancer in Caucasians (G vs T OR (95 % CI) = 1.26 (1.02-1.56), P = 0.033; TG vs TT OR (95 % CI) = 1.44 (1.06-1.94), P = 0.019; GG/TG vs T OR (95 % CI) = 1.45 (1.08-1.94), P = 0.013). The meta-analysis suggests that APE1 T1349G polymorphism is associated with increased risk of prostate cancer, especially in Caucasians. More studies are needed to further identify the obvious association above.LiXinXDepartment of Urinary Surgery, General Hospital of Shenyang Military Region, Shenyang, 110840, China.ZhangGengGHuaiYong-JunYJCaoZhi-QiangZQengJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov'tRetracted Publication20140715
United StatesTumour Biol84099221010-4283EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMTumour Biol. 2017 Apr 20;:28792236Indian J Med Res. 2012;135:64-7122382185N Engl J Med. 2012 Mar 15;366(11):981-9022417251PLoS One. 2013 Jun 21;8(6):e6699923805288Cancer Causes Control. 2010 Feb;21(2):289-30019902366Lancet. 2008 May 17;371(9625):1710-2118486743J Urol. 2006 Jan;175(1):108-12; discussion 11216406883Control Clin Trials. 1986 Sep;7(3):177-883802833Mol Biol Rep. 2011 Mar;38(3):1585-9120852942Prostate. 2010 Feb 1;70(2):113-919760636Am J Epidemiol. 2005 Jan 15;161(2):147-5215632264BMJ. 2003 Sep 6;327(7414):557-6012958120Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Methods Mol Biol. 2009;471:305-3319109787Mutagenesis. 2009 Nov;24(6):507-1219762350DNA Repair (Amst). 2006 Dec 9;5(12 ):1439-4816982218Carcinogenesis. 2006 Mar;27(3):560-716195237J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060Tumour Biol. 2014 Jul;35(7):6665-7124705777PLoS One. 2013 Jul 04;8(7):e6863423861929Hum Exp Toxicol. 2012 Oct;31(10):981-100523023028Carcinogenesis. 2012 Jul;33(7):1259-6922523086BMJ. 1997 Sep 13;315(7109):629-349310563BMC Cancer. 2011 Dec 18;11:52122176746Cancer Biol Ther. 2010 Jul 1;10(1):13-820495366Clin Lab. 2013;59(1-2):163-823505922Genet Test Mol Biomarkers. 2013 Dec;17(12):926-3124093803Mech Ageing Dev. 2012 Apr;133(4):127-3222019847Mol Biol Rep. 2013 Jan;40(1):171-623143180AdenocarcinomageneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGenetic Predisposition to DiseasegeneticsHumansMaleOdds RatioPolymorphism, Single NucleotidegeneticsProstatic Neoplasmsgenetics
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1873-33362782014Aug15Journal of hazardous materialsJ. Hazard. Mater.Effects of CEES and LPS synergistically stimulate oxidative stress inactivates OGG1 signaling in macrophage cells.236-4910.1016/j.jhazmat.2014.05.096S0304-3894(14)00451-82-chloroethyl ethyl sulphide (CEES), a monofunctional analogue of sulfur mustard, is a strong vesicant and an alkylating chemical warfare agent. We studied the molecular mechanism of oxidative stress triggered signaling cascades in murine macrophages exposed to CEES with lipopolysaccharide (LPS). Exposure of CEES with specific dose of LPS stimulates oxidative stress caused increasing level of intracellular ROS and RNS, decreased antioxidant enzymes, increasing bimolecular damage, reduced cell viability, and cell cycle arrest. Synergistic exposure of CEES and LPS provoked significant increase in phosphorylation of MAPKs, Akt, tuberin, that down regulate OGG1 expression and 8-OHdG accumulations. Treatment with Akt and ERK1/2 inhibitors, the cells with constitutively active inhibiting activity of Akt and ERK1/2MAPK significant reduce CEES and LPS challenge tuberin but not the OGG1. In addition, the N-acetylcysteine inhibited ROS/RNS generation, elevation of antioxidants level, expression of ERK1/2, Akt, tuberin phosphorylation, resulted in deceased 8-OHdG accumulation and upregulation of OGG1 protein expression suggesting no involvement of Akt and ERK1/2MAPK pathways after CEES and LPS challenge. Collectively, our results indicate that exposure of CEES and LPS induces oxidative stress and the activation of tuberin, and 8-OHdG accumulation via upstream signaling pathways including Akt and ERK1/2MAPK pathway in macrophages but not the down regulation of OGG1. Copyright © 2014 Elsevier B.V. All rights reserved.SagarSatishSSchool of Biotechnology, KIIT University, Campus 11, Bhubaneswar 751024, India.KumarPremranjanPSchool of Biotechnology, KIIT University, Campus 11, Bhubaneswar 751024, India.BeheraReena RaniRRSchool of Biotechnology, KIIT University, Campus 11, Bhubaneswar 751024, India.PalArttatranaASchool of Biotechnology, KIIT University, Campus 11, Bhubaneswar 751024, India. Electronic address: arttatrana@yahoo.com.engJournal ArticleResearch Support, Non-U.S. Gov't20140606
NetherlandsJ Hazard Mater94226880304-38940Chemical Warfare Agents0Lipopolysaccharides0Reactive Nitrogen Species0Reactive Oxygen Species0Tumor Suppressor Proteins4JG2LF96VFtuberous sclerosis complex 2 protein693-07-22-chloroethyl ethyl sulfide88847-89-68-oxo-7-hydrodeoxyguanosineEC 1.11.1.6CatalaseEC 1.15.1.1Superoxide DismutaseEC 2.7.11.24Mitogen-Activated Protein KinasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseG9481N71RODeoxyguanosineT8KEC9FH9PMustard GasIMAnimalsApoptosisdrug effectsCatalasemetabolismCell Cycledrug effectsCell LineCell Survivaldrug effectsChemical Warfare AgentstoxicityDNA DamageDNA GlycosylasesmetabolismDeoxyguanosineanalogs & derivativesmetabolismLipopolysaccharidestoxicityMacrophagesdrug effectsmetabolismMiceMitogen-Activated Protein KinasesmetabolismMustard Gasanalogs & derivativestoxicityOxidative Stressdrug effectsReactive Nitrogen SpeciesmetabolismReactive Oxygen SpeciesmetabolismSuperoxide DismutasemetabolismTumor Suppressor Proteinsmetabolism8-OHdGCEESLPSOGG1Oxidative stressSignaling
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1552-57835572014Jun26Investigative ophthalmology & visual scienceInvest. Ophthalmol. Vis. Sci.Suppression of choroidal neovascularization through inhibition of APE1/Ref-1 redox activity.4461-910.1167/iovs.14-14451The redox function of APE1/Ref-1 is a key regulator in pathological angiogenesis, such as retinal neovascularization and tumor growth. In this study, we examined whether inhibition of APE1/Ref-1 redox function by a small molecule inhibitor E3330 suppresses experimental choroidal neovascularization (CNV) in vitro and in vivo.Primate choroid endothelial cells (CECs) received treatment of 0 to 100 μM E3330 alone or cotreatment of E3330 and 500 μg/mL anti-VEGF antibody bevacizumab. Choroid endothelial cell angiogenic function was examined by cell proliferation, migration, and tube formation assays. The effects of E3330 on NF-κB and STAT3 signaling pathways were determined by reporter gene assay, Western blot, and ELISA. Laser-induced CNV mouse model was used to test the effects of E3330 in vivo. Potential toxicity of E3330 was evaluated by TUNEL assay.The E3330 of 25 to 100 μM dose-dependently suppressed CEC proliferation, migration, and tube formation, in the absence of noticeable cell toxicity. Lower doses of E3330 (10-20 μM) reduced the transcriptional activity of NF-κB and STAT3 without affecting protein phosphorylation of both molecules. At the same time, E3330 downregulated MCP-1 production in CECs. The antiangiogenic effect of E3330 was comparable and additive to bevacizumab. The E3330 effectively attenuated the progression of laser-induced CNV in mice after a single intravitreal injection.The APE1/Ref-1 redox function regulates multiple transcription factors and inflammatory molecules, and is essential for CEC angiogenesis. Specific inhibition of APE1/Ref-1 redox function with E3330 may represent a promising novel treatment for wet AMD.Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.LiYueYDepartment of Ophthalmology, Henry Ford Health System, Detroit, Michigan, United States Department of Ophthalmology, Shaanxi Maternity and Child Healthcare Hospital, Xi'an, Shaanxi, People's Republic of China.LiuXiuliXDepartment of Ophthalmology, Henry Ford Health System, Detroit, Michigan, United States.ZhouTongrongTDepartment of Ophthalmology, Henry Ford Health System, Detroit, Michigan, United States.KelleyMark RMRHerman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States.EdwardsPaul APADepartment of Ophthalmology, Henry Ford Health System, Detroit, Michigan, United States.GaoHuaHDepartment of Ophthalmology, Henry Ford Health System, Detroit, Michigan, United States.QiaoXiaoxiXDepartment of Ophthalmology, Henry Ford Health System, Detroit, Michigan, United States.engCA121168CANCI NIH HHSUnited StatesR41 EY019784EYNEI NIH HHSUnited StatesCA167291CANCI NIH HHSUnited StatesR01 CA121168CANCI NIH HHSUnited StatesR01 CA167291CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20140626
United StatesInvest Ophthalmol Vis Sci77037010146-04040Antibodies, Monoclonal, Humanized0Benzoquinones0Chemokine CCL20NF-kappa B0Propionates0STAT3 Transcription Factor0Stat3 protein, mouse136164-66-4E 33302S9ZZM9Q9VBevacizumabEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMInvest Ophthalmol Vis Sci. 2007 Apr;48(4):1839-4317389519Redox Biol. 2014;2:485-9424624338Med Res Rev. 2008 Mar;28(2):185-20017457812Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Mol Vis. 2005 Jul 14;11:509-1716052166Am J Ophthalmol. 2006 Jan;141(1):149-5616386991N Engl J Med. 2006 Oct 5;355(14):1419-3117021318N Engl J Med. 2006 Oct 5;355(14):1432-4417021319Cell Death Differ. 2000 Mar;7(3):272-8110745272Nat Biotechnol. 2000 Aug;18(8):877-8110932159Mutat Res. 2000 Oct 16;461(2):83-10811018583Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):E83-811073859Mol Vis. 2002 Apr 21;8:119-2611979237Nat Rev Mol Cell Biol. 2004 Apr;5(4):261-7015071551Arch Ophthalmol. 2004 Apr;122(4):564-7215078675Circ Res. 2004 Oct 29;95(9):902-1015472121Proc Natl Acad Sci U S A. 1991 May 15;88(10):4328-321903539EMBO J. 1992 Feb;11(2):653-651537340EMBO J. 1992 Sep;11(9):3323-351380454Nucleic Acids Res. 1992 Aug 11;20(15):3821-301508666Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414J Exp Med. 1994 Feb 1;179(2):503-127507507J Biol Chem. 1996 Dec 13;271(50):32253-98943284Genes Dev. 1997 Mar 1;11(5):558-709119221J Cell Biol. 1997 Apr 21;137(2):481-929128257J Immunol. 1998 Jan 15;160(2):810-99551916Invest Ophthalmol Vis Sci. 1999 Feb;40(2):477-869950608Mol Cancer Res. 2007 Jan;5(1):61-7017259346Blood. 2007 Mar 1;109(5):1917-2217053053Mol Cancer Ther. 2008 Jul;7(7):2012-2118645011Nucleic Acids Res. 2008 Aug;36(13):4327-3618586825Antioxid Redox Signal. 2008 Nov;10(11):1853-6718627350Ophthalmology. 2009 Jan;116(1):57-65.e519118696Cancer Biol Ther. 2008 Dec;7(12):1994-200318981713Invest Ophthalmol Vis Sci. 2009 Feb;50(2):844-5018936153J Cell Physiol. 2009 Apr;219(1):209-1819097035Mol Endocrinol. 2009 Sep;23(9):1346-5919460860Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116J Med Chem. 2010 Feb 11;53(3):1200-1020067291Br J Pharmacol. 2010 Mar;159(6):1294-30320136831Invest Ophthalmol Vis Sci. 2010 May;51(5):2697-70420007826BMJ. 2010;340:c245920538634Mediators Inflamm. 2010;2010. pii: 546826. doi: 10.1155/2010/54682620871825Cancer Res. 2010 Oct 15;70(20):8222-3220807804Biochim Biophys Acta. 2010 Oct-Dec;1799(10-12):775-8720493977J Neuroinflammation. 2010;7:8721126357Vision Res. 2011 Jan;51(1):93-10020937296Curr Opin Ophthalmol. 2011 May;22(3):199-20421427571Invest Ophthalmol Vis Sci. 2011 May;52(6):3193-921296829N Engl J Med. 2011 May 19;364(20):1897-90821526923J Cell Physiol. 2012 Jan;227(1):116-2621374591Br J Ophthalmol. 2011 Dec;95(12):1631-721546514Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463J Biol Chem. 2012 Apr 6;287(15):12331-4222337883J Cell Sci. 2012 May 15;125(Pt 10):2407-1522357958PLoS One. 2012;7(10):e4746223094050Invest Ophthalmol Vis Sci. 2008 Jan;49(1):407-1518172119AnimalsAntibodies, Monoclonal, HumanizedpharmacologyBenzoquinonespharmacologyBevacizumabBlotting, WesternCell LineCell Movementdrug effectsCell Proliferationdrug effectsChemokine CCL2metabolismChoroidblood supplyChoroidal Neovascularizationpathologyprevention & controlDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsDisease Models, AnimalDose-Response Relationship, DrugEndothelial Cellsdrug effectsmetabolismpathologyEnzyme-Linked Immunosorbent AssayHumansIn Situ Nick-End LabelingIntravitreal InjectionsMacaca mulattaMaleMiceMice, Inbred C57BLNF-kappa BmetabolismPropionatespharmacologySTAT3 Transcription FactormetabolismAPE1/Ref-1antiangiogenesischoroidal neovascularizationredox functiontranscription factors
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1792-1074742014AprOncology lettersOncol LettAberrant expression of redox protein Ape1 in colon cancer stem cells.1078-1082Ape1 is an important redox protein, essential for specific cytokine-induced signal transduction. Ape1 signaling is also important in regulating the growth of cancer cells, including colon cancer cells. The present study investigated whether Ape1 signaling plays a role in the regulation of colon cancer stem cell (CCSC) growth. The results showed that Ape1 was aberrantly expressed in CCSCs, as determined by quantitative (q)PCR assay. A laser confocal microscopy assay demonstrated that the Ape1 protein was mainly distributed in the nuclei, but not the cytoplasm, of the CSCs. Treatment of CCSCs with Ape1 redox inhibitor (E3330) significantly affected growth in vitro. In colon cancer xenograft mice, in vivo administration of E3330 enhanced tumor responses to the chemotherapeutic drug, 5-fluorouracil (5-FU). Furthermore, the combination of E3330 and 5-FU evidently increased the cytotoxicity of 5-FU in CSC growth. In the qPCR assay, the CCSCs were demonstrated to express the dominant ATP-binding cassette sub-family G member 2 (ABC-G2), but not the multidrug resistance 1, genes. Thus, we hypothesized that drug resistance in CCSCs is mediated by ABC-G2. Since CSCs are involved in cancer metastasis, the Ape1 inhibitor may be a potential agent in the inhibition of colon cancer growth and metastasis.LouDebaoDDepartment of Pharmacy, Shanghai Eighth People's Hospital, Shanghai 200235, P.R. China.ZhuLinaLDepartment of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.DingHuaweiHShanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.DaiHai-YanHYShanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.ZouGang-MingGMShanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200240, P.R. China ; Shanghai Institute for Pediatrics Research, Xin Hua Hospital, Shanghai Jiao Tong University Shanghai of Medicine, Shanghai 200092, P.R. China.engJournal Article20140210
GreeceOncol Lett1015312361792-1074Cancer Invest. 2013 Feb;31(2):97-10223245395Wien Med Wochenschr. 1988 Jun 30;138(11-12):288-923051690Clin Cancer Res. 2005 Sep 1;11(17):6205-1116144922Anticancer Res. 2001 Nov-Dec;21(6A):4041-911911289Oncogene. 2011 Jan 27;30(4):482-9320856196Nat Rev Cancer. 2005 Apr;5(4):275-8415803154Blood. 2002 Jan 15;99(2):507-1211781231Acta Histochem. 2012 Oct;114(6):594-60222154301J Biol Chem. 2011 Feb 18;286(7):4968-7721081487Nat Cell Biol. 2006 May;8(5):501-816604061Cell Growth Differ. 1994 Feb;5(2):125-318180125Cell Stem Cell. 2010 Jun 4;6(6):603-1520569697Mol Cancer Ther. 2008 Jul;7(7):2012-2118645011Mol Immunol. 2008 Aug;45(14):3731-918617267J Cell Physiol. 2009 Apr;219(1):209-1819097035CA Cancer J Clin. 2008 Mar-Apr;58(2):71-9618287387Biochem Biophys Res Commun. 2012 Apr 13;420(3):628-3422450323Gastroenterology. 2011 Jan;140(1):297-30920951698Curr Med Res Opin. 2011 Jul;27(7):1295-30221561390Blood. 2007 Mar 1;109(5):1917-2217053053Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Curr Opin Pharmacol. 2010 Aug;10(4):362-8206276825-fluorouracilABC-G2E3330MDR1Ref-1colon cancer
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1559-131X3172014JulMedical oncology (Northwood, London, England)Med. Oncol.Association between OGG1 gene single nucleotide polymorphisms and risk of pancreatic cancer in Chinese.4010.1007/s12032-014-0040-6Previous studies have suggested that the 8-oxoguanine DNA glycosylase gene (OGG1) has potentially influenced the risk of pancreatic cancer. The objective of this study was to assess the association between single nucleotide polymorphisms (SNPs) of OGG1 gene and risk of pancreatic cancer. A case-control study has been conducted in 370 pancreatic cancer patients and 395 healthy controls. Genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. The association analysis was evaluated by the unconditional logistic regression test. Our data suggested that the distributions of alleles and genotypes were statistically different between pancreatic cancer patients and healthy controls. The c.307G>C SNP was associated with the decreased risk of pancreatic cancer (C vs. G: OR 0.73, 95 % CI 0.59-0.91, P = 0.006). As for c.828A>G SNP, the significantly decreased risk of pancreatic cancer was detected (G vs. A: OR 0.74, 95 % CI 0.59-0.92, P = 0.006). The allele C of c.307G>C and allele G of c.828A>G SNPs might be associated with a protection from pancreatic cancer. Findings from this study indicate that OGG1 SNPs are associated with pancreatic cancer risk in Chinese Han population and could be useful molecular biomarkers for assessing the risk of pancreatic cancer.LiuChengliCDepartment of Hepatobiliary Surgery, The Air Force General Hospital of People's Liberation Army, No. 30 Fucheng Road, Haidian District, Beijing, 100142, People's Republic of China, chengli_liu@sina.com.HuangHuiHWangChengCKongYalinYZhangHuiHZhangHongyiHengJournal Article20140617
United StatesMed Oncol94355121357-0560EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMCancer. 2011 Feb 15;117(4):744-5120922799Cancer Res. 2008 Jun 15;68(12):4928-3518544627Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1470-918559563Pancreatology. 2003;3(1):1-712683400Tumour Biol. 2013 Dec;34(6):3417-2123807675Int J Cancer. 2007 May 1;120(9):1993-817266034Asian Pac J Cancer Prev. 2001;2(4):271-28012718618Tumour Biol. 2014 Mar;35(3):2397-40224186001JOP. 2010 May 05;11(3):203-1220442513Cancer Causes Control. 2007 Aug;18(6):603-1217401636Tumour Biol. 2014 Jan;35(1):809-1323999824Best Pract Res Clin Gastroenterol. 2006 Apr;20(2):197-20916549324J Epidemiol. 2012;22(6):477-8322850545Mutat Res. 2009 Mar-Jun;681(2-3):299-30719150414Annu Rev Genomics Hum Genet. 2003;4:237-5614527303Int J Mol Epidemiol Genet. 2011 Aug 30;2(3):236-4421915362Dig Dis. 2011;29(2):235-4221734390Clin Cancer Res. 2009 Jan 15;15(2):740-619147782Int J Cancer. 2007 Apr 15;120(8):1748-5417230526J Clin Oncol. 2006 Apr 10;24(11):1720-816520463Curr Drug Targets. 2012 Jun;13(6):731-4322458519CA Cancer J Clin. 2007 Jan-Feb;57(1):43-6617237035AdultAgedAsian Continental Ancestry GroupgeneticsCase-Control StudiesDNA GlycosylasesgeneticsFemaleGene FrequencyGenetic Predisposition to DiseaseHumansMaleMiddle AgedPancreatic NeoplasmsgeneticsPolymorphism, Single Nucleotide
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1365-313X7952014SepThe Plant journal : for cell and molecular biologyPlant J.Arabidopsis ZDP DNA 3'-phosphatase and ARP endonuclease function in 8-oxoG repair initiated by FPG and OGG1 DNA glycosylases.824-3410.1111/tpj.12588Oxidation of guanine in DNA generates 7,8-dihydro-8-oxoguanine (8-oxoG), an ubiquitous lesion with mutagenic properties. 8-oxoG is primarily removed by DNA glycosylases distributed in two families, typified by bacterial Fpg proteins and eukaryotic Ogg1 proteins. Interestingly, plants possess both Fpg and Ogg1 homologs but their relative contributions to 8-oxoG repair remain uncertain. In this work we used Arabidopsis cell-free extracts to monitor 8-oxoG repair in wild-type and mutant plants. We found that both FPG and OGG1 catalyze excision of 8-oxoG in Arabidopsis cell extracts by a DNA glycosylase/lyase mechanism, and generate repair intermediates with blocked 3'-termini. An increase in oxidative damage is detected in both nuclear and mitochondrial DNA from double fpg ogg1 mutants, but not in single mutants, which suggests that a single deficiency in one of these DNA glycosylases may be compensated by the other. We also found that the DNA 3'-phosphatase ZDP (zinc finger DNA 3'-phosphoesterase) and the AP(apurinic/apyirmidinic) endonuclease ARP(apurinic endonuclease redox protein) are required in the 8-oxoG repair pathway to process the 3'-blocking ends generated by FPG and OGG1. Furthermore, deficiencies in ZDP and/or ARP decrease germination ability after seed deteriorating conditions. Altogether, our results suggest that Arabidopsis cells use both FPG and OGG1 to repair 8-oxoG in a pathway that requires ZDP and ARP in downstream steps. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.Córdoba-CañeroDoloresDDepartment of Genetics, University of Córdoba/Maimónides Institute for Research in Biomedicine of Córdoba (IMIBIC)/Reina Sofía University Hospital, 14071, Córdoba, Spain.Roldán-ArjonaTeresaTArizaRafael RRRengJournal ArticleResearch Support, Non-U.S. Gov't20140725
EnglandPlant J92073970960-741207,8-dihydro-8-oxoguanine0Arabidopsis Proteins5614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.1.-Arp protein, ArabidopsisEC 3.1.-EndonucleasesEC 3.1.3.-NucleotidasesEC 3.1.3.34deoxynucleotide 3'-phosphataseEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-OGG1 protein, ArabidopsisIMArabidopsisenzymologygeneticsArabidopsis ProteinsgeneticsmetabolismDNA DamageDNA GlycosylasesgeneticsmetabolismDNA RepairEndonucleasesgeneticsmetabolismGerminationGuanineanalogs & derivativesmetabolismMutagenesis, InsertionalNucleotidasesgeneticsmetabolismOxidative StressSeedsAP endonucleaseArabidopsis thalianaDNA glycosylaseDNA phosphatasebase-excision repairoxidative DNA damageseed vigor
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1091-6490111252014Jun24Proceedings of the National Academy of Sciences of the United States of AmericaProc. Natl. Acad. Sci. U.S.A.Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation.9217-2210.1073/pnas.1405590111Somatic hypermutation (SHM) of antibody variable region genes is initiated in germinal center B cells during an immune response by activation-induced cytidine deaminase (AID), which converts cytosines to uracils. During accurate repair in nonmutating cells, uracil is excised by uracil DNA glycosylase (UNG), leaving abasic sites that are incised by AP endonuclease (APE) to create single-strand breaks, and the correct nucleotide is reinserted by DNA polymerase β. During SHM, for unknown reasons, repair is error prone. There are two APE homologs in mammals and, surprisingly, APE1, in contrast to its high expression in both resting and in vitro-activated splenic B cells, is expressed at very low levels in mouse germinal center B cells where SHM occurs, and APE1 haploinsufficiency has very little effect on SHM. In contrast, the less efficient homolog, APE2, is highly expressed and contributes not only to the frequency of mutations, but also to the generation of mutations at A:T base pair (bp), insertions, and deletions. In the absence of both UNG and APE2, mutations at A:T bp are dramatically reduced. Single-strand breaks generated by APE2 could provide entry points for exonuclease recruited by the mismatch repair proteins Msh2-Msh6, and the known association of APE2 with proliferating cell nuclear antigen could recruit translesion polymerases to create mutations at AID-induced lesions and also at A:T bp. Our data provide new insight into error-prone repair of AID-induced lesions, which we propose is facilitated by down-regulation of APE1 and up-regulation of APE2 expression in germinal center B cells. StavnezerJanetJDepartment of Microbiology and Physiological Systems, Immunology and Microbiology Program, University of Massachusetts Medical School, Worcester, MA 01655; and.LinehanErin KEKDepartment of Microbiology and Physiological Systems, Immunology and Microbiology Program, University of Massachusetts Medical School, Worcester, MA 01655; and.ThompsonMikayla RMRDepartment of Microbiology and Physiological Systems, Immunology and Microbiology Program, University of Massachusetts Medical School, Worcester, MA 01655; and.HabboubGhaithGDepartment of Microbiology and Physiological Systems, Immunology and Microbiology Program, University of Massachusetts Medical School, Worcester, MA 01655; and.UcherAnna JAJDepartment of Microbiology and Physiological Systems, Immunology and Microbiology Program, University of Massachusetts Medical School, Worcester, MA 01655; and.KadungureTatendaTDepartment of Microbiology and Physiological Systems, Immunology and Microbiology Program, University of Massachusetts Medical School, Worcester, MA 01655; and.TsuchimotoDaisukeDDepartment of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.NakabeppuYusakuYDepartment of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.SchraderCarol ECEDepartment of Microbiology and Physiological Systems, Immunology and Microbiology Program, University of Massachusetts Medical School, Worcester, MA 01655; and carol.schrader@umassmed.edu.engR01 AI023283AINIAID NIH HHSUnited StatesR01 AI23283AINIAID NIH HHSUnited StatesR01 AI065639AINIAID NIH HHSUnited StatesR21 AI088578AINIAID NIH HHSUnited StatesR03 AI092528AINIAID NIH HHSUnited StatesR21 AI88578AINIAID NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20140609
United StatesProc Natl Acad Sci U S A75058760027-84240DNA-Binding Proteins0Msh6 protein, mouse0Proliferating Cell Nuclear AntigenEC 3.1.-Apex2 protein, mouseEC 3.1.-EndonucleasesEC 3.2.2.-DNA GlycosylasesEC 3.6.1.3Msh2 protein, mouseEC 3.6.1.3MutS Homolog 2 ProteinEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Exp Med. 2000 Feb 7;191(3):579-8410662804Eur J Immunol. 2014 Jul;44(7):1925-3524771041Cell. 2000 Sep 1;102(5):565-7511007475Environ Mol Mutagen. 2000;36(4):312-2411152564Nucleic Acids Res. 2001 Jun 1;29(11):2349-6011376153Cancer Res. 2001 Jul 15;61(14):5552-711454706EMBO J. 2001 Nov 15;20(22):6530-911707423Nature. 2002 Feb 7;415(6872):655-911832948J Mol Biol. 2002 Feb 22;316(3):853-6611866537Nature. 2002 Jul 4;418(6893):99-10312097915J Biol Chem. 2002 Oct 18;277(42):39926-3612161446Curr Biol. 2002 Oct 15;12(20):1748-5512401169Genomics. 2003 Jan;81(1):47-5712573260J Exp Med. 2003 Aug 18;198(4):635-4312925679DNA Repair (Amst). 2003 Sep 18;2(9):955-6912967653Nat Immunol. 2004 Feb;5(2):224-914716311J Biol Chem. 2004 Apr 30;279(18):18425-3314973123Mol Cell. 2004 May 21;14(4):491-50015149598Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-99207062Immunity. 1998 Jul;9(1):135-419697843Blood. 2004 Dec 15;104(13):4097-10315319281Mol Cell. 2005 Feb 4;17(3):463-7015694346Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325J Immunol. 2005 Jun 15;174(12):7781-615944281Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18361-616344468Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1166-7110655502Nucleic Acids Res. 2006;34(9):2508-1516687656J Exp Med. 2007 Jan 22;204(1):17-2317190840DNA Repair (Amst). 2007 Jun 1;6(6):695-71117337257Nucleic Acids Res. 2007;35(12):3879-9217537817J Exp Med. 2007 Aug 6;204(8):1989-9817664295J Exp Med. 2007 Nov 26;204(12):3017-2618025127Nat Rev Immunol. 2008 Apr;8(4):302-1218340343Annu Rev Immunol. 2008;26:481-51118304001Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16248-5318854411Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5593-819307563Nucleic Acids Res. 2009 Jul;37(13):4247-5519443450Int Immunol. 2009 Aug;21(8):947-5519556307Mol Cell Biol. 2009 Sep;29(18):5148-5719596785J Exp Med. 2009 Nov 23;206(12):2603-1119901081Nucleic Acids Res. 2010 Jan;38(3):832-4519934257Adv Immunol. 2010;105:159-9120510733PLoS One. 2010;5(6):e1118220567595Nat Biotechnol. 2010 Dec;28(12):1248-5021139605J Immunol. 2011 Feb 15;186(4):1943-5021228350J Exp Med. 2011 Oct 24;208(11):2209-1621967769Blood. 2012 Sep 13;120(11):2240-822740445Mol Cell Biol. 2013 Apr;33(7):1468-7323382073Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):E2470-923754438Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):E3695-70324023064Nat Immunol. 2013 Nov;14(11):1183-924097111Immunity. 2013 Nov 14;39(5):912-2424184055DNA Repair (Amst). 2013 Dec;12(12):1087-9324084171Cell Rep. 2014 Jan 16;6(1):1-824388753Cell. 2000 Sep 1;102(5):553-6311007474AnimalsB-LymphocytescytologymetabolismDNA GlycosylasesgeneticsmetabolismDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisgeneticsDNA-Binding ProteinsgeneticsmetabolismEndonucleasesbiosynthesisgeneticsGene Expression Regulation, EnzymologicphysiologyGerminal CentercytologymetabolismMiceMice, KnockoutMutS Homolog 2 ProteingeneticsmetabolismMutationProliferating Cell Nuclear AntigengeneticsmetabolismSomatic Hypermutation, Immunoglobulinphysiology
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1932-6203962014PloS onePLoS ONEPrognostic value of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in breast cancer.e9952810.1371/journal.pone.0099528Human apurinic/apyrimidinic endonuclease 1 (APE1) is an essential protein for DNA base excision repair (BER) and redox regulation. The ability of cancer cells to recognize DNA damage and initiate DNA repair is an important mechanism for therapeutic resistance. Several recent studies have suggested that APE1 expression levels and/or subcellular dysregulation may be used to indicate the sensitivity of tumors to radiotherapy or chemotherapy. In this study, we assessed the prognostic significance of APE1 and differences in APE1 expression levels according to breast cancer molecular subtypes. We analyzed formalin-fixed, paraffin-embedded tumor tissue sections from 243 cases diagnosed as invasive breast cancer at Ewha Womans University Medical Center between January 2003 and December 2008. Immunohistochemistry was performed and the nuclear level of APE1 was scored by taking into account the percentage of positive cells. Medical records were reviewed to investigate clinicopathologic characteristics. We found that nuclear APE1 high-level expression (proportion ≥50%) in breast cancer showed a tendency towards unfavorable prognosis regarding disease-free survival (p = 0.093). However, there was no significant difference in overall survival between low and high-level expression groups (p = 0.294). Interestingly, within the Ki-67 low-level expression group, APE1 low-level expression was significantly associated with poor overall survival (p = 0.007). A significant positive correlation was observed between APE1 nuclear expression and estrogen receptor status (75.7% vs. 59.7%, p = 0.022). Also, the luminal A subtype was the most commonly observed breast cancer subtype in the APE1 high-level expression group (61.6% vs. 45.2%, p = 0.000). This study suggests that APE1 expression may be associated with breast cancer prognosis. In particular, its role as a prognostic factor would be significant for breast cancers with a low Ki-67 proliferation index. It is proposed that nuclear APE1 may be a novel target in breast cancer with a low proliferation rate to obtain better outcome. WooJoohyunJDepartment of Surgery, Ewha Womans University School of Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea.ParkHeejungHDepartment of Pathology, Ewha Womans University School of Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea.SungSun HeeSHDepartment of Pathology, Ewha Womans University School of Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea.MoonByung-InBIDepartment of Surgery, Ewha Womans University School of Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea.SuhHyunsukHDepartment of Plastic surgery, Ewha Womans University School of Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea.LimWoosungWDepartment of Surgery, Ewha Womans University School of Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea.engJournal ArticleResearch Support, Non-U.S. Gov't20140610
United StatesPLoS One1012850811932-62030Ki-67 AntigenEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Pathol. 1999 Nov;189(3):351-710547596Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463Cancer Res. 2001 Mar 1;61(5):2220-511280790Int J Radiat Oncol Biol Phys. 2001 May 1;50(1):27-3611316543Antioxid Redox Signal. 2001 Aug;3(4):535-4811554443Oncol Rep. 2002 Jan-Feb;9(1):11-711748448J Biol Chem. 2004 Apr 16;279(16):16875-8214761960Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Pathologe. 1987 May;8(3):138-403303008Nucleic Acids Res. 1991 Oct 25;19(20):5519-231719477Nucleic Acids Res. 1992 Sep 11;20(17):4417-211383925Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414Nucleic Acids Res. 1994 Nov 25;22(23):4884-97800476Nucleic Acids Res. 1997 Oct 15;25(20):4035-409321654Br J Cancer. 1998 Apr;77(7):1169-739569057Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Mol Endocrinol. 2006 Sep;20(9):1982-9516690750Mol Med. 2007 Jan-Feb;13(1-2):89-9617515960J Natl Cancer Inst. 2009 May 20;101(10):736-5019436038Mol Endocrinol. 2009 Sep;23(9):1346-5919460860Lung Cancer. 2009 Dec;66(3):298-30419324449Br J Cancer. 2010 Feb 16;102(4):704-920087352Ann Oncol. 2011 Aug;22(8):1736-4721709140Biochem Biophys Res Commun. 2012 Jul 20;424(1):34-922713458Clin Cancer Res. 2000 Feb;6(2):602-910690545Breast NeoplasmsmetabolismpathologyCohort StudiesDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismFemaleHumansImmunohistochemistryKaplan-Meier EstimateKi-67 AntigenmetabolismMiddle AgedNeoplasm InvasivenessPrognosisProportional Hazards Models
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1460-22024042015AprCurrent eye researchCurr. Eye Res.The changes of 8-OHdG, hOGG1, APE1 and Pol β in lenses of patients with age-related cataract.378-8510.3109/02713683.2014.924148To evaluate the changes of oxidative DNA damage (in the form of 8-OHdG) and three key DNA base-excision repair (BER) proteins, human 8-oxoguanine DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease 1 (APE1) and DNA polymerase β (Pol β), in lens epithelium cells (LECs), cortex and nucleus of lenses with age-related cataract (ARC) and age-matched controls.A total of 90 patients with ARC and 21 control subjects were enrolled. The samples included the anterior lens capsules (mainly composed of LECs) and various portions of lens. An ELISA assay was used to assess the 8-OHdG levels of genomic DNA extracted. Immunofluorescence and Western blot were used to analyze the localization and quantification of three BER proteins, respectively.The 8-OHdG levels in lenses with ARC were higher than those of controls, and were not different among ARC subtypes. The 8-OHdG levels were the highest in the nucleus, followed by the LECs and cortex. The repair proteins were predominantly detected in the cellular nuclei of the LECs and superficial cortical cells. In the LECs, the protein levels of the three BER enzymes were higher in ARC than in controls. In the cortex, a downward trend of the levels of three BER enzymes was found with the increasing opaque degrees. In the nucleus, no enzymes were detected.Our findings indicate that the oxidative DNA damage increases in lenses with ARC, and the three BER enzymes compensatively increase in the LECs, while decreasing in the opaque cortex. The results suggest that the oxidative DNA damage may be related ARC and the alteration of DNA repair enzyme levels in ARC is associated with the location and opaque degrees of lens.XuBiweiBEye Institute, Affiliated Hospital of Nantong University , Nantong , China.KangLihuaLZhangGuoweiGWuJianJZhuRongrongRYangMeiMGuanHuaijinHengJournal ArticleResearch Support, Non-U.S. Gov't20140609
EnglandCurr Eye Res81043120271-368388847-89-68-oxo-7-hydrodeoxyguanosineEC 2.7.7.-DNA Polymerase betaEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseG9481N71RODeoxyguanosineIMAgedAgingphysiologyBlotting, WesternCataractenzymologypathologyDNA DamageDNA GlycosylasesmetabolismDNA Polymerase betametabolismDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismDeoxyguanosineanalogs & derivativesgeneticsmetabolismEnzyme-Linked Immunosorbent AssayFemaleFluorescent Antibody Technique, IndirectGene Expression RegulationphysiologyHumansLens, CrystallineenzymologypathologyMaleOxidative Stress8-OHdGAPE1DNA damageDNA repairPol βage-related cataracthOGG1
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1746-159692014Jun03Diagnostic pathologyDiagn PatholAssociation between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast cancer risk: a meta-analysis.10810.1186/1746-1596-9-108The base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents. OGG1 and APE1 are two important genes in the BER pathway. Many epidemiological studies have evaluated the association between polymorphisms in the two BER genes (OGG1 Ser326Cys and APE1 Asp148Glu) and breast cancer risk. However, the results are inconsistent.We searched the electronic databases including PubMed, Embase and Cochrane library for all eligible studies for the period up to February 2014. Data were extracted by two independent authors and pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the association.A total of 17 studies including 9,040 cases and 10,042 controls were available for OGG1 Ser326Cys polymorphism and 7 studies containing 2,979 cases and 3,111 controls were included for APE1 Asp148Glu polymorphism. With respect to OGG1 Ser326Cys polymorphism, we did not find a significant association with breast cancer risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and menopausal status, statistical significant increased breast cancer risk was found in Asian populations (Cys/Cys vs. Ser/Ser: OR=1.157, 95% CI 1.013-1.321, P=0.011; Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.113, 95% CI 1.009-1.227, P=0.014) and postmenopausal patients (Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.162, 95% CI 1.003-1.346, P=0.024). In subgroup analysis according to quality score, source of control, and HWE in controls, no any significant association was detected. With respect to APE1 Asp148Glu polymorphism, no significant association with breast cancer risk was demonstrated in the overall and stratified analyses.The present meta-analysis suggests that the OGG1 Ser326Cys polymorphism may be a risk factor for breast cancer in Asians and postmenopausal patients. Further large and well-designed studies are needed to confirm this association.The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1156934297124915.PengQiliuQLuYuYLaoXianjunXChenZhipingZLiRuolinRSuiJingzheJQinXueXDepartment of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. qinxue919@126.com.LiShanSengJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov'tReview20140603
EnglandDiagn Pathol1012515581746-1596EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMTumour Biol. 2014 Apr;35(4):3495-50224402573Diagn Pathol. 2013;8:17224143964Mutat Res. 1999 Mar 8;424(1-2):107-1510064854Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Cancer Epidemiol Biomarkers Prev. 2003 Feb;12(2):170-112582029J Hum Genet. 2009 Dec;54(12):739-4519881468Stat Med. 2002 Jun 15;21(11):1539-5812111919Mutat Res. 2010 Feb 3;684(1-2):43-819962393Breast Cancer Res. 2005;7(1):21-3215642178Diagn Pathol. 2013;8:12923915145PLoS One. 2014;8(6):e6489623755158Pharmacogenetics. 2004 Feb;14(2):103-915077011Oncol Rep. 2008 Apr;19(4):1033-818357393Mutat Res. 2008 Dec 15;648(1-2):65-7218977234Pol J Pathol. 2008;59(4):201-419391486Breast. 2013 Oct;22(5):707-1223369609Carcinogenesis. 1990 Sep;11(9):1447-502205403Free Radic Biol Med. 1998 Jan 15;24(2):341-89433910Control Clin Trials. 1986 Sep;7(3):177-883802833Breast Cancer Res Treat. 2010 Aug;122(3):835-4220058067Oncogene. 2004 Aug 23;23(38):6404-2815322514Breast Cancer Res Treat. 2008 Sep;111(2):279-8817922186Breast Cancer Res Treat. 2003 May;79(1):59-6212779082Clin Chim Acta. 2005 Sep;359(1-2):150-516002061Dig Dis Sci. 2012 Sep;57(9):2451-722565339Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Ann Surg Oncol. 2010 Mar;17(3):760-7120183911Carcinogenesis. 2000 Jul;21(7):1329-3410874010Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1109-1515279799Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):353-816492928Gene. 2013 Dec 15;532(2):192-624076439Diagn Pathol. 2012;7:17023216981Science. 2001 Feb 16;291(5507):1284-911181991PLoS One. 2012;7(12):e5085723272074Oncogene. 1998 Jun 25;16(25):3219-259681819Am J Epidemiol. 2005 Aug 1;162(3):201-1115987731J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060Cancer Epidemiol Biomarkers Prev. 2006 Mar;15(3):536-4216537713Breast Cancer Res Treat. 2009 Jun;115(3):623-718553220J Cancer Res Clin Oncol. 2010 Apr;136(4):631-620140625Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):403-416492938Carcinogenesis. 2008 Nov;29(11):2132-818701435Carcinogenesis. 2000 Mar;21(3):361-7010688856Carcinogenesis. 2011 Aug;32(8):1223-3021622940Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):811-516614128Clin Cancer Res. 2001 Apr;7(4):824-3011309329Curr Med Res Opin. 2011 Jul;27(7):1295-30221561390J Appl Genet. 2010;51(3):343-5220720310Breast Cancer Res Treat. 2010 Jul;122(2):527-3120054639Nature. 2001 May 17;411(6835):366-7411357144Age FactorsAsian Continental Ancestry GroupgeneticsBreast NeoplasmsenzymologyethnologygeneticspathologyCase-Control StudiesChi-Square DistributionDNA GlycosylasesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleGenetic Predisposition to DiseaseHumansOdds RatioPhenotypePolymorphism, GeneticPostmenopauseRisk AssessmentRisk Factors
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1177-888182014Drug design, development and therapyDrug Des Devel TherIdentification of a novel potential antitumor activity of gossypol as an APE1/Ref-1 inhibitor.485-9610.2147/DDDT.S62963The human apurinic/apyrimidinic endonuclease 1/redox enhancing factor-1 (APE1/Ref-1), an essential multifunctional protein involved in the repair of oxidative deoxyribonucleic acid (DNA) damage and transcriptional regulation, is often overexpressed in tumor tissues and cancer cells. Moreover, APE1/Ref-1 (APE1) overexpression has been linked to chemoresistance in human tumors. Thus, inhibiting APE1 function in cancer cells is considered a promising strategy to overcome resistance to therapeutic agents. Gossypol is a Bcl-2 homology 3 (BH3)-mimetic agent and is able to bind to the BH3 domain of B-cell lymphoma 2 (Bcl-2) family members. Other studies demonstrated that Bcl-2 directly interacted with APE1 via its BH domains. Using apurinic/apyrimidinic (AP) endonuclease assays, we found that gossypol inhibits the repair activity of APE1. Electrophoretic mobility shift assays and dual luciferase assays showed that gossypol could also inhibit the redox function of APE1. Using dual polarization interferometry technology, we show that gossypol can directly interact with APE1. Furthermore, addition of gossypol, in conjunction with APE1 overexpression, leads to cancer cell death. The addition of gossypol also enhances the cell killing effect of the laboratory alkylating agent methyl methanesulfonate and the clinical agent cisplatin (DDP). Administration of gossypol significantly inhibited the growth of xenografts. Furthermore, the combined treatment of gossypol and DDP resulted in a statistically higher antitumor activity compared with DDP alone in vivo. In conclusion, we have demonstrated that gossypol effectively inhibits the repair and redox activity of APE1 through a direct interaction. QianChengyuanCCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.LiMengxiaMCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.SuiJiangdongJCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.RenTaoTCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.LiZhengZCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.ZhangLiangLCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.ZhouLiweiLCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.ChengYiYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.WangDongDCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.engJournal ArticleResearch Support, Non-U.S. Gov't20140509
New ZealandDrug Des Devel Ther1014757451177-88810Antineoplastic AgentsEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseKAV15B369OGossypolQ20Q21Q62JCisplatinIMIn Vitro Cell Dev Biol. 1986 Oct;22(10):583-83771439Cancer Res. 1984 Feb;44(2):768-716581864Gynecol Oncol. 1989 Mar;32(3):273-72920946Nucleic Acids Res. 1991 Oct 25;19(20):5519-231719477Nucleic Acids Res. 1991 Nov 11;19(21):5907-141719484Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-41722334EMBO J. 1992 Feb;11(2):653-651537340Adv Exp Med Biol. 1996;387:69-758794196Nucleic Acids Res. 1997 Mar 1;25(5):933-99023101Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Expert Opin Investig Drugs. 2005 Nov;14(11):1419-3416255680Mol Cancer Ther. 2005 Dec;4(12):1923-3516373707Cytokine Growth Factor Rev. 2006 Jun;17(3):147-5616516532Anticancer Res. 2006 May-Jun;26(3A):1925-3316827126J Thorac Cardiovasc Surg. 2006 Dec;132(6):1356-6217140955Anal Chem. 2007 Apr 15;79(8):3023-3117367112Nat Rev Cancer. 2008 Mar;8(3):193-20418256616J Biol Chem. 2008 Apr 11;283(15):9925-3218263880Free Radic Biol Med. 2008 Sep 1;45(5):592-60118515104Antioxid Redox Signal. 2008 Nov;10(11):1853-6718627350Proteomics. 2009 Feb;9(4):1058-7419180539Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116J Med Chem. 2010 Feb 11;53(3):1200-1020067291Mol Cancer Ther. 2010 Feb;9(2):461-7020124455Br J Cancer. 2010 Feb 16;102(4):704-920087352BMC Cancer. 2010;10:7120184742Antioxid Redox Signal. 2010 Jun 1;12(11):1247-6919764832Clin Lymphoma Myeloma Leuk. 2010 Oct;10(5):385-9321030352J Biol Chem. 2010 Nov 12;285(46):35418-2720837473Antioxid Redox Signal. 2011 Apr 15;14(8):1387-40120874257Mol Biol Cell. 2011 Oct;22(20):3887-90121865600Mol Endocrinol. 2011 Dec;25(12):2041-5322053001Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):130-721075552Curr Mol Pharmacol. 2012 Jan;5(1):14-3522122462Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463Med Oncol. 2012 Jun;29(2):1265-7121479902Free Radic Biol Med. 2012 Jul 15;53(2):237-4822580151PLoS One. 2013;8(2):e5531323418439Med Oncol. 2013 Jun;30(2):50523430444Ann Surg Oncol. 2013 Dec;20 Suppl 3:S336-4722688662Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463Anal Biochem. 2004 Jun 15;329(2):190-815158477Mol Cell Biol. 2000 Jan;20(1):402-1510594042Nat Biotechnol. 2000 Aug;18(8):877-8110932159Cancer Res. 2001 Mar 1;61(5):2220-511280790Clin Cancer Res. 2001 Apr;7(4):824-3011309329Breast Cancer Res Treat. 2001 Apr;66(3):239-4811510695Pharmacol Res. 2002 Dec;46(6):551-512457630J Med Chem. 2003 Sep 25;46(20):4259-6413678404Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Nucleic Acids Res. 2004;32(12):3531-615247342Contraception. 1987 Nov;36(5):581-923447817AnimalsAntineoplastic AgentspharmacologyCisplatinpharmacologyDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsGossypolpharmacologyHeLa CellsHumansMiceXenograft Model Antitumor AssaysBH3-mimeticcanceroxidative DNA damage
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1090-0535202014Molecular visionMol. Vis.Polymorphisms of DNA repair genes OGG1 and XPD and the risk of age-related cataract in Egyptians.661-9To analyze the association of the polymorphisms of xeroderma pigmentosum complementation group D (XPD) and 8-oxoguanine glycosylase-1 (OGG1) genes with the risk of age-related cataract (ARC) in an Egyptian population.This case-control study included 150 patients with ARC and 50 controls. Genotyping of XPD Asp³¹²Asn was performed by amplification refractory mutation system PCR assay and genotyping of OGG1 Ser³²⁶Cys was carried out by PCR including confronting two-pair primers.The Asn/Asn genotype of XPD gene was significantly associated with increased risk of ARC (odds ratio [OR] = 2.74, 95% confidence interval [CI] = 1.01-7.43, p = 0.04) and cortical cataract (OR = 5.06, 95% CI = 1.70-15.05, p = 0.002). The Asn³¹² allele was significantly associated with an increased risk of ARC (OR = 1.75, 95% CI 1.06-2.89, p = 0.03) and cortical cataract (OR = 2.81, 95% CI = 1.56-5.08, p<0.001). The OGG1 Cys/Cys genotype frequency was significantly higher in ARC (OR = 4.13, 95% CI = 0.93-18.21, p = 0.04) and the Cys(³²⁶ allele (OR = 1.85, 95% CI = 1.07-3.20, p = 0.03). Moreover, the Cys/Cys genotype of the OGG1 gene was significantly higher in cortical cataract (OR = 6.00, 95% CI = 1.24-28.99, p = 0.01) and the Cys³²⁶ allele was also significantly associated with cortical cataract (OR = 2.45, 95% CI = 1.30-4.63, p = 0.005).The results suggest that the Asn/Asn genotype and Asn³¹² allele of XPD polymorphism, as well as the Cys/Cys genotype and Cys³²⁶ allele of the OGG1 polymorphism, may be associated with increased risk of the development of ARC, particularly the cortical type, in the Egyptian population.GharibAmal FAFDepartment of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt.DabourSherif ASADepartment of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.EtewaRasha LRLDepartment of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt.FouadRania ARADepartment of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt.engJournal Article20140521
United StatesMol Vis96053511090-0535EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanIMJ Radiat Res. 2003 Mar;44(1):31-512841596Breast Cancer Res Treat. 2003 May;79(1):59-6212779082Invest Ophthalmol Vis Sci. 2004 Jun;45(6):1916-2115161858Invest Ophthalmol Vis Sci. 1979 Oct;18(10):1000-18225285Ophthalmology. 1987 Jul;94(7):875-803309772Arch Ophthalmol. 1988 Dec;106(12):1683-73058100Mutat Res. 1990 Jan;240(1):35-452152969Nippon Ganka Gakkai Zasshi. 1990 Feb;94(2):176-802368644Arch Ophthalmol. 1991 Feb;109(2):244-511993036Invest Ophthalmol Vis Sci. 1989 Feb;30(2):330-22914761Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):261-51729695Mutagenesis. 1991 Nov;6(6):495-91800897J Bacteriol. 1992 Oct;174(20):6321-51328155Arch Ophthalmol. 1993 Jun;111(6):831-68512486Curr Eye Res. 1993 May;12(5):423-318344066Invest Ophthalmol Vis Sci. 1994 Jan;35(1):262-78300354Am J Epidemiol. 1994 Sep 15;140(6):555-648067349Invest Ophthalmol Vis Sci. 1995 Jan;36(1):227-357822150FASEB J. 1995 Sep;9(12):1173-827672510Trends Biochem Sci. 1995 Oct;20(10):402-58533152Genes Dev. 1996 May 15;10(10):1219-328675009Invest Ophthalmol Vis Sci. 1998 Feb;39(2):344-509477992Exp Eye Res. 1994 Nov;59(5):557-649492757Nucleic Acids Res. 2000 Mar 15;28(6):1355-6410684930Carcinogenesis. 2000 Mar;21(3):453-6010688865FEBS Lett. 2000 Jun 30;476(1-2):73-710878254Genes Dev. 2001 Jan 1;15(1):15-2311156600Invest Ophthalmol Vis Sci. 2001 Mar;42(3):601-511222516Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1677-811431427Invest Ophthalmol Vis Sci. 1998 Mar;39(3):544-529501865Oncogene. 1998 Jun 25;16(25):3219-259681819Mutat Res. 1998 May 25;400(1-2):15-249685572Nucleic Acids Res. 1999 Oct 15;27(20):4001-710497264Nucleic Acids Res. 2005;33(6):1813-2415800211Gynecol Oncol. 2005 Oct;99(1):43-915990162Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4661-7016303963Exp Eye Res. 2007 Sep;85(3):328-3417637462Cancer Res. 2009 Apr 15;69(8):3642-919351836Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4732-720375340Mol Vis. 2011;17:127-3321245954Ophthalmology. 2012 May;119(5):900-622306120Mutat Res. 2001 Aug 9;486(3):207-1611459633Antioxid Redox Signal. 2001 Aug;3(4):597-60911554447Environ Mol Mutagen. 2001;38(2-3):180-9011746753Carcinogenesis. 2002 Feb;23(2):295-911872635Carcinogenesis. 2002 Apr;23(4):599-60311960912Ann N Y Acad Sci. 2002 Apr;959:360-711976210Int J Cancer. 2002 Jul 1;100(1):9-1312115580Free Radic Biol Med. 2002 Aug 15;33(4):450-612160927Exp Biol Med (Maywood). 2002 Oct;227(9):671-8212324649Mutat Res. 2002 Nov 30;509(1-2):165-7412427537Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Mech Ageing Dev. 2003 Jan;124(1):27-3212618003Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):23-914744728AgedAginggeneticsAllelesCase-Control StudiesCataractenzymologygeneticsDNA GlycosylasesgeneticsDNA RepairgeneticsDemographyEgyptFemaleGene FrequencygeneticsGenetic Predisposition to DiseaseHumansMaleMiddle AgedPolymorphism, Single NucleotidegeneticsRisk FactorsXeroderma Pigmentosum Group D Proteingenetics
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1872-8278172014JulMitochondrionMitochondrionMitochondrial APE1/Ref-1 suppressed protein kinase C-induced mitochondrial dysfunction in mouse endothelial cells.42-910.1016/j.mito.2014.05.006S1567-7249(14)00080-4Protein kinase C (PKC) induces mitochondrial dysfunction, which is an important pathological factor in cardiovascular diseases. The role of apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) on PKC-induced mitochondrial dysfunction has not been variously investigated. In this study, phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, induced mitochondrial hyperpolarization and reactive oxygen species generation and also increased mitochondrial translocation of APE1/Ref-1. APE1/Ref-1 overexpression suppressed PMA-induced mitochondrial dysfunction. In contrast, gene silencing of APE1/Ref-1 increased the sensitivity of mitochondrial dysfunction. Moreover, mitochondrial targeting sequence (MTS)-fused APE1/Ref-1 more effectively suppressed PMA-induced mitochondrial dysfunctions. These results suggest that mitochondrial APE1/Ref-1 is contributed to the protective role to protein kinase C-induced mitochondrial dysfunction in endothelial cells. Copyright © 2014 © Elsevier B.V. and Mitochondria Research Society. Published by Elsevier B.V. All rights reserved.JooHee KyoungHKDepartment of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea; Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.LeeYu RanYRDepartment of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea; Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.ParkMyoung SooMSDepartment of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea; Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.ChoiSungaSDepartment of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea; Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.ParkKyoungsookKBioNano Health Guard Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.LeeSang KiSKDepartment of Sports Science, Chungnam National University, Daejeon 305-765, Republic of Korea.KimCuk-SeongCSDepartment of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.ParkJin BongJBDepartment of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea; Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.JeonByeong HwaBHDepartment of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea; Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.engJournal ArticleResearch Support, Non-U.S. Gov't20140523
NetherlandsMitochondrion1009687511567-72490Reactive Oxygen SpeciesEC 2.7.11.13Protein Kinase CEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismEndothelial CellsphysiologyMembrane Potential, MitochondrialMiceMitochondriaphysiologyProtein Kinase CmetabolismReactive Oxygen SpeciesmetabolismAPE1/Ref-1Endothelial cellMitochondriaMitochondrial membrane potentialPhorbol 12-myristate 13-acetate
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248303502015012320170922
1949-25535102014May30OncotargetOncotargetTargeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy.3273-86Phosphatase and tensin homolog (PTEN) loss is associated with genomic instability. APE1 is a key player in DNA base excision repair (BER) and an emerging drug target in cancer. We have developed small molecule inhibitors against APE1 repair nuclease activity. In the current study we explored a synthetic lethal relationship between PTEN and APE1 in melanoma. Clinicopathological significance of PTEN mRNA and APE1 mRNA expression was investigated in 191 human melanomas. Preclinically, PTEN-deficient BRAF-mutated (UACC62, HT144, and SKMel28), PTEN-proficient BRAF-wildtype (MeWo), and doxycycline-inducible PTEN-knockout BRAF-wildtype MeWo melanoma cells were DNA repair expression profiled and investigated for synthetic lethality using a panel of four prototypical APE1 inhibitors. In human tumours, low PTEN mRNA and high APE1 mRNA was significantly associated with reduced relapse free and overall survival. Pre-clinically, compared to PTEN-proficient cells, PTEN-deficient cells displayed impaired expression of genes involved in DNA double strand break (DSB) repair. Synthetic lethality in PTEN-deficient cells was evidenced by increased sensitivity, accumulation of DSBs and induction of apoptosis following treatment with APE1 inhibitors. We conclude that PTEN deficiency is not only a promising biomarker in melanoma, but can also be targeted by a synthetic lethality strategy using inhibitors of BER, such as those targeting APE1. AbbottsRachelRAcademic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals, Nottingham, UK.JewellRosalynRNsengimanaJérémieJMaloneyDavid JDJSimeonovAntonASeedhouseClaireCElliottFayeFLayeJonJWalkerChristyCJadhavAjitAGrabowskaAnnaABallGrahamGPatelPoulam MPMNewton-BishopJuliaJWilsonDavid MDM3rdMadhusudanSrinivasanSengR01 CA083115CANCI NIH HHSUnited StatesC8216/A6129Cancer Research UKUnited KingdomR01 CA83115CANCI NIH HHSUnited StatesG0802123Medical Research CouncilUnited KingdomC588/A10589Cancer Research UKUnited Kingdom1 R03 MH086444-01MHNIMH NIH HHSUnited StatesG1000252Medical Research CouncilUnited KingdomC8216/A8168Cancer Research UKUnited KingdomC588/A4994Cancer Research UKUnited Kingdom10589Cancer Research UKUnited KingdomJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't
United StatesOncotarget1015329651949-25530Antineoplastic Agents0RNA, MessengerEC 3.1.3.67PTEN PhosphohydrolaseEC 3.1.3.67PTEN protein, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMExp Mol Pathol. 2012 Feb;92(1):20-622019339J Med Chem. 2012 Apr 12;55(7):3101-1222455312Cell Mol Life Sci. 2012 May;69(9):1475-9122076652Nat Rev Mol Cell Biol. 2012 May;13(5):283-9622473468Cancer Discov. 2012 Jun;2(6):503-1122628410J Clin Oncol. 2012 Jul 10;30(20):2522-922614978Cancer Res. 2003 Jun 1;63(11):2881-9012782594Nat Cell Biol. 2003 Aug;5(8):741-712855956Mutat Res. 2003 Oct 29;531(1-2):157-6314637252Curr Opin Investig Drugs. 2004 Jun;5(6):623-715242251Clin Cancer Res. 2004 Nov 1;10(21):7252-915534099Cancer Cell. 2005 Feb;7(2):193-20415710331Nature. 2005 Apr 14;434(7035):913-715829966Nature. 2005 Apr 14;434(7035):917-2115829967Nucleic Acids Res. 2005;33(15):4711-2416113242Cell. 2007 Jan 12;128(1):157-7017218262Nat Genet. 2009 May;41(5):544-5219282848PLoS One. 2009;4(6):e574019484131Cell Cycle. 2009 Jul 15;8(14):2198-21019502790J Clin Oncol. 2009 Nov 10;27(32):5439-4419770375Lung Cancer. 2009 Dec;66(3):298-30419324449Antioxid Redox Signal. 2009 Mar;11(3):639-5018715151EMBO Mol Med. 2009 Sep;1(6-7):315-2220049735Nat Genet. 2010 May;42(5):454-820400965Cancer Res. 2010 Jul 1;70(13):5457-6420530668Cancer Treat Rev. 2010 Aug;36(5):425-3520056333Sci Transl Med. 2010 Oct 13;2(53):53ra7520944090Cell Mol Life Sci. 2010 Nov;67(21):3621-3120809131Eur J Cancer. 2010 Nov;46(16):2889-9520724143Br J Cancer. 2011 Feb 15;104(4):653-6321266972Cancer Res. 2011 Apr 1;71(7):2750-6021317224Int J Radiat Oncol Biol Phys. 2011 May 1;80(1):240-821481725N Engl J Med. 2011 Jun 30;364(26):2507-1621639808Int J Cancer. 2012 Nov 15;131(10):2433-4422377908Future Oncol. 2012 Sep;8(9):1109-2023030486PLoS One. 2012;7(10):e4797423110144Clin Cancer Res. 2012 Dec 15;18(24):6792; author's reply p. 679323169438Science. 2013 Jul 26;341(6144):395-923888040Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463Breast Cancer Res. 2012;14(6):R14223116406Cancer Res. 2011 Aug 1;71(15):5287-9521771908Clin Cancer Res. 2012 Feb 15;18(4):1015-2722114138Mutat Res. 2000 Oct 16;461(2):83-10811018583Am J Pathol. 2000 Oct;157(4):1123-811021816Br J Cancer. 2001 Jan 5;84(1):106-1211139322Hum Mol Genet. 2002 Feb 15;11(4):445-5011854177Antineoplastic AgentspharmacologyApoptosisBlotting, WesternCell Line, TumorComet AssayDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsFlow CytometryGene Knockdown TechniquesGenome-Wide Association StudyHumansImmunohistochemistryKaplan-Meier EstimateMelanomageneticsmortalitypathologyMolecular Targeted TherapyPTEN PhosphohydrolasedeficiencyRNA, MessengeranalysisReal-Time Polymerase Chain ReactionTransfection
201451760201451760201512460ppublish248303501926PMC410280910.18632/oncotarget.1926
247944002015010620170922
1568-7856182014JunDNA repairDNA Repair (Amst.)Redox and epigenetic regulation of the APE1 gene in the hippocampus of piglets: The effect of early life exposures.52-6210.1016/j.dnarep.2014.03.011S1568-7864(14)00082-2Oxidative stress via redox reactions can regulate DNA repair pathways. The base excision repair (BER) enzyme apurinic/apyrimidinic endonuclease 1 (APE1) is a key player in the redox regulation of DNA repair. Environmental factors can alter the methylation of DNA repair genes, change their expression and thus modulate BER activity and susceptibility to oxidative DNA damage. Therefore, we hypothesized that epigenetic modifications play a role in the redox regulation of APE1 in hippocampi of newborns and investigated the effect of supplementation of pregnant sows with a diet enriched in antioxidants and other nutrients on oxidative stress, DNA methylation and DNA repair in their offspring. High levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and low levels of glutathione were detected in control piglets after birth compared with supplemented piglets, indicating the presence of oxidative stress. In control animals, this oxidative stress was associated with genomic DNA demethylation, decreased APE1 promoter methylation, increased APE1 expression and with slightly but not statistically significant increased BER-related DNA incision activity. Supplementation of piglets with antioxidants and other nutrients significantly lowered 8-oxodG levels compared to control animals, which was accompanied by overall lower APE1 promoter methylation and enhanced APE1 expression at day 7-28 after birth in supplemented piglets, although DNA incision activity was not significantly different between groups. Preliminary attempts to study the interaction between redox and epigenetic regulatory mechanisms revealed an inverse correlation between APE1 expression and methylation of CpG-sites 11 and 13 in the promoter region, which according to Genomatix "MatInspector" are located in the core binding sites of redox-sensitive transcription factors. We are the first to study methylation of the APE1 promoter and its role in mediating the functional effects of redox reactions induced by oxidative stress. Epigenetic and redox mechanisms may interact in regulating APE1-related DNA repair processes, involving redox-sensitive TFs.Copyright © 2014 Elsevier B.V. All rights reserved.LangieSabine A SSACentre for Brain Ageing and Vitality, Human Nutrition Research Centre, Institute for Ageing & Health, Newcastle University, Campus for Ageing and Vitality, NE4 5PL Newcastle upon Tyne, UK. Electronic address: sabine.langie@newcastle.ac.uk.KowalczykPawelPWarsaw University of Life Sciences, Faculty of Agriculture and Biology, Department of Biochemistry, 02-787 Warsaw, Poland.TomaszewskiBartłomiejBCentre for Brain Ageing and Vitality, Human Nutrition Research Centre, Institute for Ageing & Health, Newcastle University, Campus for Ageing and Vitality, NE4 5PL Newcastle upon Tyne, UK.VasilakiAphroditeADepartment of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, Liverpool L69 3GA, UK.MaasLou MLMDepartment of Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands.MoonenEdwin JEJDepartment of Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands.PalaganiAjayAPPES, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.GodschalkRoger W LRWDepartment of Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands.TudekBarbaraBInstitute of Biochemistry and Biophysics PAS, 02-106 Warsaw, Poland; Institute of Genetics and Biotechnology University of Warsaw, 02-106 Warsaw, Poland.van SchootenFrederik JFJDepartment of Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands.BergheWim VandenWVPPES, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.ZabielskiRomualdRDepartment of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, 02-766 Warsaw, Poland.MathersJohn CJCCentre for Brain Ageing and Vitality, Human Nutrition Research Centre, Institute for Ageing & Health, Newcastle University, Campus for Ageing and Vitality, NE4 5PL Newcastle upon Tyne, UK.engBB/G007993/1Biotechnology and Biological Sciences Research CouncilUnited KingdomG0700718Medical Research CouncilUnited KingdomBiotechnology and Biological Sciences Research CouncilUnited KingdomMedical Research CouncilUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20140429
NetherlandsDNA Repair (Amst)1011391381568-78560Antioxidants88847-89-68-oxo-7-hydrodeoxyguanosineEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseG9481N71RODeoxyguanosineGAN16C9B8OGlutathioneIMAnimalsAnimals, NewbornAntioxidantspharmacologyCpG IslandsDNA Methylationdrug effectsDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismDeoxyguanosineanalogs & derivativesmetabolismEpigenesis, GeneticFemaleGene Expression Regulation, DevelopmentalGlutathionemetabolismHippocampusmetabolismMaleOxidation-ReductionPregnancyPromoter Regions, GeneticSwineBase excision repairDevelopmental originEpigeneticsOxidative stress
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1460-210510652014Apr26Journal of the National Cancer InstituteJ. Natl. Cancer Inst.Re: Role of the oxidative DNA damage repair gene OGG1 in colorectal tumorigenesis.10.1093/jnci/dju086dju086KinnersleyBenBAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).BuchStephanSAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).Castellví-BelSergiSAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).FarringtonSusan MarySMAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).ForstiAstaAAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).HampeJochenJAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).HemminkiKariKAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).HofstraRobert M WRMAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).NorthwoodEmmaEAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).PallesClaireCAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).PinheiroManuelaMAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).Ruiz-PonteClaraCAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).SchafmayerClemensCAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).TeixeiraManuel RMRAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).WestersHelgaHAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).WezelTom vanTvAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).BishopD TimothyDTAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).TomlinsonIanIAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).DunlopMalcolm GMGAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW).HoulstonRichard SRSAffiliations of authors: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK (BK, RSH); Department of Medicine I, University Hospital Dresden, Dresden, Germany (SB); Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain (SCB); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, UK (MGD, SMF); German Cancer Research Center, Heidelberg, Germany (AF, KH); Department of Internal Medicine I, Hospital Schleswig-Holstein, Kiel, Germany (JH); Leeds Cancer Research UK Centre, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer Studies and Pathology, St James's University Hospital, Leeds, UK (EN, DTB); Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK (CP, IT); Department of Genetics, Portugese Oncology Institute, Porto, Portugal (MP, MRT); Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Rad de Enfermedades Rares, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain (CRP); Department of General and Thoraci Surgery, University Hospital Schleswig-Holstein, Kiel, Germany (CS); University of Gronigen, University Medical Centre Gronigen, Department of Genetics, Gronigen, The Netherlands (HW, RMWH); Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands (RMWH); Leiden Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands (TW). richard.houlston@icr.ac.uk.engCZB/4/449Chief Scientist OfficeUnited KingdomG1001799Medical Research CouncilUnited KingdomMC_PC_U127527198Medical Research CouncilUnited Kingdom12076Cancer Research UKUnited KingdomMC_U127527198Medical Research CouncilUnited Kingdom090532Wellcome TrustUnited KingdomCZD/16/6/4Chief Scientist OfficeUnited Kingdom10589Cancer Research UKUnited KingdomMR/L01629X/1Medical Research CouncilUnited KingdomCommentLetterResearch Support, Non-U.S. Gov't20140426
United StatesJ Natl Cancer Inst75030890027-8874EC 3.2.2.-DNA GlycosylasesIMJ Natl Cancer Inst. 2013 Aug 21;105(16):1249-5323852950J Natl Cancer Inst. 2014 May;106(5). pii: dju087. doi: 10.1093/jnci/dju08724771876J Natl Cancer Inst. 2013 Aug 21;105(16):1249-5323852950AdenomageneticsCarcinomageneticsColorectal NeoplasmsgeneticsDNA DamageDNA GlycosylasesgeneticsDNA RepairgeneticsFemaleHumansMaleMutation
20144296020144296020147960epublish24771875dju08610.1093/jnci/dju086PMC4677263
247293902014112520171116
1097-0215135112014Dec01International journal of cancerInt. J. CancerAssociation of DNA base excision repair genes (OGG1, APE1 and XRCC1) polymorphisms with outcome to platinum-based chemotherapy in advanced nonsmall-cell lung cancer patients.2687-9610.1002/ijc.28892Polymorphism of DNA base excision repair (BER) genes affects DNA repair capacity and may alter sensitivity to platinum-based chemotherapy regimens. This study investigated polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu APE1-141T/G and XRCC1 Arg399Gln for association with clinical outcome in 235 advanced inoperable nonsmall-cell lung cancer (NSCLC) patients after treatment with platinum-based chemotherapy. The multivariate analysis showed that OGG1 326 GC was associated with poor PFS [hazard ratio (HR) 1.730, p = 0.005], while XRCC1 399 GA, or GA+AA, was associated with poor OS in short-term period (HR 1.718, p = 0.003; HR 1.691, p = 0.003, respectively). Patients with OGG1 326/XRCC1 399 variant alleles had a higher risk to die early in short-term period (HR 1.929, p < 0.001). Furthermore, patients with XRCC1 399 variant allele (GA+AA) had higher risk of hematologic toxicity (p = 0.009), whereas patients carrying the OGG1 326 variant (GG), or the APE1-141 GG variant, had reduced risk of gastrointestinal toxicity (p = 0.015 and p = 0.023, respectively). The data from the current study provide evidence that OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and APE1-141T/G polymorphisms may be useful in predicting clinical outcomes in patients with advanced inoperable NSCLC that will undergo platinum-based chemotherapy.© 2014 UICC.PengYuYCancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.LiZhengZZhangShihengSXiongYanliYCunYanpingYQianChengyuanCLiMengxiaMRenTaoTXiaLeiLChengYiYWangDongDengJournal ArticleResearch Support, Non-U.S. Gov't20140425
United StatesInt J Cancer00421240020-71360Biomarkers, Tumor0DNA-Binding Proteins0Taxoids0X-ray Repair Cross Complementing Protein 10XRCC1 protein, human0W860991D6Deoxycytidine15H5577CQDdocetaxelB76N6SBZ8RgemcitabineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseP88XT4IS4DPaclitaxelQ20Q21Q62JCisplatinIMAdenocarcinomadrug therapygeneticsmortalitysecondaryAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy Protocolstherapeutic useBiomarkers, TumorgeneticsCarcinoma, Non-Small-Cell Lungdrug therapygeneticsmortalitysecondaryCarcinoma, Squamous Celldrug therapygeneticsmortalitysecondaryCase-Control StudiesCisplatinadministration & dosageDNA GlycosylasesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsDeoxycytidineadministration & dosageanalogs & derivativesFemaleFollow-Up StudiesHumansLung Neoplasmsdrug therapygeneticsmortalitypathologyLymphatic MetastasisMaleMiddle AgedNeoplasm StagingPaclitaxeladministration & dosagePolymorphism, Single NucleotidegeneticsPrognosisProspective StudiesSurvival RateTaxoidsadministration & dosageX-ray Repair Cross Complementing Protein 1base excision repairchemotherapynonsmall-cell lung cancerpolymorphismstoxicity
2013093020140312201403262014415602014415602014121560ppublish2472939010.1002/ijc.28892
247057772014100620171111
1423-03803572014JulTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Genetic polymorphism of APE1 rs1130409 can contribute to the risk of lung cancer.6665-7110.1007/s13277-014-1829-9Accumulative evidence suggests that polymorphism in the APE1 gene may have association with the etiology of lung cancer by modulating DNA repair capacity. Many studies have evaluated the association with great discrepancies in the results. The present meta-analysis was undertaken to clarify the effects of this polymorphism on lung cancer. A meta-analysis of 15 studies with 4,932 lung cancer patients and 6,555 cancer-free controls was conducted to evaluate the strength of the association using odds ratios (ORs) with 95 % confidence intervals (CIs). Overall, no significant association was found between APE1 polymorphism and lung cancer risk. We also did not observe any statistical evidence of modified lung cancer risk either in smokes or in nonsmokers. In the stratified analysis by ethnicity, however, it was found that the Glu/Clu genotype carriers had 1.16-fold higher risk of suffering lung cancer compared with the carriers of Arg/Glu + Arg/Arg genotypes in Asian population (OR = 1.16, 95 % CI = 1.01-1.32, P = 0.242). This meta-analysis provides statistical evidence for a potential association between APE1 polymorphism and an increased risk of lung cancer in Asian population.JinFengFCancer Center, Research Institute of Surgery and Daping Hospital, Third Military Medical University, No.10 Changjiang Zhilu, Yuzhong District, Chongqing, 400042, China.QianChengyuanCQingYiYZhangZhiminZWangGeGShanJinluJDaiNanNLiZhengZWangDongDengJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov't20140406
United StatesTumour Biol84099221010-4283EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBiochimie. 2003 Nov;85(11):1053-7114726013Mutat Res. 2002 Nov 30;509(1-2):165-7412427537Asian Pac J Cancer Prev. 2010;11(5):1181-621198260Anticancer Res. 2013 Jun;33(6):2775-823749940Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Anticancer Res. 2005 Jan-Feb;25(1B):537-4215816625PLoS One. 2013 Jul 11;8(7):e6901823874853Int J Cancer. 2001 Oct 15;94(2):153-611668491Control Clin Trials. 1986 Sep;7(3):177-883802833Mol Biol Rep. 2011 Oct;38(7):4537-4321132382Cell Biochem Biophys. 2001;35(2):141-7011892789Cancer Lett. 2003 Mar 10;191(2):171-812618330Carcinogenesis. 2006 May;27(5):997-100716308313Med Oncol. 2011 Sep;28(3):667-7220354815Mutat Res. 2007 Jul 28;631(2):101-1017531525Anticancer Res. 2009 Jun;29(6):2417-2019528510Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Cancer Epidemiol Biomarkers Prev. 2003 Aug;12(8):689-9812917198BMJ. 2003 Sep 6;327(7414):557-6012958120Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Carcinogenesis. 2000 Jul;21(7):1329-3410874010Oncogene. 2002 Oct 7;21(45):6870-612362269Carcinogenesis. 2004 Aug;25(8):1395-40115044328J Natl Cancer Inst. 2000 Nov 1;92(21):1764-7211058619Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1054-6412376507Arch Med Res. 2011 Apr;42(3):226-3421722819Carcinogenesis. 2006 Mar;27(3):560-716195237Genomics. 2004 Jun;83(6):970-915177551Surg Oncol Clin N Am. 2011 Oct;20(4):605-1821986260Int J Cancer. 2003 Oct 20;107(1):84-812925960J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060World J Surg Oncol. 2012 Aug 24;10:17022917490Hum Exp Toxicol. 2012 Oct;31(10):981-100523023028Mol Biol Rep. 2012 Dec;39(12):11249-6223065211BMJ. 1997 Sep 13;315(7109):629-349310563Carcinogenesis. 2004 Dec;25(12):2433-4115333465Toxicol Pathol. 2010 Oct;38(6):849-5520805318FASEB J. 2009 Oct;23(10):3459-6919541747J Clin Oncol. 2000 Jun;18(11):2309-1510829052Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Asian Continental Ancestry GroupgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGenetic Association StudiesGenetic Predisposition to DiseaseHumansLung NeoplasmsgeneticsPolymorphism, Single NucleotideRisk FactorsSmokingadverse effectsgenetics
20131230201403052014486020144860201410760ppublish2470577710.1007/s13277-014-1829-9
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1089-8638426112014May29Journal of molecular biologyJ. Mol. Biol.APE1 incision activity at abasic sites in tandem repeat sequences.2183-9810.1016/j.jmb.2014.03.014S0022-2836(14)00159-4Repetitive DNA sequences, such as those present in microsatellites and minisatellites, telomeres, and trinucleotide repeats (linked to fragile X syndrome, Huntington disease, etc.), account for nearly 30% of the human genome. These domains exhibit enhanced susceptibility to oxidative attack to yield base modifications, strand breaks, and abasic sites; have a propensity to adopt non-canonical DNA forms modulated by the positions of the lesions; and, when not properly processed, can contribute to genome instability that underlies aging and disease development. Knowledge on the repair efficiencies of DNA damage within such repetitive sequences is therefore crucial for understanding the impact of such domains on genomic integrity. In the present study, using strategically designed oligonucleotide substrates, we determined the ability of human apurinic/apyrimidinic endonuclease 1 (APE1) to cleave at apurinic/apyrimidinic (AP) sites in a collection of tandem DNA repeat landscapes involving telomeric and CAG/CTG repeat sequences. Our studies reveal the differential influence of domain sequence, conformation, and AP site location/relative positioning on the efficiency of APE1 binding and strand incision. Intriguingly, our data demonstrate that APE1 endonuclease efficiency correlates with the thermodynamic stability of the DNA substrate. We discuss how these results have both predictive and mechanistic consequences for understanding the success and failure of repair protein activity associated with such oxidatively sensitive, conformationally plastic/dynamic repetitive DNA domains. Published by Elsevier Ltd.LiMengxiaMLaboratory of Molecular Gerontology, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.VölkerJensJDepartment of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854, USA.BreslauerKenneth JKJDepartment of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854, USA; Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA.WilsonDavid MDM3rdLaboratory of Molecular Gerontology, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA. Electronic address: wilsonda@mail.nih.gov.engCA47995CANCI NIH HHSUnited StatesR01 GM034469GMNIGMS NIH HHSUnited StatesR01 GM023509GMNIGMS NIH HHSUnited StatesZIA AG000743-12NULLIntramural NIH HHSUnited StatesP01 CA047995CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20140401
EnglandJ Mol Biol2985088R0022-28369007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBiochem J. 2010 Aug 1;429(3):573-8220528769PLoS Genet. 2010 May;6(5):e100095120485567DNA Repair (Amst). 2011 Aug 15;10(8):887-9621727036Hum Mutat. 2011 Oct;32(10):1075-9921853507Biochemistry. 2012 Jan 10;51(1):52-6222148399Curr Mol Pharmacol. 2012 Jan;5(1):3-1322122461J Am Chem Soc. 2012 Apr 4;134(13):6033-4422397401Biochemistry. 2012 May 8;51(18):3919-3222497302Biochemistry (Mosc). 2012 Mar;77(3):270-922803944Cell Cycle. 2012 Mar 1;11(5):998-100722336916Hum Mol Genet. 2012 Nov 15;21(22):4939-4722914735J Clin Invest. 2013 Mar;123(3):996-100223454763PLoS One. 2013;8(2):e5696023468897Neuron. 2013 Mar 6;77(5):825-4323473314PLoS Genet. 2013;9(7):e100363923874233Radiat Res. 2013 Jul;180(1):100-923682596J Biol Chem. 2013 Sep 20;288(38):27263-7223926102Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17844-924127576Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463Nucleic Acids Res. 2013 Apr 1;41(6):3483-9023408852Nature. 2000 Jan 27;403(6768):451-610667800Trends Biochem Sci. 2002 Jul;27(7):339-4412114022Biochemistry. 2004 Apr 13;43(14):4188-9515065862DNA Repair (Amst). 2004 May 4;3(5):527-3315084314Cancer Res. 2004 Jun 1;64(11):3830-715172990Ann N Y Acad Sci. 2004 Jun;1019:278-8415247029Nucleic Acids Res. 2004;32(17):5134-4615459284J Biol Chem. 1980 Dec 25;255(24):11743-526254980Annu Rev Genet. 1986;20:201-303545059J Biol Chem. 1987 Jul 25;262(21):10171-92440861Biopolymers. 1987 Sep;26(9):1601-203663875Nature. 1993 Apr 22;362(6422):709-158469282Methods Mol Biol. 1994;26:347-727508801J Biol Chem. 1995 Jul 7;270(27):16002-77608159Anal Biochem. 1995 Nov 20;232(1):79-858600837Nucleic Acids Res. 1997 Mar 1;25(5):933-99023101J Biol Chem. 1997 May 23;272(21):13916-229153253Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6126-319177181J Biol Chem. 1997 Jun 20;272(25):15650-59188454Nucleic Acids Res. 1998 Jun 1;26(11):2771-89592167J Biol Chem. 1998 Dec 11;273(50):33406-139837917Biopolymers. 1999 Sep;50(3):303-1810397791Chem Res Toxicol. 1999 Oct;12(10):917-2310525266J Mol Biol. 2005 Feb 4;345(5):1003-1415644200Nucleic Acids Res. 2005;33(4):1230-915731343DNA Repair (Amst). 2005 Dec 8;4(12):1442-916199212Cancer Res. 2006 Jan 1;66(1):113-2416397223J Biol Chem. 2006 Feb 17;281(7):3889-9816356936Chem Res Toxicol. 2006 Sep;19(9):1215-2016978026J Am Chem Soc. 2006 Oct 11;128(40):13034-517017766J Am Chem Soc. 2007 Apr 25;129(16):5272-8017397164Nature. 2007 May 24;447(7143):447-5217450122Nucleic Acids Res. 2008 May;36(8):2717-2718353858J Mol Biol. 2008 May 23;379(1):17-2718439621J Biol Chem. 2009 Jun 5;284(23):15835-4619324873J Am Chem Soc. 2009 Jul 8;131(26):9354-6019566100Biochemistry. 2009 Jul 21;48(28):6655-6319527055J Biol Chem. 2009 Oct 9;284(41):28352-6619674974PLoS Genet. 2009 Dec;5(12):e100074919997493Biopolymers. 2010 Apr;93(4):355-6919890964J Am Chem Soc. 2010 Mar 31;132(12):4095-720218680DNA Repair (Amst). 2011 Jan 2;10(1):34-4420951653Base CompositionphysiologyBase SequenceDNAchemistrymetabolismDNA CleavageDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismHeLa CellsHumansNucleic Acid ConformationProtein BindingTandem Repeat SequencesTelomerechemistrymetabolismThermodynamicsAP or abasic siteAPEX1tandem repeattelomeretrinucleotide expansion
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1090-210444712014Apr25Biochemical and biophysical research communicationsBiochem. Biophys. Res. Commun.Cellular accumulation of Cys326-OGG1 protein complexes under conditions of oxidative stress.12-810.1016/j.bbrc.2014.03.044S0006-291X(14)00486-0The common Ser326Cys polymorphism in the base excision repair protein 8-oxoguanine glycosylase 1 is associated with a reduced capacity to repair oxidative DNA damage particularly under conditions of intracellular oxidative stress and there is evidence that Cys326-OGG1 homozygous individuals have increased susceptibility to specific cancer types. Indirect biochemical studies have shown that reduced repair capacity is related to OGG1 redox modification and also possibly OGG1 dimer formation. In the current study we have used bimolecular fluorescence complementation to study for the first time a component of the base excision repair pathway and applied it to visualise accumulation of Cys326-OGG1 protein complexes in the native cellular environment. Fluorescence was observed both within and around the cell nucleus, was shown to be specific to cells expressing Cys326-OGG1 and only occurred in cells under conditions of cellular oxidative stress following depletion of intracellular glutathione levels by treatment with buthionine sulphoximine. Furthermore, OGG1 complex formation was inhibited by incubation of cells with the thiol reducing agents β-mercaptoethanol and dithiothreitol and the antioxidant dimethylsulfoxide indicating a causative role for oxidative stress in the formation of OGG1 cellular complexes. In conclusion, this study has provided for the first time evidence of redox sensitive Cys326-OGG1 protein accumulation in cells under conditions of intracellular oxidative stress that may be related to the previously reported reduced repair capacity of Cys326-OGG1 specifically under conditions of oxidative stress.Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.KaurM PMPSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.GuggenheimE JEJSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.PuliscianoCCSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.AkbarSSSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.KershawR MRMSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.HodgesN JNJSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. Electronic address: N.Hodges@bham.ac.uk.engBiotechnology and Biological Sciences Research CouncilUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20140327
United StatesBiochem Biophys Res Commun03725160006-291X5072-26-4Buthionine SulfoximineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanYOW8V9698HDimethyl SulfoxideIMProc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Nucleic Acids Res. 2012 Jan;40(2):701-1121933813Nature. 2000 Feb 24;403(6772):859-6610706276Biochem Soc Trans. 2001 May;29(Pt 2):350-311356181Carcinogenesis. 2001 Sep;22(9):1459-6311532868Carcinogenesis. 2002 Jan;23(1):55-6011756223Biol Chem. 2002 Mar-Apr;383(3-4):467-7512033436Nucleic Acids Res. 2002 Jun 1;30(11):2349-5712034821Biochim Biophys Acta. 2012 Jun;1820(6):730-521571039Mutagenesis. 2012 Jul;27(4):501-1022451681DNA Repair (Amst). 2013 Mar 1;12(3):227-3723332971Free Radic Biol Med. 2013 Oct;63:401-923726996Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Carcinogenesis. 2002 Dec;23(12):2005-1012507922DNA Repair (Amst). 2003 Jun 11;2(6):707-1812767349Anal Biochem. 1976 Jul;74(1):214-26962076Trends Genet. 1993 Jul;9(7):246-98379000Chem Res Toxicol. 1993 Sep-Oct;6(5):690-7008292748Curr Biol. 1997 Jun 1;7(6):397-4079197244Environ Health Perspect. 1998 Feb;106 Suppl 1:289-959539021Oncogene. 1998 Jun 25;16(25):3219-259681819Nucleic Acids Res. 1999 Oct 15;27(20):4001-710497264Mol Carcinog. 2005 Mar;42(3):127-4115584022Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):497-50515734978Nucleic Acids Res. 2005;33(6):1813-2415800211Nucleic Acids Res. 2005;33(10):3271-8215942030Cancer Res. 2005 Jul 15;65(14):6006-1016024598Mol Cell Biol. 2006 Mar;26(5):1654-6516478987Nucleic Acids Res. 2006;34(5):1620-3216549874Mol Cell Biol. 2006 Oct;26(20):7430-616923968DNA Repair (Amst). 2006 Nov 8;5(11):1337-4516861056J Cell Sci. 2007 Jan 1;120(Pt 1):23-3217148573Mutagenesis. 2007 May;22(3):189-9417284772Mol Cell. 2008 Feb 29;29(4):477-8718313385J Radiat Res. 2008 Jul;49(4):329-4018596371Biochem J. 2009 Jan 1;417(1):1-1319061483Cancer Res. 2009 Apr 15;69(8):3642-919351836EMBO J. 2009 Oct 21;28(20):3207-1519713937Mutat Res. 2010 Mar 1;685(1-2):61-919800894Toxicol Appl Pharmacol. 2011 Jan 1;250(1):19-2820934443J Biochem Mol Toxicol. 2011 Jan-Feb;25(1):1-721322094Carcinogenesis. 2000 Mar;21(3):361-7010688856Buthionine SulfoximinepharmacologyCell Line, TumorDNA GlycosylasesbiosynthesisgeneticsDNA Repairdrug effectsDimethyl SulfoxidepharmacologyHumansOxidative StressgeneticsSpectrometry, FluorescenceBiFC visualisationDimerOGG1Oxidative stress
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1837-9664532014Journal of CancerJ CancerAssociation between APE1 Single Nucleotide Polymorphism (rs1760944) and Cancer Risk: a Meta-Analysis Based on 6,419 Cancer Cases and 6,781 Case-free Controls.253-910.7150/jca.8085Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway. Epidemiological studies have suggested associations between APE1 rs1760944 polymorphism and cancer risk. This study was aimed to evaluate the relationship between APE1 rs1760944 polymorphism and cancer risk. We searched Pubmed, ISI Web of Knowledge, Embase, Chinese National Knowledge Infrastructure (CNKI) databases until September 2013 to identify eligible studies. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to estimate the strength of the associations. 12 studies from 11 articles on APE1 rs1760944 genotypes and cancer risk were identified, including a total of 6,419 cancer cases and 6,781 case-free controls. Overall, APE1 rs1760944 polymorphism was significantly associated with the decreased risk of cancer in any genetic models (G vs. T: OR = 0.86, 95% CI = 0.82-0.90; homozygote comparison: OR = 0.74, 95% CI = 0.67-0.82; heterozygote comparison: OR =0.88, 95%CI = 0.81-0.95; dominant model TG+GG vs. TT: OR = 0.82, 95% CI = 0.76-0.89; recessive model GG vs. TT+TG: OR = 0.81, 95%CI = 0.75-0.88). In the stratified analysis by populations, the effect was remain in studies of Asian population (homozygote comparison: OR = 0.71, 95%CI = 0.63-0.79; heterozygote comparison: OR = 0.86, 95 %CI = 0.79- 0.94; dominant model: OR = 0.80, 95% CI = 0.74 -0.87 and recessive model: OR = 0.78, 95%CI = 0.71-0.86). Moreover, a significantly decreased risk was found in lung cancer studies (homozygote comparison: OR = 0.68, 95% CI = 0.59-0.79; heterozygote comparison: OR = 0.86, 95%CI = 0.77- 0.98; dominant model: OR = 0.80, 95%CI = 0.72-0.90 and recessive model: OR= 0.77, 95% CI= 0.68-0.87). These findings support that APE1 rs1760944 polymorphism has a possible protective effect on cancer susceptibility particularly among Asians. Further studies based on different ethnicity and various cancer types are warranted to verify our findings. DaiZhi-JunZJ1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;WangXi-JingXJ1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;KangAn-JingAJ2. Department of Pathology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;MaXiao-BinXB1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;MinWei-LiWL1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;LinShuaiS1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;ZhaoYangY1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;YangPeng-TaoPT1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;WangMengM1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;KangHua-FengHF1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;engJournal Article20140313
AustraliaJ Cancer1015359201837-9664Cancer Res. 2007 Feb 1;67(3):1395-40417283177PLoS One. 2013 Jul 11;8(7):e6901823874853DNA Cell Biol. 2010 Jun;29(6):303-1120218899Mutat Res. 2005 Sep 4;577(1-2):275-8315922366PLoS One. 2013;8(4):e6060723577132Mol Carcinog. 2011 Nov;50(11):863-7021538578Am J Obstet Gynecol. 2013 Oct;209(4):360.e1-723871947Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084BMC Cancer. 2011 Mar 23;11:10421429202Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501PLoS One. 2012;7(12 ):e5085723272074Mutagenesis. 2009 Nov;24(6):507-1219762350Cancer Sci. 2011 Jul;102(7):1293-721615620Arch Med Res. 2011 Apr;42(3):226-3421722819Genomics. 2004 Jun;83(6):970-915177551Antioxid Redox Signal. 2014 Feb 1;20(4):678-70723834463FEBS Lett. 2000 Jun 30;476(1-2):73-710878254Environ Mol Mutagen. 2002;39(2-3):208-1511921191FASEB J. 2009 Oct;23(10):3459-6919541747BMC Cancer. 2011 Dec 18;11:52122176746Clin Lab. 2013;59(1-2):163-823505922Mutat Res. 2003 May 15;526(1-2):93-12512714187Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766Gene. 2013 Nov 15;531(1):97-10023994194APE1cancer susceptibilitymeta-analysis.single nucleotide polymorphism
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1559-02836932014JulCell biochemistry and biophysicsCell Biochem. Biophys.Genistein alleviates radiation-induced pneumonitis by depressing Ape1/Ref-1 expression to down-regulate inflammatory cytokines.725-33The aim of the study was to investigate the role of genistein in alleviating radiation-induced pneumonitis(RIP) through down-regulating levels of the inflammatory cytokines by inhibiting the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1). Fifty female C57BL/6J mice (8 weeks old) were randomly divided into a control group, a pure irradiation (IR) group and a genistein + IR group. At the four time points after IR, hematoxylin, and Masson’s trichrome stainings were used to examine the pathological changes and collagen fiber deposition. Flow cytometry was used to detect reactive oxygen system (ROS) changes, EMSA was used to estimate the nuclear factor kappa B (NF-κB) transcriptional activities and an ELISA assay was used to measure the levels of TGF-β1, IL-1β, TNF-α, and IL-6 in the serum and bronchoalveolar lavage fluid (BALF) 2 weeks after IR.The pathological detection results showed acute inflammatory/fibrinoid exudation of the thoracic tissue after IR,which was significantly alleviated with genistein. The IR inducedan APE1 protein expression increase and NF-jB was effectively suppressed by genistein (P < 0.05). The induction of the inflammatory cytokines TGF-β1, IL-1β,TNF-α, and IL-6 by IR were in turn inhibited in the serum and BALF of the genistein-pretreated mice (P < 0.05). In addition, the ROS production was significantly boosted in the A549 cells after IR, which could be down-regulated by the pretreatment of genistein. The results demonstrate that genistein alleviates RIP by attenuating the inflammatory response in the initiation of RIP. A possible target of genistein is the Ape1/ref-1, which regulates key inflammatory cytokines by activating the NF-κB.LiuGuo-DongGDXiaLeiLZhuJian-WuJWOuShanSLiMeng-XiaMXHeYongYLuoWeiWLiJuanJZhouQianQYangXue-QinXQShanJin-LuJLWangGeGWangDongDYangZhen-ZhouZZengJournal ArticleResearch Support, Non-U.S. Gov't
United StatesCell Biochem Biophys97019341085-91950Cytokines0NF-kappa B0Radiation-Protective Agents0Reactive Oxygen SpeciesDH2M523P0HGenisteinEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsBronchoalveolar Lavage FluidchemistryCell Line, TumorCytokinesmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismDown-Regulationdrug effectsFemaleGenisteinpharmacologytherapeutic useHumansMiceMice, Inbred C57BLNF-kappa BmetabolismRadiation Pneumonitisdrug therapymetabolismpathologyRadiation-Protective Agentspharmacologytherapeutic useReactive Oxygen SpeciesmetabolismThoraxdrug effectspathologyradiation effects
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diff --git a/easyPM_example02.xml b/easyPM_example02.xml new file mode 100644 index 0000000..933cb4c --- /dev/null +++ b/easyPM_example02.xml @@ -0,0 +1,10 @@ + + +246243382015061620171116
2213-231722014Redox biologyRedox BiolInhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization.485-9410.1016/j.redox.2014.01.023The effectiveness of current treatment for age related macular degeneration (AMD) by targeting one molecule is limited due to its multifactorial nature and heterogeneous pathologies. Treatment strategy to target multiple signaling pathways or pathological components in AMD pathogenesis is under investigation for better clinical outcome. Inhibition of the redox function of apurinic endonuclease 1/redox factor-1 (APE1) was found to suppress endothelial angiogenesis and promote neuronal cell recovery, thereby may serve as a potential treatment for AMD. In the current study, we for the first time have found that a specific inhibitor of APE1 redox function by a small molecule compound E3330 regulates retinal pigment epithelium (RPEs) cell response to oxidative stress. E3330 significantly blocked sub-lethal doses of oxidized low density lipoprotein (oxLDL) induced proliferation decline and senescence advancement of RPEs. At the same time, E3330 remarkably decreased the accumulation of intracellular reactive oxygen species (ROS) and down-regulated the productions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), as well as attenuated the level of nuclear factor-κB (NF-κB) p65 in RPEs. A panel of stress and toxicity responsive transcription factors that were significantly upregulated by oxLDL was restored by E3330, including Nrf2/Nrf1, p53, NF-κB, HIF1, CBF/NF-Y/YY1, and MTF-1. Further, a single intravitreal injection of E3330 effectively reduced the progression of laser-induced choroidal neovascularization (CNV) in mouse eyes. These data revealed that E3330 effectively rescued RPEs from oxidative stress induced senescence and dysfunctions in multiple aspects in vitro, and attenuated laser-induced damages to RPE-Bruch׳s membrane complex in vivo. Together with its previously established anti-angiogenic and neuroprotection benefits, E3330 is implicated for potential use for AMD treatment. LiYYDepartment of Ophthalmology, Henry Ford Health System, 1 Ford Place 5D, Detroit, MI, United States ; Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi׳an, Shanxi, People׳s Republic of China.LiuXXDepartment of Ophthalmology, Henry Ford Health System, 1 Ford Place 5D, Detroit, MI, United States.ZhouTTDepartment of Ophthalmology, Henry Ford Health System, 1 Ford Place 5D, Detroit, MI, United States.KelleyM RMRHerman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States.EdwardsPPDepartment of Ophthalmology, Henry Ford Health System, 1 Ford Place 5D, Detroit, MI, United States.GaoHHDepartment of Ophthalmology, Henry Ford Health System, 1 Ford Place 5D, Detroit, MI, United States.QiaoXXDepartment of Ophthalmology, Henry Ford Health System, 1 Ford Place 5D, Detroit, MI, United States.engR01 CA121168CANCI NIH HHSUnited StatesR01 CA167291CANCI NIH HHSUnited StatesCA121168CANCI NIH HHSUnited StatesCA16729CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20140221
NetherlandsRedox Biol1016056392213-23170Benzoquinones0Neuroprotective Agents0Propionates136164-66-4E 3330EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAntioxid Redox Signal. 2005 May-Jun;7(5-6):726-4015890019Physiol Rev. 2005 Jul;85(3):845-8115987797Mol Vis. 2005 Jul 14;11:509-1716052166Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1355-6117325184Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):755-6117272744Am J Ophthalmol. 2007 Apr;143(4):607-1517280640Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642DNA Repair (Amst). 2008 Feb 1;7(2):177-8617974506Am J Public Health. 2008 Mar;98(3):454-6118235074Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1665-7018385089J Neurochem. 2008 May;105(4):1187-9718182060Nucleic Acids Res. 2008 Aug;36(13):4327-3618586825Antioxid Redox Signal. 2008 Nov;10(11):1853-6718627350Ophthalmology. 2009 Jan;116(1):57-65.e519118696J Cell Physiol. 2009 Apr;219(1):209-1819097035Ageing Res Rev. 2009 Oct;8(4):349-5819589398Exp Gerontol. 2009 Nov;44(11):685-819751815Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116J Med Chem. 2010 Feb 11;53(3):1200-1020067291J Biomed Biotechnol. 2010;2010:19072420182540Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1275-8120185837BMJ. 2010;340:c245920538634Oncogene. 2010 Jul 29;29(30):4330-4020498636Cancer Invest. 2010 Nov;28(9):885-9520919954Arch Ophthalmol. 2010 Oct;128(10):1281-620937997Respir Physiol Neurobiol. 2010 Dec 31;174(3):265-7120883826J Neuroinflammation. 2010;7:8721126357Vision Res. 2011 Jan;51(1):93-10020937296PLoS One. 2011;6(4):e1945621559389Free Radic Biol Med. 2011 Jun 15;50(12):1749-5921443946N Engl J Med. 2011 May 19;364(20):1897-90821526923Mol Cancer Ther. 2011 Sep;10(9):1698-70821700832J Cell Physiol. 2012 Jan;227(1):116-2621374591Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18277-8221969589Mol Vis. 2011;17:3072-722162626Adv Exp Med Biol. 2012;723:269-7722183342Brain Res. 2012 Mar 20;1444:87-9522325097Med Hypotheses. 2012 Apr;78(4):505-1022296808Ann N Y Acad Sci. 2000;926:64-7811193042Prog Retin Eye Res. 2001 May;20(3):385-41411286898Invest Ophthalmol Vis Sci. 2001 Oct;42(11):2714-2011581220Mutat Res. 2001 May 10;485(4):283-30711585362J Biol Chem. 2002 Nov 15;277(46):44548-5612213807Prog Retin Eye Res. 2003 Jan;22(1):1-2912597922Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1753-912657618J Lipid Res. 2004 Feb;45(2):263-7114594998Ophthalmology. 2004 Jul;111(7):1280-715234127Graefes Arch Clin Exp Ophthalmol. 2004 Aug;242(8):710-615309554Free Radic Res. 2004 Jun;38(6):541-5115346645Arch Ophthalmol. 1984 Nov;102(11):1640-26208888EMBO J. 1992 Feb;11(2):653-651537340EMBO J. 1992 Sep;11(9):3323-351380454Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414Mutat Res. 1994 Jul;315(1):55-637517011Nucleic Acids Res. 1994 Nov 25;22(23):4884-97800476Mol Pharmacol. 1996 May;49(5):860-738622636Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463Int J Biochem Cell Biol. 2012 May;44(5):808-1422349216Mol Aspects Med. 2012 Aug;33(4):376-9822575354PLoS One. 2012;7(10):e4417623071493Invest Ophthalmol Vis Sci. 2012 Dec;53(13):8350-6623139272J Immunol. 2013 May 1;190(9):4786-9423530143Biochemistry. 2013 Apr 30;52(17):2955-6623597102Mol Biol Cell. 2010 Jun 15;21(12):2087-9620427574Mol Vis. 1999 Nov 3;5:2710562651Cell Death Differ. 2000 Mar;7(3):272-8110745272Nat Biotechnol. 2000 Aug;18(8):877-8110932159Mutat Res. 2000 Oct 16;461(2):83-10811018583Surv Ophthalmol. 2000 Sep-Oct;45(2):115-3411033038Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Genes Dev. 1997 Mar 1;11(5):558-709119221J Immunol. 1998 Jan 15;160(2):810-99551916J Immunol. 1999 Jan 15;162(2):727-349916692Invest Ophthalmol Vis Sci. 1999 Feb;40(2):477-869950608Br J Ophthalmol. 2004 Dec;88(12):1590-415548818Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084AnimalsBenzoquinonesadministration & dosageCellular Senescencedrug effectsChoroidal Neovascularizationdrug therapymetabolismpathologyDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsmetabolismDisease Models, AnimalGene Expression Regulationdrug effectsHumansIntravitreal InjectionsMiceNeuroprotective Agentsadministration & dosageOxidative Stressdrug effectsPropionatesadministration & dosageRetinal Pigment Epitheliumdrug effectsmetabolismpathologyAMD, age related macular degenerationAP-1, activator protein 1APE1, apurinic endonuclease 1/redox factor-1APE1/Ref-1redox functionAge-related macular degeneration.AhR, aryl hydrocarbon receptorApoE, apolipoprotein ECBF/NF-Y/YY1, CCAAT binding factor/nuclear factor-Y/Yin Yang 1CECs, choroidal endothelial cellsCNV, choroidal neovascularizationDCFH-DA, dichlorodihydrofluorescin diacetateDMSO, dimethylsulphoxideE3330Fluc, firefly luciferaseHIF-1α, hypoxia inducible factor-1αHSF1, heat-shock factor 1IκB-α, inhibitory NF-κB-αMCP-1, monocyte chemoattractant protein-1MTF1, metal regulatory transcription factor 1NF-κB, nuclear factor-κBNox, NADPH oxidaseNrf, nuclear factor erythroid-2-related factorOxidative stressRNV, retinal neovascularizationROS, reactive oxygen speciesRPE, retinal pigment epitheliumRVECs, retinal vascular endothelial cellsRetinal pigment epithelial cellRluc, renilla luciferaseSA-β-gal, senescence associated β-galSDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresisTUNEL, TdT mediated dUTP-fluorescein nick end-labelingTranscription factorVEGF, vascular endothelial growth factoroxLDL, oxidized low density lipoproteinredox, reduction/oxidationOriginal DateCompleted: 20140313
201312162014012920140131201431460201431460201431461epublish2462433810.1016/j.redox.2014.01.023S2213-2317(14)00038-XPMC3949093
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2476-762X1532014Asian Pacific journal of cancer prevention : APJCPAsian Pac. J. Cancer Prev.Single nucleotide polymorphisms of DNA base-excision repair genes (APE1, OGG1 and XRCC1) associated with breast cancer risk in a Chinese population.1133-40Altered DNA repair capacity can result in increased susceptibility to cancer. The base excision repair (BER) pathway effectively removes DNA damage caused by ionizing radiation and reactive oxidative species (ROS). In the current study, we analyzed the possible relation of polymorphisms in BER genes, including 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and X-ray repair cross-complementing group 1 protein (XRCC1), with breast cancer risk in Chinese Han women. This case-control study examined 194 patients with breast cancer and 245 cancer-free hospitalized control subjects. Single nucleotide polymorphisms (SNPs) of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), and APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their association with breast cancer risk using multivariate logistic regression models. We found that XRCC1 Arg399Gln was significantly associated with an increased risk of breast cancer. Similarly, the XRCC1 Gln allele was significantly associated with an elevated risk in postmenopausal women and women with a high BMI (≥ 24 kg/m2). The OGG1 Cys allele provided a significant protective effect against developing cancer in women with a low BMI (< 24 kg/m2). When analyzing the combined effects of these alleles on the risk of breast cancer, we found that individuals with ≥ 2 adverse genotypes (XRCC1 399Gln, APE1 148Asp, and OGG1 326Ser) were at a 2.18-fold increased risk of breast cancer (P = 0.027). In conclusion, our data indicate that Chinese women with the 399Gln allele of XRCC1 have an increased risk of breast cancer, and the combined effects of polymorphisms of BER genes may contribute to tumorigenesis. LuoHaoHCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China E-mail : dongwang64@hotmail.com.LiZhengZQingYiYZhangShi-HengSHPengYuYLiQingQWangDongDengJournal Article
ThailandAsian Pac J Cancer Prev1011306251513-73680DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBreast NeoplasmsgeneticsCarcinogenesisgeneticsCase-Control StudiesChinaDNA DamagegeneticsDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGenetic Predisposition to DiseaseGenotypeHumansMiddle AgedMultivariate AnalysisPolymorphism, Single NucleotidePostmenopauseRiskX-ray Repair Cross Complementing Protein 1
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1932-6203922014PloS onePLoS ONEThe redox function of APE1 is involved in the differentiation process of stem cells toward a neuronal cell fate.e8923210.1371/journal.pone.0089232Low-to-moderate levels of reactive oxygen species (ROS) govern different steps of neurogenesis via molecular pathways that have been decrypted only partially. Although it has been postulated that redox-sensitive molecules are involved in neuronal differentiation, the molecular bases for this process have not been elucidated yet. The aim of this work was therefore to study the role played by the redox-sensitive, multifunctional protein APE1/Ref-1 (APE1) in the differentiation process of human adipose tissue-derived multipotent adult stem cells (hAT-MASC) and embryonic carcinoma stem cells (EC) towards a neuronal phenotype.Applying a definite protocol, hAT-MASC can adopt a neural fate. During this maturation process, differentiating cells significantly increase their intracellular Reactive Oxygen Species (ROS) levels and increase the APE1 nuclear fraction bound to chromatin. This latter event is paralleled by the increase of nuclear NF-κB, a transcription factor regulated by APE1 in a redox-dependent fashion. Importantly, the addition of the antioxidant N-acetyl cysteine (NAC) to the differentiation medium partially prevents the nuclear accumulation of APE1, increasing the neuronal differentiation of hAT-MASC. To investigate the involvement of APE1 in the differentiation process, we employed E3330, a specific inhibitor of the APE1 redox function. The addition of E3330, either to the neurogenic embryonic carcinoma cell line NT2-D1or to hAT-MASC, increases the differentiation of stem cells towards a neural phenotype, biasing the differentiation towards specific subtypes, such as dopaminergic cells. In conclusion, during the differentiation process of stem cells towards a neuroectodermic phenotype, APE1 is recruited, in a ROS-dependent manner, to the chromatin. This event is associated with an inhibitory effect of APE1 on neurogenesis that may be reversed by E3330. Therefore, E3330 may be employed both to boost neural differentiation and to bias the differentiation potential of stem cells towards specific neuronal subtypes. These findings provide a molecular basis for the redox-mediated hypothesis of neuronal differentiation program.DomenisRossanaRDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.BergaminNataschaNDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.GianfranceschiGiuseppeGDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.VascottoCarloCDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.RomanelloMilenaMDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.RigoSilviaSDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.VagnarelliGiovannaGDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.FaggianiMassimoMDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.ParodiPiercamilloPDepartment of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.KelleyMark RMRDepartment of Pediatrics (Section of Hematology/Oncology), Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.BeltramiCarlo AlbertoCADepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.CesselliDanielaDDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.TellGianlucaGDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.BeltramiAntonio PaoloAPDepartment of Medical and Biological Sciences, University of Udine, Udine, Italy.engR01 CA167291CANCI NIH HHSUnited StatesCA121168CANCI NIH HHSUnited StatesCA167291CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20140219
United StatesPLoS One1012850811932-62030Benzoquinones0Chromatin0NF-kappa B0Propionates0Reactive Oxygen Species136164-66-4E 3330EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMNat Methods. 2012 Jul;9(7):671-522930834Cell Mol Life Sci. 2012 Jan;69(2):215-2121947442Stem Cells Dev. 2013 Mar 15;22(6):913-2723199293Curr Eye Res. 2013 Apr;38(4):451-6323373736Biochemistry. 2013 Apr 30;52(17):2955-6623597102Orphanet J Rare Dis. 2013;8:3423433359Biochem J. 2013 Jun 15;452(3):545-5723544830PLoS One. 2013;8(8):e7090923967134Int J Environ Res Public Health. 2013 Oct;10(10):5244-5624157519Nat Biotechnol. 2000 Aug;18(8):877-8110932159Neurobiol Dis. 2001 Jun;8(3):380-9011447995Nucleic Acids Res. 2002 Feb 1;30(3):823-911809897J Biol Chem. 2002 Nov 15;277(46):44548-5612213807J Vasc Surg. 2003 Feb;37(2):446-5212563220Science. 1993 May 21;260(5111):1130-28493557Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414J Neurooncol. 1995;25(3):183-928592168Mutat Res. 1996 Apr 2;362(3):237-488637502J Biol Chem. 1996 Apr 12;271(15):8593-88621488Brain Res Mol Brain Res. 1997 Feb;44(1):167-709030714Science. 1997 Oct 17;278(5337):477-839334309J Neurosci. 1998 May 15;18(10):3620-99570793Mutat Res. 1998 Oct 21;409(1):17-299806499Mol Cell. 2005 Feb 4;17(3):463-7015694346Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Nucleic Acids Res. 2005;33(14):4379-9416077024Blood. 2007 Mar 1;109(5):1917-2217053053Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Blood. 2007 Nov 1;110(9):3438-4617525288Mol Cancer Ther. 2008 Jul;7(7):2012-2118645011Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Mol Cell Biol. 2009 Apr;29(8):2264-7719188437Cell Tissue Res. 2009 Jun;336(3):439-5219377856Brain Res Bull. 2009 Aug 28;80(1-2):62-819463914Neurosci Lett. 2009 Dec 11;466(3):124-719782121Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Mol Cell Biol. 2010 Jan;30(2):366-7119901076Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766PLoS One. 2011;6(1):e1617421283767Eur J Neurosci. 2011 Oct;34(7):1040-5221899604Mol Biol Cell. 2011 Oct;22(20):3887-90121865600Biochemistry. 2011 Jan 11;50(1):82-9221117647Adipose TissuecytologyAdultAdult Stem CellsmetabolismphysiologyBenzoquinonesBlotting, WesternCell DifferentiationphysiologyChromatinmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismFlow CytometryHumansMicroscopy, FluorescenceMultipotent Stem CellsmetabolismphysiologyNF-kappa BmetabolismNeurogenesisphysiologyOxidation-ReductionPropionatesReactive Oxygen SpeciesmetabolismReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionStatistics, Nonparametric
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1423-03803562014JunTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.APE1 Asp148Glu polymorphism and lung cancer susceptibility.5237-4410.1007/s13277-014-1681-yApurinic/apyrimidinic endonuclease 1 (APE1) is a key enzyme in base excision repair (BER) pathway for the removal of many oxidized and alkylated bases. Single-nucleotide polymorphisms of the APE1gene have been demonstrated to be involved in carcinogenesis. However, the association between APE1 Asp148Glu polymorphism and lung cancer risk remains inconclusive. To derive a precise estimate for this association, we carried out an updated meta-analysis by pooling data thus far published. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to assess the role of APE1 Asp148Glu polymorphism in lung carcinogenesis. The pooled ORs suggested that variant genotypes of APE1 Asp148Glu were modestly associated with an elevated risk of lung cancer (GluGlu vs. AspAsp, OR=1.22, 95 % CI 1.01-1.48, P=0.038; GluGlu vs. AspAsp + AspGlu, OR=1.19, 95 % CI 1.02-1.39, P=0.023). The relationship was also observed in studies conducted among Asians, but not Caucasians. Sensitivity analysis further confirmed the findings. The meta-analysis shows that the polymorphism of APE1 Asp148Glu exerts risk effect on lung cancer development.CaiLiyunLDepartment of Emergency Internal Medicine, Tangshan Worker's Hospital, No. 27 Wenhua Road, Tangshan, Hebei, 063000, China, cailiyun2003@sina.com.FuYingjvYZhangYuanyueYengJournal ArticleMeta-Analysis20140213
United StatesTumour Biol84099221010-4283EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAsian Pac J Cancer Prev. 2010;11(5):1181-621198260Lung Cancer. 1997 May;17(1):1-609194026Anticancer Res. 2005 Jan-Feb;25(1B):537-4215816625Mutat Res. 2003 Oct 29;531(1-2):157-6314637252Tumour Biol. 2013 Oct;34(5):2511-2023812725PLoS One. 2013 Jul 11;8(7):e6901823874853Carcinogenesis. 2012 Dec;33(12):2409-1623042301Lung Cancer. 1996 Mar;14 Suppl 1:S39-458785666DNA Cell Biol. 2010 Jun;29(6):303-1120218899Int J Biomed Sci. 2012 Jun;8(2):121-823675264BMJ. 1998 Feb 7;316(7129):469; author reply 470-19492685Biometrika. 1950 Dec;37(3-4):256-6614801052Cancer Detect Prev. 2006;30(3):257-6116844322Control Clin Trials. 1986 Sep;7(3):177-883802833Lung Cancer. 2007 Aug;57(2):135-4217428572Am J Epidemiol. 2009 Dec 1;170(11):1333-4319901000Cancer Lett. 2003 Mar 10;191(2):171-812618330Carcinogenesis. 2006 May;27(5):997-100716308313Med Oncol. 2011 Sep;28(3):667-7220354815Mutat Res. 2007 Jul 28;631(2):101-1017531525Anticancer Res. 2009 Jun;29(6):2417-2019528510Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-69560228JAMA. 2000 Apr 19;283(15):2008-1210789670BMJ. 2003 Sep 6;327(7414):557-6012958120Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Arh Hig Rada Toksikol. 2013 Jun;64(2):61-723819933Carcinogenesis. 2004 Aug;25(8):1395-40115044328Mutagenesis. 2009 Nov;24(6):507-1219762350Tumour Biol. 2014 Jan;35(1):821-923979979Arch Med Res. 2011 Apr;42(3):226-3421722819Am J Ind Med. 2002 Jul;42(1):29-3712111688Carcinogenesis. 2006 Mar;27(3):560-716195237Mutagenesis. 2013 Sep;28(5):561-723804708Surg Oncol Clin N Am. 2011 Oct;20(4):605-1821986260J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060Mol Biol Rep. 2012 Dec;39(12):11249-6223065211BMJ. 1997 Sep 13;315(7109):629-349310563Carcinogenesis. 2004 Dec;25(12):2433-4115333465Carcinogenesis. 2012 Aug;33(8):1531-722637743Mutat Res. 2013 Jul 4;755(1):42-823669291FASEB J. 2009 Oct;23(10):3459-6919541747CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855J Epidemiol. 2012;22(6):537-4223038158PLoS One. 2013 Dec 12;8(12):e8352724349526PLoS One. 2013 Aug 12;8(8):e7115723951099Curr Med Res Opin. 2011 Jul;27(7):1295-30221561390DNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGenetic Predisposition to DiseaseHumansLung NeoplasmsgeneticsPolymorphism, Single NucleotideRisk
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1943-772214132014MarAmerican journal of clinical pathologyAm. J. Clin. Pathol.Expression and prognostic significance of APE1/Ref-1 and NPM1 proteins in high-grade ovarian serous cancer.404-1410.1309/AJCPIDKDLSGE26CXTo correlate the expression profile of human apurinic endonuclease/redox factor 1 (APE1/Ref-1) with that of nucleolar/nucleoplasmic protein nucleophosmin 1 (NPM1) in association with the aggressiveness and progression of high-grade ovarian serous cancer.Retrospective study analyzing a tissue microarray of 73 women affected by high-grade ovarian serous cancer. Protein expression was assessed by immunohistochemistry on primary tumor masses and synchronous peritoneal metastases if present.APE1/Ref-1 and NPM1 showed a significant correlation in ovarian serous cancer. Patients with a poorer outcome showed a significant overexpression of nuclear NPM1 protein. A Cox proportional hazards multivariate regression model revealed NPM1 expression to be independently significant for overall survival in high-grade ovarian serous cancers after correcting for stage, age, cytoreduction completeness, and platinum resistance.APE1/Ref-1 interacts with NPM1 to control the DNA damage repair system, and it is likely that this interaction plays a defining role in high-grade ovarian serous carcinoma. A high NPM1 immunohistochemical expression was independently correlated with a shorter survival period and thus appears to be an important prognostic factor.LonderoAmbrogio PAPDept of Experimental Clinical and Medical Science, Clinic of Obstetrics and Gynecology, University of Udine, Piazzale SM della Misericordia, 15-33100 Udine, Italy; ambrogio.londero@gmail.com.OrsariaMariaMTellGianlucaGMarzinottoStefaniaSCapodicasaValentinaVPolettoMattiaMVascottoCarloCSaccoCosimoCMariuzziLauraLengJournal ArticleResearch Support, Non-U.S. Gov't
EnglandAm J Clin Pathol03704700002-91730Nuclear Proteins117896-08-9nucleophosminEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseAIMIMAgedAged, 80 and overCystadenocarcinoma, SerousdiagnosismetabolismpathologyDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismFemaleHumansMiddle AgedNeoplasm GradingNuclear ProteinsmetabolismOvarian NeoplasmsdiagnosismetabolismpathologyPrognosisRetrospective StudiesAPE1/Ref-1NPM1Ovarian cancerPrognostic factorsSurvival
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1083-351X28992014Feb28The Journal of biological chemistryJ. Biol. Chem.Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells.6165-7610.1074/jbc.M113.515130Mitochondria-targeted human 8-oxoguanine DNA glycosylase (mt-hOgg1) and aconitase-2 (Aco-2) each reduce oxidant-induced alveolar epithelial cell (AEC) apoptosis, but it is unclear whether protection occurs by preventing AEC mitochondrial DNA (mtDNA) damage. Using quantitative PCR-based measurements of mitochondrial and nuclear DNA damage, mtDNA damage was preferentially noted in AEC after exposure to oxidative stress (e.g. amosite asbestos (5-25 μg/cm(2)) or H2O2 (100-250 μM)) for 24 h. Overexpression of wild-type mt-hOgg1 or mt-long α/β 317-323 hOgg1 mutant incapable of DNA repair (mt-hOgg1-Mut) each blocked A549 cell oxidant-induced mtDNA damage, mitochondrial p53 translocation, and intrinsic apoptosis as assessed by DNA fragmentation and cleaved caspase-9. In contrast, compared with controls, knockdown of Ogg1 (using Ogg1 shRNA in A549 cells or primary alveolar type 2 cells from ogg1(-/-) mice) augmented mtDNA lesions and intrinsic apoptosis at base line, and these effects were increased further after exposure to oxidative stress. Notably, overexpression of Aco-2 reduced oxidant-induced mtDNA lesions, mitochondrial p53 translocation, and apoptosis, whereas siRNA for Aco-2 (siAco-2) enhanced mtDNA damage, mitochondrial p53 translocation, and apoptosis. Finally, siAco-2 attenuated the protective effects of mt-hOgg1-Mut but not wild-type mt-hOgg1 against oxidant-induced mtDNA damage and apoptosis. Collectively, these data demonstrate a novel role for mt-hOgg1 and Aco-2 in preserving AEC mtDNA integrity, thereby preventing oxidant-induced mitochondrial dysfunction, p53 mitochondrial translocation, and intrinsic apoptosis. Furthermore, mt-hOgg1 chaperoning of Aco-2 in preventing oxidant-mediated mtDNA damage and apoptosis may afford an innovative target for the molecular events underlying oxidant-induced toxicity.KimSeok-JoSJFrom the Department of Medicine, Division of Pulmonary and Critical Care Medicine, Jesse Brown Veterans Affairs Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611.ChereshPaulPWilliamsDavidDChengYuanYRidgeKarenKSchumackerPaul TPTWeitzmanSigmundSBohrVilhelm AVAKampDavid WDWengP01 HL071643HLNHLBI NIH HHSUnited StatesR01 ES020357ESNIEHS NIH HHSUnited StatesR01 HL079190HLNHLBI NIH HHSUnited StatesP01HL071643HLNHLBI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, U.S. Gov't, Non-P.H.S.20140115
United StatesJ Biol Chem2985121R0021-92580DNA, Mitochondrial0Oxidants0TP53 protein, human0Tumor Suppressor Protein p5312172-73-5Asbestos, AmositeEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-OGG1 protein, ratEC 3.2.2.-Ogg1 protein, mouseEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.1.3ACO2 protein, humanEC 4.2.1.3Aconitate HydrataseEC 4.2.1.3.aconitase 2, mouseIMNat Cell Biol. 2002 Sep;4(9):674-8012198491Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L205-1012060578J Biol Chem. 2003 Jan 17;278(3):1728-3412424245Am J Respir Cell Mol Biol. 2003 Feb;28(2):241-812540492J Natl Cancer Inst. 2003 Sep 3;95(17):1312-912953085Am J Physiol Lung Cell Mol Physiol. 2003 Nov;285(5):L1018-2512909582Biochemistry. 2003 Dec 23;42(50):14846-5514674759Am J Physiol Lung Cell Mol Physiol. 2004 Jun;286(6):L1220-714766669Science. 2004 Jul 9;305(5681):242-515247478Nucleic Acids Res. 2004;32(18):5596-60815494448Proc Natl Acad Sci U S A. 1988 Sep;85(17):6465-73413108Am J Respir Cell Mol Biol. 1996 Apr;14(4):309-158600933Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-99012815Science. 2005 Feb 4;307(5710):714-715692048Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L530-515563690Oncogene. 2005 Jun 30;24(28):4496-50815856018J Biol Chem. 2005 Nov 4;280(44):37169-7716148012Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):17993-816332961DNA Repair (Amst). 2006 Feb 3;5(2):145-5215878696Am J Respir Cell Mol Biol. 2006 Apr;34(4):443-5216357363Cell Death Differ. 2006 Jun;13(6):941-5016601750Cancer Biol Ther. 2007 Feb;6(2):160-917218778Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13738-4317698960Mol Cancer Res. 2007 Oct;5(10):1083-9817951408Environ Mol Mutagen. 2008 May;49(4):265-7518338377Biochim Biophys Acta. 2009 May;1787(5):414-2019007744Free Radic Biol Med. 2009 Sep 15;47(6):750-919524665Am J Respir Crit Care Med. 2010 Feb 1;181(3):254-6319850947Discov Med. 2010 Feb;9(45):145-5220193641PLoS One. 2010;5(8):e1234120808790Am J Physiol Cell Physiol. 2010 Oct;299(4):C736-4920554909Prostate. 2011 Jan 1;71(1):62-7020607720Free Radic Biol Med. 2011 May 1;50(9):1107-1320969951J Neurosci. 2011 Jun 29;31(26):9746-5121715639Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H2073-8021873502Lancet. 2011 Dec 3;378(9807):1949-6121719092Cell Physiol Biochem. 2011;28(5):873-8622178940J Biol Chem. 2012 Jun 15;287(25):20769-7322568941Cell. 2012 Jun 22;149(7):1536-4822726440J Clin Invest. 2012 Aug;122(8):2756-6222850886Am J Respir Crit Care Med. 2012 Dec 1;186(11):1140-923024021Sci Rep. 2013;3:107723326634Annu Rev Pathol. 2013 Jan 24;8:161-8723347351Antioxid Redox Signal. 2013 Jun 1;18(16):2029-7423244576Cancer Cell. 2013 Apr 15;23(4):450-6323562301Biochim Biophys Acta. 2013 Jul;1832(7):1028-4023219955Mitochondrion. 2013 Jul;13(4):277-8123499753Neurochem Res. 2013 Jul;38(7):1315-2323519932Endocrinology. 2013 Aug;154(8):2640-923748360Am J Respir Cell Mol Biol. 2013 Dec;49(6):892-90123885834Free Radic Biol Med. 2013 Aug;61:384-9423612479Cancer Res. 2003 Mar 1;63(5):902-512615700Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Am J Physiol Lung Cell Mol Physiol. 2001 Jun;280(6):L1300-811350811Cancer Res. 2001 Jul 15;61(14):5378-8111454679Methods Mol Biol. 2002;197:159-7612013794Gene. 2002 Mar 6;286(1):127-3411943468Intern Med. 2001 Dec;40(12):1177-8211813840Free Radic Biol Med. 2002 Jun 1;32(11):1102-1512031895Carcinogenesis. 2002 Dec;23(12):2005-1012507922Aconitate HydratasegeneticsmetabolismAnimalsApoptosisdrug effectsAsbestos, AmositetoxicityCell Line, TumorDNA DamageDNA GlycosylasesgeneticsmetabolismDNA, MitochondrialgeneticsmetabolismEpithelial CellsenzymologypathologyHumansMiceMice, KnockoutMitochondriaenzymologygeneticspathologyMutationOxidantsadverse effectspharmacologyOxidative Stressdrug effectsPulmonary AlveolienzymologypathologyRatsTumor Suppressor Protein p53geneticsmetabolismDNA DamageDNA RepairEpithelial CellFibrosisLung FibrosisMitochondrial AconitaseMitochondrial DNA DamageMitochondrial hOgg1Oxidative Stress
201411760201411760201442660ppublish24429287M113.51513010.1074/jbc.M113.515130PMC3937682
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1423-03803552014MayTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.The association between the APE1 Asp148Glu polymorphism and breast cancer susceptibility: a meta-analysis based on case-control studies.4727-3410.1007/s13277-014-1618-5Published data regarding the association between the APE1 Asp148Glu polymorphism and breast cancer susceptibility showed inconclusive results. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase, Elsevier, and Springer for relevant articles published before December 10. 2013. The strength of association between APE1 Asp148Glu polymorphism and breast cancer susceptibility was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI) using the software Stata (version 10.0). A total of 7 case-control studies including 3,460 cases and 3,909 controls were included for analysis. Overall, no significant associations were found between the APE1 Asp148Glu polymorphism and breast cancer susceptibility for GG vs TT (OR = 1.00, 95% CI = 0.87-1.14); TG vs TT (OR = 1.06, 95% CI = 0.95-1.18); the dominant model GG + TG vs TT (OR = 1.04, 95% CI = 0.94-1.16) and the recessive model GG vs TG + TT (OR = 0.99, 95% CI = 0.88-1.11). In subgroup analysis, a significant association was found for TG vs TT in Asian subgroup (OR = 1.17, 95% CI = 1.00 ~ 1.36) and in population-based subgroup (OR = 1.18, 95% CI = 1.00 ~ 1.38). This meta-analysis suggested that the APE1 Asp148Glu polymorphism was a risk factor for breast cancer susceptibility among Asian population.ZhaoZhiyongZChinese PLA General Hospital, Medical School of Chinese PLA, Beijing, People's Republic of China, zhaoziyong1229@163.com.LiuChuanCZengYongYGuLeiLYingMingzhenMWangNingNHaoBinBYaoHuiyanHSuChangqingCWangYajieYMaYuchenYengJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov't20140114
United StatesTumour Biol84099221010-4283EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBiometrics. 1994 Dec;50(4):1088-1017786990Control Clin Trials. 1986 Sep;7(3):177-883802833J Cell Sci Suppl. 1995;19:73-78655650Int J Epidemiol. 2008 Feb;37(1):120-3217898028J Surg Oncol. 2013 Nov;108(6):337-4123900832Breast Cancer Res Treat. 2008 Sep;111(2):279-8817922186Int J Epidemiol. 2008 Feb;37(1):136-4618037675DNA Repair (Amst). 2007 Jun 1;6(6):695-71117337257BMJ. 2003 Sep 6;327(7414):557-6012958120Carcinogenesis. 2001 Jun;22(6):917-2211375899PLoS One. 2012;7(12):e5244523272245Carcinogenesis. 2000 Jul;21(7):1329-3410874010Carcinogenesis. 2006 Sep;27(9):1894-90116621887Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):353-816492928Environ Mol Mutagen. 2004;44(1):74-8215199549Gene. 2013 Dec 15;532(2):192-624076439Nat Rev Cancer. 2004 Nov;4(11):850-6015516958Science. 2001 Feb 16;291(5507):1284-911181991Circ Res. 2001 Jun 22;88(12):1247-5311420300Genomics. 2004 Jun;83(6):970-915177551Asian Pac J Cancer Prev. 2012;13(4):1355-6022799331Oncol Res. 2008;17(3):127-3518669164Med Decis Making. 2005 Nov-Dec;25(6):646-5416282215BMJ. 1997 Sep 13;315(7109):629-349310563Carcinogenesis. 2008 Nov;29(11):2132-818701435CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855Nucleic Acids Res. 1992 Sep 11;20(17):4417-211383925J Appl Genet. 2010;51(3):343-5220720310Gene. 2013 Nov 15;531(1):97-10023994194Eur J Epidemiol. 2010 Sep;25(9):603-520652370Breast NeoplasmsgeneticsCase-Control StudiesDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleGenetic Predisposition to DiseaseGenotypeHumansPolymorphism, GeneticPublication Bias
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1468-20799832014MarThe British journal of ophthalmologyBr J OphthalmolDysregulation of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in advanced retinoblastoma.402-710.1136/bjophthalmol-2013-304166Retinoblastoma (RB) is a childhood eye tumour. Dysregulation of DNA repair may not only influence pathogenesis but could also adversely impact on response to cytotoxic chemotherapy frequently used in RB therapy. We studied the expression of human apurinic/apyrimidinic endonuclease (APE1), a key multifunctional protein involved in DNA base excision repair in RB.Expression of APE1 was evaluated by immunohistochemistry in a series of 55 RBs and in retina. In tumours, APE1 expression was analysed in cytoplasm and nucleus independently and correlated with histopathological features, including invasion, differentiation and International Intraocular Retinoblastoma Classification groups. Relative APE1 mRNA and protein expressions were evaluated by real-time PCR and western blot. The expression of APE1 in tumour groups was compared with retinal tissue.APE1 cytoplasmic expression was observed in 98% and nuclear positivity was observed in 83% of tumours analysed. Tumour cells invading the optic nerve showed predominant cytoplasmic immunoreactivity. An inverse correlation between cytoplasmic and nuclear positivity was observed. Real-time PCR revealed an increase in APE1 transcripts compared with retina. Western blot revealed a decreased protein concentration compared with retinal tissue.This is the first study of APE1 expression in RB. Our observation suggests that subcellular localisation of APE1 is altered in RB. APE1 could be a potential drug target in RB.SudhakarJobJLarsen and Toubro Ocular Pathology Department, Vision Research Foundation, Sankara Nethralaya, , Chennai, India.KhetanVikasVMadhusudanSrinivasanSKrishnakumarSubramanianSengJournal ArticleResearch Support, Non-U.S. Gov't20140102
EnglandBr J Ophthalmol04210410007-11610RNA, MessengerEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBlotting, WesternCell NucleusenzymologyChildChild, PreschoolCytoplasmenzymologyDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismFemaleGene ExpressionHumansImmunohistochemistryInfantMalePrognosisRNA, MessengermetabolismReal-Time Polymerase Chain ReactionRetinal NeoplasmsenzymologygeneticsRetinoblastomaenzymologygeneticsYoung AdultChild health (paediatrics)Pathology
2014146020141560201441160ppublish24385289bjophthalmol-2013-30416610.1136/bjophthalmol-2013-304166
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1573-721714332014FebBreast cancer research and treatmentBreast Cancer Res. Treat.Clinicopathological significance of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in oestrogen-receptor-positive breast cancer.411-2110.1007/s10549-013-2820-7Oestrogen metabolites can induce oxidative DNA base damage and generate potentially mutagenic apurinic sites (AP sites) in the genomic DNA. If unrepaired, mutagenic AP sites could drive breast cancer pathogenesis and aggressive phenotypes. Human apurinic/apyrimidinic endonuclease 1 (APE1) is a key DNA base excision repair (BER) protein and essential for processing AP sites generated either directly by oestrogen metabolites or during BER of oxidative base damage. Our hypothesis is that altered APE1 expression may be associated with aggressive tumour biology and impact upon clinical outcomes in breast cancer. In the current study, we have investigated APE1 protein expression in a large cohort of breast cancers (n = 1285) and correlated to clinicopathological features and survival outcomes. Low APE1 protein expression was associated with high histological grade (p < 0.000001), high mitotic index (p < 0.000001), glandular de-differentiation (p < 0.000001), pleomorphism (p = 0.003), absence of hormonal receptors (ER-/PgR-/AR-) (p < 0.0001) and presence of triple negative phenotype (p = 0.001). Low APE1 protein expression was associated with loss of BRCA1, low XRCC1, low FEN1, low SMUG1 and low pol β (ps < 0.0001). High MIB1 (p = 0.048), bcl-2 negativity (p < 0.0001) and low TOP2A (p < 0.0001) were likely in low APE1 tumours. In the ER-positive sub-group, specifically, low APE1 remains significantly associated with high histological grade, high mitotic index, glandular de-differentiation (ps < 0.00001) and poor breast cancer specific survival (p = 0.007). In the ER-positive cohort that received adjuvant endocrine therapy, low APE1 protein expression is associated with poor survival (p = 0.006). In multivariate analysis, low APE1 remains independently associated with poor survival in ER-positive tumours (p = 0.048). We conclude that low APE1 expression may have prognostic and predictive significance in ER-positive breast cancers.Abdel-FatahTarek M ATMDepartment of Oncology, Nottingham University Hospitals, Nottingham, NG51PB, UK.PerryChristinaCMoseleyPaulPJohnsonKerstieKAroraArvindAChanStephenSEllisIan OIOMadhusudanSrinivasanSengMR/J008001/1Medical Research CouncilUnited KingdomJournal Article20140101
NetherlandsBreast Cancer Res Treat81111040167-68060Biomarkers, Tumor0Receptors, EstrogenEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBiomarkers, TumorbiosynthesisBreast NeoplasmsgeneticspathologyDNA DamagegeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticgeneticsHumansMCF-7 CellsNeoplasm GradingPrognosisReceptors, Estrogengenetics
20131219201312202014126020141260201492360ppublish2438105510.1007/s10549-013-2820-7
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1233-96876442013DecPolish journal of pathology : official journal of the Polish Society of PathologistsPol J PatholThe role of the 148 Asp/Glu polymorphism of the APE1 gene in the development and progression of primary open angle glaucoma development in the Polish population.296-302Glaucoma is an ocular disorder that is characterized by progressive degeneration of the optic nerve and loss of visual field (VF). Recent data have suggested that the level of oxidative DNA damage in human trabecular meshwork is significantly increased in glaucomatous patients as compared to controls. It was also noted that progressive loss of visual field may by connected with elevated levels of oxidative DNA lesions. This hypothesis may suggest the role of an inefficient base excision repair pathway in primary open angle glaucoma (POAG) pathogenesis. The aim of the study was to evaluate the association of the 148 Asp/Glu APE1 gene polymorphism with the risk of POAG development. One hundred fifty patients with POAG and 190 controls were enrolled in our study. Gene polymorphisms were analyzed by PCR-CTPP. We did not observe a statistically significant difference between the frequencies of alleles and genotypes of the 148 Asp/Glu APE1 gene polymorphism in POAG patients and controls. However, the presented study indicated that 148 Asp/Glu of the APE1 gene was associated with decreased risk of progression of POAG with reference to the parameter VF. We suggest that the 148 Asp/Glu APE1 gene polymorphism may decrease the risk of POAG progression. CuchraMMIreneusz Majsterek, Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Hallera 1 square, 90-647 Lodz, Poland, e-mail: ireneusz.majsterek@umed.lodz.pl.SzaflikJ PJPPrzybylowska-SygutKKGacekMMKaminskaAASzaflikJJMajsterekIIengJournal ArticleResearch Support, Non-U.S. Gov't
PolandPol J Pathol94374321233-96870Dipeptides6157-06-8aspartylglutamate9007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseGlaucoma, Primary Open AngleIMAgedAged, 80 and overDNAgeneticsDNA DamageDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismDipeptidesgeneticsDisease ProgressionFemaleGene FrequencyGenetic Predisposition to DiseaseGenotypeGlaucoma, Open-AngleepidemiologygeneticsHumansMaleMiddle AgedPolandepidemiologyPolymorphism, Genetic
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1939-45862542014FebMolecular biology of the cellMol. Biol. CellSIRT1 gene expression upon genotoxic damage is regulated by APE1 through nCaRE-promoter elements.532-4710.1091/mbc.E13-05-0286Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein contributing to genome stability via repair of DNA lesions via the base excision repair pathway. It also plays a role in gene expression regulation and RNA metabolism. Another, poorly characterized function is its ability to bind to negative calcium responsive elements (nCaRE) of some gene promoters. The presence of many functional nCaRE sequences regulating gene transcription can be envisioned, given their conservation within ALU repeats. To look for functional nCaRE sequences within the human genome, we performed bioinformatic analyses and identified 57 genes potentially regulated by APE1. We focused on sirtuin-1 (SIRT1) deacetylase due to its involvement in cell stress, including senescence, apoptosis, and tumorigenesis, and its role in the deacetylation of APE1 after genotoxic stress. The human SIRT1 promoter presents two nCaRE elements stably bound by APE1 through its N-terminus. We demonstrate that APE1 is part of a multiprotein complex including hOGG1, Ku70, and RNA Pol II, which is recruited on SIRT1 promoter to regulate SIRT1 gene functions during early response to oxidative stress. These findings provide new insights into the role of nCaRE sequences in the transcriptional regulation of mammalian genes. AntonialiGiuliaGDepartment of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, 80147 Naples, Italy Department of Biomedical and Pharmaceutical Sciences, University of Salerno, 84084 Fisciano (Salerno), Italy Department of Pharmacy, University of Naples "Federico II," 80134 Naples, Italy Institute of Biostructures and Bioimaging, National Research Council, 80134 Naples, Italy.LirussiLisaLD'AmbrosioChiaraCDal PiazFabrizioFVascottoCarloCCasaranoElenaEMarascoDanielaDScaloniAndreaAFogolariFedericoFTellGianlucaGengJournal ArticleResearch Support, Non-U.S. Gov't20131219
United StatesMol Biol Cell92013901059-15240Antigens, Nuclear0DNA-Binding Proteins0RNA, Small InterferingAT5C31J09GMethyl MethanesulfonateBBX060AN9VHydrogen PeroxideEC 2.7.7.-RNA Polymerase IIEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.5.1.-SIRT1 protein, humanEC 3.5.1.-Sirtuin 1EC 3.6.4.12Xrcc6 protein, humanEC 4.2.99.-Ku AutoantigenEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMMol Cell Biol. 2009 Apr;29(7):1834-5419188445Gastroenterology. 2009 Jun;136(7):2258-6919505426Nucleic Acids Res. 2009 Jul;37(Web Server issue):W317-2219465387Nucleic Acids Res. 2009 Jul;37(12):3946-5819401441Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Mol Cell Biol. 2010 Jan;30(2):366-7119901076Nucleic Acids Res. 2010 Jan;38(3):832-4519934257Annu Rev Biochem. 2010;79:181-21120192759Oncogene. 2010 Jun 24;29(25):3691-70220418916Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766Cell Mol Life Sci. 2010 Nov;67(21):3621-3120809131Respir Physiol Neurobiol. 2010 Dec 31;174(3):244-5120831905Nucleic Acids Res. 2010 Dec;38(22):8239-5620699270FEBS Lett. 2011 Sep 16;585(18):2876-8221640108Nucleic Acids Res. 2012 Jul;40(Web Server issue):W478-8322573175Mol Cell Proteomics. 2012 Aug;11(8):411-2122535209Nature. 2012 Aug 9;488(7410):231-522722852Mol Biol Cell. 2012 Oct;23(20):4079-9622918947Biochem J. 2013 Jun 15;452(3):545-5723544830PLoS One. 2013;8(6):e6541523755229Methods Mol Biol. 2000;132:185-21910547837J Mol Biol. 2000 Mar 10;296(5):1169-7310698623J Mol Biol. 2001 Apr 6;307(4):1023-3411286553Nature. 2001 Aug 9;412(6847):607-1411493912Cell. 2001 Oct 19;107(2):149-5911672523Science. 2001 Dec 14;294(5550):2348-5111743200Nucleic Acids Res. 2002 Feb 1;30(3):823-911809897J Cell Biochem. 2002;87(2):194-20712244572Mol Biol Evol. 2002 Nov;19(11):1964-7212411605J Hypertens. 2003 Feb;21(2):327-3512569263EMBO J. 2003 Mar 17;22(6):1398-40912628932Mol Cell Biol. 2003 Dec;23(23):8740-5014612414EMBO J. 2003 Dec 1;22(23):6299-30914633989BMC Bioinformatics. 2004 May 11;5:5715137914Science. 2004 Jul 16;305(5682):390-215205477J Biol Chem. 2004 Aug 20;279(34):35377-8315208332BMC Evol Biol. 2004 Oct 4;4:3715461819Nucleic Acids Res. 1980 Mar 25;8(6):1201-157433120J Mol Biol. 1981 Sep 5;151(1):17-336276559J Clin Invest. 1989 Mar;83(3):1053-62493484J Mol Biol. 1991 Jun 5;219(3):555-652051488J Biol Chem. 1991 Nov 15;266(32):21903-101939213Nucleic Acids Res. 1991 Oct 25;19(20):5519-231719477Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-41722334EMBO J. 1992 Feb;11(2):653-651537340J Clin Invest. 1992 Apr;89(4):1268-731532588DNA Cell Biol. 1993 Apr;12(3):265-738466649Biochemistry. 1994 Nov 29;33(47):14185-967947830Bone. 1995 Jul;17(1):11-47577152J Biol Chem. 1996 Apr 12;271(15):8593-88621488Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Biochemistry. 1996 Nov 26;35(47):14679-838942627J Mol Biol. 1997 Jul 11;270(2):169-789236119EMBO J. 1997 Nov 3;16(21):6548-589351835J Mol Biol. 1998 Apr 10;277(4):945-589545383Biochem Biophys Res Commun. 1998 Nov 9;252(1):178-839813166Biochemistry. 1999 Jan 5;38(1):64-729890883J Mol Biol. 1999 Mar 19;287(1):47-5710074406EMBO J. 1999 Oct 15;18(20):5609-2110523305Nat Rev Cancer. 2005 Feb;5(2):102-1215685195Mol Cell. 2005 Feb 4;17(3):463-7015694346Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084FASEB J. 2005 Mar;19(3):387-9415746182J Biol Chem. 2006 Feb 17;281(7):3889-9816356936Genome Biol. 2007;8(1):R317204154Proteins. 2007 Apr 1;67(1):189-9717243156Trends Genet. 2007 Apr;23(4):158-6117307271Brief Funct Genomic Proteomic. 2007 Sep;6(3):202-1917967807Science. 2008 Jan 11;319(5860):202-618187655Trends Cell Biol. 2008 Feb;18(2):77-8318215521J Mol Biol. 2008 May 23;379(1):17-2718439621Mutat Res. 2008 Aug 25;643(1-2):54-6318579163BMB Rep. 2008 Nov 30;41(11):751-619017485Proteomics. 2009 Feb;9(4):1058-7419180539Antigens, NucleargeneticsmetabolismBase SequenceBinding SitesComputational BiologyDNA DamageDNA GlycosylasesgeneticsmetabolismDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsgeneticsmetabolismDNA-Binding ProteinsgeneticsmetabolismGene Expression Regulationdrug effectsGenome, HumanHeLa CellsHumansHydrogen PeroxidepharmacologyKu AutoantigenMethyl MethanesulfonatepharmacologyMolecular Sequence AnnotationMolecular Sequence DataProtein BindingRNA Polymerase IIgeneticsmetabolismRNA, Small InterferinggeneticsmetabolismResponse ElementsSignal TransductionSirtuin 1geneticsmetabolismTranscription, Genetic
20131221602013122160201511560ppublish24356447mbc.E13-05-028610.1091/mbc.E13-05-0286PMC3923644
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1423-03803542014AprTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.The association of APE1 Asp148Glu gene polymorphisms and lung cancer risk: an updated meta-analysis.3597-60310.1007/s13277-013-1474-8Many studies have examined the association between APE1 Asp148Glu (rs3136820) polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. PubMed and CNKI databases were searched for case-control studies published up to October 2013. Data were extracted, and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 14 studies, comprising 4,165 lung cancer cases and 5,438 controls were included. Overall, for Glu carriers (Asp/Glu + Glu/Glu) versus wild-type homozygotes (Asp/Asp), the pooled OR was 1.05 (95% CI = 0.96-1.15 P = 0.000 for heterogeneity); for Glu/Glu versus Asp/Asp, the pooled OR was 1.07 (95% CI = 0.95-1.21 P = 0.007 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were not found among Asians or Caucasians. This updated meta-analysis suggests that the APE1 Asp148Glu polymorphisms are not associated with lung cancer risk among Asians or Caucasians.ChenWenWShanghai Xujiahui Community Medical Service Center, Shanghai, 200030, China.WangQinQLiuMangMDingXiao-bingXBengJournal ArticleMeta-Analysis20131206
United StatesTumour Biol84099221010-4283EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAntioxid Redox Signal. 2009 Mar;11(3):621-3818715144Asian Pac J Cancer Prev. 2010;11(5):1181-621198260Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Anticancer Res. 2005 Jan-Feb;25(1B):537-4215816625J Thorac Oncol. 2009 Sep;4(9):1094-10319687765Control Clin Trials. 1986 Sep;7(3):177-883802833J Cell Sci Suppl. 1995;19:73-78655650Cancer Lett. 2003 Mar 10;191(2):171-812618330Carcinogenesis. 2006 May;27(5):997-100716308313Med Oncol. 2011 Sep;28(3):667-7220354815Mutat Res. 2007 Jul 28;631(2):101-1017531525Anticancer Res. 2009 Jun;29(6):2417-2019528510Transl Androl Urol. 2013 Jun;2(2):99-10526816732Hepatobiliary Surg Nutr. 2013 Aug;2(4):209-1524570945Carcinogenesis. 2001 Jun;22(6):917-2211375899Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Carcinogenesis. 2000 Jul;21(7):1329-3410874010Epidemiology. 1997 Nov;8(6):653-79345665Carcinogenesis. 2004 Aug;25(8):1395-40115044328J Clin Oncol. 2006 May 20;24(15):2245-5116710022Mutagenesis. 2009 Nov;24(6):507-1219762350Hepatobiliary Surg Nutr. 2013 Jun;2(3):148-5524570933Arch Med Res. 2011 Apr;42(3):226-3421722819Mayo Clin Proc. 2008 May;83(5):584-9418452692Bioessays. 1995 Aug;17(8):713-97661852Carcinogenesis. 2006 Mar;27(3):560-716195237Genomics. 2004 Jun;83(6):970-915177551J Thorac Dis. 2013 Feb;5(1):40-723372950J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060BMJ. 1997 Sep 13;315(7109):629-349310563Carcinogenesis. 2004 Dec;25(12):2433-4115333465FASEB J. 2009 Oct;23(10):3459-6919541747PLoS One. 2013 Aug 12;8(8):e7115723951099Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766Chest. 2003 Jan;123(1 Suppl):21S-49S12527563DNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGenetic Predisposition to DiseaseHumansLung NeoplasmsetiologygeneticsPolymorphism, GeneticPublication BiasRisk Factors
2013102520131126201312760201312760201461060ppublish2431050310.1007/s13277-013-1474-8
242973372014090320131223
1791-24313122014FebOncology reportsOncol. Rep.APE1/Ref-1 enhances DNA binding activity of mutant p53 in a redox-dependent manner.901-910.3892/or.2013.2892Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a dual function protein; in addition to its DNA repair activity, it can stimulate DNA binding activity of numerous transcription factors as a reduction-oxidation (redox) factor. APE1/Ref-1 has been found to be a potent activator of wild-type p53 (wtp53) DNA binding in vitro and in vivo. Although p53 is mutated in most types of human cancer including hepatocellular carcinoma (HCC), little is known about whether APE1/Ref-1 can regulate mutant p53 (mutp53). Herein, we reported the increased APE1/Ref-1 protein and accumulation of mutp53 in HCC by immunohistochemistry. Of note, it was observed that APE1/Ref-1 high-expression and mutp53 expression were associated with carcinogenesis and progression of HCC. To determine whether APE1/Ref-1 regulates DNA binding of mutp53, we performed electromobility shift assays (EMSAs) and quantitative chromatin immunoprecipitation (ChIP) assays in HCC cell lines. In contrast to sequence-specific and DNA structure-dependent binding of wtp53, reduced mutp53 efficiently bound to nonlinear DNA, but not to linear DNA. Notably, overexpression of APE1/Ref-1 resulted in increased DNA binding activity of mutp53, while downregulation of APE1/Ref-1 caused a marked decrease of mutp53 DNA binding. In addition, APE1/Ref-1 could not potentiate the accumulation of p21 mRNA and protein in mutp53 cells. These data indicate that APE1/Ref-1 can stimulate mutp53 DNA binding in a redox-dependent manner.CunYanpingYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, P.R. China.DaiNanNCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, P.R. China.LiMengxiaMCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, P.R. China.XiongChengjieCDepartment of Orthopedics, Wuhan General Hospital, Guangzhou Military Area Command, Wuhan, P.R. China.ZhangQinhongQCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, P.R. China.SuiJiangdongJCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, P.R. China.QianChengyuanCCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, P.R. China.WangDongDCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, P.R. China.engJournal ArticleResearch Support, Non-U.S. Gov't20131202
GreeceOncol Rep94227561021-335X0Cyclin-Dependent Kinase Inhibitor p210DNA-Binding Proteins0RNA, Messenger0Tumor Suppressor Protein p539007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCarcinoma, HepatocellulargeneticsCell Line, TumorCell Transformation, NeoplasticgeneticsCyclin-Dependent Kinase Inhibitor p21geneticsDNAmetabolismDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisgeneticsmetabolismDNA-Binding ProteinsgeneticsmetabolismDisease ProgressionFemaleHep G2 CellsHumansLiver NeoplasmsgeneticsMaleMiddle AgedMutationOxidation-ReductionPromoter Regions, GeneticgeneticsProtein BindinggeneticsRNA, MessengerbiosynthesisTranscriptional ActivationgeneticsTumor Suppressor Protein p53geneticsmetabolism
201310182013111820131246020131246020149460ppublish2429733710.3892/or.2013.2892
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1423-03803532014MarTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.The APE1 Asp148Glu polymorphism and colorectal cancer susceptibility: a meta-analysis.2529-3510.1007/s13277-013-1334-6Published data regarding the association between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility remained controversial. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship.We systematically searched PubMed, Embase, and Web of Science with a time limit of August 19, 2013. Summary odds ratios (ORs) with 95% CIs were used to assess the strength of association between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility using random-effects model.A total of eight case-control studies including 2,597 cases and 3,063 controls were included for analysis. Overall, no significant associations were found between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility for GG vs TT (OR = 1.00, 95% CI = 0.73-1.36, p = 0.00 for heterogeneity), TG vs TT (OR = 1.17, 95% CI = 0.88-1.55, p = 0.00 for heterogeneity), the dominant model GG + TG vs TT (OR = 1.21, 95% CI = 0.91-1.60, p = 0.00 for heterogeneity) nor the recessive model GG vs TG + TT(OR = 0.95, 95% CI = 0.75-1.20, p = 0.02 for heterogeneity). In subgroup analysis, no significant associations were found in the Asian or Caucasian populations.This meta-analysis suggested that the APE1 Asp148Glu polymorphism was not associated with colorectal cancer susceptibility among Asians or Caucasians.ShenErdongEDepartment of Oncology, First People's Hospital of Yueyang, East Maoling Road 39, Yueyang, Hunan, People's Republic of China, 414000, sed032181@sina.com.LiuChuanCWeiLiLHuJianbingJWengJieJYinQinghuaQWangYajieYengJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov't20131120
United StatesTumour Biol84099221010-4283EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMTumour Biol. 2014 Dec;35(12):12775-625384510Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Mol Biol Rep. 2012 Oct;39(10):9669-7922729883Clin Res Hepatol Gastroenterol. 2012 Apr;36(2):169-7722322158Cancer Res. 2007 Feb 1;67(3):1395-40417283177Stat Med. 2002 Jun 15;21(11):1539-5812111919Mutat Res. 2000 Oct 16;461(2):83-10811018583Biometrics. 1994 Dec;50(4):1088-1017786990Tumour Biol. 2013 Feb;34(1):555-6323188703Genet Med. 2002 Mar-Apr;4(2):45-6111882781Control Clin Trials. 1986 Sep;7(3):177-883802833J Cell Sci Suppl. 1995;19:73-78655650Int J Epidemiol. 2008 Feb;37(1):120-3217898028Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Am J Epidemiol. 2005 Jan 1;161(1):1-1415615908Int J Epidemiol. 2008 Feb;37(1):136-4618037675Mutat Res. 2008 Feb 1;638(1-2):146-5317991492Carcinogenesis. 2001 Jun;22(6):917-2211375899Carcinogenesis. 2000 Jul;21(7):1329-3410874010J Exp Clin Cancer Res. 2008 Sep 30;27:4918823566Mutagenesis. 2009 Nov;24(6):507-1219762350Genomics. 2004 Jun;83(6):970-915177551Cancer Epidemiol Biomarkers Prev. 2010 Dec;19(12):3167-7321037106Int J Cancer. 2007 Nov 1;121(9):2065-7217640039Med Oncol. 2013 Jun;30(2):50523430444Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2101-816609022Med Decis Making. 2005 Nov-Dec;25(6):646-5416282215BMJ. 1997 Sep 13;315(7109):629-349310563J Clin Oncol. 2000 Jun;18(11):2309-1510829052CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Curr Med Res Opin. 2011 Jul;27(7):1295-30221561390Nucleic Acids Res. 1992 Sep 11;20(17):4417-211383925J Appl Genet. 2010;51(3):343-5220720310Cancer Res. 2001 Feb 15;61(4):1354-711245433Nature. 2001 May 17;411(6835):366-7411357144Eur J Epidemiol. 2010 Sep;25(9):603-520652370Asian Continental Ancestry GroupgeneticsCase-Control StudiesColorectal NeoplasmsgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsEuropean Continental Ancestry GroupgeneticsGenetic Predisposition to DiseasegeneticsHumansOdds RatioPolymorphism, Single Nucleotidegenetics
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0219-10323652013NovMolecules and cellsMol. CellsCytoplasmic localization and redox cysteine residue of APE1/Ref-1 are associated with its anti-inflammatory activity in cultured endothelial cells.439-4510.1007/s10059-013-0195-6Apurinic/apyrimidinic endonuclease1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in base excision DNA repair and transcriptional regulation of gene expression. APE1/Ref-1 is mainly localized in the nucleus, but cytoplasmic localization has also been reported. However, the functional role of cytoplasmic APE1/Ref-1 and its redox cysteine residue are still unknown. We investigated the role of cytoplasmic APE1/Ref-1 on tumor necrosis factor-α (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) expressions in endothelial cells. Endogenous APE1/Ref-1 was mainly observed in the nucleus, however, cytoplasmic APE1/Ref-1 was increased by TNF-α. Cytoplasmic APE1/Ref-1 expression was not blunted by cycloheximide, a protein synthesis inhibitor, suggesting cytoplasmic translocation of APE1/Ref-1. Transfection of an N-terminus deletion mutant APE1/Ref-1(29-318) inhibited TNF-α-induced VCAM-1 expression, indicating an anti-inflammatory role for APE1/Ref-1 in the cytoplasm. In contrast, redox mutant of APE1/Ref-1 (C65A/C93A) transfection led to increased TNF-α-induced VCAM-1 expression. Our findings suggest cytoplasmic APE1/Ref-1 localization and redox cysteine residues of APE1/Ref-1 are associated with its anti-inflammatory activity in endothelial cells. ParkMyoung SooMSDepartment of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Korea.KimCuk-SeongCSJooHee KyoungHKLeeYu RanYRKangGunGKimSoo JinSJChoiSungaSLeeSang DoSDParkJin BongJBJeonByeong HwaBHengJournal ArticleResearch Support, Non-U.S. Gov't20131106
Korea (South)Mol Cells96109361016-84780Anti-Inflammatory Agents0Reactive Oxygen Species0Tumor Necrosis Factor-alpha0Vascular Cell Adhesion Molecule-198600C0908CycloheximideEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseK848JZ4886CysteineIMAntioxid Redox Signal. 2009 Mar;11(3):601-2018976116Circ Res. 2004 Oct 29;95(9):902-1015472121Cardiovasc Res. 2006 Feb 1;69(2):520-616325162Anesthesiology. 2009 Jan;110(1):106-1219104177Nucleic Acids Res. 2005;33(10):3303-1215942031Mutat Res. 2000 Oct 16;461(2):83-10811018583Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414J Mol Endocrinol. 2000 Jun;24(3):383-9010828831Cardiovasc Res. 2011 Aug 1;91(3):502-921467074Antioxid Redox Signal. 2009 Mar;11(3):571-418715142EMBO J. 2003 Dec 1;22(23):6299-30914633989Biochem Biophys Res Commun. 2013 Jun 7;435(3):403-723665318Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Mol Cells. 2011 Dec;32(6):491-50922207195Korean J Physiol Pharmacol. 2012 Jun;16(3):199-20422802702Cell Death Differ. 2002 Jul;9(7):717-2512058277FASEB J. 2002 Jun;16(8):889-9012039869Histopathology. 1998 Dec;33(6):561-99870152Cancer Res. 1995 Dec 15;55(24):6097-1028521399Nucleic Acids Res. 2007;35(8):2522-3217403694EMBO J. 1992 Sep;11(9):3323-351380454Circ Res. 2009 Jan 30;104(2):219-27, 5p following 22719038866Nucleic Acids Res. 2000 Mar 1;28(5):1099-10510666449Chem Rev. 2001 Aug;101(8):2449-7611749383Mol Immunol. 2008 Apr;45(8):2225-3518179823Mol Cells. 2013 May;35(5):396-40123639968Anti-Inflammatory AgentsmetabolismCell NucleusgeneticsmetabolismCycloheximidepharmacologyCysteinemetabolismCytoplasmmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismGene Expression RegulationHuman Umbilical Vein Endothelial CellsHumansMutationOxidation-ReductionReactive Oxygen SpeciesmetabolismTransfectionTumor Necrosis Factor-alphametabolismVascular Cell Adhesion Molecule-1metabolism
2013070520130906201308302013111260201311126020147660ppublish2421367310.1007/s10059-013-0195-6PMC3887937
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1568-785612122013DecDNA repairDNA Repair (Amst.)Coordination of MYH DNA glycosylase and APE1 endonuclease activities via physical interactions.1043-5210.1016/j.dnarep.2013.09.007S1568-7864(13)00237-1MutY homologue (MYH) is a DNA glycosylase which excises adenine paired with the oxidative lesion 7,8-dihydro-8-oxoguanine (8-oxoG, or G(o)) during base excision repair (BER). Base excision by MYH results in an apurinic/apyrimidinic (AP) site in the DNA where the DNA sugar-phosphate backbone remains intact. A key feature of MYH activity is its physical interaction and coordination with AP endonuclease I (APE1), which subsequently nicks DNA 5' to the AP site. Because AP sites are mutagenic and cytotoxic, they must be processed by APE1 immediately after the action of MYH glycosylase. Our recent reports show that the interdomain connector (IDC) of human MYH (hMYH) maintains interactions with hAPE1 and the human checkpoint clamp Rad9-Rad1-Hus1 (9-1-1) complex. In this study, we used NMR chemical shift perturbation experiments to determine hMYH-binding site on hAPE1. Chemical shift perturbations indicate that the hMYH IDC peptide binds to the DNA-binding site of hAPE1 and an additional site which is distal to the APE1 DNA-binding interface. In these two binding sites, N212 and Q137 of hAPE1 are key mediators of the MYH/APE1 interaction. Intriguingly, despite the fact that hHus1 and hAPE1 both interact with the MYH IDC, hHus1 does not compete with hAPE1 for binding to hMYH. Rather, hHus1 stabilizes the hMYH/hAPE1 complex both in vitro and in cells. This is consistent with a common theme in BER, namely that the assembly of protein-DNA complexes enhances repair by efficiently coordinating multiple enzymatic steps while simultaneously minimizing the release of harmful repair intermediates. Copyright © 2013 Elsevier B.V. All rights reserved.LuncsfordPaz JPJDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, United States.ManvillaBrittney ABAPattersonDimeka NDNMalikShuja SSSJinJinJHwangBor-JangBJGuntherRandallRKalvakolanuSnigdhaSLipinskiLeonora JLJYuanWeirongWLuWuyuanWDrohatAlexander CACLuA-LienALTothEric AEAengR56 CA078391CANCI NIH HHSUnited StatesGM 72711GMNIGMS NIH HHSUnited StatesCA 78391CANCI NIH HHSUnited StatesR01 GM072711GMNIGMS NIH HHSUnited StatesR01 CA078391CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20131024
NetherlandsDNA Repair (Amst)1011391381568-78560Cell Cycle Proteins9007-49-2DNAEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMNucleic Acids Res. 2000 Sep 1;28(17):3206-1510954587Nat Struct Biol. 2000 Mar;7(3):176-810700268Nucleic Acids Res. 2001 Feb 1;29(3):743-5211160897J Mol Biol. 2001 Apr 6;307(4):1023-3411286553Curr Biol. 2002 Jan 8;12(1):73-711790307Nat Genet. 2002 Feb;30(2):227-3211818965J Biol Chem. 2002 Aug 23;277(34):31115-2312063248J Biol Chem. 2003 Jan 24;278(4):2411-812441341Nucleic Acids Res. 2004;32(11):3316-2415314187J Pept Res. 2004 Sep;64(3):118-2515317502Anal Biochem. 1976 May 7;72:248-54942051Biochemistry. 1988 Oct 18;27(21):8063-83233195Gene. 1989 Apr 15;77(1):51-92744487Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958-621495986Nat Struct Biol. 1995 Jul;2(7):561-87664124J Biomol NMR. 1995 Nov;6(3):277-938520220Nucleic Acids Res. 1996 Nov 1;24(21):4217-218932375Nucleic Acids Res. 1997 Mar 1;25(5):933-99023101EMBO J. 1997 Nov 3;16(21):6548-589351835Bioessays. 1998 Mar;20(3):195-99631646Nat Struct Biol. 1998 Dec;5(12):1058-649846876J Biol Chem. 1999 Feb 12;274(7):4354-639933638Bioessays. 1999 Mar;21(3):238-4610333733Annu Rev Biophys Biomol Struct. 1999;28:101-2810410797Biochemistry. 1999 Jul 20;38(29):9533-4010413531J Biol Chem. 1999 Sep 17;274(38):26647-5310480866Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16762-715556996J Biol Chem. 2004 Dec 10;279(50):52653-6315456766DNA Repair (Amst). 2005 Mar 2;4(3):315-2515661655J Mol Biol. 2005 Mar 11;346(5):1259-7415713479Free Radic Biol Med. 2005 May 1;38(9):1121-3815808410Biochem J. 2005 Jul 1;389(Pt 1):13-715871698J Mol Biol. 2005 Nov 11;353(5):980-916216273J Biol Chem. 2006 Jul 28;281(30):20865-7216731526J Am Chem Soc. 2006 Sep 27;128(38):12510-916984202Biochem J. 2006 Nov 15;400(1):53-6216879101DNA Repair (Amst). 2007 Mar 1;6(3):317-2817126083DNA Repair (Amst). 2007 Jun 1;6(6):695-71117337257Nucleic Acids Res. 2007;35(8):2463-7217395641Nucleic Acids Res. 2007;35(8):2596-60817426133Nature. 2007 Jun 21;447(7147):941-5017581577J Biol Chem. 2008 Nov 21;283(47):32680-9018805789Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Biochemistry. 2009 Jun 30;48(25):6022-3319449863J Mol Biol. 2009 Jul 17;390(3):490-50219464297Mol Cell. 2009 Jun 26;34(6):735-4519446481Nucleic Acids Res. 2009 Jul;37(12):3946-5819401441J Biol Chem. 2009 Jul 31;284(31):20457-6119535328DNA Repair (Amst). 2009 Oct 2;8(10):1190-20019615952Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18497-50219841264Mol Cell Biol. 2010 Jan;30(2):366-7119901076Biomol NMR Assign. 2010 Apr;4(1):5-819888678J Mol Biol. 2010 Oct 29;403(3):351-7020816984Nucleic Acids Res. 2010 Dec;38(22):8239-5620699270J Biol Chem. 2010 Dec 24;285(52):40479-8820952393Nucleic Acids Res. 2011 Mar;39(6):2319-2921097883Biochemistry. 2011 Dec 6;50(48):10540-922032234Mol Biol Cell. 2012 Oct;23(20):4079-9622918947Biochemistry. 2001 Oct 23;40(42):12639-4411601988Science. 1999 Dec 3;286(5446):1897-90510583946Nature. 2000 Jan 27;403(6768):451-610667800J Biol Chem. 2001 Feb 23;276(8):5547-5511092888Binding SitesBiocatalysisCell Cycle ProteinsgeneticsmetabolismDNAmetabolismDNA DamageDNA GlycosylaseschemistrymetabolismDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasechemistrymetabolismHumansMagnetic Resonance ImagingMagnetic Resonance SpectroscopyModels, MolecularMutationProtein BindingProtein Stability7,8-dihydro-8-oxoguanine8-oxoG or G(o)9–1–1APAP endonucleaseAP-endonuclease 1APE1BERBSABacillus stearothermophilus MutYBase excision repairBstMutYCheckpoint clampDNA glycosylaseEc-cMutYEscherichia coli MutY catalytic domainEtBrFGSTHSQCIDCLPMAPMEFMYH or MUTYHMYH-associated polyposisMutY homologueODNRad9–Rad1–Hus1Regulatory protein interactionsS. cerevisiaeS. pombeSNSaccharomyces cerevisiaeSchizosaccharomyces pombeapurinic/apyrimidinicbase excision repairbovine serum albuminethidium bromideglutathione S-transferasehheteronuclear spin quantum coherencehumaninterdomain connectorlong-patchmouse embryonic fibroblastoligodeoxynucleotidessingle-nucleotide patchtetrahydrofuran abasic site analog
20130503201308302013092020131112602013111260201471660ppublish24209961S1568-7864(13)00237-110.1016/j.dnarep.2013.09.007PMC3857741NIHMS531335
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1432-07388832014MarArchives of toxicologyArch. Toxicol.Ogg1 genetic background determines the genotoxic potential of environmentally relevant arsenic exposures.585-9610.1007/s00204-013-1151-0Inorganic arsenic (i-As) is a well-established human carcinogen to which millions of people are exposed worldwide. It is generally accepted that the genotoxic effects of i-As after an acute exposure are partially linked to the i-As-induced production of reactive oxygen species, but it is necessary to better determine whether chronic sub-toxic i-As doses are able to induce biologically significant levels of oxidative DNA damage (ODD). To fill in this gap, we have tested the genotoxic and oxidative effects of environmentally relevant arsenic exposures using mouse embryonic fibroblast MEF mutant Ogg1 cells and their wild-type counterparts. Effects were examined by using the comet assay complemented with the use of FPG enzyme. Our findings indicate that MEF Ogg1-/- cells are more sensitive to arsenite-induced acute toxicity, genotoxicity and ODD. Long-term exposure to sub-toxic doses of arsenite generates a detectable increase in ODD and genotoxic DNA damage only in MEF Ogg1-deficient cells. Altogether, the data presented here point out the relevance of ODD and Ogg1 genetic background on the genotoxic risk of i-As at environmentally plausible doses. The persistent accumulation of DNA 8-OH-dG lesions in Ogg1-/- cells during the complete course of the exposure suggests a relevant role in arsenic-associated carcinogenic risk in turn.BachJordiJGrup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Edifici Cn, Campus de Bellaterra, 08193, Cerdanyola del Vallès, Spain.Sampayo-ReyesAdrianaAMarcosRicardRHernándezAlbaAengJournal ArticleResearch Support, Non-U.S. Gov't20131105
GermanyArch Toxicol04176150340-576188847-89-68-oxo-7-hydrodeoxyguanosineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseG9481N71RODeoxyguanosineN712M78A8GArsenicIMAnimalsArsenictoxicityCell Survivaldrug effectsCells, CulturedComet AssayDNA Damagedrug effectsDNA GlycosylasesgeneticsmetabolismDeoxyguanosineanalogs & derivativesmetabolismFibroblastsdrug effectsphysiologyMiceMice, KnockoutMutagenicity Tests
2013080720131022201311660201311660201551360ppublish2419050210.1007/s00204-013-1151-0
241860012014060320170220
1423-03803532014MarTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Association of OGG1 Ser326Cys polymorphism and pancreatic cancer susceptibility: evidence from a meta-analysis.2397-40210.1007/s13277-013-1317-7The 8-oxoguanine DNA glycosylase (OGG1) gene has been considered to be associated with cancer susceptibility. The OGG1 Ser326Cys polymorphism has been reported to be associated with pancreatic cancer (PC), but the published studies have yielded inconsistent results. For better understanding of the effect of OGG1 Ser326Cys polymorphism on PC susceptibility, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database before May 2013. The association between the OGG1 Ser326Cys polymorphism and PC risk was conducted by odds ratios (ORs) and 95% confidence intervals (CIs). A total of five case-control studies with 1,690 cases and 3,650 controls were eventually collected. Overall, we found that OGG1 Ser326Cys polymorphism was not associated with PC susceptibility (Cys/Cys vs. Ser/Ser: OR = 0.95, 95% CI = 0.80-1.14; Cys/Cys vs. Ser/Ser + Ser/Cys: OR = 0.95, 95% CI = 0.78-1.14; Cys/Cys + Ser/Cys vs. Ser/Ser (OR = 1.00, 95% CI = 0.89-1.12)). In the subgroup analysis based on ethnicity, source of control, sample size, and genotyping method, no significant association was found in any genetic models. This meta-analysis suggests that the OGG1 Ser326Cys polymorphism may not associated with PC susceptibility. Considering the limited sample size and ethnicity included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results.YanYulanYDepartment of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China, xueying201120521@163.com.ChenXuXLiTaijieTLiMengMLiangHongjieHengJournal ArticleMeta-Analysis20131103
United StatesTumour Biol84099221010-4283EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMCancer Res. 2008 Jun 15;68(12):4928-3518544627Ann Oncol. 2009 Aug;20(8):1387-9619502533Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1470-918559563BMJ. 1998 Feb 7;316(7129):469; author reply 470-19492685Biometrika. 1950 Dec;37(3-4):256-6614801052J Gastroenterol. 2011 Dec;46(12):1345-5222048257JAMA. 2008 May 28;299(20):2423-3618505952Control Clin Trials. 1986 Sep;7(3):177-883802833Breast Cancer Res Treat. 2010 Aug;122(3):835-4220058067DNA Repair (Amst). 2006 Jan 5;5(1):43-5116111924Mol Carcinog. 2005 Mar;42(3):127-4115584022Carcinogenesis. 2007 Mar;28(3):657-6417028303Genome Res. 2004 Oct;14(10B):2121-715489334Int J Colorectal Dis. 2011 Dec;26(12):1525-3021695387PLoS One. 2011;6(7):e2231521811587CA Cancer J Clin. 2012 Jan-Feb;62(1):10-2922237781Ann Oncol. 2012 Feb;23(2):374-8221536662Nucleic Acids Res. 1999 Oct 15;27(20):4001-710497264Oncogene. 1998 Jun 25;16(25):3219-259681819J Epidemiol. 2012;22(6):477-8322850545J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060CA Cancer J Clin. 2008 Mar-Apr;58(2):71-9618287387Int J Mol Epidemiol Genet. 2011 Aug 30;2(3):236-4421915362BMJ. 1997 Sep 13;315(7109):629-349310563Tumour Biol. 2012 Aug;33(4):1237-4322396042Gut. 2007 Aug;56(8):1134-5217625148CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855Clin Cancer Res. 2009 Jan 15;15(2):740-619147782J Epidemiol Community Health. 1999 Sep;53(9):583-410562886PLoS One. 2012;7(4):e3597022540013Asian Pac J Cancer Prev. 2011;12(12):3427-3122471492HPB (Oxford). 2008;10(1):58-6218695761Ann Oncol. 2012 Feb;23(2):401-521515665PLoS One. 2011;6(11):e2792122125638Langenbecks Arch Surg. 2008 Jul;393(4):535-4518193270Ann Oncol. 2012 Oct;23(10):2536-4622539563Case-Control StudiesDNA GlycosylasesgeneticsGenetic Predisposition to DiseasegeneticsGenotypeHumansOdds RatioPancreatic NeoplasmsgeneticsPolymorphism, Single Nucleotidegenetics
201306192013101420131156020131156020146460ppublish2418600110.1007/s13277-013-1317-7PMC3967056
241757912014123120171116
2476-762X1492013Asian Pacific journal of cancer prevention : APJCPAsian Pac. J. Cancer Prev.Association of DNA base-excision repair XRCC1, OGG1 and APE1 gene polymorphisms with nasopharyngeal carcinoma susceptibility in a Chinese population.5145-51Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles.To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma.We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models.After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02- 3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1- 141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants ,was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004).This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1- 141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.LiQingQCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China E-mail : dongwang64@hotmail.com.WangJian-MinJMPengYuYZhangShi-HengSHRenTaoTLuoHaoHChengYiYWangDongDengJournal ArticleResearch Support, Non-U.S. Gov't
ThailandAsian Pac J Cancer Prev1011306251513-73680DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseNasopharyngeal carcinomaIMAsian Continental Ancestry GroupgeneticsCarcinomaetiologygeneticsCase-Control StudiesChinaDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGenetic Predisposition to DiseaseHumansLogistic ModelsMaleMiddle AgedMultivariate AnalysisNasopharyngeal NeoplasmsetiologygeneticsPolymorphism, Single NucleotideProtective FactorsSmokingadverse effectsX-ray Repair Cross Complementing Protein 1
20131126020131126020151160ppublish24175791
241275762014010820161019
1091-6490110442013Oct29Proceedings of the National Academy of Sciences of the United States of AmericaProc. Natl. Acad. Sci. U.S.A.Essential role for mammalian apurinic/apyrimidinic (AP) endonuclease Ape1/Ref-1 in telomere maintenance.17844-910.1073/pnas.1304784110The major mammalian apurinic/apyrimidinic endonuclease Ape1 is a multifunctional protein operating in protection of cells from oxidative stress via its DNA repair, redox, and transcription regulatory activities. The importance of Ape1 has been marked by previous work demonstrating its requirement for viability in mammalian cells. However, beyond a requirement for Ape1-dependent DNA repair activity, deeper molecular mechanisms of the fundamental role of Ape1 in cell survival have not been defined. Here, we report that Ape1 is an essential factor stabilizing telomeric DNA, and its deficiency is associated with telomere dysfunction and segregation defects in immortalized cells maintaining telomeres by either the alternative lengthening of telomeres pathway (U2OS) or telomerase expression (BJ-hTERT), or in normal human fibroblasts (IMR90). Through the expression of Ape1 derivatives with site-specific changes, we found that the DNA repair and N-terminal acetylation domains are required for the Ape1 function at telomeres. Ape1 associates with telomere proteins in U2OS cells, and Ape1 depletion causes dissociation of TRF2 protein from telomeres. Consistent with this effect, we also observed that Ape1 depletion caused telomere shortening in both BJ-hTERT and in HeLa cells. Thus, our study describes a unique and unpredicted role for Ape1 in telomere protection, providing a direct link between base excision DNA repair activities and telomere metabolism. MadlenerSibylleSMolecular Neuro-Oncology Research Unit, Department of Pediatrics and Adolescent Medicine and Institute of Neurology, Medical University of Vienna, A-1090 Vienna, Austria.StröbelThomasTVoseSarahSSaydamOkayOPriceBrendan DBDDempleBruceBSaydamNurtenNengR01 CA177884CANCI NIH HHSUnited StatesR01 GM040000GMNIGMS NIH HHSUnited StatesT32 ES016645ESNIEHS NIH HHSUnited StatesGM040000GMNIGMS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20131014
United StatesProc Natl Acad Sci U S A75058760027-84240DNA PrimersEC 2.7.7.49TelomeraseEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMScience. 1999 Dec 3;286(5446):1897-90510583946Nature. 2000 Jan 27;403(6768):451-610667800Cancer Res. 2001 Jul 15;61(14):5552-711454706Trends Biochem Sci. 2002 Jul;27(7):339-4412114022Mol Cell Biol. 2003 Jan;23(1):382-812482989Nat Biotechnol. 2003 Mar;21(3):229-3012610563EMBO J. 2003 Dec 1;22(23):6299-30914633989Methods Enzymol. 2003;371:292-30014712709Biochemistry. 1972 Sep 12;11(19):3618-234559796Annu Rev Genet. 1986;20:201-303545059Nucleic Acids Res. 1991 Mar 11;19(5):1087-921708495Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-41722334Nature. 1993 Apr 22;362(6422):709-158469282Mol Cell Biol. 1993 Sep;13(9):5370-68355688Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414J Biol Chem. 1994 Nov 11;269(45):27855-627961715Proc Natl Acad Sci U S A. 1995 May 9;92(10):4337-417753808EMBO J. 1995 Sep 1;14(17):4240-87556065Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Nucleic Acids Res. 2005;33(4):1230-915731343Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Cell. 2009 Jan 9;136(1):175-8619135898Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Nucleic Acids Res. 2009 Jul;37(12):3946-5819401441EMBO J. 2010 Jan 20;29(2):398-40919942858DNA Repair (Amst). 2011 Jan 2;10(1):34-4420951653Mol Cell Proteomics. 2011 Feb;10(2):M110.00162821044950Mol Cell Biol. 2011 Jun;31(12):2369-7921464209Cell Cycle. 2012 Mar 1;11(5):998-100722336916Nucleic Acids Res. 1996 Nov 1;24(21):4217-218932375Genes Dev. 1997 Mar 1;11(5):558-709119221Science. 1998 Jan 16;279(5349):349-529454332Cell. 1998 Feb 6;92(3):401-139476899Exp Cell Res. 1998 Feb 25;239(1):152-609511733Mutat Res. 1998 Oct 21;409(1):17-299806499J Biol Chem. 1999 Jan 8;274(2):962-719873038Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3723-810097104EMBO J. 1999 Oct 15;18(20):5609-2110523305Mol Cell. 2005 Feb 4;17(3):463-7015694346Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Blotting, WesternCell Line, TumorChromatin ImmunoprecipitationDNA PrimersgeneticsDNA RepairphysiologyDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismFluorescent Antibody TechniqueHumansImmunoprecipitationIn Situ Hybridization, FluorescenceTelomerasemetabolismTelomere Homeostasisgeneticsphysiologychromosome stabilityendogenous DNA damagegenome stability
2013101660201310166020141960ppublish24127576130478411010.1073/pnas.1304784110PMC3816401
241211182014070920161128
1872-6216134102013OctMechanisms of ageing and developmentMech. Ageing Dev.Transient OGG1, APE1, PARP1 and Polβ expression in an Alzheimer's disease mouse model.467-7710.1016/j.mad.2013.09.002S0047-6374(13)00109-7Alzheimer's disease (AD) is a disease of major public health significance, whose pathogenesis is strongly linked to the presence of fibrillar aggregates of amyloid-beta (Aβ) in the aging human brain. We exploited the transgenic (Tg)-ArcSwe mouse model for human AD to explore whether oxidative stress and the capacity to repair oxidative DNA damage via base excision repair (BER) are related to Aβ pathology in AD. Tg-ArcSwe mice express variants of Aβ, accumulating senile plaques at 4-6 months of age, and develop AD-like neuropathology as adult animals. The relative mRNA levels of genes encoding BER enzymes, including 8-oxoguanine glycosylase (OGG1), AP endonuclease 1 (APE1), polymerase β (Polβ) and poly(ADP-ribose) polymerase 1 (PARP1), were quantified in various brain regions of 6 weeks, 4 months and 12 months old mice. The results show that OGG1 transcriptional expression was higher, and APE1 expression lower, in 4 months old Tg-ArcSwe than in wildtype (wt) mice. Furthermore, Polβ transcriptional expression was significantly lower in transgenic 12 months old mice than in wt. Transcriptional profiling also showed that BER repair capacity vary during the lifespan in Tg-ArcSwe and wt mice. The BER expression pattern in Tg-ArcSwe mice thus reflects responses to oxidative stress in vulnerable brain structures. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.LillenesMeryl SMSCentre for Molecular Biology and Neuroscience, Department of Microbiology, Oslo University Hospital, Norway.StøenMariMGómez-MuñozMartaMTorpReidunRGüntherClara-CecilieCCNilssonLars N GLNTønjumToneTengJournal ArticleResearch Support, Non-U.S. Gov't20131011
IrelandMech Ageing Dev03472270047-63740Nerve Tissue ProteinsEC 2.4.2.30Parp1 protein, mouseEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 2.7.7.-DNA Polymerase betaEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAlzheimer DiseaseenzymologygeneticspathologyAnimalsBrainenzymologypathologyDNA DamageDNA GlycosylasesbiosynthesisgeneticsDNA Polymerase betabiosynthesisgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasebiosynthesisgeneticsDisease Models, AnimalGene Expression Regulation, EnzymologicHumansMiceMice, TransgenicNerve Tissue ProteinsbiosynthesisgeneticsOxidative StressgeneticsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesbiosynthesisgeneticsTranscription, GeneticgeneticsAlzheimer's diseaseAβPP mutationBase excision repair (BER)DNA repairOGG1, APE1, PARP1, PolβTransgenic (Tg-ArcSwe) mice
20130510201309232013092820131015602013101560201471060ppublish24121118S0047-6374(13)00109-710.1016/j.mad.2013.09.002
241013882014051220131008
1899-15056442013AugJournal of physiology and pharmacology : an official journal of the Polish Physiological SocietyJ. Physiol. Pharmacol.Influence of fundectomy and intraperitoneal or intragastric administration of apelin on apoptosis, mitosis, and DNA repair enzyme OGG1,2 expression in adult rats gastrointestinal tract and pancreas.423-8Apelin, endogenous ligand of G protein-coupled apelin receptor (APJ), is released into the gastrointestinal lumen, however, local effect of luminal apelin on gut epithelium has not been elucidated so far. The present study aimed to determine the effects of fundectomy, and intraperitoneal or intragastric administration of apelin on pancreatic, gastric and intestinal epithelium apoptosis, mitosis and DNA repair enzyme OGG1,2 expression in adult Wistar rats. Apelin-13 was given by intraperitoneal or gastric gavage twice a day for 10 days (100 nmol/kg b. wt./day). Fundectomized rats did not receive apelin. Control groups received saline as placebo. At the end of the experiment the rats were sacrificed and the pancreas, gastric fundus, duodenum, middle jejunum and colon tissue samples were harvested for immunofluorescence studies. Intraperitoneal and intragastric apelin-13 reduced apoptosis, mitosis and number of DNA damages in rats gastrointestinal tract (p≤0.001) as compared to control. In fundectomized rats, the apoptotic index in the pancreas and colon was decreased (p<0.001), and in the stomach and jejunum was increased (p<0.001). Mitotic index was decreased in all gastrointestinal tissues. Number of DNA damages (p≤0.001) in fundectomized rats was reduced except stomach where OGG1,2 expression was increased (p≤0.001) as compared to control. In conclusion, circulating and luminal exogenous apelin-13 caused similar effects on intestinal epithelium. Endogenous (gastric) apelin is important for renewal of intestinal epithelium in adult rats. Pharmacological doses of apelin-13 may reduce the cell turnover in the upper gastrointestinal tract epithelium and pancreas, and improve the overall gut health. AntushevichHHThe Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Jablonna, Poland. antuszewicz@op.pl.PawlinaBBKapicaMMKrawczynskaAAHermanA PAPKuwaharaAAKatoIIZabielskiRRengJournal ArticleResearch Support, Non-U.S. Gov't
PolandJ Physiol Pharmacol91145010867-59100Intercellular Signaling Peptides and Proteins0Ki-67 Antigen0apelin-13 peptideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-OGG1 protein, ratEC 3.4.22.-Caspase 3IMAnimalsApoptosisdrug effectsCaspase 3metabolismDNA Damagedrug effectsDNA GlycosylasesmetabolismDrug Administration RoutesGastrointestinal Tractdrug effectsmetabolismsurgeryIntercellular Signaling Peptides and ProteinspharmacologyIntestinal Mucosacytologydrug effectsmetabolismKi-67 AntigenmetabolismMaleMitosisdrug effectsPancreasdrug effectsmetabolismRatsRats, Wistar
2013052120130815201310960201310960201451360ppublish24101388
240754202014071520131125
1568-785612122013DecDNA repairDNA Repair (Amst.)The 8-oxoguanine DNA glycosylase 1 (ogg1) decreases the vulnerability of the developing brain to DNA damage.1094-10410.1016/j.dnarep.2013.08.018S1568-7864(13)00230-9The developing brain is particularly vulnerable to oxidative DNA damage, which may be the cause of most major congenital mental anomalies. The repair enzyme ogg1 initiates the highly conserved base-excision repair pathway. However, its function in the embryonic brain is largely unknown. This study is the first to validate the function of ogg1 during brain development using zebrafish embryos. Ogg1 was found to be highly expressed in the brain throughout early embryonic development, with particularly enrichment observed in the midbrain. The lack of ogg1 causes severe brain defects including changes in brain volume and integrity, destruction of the midbrain-hindbrain boundary, and balance and motor impairment, while overexpression of ogg1 can partially rescue these defects. Multiple cellular and molecular events were involved in the manifestation of brain defects due primarily to the lack of ogg1. These included (1) increased apoptosis; (2) decreased proliferation; and (3) aberrant axon distribution and extension from the inner surface towards the outer layers. The results of a microarray analysis showed that the expression of genes involved in cell cycle checkpoint, apoptosis, and neurogenesis were significantly changed in response to ogg1 knockdown. Cmyb was the key downstream gene that responses to DNA damage caused by ogg1 deficiency. Notably, the recruitment of ogg1 mRNA can alleviate the effects on the brain due to neural DNA damage. In summary, we introduce here that ogg1 is fundamentally required for protecting the developing brain, which may be helpful in understanding the aetiology of congenital brain deficits. Copyright © 2013 Elsevier B.V. All rights reserved.GuAihuaAState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China. Electronic address: aihuagu@njmu.edu.cn.JiGuixiangGYanLifengLZhouYongYengJournal ArticleResearch Support, Non-U.S. Gov't20130925
NetherlandsDNA Repair (Amst)1011391381568-785608-oxoguanine DNA glycosylase 1, zebrafish0Multifunctional Enzymes0Zebrafish ProteinsEC 3.2.2.-DNA GlycosylasesEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsBrainabnormalitiesembryologyphysiologyCloning, MolecularDNA DamageDNA GlycosylasesmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismEmbryo, NonmammalianGene Expression Regulation, DevelopmentalGene Knockdown TechniquesLarvametabolismMultifunctional EnzymesmetabolismOligonucleotide Array Sequence AnalysisOxidative StressPhenotypeZebrafishembryologygeneticsmetabolismZebrafish Proteinsmetabolismphysiology
201306212013081720130827201310160201310160201471660ppublish24075420S1568-7864(13)00230-910.1016/j.dnarep.2013.08.018
239998242014032620171111
1423-03803512014JanTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Association between single-nucleotide polymorphisms of OGG1 gene and pancreatic cancer risk in Chinese Han population.809-1310.1007/s13277-013-1111-6The purpose of this study was to test the association between single-nucleotide polymorphisms (SNPs) of 8-oxoguanine DNA glycosylase (OGG1) gene and susceptibility to pancreatic cancer (PC). A total of 347 PC patients and 364 healthy subjects were enrolled in this case-control study. The c.269C>A genetic variant was investigated using the created restriction site-polymerase chain reaction method. The c.627T>C genetic variant was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Our data indicated that the alleles and genotypes frequencies of these two SNPs were statistically different in PC cases and controls. As for c.269C>A, the AA genotype was statistically associated with decreased PC susceptibility compared to CC wild genotype (odds ratio (OR) = 0.44, 95% confidence interval (CI) 0.27-0.73, P = 0.001). As for c.627T>C, statistically significant decreased PC susceptibility was detected in CC genotype compared to TT wild genotype (OR = 0.57, 95% CI 0.35-0.94, P = 0.028). The allele A of c.269C>A and allele C of c.627T>C might be associated with a protection from PC (for c.269C>A, A versus (vs.) C, OR = 0.69, 95% CI 0.55-0.86, P < 0.001; for c.627T>C, C vs. T, OR = 0.72, 95% CI 0.58-0.91, P = 0.005). Results from this study indicate that the c.269C>A and c.627T>C SNPs of OGG1 gene are associated with PC susceptibility in Chinese Han ethnicity.ChenHongxuHDepartment of Hepatobiliary Surgery, Daping Hospital, The Third Military Medical University, No. 10 Changjiangzhilu Daping, Chongqing, 400042, People's Republic of China.ZhouBoBLanXiangXWeiDongDYuanTaoTChenPingPengJournal ArticleRetracted Publication20130903
United StatesTumour Biol84099221010-4283EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMTumour Biol. 2017 Apr 20;:28792236Cancer. 2011 Feb 15;117(4):744-5120922799Cancer Res. 2008 Jun 15;68(12):4928-3518544627Nucleic Acids Res. 1989 May 11;17(9):36062726503Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1470-918559563Pancreatology. 2003;3(1):1-712683400Int J Cancer. 2007 May 1;120(9):1993-817266034Mol Biol Rep. 2013 Feb;40(2):1947-5423143182Asian Pac J Cancer Prev. 2001;2(4):271-28012718618Mol Biol Rep. 2013 Jan;40(1):7-1223114911JOP. 2010 May 05;11(3):203-1220442513Cancer Causes Control. 2007 Aug;18(6):603-1217401636Yi Chuan. 2003 May;25(3):327-915639881Best Pract Res Clin Gastroenterol. 2006 Apr;20(2):197-20916549324J Epidemiol. 2012;22(6):477-8322850545Mutat Res. 2009 Mar-Jun;681(2-3):299-30719150414Gene. 2012 Aug 15;505(1):190-422583824Int J Mol Epidemiol Genet. 2011 Aug 30;2(3):236-4421915362Dig Dis. 2011;29(2):235-4221734390Clin Cancer Res. 2009 Jan 15;15(2):740-619147782Int J Cancer. 2007 Apr 15;120(8):1748-5417230526J Clin Oncol. 2006 Apr 10;24(11):1720-816520463CA Cancer J Clin. 2007 Jan-Feb;57(1):43-6617237035AdultAgedAllelesAsian Continental Ancestry GroupgeneticsCase-Control StudiesChinaDNA GlycosylasesgeneticsFemaleGene FrequencyGenetic Association StudiesGenotypeHumansMaleMiddle AgedOdds RatioPancreatic NeoplasmsgeneticsPolymorphism, Single NucleotideRisk
20130722201308122013946020139460201432960ppublish2399982410.1007/s13277-013-1111-6
239941942013121020131007
1879-003853112013Nov15GeneGeneA genetic variant in the promoter of APE1 gene (-656 T>G) is associated with breast cancer risk and progression in a Chinese population.97-10010.1016/j.gene.2013.08.052S0378-1119(13)01095-0APE1 is an important DNA repair protein in the base excision repair pathway. Genetic variations in APE1 have been suggested to influence individuals' susceptibility to human malignancies. The present study was aimed to investigate the associations between two functional polymorphisms in APE1 (-656T>G and 1349T>G) and breast cancer risk.We genotyped the two polymorphisms in a case-control study of 500 breast cancer patients and 799 age-matched cancer-free controls using the TaqMan method. Unconditional logistic regression adjusted for potential confounding factors was used to assess the associations.We found that the variant genotypes of the -656T>G were significantly associated with decreased breast cancer risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR)=0.71, 95% confidence interval (CI)=0.56-0.91], and the protective effect of this polymorphism was more predominant among the subgroups of younger subjects (<52 years) (OR=0.65, 95% CI=0.46-0.92). Besides, we found that the variant genotypes were associated with less frequent lymph node metastasis (P=0.020, OR=0.64, 95% CI=0.44-0.94). We did not observe any significant association between the 1349T>G polymorphism and breast cancer risk.Our results suggest that the APE1 -656T>G but not the 1349T>G polymorphism may influence the susceptibility and progression of breast cancer in the Chinese population. Large population-based prospective studies are required to validate these findings.© 2013 Elsevier B.V. All rights reserved.KangHuafengHDepartment of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China. Electronic address: xa_khf@126.com.DaiZhijunZMaXiaobinXMaLiLJinYaofengYLiuXiaoxuXWangXijingXengJournal Article20130828
NetherlandsGene77067610378-1119EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdultAgedAllelesAsian Continental Ancestry GroupgeneticsBreast NeoplasmsgeneticsmetabolismpathologyCase-Control StudiesChinaDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDisease ProgressionFemaleGenetic Predisposition to DiseaseGenotypeHumansMiddle AgedOdds RatioPolymorphism, Single NucleotidePromoter Regions, GeneticRiskAP endonuclease 1APE1BERBreast cancerCIORPolymorphismSNPSusceptibilitybase excision repairconfidence intervalodds ratiosingle nucleotide polymorphism
20130619201308072013081420139360201393602013121660ppublish23994194S0378-1119(13)01095-010.1016/j.gene.2013.08.052
239671342014092320161025
1932-6203882013PloS onePLoS ONESpecific inhibition of the redox activity of ape1/ref-1 by e3330 blocks tnf-α-induced activation of IL-8 production in liver cancer cell lines.e7090910.1371/journal.pone.0070909APE1/Ref-1 is a main regulator of cellular response to oxidative stress via DNA-repair function and co-activating activity on the NF-κB transcription factor. APE1 is central in controlling the oxidative stress-based inflammatory processes through modulation of cytokines expression and its overexpression is responsible for the onset of chemoresistance in different tumors including hepatic cancer. We examined the functional role of APE1 overexpression during hepatic cell damage related to fatty acid accumulation and the role of the redox function of APE1 in the inflammatory process. HepG2 cells were stably transfected with functional and non-functional APE1 encoding plasmids and the protective effect of APE1 overexpression toward genotoxic compounds or FAs accumulation, was tested. JHH6 cells were stimulated with TNF-α in the presence or absence of E3330, an APE1 redox inhibitor. IL-8 promoter activity was assessed by a luciferase reporter assay, gene expression by Real-Time PCR and cytokines (IL-6, IL-8, IL-12) levels measured by ELISA. APE1 over-expression did not prevent cytotoxicity induced by lipid accumulation. E3330 treatment prevented the functional activation of NF-κB via the alteration of APE1 subcellular trafficking and reduced IL-6 and IL-8 expression induced by TNF-α and FAs accumulation through blockage of the redox-mediated activation of NF-κB. APE1 overexpression observed in hepatic cancer cells may reflect an adaptive response to cell damage and may be responsible for further cell resistance to chemotherapy and for the onset of inflammatory response. The efficacy of the inhibition of APE1 redox activity in blocking TNF-α and FAs induced inflammatory response opens new perspectives for treatment of inflammatory-based liver diseases. CesarattoLauraLDipartimento di Scienze Mediche e Biologiche, Università di Udine, Udine, Italy.CodarinErikaEVascottoCarloCLeonardiAntonioAKelleyMark RMRTiribelliClaudioCTellGianlucaGengR01 CA167291CANCI NIH HHSUnited StatesJournal ArticleResearch Support, Non-U.S. Gov't20130815
United StatesPLoS One1012850811932-62030Benzoquinones0Fatty Acids0Interleukin-80NF-kappa B0Propionates0Tumor Necrosis Factor-alpha136164-66-4E 3330EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMProg Nucleic Acid Res Mol Biol. 2001;68:41-5411554312PLoS One. 2012;7(10):e4746223094050Hepatology. 2002 Apr;35(4):964-611915046Methods Enzymol. 2002;353:81-812078530Hepatology. 2003 Feb;37(2):343-5012540784Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H804-1212730053Clin Sci (Lond). 2004 Jun;106(6):635-4314720121Mayo Clin Proc. 1980 Jul;55(7):434-87382552Nature. 1979 Dec 6;282(5739):615-6233137Cancer Res. 1982 Sep;42(9):3858-636286115J Cell Biol. 1985 Mar;100(3):965-733972906Br J Cancer. 1987 Sep;56(3):279-853663476J Biol Chem. 1990 Dec 5;265(34):21128-332250017Hepatogastroenterology. 1990 Oct;37(5):457-601701409J Pharmacol Exp Ther. 1992 Jul;262(1):145-501625194J Pharmacol Exp Ther. 1993 Aug;266(2):1085-908394904J Interferon Cytokine Res. 1999 May;19(5):429-3810386854Curr Biol. 2005 Feb 8;15(3):R99-R10215694301Mol Cell. 2005 Feb 4;17(3):463-7015694346Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4120-515738389Nucleic Acids Res. 2005;33(10):3303-1215942031Hepatogastroenterology. 2005 Sep-Oct;52(65):1549-5316201116Gastroenterology. 2005 Nov;129(5):1663-7416285964Diabetes. 2005 Dec;54(12):3458-6516306362Crit Care Med. 2005 Dec;33(12 Suppl):S466-716340423World J Gastroenterol. 2005 Oct 28;11(40):6258-6116419152J Immunol. 2006 Dec 1;177(11):7990-917114472Mol Cancer Res. 2007 Jan;5(1):61-7017259346Mol Carcinog. 2007 Feb;46(2):91-917013835J Hepatol. 2007 Apr;46(4):708-1817275126Mol Med. 2007 Jan-Feb;13(1-2):89-9617515960Gastroenterology. 2007 Jun;132(7):2601-417570232Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Hepatology. 2007 Sep;46(3):823-3017680645Trends Mol Med. 2008 Feb;14(2):72-8118218340Mutat Res. 2008 May 10;641(1-2):43-718423498Mol Cancer Ther. 2008 Jul;7(7):2012-2118645011Proteomics. 2009 Feb;9(4):1058-7419180539Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Cytokine. 2009 Jun;46(3):359-6919376732DNA Repair (Amst). 2009 Nov 2;8(11):1273-8219726241Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116J Pharmacol Exp Ther. 2010 Sep 1;334(3):988-9820504914Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766Cell Mol Life Sci. 2010 Nov;67(21):3569-7220706767Exp Hematol. 2010 Dec;38(12):1178-8820826193J Gastrointestin Liver Dis. 2010 Dec;19(4):415-2321188334Anticancer Res. 2011 Feb;31(2):379-8521378315Curr Med Chem. 2011;18(7):1079-8421254970Antioxid Redox Signal. 2011 Apr 15;14(8):1387-40120874257Mol Cancer Ther. 2011 Sep;10(9):1698-70821700832Mol Biol Cell. 2011 Oct;22(20):3887-90121865600Biochemistry. 2011 Dec 6;50(48):10540-922032234BMC Gastroenterol. 2012;12:2022380754Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463Free Radic Biol Med. 2012 Jul 15;53(2):237-4822580151Biochemistry. 2011 Jan 11;50(1):82-9221117647Mol Biol Cell. 2012 Oct;23(20):4079-9622918947Hepatology. 2001 Dec;34(6):1158-6311732005BenzoquinonespharmacologyCarcinoma, HepatocellulargeneticsmetabolismCell Line, TumorDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismFatty AcidsmetabolismGene ExpressionGene Expression Regulation, Neoplasticdrug effectsHep G2 CellsHumansInterleukin-8biosynthesisgeneticsLiver NeoplasmsgeneticsmetabolismNF-kappa BmetabolismOxidation-Reductiondrug effectsPromoter Regions, GeneticPropionatespharmacologyTranscriptional Activationdrug effectsTumor Necrosis Factor-alphapharmacology
2013031120130624201382360201382460201492460epublish2396713410.1371/journal.pone.0070909PONE-D-13-10298PMC3744539
239590142014100220171116
0717-62874622013Biological researchBiol. Res.DNA Repair Genes XRCC1, XRCC3, XPD, and OGG1 Polymorphisms among the Central Region Population of Saudi Arabia.161-710.4067/S0716-97602013000200007S0716-97602013000200007DNA repair is one of the central defense mechanisms against mutagenic exposures. Inherited SNPs of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. Saudi Arabia harbors enormous genetic and cultural diversity. In the present study we aimed to determine the genotype and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 386 healthy individuals residing in the central region of Saudi Arabia and compare them with HapMap and other populations. The genotype and allele frequencies of the four DNA repair gene loci in central Saudi population showed a distinctive pattern. Furthermore, comparison of polymorphisms in these genes with other populations also showed a unique pattern for the central Saudi population. To the best of our knowledge, this is the first report that deals with these DNA repair gene polymorphisms among the central Saudi population. AlanaziMohammadMGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.PathanAkbar Ali KhanAAAjajSana AbdullaSAKhanWajahatullahWShaikJilani PJPAl TassanNadaNParineNarasimha ReddyNRengJournal ArticleResearch Support, Non-U.S. Gov't
EnglandBiol Res93082710716-97600DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10X-ray repair cross complementing protein 30XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanIMAdultAgedAllelesChi-Square DistributionDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-Binding ProteinsgeneticsFemaleGene FrequencyGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotidegeneticsSaudi ArabiaX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
2012112820130415201382160201382160201410360ppublish23959014S0716-9760201300020000710.4067/S0716-97602013000200007
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1932-6203882013PloS onePLoS ONEThe joint effect of hOGG1, APE1, and ADPRT polymorphisms and cooking oil fumes on the risk of lung adenocarcinoma in Chinese non-smoking females.e7115710.1371/journal.pone.0071157The human 8-oxoguanine DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and adenosine diphosphate ribosyl transferase (ADPRT) genes play an important role in the DNA base excision repair pathway. Single nucleotide polymorphisms (SNPs) in critical genes are suspected to be associated with the risk of lung cancer. This study aimed to identify the association between the polymorphisms of hOGG1 Ser326Cys, APE1 Asp148Glu, and ADPRT Val762Ala, and the risk of lung adenocarcinoma in the non-smoking female population, and investigated the interaction between genetic polymorphisms and environmental exposure in lung adenocarcinoma.We performed a hospital-based case-control study, including 410 lung adenocarcinoma patients and 410 cancer-free hospital control subjects who were matched for age. Each case and control was interviewed to collect information by well-trained interviewers. A total of 10 ml of venous blood was collected for genotype testing. Three polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism technique.We found that individuals who were homozygous for the variant hOGG1 326Cys/Cys showed a significantly increased risk of lung adenocarcinoma (OR = 1.54; 95% CI: 1.01-2.36; P = 0.045). When the combined effect of variant alleles was analyzed, we found an increased OR of 1.89 (95% CI: 1.24-2.88, P = 0.003) for lung adenocarcinoma individuals with more than one homozygous variant allele. In stratified analyses, we found that the OR for the gene-environment interaction between Ser/Cys and Cys/Cys genotypes of hOGG1 codon 326 and cooking oil fumes for the risk of lung adenocarcinoma was 1.37 (95% CI: 0.77-2.44; P = 0.279) and 2.79 (95% CI: 1.50-5.18; P = 0.001), respectively.The hOGG1 Ser326Cys polymorphism might be associated with the risk of lung adenocarcinoma in Chinese non-smoking females. Furthermore, there is a significant gene-environment association between cooking oil fumes and hOGG1 326 Cys/Cys genotype in lung adenocarcinoma among female non-smokers.XueXiaoxiaXThe Third Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, PR China.YinZhihuaZLuYaoYZhangHaiboHYanYingYZhaoYuxiaYLiXuelianXCuiZeshiZYuMiaoMYaoLuLZhouBaosenBengJournal ArticleResearch Support, Non-U.S. Gov't20130812
United StatesPLoS One1012850811932-62030Dietary Fats, UnsaturatedEC 2.4.2.-ADP Ribose TransferasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMNat Rev Genet. 2005 Apr;6(4):287-9815803198Anticancer Res. 2005 Jan-Feb;25(1B):537-4215816625J Natl Cancer Inst. 2005 Apr 20;97(8):567-7615840879Cell Mol Life Sci. 2005 Apr;62(7-8):769-8315868402Chest. 2005 Jul;128(1):370-8116002959Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Carcinogenesis. 2006 Mar;27(3):560-716195237Carcinogenesis. 2006 May;27(5):997-100716308313Gastroenterology. 2006 Aug;131(2):420-716890595Lung Cancer. 2006 Dec;54(3):267-8316982113Lung Cancer. 2006 Dec;54(3):285-9217034901Lung Cancer. 2007 Jan;55(1):15-2317084482Mutat Res. 2007 Jul 28;631(2):101-1017531525Mol Aspects Med. 2007 Jun-Aug;28(3-4):258-7517628657Environ Mol Mutagen. 2008 May;49(4):265-7518338377Cancer Epidemiol Biomarkers Prev. 2008 Jul;17(7):1739-4518628426Lung Cancer. 2008 Nov;62(2):145-5118407370Carcinogenesis. 2009 Jan;30(1):78-8719029194Cell Mol Life Sci. 2009 Mar;66(6):981-9319153658Am J Epidemiol. 2009 Sep 15;170(6):695-70219671832J Exp Clin Cancer Res. 2009;28:15320003391Zhongguo Fei Ai Za Zhi. 2010 May;13(5):488-9320677647Anticancer Res. 2010 Oct;30(10):4141-521036733Breast Cancer Res Treat. 2011 Jan;125(2):479-8720549339Int J Cancer. 2010 Dec 15;127(12):2893-91721351269Carcinogenesis. 2011 Mar;32(3):336-4221148629Asian Pac J Cancer Prev. 2011;12(4):1067-7221790253Mutat Res. 2012 Mar 1;731(1-2):1-1322155132Curr Mol Pharmacol. 2012 Jan;5(1):115-2422122468Carcinogenesis. 2013 Apr;34(4):936-4223275154Nucleic Acids Res. 2013 Aug;41(15):7332-4323761438Am J Epidemiol. 2000 Jan 15;151(2):140-710645816Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):669-7410744126Arch Biochem Biophys. 2000 May 1;377(1):1-810775435Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Int J Cancer. 2000 Dec 15;88(6):932-711093817Science. 2001 Feb 16;291(5507):1284-911181991Antioxid Redox Signal. 2001 Aug;3(4):597-60911554447Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502Int J Cancer. 2002 Jun 1;99(4):624-711992556Science. 2002 Jul 12;297(5579):259-6312114629Cancer Epidemiol Biomarkers Prev. 2002 Aug;11(8):730-812163326J Epidemiol. 2002 May;12(3):258-6512164330Cancer Lett. 2003 Mar 10;191(2):171-812618330J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2003 May;21(1):1-2812826030Cancer Epidemiol Biomarkers Prev. 2003 Aug;12(8):689-9812917198Cancer Res. 2003 Aug 15;63(16):4899-90212941813Cancer Epidemiol Biomarkers Prev. 2003 Sep;12(9):947-914504211Biochem Biophys Res Commun. 2003 Oct 17;310(2):522-814521941Mutat Res. 2003 Oct 29;531(1-2):157-6314637252Pharmacogenetics. 2004 Feb;14(2):103-915077011Genomics. 2004 Jun;83(6):970-915177551Carcinogenesis. 2004 Aug;25(8):1395-40115044328Cancer Res. 2004 Sep 1;64(17):6344-815342424Int J Cancer. 1987 Nov 15;40(5):604-92824385J Natl Cancer Inst. 1996 Feb 21;88(3-4):183-928632492Mol Gen Genet. 1997 Mar 26;254(2):171-89108279Int J Epidemiol. 1997 Feb;26(1):24-319126500Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-69560228Oncogene. 1998 Jun 25;16(25):3219-259681819Carcinogenesis. 2004 Nov;25(11):2177-8115284179Carcinogenesis. 2004 Dec;25(12):2433-4115333465Cancer Res. 2005 Feb 1;65(3):722-615705867Mol Carcinog. 2005 Mar;42(3):127-4115584022Int J Cancer. 2005 May 1;114(5):730-715609317ADP Ribose TransferasesgeneticsAdenocarcinomaetiologygeneticsAir Pollution, Indooradverse effectsCase-Control StudiesDNA GlycosylasesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDietary Fats, Unsaturatedadverse effectsFemaleGene-Environment InteractionGenotypeHumansLung NeoplasmsetiologygeneticsMiddle AgedOdds RatioPolymorphism, GeneticPolymorphism, Single NucleotideRisk
201305242013062620138176020138216020143760epublish2395109910.1371/journal.pone.0071157PONE-D-13-21566PMC3741325
239228452014032520161019
1932-6203872013PloS onePLoS ONEIdentification and quantification of DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in human cells by liquid chromatography/isotope-dilution tandem mass spectrometry.e6989410.1371/journal.pone.0069894Unless repaired, DNA damage can drive mutagenesis or cell death. DNA repair proteins may therefore be used as biomarkers in disease etiology or therapeutic response prediction. Thus, the accurate determination of DNA repair protein expression and genotype is of fundamental importance. Among DNA repair proteins involved in base excision repair, apurinic/apyrimidinic endonuclease 1 (APE1) is the major endonuclease in mammals and plays important roles in transcriptional regulation and modulating stress responses. Here, we present a novel approach involving LC-MS/MS with isotope-dilution to positively identify and accurately quantify APE1 in human cells and mouse tissue. A completely (15)N-labeled full-length human APE1 was produced and used as an internal standard. Fourteen tryptic peptides of both human APE1 (hAPE1) and (15)N-labeled hAPE1 were identified following trypsin digestion. These peptides matched the theoretical peptides expected from trypsin digestion and provided a statistically significant protein score that would unequivocally identify hAPE1. Using the developed methodology, APE1 was positively identified and quantified in nuclear and cytoplasmic extracts of multiple human cell lines and mouse liver using selected-reaction monitoring of typical mass transitions of the tryptic peptides. We also show that the methodology can be applied to the identification of hAPE1 variants found in the human population. The results describe a novel approach for the accurate measurement of wild-type and variant forms of hAPE1 in vivo, and ultimately for defining the role of this protein in disease development and treatment responses. KirkaliGüldalGBiomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, Maryland, United States of America.JarugaPawelPReddyPrasad TPTTonaAlessandroANelsonBryant CBCLiMengxiaMWilsonDavid MDM3rdDizdarogluMiralMengIntramural NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Intramural20130729
United StatesPLoS One1012850811932-6203EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMProc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128J Biol Chem. 1995 Jul 7;270(27):16002-77608159Carcinogenesis. 1998 Mar;19(3):525-79525290Nucleic Acids Res. 1998 Jun 1;26(11):2771-89592167Neurology. 1999 Jun 10;52(9):1899-90110371543DNA Repair (Amst). 2005 Mar 2;4(3):367-7915661660Mol Cell. 2005 Feb 4;17(3):463-7015694346Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325DNA Repair (Amst). 2005 Dec 8;4(12):1442-916199212Carcinogenesis. 2006 Sep;27(9):1894-90116621887Neoplasma. 2008;55(4):330-718505345Mol Syst Biol. 2008;4:22218854821Cell Mol Life Sci. 2009 Mar;66(6):981-9319153658DNA Repair (Amst). 2009 Nov 2;8(11):1273-8219726241Mutagenesis. 2009 Nov;24(6):507-1219762350Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Mol Cell Biol. 2010 Jan;30(2):366-7119901076Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3204-920133634Immunol Rev. 2010 May;235(1):93-10420536557Antioxid Redox Signal. 2011 Jun 15;14(12):2491-50720649466Mutat Res. 2011 Jun 3;711(1-2):100-1221167187J Proteome Res. 2011 Aug 5;10(8):3802-1321619077Mol Cell Biochem. 2012 Mar;362(1-2):195-20122042551Cell Mol Life Sci. 2012 Mar;69(5):727-4021952828Curr Med Chem. 2012;19(23):3922-3622788768Cancer Lett. 2012 Dec 31;327(1-2):26-4722293091J Proteome Res. 2013 Feb 1;12(2):1049-6123268652Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Cancer Res. 2001 Jul 15;61(14):5552-711454706Mutat Res. 2001 Jan;432(3-4):53-911465542Mutat Res. 2001 May 10;485(4):283-30711585362Nature. 2002 Feb 7;415(6872):655-911832948Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1054-6412376507Nucleic Acids Res. 2004;32(1):73-8114704345Cell Mol Life Sci. 2004 Jun;61(12):1455-7415197470Mol Cell Biol. 2004 Sep;24(18):8145-5315340075Anal Biochem. 1976 May 7;72:248-54942051Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-41722334EMBO J. 1992 Feb;11(2):653-651537340Mol Cell Biol. 1993 Sep;13(9):5370-68355688Nucleic Acids Res. 1994 Nov 25;22(23):4884-97800476Neuroreport. 1998 Jan 26;9(2):239-429507962AnimalsChromatography, LiquidmethodsDNA RepairphysiologyDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismLivermetabolismMiceTandem Mass Spectrometrymethods
20130503201306132013886020138860201432660epublish2392284510.1371/journal.pone.0069894PONE-D-13-18080PMC3726725
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1945-025717102013OctGenetic testing and molecular biomarkersGenet Test Mol BiomarkersThe OGG1 Ser326Cys polymorphism and the risk of esophageal cancer: a meta-analysis.780-510.1089/gtmb.2013.0224The oxoguanine DNA glycosylase (OGG1) Ser326Cys polymorphism has been implicated in susceptibility to esophageal cancer. Several studies investigated the association of this polymorphism with esophageal cancer in different populations. However, the results were contradictory. A meta-analysis was conducted to assess the association between the OGG1 Ser326Cys polymorphism and esophageal cancer susceptibility.Databases, including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A random-effects model was used.Twelve studies involving 2363 cases and 3621 controls were included. Overall, a significant association between the OGG1 Ser326Cys polymorphism and esophageal cancer was observed for Cys/Cys versus Cys/Ser+Ser/Ser (OR=1.40; 95% CI 1.12-1.74; p=0.003; Pheterogeneity=0.18). In the subgroup analysis by ethnicity, a significant association was found among Asians (OR=1.51; 95% CI 1.15-1.96; p=0.002; Pheterogeneity=0.22), but not among Caucasians (OR=1.21; 95% CI 0.81-1.81; p=0.35; Pheterogeneity=0.21). In the subgroup analysis by pathologic type, we found that the Cys/Cys genotype was associated with increased esophageal squamous cell carcinoma risk (OR=1.86; 95% CI 1.36-2.53; p<0.0001; Pheterogeneity=0.73).This meta-analysis suggested that the OGG1 Ser326Cys polymorphism was a risk factor of esophageal cancer.WangZhanZ1 Department of Oncology, Shanghai Changzheng Hospital, Second Military Medical University , Shanghai, China .GanLuLNieWeiWGengYanYengJournal ArticleMeta-AnalysisReview20130803
United StatesGenet Test Mol Biomarkers1014942101945-0257EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAmino Acid SubstitutionDNA GlycosylasesgeneticsEsophageal NeoplasmsenzymologygeneticsFemaleHumansMaleModels, GeneticMutation, MissensePolymorphism, GeneticPubMedRisk Factors
2013866020138660201442060ppublish2390955710.1089/gtmb.2013.0224
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1879-12201382013NovThe Journal of steroid biochemistry and molecular biologyJ. Steroid Biochem. Mol. Biol.17β-estradiol increases expression of the oxidative stress response and DNA repair protein apurinic endonuclease (Ape1) in the cerebral cortex of female mice following hypoxia.410-2010.1016/j.jsbmb.2013.07.007S0960-0760(13)00136-2While it is well established that 17β-estradiol (E2) protects the rodent brain from ischemia-induced damage, it has been unclear how this neuroprotective effect is mediated. Interestingly, convincing evidence has also demonstrated that maintaining or increasing the expression of the oxidative stress response and DNA repair protein apurinic endonuclease 1 (Ape1) is instrumental in reducing ischemia-induced damage in the brain. Since E2 increases expression of the oxidative stress response proteins Cu/Zn superoxide dismutase and thioredoxin in the brain, we hypothesized that E2 may also increase Ape1 expression and that this E2-induced expression of Ape1 may help to mediate the neuroprotective effects of E2 in the brain. To test this hypothesis, we utilized three model systems including primary cortical neurons, brain slice cultures, and whole animals. Although estrogen receptor α and Ape1 were expressed in primary cortical neurons, E2 did not alter Ape1 expression in these cells. However, immunofluorescent staining and quantitative Western blot analysis demonstrated that estrogen receptor α and Ape1 were expressed in the nuclei of cortical neurons in brain slice cultures and that E2 increased Ape1 expression in the cerebral cortex of these cultures. Furthermore, Ape1 expression was increased and oxidative DNA damage was decreased in the cerebral cortices of ovariectomized female C57Bl/6J mice that had been treated with E2 and exposed to hypoxia. Taken together, our studies demonstrate that the neuronal microenvironment may be required for increased Ape1 expression and that E2 enhances expression of Ape1 and reduces oxidative DNA damage, which may in turn help to reduce ischemia-induced damage in the cerebral cortex and mediate the neuroprotective effects of E2. Published by Elsevier Ltd.DietrichAlicia KAKDepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.HumphreysGwendolyn IGINardulliAnn MAMengR01 DK053884DKNIDDK NIH HHSUnited StatesT32 ES007326ESNIEHS NIH HHSUnited StatesR01DK 053884DKNIDDK NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20130729
EnglandJ Steroid Biochem Mol Biol90154830960-07604TI98Z838EEstradiolEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMPsychoneuroendocrinology. 1999 Aug;24(6):657-7710399774J Neurosci. 1999 Aug 1;19(15):6385-9310414967J Neurochem. 2005 Apr;93(2):351-815816858Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Cerebrovasc Dis. 2006;21 Suppl 2:48-5316651814Endocrinology. 2006 Jun;147(6):3076-8416527848Science. 2006 Jun 30;312(5782):1882-316809515Neuroscience. 2006 Sep 15;141(4):1721-3016777351Mutat Res. 2007 Jan 3;614(1-2):24-3616879837J Comp Neurol. 2007 Feb 20;500(6):1064-7517183542DNA Repair (Amst). 2007 Mar 1;6(3):317-2817126083JAMA. 2007 Apr 4;297(13):1465-7717405972Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6013-817389368Steroids. 2007 May;72(5):381-40517379265Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12365-7017640893Cell Res. 2008 Jan;18(1):27-4718166975Mol Endocrinol. 2008 May;22(5):1113-2418258688J Vis Exp. 2007;(10):56218989405Brain Res. 2009 Jun 5;1274:1-1019374886Front Neuroendocrinol. 2009 Jul;30(2):201-1119401209Glia. 2010 Jan 1;58(1):93-10219533603J Mol Endocrinol. 2009 Dec;43(6):251-6119620238Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3204-920133634J Cereb Blood Flow Metab. 2010 May;30(5):935-4220010956Biochim Biophys Acta. 2010 Oct;1800(10):1106-1219818384Mol Cell Neurosci. 2010 Nov;45(3):267-7620637286Endocrinology. 2010 Oct;151(10):4916-2520685874BMC Genomics. 2011;12:49921988864Drug Discov Today. 2005 Jul 15;10(14):993-100016023058J Cereb Blood Flow Metab. 2006 Feb;26(2):181-9816001017BMC Neurosci. 2006;7:2416533397Exp Biol Med (Maywood). 2006 May;231(5):514-2116636299J Steroid Biochem Mol Biol. 2011 Nov;127(3-5):382-921704159Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20265-7022114196Climacteric. 2012 Jun;15(3):217-2822612607EMBO J. 2012 May 30;31(11):2448-6022562152Arteriosclerosis. 1990 Nov-Dec;10(6):1051-72244855Prev Med. 1991 Jan;20(1):47-631826173Cell. 1991 Aug 23;66(4):685-961652370J Neurosci Methods. 1991 Apr;37(2):173-821715499Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11158-621763030Endocrinology. 1992 Feb;130(2):805-101733727EMBO J. 1992 Feb;11(2):653-651537340Cancer Res. 1994 Jan 1;54(1):12-58261431J Biol Chem. 1994 Dec 9;269(49):31234-427983067Stroke. 1999 Nov;30(11):2408-1510548678Stroke. 2000 Jan;31(1):155-6010625732J Biol Chem. 2000 Feb 18;275(7):4618-2710671489Nat Struct Biol. 2000 Mar;7(3):176-810700268Am J Pathol. 2000 Mar;156(3):965-7610702412J Neurosci. 2000 Jul 15;20(14):5329-3810884317Mutat Res. 2000 Oct 16;461(2):83-10811018583Prog Neurobiol. 2001 Jan;63(1):29-6011040417Nucleic Acids Res. 2001 Jan 15;29(2):430-811139613J Cereb Blood Flow Metab. 2001 Jan;21(1):2-1411149664Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1952-711172057Nucleic Acids Res. 2001 Mar 15;29(6):1285-9211238994Mutat Res. 2001 Jun 5;486(1):31-4011356334J Neurocytol. 2000 May-Jun;29(5-6):401-1011424956Brain Res Brain Res Rev. 2001 Nov;37(1-3):313-911744096Brain. 2002 Nov;125(Pt 11):2549-5712390979J Biol Chem. 2002 Nov 15;277(46):44548-5612213807J Neurosci. 2003 Jan 15;23(2):384-9112533598Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2842-712604781FASEB J. 2003 May;17(8):947-812626428Endocrine. 2003 Jun;21(1):11-512777698Eur J Neurosci. 2003 Jul;18(1):85-9412859340FASEB J. 2003 Aug;17(11):1541-312824304Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9614-912878732J Cereb Blood Flow Metab. 2003 Nov;23(11):1324-3914600440Sci Aging Knowledge Environ. 2001 Oct 3;2001(1):oa514602949J Neurosci. 2003 Dec 10;23(36):11420-614673006Antioxid Redox Signal. 2004 Feb;6(1):81-714713338Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4130-515024130Brain Res. 2004 Jun 4;1010(1-2):22-3415126114Dev Cell. 2004 Aug;7(2):205-1615296717Biol Reprod. 1981 May;24(4):820-307018601Circulation. 1987 Jun;75(6):1102-93568321BMJ. 1988 Aug 20-27;297(6647):519-223139181Annu Rev Biochem. 1988;57:29-673052275Maturitas. 1990 Sep;12(3):259-852145495Mol Cell Biol. 1995 Oct;15(10):5363-87565686Mol Endocrinol. 1995 Nov;9(11):1441-548584021Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Genes Dev. 1997 Mar 1;11(5):558-709119221Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-89108029J Cereb Blood Flow Metab. 1998 Nov;18(11):1253-89809515Neurosurgery. 1998 Dec;43(6):1382-96; discussion 1396-79848853Neuroreport. 1998 Dec 21;9(18):4015-89926839Stroke. 1999 Feb;30(2):441-8; discussion 4499933285Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4131-610097175J Cereb Blood Flow Metab. 1999 May;19(5):495-50110326716AnimalsCerebral Cortexdrug effectsmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismEstradiolpharmacologyFemaleHypoxiaMiceMice, Inbred C57BLOxidation-Reductiondrug effectsOxidative Stressdrug effects17β-estradiol4′,6-diamidino-2-phenylindole8-OHG8-hydroxydeoxyguanosineApe1Apurinic endonuclease 1DAPIE(2)ERαERβEstrogenEstrogen receptorHypoxiaNeuroprotectionROSRPL7Reactive oxygen speciesapurinic endonuclease 1estrogen receptor αestrogen receptor βreactive oxygen speciesribosomal protein L7
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1090-2422319192013Nov15Experimental cell researchExp. Cell Res.8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish.2954-6310.1016/j.yexcr.2013.07.012S0014-4827(13)00301-7Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes and nkx2.5(+) cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits.© 2013 Elsevier Inc. All rights reserved.YanLifengLState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.ZhouYongYYuShanheSJiGuixiangGWangLeiLLiuWeiWGuAihuaAengJournal ArticleResearch Support, Non-U.S. Gov't20130724
United StatesExp Cell Res03732260014-482708-oxoguanine DNA glycosylase 1, zebrafish0Multifunctional Enzymes0Transcription Factors0Zebrafish ProteinsEC 3.2.2.-DNA GlycosylasesEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsDNA DamagephysiologyDNA GlycosylasesmetabolismDNA RepairphysiologyDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismEmbryonic Stem CellsmetabolismHeartembryologyMesodermmetabolismMultifunctional EnzymesmetabolismMyocardiumcytologymetabolismPhenotypeTranscription FactorsmetabolismZebrafishembryologygeneticsmetabolismZebrafish ProteinsmetabolismCardiac progenitor cellsDNA repairHeart developmentOgg1Oxidative DNA damage
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1557-77162042014Feb01Antioxidants & redox signalingAntioxid. Redox Signal.Emerging roles of the nucleolus in regulating the DNA damage response: the noncanonical DNA repair enzyme APE1/Ref-1 as a paradigmatical example.621-3910.1089/ars.2013.5491An emerging concept in DNA repair mechanisms is the evidence that some key enzymes, besides their role in the maintenance of genome stability, display also unexpected noncanonical functions associated with RNA metabolism in specific subcellular districts (e.g., nucleoli). During the evolution of these key enzymes, the acquisition of unfolded domains significantly amplified the possibility to interact with different partners and substrates, possibly explaining their phylogenetic gain of functions.After nucleolar stress or DNA damage, many DNA repair proteins can freely relocalize from nucleoli to the nucleoplasm. This process may represent a surveillance mechanism to monitor the synthesis and correct assembly of ribosomal units affecting cell cycle progression or inducing p53-mediated apoptosis or senescence.A paradigm for this kind of regulation is represented by some enzymes of the DNA base excision repair (BER) pathway, such as apurinic/apyrimidinic endonuclease 1 (APE1). In this review, the role of the nucleolus and the noncanonical functions of the APE1 protein are discussed in light of their possible implications in human pathologies.A productive cross-talk between DNA repair enzymes and proteins involved in RNA metabolism seems reasonable as the nucleolus is emerging as a dynamic functional hub that coordinates cell growth arrest and DNA repair mechanisms. These findings will drive further analyses on other BER proteins and might imply that nucleic acid processing enzymes are more versatile than originally thought having evolved DNA-targeted functions after a previous life in the early RNA world.AntonialiGiuliaGDepartment of Medical and Biological Sciences, University of Udine , Udine, Italy .LirussiLisaLPolettoMattiaMTellGianlucaGengJournal ArticleResearch Support, Non-U.S. Gov'tReview20130921
United StatesAntioxid Redox Signal1008888991523-08640Nuclear Proteins117896-08-9nucleophosminEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 6.5.1.-DNA Repair EnzymesIMJ Biol Chem. 2011 Feb 25;286(8):6006-1621169365Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12586-909770529EMBO J. 2001 Feb 15;20(4):914-2311179235Genes Cancer. 2010 Jul 1;1(7):681-68921113400Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1235-4011805286EMBO J. 2003 Nov 17;22(22):6068-7714609953Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Mol Cell Biol. 2002 Aug;22(16):6014-2212138209Mol Cell Biol. 2002 Nov;22(22):8088-9912391174Expert Opin Drug Discov. 2012 Jun;7(6):475-8822559227Biochemistry. 2000 Dec 19;39(50):15493-911112535Cancer Sci. 2012 Apr;103(4):632-722320853Mol Biol Cell. 2003 Dec;14(12):4826-3414638871Nat Cell Biol. 2000 Jun;2(6):E107-1210854340Nature. 2012 Aug 9;488(7410):231-522722852DNA Repair (Amst). 2008 Feb 1;7(2):177-8617974506RNA. 2010 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Aug 20;93(17):8919-238799128AnimalsCell NucleolusenzymologyphysiologyDNA DamageDNA RepairDNA Repair EnzymesphysiologyDNA-(Apurinic or Apyrimidinic Site) LyasechemistryphysiologyHumansMolecular Targeted TherapyNeoplasmsdrug therapyenzymologyNuclear ProteinsmetabolismProtein Structure, Tertiary
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1932-6203872013PloS onePLoS ONEContributory role of five common polymorphisms of RAGE and APE1 genes in lung cancer among Han Chinese.e6901810.1371/journal.pone.0069018Lung cancer is the leading cause of cancer mortality in China. Given the ubiquitous nature of gene-to-gene interaction in lung carcinogenesis, we sought to evaluate five common polymorphisms from advanced glycosylation end product-specific receptor (RAGE) and apurinic/apyrimidinic endonuclease 1 (APE1) genes in association with lung cancer among Han Chinese.819 patients with lung cancer and 803 cancer-free controls were recruited from Qiqihar city. Genotypes of five examined polymorphisms (RAGE gene: rs1800625, rs1800624, rs2070600; APE1 gene: rs1760944, rs1130409) were determined by ligase detection reaction method. Data were analyzed by R software and multifactor dimensionality reduction (MDR). Hardy-Weinberg equilibrium was satisfied for all five polymorphisms. Overall differences in the genotype and allele distributions were significant for rs1800625 (Pgenotype<0.0005; Pallele<0.0005), rs2070600 (Pgenotype = 0.005; Pallele = 0.004) and rs1130409 (Pgenotype = 0.009; Pallele = 0.004) polymorphisms. Haplotype C-A-A (alleles in order of rs1800625, rs1800624 and rs2070600) of RAGE gene was overrepresented in patients, and conferred a 2.1-fold increased risk of lung cancer (95% confidence interval: 1.52-2.91), independent of confounding factors. Further application of MDR method to five examined polymorphisms identified the overall best interaction model including rs2070600 and rs1130409 polymorphisms. This model had a maximal testing accuracy of 64.63% and a maximal cross-validation consistency of 9 out of 10 at the significant level of 0.006.Our findings demonstrated a potential interactive contribution of RAGE and APE1 genes to the pathogenesis of lung cancer among Han Chinese. Further studies are warranted to confirm or refute these findings.PanHongmingHSchool of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning, China.NiuWenquanWHeLanLWangBinBCaoJunJZhaoFengFLiuYingYLiShenSWuHuijianHengJournal ArticleResearch Support, Non-U.S. Gov't20130711
United StatesPLoS One1012850811932-62030Receptor for Advanced Glycation End ProductsEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMNat Rev Genet. 2001 Feb;2(2):91-911253062Lung Cancer. 2001 Apr;32(1):7-1211282423Bioinformatics. 2003 Feb 12;19(3):376-8212584123Hum Hered. 2003;55(4):179-9014566096Genes Cells. 2004 Feb;9(2):165-7415009093JAMA. 2004 Apr 7;291(13):1642-315069055Pharmacogenomics. 2005 Dec;6(8):823-3416296945Am J Respir Cell Mol Biol. 2006 Jan;34(1):83-9116166741Genet Epidemiol. 2009 Jan;33(1):87-9418671250Am J Hum Genet. 2009 Sep;85(3):309-2019733727FASEB J. 2009 Oct;23(10):3459-6919541747Neoplasma. 2010;57(1):55-6119895173J Biomed Biotechnol. 2010;2010:91710820145712Cancer Sci. 2010 Jan;101(1):180-719860842Genet Test Mol Biomarkers. 2010 Jun;14(3):355-6120578941Hum Hered. 2010;70(3):219-2520924193Adv Genet. 2010;72:101-1621029850Adv Cancer Res. 2010;109:51-7221070914Genet Epidemiol. 2011 Nov;35(7):671-821818775PLoS One. 2011;6(12):e2943122206016PLoS One. 2012;7(6):e3797022701590PLoS One. 2012;7(6):e3981422761909Mol Biol Rep. 2012 Dec;39(12):11249-6223065211PLoS One. 2013;8(2):e5621323409158Cell Signal. 2013 Apr;25(4):939-5423333461Asian Continental Ancestry GroupgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleGenetic Predisposition to DiseaseHaplotypesHumansLung NeoplasmsgeneticsMaleMiddle AgedPolymorphism, GeneticReceptor for Advanced Glycation End Productsgenetics
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1932-6203872013PloS onePLoS ONEDual regulatory roles of human AP-endonuclease (APE1/Ref-1) in CDKN1A/p21 expression.e6846710.1371/journal.pone.0068467The human AP-endonuclease (APE1/Ref-1), an essential multifunctional protein involved in repair of oxidative DNA damage as well as in transcriptional regulation, is often overexpressed in tumor cells. APE1 was earlier shown to stimulate p53's DNA binding and its transactivation function in the expression of cyclin-dependent kinase inhibitor p21 (CDKN1A) gene. Here, we show APE1's stable binding to p53 cis elements which are required for p53-mediated activation of p21 in p53-expressing wild type HCT116 cells. However, surprisingly, we observed APE1-dependent repression of p21 in isogenic p53-null HCT116 cells. Ectopic expression of p53 in the p53-null cells abrogated this repression suggesting that APE1's negative regulatory role in p21 expression is dependent on the p53 status. We then identified APE1's another binding site in p21's proximal promoter region containing cis elements for AP4, a repressor of p21. Interestingly, APE1 and AP4 showed mutual dependence for p21 repression. Moreover, ectopic p53 in p53-null cells inhibited AP4's association with APE1, their binding to the promoter and p21 repression. These results together establish APE1's role as a co-activator or co-repressor of p21 gene, dependent on p53 status. It is thus likely that APE1 overexpression and inactivation of p53, often observed in tumor cells, promote tumor cell proliferation by constitutively downregulating p21 expression. SenguptaShiladityaSDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, United States of America.MitraSankarSBhakatKishor KKKengR01 CA148941CANCI NIH HHSUnited StatesR01 CA53791CANCI NIH HHSUnited StatesR01 ES08457ESNIEHS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20130716
United StatesPLoS One1012850811932-62030Cyclin-Dependent Kinase Inhibitor p210Tumor Suppressor Protein p53EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAntioxid Redox Signal. 2009 Mar;11(3):621-3818715144Apoptosis. 2010 Feb;15(2):162-7220041303Nat Cell Biol. 2010 Jun;12(6):563-7120473298Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116EMBO J. 2001 Nov 15;20(22):6530-911707423Anticancer Res. 2002 Mar-Apr;22(2A):825-3012014658Nucleic Acids Res. 2011 Oct;39(18):8017-2821727086DNA Repair (Amst). 2008 Feb 1;7(2):177-8617974506Oncogene. 2011 Jan 27;30(4):482-9320856196Mutat Res. 2000 Oct 16;461(2):83-10811018583Expert Rev Mol Med. 2008;10:e1918590585Cell Cycle. 2009 Apr 1;8(7):982-919270520Nucleic Acids Res. 2004;32(10):3033-915175427Mol Endocrinol. 2010 Feb;24(2):391-40120032196Genes Dev. 1997 Mar 1;11(5):558-709119221Exp Cell Res. 1999 Feb 1;246(2):280-99925742Cancer Res. 2001 Jul 15;61(14):5552-711454706Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):288-9318162533Nature. 1995 Mar 23;374(6520):386-87885482Nucleic Acids Res. 2010 Jan;38(3):832-4519934257J Biol Chem. 1994 Nov 11;269(45):27855-627961715Nucleic Acids Res. 2004;32(1):73-8114704345EMBO J. 2003 Dec 1;22(23):6299-30914633989Cell. 1993 Nov 19;75(4):817-258242752Mol Cell Biol. 2008 Dec;28(23):7066-8018809583J Hypertens. 2012 May;30(5):917-2522441348Cancer Invest. 2010 Nov;28(9):885-9520919954Free Radic Res. 2008 Jan;42(1):20-918324520Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-69560228Science. 1998 Nov 20;282(5393):1497-5019822382Biotechniques. 2005 Nov;39(5):715-2516315372Cancer Res. 2008 Aug 1;68(15):6425-3418676868Cell Growth Differ. 1997 Apr;8(4):443-99101090Nat Rev Cancer. 2009 Oct;9(10):714-2319730431Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Environ Health Perspect. 1997 Jun;105 Suppl 4:931-49255583J Biol Chem. 2007 Sep 28;282(39):28474-8417686777Mol Cancer Ther. 2008 Jul;7(7):2012-2118645011Mutat Res. 1990 Sep-Nov;236(2-3):173-2011697933Anticancer Res. 1997 Sep-Oct;17(5B):3713-199427767Mol Cell Proteomics. 2009 Sep;8(9):2034-5019505873J Biol Chem. 1998 Jun 5;273(23):14435-419603956Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143J Hypertens. 2003 Feb;21(2):327-3512569263EMBO J. 1999 Oct 15;18(20):5609-2110523305Mol Cell Biol. 2009 Apr;29(7):1834-5419188445J Cell Physiol. 2009 Apr;219(1):209-1819097035PLoS One. 2012;7(5):e3709622615908Proteomics. 2009 Feb;9(4):1058-7419180539Int J Surg Pathol. 2009 Feb;17(1):16-2118480385Med Oncol. 2012 Jun;29(2):871-721336989Cancer Res. 2001 Mar 1;61(5):2220-511280790DNA Repair (Amst). 2009 Nov 2;8(11):1273-8219726241Nucleic Acids Res. 2008 Mar;36(5):1555-6618208837Mol Cell Biol. 1998 Jan;18(1):629-439418909Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Nat Rev Cancer. 2009 Jun;9(6):400-1419440234Cancer Res. 1995 Jul 1;55(13):2910-97796420Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15046-5118818310Gastroenterology. 2009 Jun;136(7):2258-6919505426Mol Cell Pharmacol. 2010 Jan 1;2(2):69-7720514355Clin Cancer Res. 2001 Apr;7(4):824-3011309329Toxicology. 2003 Nov 15;193(1-2):43-6514599767DNA Repair (Amst). 2007 Jan 4;6(1):8-1816978929Oncogene. 2009 Apr 2;28(13):1616-2519219073Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8493-77667317Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Mol Cancer Res. 2009 Jun;7(6):897-90619470598Binding SitesgeneticsCyclin-Dependent Kinase Inhibitor p21geneticsmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismHCT116 CellsHumansPromoter Regions, GeneticgeneticsProtein BindinggeneticsTumor Suppressor Protein p53geneticsmetabolism
2013012820130529201372360201372360201422060epublish2387463610.1371/journal.pone.0068467PONE-D-13-04011PMC3713036
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1873-6351592013SepFood and chemical toxicology : an international journal published for the British Industrial Biological Research AssociationFood Chem. Toxicol.Wogonin attenuates etoposide-induced oxidative DNA damage and apoptosis via suppression of oxidative DNA stress and modulation of OGG1 expression.724-3010.1016/j.fct.2013.07.022S0278-6915(13)00477-8Damage to DNA can lead to many different acute and chronic pathophysiological conditions, ranging from cancer to endothelial damage. The current study has been initiated to determine whether the flavonoid wogonin can attenuate etoposide-induced oxidative DNA damage and apoptosis in mouse bone marrow cells. We found that oral administration of wogonin before etoposide injection significantly attenuates etoposide-induced oxidative DNA damage and apoptosis in a dose dependent manner. Etoposide induced a significant down-regulation of mRNA expression of the OGG1 repair gene and marked biochemical alterations characteristic of oxidative DNA stress, including increased 8-OHdG, enhanced lipid peroxidation and reduction in reduced glutathione. Prior administration of wogonin ahead of etoposide challenge restored these altered parameters. Importantly, wogonin had no antagonizing effect on etoposide-induce topoisomerase-II inhibition. Conclusively, our study indicates that wogonin has a protective role in the abatement of etoposide-induced oxidative DNA damage and apoptosis in the bone marrow cells of mice via suppression of oxidative DNA stress and enhancing DNA repair through modulation of OGG1 repair gene expression. Therefore, wogonin can be a promising chemoprotective agent and might be useful to avert secondary leukemia and other drug-related cancers in cured cancer patients and medical personnel exposing to the potent carcinogen etoposide. Copyright © 2013 Elsevier Ltd. All rights reserved.AttiaSabry MSMDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. attiasm@ksu.edu.saAhmadSheikh FayazSFHarisaGamaleldin IGIMansourAhmed MAMEl SayedEl Sayed Mel SMBakheetSaleh ASAengJournal ArticleResearch Support, Non-U.S. Gov't20130717
EnglandFood Chem Toxicol82074830278-69150Anticarcinogenic Agents0Antioxidants0Flavanones0RNA, Messenger0Topoisomerase II Inhibitors6PLQ3CP4P3EtoposideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mousePOK93PO28WwogoninIMAnimalsAnticarcinogenic Agentsadministration & dosageadverse effectstherapeutic useAntioxidantsadministration & dosageadverse effectstherapeutic useApoptosisdrug effectsBone Marrow Cellsdrug effectsmetabolismpathologyDNA Damagedrug effectsDNA GlycosylasesbiosynthesisgeneticsmetabolismDose-Response Relationship, DrugEtoposideadverse effectsantagonists & inhibitorsFlavanonesadministration & dosageadverse effectstherapeutic useGene Expression Regulationdrug effectsLeukemiachemically inducedmetabolismpathologyprevention & controlMaleMiceMicronucleus TestsMutagenicity TestsOxidative Stressdrug effectsRNA, MessengermetabolismRandom AllocationTopoisomerase II Inhibitorsadverse effectschemistryApoptosisDNA damage/repairOxidative DNA stressSecondary tumors
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238719472013121120130927
1097-686820942013OctAmerican journal of obstetrics and gynecologyAm. J. Obstet. Gynecol.Genetic variant in APE1 gene promoter contributes to cervical cancer risk.360.e1-710.1016/j.ajog.2013.07.010S0002-9378(13)00742-4Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway, which plays an important role in repairing DNA damage caused by oxidation and alkylation. However, the exact mechanism of APE1 associated with cervical cancer risk is still unknown. In this study, we explored whether the APE1 -656T>G polymorphism contributed to the risk of cervical cancer.In the hospital-based case-control study, 306 cervical cancer cases and 306 cancer-free controls were genotyped for the APE1 -656T>G polymorphism using the polymerase chain reaction restriction fragment length polymorphism method. Luciferase reporter assay and electrophoretic mobility shift assay were used to evaluate the APE1 transcriptional activity and the binding ability of transcriptional factors to the APE1 promoter, respectively.Logistic regression analysis showed that individuals with the APE1 -656 TG/GG genotypes had a significantly reduced risk of cervical cancer compared with the TT genotype (adjusted odds ratio, 0.61; 95% confidence interval, 0.42-0.89). The luciferase assays in 3 cell lines showed that the APE1 -656T>G substitution can increase the expression of APE1, which was consistent with the finding of association study. Electrophoretic mobility shift assay further indicated that the APE1 -656T>G polymorphism enhanced the binding affinity of transcriptional factors to the promoter region.These findings suggested that the APE1 -656T>G polymorphism was associated with cervical cancer risk in a Chinese population by affecting the binding affinity of transcriptional factors to the promoter, leading to an increased expression level of APE1.Copyright © 2013 Mosby, Inc. All rights reserved.WangMiaomiaoMInstitute of Toxicology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention, and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.ChuHaiyanHWangShizhiSWangMeilinMWangWeiWHanSupingSZhangZhengdongZengJournal ArticleResearch Support, Non-U.S. Gov't20130716
United StatesAm J Obstet Gynecol03704760002-9378EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseAIMIMAdenocarcinomageneticsAdultAsian Continental Ancestry GroupgeneticsCarcinoma, AdenosquamousgeneticsCarcinoma, Squamous CellgeneticsCase-Control StudiesDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleGenetic Predisposition to DiseaseHumansMiddle AgedPolymorphism, Single NucleotidePromoter Regions, GeneticgeneticsUterine Cervical NeoplasmsgeneticsApurinic/apyrimidinic endonuclease 1base excision repair pathwaycervical cancerfunctional polymorphismmolecular epidemiology
2012101120130221201307102013723602013723602013121660ppublish23871947S0002-9378(13)00742-410.1016/j.ajog.2013.07.010
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2041-488942013Jul18Cell death & diseaseCell Death DisInteraction of Sirt3 with OGG1 contributes to repair of mitochondrial DNA and protects from apoptotic cell death under oxidative stress.e73110.1038/cddis.2013.254Sirtuin 3 (Sirt3), a major mitochondrial NAD(+)-dependent deacetylase, targets various mitochondrial proteins for lysine deacetylation and regulates important cellular functions such as energy metabolism, aging, and stress response. In this study, we identified the human 8-oxoguanine-DNA glycosylase 1 (OGG1), a DNA repair enzyme that excises 7,8-dihydro-8-oxoguanine (8-oxoG) from damaged genome, as a new target protein for Sirt3. We found that Sirt3 physically associated with OGG1 and deacetylated this DNA glycosylase and that deacetylation by Sirt3 prevented the degradation of the OGG1 protein and controlled its incision activity. We further showed that regulation of the acetylation and turnover of OGG1 by Sirt3 played a critical role in repairing mitochondrial DNA (mtDNA) damage, protecting mitochondrial integrity, and preventing apoptotic cell death under oxidative stress. We observed that following ionizing radiation, human tumor cells with silencing of Sirt3 expression exhibited deteriorated oxidative damage of mtDNA, as measured by the accumulation of 8-oxoG and 4977 common deletion, and showed more severe mitochondrial dysfunction and underwent greater apoptosis in comparison with the cells without silencing of Sirt3 expression. The results reported here not only reveal a new function and mechanism for Sirt3 in defending the mitochondrial genome against oxidative damage and protecting from the genotoxic stress-induced apoptotic cell death but also provide evidence supporting a new mtDNA repair pathway. ChengYYDepartment of Pharmacology, Milton S Hershey Medical Center, Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033-0850, USA. yxc24@psu.eduRenXXGowdaA S PASShanYYZhangLLYuanY-SYSPatelRRWuHHHuber-KeenerKKYangJ WJWLiuDDSprattT ETEYangJ-MJMengR01 CA135038CANCI NIH HHSUnited StatesR01CA135038CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.20130718
EnglandCell Death Dis1015240920DNA, MitochondrialEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.4.22.-CalpainEC 3.5.1.-SIRT3 protein, humanEC 3.5.1.-Sirtuin 3IMCell Metab. 2010 Dec 1;12(6):662-721109198J Cell Sci. 2010 Dec 1;123(Pt 23):4117-2721062897Mol Cell. 2010 Dec 22;40(6):893-90421172655BMC Med Genet. 2011;12:821232124Cancer Cell. 2011 Mar 8;19(3):416-2821397863Cancer. 2011 Apr 15;117(8):1670-821472714EMBO Rep. 2011 Jun;12(6):534-4121566644Biochim Biophys Acta. 2011 Aug;1816(1):80-821586315Oncogene. 2011 Jun 30;30(26):2986-9621358671EMBO Rep. 2011 Aug;12(8):840-621720390Cell Death Differ. 2012 Nov;19(11):1815-2522595756Cancer Res. 2012 May 15;72(10):2468-7222589271J Biol Chem. 2012 Apr 20;287(17):14078-8622416140Biochem Biophys Res Commun. 2013 Jan 11;430(2):798-80323201401Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4156-6110725358Trends Biochem Sci. 2000 Nov;25(11):555-6011084368J Biol Chem. 2000 Dec 1;275(48):37518-2310982789Cancer Res. 2001 Jul 15;61(14):5378-8111454679Gene. 2002 Mar 6;286(1):127-3411943468Oncogene. 2002 Aug 8;21(34):5204-1212149642Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13653-812374852J Biol Chem. 2003 May 23;278(21):19541-812644468FEBS Lett. 2004 Jul 30;571(1-3):227-3215280047Proc Natl Acad Sci U S A. 1988 Sep;85(17):6465-73413108J Biol Chem. 1992 Jan 5;267(1):166-721730583Trends Genet. 1993 Jul;9(7):246-98379000Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8016-209223306Nucleic Acids Res. 1998 Jun 15;26(12):2917-229611236Mol Cell Biol. 2006 Mar;26(5):1654-6516478987Diabetes. 2006 Apr;55(4):1022-816567524Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10230-516790548Br J Cancer. 2006 Oct 23;95(8):1056-6117003781Exp Biol Med (Maywood). 2007 May;232(5):592-60617463155Mol Cell Biol. 2007 Dec;27(24):8807-1417923681EMBO J. 2008 Jan 23;27(2):421-3218188152Am J Physiol Cell Physiol. 2008 Feb;294(2):C413-2218077603DNA Repair (Amst). 2008 Apr 2;7(4):648-5418294929Oncogene. 2008 Jun 12;27(26):3710-2018246124J Mol Biol. 2008 Oct 10;382(3):790-80118680753Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14447-5218794531Mol Cell Biol. 2008 Oct;28(20):6384-40118710944Methods Mol Biol. 2009;554:199-21219513676Nature. 2009 Jul 30;460(7255):587-9119641587Biochemistry. 2010 Jan 19;49(2):304-1120000467Cancer Cell. 2010 Jan 19;17(1):41-5220129246J Cell Sci. 2010 Mar 15;123(Pt 6):894-90220159966Cell. 2010 Nov 24;143(5):802-1221094524AcetylationApoptosisCalpainmetabolismCell Line, TumorCell ProliferationDNA DamageDNA GlycosylasesmetabolismDNA RepairDNA, MitochondrialgeneticsGene Knockdown TechniquesHEK293 CellsHumansMembrane Potential, MitochondrialOxidative StressProtein BindingProtein Interaction MappingProtein Processing, Post-TranslationalProteolysisSirtuin 3geneticsmetabolism
201303062013052020130604201372360201372360201422660epublish23868064cddis201325410.1038/cddis.2013.254PMC3730425
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1460-2105105162013Aug21Journal of the National Cancer InstituteJ. Natl. Cancer Inst.Role of the oxidative DNA damage repair gene OGG1 in colorectal tumorigenesis.1249-5310.1093/jnci/djt183Biallelic inherited mutations in the oxidative DNA damage repair gene MUTYH predispose to colorectal adenomas and colorectal carcinoma (CRC) with high penetrance. We investigated whether rare inherited variants in other oxidative DNA damage repair genes predisposed to CRC. Single marker association analyses were assessed under an allelic model with Bonferroni correction for multiple testing. All statistical tests were two-sided. A rare inherited nonsynonymous variant in OGG1 (Gly308Glu), the functional partner of MUTYH, was over-represented in case patients with advanced CRC compared with population-based control subjects (n = 36 of 2142 case patients vs n = 15 of 2175 control subjects in the training phase, P = 1.8×10(-3); and n = 22 of 1005 case patients vs n = 8 of 1389 control subjects in the validation phase, P = 4.8×10(-4); P = 1.4×10(-5) combined; odds ratio = 2.92, 95% confidence interval = 1.80 to 4.74). Glycine at residue 308 was highly conserved through evolution, and the glutamic acid substitution was predicted as likely to interfere with function. Biallelic inherited and somatic OGG1 mutations were rarely observed in OGG1 (Gly308Glu) carriers, nor did we find any associated somatic mutator phenotype. These data suggest that OGG1 (Gly308Glu) may act as a low-penetrance allele that contributes to colorectal tumorigenesis. SmithChristopher GCGInstitute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.WestHannahHHarrisRebeccaRIdziaszczykShelleySMaughanTimothy STSKaplanRichardRRichmanSusanSQuirkePhilipPSeymourMatthewMMoskvinaValentinaVSteinkeVerenaVProppingPeterPHesFrederik JFJWijnenJuulJCheadleJeremy PJPengMC_U122861325Medical Research CouncilUnited KingdomMC_UU_12023/3Medical Research CouncilUnited KingdomCancer Research UKUnited KingdomMedical Research CouncilUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20130712
United StatesJ Natl Cancer Inst75030890027-88743KX376GY7LGlutamic AcidEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanTE7660XO1CGlycineIMJ Natl Cancer Inst. 2014 May;106(5). pii: dju086. doi: 10.1093/jnci/dju08624771875J Natl Cancer Inst. 2014 May;106(5). pii: dju087. doi: 10.1093/jnci/dju08724771876AdenomageneticsAdultAgedAged, 80 and overAllelesCarcinomageneticsCase-Control StudiesColorectal NeoplasmsgeneticsDNA DamageDNA GlycosylasesgeneticsDNA RepairgeneticsFemaleGene Expression Regulation, NeoplasticGlutamic AcidGlycineHumansMaleMiddle AgedMutationOdds RatioOxidation-ReductionPenetranceUp-Regulation
201371660201371660201311560ppublish23852950djt18310.1093/jnci/djt183
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1791-24313042013OctOncology reportsOncol. Rep.A novel chemopreventive mechanism of selenomethionine: enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair.1581-610.3892/or.2013.2613Organic selenium compounds have been documented to play a role in cancer prevention. Our previous study showed that selenomethionine (SeMet) induces p53 activation without genotoxic effects including apoptosis and cell cycle arrest. In this study, we investigated the mechanism by which organic selenium compounds promote p53-mediated base excision repair (BER) activity. Our data demonstrated for the first time that the interaction between growth arrest and DNA damage-inducible protein 45A (Gadd45a), which is a p53-activated downstream gene, and two BER-mediated repair proteins, proliferating cell nuclear antigen (PCNA) and apurinic/apyrimidinic endonuclease (APE1/Ref-1), was significantly increased in a p53-dependent manner following treatment with organic selenium compounds. Furthermore, we observed that the activity of APE1 was significantly increased in a p53-dependent manner in response to the organic selenium compounds. These results suggest that BER activity is dependent on wild-type p53 activity and is mediated by the modulation of protein interactions between Gadd45a and repair proteins in response to organic selenium compounds. We propose that p53-dependent BER activity is a distinct chemopreventive mechanism mediated by organic selenium compounds, and that this may provide insight into the development of effective chemopreventive strategies against various oxidative stresses that contribute to a variety of human diseases, particularly cancer. JungHwa JinHJDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.KimHye LimHLKimYeo JinYJWeonJong-IlJISeoYoung RokYRengJournal ArticleResearch Support, Non-U.S. Gov't20130711
GreeceOncol Rep94227561021-335X0Cell Cycle Proteins0GADD45A protein, human0Multiprotein Complexes0Nuclear Proteins0Proliferating Cell Nuclear Antigen0RNA, Small Interfering0Tumor Suppressor Protein p53964MRK2PELSelenomethionineEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMScience. 1994 Nov 25;266(5189):1376-807973727JAMA. 2009 Jan 7;301(1):39-5119066370Oncogene. 1995 Mar 16;10(6):1053-97700629Oncogene. 1995 Jul 6;11(1):199-2107624128Trends Biochem Sci. 1995 Oct;20(10):391-78533150Genes Dev. 1996 May 1;10(9):1054-728654922Cancer Lett. 1996 Oct 22;107(2):277-848947525JAMA. 1996 Dec 25;276(24):1957-638971064Cancer Epidemiol Biomarkers Prev. 1997 Jan;6(1):63-98993799J Natl Cancer Inst. 1998 Mar 18;90(6):440-69521168Genes Dev. 1998 Oct 1;12(19):2973-839765199Free Radic Biol Med. 1999 Jan;26(1-2):42-89890639Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):424-89892649J Pathol. 1999 Jan;187(1):112-2610341712EMBO J. 1999 Oct 15;18(20):5609-2110523305J Mol Biol. 2005 Mar 11;346(5):1259-7415713479Oncogene. 2005 Feb 24;24(9):1641-715674341FEBS J. 2006 Apr;273(8):1620-916623699Oncogene. 2007 Nov 29;26(54):7517-2517599061J Natl Cancer Inst. 2009 Apr 1;101(7):507-1819318634Cancer Prev Res (Phila). 2009 May;2(5):473-8319401531J Med Food. 2009 Apr;12(2):340-419459735Mol Cell Biol. 2000 May;20(10):3705-1410779360J Biol Chem. 2000 Jun 2;275(22):16810-910828065Cancer Res. 2001 Jan 1;61(1):88-9611196204EMBO J. 2001 Feb 15;20(4):914-2311179235Oncogene. 2002 May 23;21(23):3663-912032834Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12985-9012242345Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14548-5312357032Exp Mol Med. 2003 Apr 30;35(2):106-1212754414Biochemistry. 1972 Sep 12;11(19):3610-84626532Biochemistry. 1972 Sep 12;11(19):3618-234559796Cancer Res. 1981 Nov;41(11 Pt 1):4386-906796257Nature. 1992 Jul 2;358(6381):15-61614522Cell. 1992 Nov 13;71(4):587-971423616Carcinogenesis. 1994 Feb;15(2):187-928313507Carcinogenesis. 1995 Mar;16(3):513-77697807Cell Cycle ProteinsmetabolismCell Line, TumorChemopreventionColonic NeoplasmsgeneticsmetabolismDNA DamageDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismEnzyme Activationdrug effectsHumansMultiprotein ComplexesmetabolismNuclear ProteinsmetabolismOxidative StressgeneticsProliferating Cell Nuclear AntigenmetabolismRNA InterferenceRNA, Small InterferingSelenomethioninepharmacologyTumor Suppressor Protein p53geneticsmetabolism
2013042220130618201371360201371360201443060ppublish2384661610.3892/or.2013.2613PMC3810451
238309272013101720161125
0027-510775522013Aug15Mutation researchMutat. Res.The impact of single-nucleotide polymorphisms (SNPs) in OGG1 and XPC on the age at onset of Huntington disease.115-910.1016/j.mrgentox.2013.04.020S1383-5718(13)00185-XThe age at onset of Huntington disease (HD) shows a strong, negative correlation with the number of CAG repeats within the huntingtin (HTT) gene. However, this does not account for all the inter-individual variability seen among patients. In order to assess whether single-nucleotide polymorphisms (SNPs) in the OGG1 and XPC genes, both implicated in responses to oxidative stress, are associated with the age of onset of HD, 9 SNPs have been genotyped in 299 individuals with HD and 582 controls. After correction for multiple testing, two OGG1/XPC haplotypes were found to be associated with younger age at onset independently of the number of CAG repeats within the HTT gene. Both haplotypes contain XPC coding variants that would be expected to impact on protein function and/or variants in the 3'UTR that could result in altered protein levels via allele-specific mIR binding. One haplotype also contains the OGG1-326Cys (rs1052133) allele that has been associated with a lower 8-oxoG repair activity and is particularly sensitive to the cellular redox status. These results highlight the potential role of oxidative stress in determining the age at onset of HD. Copyright © 2013 Elsevier B.V. All rights reserved.BergerFrédériqueFInstitut Curie, Centre de Recherche, 91405 Orsay, France.VaslinLaurenceLBelinLisaLAsselainBernardBForlaniSylvieSHumbertSandrineSDurrAlexandraAHallJanetJengJournal ArticleResearch Support, Non-U.S. Gov't20130702
NetherlandsMutat Res04007630027-510703' Untranslated Regions0DNA-Binding Proteins0HTT protein, human0Huntingtin Protein0MicroRNAs0Nerve Tissue Proteins0RNA, Messenger156533-34-5XPC protein, human5614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIM3' Untranslated RegionsgeneticsAdultAge of OnsetDNA DamageDNA GlycosylasesgeneticsphysiologyDNA RepairgeneticsDNA-Binding ProteinsgeneticsphysiologyFemaleGenotypeGuanineanalogs & derivativesmetabolismHaplotypesgeneticsHumansHuntingtin ProteinHuntington DiseaseepidemiologygeneticsMaleMicroRNAsmetabolismMiddle AgedNerve Tissue ProteinsgeneticsOxidative StressgeneticsPolymorphism, Single NucleotideRNA, MessengermetabolismTrinucleotide RepeatsAge at onsetHuntington diseaseOGG1XPC
20121208201304112013041520137960201379602013101860ppublish23830927S1383-5718(13)00185-X10.1016/j.mrgentox.2013.04.020
238087922015013020140422
1365-29904042014JunNeuropathology and applied neurobiologyNeuropathol. Appl. Neurobiol.Down-regulation of apurinic/apyrimidinic endonuclease 1 (APE1) in spinal motor neurones under oxidative stress.435-5110.1111/nan.12071Apurinic/apyrimidinic endonuclease 1 (APE1) is an intermediate enzyme in base excision repair which is important for removing damaged nucleotides under normal and pathological conditions. Accumulation of damaged bases causes genome instability and jeopardizes cell survival. Our study is to examine APE1 regulation under oxidative stress in spinal motor neurones which are vulnerable to oxidative insult.We challenged the motor neurone-like cell line NSC-34 with hydrogen peroxide and delineated APE1 function by applying various inhibitors. We also examined the expression of APE1 in spinal motor neurones after spinal root avulsion in adult rats.We showed that hydrogen peroxide induced APE1 down-regulation and cell death in a differentiated motor neurone-like cell line. Inhibiting the two functional domains of APE1, namely, DNA repair and redox domains potentiated hydrogen peroxide induced cell death. We further showed that p53 phosphorylation early after hydrogen peroxide treatment might contribute to the down-regulation of APE1. Our in vivo results similarly showed that APE1 was down-regulated after root avulsion injury in spinal motor neurones. Delay of motor neurone death suggested that APE1 might not cause immediate cell death but render motor neurones vulnerable to further oxidative insults.We conclude that spinal motor neurones down-regulate APE1 upon oxidative stress. This property renders motor neurones susceptible to continuous challenge of oxidative stress in pathological conditions.© 2013 British Neuropathological Society.ChuTak-HoTHDepartment of Anatomy, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong, China; Research Center of Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong, China.GuoAnchenAWuWutianWengJournal ArticleResearch Support, Non-U.S. Gov't
EnglandNeuropathol Appl Neurobiol76098290305-1846EC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsCell SurvivalCells, CulturedDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismDown-RegulationMaleMotor NeuronsenzymologyOxidative StressPhosphorylationRatsRats, Sprague-DawleySpinal CordenzymologyNSC-34base excision repairroot avulsion
20120714201306252013726020137360201513160ppublish2380879210.1111/nan.12071
237765692014011620171216
1932-6203862013PloS onePLoS ONEFunctional assessment of population and tumor-associated APE1 protein variants.e6592210.1371/journal.pone.0065922Apurinic/apyrimidinic endonuclease 1 (APE1) is the predominant AP site repair enzyme in mammals. APE1 also maintains 3'-5' exonuclease and 3'-repair activities, and regulates transcription factor DNA binding through its REF-1 function. Since complete or severe APE1 deficiency leads to embryonic lethality and cell death, it has been hypothesized that APE1 protein variants with slightly impaired function will contribute to disease etiology. Our data indicate that except for the endometrial cancer-associated APE1 variant R237C, the polymorphic variants Q51H, I64V and D148E, the rare population variants G241R, P311S and A317V, and the tumor-associated variant P112L exhibit normal thermodynamic stability of protein folding; abasic endonuclease, 3'-5' exonuclease and REF-1 activities; coordination during the early steps of base excision repair; and intracellular distribution when expressed exogenously in HeLa cells. The R237C mutant displayed reduced AP-DNA complex stability, 3'-5' exonuclease activity and 3'-damage processing. Re-sequencing of the exonic regions of APE1 uncovered no novel amino acid substitutions in the 60 cancer cell lines of the NCI-60 panel, or in HeLa or T98G cancer cell lines; only the common D148E and Q51H variants were observed. Our results indicate that APE1 missense mutations are seemingly rare and that the cancer-associated R237C variant may represent a reduced-function susceptibility allele.IlluzziJennifer LJLLaboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.HarrisNicole ANAManvillaBrittney ABAKimDaemyungDLiMengxiaMDrohatAlexander CACWilsonDavid MDM3rdengT32GM 066706-07GMNIGMS NIH HHSUnited StatesR01-GM72711GMNIGMS NIH HHSUnited StatesT32 HL007381HLNHLBI NIH HHSUnited StatesIntramural NIH HHSUnited StatesR01 GM072711GMNIGMS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, N.I.H., IntramuralResearch Support, Non-U.S. Gov't20130611
United StatesPLoS One1012850811932-6203EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMProc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414Nature. 1993 Apr 22;362(6422):709-158469282Nucleic Acids Res. 1995 May 11;23(9):1544-507784208J Biol Chem. 1995 Jul 7;270(27):16002-77608159Nature. 1996 Jan 11;379(6561):183-68538772Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Dev Biol. 1999 Apr 15;208(2):513-2910191063Biochemistry. 1999 Jul 20;38(29):9533-4010413531Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14350-516179390Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Cancer Res. 2006 Aug 1;66(15):7460-516885342DNA Repair (Amst). 2007 Jan 4;6(1):8-1816978929DNA Repair (Amst). 2007 Apr 1;6(4):398-40917129767EMBO J. 2008 Feb 20;27(4):589-60518285820Mutat Res. 2008 Aug 25;643(1-2):54-6318579163Cell Mol Life Sci. 2009 Mar;66(6):981-9319153658Nucleic Acids Res. 2009 Jul;37(12):3946-5819401441J Biol Chem. 2010 Jun 18;285(25):19246-5820404327Cancer Treat Rev. 2010 Aug;36(5):425-3520056333Nucleic Acids Res. 2010 Aug;38(15):5023-3520385586Cell Mol Life Sci. 2010 Nov;67(21):3609-2020711647Semin Cancer Biol. 2010 Oct;20(5):320-820955798Mutat Res. 2011 Jun 3;711(1-2):100-1221167187Nat Rev Cancer. 2011 Jun;11(6):450-721593786Nucleic Acids Res. 2011 Oct;39(18):7992-800421737425Cell Mol Life Sci. 2012 Mar;69(5):727-4021952828Curr Mol Pharmacol. 2012 Jan;5(1):36-5322122463Nucleic Acids Res. 1997 Mar 1;25(5):933-99023101Nucleic Acids Res. 1998 Jun 1;26(11):2771-89592167Nat Genet. 1999 Mar;21(3):323-510080189Curr Med Chem. 2012;19(23):3922-3622788768Nat Rev Genet. 2012 Nov;13(11):795-80623044827PLoS Genet. 2012;8(11):e100305223144635Nat Struct Biol. 2000 Mar;7(3):176-810700268EMBO J. 2000 Mar 15;19(6):1397-40410716939J Mol Biol. 2000 May 5;298(3):447-5910772862Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Mutat Res. 2001 Jan;432(3-4):53-911465542Mutat Res. 2001 May 10;485(4):283-30711585362Nucleic Acids Res. 2002 Apr 15;30(8):1817-2511937636J Mol Biol. 2003 Jul 25;330(5):1027-3712860125Genomics. 2004 Jun;83(6):970-915177551Mol Cell. 2004 Jul 23;15(2):209-2015260972Annu Rev Genet. 1986;20:201-303545059Biochemistry. 1988 Oct 18;27(21):8063-83233195Biochim Biophys Acta. 1991 Aug 9;1079(1):57-641716153EMBO J. 1992 Feb;11(2):653-651537340Annu Rev Biochem. 1994;63:915-487979257Amino Acid SubstitutiongeneticsCell Line, TumorDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismEndometrial NeoplasmsgeneticsmetabolismFemaleHeLa CellsHumansMutationMutation, MissenseNeoplasmsgeneticsmetabolismSubstrate Specificity
2013031220130429201361960201361960201411760epublish2377656910.1371/journal.pone.0065922PONE-D-13-10376PMC3679070
237483602013102920161019
1945-717015482013AugEndocrinologyEndocrinologyAlteration of mitochondrial function and insulin sensitivity in primary mouse skeletal muscle cells isolated from transgenic and knockout mice: role of ogg1.2640-910.1210/en.2013-1076Recent evidence has linked mitochondrial dysfunction and DNA damage, increased oxidative stress in skeletal muscle, and insulin resistance (IR). The purpose of this study was to determine the role of the DNA repair enzyme, human 8-oxoguanine DNA glycosylase/apurinic/apyrimidinic lyase (hOGG1), on palmitate-induced mitochondrial dysfunction and IR in primary cultures of skeletal muscle derived from hind limb of ogg1(-/-) knockout mice and transgenic mice, which overexpress human (hOGG1) in mitochondria (transgenic [Tg]/MTS-hOGG1). Following exposure to palmitate, we evaluated mitochondrial DNA (mtDNA) damage, mitochondrial function, production of mitochondrial reactive oxygen species (mtROS), mitochondrial mass, JNK activation, insulin signaling pathways, and glucose uptake. Palmitate-induced mtDNA damage, mtROS, mitochondrial dysfunction, and activation of JNK were all diminished, whereas ATP levels, mitochondrial mass, insulin-stimulated phosphorylation of Akt (Ser 473), and insulin sensitivity were increased in primary myotubes isolated from Tg/MTS-hOGG1 mice compared to myotubes isolated from either knockout or wild-type mice. In addition, both basal and maximal respiratory rates during mitochondrial oxidation on pyruvate showed a variable response, with some animals displaying an increased respiration in muscle fibers isolated from the transgenic mice. Our results support the model that DNA repair enzyme OGG1 plays a pivotal role in repairing mtDNA damage, and consequently, in mtROS production and regulating downstream events leading to IR in skeletal muscle. YuzefovychLarysa VLVDepartment of Cell Biology and Neuroscience, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.SchulerA MicheleAMChenJemimahJAlvarezDiego FDFEideLarsLLedouxSusan PSPWilsonGlenn LGLRachekLyudmila ILIengR01 DK073808DKNIDDK NIH HHSUnited StatesDK073808DKNIDDK NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20130607
United StatesEndocrinology03750400013-72270DNA, Mitochondrial0Insulin0Palmitates0Reactive Oxygen Species8L70Q75FXEAdenosine TriphosphateEC 2.7.11.1Proto-Oncogene Proteins c-aktEC 2.7.11.24JNK Mitogen-Activated Protein KinasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 3.2.2.-oxoguanine glycosylase 1, humanAIMIMHum Hered. 2010;70(2):97-10120606456Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315J Biol Chem. 2000 Dec 1;275(48):37518-2310982789Am J Physiol Endocrinol Metab. 2001 Jul;281(1):E16-2411404219Cancer Res. 2001 Jul 15;61(14):5378-8111454679Clin Orthop Relat Res. 2002 Oct;(403 Suppl):S153-6212394464J Biol Chem. 2002 Nov 22;277(47):44932-712244119Cancer Res. 2003 Mar 1;63(5):902-512615700Mol Endocrinol. 2004 Aug;18(8):2024-3415143153Diabetes. 1988 Jun;37(6):667-873289989Baillieres Clin Haematol. 1989 Apr;2(2):195-2562660928J Neurochem. 1990 Jul;55(1):186-912355219Nature. 1991 Jan 31;349(6308):431-41992344Am J Physiol. 1994 Mar;266(3 Pt 1):C751-88166238Biochem J. 1996 Jan 1;313 ( Pt 1):17-298546679Nucleic Acids Res. 1997 Nov 1;25(21):4362-99336469Biochimie. 1999 Jan-Feb;81(1-2):59-6710214911Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L530-515563690Free Radic Biol Med. 2005 Mar 15;38(6):737-4515721984Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1864-916446448Free Radic Biol Med. 2006 Mar 1;40(5):754-6216520228Diabetes. 2006 Apr;55(4):1022-816567524Toxicology. 2006 Apr 17;221(2-3):179-8616494984Endocrinology. 2007 Jan;148(1):293-917023529Anal Bioanal Chem. 2007 Apr;387(8):2775-8217377779Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12587-9417640906Carcinogenesis. 2007 Aug;28(8):1629-3717389610Mech Ageing Dev. 2007 Nov-Dec;128(11-12):637-4918006041J Clin Invest. 2008 Feb;118(2):789-80018188455Am J Physiol Cell Physiol. 2008 Feb;294(2):C413-2218077603Cell Motil Cytoskeleton. 2008 Dec;65(12):945-5418792955Free Radic Biol Med. 2009 Sep 15;47(6):750-919524665Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17787-9219805130Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E1096-10520876761Am J Pathol. 2011 Apr;178(4):1715-2721435453J Clin Invest. 2009 Mar;119(3):573-8119188683Free Radic Biol Med. 2011 May 1;50(9):1107-1320969951J Lipid Res. 2011 Jun;52(6):1234-4621447485Eur J Endocrinol. 2011 Jun;164(6):899-90421436346J Neurosci. 2011 Jun 29;31(26):9746-5121715639Endocrinology. 2012 Jan;153(1):92-10022128025Gene. 2012 Aug 15;505(1):121-722652274Diabetologia. 2012 Oct;55(10):2759-6822782287PLoS One. 2012;7(12):e5169723284747PLoS One. 2013;8(1):e5405923342074Adenosine TriphosphatemetabolismAnimalsBlotting, WesternCells, CulturedDNA DamageDNA GlycosylasesgeneticsmetabolismDNA, MitochondrialgeneticsmetabolismEnzyme Activationdrug effectsHumansInsulinmetabolismpharmacologyphysiologyJNK Mitogen-Activated Protein KinasesmetabolismMiceMice, KnockoutMice, TransgenicMitochondria, MusclegeneticsmetabolismphysiologyMuscle, Skeletalcytologydrug effectsmetabolismPalmitatespharmacologyPhosphorylationdrug effectsProto-Oncogene Proteins c-aktmetabolismReactive Oxygen SpeciesmetabolismSignal Transductiondrug effects
2013611602013612602013103060ppublish23748360en.2013-107610.1210/en.2013-1076PMC3713209
237269962013110120130729
1873-4596632013OctFree radical biology & medicineFree Radic. Biol. Med.Genotype-phenotype analysis of S326C OGG1 polymorphism: a risk factor for oxidative pathologies.401-910.1016/j.freeradbiomed.2013.05.031S0891-5849(13)00241-48-Oxoguanine DNA glycosylase (OGG) activity was measured by an in vitro assay in lymphocytes of healthy volunteers genotyped for various OGG1 polymorphisms. Only homozygous carriers of the polymorphic C326 allele showed a significantly lower OGG activity compared to the homozygous S326 genotype. The purified S326C OGG1 showed a decreased ability to complete the repair synthesis step in a base excision repair reaction reconstituted in vitro. The propensity of this variant to dimerize as well as its catalytic impairment were shown to be enhanced under oxidizing conditions. Mass spectrometry revealed that the extra cysteine of the variant protein is involved in disulfide bonds compatible with significant conformational changes and/or dimerization. We propose that the S326C OGG1 catalytic impairment and its susceptibility to dimerization and disulfide bond formation in an oxidizing environment all concur to decrease repair capacity. Consequently, the C326 homozygous carriers may be at increased risk of oxidative pathologies. Copyright © 2013 Elsevier Inc. All rights reserved.SimonelliValeriaVDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, 00161 Rome, Italy.CameriniSerenaSMazzeiFilomenaFVan LoonBarbaraBAllioneAlessandraAD'ErricoMariarosariaMBaroneFlaviaFMinoprioAnnaARicceriFulvioFGuarreraSimonettaSRussoAlessiaADalhusBjørnBCrescenziMarcoMHübscherUlrichUBjøråsMagnarMMatulloGiuseppeGDogliottiEugeniaEengJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20130528
United StatesFree Radic Biol Med87091590891-5849EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultAllelesDNA DamagegeneticsDNA GlycosylasesgeneticsmetabolismDNA RepairgeneticsFemaleGenetic Association StudiesHomozygoteHumansLymphocytesmetabolismMaleMiddle AgedOxidation-ReductionOxidative StressPolymorphism, Single NucleotideRisk FactorsDNA repairDisulfide bond profileFree radicalsGenotype–phenotype analysisSingle-nucleotide polymorphisms
2013010420130507201305212013646020136460201311260ppublish23726996S0891-5849(13)00241-410.1016/j.freeradbiomed.2013.05.031
237001562013112620171116
1423-03803452013OctTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Polymorphisms of DNA repair genes XPD, XRCC1, and OGG1, and lung adenocarcinoma susceptibility in Chinese population.2843-810.1007/s13277-013-0844-6Lung adenocarcinoma (ADC) is one of the major histological types of lung cancer. Genetic polymorphism in DNA repair genes and lung ADC susceptibility is well documented. In this case-control study, the association between the polymorphic sites of DNA repair genes XPD-751, XRCC1-399, and OGG1-326, and lung ADC susceptibility in ethnic Han Chinese population has been investigated. Genomic DNA was isolated from the peripheral blood of 201 healthy controls and 82 lung ADC patients from the people of Hunan Province, China. Polymorphisms of the investigated genes were analyzed by using polymerase chain reaction-restriction fragment length polymorphism. There was no significant difference between the samples from lung ADC patients and healthy controls about the genotype frequencies of XPD-751, XRCC1-399, and OGG1-326 sites. However, multifactor dimensionality reduction analysis showed that the genetic polymorphisms of the three-loci models of DNA repair genes (XPD-751/XRCC1-399/OGG1-326) are associated with lung ADC. Thus, this study reveals that a three-order interaction among the polymorphic sites of XPD-751, XRCC1-399, and OGG1-326 is associated with lung ADC risk in the studied population, although polymorphism in individual gene was not associated.OuyangFang-danFDDepartment of Biochemistry, School of Life Sciences, Central South University, Changsha, Hunan, 410013, China.YangFu-lanFLChenHan-chunHCKhanMd AsaduzzamanMAHuangFeng-maoFMWanXin-xingXXXuAi-huaAHHuangXingXZhouMei-juanMJFangQianQZhangDian-zhengDZengJournal ArticleResearch Support, Non-U.S. Gov't20130523
United StatesTumour Biol84099221010-42830DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanAdenocarcinoma of lungIMLung Cancer. 2007 May;56(2):153-6017316890Mutat Res. 1998 May 25;400(1-2):15-249685572Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):669-7410744126Mutat Res. 2011 Jun 3;711(1-2):100-1221167187Cancer Sci. 2006 Aug;97(8):724-816800823Carcinogenesis. 2002 Apr;23(4):599-60311960912Pharmacogenetics. 2004 Feb;14(2):103-915077011BMC Cancer. 2007 Aug 16;7:16217705814Int J Surg Pathol. 2006 Jan;14(1):21-3316501831Carcinogenesis. 2009 Jan;30(1):2-1018978338Ophthalmology. 2012 May;119(5):900-622306120Mutat Res. 2001 Jan 5;461(4):273-811104903Antioxid Redox Signal. 2001 Aug;3(4):597-60911554447Mutagenesis. 2010 Nov;25(6):569-7520817763Mol Biol Rep. 2012 Oct;39(10):9535-4722729882EMBO J. 2008 Feb 20;27(4):589-60518285820Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Carcinogenesis. 2001 Aug;22(8):1185-811470747Arch Med Res. 2011 Apr;42(3):226-3421722819Mutat Res. 2004 Feb 26;546(1-2):65-7414757194Oncogene. 1998 Jun 25;16(25):3219-259681819Genomics. 2004 Jun;83(6):970-915177551Int J Cancer. 2003 Oct 20;107(1):84-812925960World J Gastroenterol. 2003 May;9(5):956-6012717837Mutat Res. 2000 Feb 16;459(1):1-1810677679Nat Genet. 1998 Oct;20(2):184-89771713CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855J Epidemiol. 2002 May;12(3):258-6512164330Zhonghua Zhong Liu Za Zhi. 2005 Dec;27(12):713-616483478Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2003 Feb;20(1):35-812579497Carcinogenesis. 2012 May;33(5):1059-6422382497Cancer Res. 2005 Feb 1;65(3):722-615705867AdenocarcinomageneticsAdultAgedCase-Control StudiesChinaDNA GlycosylasesgeneticsDNA-Binding ProteinsgeneticsFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseHumansLung NeoplasmsgeneticsMaleMiddle AgedPolymorphism, Restriction Fragment LengthRisk FactorsSequence Analysis, DNAX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
20130423201305032013524602013524602013121660ppublish2370015610.1007/s13277-013-0844-6
236975962013112620161019
1471-2407132013May22BMC cancerBMC CancerAntioxidant-mediated up-regulation of OGG1 via NRF2 induction is associated with inhibition of oxidative DNA damage in estrogen-induced breast cancer.25310.1186/1471-2407-13-253Estrogen metabolism-mediated oxidative stress is suggested to play an important role in estrogen-induced breast carcinogenesis. We have earlier demonstrated that antioxidants, vitamin C (Vit C) and butylated hydroxyanisole (BHA) inhibit 17β-estradiol (E2)-mediated oxidative stress and oxidative DNA damage, and breast carcinogenesis in female August Copenhagen Irish (ACI) rats. The objective of the present study was to characterize the mechanism by which above antioxidants prevent DNA damage during breast carcinogenesis.Female ACI rats were treated with E2; Vit C; Vit C + E2; BHA; and BHA + E2 for up to 240 days. mRNA and protein levels of a DNA repair enzyme 8-Oxoguanine DNA glycosylase (OGG1) and a transcription factor NRF2 were quantified in the mammary and mammary tumor tissues of rats after treatment with E2 and compared with that of rats treated with antioxidants either alone or in combination with E2.The expression of OGG1 was suppressed in mammary tissues and in mammary tumors of rats treated with E2. Expression of NRF2 was also significantly suppressed in E2-treated mammary tissues and in mammary tumors. Vitamin C or BHA treatment prevented E2-mediated decrease in OGG1 and NRF2 levels in the mammary tissues. Chromatin immunoprecipitation analysis confirmed that antioxidant-mediated induction of OGG1 was through increased direct binding of NRF2 to the promoter region of OGG1. Studies using silencer RNA confirmed the role of OGG1 in inhibition of oxidative DNA damage.Our studies suggest that antioxidants Vit C and BHA provide protection against oxidative DNA damage and E2-induced mammary carcinogenesis, at least in part, through NRF2-mediated induction of OGG1.SinghBhupendraBDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Room 5251, Kansas City, MO 64108, USA.ChatterjeeAnweshaARongheAmruta MAMBhatNimee KNKBhatHari KHKengCA109551CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20130522
EnglandBMC Cancer1009678001471-24070Antioxidants0Estrogens0NF-E2-Related Factor 20Nfe2l2 protein, rat88847-89-68-oxo-7-hydrodeoxyguanosineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-OGG1 protein, ratG9481N71RODeoxyguanosineIMFood Chem Toxicol. 1999 Sep-Oct;37(9-10):993-710541456Cancer Lett. 2012 Mar;316(1):62-922082530Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2779-8410688907Arch Biochem Biophys. 2000 May 1;377(1):1-810775435J Natl Cancer Inst Monogr. 2000;(27):67-7310963620Mutat Res. 2000 Oct 16;461(2):109-1811018584J Biol Chem. 2000 Dec 22;275(51):40134-4111013233Anal Cell Pathol. 2001;23(1):21-811790856Mol Carcinog. 2002 Jan;33(1):56-6511807958J Biol Chem. 2003 Mar 7;278(10):8135-4512506115Carcinogenesis. 2003 Mar;24(3):511-512663512Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3913-812655060Ann N Y Acad Sci. 2004 Apr;1011:101-1115126288Mutat Res. 2004 Sep;567(1):1-6115341901Cancer Res. 1982 Jul;42(7):2609-156805943J Steroid Biochem. 1986 Jan;24(1):353-63009986Carcinogenesis. 1994 May;15(5):997-10008200107Cancer Res. 1997 Jun 1;57(11):2151-69187114Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-59223305Carcinogenesis. 1997 Aug;18(8):1595-6019276635Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10937-429380738Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18123-815601761J Steroid Biochem Mol Biol. 2004 Dec;92(5):391-815698544Neuroscience. 2005;136(1):135-4616182450Clin Chim Acta. 2006 Mar;365(1-2):30-4916214123Carcinogenesis. 2006 Mar;27(3):491-816311245Mol Cell Biol. 2006 Oct;26(20):7430-616923968Annu Rev Pharmacol Toxicol. 2007;47:89-11616968214J Physiol Pharmacol. 2006 Nov;57 Suppl 7:33-4917228095Oncogene. 2007 May 24;26(24):3587-9017160017Physiol Genomics. 2007 Dec 19;32(1):74-8117895394Toxicol Appl Pharmacol. 2008 Oct 1;232(1):78-8518640140Mol Carcinog. 2009 Feb;48(2):91-10418618599J Biochem Mol Toxicol. 2009 May-Jun;23(3):202-1119526586Carcinogenesis. 2009 Jul;30(7):1202-819406931Carcinogenesis. 2010 Jan;31(1):90-919793802Toxicol Appl Pharmacol. 2010 Sep 1;247(2):83-9020600213PLoS One. 2011;6(9):e2512521966433Toxicol Lett. 2011 Nov 30;207(2):143-821925250Br J Cancer. 2012 Jan 17;106(2):344-722108520Carcinogenesis. 2012 Dec;33(12):2601-1023027624Carcinogenesis. 2012 Jan;33(1):156-6322072621Carcinogenesis. 2000 Mar;21(3):427-3310688862AnimalsAntioxidantspharmacologyBlotting, WesternCell Line, TumorChromatin ImmunoprecipitationDNA DamagephysiologyDNA GlycosylasesbiosynthesisDeoxyguanosineanalogs & derivativesanalysisbiosynthesisEstrogenstoxicityFemaleHumansMammary Neoplasms, Experimentalchemically inducedmetabolismpathologyNF-E2-Related Factor 2biosynthesisOxidation-Reductiondrug effectsOxidative Stressdrug effectsRNA InterferenceRatsRats, Inbred ACIReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionSignal Transductiondrug effectsUp-Regulation
20130122201305072013524602013524602013121660epublish236975961471-2407-13-25310.1186/1471-2407-13-253PMC3665669
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1090-210443542013Jun14Biochemical and biophysical research communicationsBiochem. Biophys. Res. Commun.Identification of plasma APE1/Ref-1 in lipopolysaccharide-induced endotoxemic rats: implication of serological biomarker for an endotoxemia.621-610.1016/j.bbrc.2013.05.030S0006-291X(13)00812-7Apurinic/apyrimidinic endonuclease1/Redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in base excision DNA repair and in transcriptional regulation of gene expression. We investigated whether APE1/Ref-1 increased in plasma of endotoxemic rats. Lipopolysaccharide (LPS) was used to induce endotoxemia in rats. Administration of LPS (10 mg/kg, i.p.) significantly induced plasma nitrite production and tumor necrosis factor-α (TNF-α). A 37 kDa immunoreactive band was detected in cell-free plasma of LPS-treated rats using anti-APE1/Ref-1, which reached a maximum at 12 h after the LPS injection. The 37 kDa immunoreactive band was identified as rat APE1/Ref-1 by liquid chromatography/tandem mass spectrometry. Interestingly, treatment with recombinant human APE1/Ref-1 protein (2-5 μg/ml for 18 h) inhibited TNF-α-induced vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells. Taken together, the level of plasma APE1/Ref-1 increased in LPS-induced endotoxemic rats, suggesting that plasma APE1/Ref-1 might serve as a serological biomarker for endotoxemia.Copyright © 2013 Elsevier Inc. All rights reserved.ParkMyoung SooMSDepartment of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.LeeYu RanYRChoiSungaSJooHee KyoungHKChoEun JungEJKimCuk SeongCSParkJin BongJBJoEun-KyeongEKJeonByeong HwaBHengJournal ArticleResearch Support, Non-U.S. Gov't20130517
United StatesBiochem Biophys Res Commun03725160006-291X0Biomarkers0LipopolysaccharidesEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsBiomarkersbloodDNA-(Apurinic or Apyrimidinic Site) LyasebloodEndotoxemiabloodchemically induceddiagnosisLipopolysaccharidesMaleRatsRats, Sprague-Dawley
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1873-4596632013OctFree radical biology & medicineFree Radic. Biol. Med.Alzheimer's disease-associated polymorphisms in human OGG1 alter catalytic activity and sensitize cells to DNA damage.115-2510.1016/j.freeradbiomed.2013.05.010S0891-5849(13)00220-7Brain tissues from Alzheimer's disease (AD) patients show increased levels of oxidative DNA damage and 7,8-dihydro-8-oxoguanine (8-oxoG) accumulation. In humans, the base excision repair protein 8-oxoguanine-DNA glycosylase (OGG1) is the major enzyme that recognizes and excises the mutagenic DNA base lesion 8-oxoG. Recently, two polymorphisms of OGG1, A53T and A288V, have been identified in brain tissues of AD patients, but little is known about how these polymorphisms may contribute to AD. We characterized the A53T and A288V polymorphic variants and detected a significant reduction in the catalytic activity for both proteins in vitro and in cells. Additionally, the A53T polymorphism has decreased substrate binding, whereas the A288V polymorphism has reduced AP lyase activity. Both variants have decreased binding to known OGG1 binding partners PARP-1 and XRCC1. We found that OGG1(-/-) cells expressing A53T and A288V OGG1 were significantly more sensitive to DNA damage and had significantly decreased survival. Our results provide both biochemical and cellular evidence that A53T and A288V polymorphic proteins have deficiencies in catalytic and protein-binding activities that could be related to the increase in oxidative damage to DNA found in AD brains. Published by Elsevier Inc.JacobKimberly DKDLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6825, USA.Noren HootenNicoleNTadokoroTakashiTLohaniAlthafABarnesJaniceJEvansMichele KMKengZIA AG000517-09NULLIntramural NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Intramural20130514
United StatesFree Radic Biol Med87091590891-584907,8-dihydro-8-oxoguanine0DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, human0Xrcc1 protein, mouse5Z93L87A1RGuanineEC 2.4.2.30PARP1 protein, humanEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMNucleic Acids Res. 2006;34(5):1620-3216549874Nucleic Acids Res. 2007;35(16):5545-5517704129Mutat Res. 2011 Jun 3;711(1-2):100-1221167187Science. 1993 Oct 29;262(5134):689-957901908Biochemistry. 2003 Feb 18;42(6):1564-7212578369Nucleic Acids Res. 2007;35(8):2759-6617426120Nature. 2000 Feb 24;403(6772):859-6610706276Mech Ageing Dev. 2013 Mar;134(3-4):139-5723428415Nature. 1995 Jun 29;375(6534):754-607596406Science. 2002 Jul 19;297(5580):353-612130773Cell Res. 2008 Jan;18(1):48-6318166976Anal Biochem. 2006 Oct 15;357(2):289-9816962548Nucleic Acids Res. 2004;32(2):570-814752045Ann Neurol. 1993 Oct;34(4):609-168215249Cancer Detect Prev. 2007;31(3):237-4317651912DNA Repair (Amst). 2007 Mar 1;6(3):317-2817126083Ann Neurol. 1997 May;41(5):646-539153527Mol Carcinog. 2005 Mar;42(3):127-4115584022J Biol Chem. 2011 Dec 30;286(52):44679-9022057269Free Radic Res. 2006 Dec;40(12):1295-30217090419Ann Neurol. 1994 Nov;36(5):747-517979220Nature. 2005 Mar 31;434(7033):612-815800616Ann Neurol. 1992;32 Suppl:S22-71510377J Neurochem. 1997 Nov;69(5):2064-749349552Nature. 1991 Feb 21;349(6311):704-61671712J Neurochem. 2006 Feb;96(3):825-3216405502FEBS J. 2009 Sep;276(18):5149-6219674107Fold Des. 1998;3(2):119-269565756J Neurochem. 1997 Sep;69(3):1326-99282961PLoS Genet. 2010 May;6(5):e100095120485567Free Radic Biol Med. 1997;23(1):134-479165306Neurobiol Aging. 2002 Sep-Oct;23(5):655-6412392766Mol Chem Neuropathol. 1997 May;31(1):53-649271005Biopolymers. 1987 Nov;26(11):1859-773689874Mutat Res. 2001 Jun 5;486(1):31-4011356334Nucleic Acids Res. 2001 Mar 15;29(6):1285-9211238994Nat Rev Mol Cell Biol. 2006 Jul;7(7):517-2816829982Neurotoxicology. 1986 Spring;7(1):195-2063714121Biochem Biophys Res Commun. 2008 Nov 14;376(2):336-4018774780Curr Protoc Mol Biol. 2001 May;Chapter 16:Unit16.718265134J Neurochem. 2006 Jun;97(6):1634-5816805774Nucleic Acids Res. 1989 Aug 11;17(15):64192771659Curr Alzheimer Res. 2009 Feb;6(1):36-4719199873J Biol Chem. 2003 Nov 7;278(45):44068-7412933815Nature. 1995 Aug 31;376(6543):775-87651536Biochemistry. 1998 May 26;37(21):7733-409601033J Nerv Ment Dis. 1953 Aug;118(2):97-13013109530J Neurochem. 1995 Nov;65(5):2146-567595501Nucleic Acids Res. 2001 Jan 15;29(2):430-811139613J Neurosci. 2001 May 1;21(9):3017-2311312286Science. 1995 Aug 18;269(5226):973-77638622Alzheimer DiseasegeneticsmetabolismpathologyCatalysisDNA DamagegeneticsDNA GlycosylasesgeneticsmetabolismDNA RepairgeneticsDNA-Binding ProteinsmetabolismGuanineanalogs & derivativesmetabolismHumansOxidative StressPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesmetabolismPolymorphism, GeneticProtein BindingSubstrate SpecificityX-ray Repair Cross Complementing Protein 17,8-dihydro-8-oxoguanine8-Oxoguanine8-Oxoguanine-DNA glycosylase8-oxoG8-oxoguanine-DNA glycosylaseADAlzheimer's diseaseBERBase excision repairDNA damageDNA repairFree radicalsMEFOGG1Oxidative stressPARPARP-1ROSX-ray cross-complementing protein 1XRCC1base excision repairmouse embryo fibroblastpoly(ADP-ribose) polymerase 1poly(ADP-ribosyl)ationreactive oxygen species
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0219-10323562013JunMolecules and cellsMol. CellsDecreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth.489-9710.1007/s10059-013-2343-4Many solid tumor cells exhibit mitochondrial respiratory impairment; however, the mechanisms of such impairment in cancer development remain unclear. Here, we demonstrate that SNU human hepatoma cells with declined mitochondrial respiratory activity showed decreased expression of mitochondrial 8-oxoguanine DNA glycosylase/lyase (mtOGG1), a mitochondrial DNA repair enzyme; similar results were obtained with human hepatocellular carcinoma tissues. Among several OGG1-2 variants with a mitochondrial-targeting sequence (OGG1-2a, -2b, -2c, -2d, and -2e), OGG1-2a was the major mitochondrial isoform in all examined hepatoma cells. Interestingly, hepatoma cells with low mtOGG1 levels showed delayed cell growth and increased intracellular reactive oxygen species (ROS) levels. Knockdown of OGG1-2 isoforms in Chang-L cells, which have active mitochondrial respiration with high mtOGG1 levels, significantly decreased cellular respiration and cell growth, and increased intracellular ROS. Overexpression of OGG1-2a in SNU423 cells, which have low mtOGG1 levels, effectively recovered cellular respiration and cell growth activities, and decreased intracellular ROS. Taken together, our results suggest that mtOGG1 plays an important role in maintaining mitochondrial respiration, thereby contributing to cell growth of hepatoma cells.LeeYoung-KyoungYKDepartment of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721, Korea.YounHwang-GuemHGWangHee-JungHJYoonGyesoonGengJournal ArticleResearch Support, Non-U.S. Gov't20130514
Korea (South)Mol Cells96109361016-84780Protein Isoforms0Reactive Oxygen SpeciesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMInt J Cancer. 1995 Jul 28;62(3):276-827543080Arch Biochem Biophys. 2000 May 1;377(1):1-810775435Science. 1956 Feb 24;123(3191):309-1413298683Nature. 1981 Apr 9;290(5806):457-657219534Exp Dermatol. 2006 Dec;15(12):1005-1517083367N Engl J Med. 2003 Jun 26;348(26):2656-6812826641Exp Cell Res. 2012 Sep 10;318(15):1808-1922652454Mutat Res. 1999 Jul 30;434(3):161-7610486590Exp Gerontol. 2006 Jan;41(1):11-2416307857J Biol Chem. 2003 Dec 19;278(51):51577-8614512425Biochim Biophys Acta. 1995 May 24;1271(1):171-67599205Cancer Res. 2002 Nov 15;62(22):6674-8112438266Curr Opin Genet Dev. 1995 Jun;5(3):315-227549425Physiol Rev. 2008 Apr;88(2):611-3818391175DNA Repair (Amst). 2004 Apr 1;3(4):403-1115010316Mol Biol Cell. 1999 May;10(5):1637-5210233168Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10771-87971961Oncogene. 2006 Aug 7;25(34):4647-6216892079Cell Death Differ. 2013 Jan;20(1):31-4222743996Prog Exp Tumor Res. 1978;22:190-274149996Mitochondrion. 2005 Apr;5(2):89-10816050976Circ Res. 2012 Oct 12;111(9):1208-2123065344J Cell Physiol. 2006 Nov;209(2):468-8016883569Methods Cell Biol. 2001;65:119-3111381589Nucleic Acids Res. 2004;32(18):5596-60815494448Cancer Res. 2001 Mar 1;61(5):1843-511280735Aging Cell. 2008 Dec;7(6):894-90718782348Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):719-2415647368Trends Biochem Sci. 1999 Feb;24(2):68-7210098401Exp Cell Res. 2011 May 1;317(8):1108-1821356207Mol Cells. 2011 Apr;31(4):327-3521448585Lancet. 1989 Mar 25;1(8639):642-52564461Nat Rev Genet. 2001 May;2(5):342-5211331900Nat Genet. 1999 Oct;23(2):14710508508Mutat Res. 2009 Nov 2;670(1-2):99-10219646455Biochim Biophys Acta. 1999 Feb 9;1410(2):103-2310076021Front Biosci (Landmark Ed). 2010;15:437-6020036829Nat Rev Cancer. 2012 Oct;12(10):685-9823001348Prog Nucleic Acid Res Mol Biol. 2001;68:257-7111554302Oncogene. 2006 Aug 7;25(34):4663-7416892080Cancer Res Treat. 2005 Feb;37(1):1-1919956504Carcinoma, HepatocellularmetabolismpathologyCell Growth ProcessesgeneticsCell Line, TumorCell RespirationgeneticsDNA GlycosylasesgeneticsmetabolismDown-RegulationGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansLiver NeoplasmsmetabolismpathologyMitochondria, LivergeneticsmetabolismProtein IsoformsgeneticsmetabolismReactive Oxygen SpeciesmetabolismTransgenesgenetics
201212272013040820130313201351760201351760201422660ppublish2367737710.1007/s10059-013-2343-4PMC3887880
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0027-510775512013Jul04Mutation researchMutat. Res.The influence of XPD, APE1, XRCC1, and NBS1 polymorphic variants on DNA repair in cells exposed to X-rays.42-810.1016/j.mrgentox.2013.05.002S1383-5718(13)00122-8Polymorphism of genes coding for proteins which participate in DNA repair may predispose to or protect against development of cancer. Here we studied how common polymorphisms of the genes XPD (Asp312Asn and Lys751Gln), APE1 (Asp148Glu), XRCC1 (Arg399Gln), and NBS1 (Gln185Glu) influence DNA repair and other responses after X-irradiation of lymphocytes from colon carcinoma patients. Genotypes with polymorphic Asp148Glu APE1 and Asp312Asn XPD showed a significantly higher level of DNA incisions immediately after irradiation (p=0.049 and p=0.047 respectively) and Asp312Asn XPD showed a significantly increased capacity to repair of DNA strand breaks as measured 180min after irradiation by comet assays (p=0.004). In contrast, it was the wild type XRCC1 genotype which was associated with a lower level of DNA breaks after irradiation (p=0.014, at 180min after irradiation) and polymorphism of NBS1 did not correlate with any changes in DNA breaks or repair capacity. To confirm the influence of XPD polymorphism on repair, we established stably-transfected HCT116 (colon carcinoma) cells which over-expressed the wild-type or variant XPD protein. Cells over-expressing Asp312Asn XPD showed a higher level of DNA breaks shortly after irradiation and more efficient repair than cells over-expressing the wild-type gene XPD312Asp, and an earlier inhibition of cell cycle transit but faster recovery from this inhibition. Polymorphisms in DNA repair genes therefore influence not only DNA repair capacity but also cell proliferation, and may serve as markers of individual repair capacity and susceptibility to environmental and occupational carcinogens. Copyright © 2013 Elsevier B.V. All rights reserved.Gdowicz-KlosokAgnieszkaAMaria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland.WidelMariaMRzeszowska-WolnyJoannaJengJournal ArticleResearch Support, Non-U.S. Gov't20130510
NetherlandsMutat Res04007630027-51070Cell Cycle Proteins0DNA-Binding Proteins0NBN protein, human0Nuclear Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, human9007-49-2DNAEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 5.99.-ERCC2 protein, humanIMAdultAgedAged, 80 and overApoptosisphysiologyradiation effectsBlotting, WesternCell Cyclephysiologyradiation effectsCell Cycle ProteinsgeneticsCell Proliferationradiation effectsColorectal NeoplasmsbloodgeneticspathologyComet AssayDNAgeneticsDNA Damagegeneticsradiation effectsDNA Repairgeneticsradiation effectsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleFlow CytometryGenetic Predisposition to DiseaseGenotypeHumansLymphocytesmetabolismradiation effectsMaleMiddle AgedNuclear ProteinsgeneticsPolymorphism, GeneticgeneticsReal-Time Polymerase Chain ReactionTumor Cells, CulturedX-RaysX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D ProteingeneticsAPE1Cell cycleDNA break repairHCT116 cellsNBSPolymorphismXPDXRCC1
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1090-210443532013Jun07Biochemical and biophysical research communicationsBiochem. Biophys. Res. Commun.Histone deacetylases inhibitor trichostatin A modulates the extracellular release of APE1/Ref-1.403-710.1016/j.bbrc.2013.04.101S0006-291X(13)00755-9Apurinic/apyrimidinic endonuclease 1/Redox factor-1 (APE1/Ref-1) can be acetylated via post-translational modification. We investigated the effect of an inhibitor of histone deacetylases on the extracellular release of APE1/Ref-1 in HEK293 cells. Trichostatin A (TSA), an inhibitor of histone deacetylases, induced APE1/Ref-1 secretion without changing cell viability. In a fluorescence quantitative assay, the secreted APE1/Ref-1 was estimated to be about 10 ng/mL in response to TSA (1 μM). However, TSA did not induce the secretion of lysine-mutated APE1/Ref-1 (K6R/K7R). TSA also caused nuclear to cytoplasmic translocation of APE1/Ref-1. Taken together, these findings suggest that APE1/Ref-1 is a protein whose secretion is governed by lysine acetylation.Copyright © 2013 Elsevier Inc. All rights reserved.ChoiSungaSDepartment of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.LeeYu RanYRParkMyoung SooMSJooHee KyoungHKChoEun JungEJKimHyo ShinHSKimCuk SeongCSParkJin BongJBIraniKaikobadKJeonByeong HwaBHengJournal ArticleResearch Support, Non-U.S. Gov't20130509
United StatesBiochem Biophys Res Commun03725160006-291X0Histone Deacetylase Inhibitors0Hydroxamic Acids0Recombinant Fusion Proteins0enhanced green fluorescent protein147336-22-9Green Fluorescent Proteins3X2S926L3Ztrichostatin AEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseK3Z4F929H6LysineIMAcetylationdrug effectsActive Transport, Cell Nucleusdrug effectsDNA-(Apurinic or Apyrimidinic Site) LyasechemistrygeneticsmetabolismExtracellular SpaceenzymologyGreen Fluorescent ProteinsgeneticsmetabolismHEK293 CellsHistone Deacetylase InhibitorspharmacologyHumansHydroxamic AcidspharmacologyLysinechemistryMutagenesis, Site-DirectedProtein Processing, Post-Translationaldrug effectsRecombinant Fusion Proteinschemistrygeneticsmetabolism
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23658942NBK133448National Center for Biotechnology Information (US)Bethesda (MD)Probe Reports from the NIH Molecular Libraries Program20102010InternetSmall Molecule Inhibitors of the Human Apurinic/apyrimidinic Endonuclease 1 (APE1)engRaiGaneshaG +NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Rockville, Maryland.VyjayantiVaddadi N.VN +National Institute on Aging, National Institutes of Health, Bethesda, Maryland.DorjsurenDorjbalD +NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Rockville, Maryland.SimeonovAntonA +NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Rockville, Maryland.JadhavAjitA +NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Rockville, Maryland.WilsonDavid M.DM +National Institute on Aging, National Institutes of Health, Bethesda, Maryland.MaloneyDavid J.DJ +NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Rockville, Maryland.ReviewProbe compound, ML199, and related inhibitors of Apurinic/apyrimidinic (AP) endonuclease (APE1) are reported herein. APE1 is a key component of the base excision repair (BER) pathway that is responsible for repair of DNA damage caused by many anti-cancer agents such as bleomycin and temozolomide. As a result, inhibition of APE1 has been postulated as a viable strategy for sensitizing tumor cells to chemotherapy. ML199 and its related analogs belong to a drug-like series that was identified and optimized through a focused medicinal chemistry effort to afford compounds which display competitive inhibition of APE1 activity in the low micromolar potency range. On target effect of the ML199 was demonstrated through a concentration depended inhibition of AP site incision activity in whole cell HeLa extracts. Moreover, ML199 potentiated the cytotoxicity of the DNA alkylating agent methylmethane sulfonate (MMS) at non-cytotoxic doses of the probe compound. The probe and its general class of compounds have shown to have good kinetic solubility, Caco-2 permeability, metabolic stability and other favorable physicochemical properties, thus making ML199 an ideal starting point for further pre-clinical development of anti-cancer agents.
Probe Structure & Characteristics
Recommendations for Scientific Use of the Probe
1Introduction
2Materials and Methods
3Results
4Discussion
5References
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0027-5107745-7462013 May-JunMutation researchMutat. Res.An association selected polymorphisms of XRCC1, OGG1 and MUTYH gene and the level of efficiency oxidative DNA damage repair with a risk of colorectal cancer.6-1510.1016/j.mrfmmm.2013.04.002S0027-5107(13)00043-2Oxidative damage has been implicated in the pathogenesis of colorectal cancer (CRC). The base excision repair (BER) pathway is the major DNA repair pathway for oxidative DNA damage and genetic variation associated with impaired BER might thus increase a risk of CRC. In this work, we evaluated associations between the repair efficiency of oxidative DNA lesions and single-nucleotide polymorphisms of BER genes: the 194Trp/Arg and the 399Arg/Gln XRCC1, the 326Ser/Cys OGG1 and the 324Gln/His MUTYH and CRC occurrence in a Polish population. These polymorphisms were genotyped in 182 CRC patients and 245 control subjects, using a PCR-RFLP approach. The level of oxidative damage and DNA repair capacity in lymphocytes and CRC tissue samples was evaluated by comet assay using FPG and Nth glycosidases. The 326Ser/Cys OGG1 and the 324Gln/His as well as the 324His/His MUTYH genotypes were found to be associated with an increased CRC risk, while no association was found for the XRCC1 gene polymorphisms. It was also demonstrated the reduced capacity of oxidative damage repair in CRC patients in comparison to healthy controls. Moreover, the decrease efficiency of DNA repair were correlated with the 399Gln/Gln XRCC1 and the 324His/His MUTYH genotypes occurrence in CRC patients. The results obtained in our study indicated an association of OGG1 and MUTYH genes polymorphisms involved in oxidative DNA lesions repair with the risk occurrence of colorectal cancer in Polish patients. It was also found that studied polymorphisms might affect DNA repair capacity suggesting their role in CRC pathogenesis. Finally, we conclude that BER pathway may be an important target for the diagnosis and treatment of colorectal patients.Copyright © 2013 Elsevier B.V. All rights reserved.PrzybylowskaKarolinaKDepartment of Clinical Chemistry and Biochemistry, Medical University of Lodz, Poland.KabzinskiJacekJSygutAndrzejADzikiLukaszLDzikiAdamAMajsterekIreneuszIengJournal Article20130423
NetherlandsMutat Res04007630027-51070DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanBBX060AN9VHydrogen PeroxideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanIMAgedCase-Control StudiesColorectal NeoplasmsgeneticspathologyComet AssayDNA DamageDNA GlycosylasesgeneticsDNA Repairdrug effectsgeneticsDNA-Binding ProteinsgeneticsEpistasis, GeneticFemaleGene FrequencyGenetic Predisposition to DiseaseHumansHydrogen PeroxidepharmacologyMaleMiddle AgedPolandPolymorphism, Single NucleotideX-ray Repair Cross Complementing Protein 1
201204272013032520130409201342760201342760201383060ppublish23618615S0027-5107(13)00043-210.1016/j.mrfmmm.2013.04.002
235814102013072320130509
0028-26856042013NeoplasmaNeoplasmaAlteration of the microRNA expression profile in human osteosarcoma cells transfected with APE1 siRNA.384-9410.4149/neo_2013_050Apurinic/apyrimidinic endonuclease1 (APE1), which has the dual functions of DNA repair and redox regulation, is considered to be a promising potential target in cancer treatment. Microarray and qRT-PCR were used to confirm the change of miRNA followed by analysis with comprehensive bioinformatics-based analysis. Both microarray and qRT-PCR demonstrated that 13 microRNAs (miRNAs) were significantly changed (>2-fold) in APE1 knockdown HOS cells; seven of them (hsa-miR-451, hsa-miR-1290, hsa-miR-765, hsa-miR-483-5p, hsa-miR-513a-5p, hsa-miR-129-5p and hsa-miR-31) were up-regulated and the other six (hsa-miR-29b, hsa-miR-197, has-let-7b, hsa-miR-324-5p, hsa-let-7i and hsa-miR-484) were down-regulated. Furthermore, pathway analysis showed that these miRNAs and their target genes affected by the expression of APE1 were involved in pathways relating to developmental processes, regulation of cellular processes, cell signaling (such as TGF-β, Wnt, MAPK and the p53 signaling pathway) and cancers. There are putative binding sites of NF-κB, p53, HIF-1α, AP-1, PEBP2, ATF, NF-Y, Pax-2,CREB and c-Myb in the promoters of several down regulated miRNAs, indicating that APE1 may regulate miRNAs via transcription factors. Our data suggest that our understanding of the biological functions of APE1 will inevitably expand due to the novel pathways that APE1 uses to regulate gene expression through miRNAs.DaiNNThird Military Medical University, Chongqing, People's Republic of China.ZhongZ YZYCunY PYPQingYYChenChChJiangPPLiM XMXWangDDengJournal ArticleResearch Support, Non-U.S. Gov't
SlovakiaNeoplasma03772660028-26850MicroRNAs0RNA, Small Interfering0Transcription FactorsEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMBinding SitesBone NeoplasmsgeneticsCell Line, TumorComputational BiologyDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsgeneticsphysiologyDown-RegulationGene Regulatory NetworksHumansMicroRNAsanalysisOsteosarcomageneticsRNA, Small InterferinggeneticsTranscription FactorsmetabolismTransfection
201341660201341660201372460ppublish2358141010.4149/neo_2013_050
235635972013102920130417
1791-24312962013JunOncology reportsOncol. Rep.Combined use of adenoviral vector Ad5/F35-mediated APE1 siRNA enhances the therapeutic efficacy of adenoviral-mediated p53 gene transfer in hepatoma cells in vitro and in vivo.2197-20410.3892/or.2013.2384Gene therapy has emerged as a novel therapeutic approach for the treatment of cancer. In order to establish a more effective therapeutic strategy against unresectable hepatocellular carcinoma (HCC), we evaluated, in the present study, the effects of combined treatment with adenoviral vector Ad5/F35-mediated APE1 siRNA (Ad5/F35-siAPE1) and adenoviral-mediated p53 gene transfer (Ad-p53) in hepatoma cells in vitro and in vivo. Infection of SMMC-7721 cells with Ad5/F35-siAPE1 resulted in a time- and dose-dependent decrease of APE1 protein, while Ad-p53 treatment led to a time- and dose-dependent increase of p53 protein expression. Ad5/F35-siAPE1 significantly enhanced the cytotoxic effect of SMMC-7721 cells to Ad-p53 in cell survival assays, associated with increased cell apoptosis. Moreover, administration of Ad5/F35-siAPE1 and Ad-p53 into nude mice resulted in tumor growth inhibition and apoptosis induction in SMMC-7721 xenografts compared to administration of either agent alone. These results suggest that combination of Ad5/F35-siAPE1 and Ad-p53 could be a promising gene therapeutic approach against human HCC.CunYanpingYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, PR China.ZhangQinhongQXiongChengjieCLiMengxiaMDaiNanNZhangShihengSWangDongDengJournal ArticleResearch Support, Non-U.S. Gov't20130404
GreeceOncol Rep94227561021-335X0RNA, Small Interfering0TP53 protein, human0Tumor Suppressor Protein p530enhanced green fluorescent protein147336-22-9Green Fluorescent ProteinsEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdenoviridaegeneticsAnimalsApoptosisCarcinoma, HepatocellularpathologytherapyCell Line, TumorCell SurvivalDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismGene ExpressionGenetic TherapyGenetic VectorsGreen Fluorescent ProteinsbiosynthesisgeneticsHumansLiver Neoplasms, ExperimentalpathologytherapyMiceMice, NudeNeoplasm TransplantationRNA, Small InterferinggeneticsTransduction, GeneticTumor BurdenTumor Suppressor Protein p53geneticsmetabolism
201301172013021420134960201349602013103060ppublish2356359710.3892/or.2013.2384
235098212013111220170220
2314-614120132013BioMed research internationalBiomed Res IntKilling effect of Ad5/F35-APE1 siRNA recombinant adenovirus in combination with hematoporphrphyrin derivative-mediated photodynamic therapy on human nonsmall cell lung cancer.95791310.1155/2013/957913The main goal of this work is to investigate the killing effects and molecular mechanism of photodynamic therapy (PDT) mediated by the Ad5/F35-APE1 siRNA recombinant adenovirus in combination with a hematoporphrphyrin derivative (HpD) in the A549 human lung adenocarcinoma cell line in vitro to provide a theoretical reference for treating lung cancer by HpD-PDT. By using the technologies of MTT, flow cytometry, ELISA, and western blot, we observed that the proliferation inhibition and apoptosis of the A549 cells were significantly higher than the control group (P < 0.05) after HpD-PDT was performed. The inhibitory efficiency is dependent on the HpD concentration and laser intensity dose. The inhibitory effect on the proliferation of A549 cells of Ad5/F35-APE1 siRNA is more significant after combining with PDT, as indicated by a significant elevation of the intracellular ROS level and the expression of inflammatory factors (P < 0.05). The HpD-PDT-induced expression of the APE1 protein reached the peak after 24 h in A549 cells. The inhibition of APE1 expression in A549 cells was most significant after 48 hours of infection by Ad5/F35-APE1 siRNA recombinant adenovirus (10 MOI). In conclusion, the Ad5/F35-APE1 siRNA recombinant adenovirus could efficiently inhibit the HpD-PDT-induced APE1 expression hence could significantly enhance the killing effect of HpD-PDT in lung cancer cells.XiaLeiLCancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.GuanWeiWWangDongDZhangYun-SongYSZengLin-LiLLLiZeng-PengZPWangGeGYangZhen-ZhouZZengJournal ArticleResearch Support, Non-U.S. Gov't20121227
United StatesBiomed Res Int1016001730Hematoporphyrins0RNA, Small Interfering0Reactive Oxygen SpeciesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMFree Radic Biol Med. 2012 Apr 1;52(7):1188-20022285766Anticancer Res. 2001 Nov-Dec;21(6A):4041-911911289Mutat Res. 2000 Oct 16;461(2):83-10811018583CA Cancer J Clin. 2011 Jul-Aug;61(4):250-8121617154Curr Opin Mol Ther. 2008 Apr;10(2):158-6718386228Cancer Lett. 2004 Dec 8;216(1):43-5415500948Biomicrofluidics. 2011 Dec;5(4):41101-41101622662052J Clin Oncol. 2006 May 10;24(14):2137-5016682732Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Mutat Res. 1994 Jul;315(1):55-637517011Lasers Surg Med. 2006 Jun;38(5):371-516788919Photodiagnosis Photodyn Ther. 2012 Mar;9(1):52-922369729Mol Cancer Res. 2007 Jan;5(1):61-7017259346Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1443-811818553Science. 2002 Apr 19;296(5567):550-311910072PLoS One. 2012;7(6):e3858322715393Nat Biotechnol. 2002 May;20(5):505-811981566FASEB J. 2004 Jun;18(9):986-815084519Clin Lymphoma Myeloma. 2007 Jan;7(4):296-30417324338Nucleic Acids Res. 1994 Nov 25;22(23):4884-97800476Cancer. 2004 Jul 1;101(1):3-2715221985Drug Discov Today. 2002 Oct 15;7(20):1040-612546893AdenoviridaegeneticsApoptosisCarcinoma, Non-Small-Cell LungpathologytherapyCell Line, TumorDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsEnzyme-Linked Immunosorbent AssayFlow CytometryGenetic TherapymethodsGenetic VectorsHematoporphyrinspharmacologyHumansInflammationLung NeoplasmspathologytherapyPhotochemotherapymethodsRNA, Small InterferingmetabolismReactive Oxygen Species
20120726201210042013320602013320602013111360ppublish2350982110.1155/2013/957913PMC3591196
235059222013040120130319
1433-6510591-22013Clinical laboratoryClin. Lab.Association of the polymorphism of APE1 gene with the risk of prostate cancer in Chinese Han population.163-8DNA damage, caused by numerous carcinogens, contributes to the increased risk of different types of cancer. The base excision repair (BER) pathway including the apurinic/apyrimidic endonuclease (APE1, also known as APEX1) gene plays an important role in preventing the accumulation of DNA damage and maintaining genomic stability. The aim of the present study is to determine whether polymorphisms of APE1 are associated with the risk of prostate cancer (PCa) in the Chinese Han population.This study consisted of 198 patients with PCa and 156 healthy controls. The polymorphisms of APE1, Asp148Glu (rs1130409) and -141T/G (rs1760944) were determined by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.The genotypic distributions of the two polymorphisms in controls were in Hardy-Weinberg equilibrium (p = 0.92 and p = 0.83, respectively). Logistic regression analysis indicated that the -141GG genotype was significantly associated with a decreased risk of PCa compared with the -141TT genotype (p = 0.03; OR 0.49; 95% CI 0.26 - 0.92). The G allele was also significantly associated with a reduced risk of PCa compared with the T allele (p = 0.02; OR 0.71; 95% CI 0.52 - 0.96). However, no association between Asp148Glu polymorphism and the risk of PCa was found.The -141GG genotype and G allele of the APE1 gene are associated with a decreased risk of PCa in the Chinese Han population.JingBaoBDepartment of Urology, The Second Hospital, Tianjin Medical University, Tianjin Institute of Urology, Tianjin, PR China.WangJuanJChangWen-LiangWLLiBoBChenJingJNiuYuan-JieYJengJournal Article
GermanyClin Lab97056111433-65100DNA PrimersEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAgedBase SequenceCase-Control StudiesChinaDNA PrimersDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsEthnic GroupsGenetic Predisposition to DiseaseHumansMalePolymerase Chain ReactionPolymorphism, GeneticPolymorphism, Restriction Fragment LengthProstatic Neoplasmsgenetics
20133206020133206020134260ppublish23505922
234992412013071620171116
0027-510775312013Apr30Mutation researchMutat. Res.Association of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326Ser/Cys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of primary open-angle glaucoma.12-2210.1016/j.mrgentox.2012.12.019S1383-5718(13)00067-3Numerous data have shown that progressive loss of human trabecular meshwork (TM) cells may be connected with oxidative stress. This hypothesis may suggest an association of base excision repair with the risk of primary open angle glaucoma development.The aim of this study was to evaluate the role of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326SerCys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of POAG.Our research included 170 patients with POAG and 193 healthy controls. Gene polymorphisms were investigated by PCR-RFLP. The Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed.The 399Arg/Gln genotype of the XRCC1 gene was associated with an increased risk for POAG (OR 2.50; 95% CI, 1.54-4.07, P=0.0002). The 399Gln/Gln XRCC1 genotype may increase the risk for POAG progression according to clinical parameters such as cup/disk ratio (c/d) (OR 1.93; 95% CI, 1-3.73, P=0.04) and Rim area (RA factor) (OR 3.88; 95% CI, 1.01-14.82, P=0.04). Moreover, an association was found of retinal nerve-fiber layer (RNFL factor) with the 399Arg/Gln XRCC1 genotype distribution and POAG progression (OR 2.46; 95% CI, 1.06-5.68, P=0.03). In contrast, analysis of the 324Gln/His MUTYH gene polymorphism distribution in the patient group according to RA factor showed that it may reduce the progression of POAG (OR 0.14; 95% CI, 0.02-0.89, P=0.05). Our current study demonstrates an association between the 326Ser/Cys OGG1 gene polymorphism and the 326Cys allele of the OGG1 gene, and progression of POAG. In addition, the presence of the 326His allele of the MUTYH gene may increase the risk for POAG progression, according to the VF parameter (OR 2.57; 95% CI, 1.47-4.57, P=0.0001).We suggest that the 399Arg/Gln genotype and the 399Gln allele of the XRCC1 gene may be risk factors for POAG development. Moreover, we postulate that the 399 Arg/Gln XRCC1, the 326 Ser/Cys OGG1 and the 324 Gln/His MUTYH genes polymorphisms may be associated with progression of POAG.Copyright © 2013 Elsevier B.V. All rights reserved.SzaflikJacek PJPDepartment of Ophthalmology II, Medical Faculty, Medical University of Warsaw, Poland.CuchraMagdaMPrzybylowska-SygutKarolinaKDzikiLukaszLKurowskaAnna KAKGacekMiraMDrzewoskiJozefJSzaflikJerzyJMajsterekIreneuszIengJournal ArticleResearch Support, Non-U.S. Gov't20130307
NetherlandsMutat Res04007630027-51070Codon0DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-mutY adenine glycosylaseEC 3.2.2.-oxoguanine glycosylase 1, humanIMAgedAged, 80 and overAllelesAmino Acid SubstitutionCardiovascular DiseasesepidemiologyCodongeneticsComorbidityDNA GlycosylasesgeneticsphysiologyDNA-Binding ProteinsgeneticsphysiologyDiabetic RetinopathyepidemiologyDisease ProgressionFemaleGenetic Predisposition to DiseaseGenotypeGlaucoma, Open-AngleepidemiologygeneticsHumansMaleMiddle AgedMutation, MissensePoint MutationPolymorphism, Single NucleotideRiskSeverity of Illness IndexSmokingepidemiologyX-ray Repair Cross Complementing Protein 1
201204172012102420121205201331960201331960201371760ppublish23499241S1383-5718(13)00067-310.1016/j.mrgentox.2012.12.019
234854692013062820130506
1090-210443422013May03Biochemical and biophysical research communicationsBiochem. Biophys. Res. Commun.A novel role for Gadd45α in base excision repair: modulation of APE1 activity by the direct interaction of Gadd45α with PCNA.185-9010.1016/j.bbrc.2013.02.066S0006-291X(13)00326-4The growth arrest and DNA damage inducible, alpha (Gadd45α) protein regulates DNA repair by interacting with proliferating cell nuclear antigen (PCNA). Our previous study suggested a potential role for Gadd45α in the base excision repair (BER) pathway by affecting apurinic/apyrimidinic endonuclease 1 (APE1) protein in addition to its accepted role in nucleotide excision repair (NER). Here, we investigated whether the interaction of Gadd45α with PCNA affects APE1 activity. To address this issue, we used a siRNA directed to Gadd45α and a form of Gadd45α with a mutation to the predicted site of PCNA binding. There was a reduction of APE1 activity in cells transfected with the Gadd45α siRNA. Furthermore, the interaction of Gadd45α with PCNA and APE1 was lower in cells transfected with mutant Gadd45α compared with cells transfected with wild-type Gadd45α. Indeed, we observed that the APE1 activity in the Gadd45α-interacting complex was significantly lower in cells that overexpress mutant Gadd45α compared with cells that overexpress wild-type Gadd45α. We conclude that the PCNA binding site on Gadd45α plays a critical role in modulating the interaction with PCNA and APE1, affecting BER activity. These results provide novel insights into the mechanisms by which BER activity is modulated, although the interaction of Gadd45α with APE1 needs to be clarified.Copyright © 2013 Elsevier Inc. All rights reserved.KimHye LimHLDepartment of Life Science, Dongguk University, 30 Pildong-ro 1-gil, Jung-gu, Seoul 100-715, Republic of Korea.KimSang UkSUSeoYoung RokYRengJournal ArticleResearch Support, Non-U.S. Gov't20130226
United StatesBiochem Biophys Res Commun03725160006-291X0Cell Cycle Proteins0GADD45A protein, human0Nuclear Proteins0Proliferating Cell Nuclear Antigen0RNA, Small InterferingEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAmino Acid SequenceBinding SitesCell Cycle ProteinsgeneticsmetabolismDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismEnzyme ActivationEnzyme AssaysHep G2 CellsHumansMolecular Sequence DataMutagenesis, Site-DirectedNuclear ProteinsgeneticsmetabolismProliferating Cell Nuclear AntigengeneticsmetabolismProtein BindingProtein Interaction MappingRNA, Small InterferinggeneticsmetabolismTransfection
201302132013021720133156020133156020137360ppublish23485469S0006-291X(13)00326-410.1016/j.bbrc.2013.02.066
234721282013120320170220
1932-6203832013PloS onePLoS ONESerum APE1 autoantibodies: a novel potential tumor marker and predictor of chemotherapeutic efficacy in non-small cell lung cancer.e5800110.1371/journal.pone.0058001Apurinic/apyrimidinic endonuclease 1 (APE1), which has the dual functions of both DNA repair and redox activity, has been reported to be highly expressed in non-small cell lung cancer (NSCLC), and this appears to be a characteristic related to chemotherapy resistance. In this study, we identified serum APE1 autoantibodies (APE1-AAbs) in NSCLC patients and healthy controls by immunoblotting and investigated the expression of APE1-AAbs by indirect ELISA from the serum of 292 NSCLC patients and 300 healthy controls. In addition, serum APE1-AAbs level alterations of 91 patients were monitored before and after chemotherapy. Our results showed that serum APE1-AAbs can be detected in both NSCLC patients and healthy controls. Serum APE1-AAbs were significantly higher than those of healthy controls and closely related to APE1 antigen levels both in tumor tissues and the peripheral blood. Moreover, the change in levels of serum APE1-AAbs in NSCLC is closely associated with the response to chemotherapy. These results suggest that APE1-AAbs is a potential tumor marker and predictor of therapeutic efficacy in NSCLC.DaiNanNCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China.CaoXiao-JingXJLiMeng-XiaMXQingYiYLiaoLingLLuXian-FengXFZhangShi-HengSHLiZhengZYangYu-XinYXWangDongDengJournal ArticleResearch Support, Non-U.S. Gov't20130305
United StatesPLoS One1012850811932-62030Antigens0Antineoplastic Agents0Autoantibodies0Biomarkers, TumorEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAntioxid Redox Signal. 2009 Mar;11(3):621-3818715144Anticancer Res. 2004 Jul-Aug;24(4):2127-3415330152Ann Oncol. 2011 Feb;22(2):383-920675559Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Cancer Treat Rev. 2010 Aug;36(5):425-3520056333Cancer Immunol Immunother. 1998 Aug;46(6):345-99756419Mol Cell Proteomics. 2011 Jun;10(6):M110.00533021474795Anticancer Res. 2001 Nov-Dec;21(6A):4041-911911289Cancer Lett. 2009 Sep 18;282(2):159-6619380192Mutat Res. 2000 Oct 16;461(2):83-10811018583Leuk Res. 2011 Jul;35(7):965-721570119Carcinogenesis. 2007 Oct;28(10):2082-817522062Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Lung Cancer. 2003 Feb;39(2):165-7212581569Nature. 2005 Apr 14;434(7035):907-1315829965Hum Immunol. 2010 Jul;71(7):643-5120433885CA Cancer J Clin. 2010 Sep-Oct;60(5):277-30020610543Mass Spectrom Rev. 2007 May-Jun;26(3):451-6617407130J Cell Mol Med. 2011 Oct;15(10):2013-2421651719Mol Cell Biol. 2008 Dec;28(23):7066-8018809583N Engl J Med. 1993 Feb 25;328(8):546-518381208Lung Cancer. 2009 Dec;66(3):298-30419324449Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Ann Oncol. 2008 Sep;19 Suppl 7:vii25-718790961Oncogene. 2010 Jul 29;29(30):4330-4020498636CJEM. 2006 Jan;8(1):19-2017175625Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Lung Cancer. 2008 Dec;62(3):364-7318485524Cell Cycle. 2006 Feb;5(3):250-916418580Cancer Causes Control. 2010 Jun;21(6):959-6520217210N Engl J Med. 2004 May 20;350(21):2129-3915118073PLoS One. 2010;5(12):e1500321170350PLoS One. 2012;7(7):e4075922815807Cancer Lett. 2005 Dec 18;230(2):187-9816297705Int J Oncol. 2009 Nov;35(5):1069-7919787261Clin Cancer Res. 1995 Dec;1(12):1463-99815945Lung Cancer. 2008 May;60(2):277-8418061304Clin Cancer Res. 2011 Mar 15;17(6):1474-8021138858Nat Immunol. 2000 Sep;1(3):181-510973269Cell Res. 2008 Jan;18(1):27-4718166975DNA Repair (Amst). 2012 Apr 1;11(4):374-8022284908PLoS One. 2008;3(10):e340918923710J Clin Oncol. 2008 Nov 1;26(31):5060-618794547FEBS J. 2009 Dec;276(23):6880-90419860826Ann Oncol. 2010 Oct;21 Suppl 7:vii199-20220943615CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855J Natl Cancer Inst. 1998 Oct 21;90(20):1563-89790550Biochim Biophys Acta. 2006 Apr;1765(2):223-3416480833Int J Proteomics. 2011;2011:72686922229091Cancer Biomark. 2010;6(3-4):123-3520660959Biochim Biophys Acta. 2006 Apr;1762(4):398-40316483750Gene. 2005 Jul 18;354:140-615979824Cancer Lett. 2006 Feb 20;233(1):48-5615913883Cancer Lett. 2006 May 8;236(1):64-7115992994Autoimmunity. 2008 Mar;41(2):123-3218324481AdultAgedAged, 80 and overAntigensimmunologyAntineoplastic Agentstherapeutic useAutoantibodiesbloodBiomarkers, TumorbloodCarcinoma, Non-Small-Cell Lungdiagnosisdrug therapymetabolismCase-Control StudiesDNA-(Apurinic or Apyrimidinic Site) LyaseimmunologyFemaleGene Expression Regulation, NeoplasticHumansLung Neoplasmsdiagnosisdrug therapymetabolismMaleMiddle AgedROC Curve
201211062013012920133960201339602013121660ppublish2347212810.1371/journal.pone.0058001PONE-D-12-35184PMC3589448
234304442013102420171116
1559-131X3022013JunMedical oncology (Northwood, London, England)Med. Oncol.Polymorphisms in genes of APE1, PARP1, and XRCC1: risk and prognosis of colorectal cancer in a northeast Chinese population.50510.1007/s12032-013-0505-zBase excision repair (BER) pathway plays critical role in maintaining genome integrity. Polymorphisms in BER genes which modulate the DNA repair capacity may affect the susceptibility and prognosis of cancer. We conducted a case-control study and followed up the cases to explore the associations between BER genes polymorphisms and the risk and prognosis of colorectal cancer (CRC). This study included 451 CRC patients and 631 controls. Four single-nucleotide polymorphisms (SNPs) in genes of apurinic/apyrimidinic endonuclease-1 (APE1), ADP-ribosyltransferase (ADPRT, also known as PARP1), and X-ray repair cross-complementing groups 1 (XRCC1) were tested by PCR-RFLP. Odds ratio (OR), hazard ratio (HR), and their 95 % confidence intervals (CIs) were calculated by unconditional logistic regression and Cox proportional hazard model. PARP1 762 recessive model (OR = 1.57, 95 % CI 1.12-2.20) and XRCC1 194 dominant model (OR = 1.45, 95 % CI 1.12-1.88) were associated with increased CRC risk. A significant increasing trend for the risk of CRC was detected with the increasing number of putative risk genotypes (P (trend) = 0.00). However, no association was found between these four SNPs and the prognosis of CRC. In conclusion, APE1 (Asp148Glu), PARP1 (Ala762Val), and XRCC1 (Arg399Gln, Arg194Trp) were associated with the susceptibility to CRC, but were not associated with the prognosis of CRC.LiYeYDepartment of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, People's Republic of China.LiShuyingSWuZhiweiZHuFulanFZhuLinLZhaoXiaojuanXCuiBinbinBDongXinshuXTianSuliSWangFanFZhaoYashuangYengJournal ArticleResearch Support, Non-U.S. Gov't20130222
United StatesMed Oncol94355121357-05600Biomarkers, Tumor0DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 2.4.2.30PARP1 protein, humanEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMGenet Epidemiol. 2012 Jan;36(1):56-6522127734J Biomed Sci. 2007 Mar;14(2):183-9317191090Cancer Res. 2007 Feb 1;67(3):1395-40417283177Tumour Biol. 2013 Feb;34(1):555-6323188703Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12 ):3384-819959686Clin Cancer Res. 2008 Sep 15;14(18):5919-2418779313Carcinogenesis. 2002 Aug;23(8):1321-512151350Cancer Epidemiol Biomarkers Prev. 2005 Nov;14(11 Pt 1):2501-816284370Mutat Res. 2008 Feb 1;638(1-2):146-5317991492J Nutrigenet Nutrigenomics. 2009;2(6):273-920559012Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2363-7218006925J Clin Oncol. 2005 Dec 1;23(34):8664-7016260700J Exp Clin Cancer Res. 2008 Sep 30;27:4918823566Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Curr Mol Pharmacol. 2012 Jan;5(1):115-2422122468Structure. 1997 Dec 15;5(12):1543-509438868Mutat Res. 2007 May-Jun;635(2-3):118-4517419091Cancer Epidemiol Biomarkers Prev. 2010 Dec;19(12):3167-7321037106Cancer Lett. 2000 Oct 16;159(1):79-8610974409Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2101-816609022J Cancer Res Clin Oncol. 2010 Oct;136(10):1517-2520229274CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855BMC Cancer. 2011 Dec 18;11:52122176746BMC Cancer. 2005 Jan 28;5:1215679883Asian Pac J Cancer Prev. 2011;12(11):2981-422393975Mol Biol Rep. 2009 Jul;36(6):1461-718716896AgedAmino Acid SubstitutiongeneticsAsian Continental Ancestry GroupethnologygeneticsBiomarkers, TumorgeneticsChinaepidemiologyColorectal NeoplasmsepidemiologyethnologygeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGenetic Predisposition to DiseaseethnologygeneticsHumansMaleMiddle AgedPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesgeneticsPolymorphism, GeneticPolymorphism, Single NucleotidegeneticsPopulation SurveillancemethodsPrognosisRisk FactorsX-ray Repair Cross Complementing Protein 1
20121222201302082013223602013223602013102560ppublish2343044410.1007/s12032-013-0505-z
234184392013080920170220
1932-6203822013PloS onePLoS ONESilencing of APE1 enhances sensitivity of human hepatocellular carcinoma cells to radiotherapy in vitro and in a xenograft model.e5531310.1371/journal.pone.0055313Resistance to radiotherapy is a key limitation for the treatment of human hepatocellular carcinoma (HCC). To overcome this problem, we investigated the correlation between radioresistance and the human apurinic/apyrimidinic endonuclease (APE1), a bifunctional protein, which plays an important role in DNA repair and redox regulation activity of transcription factors. In the present study, we examined the radiosensitivity profiles of three human HCC cell lines, HepG2, Hep3B, and MHCC97L, using the adenoviral vector Ad5/F35-mediated APE1 siRNA (Ad5/F35-siAPE1). The p53 mutant cell lines MHCC97L showed radioresistance, compared with HepG2 and Hep3B cells. APE1 was strongly expressed in MHCC97L cells and was induced by irradiation in a dose-dependent manner, and Ad5/F35-siAPE1 effectively inhibited irradiation-induced APE1 and p53 expression. Moreover, silencing of APE1 significantly potentiated the growth inhibition and apoptosis induction by irradiation in all tested human HCC cell lines. In addition, Ad5/F35-siAPE1 significantly enhanced inhibition of tumor growth and potentiated cell apoptosis by irradiation both in HepG2 and MHCC97L xenografts. In conclusion, down regulation of APE1 could enhance sensitivity of human HCC cells to radiotherapy in vitro and in vivo.CunYanpingYCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.DaiNanNXiongChengjieCLiMengxiaMSuiJiangdongJQianChengyuanCLiZhengZWangDongDengJournal ArticleResearch Support, Non-U.S. Gov't20130213
United StatesPLoS One1012850811932-62030RNA, Small InterferingEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAntioxid Redox Signal. 2009 Mar;11(3):601-2018976116J Biol Chem. 2002 Feb 8;277(6):3870-711698412Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a00110720182618Oncogene. 1995 Jun 1;10(11):2103-117784055Science. 1999 Sep 10;285(5434):1733-710481009Genes Dev. 1997 Mar 1;11(5):558-709119221Br J Cancer. 1998 Nov;78(9):1128-339820167Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Cancer Gene Ther. 2008 Oct;15(10):625-3518535621FASEB J. 1993 Nov;7(14):1407-138224613Cancer Sci. 2007 Dec;98(12):1993-200117892509Curr Gene Ther. 2006 Feb;6(1):111-2316475949Int J Radiat Biol. 2010 Jun;86(6):445-5720470195Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12245-5019617533Gynecol Oncol. 2004 Feb;92(2):568-7714766249Free Radic Biol Med. 2005 May 1;38(9):1121-3815808410J Biol Chem. 2003 Mar 14;278(11):9592-60112515829Radiologe. 2008 Sep;48(9):839-4918766324Apoptosis. 2007 Feb;12(2):387-9317191126J Cell Biochem. 2007 Mar 1;100(4):883-9617031865Radiother Oncol. 2007 Sep;84(3):266-7117716760Invest New Drugs. 2011 Oct;29(5):861-7220414698Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Cancer Lett. 2000 Mar 31;150(2):191-910704742Am J Chin Med. 2006;34(1):125-3516437745Int J Oncol. 2001 Oct;19(4):799-80211562758Nature. 1991 Apr 4;350(6317):429-311672732CA Cancer J Clin. 2012 Jan-Feb;62(1):10-2922237781Radiother Oncol. 2009 Sep;92(3):293-819726094Ann N Y Acad Sci. 1994 Jul 29;726:306-87522424Cancer Treat Rev. 2005 Dec;31(8):603-1716298073Trends Pharmacol Sci. 2006 Jun;27(6):338-4416697054Carcinogenesis. 2004 Jan;25(1):11-914555612Mol Med. 2007 Jan-Feb;13(1-2):89-9617515960Nat Rev Mol Cell Biol. 2007 Apr;8(4):275-8317380161Gastroenterology. 2004 Nov;127(5 Suppl 1):S104-715508072Lung Cancer. 2008 May;60(2):277-8418061304Int J Cancer. 2010 Dec 15;127(12):2893-91721351269Int J Cancer. 2001 Oct 15;94(2):290-611668511Cancer Res. 2001 Mar 1;61(5):2220-511280790Evid Based Complement Alternat Med. 2011;2011:75832621799693Clin Lymphoma Myeloma. 2007 Jan;7(4):296-30417324338Oncogene. 2005 Feb 24;24(9):1641-715674341Hepatology. 1995 Oct;22(4 Pt 1):1279-887557882Oncogene. 2011 Apr 21;30(16):1947-5521132005AnimalsApoptosisgeneticsradiation effectsCarcinoma, HepatocellulargeneticsradiotherapyCell Line, TumorDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismDose-Response Relationship, RadiationDown-RegulationGene SilencingphysiologyHumansLiver NeoplasmsgeneticsradiotherapyMiceNeoplasm TransplantationRNA, Small InterferingRadiation ToleranceTransplantation, Heterologous
2012080620121221201321960201321960201381060ppublish2341843910.1371/journal.pone.0055313PONE-D-12-23652PMC3572126
233780242013121720130506
1477-9137126Pt 62013Mar15Journal of cell scienceJ. Cell. Sci.The presence of a truncated base excision repair pathway in human spermatozoa that is mediated by OGG1.1488-9710.1242/jcs.121657DNA repair has long been considered impossible in human spermatozoa due to the high level of DNA compaction observed in these cells. However, detailed examination of the base excision repair pathway in human spermatozoa has revealed the presence of an enzyme critical to this pathway, 8-oxoguanine DNA glycosylase 1 (OGG1). This glycosylase was associated with the sperm nucleus and mitochondria and could actively excise 8-hydroxy-2'-deoxyguanosine (8OHdG), releasing this adduct into the extracellular space. This activity was significantly reduced in the presence of cadmium (II), a recognized inhibitor of OGG1, in a time- and dose-dependent manner (P<0.001). Remarkably, spermatozoa do not possess the downstream components of the base excision repair pathway, apurinic endonuclease 1 (APE1) and X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1). The absence of these proteins was particularly significant, as APE1 is required to create a 3'-hydroxyl (3'-OH) terminus at the apurinic site created by OGG1, which would be recognized by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. As a result, TUNEL was unable to detect oxidatively induced DNA damage in spermatozoa following exposure to hydrogen peroxide. In the same cells, intracellular and extracellular 8OHdG could be clearly detected in a manner that was highly correlated with the outcome of the sperm chromatin structure assay (SCSA). However, incubation of these cells for 48 hours revealed a time-dependent increase in TUNEL positivity, suggesting the perimortem activation of a nuclease. These results emphasize the limited capacity of mature spermatozoa to mount a DNA repair response to oxidative stress, and highlight the importance of such mechanisms in the oocyte in order to protect the embryo from paternally mediated genetic damage.SmithTegan BTBPriority Research Centre in Reproductive Science, Discipline of Biological Sciences, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.DunMatthew DMDSmithNathan DNDCurryBen JBJConnaughtonHaley SHSAitkenRobert JRJengJournal ArticleResearch Support, Non-U.S. Gov't20130201
EnglandJ Cell Sci00524570021-95330DNA Adducts00BH33GNGHCadmiumBBX060AN9VHydrogen PeroxideEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAnimalsCOS CellsCadmiummetabolismCell NucleusmetabolismCercopithecus aethiopsCricetinaeDNA AdductsmetabolismDNA DamageDNA GlycosylasesmetabolismDNA RepairphysiologyHumansHydrogen PeroxidemetabolismMaleMitochondriametabolismOxidative StressProtein TransportSignal TransductionSpermatozoaphysiologyDNA damageHuman spermatozoaOGG1Oxidative stress
20132560201325602013121860ppublish23378024jcs.12165710.1242/jcs.121657
233764762013042920131121
1879-316921822013Apr12Toxicology lettersToxicol. Lett.OGG1 Ser326Cys polymorphism interacts with cigarette smoking to increase oxidative DNA damage in human sperm and the risk of male infertility.144-910.1016/j.toxlet.2013.01.017S0378-4274(13)00039-88-Oxoguanine DNA glycosylase 1 (OGG1) plays an important role in repairing oxidative DNA damage induced by chemical agents, such as tobacco. This study examined the effects of OGG1 Ser326Cys polymorphism and cigarette smoking, alone or combined, on sperm oxidative DNA damage and the risk of male infertility. A total of 620 idiopathic infertile subjects and 480 fertile controls were recruited in this study. Sperm 8-hydroxydeoxyguanine (8-OHdG) was measured by immunofluorescent assay using flow cytometry and genotypes were determined by OpenArray platform with a chip-based Taq-Man genotyping technology. Our results demonstrated that both cigarette smoking and OGG1 polymorphism can affect the sperm 8-OHdG levels. Individuals with variant Cys/Cys homozygote showed higher levels of sperm 8-OHdG than wide-type homozygote carriers (Ser/Ser). Stratified analysis found that the association between OGG1 polymorphism and sperm 8-OHdG levels was only observed among smokers with pack-years ≥5 but not among those subjects with pack-years<5 (pack-years=packs smoked per day×years as a smoker). Further analysis based on the case-control study revealed that variant allele (Cys) of OGG1 was significantly associated with male infertility risk in a dominant model (OR=1.35, 95% CI: 1.01-1.82; trend P<0.001). Furthermore, we found a significant gene-environment interaction between OGG1 Ser326Cys polymorphism and cigarette smoking in relation to male infertility risk (Pinteration=0.0003). These findings provided the first evidence about potential interactive effects of OGG1 polymorphism and cigarette smoking on male infertility risk.Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.JiGuixiangGNanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042, China.YanLifengLLiuWeiWQuJianhuaJGuAihuaAengJournal ArticleResearch Support, Non-U.S. Gov't20130131
NetherlandsToxicol Lett77090270378-42745Z93L87A1RGuanine6957-76-28-oxo-7,8-dihydrodeoxyguanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultCase-Control StudiesDNA Damagedrug effectsDNA GlycosylasesgeneticsmetabolismGene-Environment InteractionGenotypeGuanineanalogs & derivativesanalysisHumansInfertility, Malechemically inducedgeneticsMaleOxidative Stressdrug effectsPolymorphism, Single NucleotideRisk FactorsSmokingadverse effectsSpermatozoadrug effectsmetabolism
2012102420130104201301232013256020132560201343060ppublish23376476S0378-4274(13)00039-810.1016/j.toxlet.2013.01.017
233700072013042420131121
1879-31853052013Mar08ToxicologyToxicologyAPE1/Ref-1 prevents oxidative inactivation of ERK for G1-to-S progression following lead acetate exposure.120-910.1016/j.tox.2013.01.010S0300-483X(13)00015-2Apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector factor-1 is a multifunctional enzyme involved in DNA base excision repair and protein redox regulation. Previously, we have showed that lead acetate (Pb) elicits EGFR activation to initiate the SFK/PKCα/Ras/Raf-1/MKK1/2/ERK signaling cascade functioning against genotoxicity. Here, we explore whether APE1 and reactive oxygen species (ROS) affect ERK signaling and cell cycle progression following Pb exposure. We found that Pb induced APE1 expression and ROS generation in CL3 human lung cancer cells. The Pb-elicited ROS levels and cytotoxicity were further enhanced by introducing small interfering RNA specific for APE1 (siAPE1). E3330, an inhibitor of APE1 redox activity, also augmented the ROS levels and cytotoxicity in Pb-treated cells. Intriguingly, the capability of Pb to activate ERK was abolished under siAPE1 or E3330 co-treatments; conversely, forced expression of APE1 up-regulated the ERK activation by Pb or serum in both Cys65-redox activity dependent and independent manners. Moreover, APE1 formed complex with ERK2, and its redox activity could rescue ERK oxidative inactivation. APE1 redox activity also facilitated the Cyclin D1 expression and G1-to-S progression following Pb exposure. In summary, the results indicate that APE1 is a direct redox regulator of ERK for maintaining the kinase activity to promote cell proliferation.Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.WangYi-TingYTMolecular Carcinogenesis Laboratory, Institute of Biotechnology & Department of Life Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.TzengDer-WanDWWangChun-YuCYHongJing-YinJYYangJia-LingJLengJournal ArticleResearch Support, Non-U.S. Gov't20130128
IrelandToxicology03610550300-483X0Benzoquinones0Organometallic Compounds0Propionates0RNA, Small Interfering0Reactive Oxygen Species136164-66-4E 3330EC 2.7.11.24Extracellular Signal-Regulated MAP KinasesEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseK848JZ4886CysteineRX077P88RYlead acetateIM3T3 CellsAnimalsBenzoquinonespharmacologyBlotting, WesternCell Line, TumorCell Survivaldrug effectsColony-Forming Units AssayCysteinemetabolismDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsphysiologyExtracellular Signal-Regulated MAP Kinasesantagonists & inhibitorsG1 Phasedrug effectsHumansImmunoprecipitationMiceMitosisdrug effectsOrganometallic CompoundstoxicityPlasmidsgeneticsPropionatespharmacologyRNA, Small InterferinggeneticsReactive Oxygen SpeciesmetabolismS Phasedrug effectsSignal Transductiondrug effectsphysiology
2012122120130115201301222013226020132260201342560ppublish23370007S0300-483X(13)00015-210.1016/j.tox.2013.01.010
233697582013110120161125
1873-4596582013MayFree radical biology & medicineFree Radic. Biol. Med.Genetic variants of the APE1 gene and the risk of vitiligo in a Chinese population: a genotype-phenotype correlation study.64-7210.1016/j.freeradbiomed.2013.01.009S0891-5849(13)00019-1Vitiligo is an acquired depigmentation disorder, and reactive oxygen species play an important role in melanocyte damage. Base excision repair is the major pathway responsible for removing reactive oxygen species-induced DNA damage, in which APE1, ADPRT, and XRCC1 play key roles. To investigate the association between genetic variations of these genes and the risk of vitiligo in Chinese populations, we genotyped APE1-Asp148Glu, ADPRT-Val762Ala, and XRCC1-Arg399Gln polymorphisms and measured serum 8-OHdG levels in a hospital-based case-control study. We found that a significantly increased risk of vitiligo was associated with the APE1 Asp/Glu (adjusted odds ratio (OR) 1.24; 95% confidence interval (CI) 1.02-1.52) and Glu/Glu genotypes (adjusted OR 1.48; 95% CI 1.13-1.93), compared with the APE1 Asp/Asp genotype, whereas no vitiligo risk was associated with the genotypes ADPRT-Val762Ala and XRCC1-Arg399Gln. Furthermore, serum 8-OHdG levels were elevated in the APE1-148Glu allele carriers (Asp/Glu+Glu/Glu), in an allele dose-response manner, with the risk of vitiligo (Ptrend<0.05). In addition, we found that the APE1-148Glu variant increased the 8-OHdG levels of cultured human melanocytes treated with H2O2, without any impact on the endonuclease activity. These data suggest that the APE1-Asp148Glu polymorphism aggravates oxidative stress in human melanocytes and contributes to genetic predisposition to vitiligo in Chinese people.Copyright © 2013 Elsevier Inc. All rights reserved.WeiChaoCDepartment of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.JianZheZWangLinLQiangHuiniHShiQiongQGuoSenSLiKaiKHuangYeYLiuLingLLiQiangQLuanQiQYiXiuliXLiXiaXWangGangGGaoTianwenTLiChunyingCengJournal ArticleResearch Support, Non-U.S. Gov't20130129
United StatesFree Radic Biol Med87091590891-58490Reactive Oxygen Species88847-89-68-oxo-7-hydrodeoxyguanosineBBX060AN9VHydrogen PeroxideEC 2.4.2.30PARP1 protein, humanEC 2.4.2.30Poly (ADP-Ribose) Polymerase-1EC 2.4.2.30Poly(ADP-ribose) PolymerasesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseG9481N71RODeoxyguanosineIMCells, CulturedChinaDNA DamagegeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDeoxyguanosineanalogs & derivativesbloodGenetic Association StudiesGenetic Predisposition to DiseaseHumansHydrogen PeroxidepharmacologyMelanocytesdrug effectsmetabolismOxidative Stressdrug effectsgeneticsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesgeneticsReactive Oxygen SpeciesbloodVitiligobloodgenetics
2012061120130113201301222013226020132260201311260ppublish23369758S0891-5849(13)00019-110.1016/j.freeradbiomed.2013.01.009
233685322013091620160511
1945-02571742013AprGenetic testing and molecular biomarkersGenet Test Mol BiomarkersIs there any association between the Ser326Cys polymorphism of the 8-oxoguanine glycosylase 1 (OGG1) gene and risk of colon polyp and abnormal glucose tolerance in acromegaly patients?267-7310.1089/gtmb.2012.0398Evidence arising from experimental studies indicates an association between increased levels of the growth hormone/insulin-like growth factor 1 and oxidative stress. The association of the Ser326Cys polymorphism in the 8-oxoguanine glycosylase (OGG1) gene with a colon carcinoma and diabetes mellitus has been examined. The aim of the study was to compare the genotypic distribution of OGG1 Ser326Cys between acromegaly patients and nonacromegalic subjects and to explore whether this polymorphism is associated with a colon polyp risk and abnormal glucose tolerance.We examined 98 acromegaly patients, and 99 healthy subjects who can be compared in terms of age and gender. All participants were evaluated by anthropometric and biochemical measurements. Also, a 75-g oral glucose test and colonoscopy was applied to the patients. Genomic DNA was isolated from peripheral blood leucocytes and the genotype was assessed by melting temperature analyses after using a real-time polymerase chain reaction protocol.Colon polyps were detected in 13 (30.2%) of 43 patients who underwent the colonoscopy. Except for diastolic blood pressure, clinical and biochemical characteristics were similar between the patients diagnosed with and without a colon polyp. A higher proportion of acromegaly patients had the Ser326Ser genotype when compared to the control group (p=0.007). Genotypes were similar between the patients with a normal glucose tolerance and an abnormal glucose tolerance (p=0.774). The frequency of the Cys allele was significantly higher in patients with polyps than those without a polyp (38.5% vs. 18.3%) (p=0.029).Our results suggest that the Cys allele may influence the colon polyp risk in acromegaly patients. Large-scale studies with acromegaly patients are required to show whether being a carrier of the Cys allele is associated with the risk of a colorectal polyp.ZengiAyhanADepartment of Endocrinology and Metabolism, Isparta Public Hospital, Isparta, Turkey.KaradenizMuammerMCetintasVildan BozokVBHarmanEceETetikAslıAOrmanMehmetMErogluZuhalZCetinkalpSevkiSOzgenAhmet GokhanAGSaygiliFusunFYilmazCandegerCengJournal Article20130131
United StatesGenet Test Mol Biomarkers1014942101945-0257EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAcromegalycomplicationsgeneticsAdultColonic NeoplasmsgeneticsmetabolismColonic PolypsdiagnosisgeneticsDNA GlycosylasesgeneticsFemaleGenetic Predisposition to DiseaseGenotypeGlucose IntolerancegeneticsGlucose Tolerance TestHumansMaleMiddle AgedOxidative StressPolymorphism, GeneticRisk Factors
2013226020132260201391760ppublish2336853210.1089/gtmb.2012.0398
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1083-351X288122013Mar22The Journal of biological chemistryJ. Biol. Chem.Conserved structural chemistry for incision activity in structurally non-homologous apurinic/apyrimidinic endonuclease APE1 and endonuclease IV DNA repair enzymes.8445-5510.1074/jbc.M112.422774Non-coding apurinic/apyrimidinic (AP) sites in DNA form spontaneously and as DNA base excision repair intermediates are the most common toxic and mutagenic in vivo DNA lesion. For repair, AP sites must be processed by 5' AP endonucleases in initial stages of base repair. Human APE1 and bacterial Nfo represent the two conserved 5' AP endonuclease families in the biosphere; they both recognize AP sites and incise the phosphodiester backbone 5' to the lesion, yet they lack similar structures and metal ion requirements. Here, we determined and analyzed crystal structures of a 2.4 Å resolution APE1-DNA product complex with Mg(2+) and a 0.92 Å Nfo with three metal ions. Structural and biochemical comparisons of these two evolutionarily distinct enzymes characterize key APE1 catalytic residues that are potentially functionally similar to Nfo active site components, as further tested and supported by computational analyses. We observe a magnesium-water cluster in the APE1 active site, with only Glu-96 forming the direct protein coordination to the Mg(2+). Despite differences in structure and metal requirements of APE1 and Nfo, comparison of their active site structures surprisingly reveals strong geometric conservation of the catalytic reaction, with APE1 catalytic side chains positioned analogously to Nfo metal positions, suggesting surprising functional equivalence between Nfo metal ions and APE1 residues. The finding that APE1 residues are positioned to substitute for Nfo metal ions is supported by the impact of mutations on activity. Collectively, the results illuminate the activities of residues, metal ions, and active site features for abasic site endonucleases.TsutakawaSusan ESELawrence Berkeley National Laboratory, Berkeley, California 94720, USA.ShinDavid SDSMolClifford DCDIzumiTadahideTArvaiAndrew SASManthaAnil KAKSzczesnyBartoszBIvanovIvaylo NINHosfieldDavid JDJMaitiBuddhadevBPiqueMike EMEFrankelKenneth AKAHitomiKenichiKCunninghamRichard PRPMitraSankarSTainerJohn AJAengPDB4HNO4IEMR01 CA158910CANCI NIH HHSUnited StatesR01 CA053791CANCI NIH HHSUnited StatesCA053791CANCI NIH HHSUnited StatesP01 CA092584CANCI NIH HHSUnited StatesHoward Hughes Medical InstituteUnited StatesP01 CA92584CANCI NIH HHSUnited StatesR01 GM046312GMNIGMS NIH HHSUnited StatesGM046312GMNIGMS NIH HHSUnited StatesComparative StudyJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.20130125
United StatesJ Biol Chem2985121R0021-92580Bacterial Proteins9007-49-2DNAEC 3.1.21.2Deoxyribonuclease IV (Phage T4-Induced)EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Biol Chem. 2011 Sep 2;286(35):30878-8721734257Mutat Res. 2008 Aug 25;643(1-2):54-6318579163EMBO J. 2005 Mar 9;24(5):885-9415692561Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13489-949811827DNA Repair (Amst). 2007 Apr 1;6(4):410-2817208522J Am Chem Soc. 2008 Jul 23;130(29):9332-4118576638Nat Struct Mol Biol. 2008 Nov;15(11):1228-3118953336J Mol Biol. 1999 Jul 9;290(2):447-5710390343J Biol Chem. 1969 Oct 10;244(19):5219-254310088Proteins. 2006 Nov 15;65(3):712-2516981200EMBO J. 1997 Nov 3;16(21):6548-589351835Nat Struct Mol Biol. 2008 May;15(5):515-2218408731J Biol Chem. 2007 Oct 19;282(42):30577-8517724035Nat Struct Biol. 1999 Dec;6(12):1096-910581547Nature. 2002 Aug 1;418(6897):562-612152085DNA Repair (Amst). 2004 Nov 2;3(11):1447-5515380100Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1465-7017242363Bioinformation. 2011;7(4):184-9822102776Nat Genet. 2003 Jul;34(3):239-4112833042Nature. 2010 Aug 5;466(7307):779-8220639861Cold Spring Harb Symp Quant Biol. 2000;65:127-3312760027Nature. 1998 Jul 2;394(6688):96-1019665136Cell. 1999 Aug 6;98(3):397-40810458614Cell. 2008 Oct 3;135(1):97-10918854158Mol Biol (Mosk). 2001 Jan-Feb;35(1):42-5111234382Acta Crystallogr D Biol Crystallogr. 2001 Mar;57(Pt 3):401-1111223517Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Sep 1;66(Pt 9):1003-1220823514Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-41722334Cell. 2011 Apr 15;145(2):198-21121496641Cell. 1985 Mar;40(3):483-42982494Nature. 2009 Jun 11;459(7248):808-1319516334Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-219757107Nucleic Acids Res. 2003 Nov 1;31(21):6344-5314576322Nat Struct Biol. 1995 Jul;2(7):561-87664124Mutat Res. 2000 Aug 30;460(3-4):211-2910946230Nature. 2000 Jan 27;403(6768):451-610667800Biochemistry. 2003 Sep 30;42(38):11373-8114503888Mol Cell Biol. 1993 Sep;13(9):5370-68355688Nucleic Acids Res. 2002 Jan 1;30(1):379-8211752342Biochemistry. 1999 Apr 20;38(16):4958-6410213597J Mol Biol. 2004 Apr 16;338(1):77-9115050824Biochemistry. 2009 Jan 13;48(1):19-2619123919J Mol Biol. 1992 Nov 5;228(1):13-221447777J Mol Biol. 1999 May 21;288(5):975-8710329193Nat Struct Biol. 1998 Dec;5(12):1058-649846876J Bacteriol. 1999 May;181(9):2834-910217775J Biol Chem. 2003 Oct 10;278(41):39951-912882965Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-2120124702Cell. 1999 Dec 10;99(6):615-2310612397J Mol Graph. 1996 Feb;14(1):33-8, 27-88744570Nature. 1996 Nov 7;384(6604):87-928900285EMBO J. 2003 Aug 1;22(15):4014-2512881435Nat Struct Mol Biol. 2009 Feb;16(2):138-4319136958Appl Environ Microbiol. 2001 Jan;67(1):82-811133431J Biol Chem. 2003 Jan 31;278(5):3048-5412444080Trends Biochem Sci. 2012 Feb;37(2):74-8422118811Biopolymers. 1996 Mar;38(3):305-208906967Biophys J. 2007 Jun 1;92(11):3817-2917351000J Mol Biol. 2008 May 23;379(1):28-3718436236Biochem J. 1985 Oct 1;231(1):83-83933490Nature. 1993 Apr 22;362(6422):709-158469282J Mol Biol. 2001 Apr 6;307(4):1023-3411286553Nucleic Acids Res. 1996 Nov 1;24(21):4217-218932375Nucleic Acids Res. 2009 Apr;37(6):1829-4219181704Nature. 2002 Feb 7;415(6872):655-911832948Mutat Res. 2005 Sep 4;577(1-2):55-7615941573Biochemistry. 2004 Jun 29;43(25):8038-4715209499Nature. 2002 Jan 10;415(6868):183-711805838Mol Cell Biol. 2005 Aug;25(15):6380-9016024777J Am Chem Soc. 2010 Oct 6;132(39):13702-1220731347Acta Crystallogr D Biol Crystallogr. 1999 Feb;55(Pt 2):484-9110089360Nucleic Acids Res. 2009 Jul;37(12):3946-5819401441Nucleic Acids Res. 2000 Jun 1;28(11):2207-1310871340J Bacteriol. 1986 Dec;168(3):1120-72430946J Biol Chem. 1998 Nov 13;273(46):30352-99804798Proteins. 2007 Jul 1;68(1):313-2317427952Mol Cell. 2010 Oct 22;40(2):179-20420965415J Biol Chem. 1988 Jun 15;263(17):8066-712453510J Mol Biol. 2003 May 30;329(2):311-2212758078Nature. 1995 Mar 23;374(6520):381-67885481Proc Natl Acad Sci U S A. 1986 Oct;83(20):7731-52429316J Mol Biol. 1999 Mar 19;287(1):47-5710074406Amino Acid SequenceAmino Acid SubstitutionBacterial ProteinschemistryCatalytic DomainConserved SequenceCrystallography, X-RayDNAchemistryDNA-(Apurinic or Apyrimidinic Site) LyasechemistrygeneticsDeoxyribonuclease IV (Phage T4-Induced)chemistryEscherichia coliHumansMolecular Dynamics SimulationMutagenesis, Site-DirectedNucleic Acid ConformationProtein BindingProtein Structure, SecondaryStructural Homology, ProteinThermotoga maritimaenzymology
201312960201312960201351760ppublish23355472M112.42277410.1074/jbc.M112.422774PMC3605660
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1096-033326732013Mar15Toxicology and applied pharmacologyToxicol. Appl. Pharmacol.Induction of base excision repair enzymes NTH1 and APE1 in rat spleen following aniline exposure.276-8310.1016/j.taap.2013.01.005S0041-008X(13)00018-5Mechanisms by which aniline exposure elicits splenotoxicity, especially a tumorigenic response, are not well-understood. Earlier, we have shown that aniline exposure leads to oxidative DNA damage and up-regulation of OGG1 and NEIL1/2 DNA glycosylases in rat spleen. However, the contribution of endonuclease III homolog 1 (NTH1) and apurinic/apyrimidinic endonuclease 1 (APE1) in the repair of aniline-induced oxidative DNA damage in the spleen is not known. This study was, therefore, focused on examining whether NTH1 and APE1 contribute to the repair of oxidative DNA lesions in the spleen, in an experimental condition preceding tumorigenesis. To achieve this, male SD rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. By quantitating the cleavage products, the activities of NTH1 and APE1 were assayed using substrates containing thymine glycol (Tg) and tetrahydrofuran, respectively. Aniline treatment led to significant increases in NTH1- and APE1-mediated BER activity in the nuclear extracts of spleen of aniline-treated rats compared to the controls. NTH1 and APE1 mRNA expression in the spleen showed 2.9- and 3.2-fold increases, respectively, in aniline-treated rats compared to the controls. Likewise, Western blot analysis showed that protein expression of NTH1 and APE1 in the nuclear extracts of spleen from aniline-treated rats was 1.9- and 2.7-fold higher than the controls, respectively. Immunohistochemistry indicated that aniline treatment also led to stronger immunoreactivity for both NTH1 and APE1 in the spleens, confined to the red pulp areas. These results, thus, show that aniline exposure is associated with induction of NTH1 and APE1 in the spleen. The increased repair activity of NTH1 and APE1 could be an important mechanism for the removal of oxidative DNA lesions. These findings thus identify a novel mechanism through which NTH1 and APE1 may regulate the repair of oxidative DNA damage in aniline-induced splenic toxicity.Copyright © 2013 Elsevier Inc. All rights reserved.MaHuaxianHDepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.WangJianlingJAbdel-RahmanSherif ZSZBoorPaul JPJKhanM FirozeMFengR01 ES006476ESNIEHS NIH HHSUnited StatesR29 ES006476ESNIEHS NIH HHSUnited StatesES06476ESNIEHS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20130123
United StatesToxicol Appl Pharmacol04165750041-008X0Aniline Compounds0CarcinogensEC 3.1.-EndodeoxyribonucleasesEC 3.1.-Nth1 protein, ratEC 4.2.99.18Apex1 protein, ratEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseSIR7XX2F1KanilineIMMutat Res. 2000 Oct 16;461(2):83-10811018583PLoS One. 2011;6(7):e2103921799731EMBO J. 2002 Jul 1;21(13):3486-9312093749J Toxicol Environ Health A. 2003 Jan 10;66(1):93-10212587293J Biol Chem. 2003 Mar 14;278(11):9005-1212519758Toxicology. 2003 Nov 15;193(1-2):43-6514599767Toxicology. 2003 Dec 15;194(1-2):95-10214636699J Biol Chem. 2003 Dec 12;278(50):49679-8414522990Carcinogenesis. 2004 Aug;25(8):1359-7015044326Nucleic Acids Res. 2004;32(17):5119-2515452279J Natl Cancer Inst. 1984 Jul;73(1):265-736588231J Natl Cancer Inst. 1985 Oct;75(4):681-903862900Food Chem Toxicol. 1987 Aug;25(8):619-263305247Arch Environ Contam Toxicol. 1993 Apr;24(3):368-748470936Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915-228367443Pharmacol Ther. 1994;63(1):37-1227972344Fundam Appl Toxicol. 1997 Jan;35(1):22-309024670Toxicol Sci. 1999 Mar;48(1):134-4010330693Toxicol Appl Pharmacol. 2005 Feb 15;203(1):36-4415694462Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084J Toxicol Environ Health A. 2005 Apr 23;68(8):657-6615901093Mech Ageing Dev. 2006 Jan;127(1):64-916257035Toxicol Appl Pharmacol. 2006 Jan 1;210(1-2):86-9316169568DNA Repair (Amst). 2007 Apr 1;6(4):470-8017116430J Biol Chem. 2008 Apr 11;283(15):9925-3218263880Toxicol Appl Pharmacol. 2008 Jul 15;230(2):227-3418420242Nucleic Acids Res. 2008 Aug;36(13):4327-3618586825DNA Repair (Amst). 2008 Sep 1;7(9):1578-8818603019Toxicol Appl Pharmacol. 2008 Dec 1;233(2):247-5318793663Mutat Res. 2009 Mar 31;674(1-2):131-618948225Mutat Res. 2009 Jun 18;666(1-2):32-819481677Carcinogenesis. 2009 Aug;30(8):1345-5219414504Int J Oncol. 2009 Nov;35(5):1069-7919787261DNA Repair (Amst). 2009 Nov 2;8(11):1328-3219782007Neurosci Lett. 2009 Dec 11;466(3):124-719782121Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):575-8818715145Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4925-3020185759J Biol Chem. 2010 Jun 18;285(25):19092-10520185827Toxicol Appl Pharmacol. 2011 Feb 15;251(1):1-721145906Antioxid Redox Signal. 2001 Aug;3(4):671-8311554453Aniline CompoundstoxicityAnimalsCarcinogenstoxicityCell Transformation, Neoplasticchemically induceddrug effectsDNA Damagedrug effectsphysiologyDNA Repairdrug effectsphysiologyDNA-(Apurinic or Apyrimidinic Site) Lyasebiosynthesistherapeutic useEndodeoxyribonucleasesbiosynthesistherapeutic useEnzyme Inductiondrug effectsphysiologyMaleRatsRats, Sprague-DawleySpleendrug effectsenzymologyUp-Regulationdrug effectsphysiology
20121128201301092013011120131296020131296020135160ppublish23352893S0041-008X(13)00018-510.1016/j.taap.2013.01.005PMC3725747NIHMS446537
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1568-78561232013Mar01DNA repairDNA Repair (Amst.)Rapid inactivation and proteasome-mediated degradation of OGG1 contribute to the synergistic effect of hyperthermia on genotoxic treatments.227-3710.1016/j.dnarep.2012.12.006S1568-7864(12)00309-6Inhibition of DNA repair has been proposed as a mechanism underlying heat-induced sensitization of tumour cells to some anticancer treatments. Base excision repair (BER) constitutes the main pathway for the repair of DNA lesions induced by oxidizing or alkylating agents. Here, we report that mild hyperthermia, without toxic consequences per se, affects cellular DNA glycosylase activities, thus impairing BER. Exposure of cells to mild hyperthermia leads to a rapid and selective inactivation of OGG1 (8-oxoguanine DNA glycosylase) associated with the relocalisation of the protein into a detergent-resistant cellular fraction. Following its inactivation, OGG1 is ubiquitinated and directed to proteasome-mediated degradation, through a CHIP (C-terminus of HSC70-interacting protein) E3 ligase-mediated process. Moreover, the residual OGG1 accumulates in the perinuclear region leading to further depletion from the nucleus. As a consequence, HeLa cells subjected to hyperthermia and exposed to a genotoxic treatment have a reduced capacity to repair OGG1 cognate base lesions and an enhanced cell growth defect. The partial alleviation of this response by OGG1 overexpression indicates that heat-induced glycosylase inactivation contributes to the synergistic effect of hyperthermia on genotoxic treatments. Taken together, our results suggest that OGG1 inhibition contributes to heat-induced chemosensitisation of cells and could lay the basis for new anticancer therapeutic protocols that include hyperthermia.Copyright © 2012 Elsevier B.V. All rights reserved.FantiniDamianoDCEA, Institute of Molecular and Cellular Radiobiology, 18 route du Panorama, Fontenay aux Roses, F-92265, France.MoritzEvaEAuvréFrédéricFAmourouxRachelRCampalansAnnaAEpeBerndBBravardAnneARadicellaJ PabloJPengJournal ArticleResearch Support, Non-U.S. Gov't20130115
NetherlandsDNA Repair (Amst)1011391381568-78560Photosensitizing Agents0Pyrrolidines0Quinolizines104604-66-2Ro 19-8022EC 2.3.2.27STUB1 protein, humanEC 2.3.2.27Ubiquitin-Protein LigasesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.4.25.1Proteasome Endopeptidase ComplexIMCell NucleusmetabolismCell ProliferationDNA DamageDNA GlycosylasesgeneticsmetabolismDNA RepairEnzyme StabilityHeLa CellsHeat-Shock ResponseHumansPhotosensitizing AgentspharmacologyProteasome Endopeptidase ComplexProtein TransportProteolysisPyrrolidinespharmacologyQuinolizinespharmacologyUbiquitin-Protein LigasesmetabolismUbiquitination
20121008201212182012122120131226020131226020138860ppublish23332971S1568-7864(12)00309-610.1016/j.dnarep.2012.12.006
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1932-62037122012PloS onePLoS ONE8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction.e5169710.1371/journal.pone.0051697Oxidative damage to DNA is mainly repaired via base excision repair, a pathway that is catalyzed by DNA glycosylases such as 8-oxoguanine DNA glycosylase (OGG1). While OGG1 has been implicated in maintaining genomic integrity and preventing tumorigenesis, we report a novel role for OGG1 in altering cellular and whole body energy homeostasis. OGG1-deficient (Ogg1(-/-)) mice have increased adiposity and hepatic steatosis following exposure to a high-fat diet (HFD), compared to wild-type (WT) animals. Ogg1(-/-) animals also have higher plasma insulin levels and impaired glucose tolerance upon HFD feeding, relative to WT counterparts. Analysis of energy expenditure revealed that HFD-fed Ogg1(-/-) mice have a higher resting VCO(2) and consequently, an increased respiratory quotient during the resting phase, indicating a preference for carbohydrate metabolism over fat oxidation in these mice. Additionally, microarray and quantitative PCR analyses revealed that key genes of fatty acid oxidation, including carnitine palmitoyl transferase-1, and the integral transcriptional co-activator Pgc-1α were significantly downregulated in Ogg1(-/-) livers. Multiple genes involved in TCA cycle metabolism were also significantly reduced in livers of Ogg1(-/-) mice. Furthermore, hepatic glycogen stores were diminished, and fasting plasma ketones were significantly reduced in Ogg1(-/-) mice. Collectively, these data indicate that OGG1 deficiency alters cellular substrate metabolism, favoring a fat sparing phenotype, that results in increased susceptibility to obesity and related pathologies in Ogg1(-/-) mice.SampathHariniHDepartment of Molecular and Medical Genetics, Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR, USA.VartanianVladimirVRollinsM RickMRSakumiKunihikoKNakabeppuYusakuYLloydR StephenRSengR01 DK075974DKNIDDK NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20121217
United StatesPLoS One1012850811932-62030DNA, Mitochondrial0Insulin0Lipids9005-79-2GlycogenEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIY9XDZ35W2GlucoseIMFree Radic Biol Med. 2010 Aug 15;49(4):587-9620483371J Hum Genet. 2009 Dec;54(12):739-4519881468Semin Cancer Biol. 2010 Oct;20(5):320-820955798Nature. 2011 Feb 17;470(7334):359-6521307849Am J Clin Nutr. 2011 Apr;93(4):884S-9021289221Acta Biochim Biophys Sin (Shanghai). 2011 Apr;43(4):248-5721325336Am J Physiol Endocrinol Metab. 2011 Apr;300(4):E724-3421285402Free Radic Biol Med. 2011 Jul 15;51(2):417-2321569841Acta Biochim Biophys Sin (Shanghai). 2011 Aug;43(8):589-9421733854Folia Neuropathol. 2011;49(2):123-3121845541Free Radic Biol Med. 2012 Jan 15;52(2):392-40122100973Free Radic Res. 2012 Apr;46(4):460-7822300253Hum Hered. 2010;70(2):97-10120606456Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Acta Neuropathol. 2002 Jan;103(1):20-511837743Pflugers Arch. 2002 Nov;445(2):273-812457248Cancer Res. 2003 Mar 1;63(5):902-512615700Int J Cancer. 2003 Sep 20;106(5):752-712866036Cancer Lett. 2004 Jan 8;203(1):25-3314670614Oncol Rep. 2004 Aug;12(2):483-815254719J Bacteriol. 1992 Oct;174(20):6321-51328155Mutat Res. 1996 May;316(5-6):277-858649461Mol Gen Genet. 1997 Mar 26;254(2):171-89108279Curr Biol. 1997 Jun 1;7(6):397-4079197244Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7429-349207108Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-59223305Oncogene. 1998 Jun 11;16(23):3083-69662341Mol Biol Cell. 1999 May;10(5):1637-5210233168Cell. 2005 Jan 28;120(2):261-7315680331Int J Obes (Lond). 2005 Mar;29 Suppl 1:S5-915711583Acta Neuropathol. 2005 Mar;109(3):256-6215841414Gene Expr. 2005;12(4-6):315-2316358418J Biochem. 2005 Dec;138(6):763-7216428305Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1864-916446448Toxicology. 2006 Apr 17;221(2-3):179-8616494984J Biol Chem. 2006 Jul 14;281(28):19000-816670093Biol Res Nurs. 2006 Oct;8(2):157-6917003255DNA Repair (Amst). 2007 Apr 1;6(4):470-8017116430DNA Repair (Amst). 2007 Apr 1;6(4):481-817127104J Neurosci Res. 2007 Apr;85(5):919-3417279544Nucleic Acids Res. 2007;35(8):2759-6617426120Cancer Lett. 2008 Jul 18;266(1):60-7218374480Free Radic Biol Med. 2008 Sep 15;45(6):813-918598755Biochem Biophys Res Commun. 2009 Aug 14;386(1):26-919486888DNA Cell Biol. 2009 Nov;28(11):579-8819630534PLoS One. 2010;5(8):e1207020706593AdiposityAnimalsDNA GlycosylasesphysiologyDNA, MitochondrialgeneticsDiet, High-Fatadverse effectsEnergy MetabolismFatty LiveretiologymetabolismpathologyGlucosemetabolismGlucose Tolerance TestGlycogenmetabolismInsulinmetabolismLipidsanalysisMaleMiceMice, Inbred C57BLMice, KnockoutObesityetiologymetabolismpathologyOxidative Stress
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1573-49784012013JanMolecular biology reportsMol. Biol. Rep.APE1 Asp148Glu gene polymorphism and bladder cancer risk: a meta-analysis.171-610.1007/s11033-012-2046-5Published data regarding the association between the apurinic/apyrimidinic endonuclease 1 (APE1) Asp148Glu polymorphism and bladder cancer risk showed inconclusive results. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase, Elsevier and Springer for relevant articles with a time limit of Jan. 2012. The strength of association between APE1 Asp148Glu polymorphism and bladder cancer risk was assessed by odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) using the software STATA(version10.0).A total of 11 case-control studies including 4,292 cases and 4,761 controls based on the search criteria were included for analysis. Overall, for GG versus TT, the pooled OR was 0.952 (95 % CI = 0.778-1.166), for the the G allele carriers (TG + GG) versus homozygote TT, the pooled OR was 0.984 (95 % CI = 0.897-1.078). In the stratified analysis by ethnicity, significantly risks were not found among Asians for GG versus TT (OR = 0.469; 95 % CI = 0.162-1.357) nor (TG + GG) versus TT (OR = 0.921, 95 % CI = 0.742-1.143). Similarly, for non-Asians, significantly risks were also not found for GG versus TT (OR = 0.992; 95 % CI = 0.861-1.144) nor (TG + GG) versus TT (OR = 1.010, 95 % CI = 0.897-1.137). This meta-analysis suggested that the APE1 T1349G (Asp148Glu) polymorphism was not associated with bladder cancer risk among Asians nor non-Asians.LiuChuanCDepartment of Oncology, Changhai Hospital, Second Military Medical University, Changhai Hospital, 168 Changhai Road, Shanghai, People's Republic of China. chuanliu2005@163.comYinQinghuaQLiLianLZhuangYing-ZhiYZZuXuyuXWangYajieYengJournal ArticleMeta-Analysis20121110
NetherlandsMol Biol Rep04032340301-48510CodonEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMStat Med. 2002 Jun 15;21(11):1539-5812111919Carcinogenesis. 2005 Jul;26(7):1263-7115746160Mutat Res. 2000 Oct 16;461(2):83-10811018583DNA Cell Biol. 2010 Oct;29(10):611-720575692Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414DNA Cell Biol. 2010 Jun;29(6):303-1120218899Control Clin Trials. 1986 Sep;7(3):177-883802833Int J Cancer. 2009 Aug 1;125(3):666-7319382179Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Am J Epidemiol. 2005 Jan 1;161(1):1-1415615908Int J Cancer. 2006 Jun 15;118(12):3170-316425270Hum Hered. 2008;65(2):105-1817898541Urology. 2011 Feb;77(2):511.e1-520947146Carcinogenesis. 2001 Jun;22(6):917-2211375899Carcinogenesis. 2006 May;27(5):1030-716311243Cell. 1991 Feb 8;64(3):615-231991323Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):84-9117220334Science. 2001 Feb 16;291(5507):1284-911181991Hum Genet. 2007 Apr;121(2):233-4217203305Genomics. 2004 Jun;83(6):970-915177551Urology. 2009 Mar;73(3):675-8019041121DNA Repair (Amst). 2010 Feb 4;9(2):191-20020061190Nature. 2003 Jan 23;421(6921):436-4012540918Med Decis Making. 2005 Nov-Dec;25(6):646-5416282215BMJ. 1997 Sep 13;315(7109):629-349310563Urology. 2010 Sep;76(3):765.e1-720630574CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Nucleic Acids Res. 1992 Sep 11;20(17):4417-211383925Anticancer Res. 2009 Apr;29(4):1389-9319414392J Urol. 1984 Apr;131(4):650-46708176Mech Ageing Dev. 2012 Apr;133(4):127-3222019847AllelesCase-Control StudiesCodonDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGenetic Predisposition to DiseaseGenotypeHumansOdds RatioPolymorphism, Single NucleotidePublication BiasRiskUrinary Bladder Neoplasmsgenetics
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0027-51077501-22013Jan20Mutation researchMutat. Res.The role of base excision repair genes OGG1, APN1 and APN2 in benzo[a]pyrene-7,8-dione induced p53 mutagenesis.121-810.1016/j.mrgentox.2012.10.003S1383-5718(12)00296-3Lung cancer is primarily caused by exposure to tobacco smoke. Tobacco smoke contains numerous carcinogens, including polycyclic aromatic hydrocarbons (PAH). The most common PAH studied is benzo[a]pyrene (B[a]P). B[a]P is metabolically activated through multiple routes, one of which is catalyzed by aldo-keto reductase (AKR) to B[a]P-7,8-dione (BPQ). BPQ undergoes a futile redox cycle in the presence of NADPH to generate reactive oxygen species (ROS). ROS, in turn, damages DNA. Studies with a yeast p53 mutagenesis system found that the generation of ROS by PAH o-quinones may contribute to lung carcinogenesis because of similarities between the patterns (types of mutations) and spectra (location of mutations) and those seen in lung cancer. The patterns were dominated by G to T transversions, and the spectra in the experimental system have mutations at lung cancer hotspots. To address repair mechanisms that are responsible for BPQ induced damage we observed the effect of mutating two DNA repair genes OGG1 and APE1 (APN1 in yeast) and tested them in a yeast reporter system for p53 mutagenesis. There was an increase in both the mutant frequency and the number of G:C/T:A transversions in p53 treated with BPQ in ogg1 yeast but not in apn1 yeast. Knocking out APN2 increased mutagenesis in the apn1 cells. In addition, we did not find a strand bias on p53 treated with BPQ in ogg1 yeast. These studies suggest that Ogg1 is involved in repairing the oxidative damage caused by BPQ, Apn1 and Apn2 have redundant functions and that the stand bias seen in lung cancer may not be due to impaired repair of oxidative lesions.Copyright © 2012 Elsevier B.V. All rights reserved.AbedinZahidurZDepartment of Pharmacology, Centers for Excellence in Environmental Toxicology and Cancer Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6084, USA.Louis-JusteMelissaMStanglMelissaMFieldJeffreyJengR25 ES021649ESNIEHS NIH HHSUnited StatesR25 ESO016146PHS HHSUnited StatesR25 ES016146ESNIEHS NIH HHSUnited StatesP30 ES013508ESNIEHS NIH HHSUnited StatesP30 ESO013508PHS HHSUnited StatesR01 ES015662ESNIEHS NIH HHSUnited StatesR01 GM048241GMNIGMS NIH HHSUnited StatesR01PHS HHSUnited StatesR01 GM48241GMNIGMS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20121029
NetherlandsMutat Res04007630027-51070Mutagens0Saccharomyces cerevisiae Proteins3417WMA06DBenzo(a)pyreneEC 3.1.-EndodeoxyribonucleasesEC 3.1.25.-Apn1 protein, S cerevisiaeEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APN2 protein, S cerevisiaeEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 6.5.1.-DNA Repair EnzymesIMMol Cell Biol. 2010 Jul;30(13):3206-1520421413Biochimie. 1997 Oct;79(9-10):559-669466693Carcinogenesis. 2003 Jun;24(6):1031-712807753Arch Biochem Biophys. 2000 May 1;377(1):1-810775435Science. 1978 Feb 17;199(4330):778-81622566Annu Rev Biochem. 1994;63:915-487979257Science. 1996 Oct 18;274(5286):430-28832894Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915-228367443Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3963-77732013DNA Repair (Amst). 2004 Jan 5;3(1):1-1214697754Mol Cell Biol. 1991 Sep;11(9):4537-441715020Chem Res Toxicol. 2006 Nov;19(11):1441-5017112231Mutat Res. 2000 Oct 16;461(2):83-10811018583Nucleic Acids Res. 1998 Mar 1;26(5):1228-339469830Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8165-97520176J Natl Cancer Inst. 1999 Jul 21;91(14):1194-21010413421Nat Rev Mol Cell Biol. 2008 Dec;9(12):958-7019023283Mutat Res. 2001 May 10;485(4):283-30711585362Carcinogenesis. 1998 Feb;19(2):347-519498287Chem Res Toxicol. 2007 Sep;20(9):1331-4117702526Carcinogenesis. 2001 Mar;22(3):367-7411238174Nucleic Acids Res. 1998 Jan 1;26(1):200-49399836Chem Res Toxicol. 2011 Nov 21;24(11):1905-1421962213Chem Res Toxicol. 2006 Sep;19(9):1215-2016978026Yeast. 2004 Sep;21(12):991-100315449310Chem Res Toxicol. 2012 Oct 15;25(10):2117-2622768918Mol Cell. 2003 Oct;12(4):959-7014580346Curr Biol. 1997 Jun 1;7(6):397-4079197244Mutagenesis. 2007 Sep;22(5):343-5117630408Physiol Rev. 1980 Oct;60(4):1107-667001511Chem Res Toxicol. 1999 Mar;12(3):237-4610077486Mutat Res. 2009 Mar 9;662(1-2):67-7419162045Science. 1991 Jul 5;253(5015):49-531905840Mutat Res. 2000 Aug 30;460(3-4):211-2910946230Mutat Res. 2009 Feb 19;673(1):3-819100859DNA Repair (Amst). 2004 May 4;3(5):483-9415084310Antioxid Redox Signal. 2001 Aug;3(4):597-60911554447Cancer Res. 2008 Sep 1;68(17):6863-7218757397DNA Repair (Amst). 2004 Nov 2;3(11):1457-6815380101Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8397-40210890888J Neurochem. 2007 Jul;102(1):13-2417506861J Natl Cancer Inst. 2008 Dec 3;100(23):1672-9419033571Cancer Res. 1982 Dec;42(12):4875-9176814745Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4091-58633021Nucleic Acids Res. 2005;33(10):3271-8215942030Hum Mutat. 2003 Mar;21(3):229-3912619108Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10422-67479797Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12244-911035769Mutat Res. 2001 Jun 5;486(1):31-4011356334Chem Res Toxicol. 2002 Jun;15(6):832-4212067251Chem Res Toxicol. 2008 May;21(5):1039-4918489080Chem Res Toxicol. 1999 Jan;12(1):1-189894013Mol Cell Biol. 1999 Apr;19(4):2929-3510082560Chem Res Toxicol. 2012 Jan 13;25(1):113-2122053912Carcinogenesis. 1993 Mar;14(3):475-828384091Mol Gen Genet. 1997 Mar 26;254(2):171-89108279Chem Res Toxicol. 2006 May;19(5):719-2816696575Carcinogenesis. 2003 Jan;24(1):113-912538356Xenobiotica. 1995 Jul;25(7):677-887483666Proc Jpn Acad Ser B Phys Biol Sci. 2006 May;82(4):127-4125792776Mol Cell Biol. 2005 Aug;25(15):6380-9016024777Proc Natl Acad Sci U S A. 2008 May 13;105(19):6846-5118474869DNA Repair (Amst). 2002 Apr 29;1(4):261-7312509245Nucleic Acids Res. 2001 Jan 15;29(2):430-811139613Biochemistry. 1977 Mar 8;16(5):932-8843522Carcinogenesis. 1992 Dec;13(12):2241-71473230Benzo(a)pyrenetoxicityDNA DamageDNA GlycosylasesgeneticsDNA RepairgeneticsDNA Repair EnzymesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsEndodeoxyribonucleasesgeneticsGenes, p53MutagenesisMutagenschemistrytoxicitySaccharomyces cerevisiae Proteinsgenetics
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1932-62037102012PloS onePLoS ONEDiverse small molecule inhibitors of human apurinic/apyrimidinic endonuclease APE1 identified from a screen of a large public collection.e4797410.1371/journal.pone.0047974The major human apurinic/apyrimidinic endonuclease APE1 plays a pivotal role in the repair of base damage via participation in the DNA base excision repair (BER) pathway. Increased activity of APE1, often observed in tumor cells, is thought to contribute to resistance to various anticancer drugs, whereas down-regulation of APE1 sensitizes cells to DNA damaging agents. Thus, inhibiting APE1 repair endonuclease function in cancer cells is considered a promising strategy to overcome therapeutic agent resistance. Despite ongoing efforts, inhibitors of APE1 with adequate drug-like properties have yet to be discovered. Using a kinetic fluorescence assay, we conducted a fully-automated high-throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR), as well as additional public collections, with each compound tested as a 7-concentration series in a 4 µL reaction volume. Actives identified from the screen were subjected to a panel of confirmatory and counterscreen tests. Several active molecules were identified that inhibited APE1 in two independent assay formats and exhibited potentiation of the genotoxic effect of methyl methanesulfonate with a concomitant increase in AP sites, a hallmark of intracellular APE1 inhibition; a number of these chemotypes could be good starting points for further medicinal chemistry optimization. To our knowledge, this represents the largest-scale HTS to identify inhibitors of APE1, and provides a key first step in the development of novel agents targeting BER for cancer treatment.DorjsurenDorjbalDNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.KimDaemyungDVyjayantiVaddadi NVNMaloneyDavid JDJJadhavAjitAWilsonDavid MDM3rdSimeonovAntonAeng1 R03 MH092154-01MHNIMH NIH HHSUnited StatesU54MH084681MHNIMH NIH HHSUnited StatesIntramural NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, N.I.H., Intramural20121023
United StatesPLoS One1012850811932-62030Enzyme Inhibitors0Small Molecule LibrariesAT5C31J09GMethyl MethanesulfonateEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnnu Rev Genet. 2004;38:445-7615568983J Biomol Screen. 2006 Apr;11(3):253-6116490778Biochimie. 2003 Nov;85(11):1053-7114726013DNA Repair (Amst). 2009 Sep 2;8(9):1153-6519501553J Med Chem. 2012 Apr 12;55(7):3101-1222455312JALA Charlottesv Va. 2008 Apr;13(2):79-8918496600Cancer Treat Rev. 2010 Aug;36(5):425-3520056333PLoS One. 2010;5(7):e1160320657644Mol Aspects Med. 2007 Jun-Aug;28(3-4):345-7417706275J Mol Biol. 2005 Feb 4;345(5):1003-1415644200Mutat Res. 2001 May 10;485(4):283-30711585362Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642J Pharmacol Exp Ther. 2010 Sep 1;334(3):988-9820504914Nat Rev Cancer. 2008 Mar;8(3):193-20418256616Nat Biotechnol. 2002 Feb;20(2):171-611821863Antivir Chem Chemother. 1998 Nov;9(6):461-729865384J Biomol Screen. 1999;4(2):67-7310838414Chem Biol. 2010 May 28;17(5):471-8220534345Antimicrob Agents Chemother. 2006 Jun;50(6):2197-20016723583Pharmacol Rev. 2006 Sep;58(3):621-8116968952Mol Pharmacol. 2008 Mar;73(3):669-7718042731Nucleic Acids Res. 1998 Jun 1;26(11):2771-89592167J Med Chem. 2011 Apr 14;54(7):2409-2121375347Nat Rev Cancer. 2005 Jul;5(7):564-7316069818Mutat Res. 2000 Aug 30;460(3-4):211-2910946230Int J Cancer. 2012 Nov 15;131(10):2433-4422377908J Med Chem. 2010 Jan 14;53(1):37-5119908840J Biol Chem. 1995 Jul 7;270(27):16002-77608159J Clin Oncol. 2008 Aug 1;26(22):3785-9018591545Biochimie. 2003 Nov;85(11):1149-6014726020Mol Cancer Res. 2007 Jan;5(1):61-7017259346Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11473-816864780Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143PLoS One. 2011;6(9):e2367921935361Science. 2011 Aug 5;333(6043):765-921764752Bioorg Med Chem Lett. 2006 Mar 15;16(6):1468-7216412638Cell Mol Life Sci. 2010 Nov;67(21):3621-3120809131Mol Cell. 2005 Feb 4;17(3):463-7015694346Bioorg Med Chem Lett. 2010 Jun 15;20(12):3785-720483604Expert Opin Drug Discov. 2011 Jan;6(1):17-3222328899Am J Hum Genet. 2008 Mar;82(3):539-6618319069PLoS One. 2009;4(6):e574019484131Nat Chem Biol. 2007 Aug;3(8):466-7917637779Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325J Med Chem. 2009 Jan 8;52(1):20-3219072053Nucleic Acids Res. 2005;33(15):4711-2416113242Chem Res Toxicol. 2006 Dec;19(12):1580-9417173371Assay Drug Dev Technol. 2008 Oct;6(5):637-5719035846J Chem Inf Comput Sci. 2000 Nov-Dec;40(6):1302-1411128088Mol Cancer Res. 2009 Jun;7(6):897-90619470598Cell Survivaldrug effectsgeneticsDNA DamageDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsmetabolismDose-Response Relationship, DrugDrug Evaluation, PreclinicalmethodsEnzyme InhibitorschemistrypharmacologyHeLa CellsHumansMethyl Methanesulfonateantagonists & inhibitorspharmacologyMolecular StructureSmall Molecule LibrariesStructure-Activity Relationship
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1860-71877122012DecChemMedChemChemMedChemReceptor-based virtual screening and biological characterization of human apurinic/apyrimidinic endonuclease (Ape1) inhibitors.2168-7810.1002/cmdc.201200372The endonucleolytic activity of human apurinic/apyrimidinic endonuclease (AP endo, Ape1) is a major factor in maintaining the integrity of the genome. Conversely, as an undesired effect, Ape1 overexpression has been linked to resistance to radio- and chemotherapeutic treatments in several human tumors. Inhibition of Ape1 using siRNA or the expression of a dominant negative form of the protein has been shown to sensitize cells to DNA-damaging agents, including various chemotherapeutic agents. Therefore, inhibition of the enzymatic activity of Ape1 might result in a potent antitumor therapy. A number of small molecules have been described as Ape1 inhibitors; however, those compounds are in the early stages of development. Herein we report the identification of new compounds as potential Ape1 inhibitors through a docking-based virtual screening technique. Some of the compounds identified have in vitro activities in the low-to-medium micromolar range. Interaction of these compounds with the Ape1 protein was observed by mass spectrometry. These molecules also potentiate the cytotoxicity of the chemotherapeutic agent methyl methanesulfonate in fibrosarcoma cells. This study demonstrates the power of docking and virtual screening techniques as initial steps in the design of new drugs, and opens the door to the development of a new generation of Ape1 inhibitors.Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.RuizFederico MFMChemical and Physical Biology, CIB (CSIC), Spain.FrancisSandrea MSMTintoréMariaMFerreiraRubénRGil-RedondoRubénRMorrealeAntonioAOrtizÁngel RÁREritjaRamonRFàbregaCarmenCengJournal ArticleResearch Support, Non-U.S. Gov't20121025
GermanyChemMedChem1012590131860-71790Enzyme Inhibitors0Intercalating Agents9007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCatalytic DomainCell Line, TumorCell Survivaldrug effectsDNAmetabolismDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorschemistrymetabolismDrug DesignEnzyme InhibitorschemistrypharmacologyHumansIntercalating AgentschemistrypharmacologyMolecular Docking SimulationNeoplasmsdrug therapy
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1460-2105104222012Nov21Journal of the National Cancer InstituteJ. Natl. Cancer Inst.N-methylpurine DNA glycosylase and OGG1 DNA repair activities: opposite associations with lung cancer risk.1765-910.1093/jnci/djs445Only a minority of smokers develop lung cancer, possibly due to genetic predisposition, including DNA repair deficiencies. To examine whether inter-individual variations in DNA repair activity of N-methylpurine DNA glycosylase (MPG) are associated with lung cancer, we conducted a blinded, population-based, case-control study with 100 lung cancer case patients and 100 matched control subjects and analyzed the data with conditional logistic regression. All statistical tests were two-sided. MPG enzyme activity in peripheral blood mononuclear cells from case patients was higher than in control subjects, results opposite that of 8-oxoguanine DNA glycosylase (OGG1) DNA repair enzyme activity. For lung cancer associated with one standard deviation increase in MPG activity, the adjusted odds ratio was 1.8 (95% confidence interval [CI] = 1.2 to 2.6; P = .006). A combined MPG and OGG1 activities score was more strongly associated with lung cancer risk than either activity alone, with an odds ratio of 2.3 (95% CI = 1.4 to 3.6; P < .001). These results form a basis for a future panel of risk biomarkers for lung cancer risk assessment and prevention.Leitner-DaganYaelYDepartment of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.SevilyaZivZPinchevMilaMKramerRanRElingerDaliaDRoismanLaila CLCRennertHedy SHSSchechtmanEdnaEFreedmanLaurenceLRennertGadGLivnehZviZPaz-ElizurTamarTengU01 CA111219CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20121027
United StatesJ Natl Cancer Inst75030890027-88740Biomarkers, TumorEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.2.2.21DNA-3-methyladenine glycosidase IIIMMol Cancer Ther. 2004 Aug;3(8):955-6715299078J Biol Chem. 2004 Apr 23;279(17):17723-3014761949Mutat Res. 1995 Jan;336(1):9-177528899Biochem J. 1997 Jul 1;325 ( Pt 1):1-169224623Nucleic Acids Res. 1998 Sep 1;26(17):4034-419705516Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9997-100029707589Cancer Res. 2005 Jul 15;65(14):6394-40016024643Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1585-716030087N Engl J Med. 2006 Oct 26;355(17):1763-7117065637Cancer Res. 2006 Dec 15;66(24):11683-917178863DNA Repair (Amst). 2007 Jan 4;6(1):45-6016982217DNA Repair (Amst). 2007 Jan 4;6(1):71-8117018265Cancer Sci. 2007 Apr;98(4):465-7017425590Cancer Res. 2007 Apr 15;67(8):3493-517440053Cancer Res. 2008 Apr 15;68(8):3049-5618413776Cancer Lett. 2008 Jul 18;266(1):60-7218374480Adv Exp Med Biol. 2005;570:125-7318727500Cell Mol Life Sci. 2009 Mar;66(6):981-9319153658Am J Respir Crit Care Med. 2009 May 15;179(10):860-819423719Biochemistry. 2009 Mar 10;48(9):1850-6119219989JAMA. 2009 Sep 16;302(11):1210-719755700Mol Cell. 2010 Mar 26;37(6):843-5320347426N Engl J Med. 2011 Aug 4;365(5):395-40921714641Nat Neurosci. 2011 Sep;14(9):1105-721878926DNA Repair (Amst). 2012 Jan 2;11(1):46-5222079122CA Cancer J Clin. 2012 Jan-Feb;62(1):10-2922237781Mutat Res. 2012 Apr 1;732(1-2):43-622266085FEBS Lett. 2000 Jun 30;476(1-2):73-710878254J Natl Cancer Inst. 2000 Nov 1;92(21):1764-7211058619Nature. 2001 May 17;411(6835):366-7411357144Cancer Res. 2003 Aug 1;63(15):4351-712907604Cancer Res. 2003 Aug 15;63(16):4899-90212941813J Natl Cancer Inst. 2003 Sep 3;95(17):1312-912953085J Clin Invest. 2003 Dec;112(12):1887-9414679184Eur J Epidemiol. 1988 Dec;4(4):461-93203727AdultAgedBiomarkers, TumorgeneticsmetabolismCase-Control StudiesDNA GlycosylasesgeneticsmetabolismDNA RepairFemaleHumansLeukocytes, MononuclearenzymologyLogistic ModelsLung NeoplasmsenzymologygeneticsMaleMiddle AgedOdds RatioRisk Factors
20121030602012103060201311560ppublish23104324djs44510.1093/jnci/djs445PMC3502197
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1932-62037102012PloS onePLoS ONEAPE1/Ref-1 regulates STAT3 transcriptional activity and APE1/Ref-1-STAT3 dual-targeting effectively inhibits pancreatic cancer cell survival.e4746210.1371/journal.pone.0047462Pancreatic cancer is a largely incurable disease, and increasing evidence supports strategies targeting multiple molecular mediators of critical functions of pancreatic ductal adenocarcinoma cells. Intracellular redox state modulates the activity of various signal transduction pathways and biological processes, including cell survival, drug resistance and responsiveness to microenvironmental factors. Recently, it has been shown that the transcription factor STAT3 is under redox control, but the mechanisms involved in its regulation are unknown. Here, we demonstrate for the first time that STAT3 DNA binding and transcriptional activity is directly regulated by the redox function of the APE1/Ref-1 endonuclease, using overexpression and redox-specific mutational strategies, and gene knockdown. Also, pharmacological blockade of APE1/Ref-1 by the redox-selective inhibitor E3330 abrogates STAT3 DNA binding. Since APE1/Ref-1 also exerts redox control on other cancer-associated transcription factors, we assessed the impact of dual-targeting of STAT3 signaling and APE1/Ref-1 redox on pancreatic cancer cell functions. We observed that disruption of APE1/Ref-1 redox activity synergizes with STAT3 blockade to potently inhibit the proliferation and viability of human PDAC cells. Mechanistically, we show that STAT3-APE1/Ref-1 dual targeting promotes marked tumor cell apoptosis, with engagement of caspase-3 signaling, which are significantly increased in comparison to the effects triggered by single target blockade. Also, we show that STAT3-APE1/Ref-1 dual blockade results in significant inhibition of tumor cell migration. Overall, this work demonstrates that the transcriptional activity of STAT3 is directly regulated by the redox function of APE1/Ref-1, and that concurrent blockade of STAT3 and APE1/Ref-1 redox synergize effectively inhibit critical PDAC cell functions.CardosoAngelo AAADivision of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.JiangYanlinYLuoMeihuaMReedApril MAMShahdaSafiSHeYingYMaitraAnirbanAKelleyMark RMRFishelMelissa LMLengCA122298CANCI NIH HHSUnited StatesCA114571CANCI NIH HHSUnited StatesCA134292CANCI NIH HHSUnited StatesCA121168CANCI NIH HHSUnited StatesCA113669CANCI NIH HHSUnited StatesCA121168S1CANCI NIH HHSUnited StatesCA134767CANCI NIH HHSUnited StatesR01 CA113669CANCI NIH HHSUnited StatesR01 CA167291CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20121019
United StatesPLoS One1012850811932-62030Aminosalicylic Acids0Benzenesulfonates0Benzoquinones0Cyclic S-Oxides0NSC 748590Propionates0RNA, Small Interfering0STAT3 Transcription Factor0STAT3 protein, human0stattic136164-66-4E 3330EC 3.4.22.-Caspase 3EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMSci Signal. 2010;3(140):ra6720858866J Pharmacol Exp Ther. 2010 Sep 1;334(3):988-9820504914Cancer Res. 2010 Oct 15;70(20):8222-3220807804Cancer Prev Res (Phila). 2010 Nov;3(11):1427-3420959520Exp Hematol. 2010 Dec;38(12):1178-8820826193Biochim Biophys Acta. 2011 Jan;1815(1):104-1420969928Cancer Chemother Pharmacol. 2011 Mar;67(3):503-920461382Mol Cancer Ther. 2011 Sep;10(9):1698-70821700832Biochemistry. 2011 Jan 11;50(1):82-9221117647J Pharmacol Exp Ther. 2008 Nov;327(2):442-5218664592Semin Cell Dev Biol. 2008 Aug;19(4):341-5018621135Int J Cancer. 2009 Apr 1;124(7):1675-8419101986World J Gastroenterol. 2009 Aug 14;15(30):3757-6619673016Nat Rev Cancer. 2009 Nov;9(11):798-80919851315Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Nature. 2010 Jan 21;463(7279):318-2520032975Gastroenterology. 2002 Dec;123(6):2052-6312454861Nat Immunol. 2003 Feb;4(2):145-5312524539Nat Rev Cancer. 2004 Feb;4(2):97-10514964307Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Biochem Biophys Res Commun. 2004 Sep 24;322(3):1005-1115336564Expert Opin Ther Targets. 2004 Oct;8(5):409-2215469392Adv Enzyme Regul. 1984;22:27-556382953EMBO J. 1992 Sep;11(9):3323-351380454Structure. 1995 Mar 15;3(3):239-437788289Annu Rev Immunol. 1997;15:351-699143692Am J Physiol. 1998 Dec;275(6 Pt 1):C1640-529843726Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):529-3615701837Circulation. 2005 Feb 15;111(6):782-9015699255Oncogene. 2005 Apr 28;24(19):3110-2015735682Curr Pharm Des. 2005;11(22):2873-8716101443Pflugers Arch. 2005 Sep;450(6):363-7116007431Cytokine Growth Factor Rev. 2006 Jun;17(3):147-5616516532J Biol Chem. 2006 Jun 16;281(24):16814-2016621805Chem Biol. 2006 Nov;13(11):1235-4217114005Proc Natl Acad Sci U S A. 2007 May 1;104(18):7391-617463090Cancer Sci. 2007 Jul;98(7):1099-10617459060Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642DNA Repair (Amst). 2008 Feb 1;7(2):177-8617974506Mol Cancer Res. 2008 May;6(5):675-8418505913Mutat Res. 2008 Aug 25;643(1-2):54-6318579163Antioxid Redox Signal. 2008 Nov;10(11):1853-6718627350Science. 2008 Sep 26;321(5897):1801-618772397Mol Endocrinol. 2010 Feb;24(2):391-40120032196Mol Cell Endocrinol. 2010 Feb 5;315(1-2):40-819879327Cytokine Growth Factor Rev. 2010 Feb;21(1):11-920018552J Pharmacol Exp Ther. 2010 May;333(2):373-8120100905Cancer Invest. 2010 Nov;28(9):885-9520919954Adenocarcinomadrug therapygeneticsmetabolismpathologyAminosalicylic AcidspharmacologyApoptosisdrug effectsBenzenesulfonatespharmacologyBenzoquinonespharmacologyCaspase 3geneticsmetabolismCell Line, TumorCell Proliferationdrug effectsCyclic S-OxidespharmacologyDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsgeneticsmetabolismGene Expression Regulation, Neoplasticdrug effectsGene Knockdown TechniquesHumansMolecular Targeted TherapyOxidation-ReductionPancreatic Neoplasmsdrug therapygeneticsmetabolismpathologyPropionatespharmacologyRNA, Small InterferinggeneticsSTAT3 Transcription Factorantagonists & inhibitorsgeneticsmetabolismSignal Transductiondrug effectsTranscription, Geneticdrug effects
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1573-497839122012DecMolecular biology reportsMol. Biol. Rep.Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis.11249-6210.1007/s11033-012-2035-8The previous published data on the association between the 8-oxo-guanine glycosylase-1 (OGG1) and apurinic/apyrimidinic-endonuclease-1 (APEX1/APE1) polymorphisms and lung cancer risk remained controversial. Several polymorphisms in the OGG1 and APEX1 gene have been described, including the commonly occurring Ser326Cys in OGG1 and Asp148Glu in APEX1. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 37 studies were identified to the meta-analysis, including 9,203 cases and 10,994 controls for OGG1 Ser326Cys (from 25 studies) and 3,491 cases and 4,708 controls for APEX1 Asp148Glu (from 12 studies). When all the eligible studies were pooled into the meta-analysis of OGG1 Ser326Cys polymorphism, significantly increased lung cancer risk was observed in recessive model (OR = 1.17, 95 % CI = 1.03-1.33) and in additive model (OR = 1.21, 95 % CI = 1.03-1.42). In the stratified analysis, significantly increased risk of lung cancer was also observed on the population-based studies (recessive model: OR = 1.26, 95 % CI = 1.08-1.46, additive model: OR = 1.42, 95 % CI = 1.06-1.73) and non-smokers (dominant model: OR = 1.20, 95 % CI = 1.02-1.42, recessive model: OR = 1.20, 95 % CI = 1.02-1.40, additive model: OR = 1.35, 95 % CI = 1.08-1.68). Additionally, when one study was deleted in the sensitive analysis, the results of OGG1 Ser326Cys were changed in Asians (recessive model: OR = 1.16, 95 % CI = 1.06-1.27, additive model: OR = 1.23, 95 % CI = 1.09-1.38). When all the eligible studies were pooled into the meta-analysis of APEX1 Asp148Glu polymorphism, there was no evidence of significant association between lung cancer risk and APEX1 Asp148Glu polymorphism in any genetic model. In the stratified analysis, significantly decreased lung adenocarcinoma risk was observed in recessive model (OR = 0.68, 95 % CI = 0.48-0.97, P (h) = 0.475, I(2) = 0.0 %). Additionally, when one study was deleted in the sensitive analysis, the results of APEX1 Asp148Glu were changed in Asians (recessive model: OR = 1.21, 95 % CI = 1.03-1.43) and smokers (dominant model: OR = 1.62, 95 % CI = 1.08-2.44, additive model: OR = 1.37, 95 % CI = 1.02-1.84). In summary, this meta-analysis indicates that OGG1 Ser326Cys show an increased lung cancer risk in Asians and non-smokers, APEX1 Asp148Glu polymorphism may be associated with decreased lung adenocarcinoma risk, and APEX1 Asp148Glu polymorphism show an increased lung cancer risk in Asians and smokers. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk.WeiWuWDepartment of Hematology, Peace Hospital of Changzhi Medical College, Changzhi, 046000, China. weiwuhxf@163.comHeXiao-FengXFQinJiang-BoJBSuJiaoJLiShao-XiaSXLiuYiYZhangYingYWangWeiWengJournal ArticleMeta-Analysis20121012
NetherlandsMol Biol Rep04032340301-4851EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnticancer Res. 2010 Oct;30(10):4141-521036733Cancer Lett. 2005 Jun 8;223(2):265-7415896461Asian Pac J Cancer Prev. 2010;11(5):1181-621198260Demography. 2003 Feb;40(1):45-6512647513Anticancer Res. 2005 Jan-Feb;25(1B):537-4215816625Biochem Genet. 2004 Dec;42(11-12):453-6015587988Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):669-7410744126J Hum Genet. 2009 Dec;54(12):739-4519881468Cancer Sci. 2006 Aug;97(8):724-816800823Asian Pac J Cancer Prev. 2011;12(4):1067-7221790253Free Radic Res. 2006 Aug;40(8):885-9117015267Biometrics. 1994 Dec;50(4):1088-1017786990J Exp Clin Cancer Res. 2009 Jan 22;28:1019161591Pharmacogenetics. 2004 Feb;14(2):103-915077011Free Radic Biol Med. 2012 Jan 1;52(1):167-7222044660Lung Cancer. 2006 Dec;54(3):267-8316982113Mutat Res. 2011 May 10;709-710:21-3121376741Cancer Epidemiol Biomarkers Prev. 2008 Jul;17(7):1739-4518628426Genet Med. 2002 Mar-Apr;4(2):45-6111882781Control Clin Trials. 1986 Sep;7(3):177-883802833Mol Biol Rep. 2011 Oct;38(7):4537-4321132382Int J Epidemiol. 2008 Feb;37(1):120-3217898028Arh Hig Rada Toksikol. 2008 Dec;59(4):241-5019064361Zhongguo Fei Ai Za Zhi. 2011 Mar;14(3):205-1021426661Cancer Lett. 2003 Mar 10;191(2):171-812618330Carcinogenesis. 2006 May;27(5):997-100716308313Med Oncol. 2011 Sep;28(3):667-7220354815Lung Cancer. 2011 Aug;73(2):138-4621195504Chemosphere. 2011 Feb;82(7):941-621183201Mutat Res. 2007 Jul 28;631(2):101-1017531525Anticancer Res. 2009 Jun;29(6):2417-2019528510Carcinogenesis. 2006 Jun;27(6):1245-5016364924Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502Am J Epidemiol. 2009 Sep 15;170(6):695-70219671832Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Carcinogenesis. 2000 Jul;21(7):1329-3410874010Int J Cancer. 2000 Dec 15;88(6):932-711093817Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Lancet. 1997 Oct 18;350(9085):11829343537Carcinogenesis. 2004 Aug;25(8):1395-40115044328J Thorac Oncol. 2011 Apr;6(4):813-721623257J Natl Cancer Inst. 2000 Nov 1;92(21):1764-7211058619Arch Med Res. 2011 Apr;42(3):226-3421722819Carcinogenesis. 2006 Mar;27(3):560-716195237Oncogene. 1998 Jun 25;16(25):3219-259681819Genomics. 2004 Jun;83(6):970-915177551Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):9886-9110944198J Clin Oncol. 2010 Nov 20;28(33):4945-5220940192Int J Cancer. 2003 Oct 20;107(1):84-812925960Cancer Epidemiol Biomarkers Prev. 2002 Aug;11(8):730-812163326J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060Cancer Res. 1996 Sep 15;56(18):4103-78797573J Prev Med Public Health. 2006 Mar;39(2):130-416615267Mutat Res. 2008 Mar 1;639(1-2):45-5418155253BMJ. 1997 Sep 13;315(7109):629-349310563Carcinogenesis. 2004 Dec;25(12):2433-4115333465FASEB J. 2009 Oct;23(10):3459-6919541747CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855J Epidemiol. 2002 May;12(3):258-6512164330Clin Cancer Res. 2001 Apr;7(4):824-3011309329Cancer Res. 2003 Aug 15;63(16):4899-90212941813J Natl Cancer Inst. 2005 Apr 20;97(8):567-7615840879Carcinogenesis. 2004 Nov;25(11):2177-8115284179Nature. 2001 May 17;411(6835):366-7411357144Amino Acid SubstitutiongeneticsCase-Control StudiesDNA GlycosylasesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsGene FrequencygeneticsGenetic Association StudiesGenetic Predisposition to DiseaseHumansLung NeoplasmsenzymologygeneticspathologyPolymorphism, Single NucleotidegeneticsPublication BiasRisk FactorsSmokinggenetics
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1349-90922262012Journal of epidemiologyJ EpidemiolThe APE1 Asp/Asp genotype and the combination of APE1 Asp/Asp and hOGG1-Cys variants are associated with increased p53 mutation in non-small cell lung cancer.537-4210.2188/jea.JE20120048The hOGG1 Ser326Cys polymorphism is associated with lung cancer risk, but there are limited data regarding an association between the APE1 Asp148Glu polymorphism and lung cancer. Biological evidence shows that the hOGG1-Cys allele results in less DNA repair activity; however, this is not associated with p53 mutation in lung cancer. Therefore, we investigated whether an interaction between hOGG1 and APE1 is associated with the frequency of p53 mutation in lung cancer.We studied 217 Taiwanese adults with primary lung cancer. DNA polymorphisms of hOGG1 and APE1 were determined by polymerase chain reaction (PCR)-based restriction fragment length polymorphism. Mutations in p53 exons 5-8 were detected by direct sequencing. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the risk of p53 mutation associated with polymorphisms of hOGG1 and APE1 in lung cancer.As expected, no association between hOGG1 polymorphism and p53 mutation was observed in this population. However, a higher risk of p53 mutation was found in participants with the APE1 Asp/Asp genotype than in those with the APE1-Glu allele (OR, 2.15; 95% CI, 1.19-3.87; P = 0.011). The risk of p53 mutation was also higher in participants with APE1 Asp/Asp plus hOGG1-Cys than in those with APE1-Glu plus hOGG1 Ser/Ser (OR, 3.72; 95% CI, 1.33-10.40; P = 0.012).These results suggest that the APE1 Asp/Asp genotype and the combination of the APE1 Asp/Asp and hOGG1-Cys variants are associated with increased risk of p53 mutation in non-small cell lung cancer.LinChun-HsuanCHDepartment of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ROC.ChenPo-MingPMChengYa-WenYWChenChih-YiCYYuanChiun-JyeCJLeeHueiHengJournal ArticleResearch Support, Non-U.S. Gov't20120929
JapanJ Epidemiol96076880917-50400Peptide Fragments0Tumor Suppressor Protein p530p53 protein (325-355), humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCarcinogenesis. 2004 Dec;25(12):2433-4115333465Oncogene. 1998 Jun 25;16(25):3219-259681819Int J Cancer. 2005 Apr 10;114(3):387-9315551330Cancer Res. 2005 Jun 15;65(12):5076-8315958551Am J Epidemiol. 2005 Nov 15;162(10):925-4216221808Carcinogenesis. 2006 Mar;27(3):560-716195237DNA Repair (Amst). 2006 Nov 8;5(11):1337-4516861056Lung Cancer. 2007 May;56(2):281-817222938Nature. 2007 Jun 21;447(7147):941-5017581577Mutat Res. 2007 Jul 28;631(2):101-1017531525Mol Aspects Med. 2007 Jun-Aug;28(3-4):258-7517628657Cancer Res. 2007 Nov 15;67(22):10686-9318006810Chem Res Toxicol. 2007 Dec;20(12):1737-4018031018Cell Res. 2008 Jan;18(1):27-4718166975Expert Rev Anticancer Ther. 2008 Apr;8(4):605-1518402527J Clin Oncol. 2008 Jul 20;26(21):3560-618640936Proc Am Thorac Soc. 2008 Dec 1;5(8):811-519017734Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):223-919124501Cancer Res. 2009 Apr 15;69(8):3642-919351836Ann Surg Oncol. 2009 Jul;16(7):1918-2419434453Am J Epidemiol. 2009 Sep 15;170(6):695-70219671832Med Oncol. 2011 Sep;28(3):667-7220354815J Clin Oncol. 2000 Jun;18(11):2309-1510829052Nucleic Acids Res. 2000 Oct 15;28(20):3871-911024165Nucleic Acids Res. 2001 Mar 15;29(6):1285-9211238994Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502Oncogene. 2002 Oct 7;21(45):6870-612362269Oncogene. 2002 Oct 21;21(48):7435-5112379884Pharmacogenetics. 2004 Feb;14(2):103-915077011Carcinogenesis. 2004 Aug;25(8):1395-40115044328Int J Cancer. 2005 Mar 10;114(1):153-615523686AdultAgedAged, 80 and overCarcinoma, Non-Small-Cell LunggeneticsDNA GlycosylasesgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsFemaleGenetic Predisposition to DiseaseGenotypeHumansLung NeoplasmsgeneticsMaleMiddle AgedMutationPeptide FragmentsgeneticsPolymorphism, GeneticTaiwanTumor Suppressor Protein p53genetics
201210660201210660201313160ppublish23038158DN/JST.JSTAGE/jea/JE20120048PMC3798566
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1687-846920122012Journal of oncologyJ OncolDNA Repair and Cancer Therapy: Targeting APE1/Ref-1 Using Dietary Agents.370481Epidemiological studies have demonstrated the cancer protective effects of dietary agents and other natural compounds isolated from fruits, soybeans, and vegetables on neoplasia. Studies have also revealed the potential for these natural products to be combined with chemotherapy or radiotherapy for the more effective treatment of cancer. In this paper we discuss the potential for targeting the DNA base excision repair enzyme APE1/Ref-1 using dietary agents such as soy isoflavones, resveratrol, curcumin, and the vitamins ascorbate and α-tocopherol. We also discuss the potential role of soy isoflavones in sensitizing cancer cells to the effects of radiotherapy. A comprehensive review of the dual nature of APE1/Ref-1 in DNA repair and redox activation of cellular transcription factors, NF-κB and HIF-1α, is also discussed. Further research efforts dedicated to delineating the role of APE1/Ref-1 DNA repair versus redox activity in sensitizing cancer cells to conventional treatment are warranted.RaffoulJulian JJJDepartment of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.HeydariAhmad RARHillmanGilda GGGengJournal Article20120910
EgyptJ Oncol1014965371687-8450J Biol Chem. 1974 Mar 10;249(5):1530-54206354J Biol Chem. 1974 Mar 10;249(5):1536-404361739Can J Biochem. 1972 Feb;50(2):217-244552312Proc Natl Acad Sci U S A. 1983 Jan;80(2):487-916300848Mutat Res. 1994 Jul;315(1):55-637517011Nucleic Acids Res. 1994 Nov 25;22(23):4884-97800476Cancer Res. 1995 Jan 15;55(2):259-667812955Cancer Res. 1994 Nov 15;54(22):5841-77954412Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128J Biol Chem. 1996 Dec 13;271(50):32253-98943284Biochem Biophys Res Commun. 1997 Apr 28;233(3):692-69168916Cancer Res. 1998 Jan 15;58(2):222-59443396Carcinogenesis. 1998 Mar;19(3):419-249525275Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-69560228Cancer Res. 1998 Oct 1;58(19):4410-69766671Mutat Res. 1998 Oct 21;409(1):17-299806499Cancer Res. 1999 Jun 1;59(11):2522-610363965Mutat Res. 2000 Oct 16;461(2):83-10811018583Cancer Res. 2001 Jul 15;61(14):5552-711454706Prog Nucleic Acid Res Mol Biol. 2001;68:151-6411554294Oncogene. 2002 May 23;21(23):3663-912032834Carcinogenesis. 2002 Sep;23(9):1419-2512189182Cancer Res. 2002 Sep 1;62(17):4945-5412208745Pancreas. 2002 Nov;25(4):e71-612409844Mutat Res. 2002 Nov 30;509(1-2):201-1012427539Mol Cell Biol. 2003 Jan;23(1):382-812482989Oncogene. 2002 Dec 16;21(58):8926-3412483509Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Int J Cancer. 2003 Mar 20;104(2):204-1212569576Front Biosci. 2003 May 1;8:d963-8112700077Mutat Res. 2003 May 15;526(1-2):93-12512714187Int J Radiat Biol. 2003 May;79(5):351-812943243Cancer Res. 2003 Nov 1;63(21):7005-3114612489Anticancer Res. 2003 Sep-Oct;23(5A):4039-4614666716J Biol Chem. 2004 Apr 30;279(18):18425-3314973123J Med Food. 2004 Summer;7(2):117-2115298755Mol Cell Biol. 2004 Sep;24(18):8145-5315340075Biochem Biophys Res Commun. 2005 Jun 17;331(4):1245-5215883009Radiat Res. 2005 Jun;163(6):700-116044501Cancer Res. 2006 Apr 1;66(7):3347-5016585150Cancer Res. 2006 Dec 1;66(23):11298-30417145876Mol Cell Biochem. 2007 Aug;302(1-2):99-10917396234Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1246-5217548692Acta Pharmacol Sin. 2007 Sep;28(9):1305-1517723164Curr Cancer Drug Targets. 2007 Dec;7(8):759-6518220535Anticancer Agents Med Chem. 2008 May;8(4):417-2518473726Cancer Lett. 2008 Oct 8;269(2):199-22518479807Free Radic Biol Med. 2009 Jun 1;46(11):1488-9919268524Cell Signal. 2009 Nov;21(11):1541-719298854Cancer Treat Rev. 2009 Nov;35(7):597-60719660870Semin Oncol. 2010 Jun;37(3):258-8120709209J Thorac Oncol. 2011 Apr;6(4):688-9821325978Ann Hepatol. 2011 Oct-Dec;10(4):516-3021911894EMBO J. 1992 Sep;11(9):3323-351380454EMBO J. 1992 Feb;11(2):653-651537340Proc Natl Acad Sci U S A. 1990 Jun;87(11):4193-71693433Biochim Biophys Acta. 1991 Aug 9;1079(1):57-641716153Science. 1997 Jan 10;275(5297):218-208985016J Biol Chem. 1998 Aug 14;273(33):21203-99694877Biochem Biophys Res Commun. 1999 Jan 27;254(3):739-439920811Cancer Res. 1999 Feb 1;59(3):597-6019973206Carcinogenesis. 2000 Jul;21(7):1329-3410874010Cancer Res. 2001 Mar 1;61(5):2220-511280790J Biol Chem. 2001 Dec 7;276(49):46290-611591703Anticancer Res. 2001 Jul-Aug;21(4B):2895-90011712783World J Gastroenterol. 2002 Feb;8(1):79-8111833076Carcinogenesis. 2002 Aug;23(8):1307-1312151348Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14548-5312357032Mol Cancer Ther. 2004 Jun;3(6):679-8615210853World J Gastroenterol. 2004 Oct 15;10(20):3048-5215378791DNA Repair (Amst). 2005 Mar 2;4(3):367-7915661660Mol Cell. 2005 Feb 4;17(3):463-7015694346Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Mol Cancer Ther. 2005 Dec;4(12):1923-3516373707Mol Cancer Ther. 2006 May;5(5):1335-4116731767Cancer Res. 2007 Mar 1;67(5):1988-9617332326Cancer Res. 2007 Mar 1;67(5):2141-917332344Cancer Res. 2007 Apr 15;67(8):3853-6117440100Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Adv Exp Med Biol. 2007;595:149-7217569209Adv Exp Med Biol. 2007;595:173-8417569210Prostate. 2007 Nov 1;67(15):1641-5317823925Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143Int J Cancer. 2009 Apr 1;124(7):1675-8419101986J Clin Oncol. 2009 Jun 1;27(16):2712-2519414669Antioxid Redox Signal. 2010 Jun 1;12(11):1247-6919764832Cancer Treat Rev. 2010 Aug;36(5):425-3520056333Nutr Cancer. 2010;62(7):996-100020924975Free Radic Biol Med. 2011 Jul 15;51(2):289-9821605661Free Radic Biol Med. 2011 Sep 1;51(5):1068-8421683786CA Cancer J Clin. 2012 Jan-Feb;62(1):10-2922237781Biochemistry. 2012 Jan 17;51(2):695-70522148505Nucleic Acids Res. 1991 Oct 25;19(20):5519-231719477J Biol Chem. 1991 Nov 5;266(31):20797-8021939131
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1860-71877102012OctChemMedChemChemMedChemDesign and synthesis of 3-carbamoylbenzoic acid derivatives as inhibitors of human apurinic/apyrimidinic endonuclease 1 (APE1).1825-3910.1002/cmdc.201200334Apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is a multifaceted protein with an essential role in the base excision repair (BER) pathway. Its implication in tumor development, progression, and resistance has been confirmed in multiple cancers, making it a viable target for intensive investigation. In this work, we designed and synthesized different classes of small-molecule inhibitors of the catalytic endonuclease function of APE1 that contain a 3-carbamoylbenzoic acid scaffold. Further structural modifications were made with the aim of increasing the activity and cytotoxicity of these inhibitors. Several of our compounds were shown to inhibit the catalytic endonuclease function of APE1 with potencies in the low-micromolar range in vitro, and therefore represent novel classes of APE1 inhibitors worthy of further development.Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.AielloFrancescaFDipartimento di Scienze Farmaceutiche, Università della Calabria, 87036 Arcavacata di Rende, CS, Italy. francesca.aiello@unical.itShabaikYumnaYEsquedaAdrianASanchezTino WTWGrandeFedoraFGarofaloAntonioANeamatiNouriNengJournal Article20120905
GermanyChemMedChem1012590131860-71790Methylurea Compounds4494-26-25-formyl-2'-deoxyuridine8SKN0B0MIMBenzoic AcidEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseN68H97CAWGcarbamolW78I7AY22CDeoxyuridineIMBenzoic Acidchemical synthesischemistrytoxicityCell LineCell Survivaldrug effectsDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsmetabolismDeoxyuridineanalogs & derivativestoxicityDrug DesignHumansMethylurea Compoundschemistry
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1939-458623202012OctMolecular biology of the cellMol. Biol. CellNucleolar accumulation of APE1 depends on charged lysine residues that undergo acetylation upon genotoxic stress and modulate its BER activity in cells.4079-9610.1091/mbc.E12-04-0299Apurinic/apyrimidinic endonuclease 1 (APE1) is the main abasic endonuclease in the base excision repair (BER) pathway of DNA lesions caused by oxidation/alkylation in mammalian cells; within nucleoli it interacts with nucleophosmin and rRNA through N-terminal Lys residues, some of which (K(27)/K(31)/K(32)/K(35)) may undergo acetylation in vivo. Here we study the functional role of these modifications during genotoxic damage and their in vivo relevance. We demonstrate that cells expressing a specific K-to-A multiple mutant are APE1 nucleolar deficient and are more resistant to genotoxic treatment than those expressing the wild type, although they show impaired proliferation. Of interest, we find that genotoxic treatment induces acetylation at these K residues. We also find that the charged status of K(27)/K(31)/K(32)/K(35) modulates acetylation at K(6)/K(7) residues that are known to be involved in the coordination of BER activity through a mechanism regulated by the sirtuin 1 deacetylase. Of note, structural studies show that acetylation at K(27)/K(31)/K(32)/K(35) may account for local conformational changes on APE1 protein structure. These results highlight the emerging role of acetylation of critical Lys residues in regulating APE1 functions. They also suggest the existence of cross-talk between different Lys residues of APE1 occurring upon genotoxic damage, which may modulate APE1 subnuclear distribution and enzymatic activity in vivo.LirussiLisaLDepartment of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.AntonialiGiuliaGVascottoCarloCD'AmbrosioChiaraCPolettoMattiaMRomanelloMilenaMMarascoDanielaDLeoneMarilisaMQuadrifoglioFrancoFBhakatKishor KKKScaloniAndreaATellGianlucaGengJournal ArticleResearch Support, Non-U.S. Gov't20120823
United StatesMol Biol Cell92013901059-15240Mutant Proteins0Nuclear Proteins0RNA, Ribosomal117896-08-9nucleophosminEC 3.5.1.-SIRT1 protein, humanEC 3.5.1.-Sirtuin 1EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseK3Z4F929H6LysineIMFree Radic Biol Med. 2006 Oct 1;41(7):1113-2316962936Oncogene. 2002 Dec 16;21(58):8926-3412483509Biochim Biophys Acta. 1981 Sep 29;670(2):190-46170344Proteomics. 2010 Oct;10(19):3414-3420707006Mutat Res. 2001 Mar 7;485(2):143-5211182545Cancer Res. 2000 Dec 1;60(23):6688-9511118054Nucleic Acids Res. 2006;34(7):2067-7616617147Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116EMBO J. 2001 Nov 15;20(22):6530-911707423Nucleic Acids Res. 2012 Jan;40(2):701-1121933813J Biomol NMR. 1995 Jul;6(1):1-1022911575Nucleic Acids Res. 2011 Oct;39(18):8017-2821727086Oncogene. 2011 Jan 27;30(4):482-9320856196Nat Cell Biol. 2002 Jul;4(7):529-3312080348Methods Mol Med. 1999;28:17-2321374023J Pharmacol Exp Ther. 2010 Sep 1;334(3):988-9820504914Mol Cell Proteomics. 2006 Jan;5(1):97-11316195223Mech Ageing Dev. 2005 Oct;126(10):1071-815951004Oncogene. 2005 Apr 28;24(19):3110-2015735682Mol Biol Cell. 2011 Oct;22(20):3887-90121865600Expert Rev Proteomics. 2010 Jun;7(3):401-920536310Nucleic Acids Res. 2010 Jan;38(3):832-4519934257J Am Chem Soc. 2006 Oct 18;128(41):13586-9117031973EMBO J. 2003 Dec 1;22(23):6299-30914633989Electrophoresis. 2010 Jan;31(3):497-50620119961Cancer Res. 1997 Dec 15;57(24):5457-99407949Mol Cell. 2008 Feb 29;29(4):477-8718313385Cell Mol Life Sci. 2010 Nov;67(21):3569-7220706767Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084J Biol Chem. 2000 Nov 24;275(47):36491-411006266Free Radic Res. 2008 Jan;42(1):20-918324520Mol Biosyst. 2011 Mar;7(3):889-9821161094Biochemistry. 2010 May 11;49(18):3786-9620377204Nat Methods. 2012 Feb;9(2):152-822290187Nat Protoc. 2007;2(8):2024-3217703215Biochem Biophys Res Commun. 2012 Jul 20;424(1):34-922713458Oncogene. 2005 Jun 2;24(24):3853-6315824742Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Cell Mol Life Sci. 2010 Nov;67(21):3621-3120809131Mol Cell Pharmacol. 2010;2(5):203-21221499571Mol Cell. 2005 Feb 4;17(3):463-7015694346J Biol Chem. 1999 Dec 10;274(50):35809-1510585464J Pept Sci. 2010 Aug;16(8):414-2320572211Proteomics. 2009 Feb;9(4):1058-7419180539Nucleic Acids Res. 2010 Dec;38(22):8239-5620699270FASEB J. 2004 Jun;18(9):986-815084519Free Radic Res. 2005 Mar;39(3):269-8115788231Mol Cell Biol. 2010 Jan;30(2):366-7119901076Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-89108029Nucleic Acids Res. 2007;35(5):1569-7717289756Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Biophys J. 2008 Jun;94(12):4579-8518192367Nucleic Acids Res. 2009 Jul;37(12):3946-5819401441Mutat Res. 2003 Feb 5;535(1):103-1512547288Cancer Res. 2005 Nov 1;65(21):9834-4216267006Nucleic Acids Res. 2007;35(12):4103-1317567611Anal Biochem. 2004 Sep 1;332(1):90-915301953Oncogene. 2009 Apr 2;28(13):1616-2519219073Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766DNA Repair (Amst). 2007 Apr 1;6(4):461-917166779Free Radic Biol Med. 2012 Jul 15;53(2):237-4822580151AcetylationCell NucleolusenzymologyCell ProliferationDNA DamageDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasechemistrymetabolismEnzyme StabilityHeLa CellsHumansLysinemetabolismMutant ProteinsmetabolismNuclear ProteinsmetabolismProtein BindingProtein ConformationProtein TransportRNA, RibosomalmetabolismSirtuin 1metabolismStructure-Activity Relationship
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2075-8251422012AprActa naturaeActa NaturaeConstruction of a Full-Atomic Mechanistic Model of Human Apurinic/Apyrimidinic Endonuclease APE1 for Virtual Screening of Novel Inhibitors.80-6A full-atomic molecular model of human apurinic/apyrimidinic endonuclease APE1, an important enzyme in the DNA repair system, has been constructed. The research consisted of hybrid quantum mechanics/molecular mechanics modeling of the enzyme-substrate interactions, as well as calculations of the ionization states of the amino acid residues of the active site of the enzyme. The choice of the APE1 mechanism with an Asp210 residue as a proton acceptor was validated by means of a generalization of modeling and experimental data. Interactions were revealed in the active site that are of greatest significance for binding the substrate and potential APE1 inhibitors (potential co-drugs of interest in the chemo- and radiotherapy of oncological diseases).KhaliullinI GIGBelozersky Institute of Physicochemical Biology, Lomonosov Moscow State University.NilovD KDKShapovalovaI VIVSvedasV KVKengJournal Article
Russia (Federation)Acta Naturae1015258232075-8251Cancer Treat Rev. 2010 Aug;36(5):425-3520056333J Am Chem Soc. 2008 Jul 23;130(29):9332-4118576638J Mol Biol. 1999 Jul 9;290(2):447-5710390343J Comput Chem. 2008 May;29(7):1019-3118072177Proteins. 2006 Nov 15;65(3):712-2516981200EMBO J. 1997 Nov 3;16(21):6548-589351835Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642DNA Repair (Amst). 2004 Nov 2;3(11):1447-5515380100Biochemistry (Mosc). 2011 Jan;76(1):24-3521568837Science. 1999 Dec 3;286(5446):1897-90510583946Biochemistry (Mosc). 2011 Jan;76(1):94-11721568843J Comput Chem. 2006 Jul 30;27(10):1101-1116691568Nature. 2000 Jan 27;403(6768):451-610667800Biochemistry. 2009 Jan 13;48(1):19-2619123919Biochemistry. 2007 Mar 20;46(11):3096-10717323932J Mol Graph. 1996 Feb;14(1):33-8, 27-88744570Proteins. 2008 Nov 15;73(3):765-8318498103Cell Mol Life Sci. 2010 Nov;67(21):3621-3120809131J Chem Inf Model. 2008 Dec;48(12):2371-8519007114Proteins. 2005 Dec 1;61(4):704-2116231289PLoS One. 2009;4(6):e574019484131Mol Biol (Mosk). 2007 May-Jun;41(3):450-6617685223Proteins. 2007 Jul 1;68(1):313-2317427952Nature. 2001 May 17;411(6835):366-7411357144QM/MMapurinic/apyrimidinic endonucleaseenzymatic mechanisminhibitionmolecular modeling
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1464-38042762012NovMutagenesisMutagenesisSkin tumours induced by narrowband UVB have higher frequency of p53 mutations than tumours induced by broadband UVB independent of Ogg1 genotype.637-4310.1093/mutage/ges029Different wavelengths of ultraviolet (UV) light have different promoting effects on skin carcinogenesis. Narrowband UVB (NB-UVB) has a single-peak wavelength of 311 nm and is widely used for treating skin diseases. Our previous work showed that, in comparison with conventional broadband UVB (BB-UVB), long-term exposure to NB-UVB induces higher frequency of skin cancer in mice, and it suggested that this is mediated through the formation of cyclobutane pyrimidine dimers (CPDs). To explore whether the frequency of p53 mutations in skin tumours correlates with CPD-induced mutations, we compared the frequency and types of p53 mutations between NB-UVB-induced and BB-UVB-induced malignant skin tumours produced in wild-type and Ogg1 knockout mice, which are deficient in repair of oxidative 8-oxoguanine (8-oxoG), a DNA damage mediated by reactive oxygen species (ROS). The frequency of p53 mutation was significantly higher in NB-UVB-induced than in BB-UVB-induced tumours in both wild-type and Ogg1 knockout mice. Most of the p53 mutations found were G:C → A:T transitions at dipyrimidine sites in both the NB-UVB- and BB-UVB-exposed groups. However, G:C → T:A mutations caused by 8-oxoG did not increase in Ogg1 knockout mice exposed to either NB-UVB or BB-UVB. Our results strongly suggest that NB-UVB induces highly malignant tumours caused by p53 dipyrimidine mutations through the formation of CPDs.YogiantiFlandianaFDivision of Dermatology, Department of Internal Related, Graduate School of Medicine, Kobe University, Kobe, Japan.KunisadaMakotoMOnoRyusukeRSakumiKunihikoKNakabeppuYusakuYNishigoriChikakoCengJournal ArticleResearch Support, Non-U.S. Gov't20120727
EnglandMutagenesis87078120267-83570Tumor Suppressor Protein p53EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMAnimalsDNA DamageDNA GlycosylasesgeneticsmetabolismGenotypeImmunohistochemistryMiceMice, Inbred C57BLMice, KnockoutMutationSkinpathologyradiation effectsSkin NeoplasmsgeneticspathologyTumor Suppressor Protein p53geneticsmetabolismUltraviolet Rays
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1873-45965392012Nov01Free radical biology & medicineFree Radic. Biol. Med.Nuclear depletion of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is an indicator of energy disruption in neurons.1782-9010.1016/j.freeradbiomed.2012.07.025S0891-5849(12)00420-0Apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is a multifunctional protein critical for cellular survival. Its involvement in adaptive survival responses includes key roles in redox sensing, transcriptional regulation, and repair of DNA damage via the base excision repair (BER) pathway. Ape1 is abundant in most cell types and central in integrating the first BER step catalyzed by different DNA glycosylases. BER is the main process for removal of oxidative DNA lesions in postmitotic brain cells, and after ischemic brain injury preservation of Ape1 coincides with neuronal survival, while its loss has been associated with neuronal death. Here, we report that in cultured primary neurons, diminution of cellular ATP by either oligomycin or H(2)O(2) is accompanied by depletion of nuclear Ape1, while other BER proteins are unaffected and retain their nuclear localization under these conditions. Importantly, while H(2)O(2) induces γH2AX phosphorylation, indicative of chromatin rearrangements in response to DNA damage, oligomycin does not. Furthermore, despite comparable diminution of ATP content, H(2)O(2) and oligomycin differentially affect critical parameters of mitochondrial respiration that ultimately determine cellular ATP content. Taken together, our findings demonstrate that in neurons, nuclear compartmentalization of Ape1 depends on ATP and loss of nuclear Ape1 reflects disruption of neuronal energy homeostasis. Energy crisis is a hallmark of stroke and other ischemic/hypoxic brain injuries. In vivo studies have shown that Ape1 deficit precedes neuronal loss in injured brain regions. Thus, our findings bring to light the possibility that energy failure-induced Ape1 depletion triggers neuronal death in ischemic brain injuries.Copyright © 2012 Elsevier Inc. All rights reserved.SinghShilpeeSDepartment of Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.EnglanderElla WEWengR01 ES014613ESNIEHS NIH HHSUnited StatesR01 NS039449NSNINDS NIH HHSUnited StatesES014613ESNIEHS NIH HHSUnited StatesNS039449NSNINDS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20120727
United StatesFree Radic Biol Med87091590891-58490DNA-Binding Proteins0Oligomycins0Oxidants0Poly-ADP-Ribose Binding Proteins0X-ray Repair Cross Complementing Protein 10Xenopus Proteins8L70Q75FXEAdenosine TriphosphateBBX060AN9VHydrogen PeroxideEC 3.6.3.-Mitochondrial Proton-Translocating ATPasesEC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 6.5.1.-DNA LigasesEC 6.5.1.1DNA Ligase ATPEC 6.5.1.1DNA ligase III alpha protein, XenopusIMNat Immunol. 2003 Feb;4(2):145-5312524539J Cell Physiol. 2002 Nov;193(2):180-612384995Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-41722334EMBO J. 1992 Sep;11(9):3323-351380454J Neurosci Res. 1993 Aug 1;35(5):567-768377226Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):23-77506414Am J Physiol. 1996 Jun;270(6 Pt 2):F1057-658764325Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128J Neurosci. 1996 Nov 1;16(21):6795-8068824320Brain Res Mol Brain Res. 1997 Feb;44(1):167-709030714Genes Dev. 1997 Mar 1;11(5):558-709119221Nat Med. 1997 Oct;3(10):1089-959334719Mutat Res. 1998 Oct 21;409(1):17-299806499Stroke. 1999 Feb;30(2):441-8; discussion 4499933285J Cereb Blood Flow Metab. 1999 May;19(5):495-50110326716Free Radic Biol Med. 2005 Jan 1;38(1):12-2315589367Nucleic Acids Res. 2005;33(4):1222-915731342Nucleic Acids Res. 2005;33(14):4379-9416077024DNA Repair (Amst). 2005 Dec 8;4(12):1442-916199212DNA Repair (Amst). 2006 Feb 3;5(2):189-20916290067Nucleic Acids Res. 2007;35(8):2522-3217403694J Cell Physiol. 2007 Jul;212(1):223-3517443679Brain Res. 2007 Sep 7;1168:129-3817706620Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Mech Ageing Dev. 2008 Jul-Aug;129(7-8):475-8218374390J Neurochem. 2008 Nov;107(3):734-4418752643Oncogene. 2009 Apr 2;28(13):1616-2519219073J Neurochem. 2009 Sep;110(6):1774-8319619136Glia. 2009 Nov 1;57(14):1480-9119306371Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3204-920133634Anal Chem. 2009 Aug 15;81(16):6868-7819555051Nat Cell Biol. 2010 Jun;12(6):563-7120473298Am J Physiol Cell Physiol. 2010 Aug;299(2):C464-7620445170Oncogene. 2010 Jul 29;29(30):4330-4020498636J Biol Chem. 2010 Sep 3;285(36):28191-920573957Cell Mol Life Sci. 2010 Nov;67(21):3609-2020711647Biochem J. 2011 Apr 15;435(2):297-31221726199Nat Cell Biol. 2011 Oct;13(10):1161-921968989Free Radic Biol Med. 2011 Nov 1;51(9):1621-3521872656Mol Biol Cell. 2011 Oct;22(20):3887-90121865600J Mol Biol. 2011 Dec 2;414(3):313-2622024594Biochemistry. 2012 Jan 17;51(2):695-70522148505J Neurochem. 2000 Mar;74(3):1098-10510693941Neurobiol Dis. 2001 Jun;8(3):380-9011447995J Neurochem. 2002 Jan;80(1):111-811796749Nucleic Acids Res. 1991 Mar 11;19(5):1087-921708495Adenosine TriphosphatemetabolismAnimalsCell NucleusenzymologyCells, CulturedDNA DamageDNA Ligase ATPDNA LigasesmetabolismDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismDNA-Binding ProteinsmetabolismEnergy MetabolismHydrogen PeroxidepharmacologyMiceMice, Inbred C57BLMitochondriametabolismMitochondrial Proton-Translocating ATPasesantagonists & inhibitorsmetabolismNeuronsmetabolismOligomycinspharmacologyOxidantspharmacologyOxygen ConsumptionPoly-ADP-Ribose Binding ProteinsProtein TransportX-ray Repair Cross Complementing Protein 1Xenopus Proteins
20120503201207162012071820127316020127316020133560ppublish22841870S0891-5849(12)00420-010.1016/j.freeradbiomed.2012.07.025PMC3487712NIHMS409395
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1573-72921142012DecFamilial cancerFam. CancerNovel mutations of OGG1 base excision repair pathway gene in laryngeal cancer patients.587-9310.1007/s10689-012-9554-2OGG1 (The human 8-oxoguanine glycosylase 1) is the primary enzyme in BER (base excision repair) pathway, responsible for the excision of 7, 8-dihydro-8-oxoguanine (8-oxoG), a mutagenic base byproduct that occurs as a result of exposure to reactive oxygen species. OGG1 gene is highly polymorphic among humans and is mutated in cancer cells. In this case control study, all exons of OGG1 gene and its exon/intron boundaries were amplified in 210 laryngeal cancer cases and 210 matched controls and then analyzed by single stranded conformational polymorphism. Amplified products showing altered mobility patterns were sequenced and analyzed. Two silent (Gln718Gln, His699-700His) and three missense (Ala597, Thr608-610Pro and Glu707Lys) mutations were observed in exon 2. In addition to this one missense mutation (1578G > A) was also observed in 3'UTR region. We found a significant association between OGG1 mutations and laryngeal cancer and observed that His699-His700, silent mutation exhibited an enhanced risk of ~9.0 folds (OR = 9.07, 95 % CI = 4.73-17.39) and 1578G > A, missense mutation ~0.4 folds (OR = 0.37, 95 % CI = 0.15-0.90). Furthermore, a positive association of OGG1 mutations with smoking was observed in laryngeal cancer cases when compared to controls. Heavy smokers have higher incidence of OGG1 mutations when compared to light smokers in present study. Our results demonstrate that OGG1 mutations are associated with an increased risk of laryngeal cancer. OGG1 mutations were found to accumulate more of 8-OHdG in smokers, which may serve as a biomarker for early diagnosis of laryngeal cancer.MahjabeenIshratICancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan. ishrat_qau@yahoo.comMasoodNosheenNBaigRuqia MehmoodRMSabirMaimoonaMInayatUzmaUMalikFaraz ArshadFAKayaniMahmood AkhtarMAengComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't
NetherlandsFam Cancer1008982111389-96000Reactive Oxygen SpeciesEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMBreast Cancer Res Treat. 2005 Jan;89(1):15-2115666192Mod Pathol. 1999 Jan;12(1):47-539950162Int J Cancer. 2001 May 20;95(3):140-311307145Biol Pharm Bull. 2004 Apr;27(4):480-515056851Cancer Res. 1996 Feb 15;56(4):683-88630995Carcinogenesis. 2007 Aug;28(8):1629-3717389610Clin Cancer Res. 2000 Apr;6(4):1394-40010778969Carcinogenesis. 1997 Sep;18(9):1763-69328173J Pharmacol Exp Ther. 2000 Oct;295(1):1-910991953Cold Spring Harb Symp Quant Biol. 2000;65:103-1112760025J Mol Biol. 2002 Mar 22;317(2):171-711902834Cancer Sci. 2004 Dec;95(12):977-8315596047Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502Carcinogenesis. 2004 Sep;25(9):1689-9415073047Cancer Res. 2000 Sep 1;60(17):4740-410987279Prog Nucleic Acid Res Mol Biol. 2001;68:305-1411554308Cancer Res. 2003 Jul 15;63(14):4287-9212874039J Epidemiol. 2003 Jan;13(1):29-3712587611Oncogene. 1998 Jun 25;16(25):3219-259681819Cell. 1996 Jul 26;86(2):321-98706136Cancer Res. 2006 Dec 15;66(24):11683-917178863Oncogene. 1998 Jun 11;16(23):3083-69662341IARC Monogr Eval Carcinog Risks Hum. 2004;83:1-143815285078Oral Oncol. 2006 Apr;42(4):350-6216324877Free Radic Res Commun. 1990;11(1-3):23-72074046J Biol Chem. 2003 Nov 28;278(48):47937-4512966098Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4156-6110725358Cancer Res. 1996 Jun 1;56(11):2546-98653695J Epidemiol. 2007 Sep;17(5):156-6017827862Curr Opin Struct Biol. 2004 Feb;14(1):43-915102448AdultCase-Control StudiesDNA GlycosylasesgeneticsFemaleHumansLaryngeal NeoplasmsgeneticspathologyMaleMiddle AgedMutationgeneticsPolymerase Chain ReactionPolymorphism, Single-Stranded ConformationalPrognosisReactive Oxygen SpeciesmetabolismSmokingadverse effects
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1872-97546152012OctNeurochemistry internationalNeurochem. Int.Ogg1 null mice exhibit age-associated loss of the nigrostriatal pathway and increased sensitivity to MPTP.721-3010.1016/j.neuint.2012.06.013S0197-0186(12)00210-0Cumulative damage to cellular macromolecules via oxidative stress is a hallmark of aging and neurodegenerative disease. Whether such damage is a cause or a subsequent effect of neurodegeneration is still unknown. This paper describes the development of an age-associated mild parkinsonian model in mice that lack the DNA repair enzyme 8-oxoguanine glycosylase 1 (Ogg1). Aged OGG1 knock-out (OGG1 KO) mice show a decreased spontaneous locomotor behavior and evidence a decrease in striatal dopamine levels, a loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN), and an increase in ubiquitin-positive inclusions in their remaining SN neurons. In addition, young OGG1 KO mice are more susceptible to the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) than their wild-type (WT) counterparts. Age-associated increases in 7,8-dihydro-2'-deoxyguanine (oxo(8)dG) have been reported in brain regions and neuronal populations affected in Parkinson's disease (PD), toxin-induced parkinsonian models, and mice harboring genetic abnormalities associated with PD. Because of these increased oxo(8)dG levels, the OGG1 KO mouse strain could shed light on molecular events leading to neuronal loss as a consequence of cumulative oxidative damage to DNA during aging and after toxicological challenge.Published by Elsevier Ltd.Cardozo-PelaezFernandoFCenter for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA. Fernando.Cardozo@umontana.eduSanchez-ContrerasMonicaMNevinAndrew B CABengP20 RR015583RRNCRR NIH HHSUnited StatesP20 RR017670RRNCRR NIH HHSUnited StatesR01 AG031184AGNIA NIH HHSUnited StatesP20RR017670RRNCRR NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20120626
EnglandNeurochem Int80069590197-0186EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMFree Radic Biol Med. 2005 Mar 15;38(6):737-4515721984Neurotoxicology. 1999 Apr-Jun;20(2-3):415-3210385901Neurology. 2005 Mar 22;64(6):1081-315781836J Neurochem. 2005 May;93(4):953-6215857398J Pineal Res. 2005 Aug;39(1):34-4215978055Gene Expr. 2005;12(4-6):315-2316358418DNA Repair (Amst). 2006 Feb 3;5(2):189-20916290067Genet Mol Res. 2005;4(4):822-3116475130Cell Death Differ. 2006 Apr;13(4):551-6316273081Neurobiol Dis. 2006 Nov;24(2):308-1716959493Front Biosci. 2007;12:1107-2317127365Mitochondrion. 2007 Feb-Apr;7(1-2):58-6217300997J Neurosci Res. 2007 Apr;85(5):919-3417279544J Neurosci. 2008 Sep 3;28(36):9047-5418768699Free Radic Biol Med. 2008 Sep 15;45(6):813-918598755J Cereb Blood Flow Metab. 2011 Feb;31(2):680-9220736962Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Mov Disord. 1999 Nov;14(6):972-8010584672Free Radic Biol Med. 2000 Mar 1;28(5):779-8510754274Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4156-6110725358Nat Neurosci. 2000 Dec;3(12):1301-611100151Brain Res. 2000 Dec 1;885(1):45-5211121528J Neurochem. 2001 Feb;76(4):998-100911181819J Neurochem. 2001 Mar;76(5):1265-7411238711Neurol Sci. 2001 Feb;22(1):83-411487213Carcinogenesis. 2001 Sep;22(9):1459-6311532868Int J Radiat Biol. 2001 Dec;77(12):1195-20511747544Free Radic Res. 2002 Feb;36(2):157-6211999383Free Radic Biol Med. 2002 Jun 1;32(11):1102-1512031895Neuron. 2002 May 16;34(4):521-3312062037Neurology. 2002 Jun 25;58(12):1809-1512084881Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8968-7312084935Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14524-912376616Neurosci Lett. 2003 Jan 16;336(2):105-812499051Clin Chim Acta. 2003 Aug;334(1-2):87-9412867278Parkinsonism Relat Disord. 2003 Aug;9 Suppl 2:S59-6412915069Neuron. 2004 Feb 19;41(4):549-6114980204J Neurosci Methods. 2004 Jun 15;136(1):69-7615126047Arch Biochem Biophys. 1986 May 1;246(2):501-143010861Life Sci. 1988;43(11):913-222901021Lancet. 1989 Jun 3;1(8649):12692566813Biochem Biophys Res Commun. 1989 Sep 29;163(3):1450-52551290Mov Disord. 1991;6(1):2-111848677Biochemistry. 1991 Jun 25;30(25):6283-92059635Ann Neurol. 1992 Dec;32(6):804-121471873Adv Neurol. 1993;60:251-88380519BMJ. 1996 Mar 16;312(7032):702-3; author reply 704-58597746BMJ. 1996 Mar 16;312(7032):703; author reply 704-58597748Neurotoxicol Teratol. 1997 Jan-Feb;19(1):17-259088007Science. 1997 Jun 27;276(5321):2045-79197268J Neurochem. 1997 Sep;69(3):1196-2039282943Nat Genet. 1998 Feb;18(2):106-89462735Acta Neuropathol. 1998 Nov;96(5):445-529829807Trends Neurosci. 1998 Dec;21(12):516-209881849Am J Pathol. 1999 May;154(5):1423-910329595Nucleic Acids Res. 2005;33(4):1230-915731343Agingdrug effectsgeneticspathologyAnimalsCorpus Striatumdrug effectsmetabolismpathologyDNA GlycosylasesdeficiencygeneticsFemaleMPTP PoisoninggeneticspathologyMaleMiceMice, 129 StrainMice, KnockoutNeural Pathwaysdrug effectsmetabolismpathologySubstantia Nigradrug effectsenzymologymetabolism
201201132012051820120618201263060201263060201373160ppublish22743193S0197-0186(12)00210-010.1016/j.neuint.2012.06.013PMC3468700NIHMS389696
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1090-210442412012Jul20Biochemical and biophysical research communicationsBiochem. Biophys. Res. Commun.Acetylation on critical lysine residues of Apurinic/apyrimidinic endonuclease 1 (APE1) in triple negative breast cancers.34-910.1016/j.bbrc.2012.06.039Protein acetylation plays many roles within living cells, modulating metabolism, signaling and cell response to environmental stimuli, as well as having an impact on pathological conditions, such as cancer pathogenesis and progression. The Apurinic/apyrimidinic endonuclease APE1 is a vital protein that exerts many functions in mammalian cells, acting as a pivotal enzyme in the base excision repair (BER) pathway of DNA lesions, as transcriptional modulator and being also involved in RNA metabolism. As an eclectic and abundant protein, APE1 is extensively modulated through post-translational modifications, including acetylation. Many findings have linked APE1 to cancer development and onset of chemo- and radio-resistance. Here, we focus on APE1 acetylation pattern in triple negative breast cancer (TNBC). We describe the validation and characterization of a polyclonal antibody that is specific for the acetylation on lysine 35 of the protein. Finally, we use the new antibody to analyze the APE1 acetylation pattern on a cohort of TNBC specimens, exploiting immunohistochemistry. Our findings reveal a profound deregulation of APE1 acetylation status in TNBC, opening new perspectives for future improvements on treatment and prognosis of this molecular subtype of breast carcinomas.Copyright © 2012 Elsevier Inc. All rights reserved.PolettoMattiaMDepartment of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.Di LoretoCarlaCMarascoDanielaDPolettoElenaEPuglisiFabioFDamanteGiuseppeGTellGianlucaGengJournal ArticleResearch Support, Non-U.S. Gov't20120616
United StatesBiochem Biophys Res Commun03725160006-291XEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseK3Z4F929H6LysineIMAcetylationAmino Acid SequenceBreast NeoplasmsenzymologyDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismFemaleHumansLysinemetabolismMolecular Sequence DataProtein Processing, Post-TranslationalTumor Cells, Cultured
2012060220120609201262160201262160201211760ppublish22713458S0006-291X(12)01127-810.1016/j.bbrc.2012.06.039
226886622014082820151119
1534-468120 Suppl 32013DecAnnals of surgical oncologyAnn. Surg. Oncol.Cytoplasmic Ape1 expression elevated by p53 aberration may predict survival and relapse in resected non-small cell lung cancer.S336-4710.1245/s10434-012-2431-2Subcellular localization of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ape1) has been demonstrated to promote lung tumor malignancy via NF-κB activation. We hypothesized that increased cytoplasmic Ape1 expression might cause NF-κB activation by p53 aberration, and result in poor outcome in non-small cell lung cancer (NSCLC).Herein, knockdown of E6 or p53 and overexpression of E6 were performed in various lung cancer cells to test whether cytoplasmic Ape1 expression could be elevated by p53 aberration. To examine whether cytoplasmic Ape1 could be associated with patients' outcome, 125 lung tumors from patients with NSCLC were collected to determine Ape1 protein and mRNA expression by immunohistochemistry and real-time RT-PCR.Our data showed that cytoplasmic Ape1 decreased in E6-knockdown TL-1 cells and increased in E6-overexpressed TL-4 and p53-knockdown H520 cells; and cell invasion capability was dependent on the presence of cytoplasmic Ape1. Increases in cytoplasmic Ape1 by p53 aberration may be through activation of Ape1 transcription and S-nitrosation of Ape1 protein. Kaplan-Meier and Cox models showed that patients with high cytoplasmic Ape1 had shorter cancer-specific survival (CSS) and relapse-free survival (RFS) periods than did those with low cytoplasmic Ape1.We suggest that cytoplasmic Ape1 expression elevated by p53 aberration may be used to predict poor survival and relapse in patients with NSCLC.WuHeng-HsiungHHInstitute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.ChuYa-ChiungYCWangLeeLTsaiLung-HungLHLeeMing-ChingMCChenChi-YiCYShiehShwn-HueySHChengYa-WenYWLeeHueiHengJournal ArticleResearch Support, Non-U.S. Gov't20120612
United StatesAnn Surg Oncol94208401068-92650Biomarkers, Tumor0RNA, Messenger0RNA, Small Interfering0TP53 protein, human0Tumor Suppressor Protein p53EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAdenocarcinomageneticsmetabolismmortalitypathologyAgedApoptosisBiomarkers, TumorgeneticsmetabolismBlotting, WesternCarcinoma, Non-Small-Cell LunggeneticsmetabolismmortalitypathologyCarcinoma, Squamous CellgeneticsmetabolismmortalitypathologyCell AdhesionCell MovementCell NucleusgeneticsmetabolismCell ProliferationChromatin ImmunoprecipitationCytoplasmmetabolismDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsgeneticsmetabolismFemaleHumansImmunoprecipitationLung NeoplasmsgeneticsmetabolismmortalitypathologyMaleMutationgeneticsNeoplasm Recurrence, LocaldiagnosisgeneticsmetabolismmortalityNeoplasm StagingPrognosisRNA, MessengergeneticsRNA, Small InterferinggeneticsReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionSurvival RateTumor Cells, CulturedTumor Suppressor Protein p53genetics
20120119201261360201261360201482960ppublish2268866210.1245/s10434-012-2431-2
226522742012092520120717
1879-003850512012Aug15GeneGeneThe role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population.121-710.1016/j.gene.2012.05.025The aim of the present study was to investigate the role of some polymorphisms in GSTs (GSTM1, GSTT1 and GSTP1) which are very important protective mechanisms against oxidative stress and in OGG1 gene which is important in DNA repair, against the risk of type 2 diabetes mellitus (T2DM). 127 T2DM and 127 control subjects were included in the study. DNA was extracted from whole blood. Analyses of GSTM1 and GSTT1 gene polymorphisms were performed by allele specific PCR and those of GSTP1 Ile105Val and OGG1 Ser326Cys by PCR-RFLP. Our data showed that GSTM1 null genotype frequency had a 2-6 times statistically significant increase in a patient group (OR=3.841, 95% CI=2.280-6.469, p<0.001) but no significance with GSTT1 null/positive and GSTP1 Ile105Val genotypes was observed. When T2DM patients with OGG1 Ser326Cys polymorphism were compared with patients with a wild genotype, a 2-3 times statistically significant increase has been observed (OR 1.858, 95% CI=1.099-3.141, p=0.021). The combined effect of GSTM1 null and OGG1 variant genotype frequencies has shown to be statistically significant. Similarly, the risk of T2DM was statistically increased with GSTM1 null (OR=3.841, 95% CI=2.28-6.469), GSTT1 null+GSTP1 (H+M) (OR=4.118, 95% CI=1.327-12.778) and GSTM1 null+OGG1 (H+M) (OR=3.322, 95% CI=1.898-5.816) and GSTT1 null+OGG1 (H+M) (OR=2.179, 95% CI=1.083-4.386) as compared to the control group. According to our study results, it has been observed that the combined evaluation of GSTM1-GSTT1-GSTP1 and OGG1 Ser326Cys gene polymorphisms can be used as candidate genes in the etiology of T2DM, especially in the development of T2DM.Copyright © 2012 Elsevier B.V. All rights reserved.GönülNüvitNRefik Saydam National Health Public Agency, Toxicology Department, National Poison Center, Ankara, Turkey. nuvitgonul@gmail.comKadiogluElaEKocabaşNeslihan AygünNAOzkayaMesutMKarakayaAli EsatAEKarahalilBensuBengJournal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov't20120528
NetherlandsGene77067610378-1119EC 2.5.1.-glutathione S-transferase T1EC 2.5.1.18GSTP1 protein, humanEC 2.5.1.18Glutathione S-Transferase piEC 2.5.1.18Glutathione TransferaseEC 2.5.1.18glutathione S-transferase M1EC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAdultAgedCase-Control StudiesDNA GlycosylasesgeneticsDiabetes Mellitus, Type 2epidemiologygeneticsFemaleGenotypeGlutathione S-Transferase pigeneticsGlutathione TransferasegeneticsHumansMaleMiddle AgedPolymorphism, GeneticRisk FactorsTurkeyepidemiology
2011122420120404201205102012626020126260201292660ppublish22652274S0378-1119(12)00600-210.1016/j.gene.2012.05.025
226492782012120720150225
1110-725120122012Journal of biomedicine & biotechnologyJ. Biomed. Biotechnol.New protein vector ApE1 for targeted delivery of anticancer drugs.46975610.1155/2012/469756A new chimeric gene ApE1 encoding the receptor-binding domain of the human alpha-fetoprotein fused to a sequence of 22 glutamic acid residues was constructed. A new bacterial producer strain E. coli SHExT7 ApE1 was selected for ApE1 production in a soluble state. A simplified method was developed to purify ApE1 from bacterial biomass. It was shown that the new vector protein selectively interacts with AFP receptors on the tumor cell surface and can be efficiently accumulated in tumor cells. In addition, ApE1 was shown to be stable in storage and during its chemical modification. An increased number of carboxyl groups in the molecule allows the production of cytotoxic compound conjugates with higher drug-loading capacity and enhanced tumor targeting potential.PozdniakovaN VNVCentre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies (Kurchatov NBIC Centre), National Research Centre Kurchatov Institute, Academician Kurchatov Square, 1, Building 348, Moscow 123182, Russia. natpo2002@mail.ruGorokhovetsN VNVGukasovaN VNVBereznikovaA VAVSeverinE SESengJournal ArticleResearch Support, Non-U.S. Gov't20120509
United StatesJ Biomed Biotechnol1011357401110-72430AFP protein, human0Antineoplastic Agents0Drug Carriers0Receptors, Peptide0Recombinant Fusion Proteins0alpha-Fetoproteins0alpha-fetoprotein receptor, human25513-46-6Polyglutamic AcidI223NX31W9Fluorescein-5-isothiocyanateIMBiochemistry (Mosc). 2000 Aug;65(8):967-7111002192Nature. 1970 Aug 15;227(5259):680-55432063Eur J Biochem. 1982 Jun;124(3):585-87106109Anal Biochem. 1985 Oct;150(1):76-853843705Dokl Biochem Biophys. 2011 Jul-Aug;439:158-6021928134Arch Biochem Biophys. 1959 May;82(1):70-713650640J Drug Target. 2008 May;16(4):321-818446611Bioorg Khim. 2010 Nov-Dec;36(6):760-821317941Anal Biochem. 1987 Apr;162(1):156-92440339Amino Acid SequenceAntineoplastic Agentsadministration & dosagechemistrypharmacokineticsBinding SitesCell Line, TumorCloning, MolecularDrug Carriersadministration & dosagechemistrypharmacokineticsEscherichia coligeneticsFluorescein-5-isothiocyanateHumansMolecular Sequence DataPolyglutamic AcidchemistrygeneticsmetabolismProtein BindingReceptors, PeptidemetabolismRecombinant Fusion Proteinsadministration & dosagechemistrygeneticspharmacokineticsalpha-Fetoproteinschemistrygeneticsmetabolism
20111130201202202012022220126160201261602012121260ppublish2264927810.1155/2012/469756PMC3357585
226094882012100920120806
0027-51077361-22012Aug01Mutation researchMutat. Res.Progress in high-throughput assays of MGMT and APE1 activities in cell extracts.25-3210.1016/j.mrfmmm.2012.05.002DNA repair activity is of interest as a potential biomarker of individual susceptibility to genotoxic agents. In view of the current trend for exploitation of large cohorts in molecular epidemiology projects, there is a pressing need for the development of phenotypic DNA repair assays that are high-throughput, very sensitive, inexpensive and reliable. Towards this goal we have developed and validated two phenotypic assays for the measurement of two DNA repair enzymes in cell extracts: (1) O(6)-methylguanine-DNA-methyltransferase (MGMT), which repairs the O(6)-alkylguanine-type of adducts induced in DNA by alkylating genotoxins; and (2) apurinic/apyrimidinic endonuclease 1 (APE 1), which participates in base excision repair (BER) by causing a rate-limiting DNA strand cleavage 5' to the abasic sites. The MGMT assay makes use of the fact that: (a) the enzyme works by irreversibly transferring the alkyl group from the O(6) position of guanine to a cystein residue in its active site and thereby becomes inactivated and (b) that the free base O(6)-benzylguanine (BG) is a very good substrate for MGMT. In the new assay, cell extracts are incubated with BG tagged with biotin and the resulting MGMT-BG-biotin complex is immobilized on anti-MGMT-coated microtiter plates, followed by quantitation using streptavidin-conjugated alkaline phosphatase and a chemiluminescence-producing substrate. A one-step/one-tube phenotypic assay for APE1 activity has been developed based on the use of a fluorescent molecular beacon (partially self-complementary oligonucleotide with a hairpin-loop structure carrying a fluorophore and a quencher at each end). It also contains a single tetrahydrofuran residue (THF) which is recognized and cleaved by APE1, and the subsequently formed single-stranded oligomer becomes a fluorescence signal emitter. Both assays are highly sensitive, require very small amounts of protein extracts, are relatively inexpensive and can be easily automated. They have been extensively validated and are being used in the context of large-scale molecular epidemiology studies.Copyright © 2012 Elsevier B.V. All rights reserved.GeorgiadisPanagiotisPNational Hellenic Research Foundation, Athens, Greece. panosg@eie.grPolychronakiNektariaNKyrtopoulosSoterios ASAengJournal ArticleResearch Support, Non-U.S. Gov't20120517
NetherlandsMutat Res04007630027-51070Cell Extracts0MutagensEC 2.1.1.63O(6)-Methylguanine-DNA MethyltransferaseEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 6.5.1.-DNA Repair EnzymesIMCell ExtractsDNA DamageDNA RepairDNA Repair EnzymesanalysisDNA-(Apurinic or Apyrimidinic Site) LyaseanalysisEnzyme-Linked Immunosorbent AssaymethodsHumansMolecular EpidemiologytrendsMutagenstoxicityO(6)-Methylguanine-DNA MethyltransferaseanalysisValidation Studies as Topic
2012011720120426201205092012522602012523602012101060ppublish22609488S0027-5107(12)00109-110.1016/j.mrfmmm.2012.05.002
225801512012121120131121
1873-45965322012Jul15Free radical biology & medicineFree Radic. Biol. Med.Human AP endonuclease/redox factor APE1/ref-1 modulates mitochondrial function after oxidative stress by regulating the transcriptional activity of NRF1.237-4810.1016/j.freeradbiomed.2012.04.002Maintenance of mitochondrial functionality largely depends on nuclear transcription because most mitochondrial proteins are encoded by the nuclear genome and transported to the mitochondria. Nuclear respiration factor 1 (NRF1) plays a crucial role in regulating the expression of a broad range of mitochondrial genes in the nucleus in response to cellular oxidative stress. However, little is known about the redox regulatory mechanism of the transcriptional activity of NRF1. In this study, we show that the human apurinic/apyrimidinic endonuclease/redox factor (APE1/Ref-1) is involved in mitochondrial function regulation by modulating the DNA-binding activity of NRF1. Our results show that both APE1 expression level and its redox activity are essential for maintenance of the mitochondrial function after tert-butylhydroperoxide-induced oxidative stress. Upon knocking down or redox mutation of APE1, NRF1 DNA-binding activity was impaired and, consequently, the expression of its downstream genes, including Tfam, Cox6c, and Tomm22, was significantly reduced. NRF1 knockdown blocked the restoration of mitochondrial function by APE1 overexpression, which further suggests APE1 regulates mitochondrial function through an NRF1-dependent pathway. Taken together, our results reveal APE1 as a new coactivator of NRF1, which highlights an additional regulatory role of APE1 in maintenance of mitochondrial functionality.Copyright © 2012 Elsevier Inc. All rights reserved.LiMengxiaMCancer Center and Department of Pathology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China.VascottoCarloCXuShangchengSDaiNanNQingYiYZhongZhaoyangZTellGianlucaGWangDongDengJournal ArticleResearch Support, Non-U.S. Gov't20120511
United StatesFree Radic Biol Med87091590891-58490COX6c protein, human0DNA-Binding Proteins0Mitochondrial Membrane Transport Proteins0Mitochondrial Proteins0NF-E2-Related Factor 10NFE2L1 protein, human0TFAM protein, human0TOMM22 protein, human0Transcription Factors955VYL842Btert-ButylhydroperoxideEC 1.9.3.1Electron Transport Complex IVEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCell NucleusgeneticsmetabolismCell Respirationdrug effectsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismDNA-Binding ProteinsgeneticsmetabolismElectron Transport Complex IVgeneticsmetabolismGene Expressiondrug effectsGene Knockdown TechniquesHeLa CellsHumansMitochondriadrug effectsgeneticsmetabolismMitochondrial Membrane Transport ProteinsgeneticsmetabolismMitochondrial ProteinsgeneticsmetabolismNF-E2-Related Factor 1geneticsmetabolismOxidative StressSignal Transductiondrug effectsTranscription FactorsgeneticsmetabolismTranscription, Geneticdrug effectsTranscriptional Activationdrug effectsTransfectiontert-Butylhydroperoxidepharmacology
2012010420120306201204062012515602012515602012121260ppublish22580151S0891-5849(12)00199-210.1016/j.freeradbiomed.2012.04.002
225647412012102220171116
1090-210442342012Jul13Biochemical and biophysical research communicationsBiochem. Biophys. Res. Commun.The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells.621-610.1016/j.bbrc.2012.04.125Embryonic neural stem cells (NSCs) exhibit self-renewal and multipotency as intrinsic characteristics that are key parameters for proper brain development. When cells are challenged by oxidative stress agents the resulting DNA lesions are repaired by DNA glycosylases through the base excision repair (BER) pathway as a means to maintain the fidelity of the genome, and thus, proper cellular characteristics. The functional roles for DNA glycosylases in NSCs have however remained largely unexplored. Here we demonstrate that RNA knockdown of the DNA glycosylases OGG1 and NEIL3 decreased NSC differentiation ability and resulted in decreased expression of both neuronal and astrocytic genes after mitogen withdrawal, as well as the stem cell marker Musashi-1. Furthermore, while cell survival remained unaffected, NEIL3 deficient cells displayed decreased cell proliferation rates along with an increase in HP1γ immunoreactivity, a sign of premature senescence. Our results suggest that DNA glycosylases play multiple roles in governing essential neural stem cell characteristics.Copyright © 2012 Elsevier Inc. All rights reserved.ReisAmilcarALinnaeus Center in Developmental Biology for Regenerative Medicine, Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm, Sweden.HermansonOlaOengJournal ArticleResearch Support, Non-U.S. Gov't20120430
United StatesBiochem Biophys Res Commun03725160006-291X0Biomarkers0Enzyme Inhibitors0Msi1h protein, rat0Nerve Tissue Proteins0RNA, Small Interfering0RNA-Binding Proteins5614-64-28-hydroxyguanine5Z93L87A1RGuanine614OI1Z5WIValproic AcidEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-OGG1 protein, ratIMAnimalsBiomarkersmetabolismCell NucleusmetabolismCell ProliferationCells, CulturedCellular SenescencegeneticsphysiologyDNA Glycosylasesantagonists & inhibitorsgeneticsphysiologyEnzyme InhibitorspharmacologyGene Knockdown TechniquesGuanineanalogs & derivativesmetabolismNerve Tissue ProteinsmetabolismNeural Stem CellscytologyphysiologyNeurogenesisgeneticsphysiologyRNA, Small InterferinggeneticsRNA-Binding ProteinsmetabolismRatsValproic Acidpharmacology
201204182012042120125960201259602012102360ppublish22564741S0006-291X(12)00807-810.1016/j.bbrc.2012.04.125
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1932-6203742012PloS onePLoS ONEThe association between OGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis of 27 studies.e3597010.1371/journal.pone.0035970Numerous studies have investigated association of OGG1 Ser326Cys polymorphism with lung cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 27 publications encompass 9663 cases and 11348 controls to comprehensively evaluate such associations.We searched publications from MEDLINE and EMBASE which were assessing the associations between OGG1 Ser326Cys polymorphism and lung cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We used genotype based mRNA expression data from HapMap for SNP rs1052133 in normal cell lines among 270 subjects with four different ethnicities.The results showed that individuals carrying the Cys/Cys genotype did not have significantly increased risk for lung cancer (OR = 1.15, 95% CI = 0.98-1.36) when compared with the Ser/Ser genotype; similarly, no significant association was found in recessive, dominant or heterozygous co-dominant model (Ser/Cys vs. Cys/Cys). However, markedly increased risks were found in relatively large sample size (Ser/Ser vs. Cys/Cys: OR = 1.29, 95% CI = 1.13-1.48, and recessive model: OR = 1.19, 95% CI = 1.07-1.32). As to histological types, we found the Cys/Cys was associated with adenocarcinoma risk (Ser/Ser vs. Cys/Cys: OR = 1.32, 95% CI = 1.12-1.56; Ser/Cys vs. Cys/Cys: OR = 1.19, 95% CI = 1.04-1.37, and recessive model OR = 1.23, 95% CI = 1.08-1.40). No significant difference of OGG1 mRNA expression was found among genotypes between different ethnicities.Despite some limitations, this meta-analysis established solid statistical evidence for an association between the OGG1 Cys/Cys genotype and lung cancer risk, particularly for studies with large sample size and adenocarcinoma, but this association warrants additional validation in larger and well designed studies.DuanWei-XunWXDepartment of Cardiothoracic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.HuaRui-XiRXYiWeiWShenLi-JunLJJinZhen-XiaoZXZhaoYu-HongYHYiDing-HuaDHChenWen-ShengWSYuShi-QiangSQengJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov't20120423
United StatesPLoS One1012850811932-62030RNA, MessengerEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMAnticancer Res. 2010 Oct;30(10):4141-521036733Cancer Lett. 2005 Jun 8;223(2):265-7415896461Carcinogenesis. 2009 Jan;30(1):78-8719029194J Hum Genet. 2009 Dec;54(12):739-4519881468Mutat Res. 2005 Dec 11;591(1-2):60-7316081110Cancer Sci. 2006 Aug;97(8):724-816800823Pharmacogenetics. 2004 Feb;14(2):103-915077011J Natl Cancer Inst. 1999 Jul 21;91(14):1194-21010413421Cancer Detect Prev. 2007;31(3):237-4317651912Mutat Res. 2011 May 10;709-710:21-3121376741Cancer Epidemiol Biomarkers Prev. 2008 Jul;17(7):1739-4518628426Control Clin Trials. 1986 Sep;7(3):177-883802833Mutat Res. 2005 Apr 4;582(1-2):53-6015781210Arh Hig Rada Toksikol. 2008 Dec;59(4):241-5019064361Carcinogenesis. 2006 May;27(5):997-100716308313Science. 2007 Feb 9;315(5813):848-5317289997Lung Cancer. 2011 Aug;73(2):138-4621195504Lancet. 2003 Sep 13;362(9387):847-5213678970J Exp Clin Cancer Res. 2009;28:1019161591FASEB J. 2002 Dec;16(14):1895-90212468454Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):409-1211927502Am J Epidemiol. 2009 Sep 15;170(6):695-70219671832Prog Nucleic Acid Res Mol Biol. 2001;68:285-9711554304Bioessays. 2001 Mar;23(3):270-8111223884J Thorac Oncol. 2011 Apr;6(4):813-721623257Science. 2001 Feb 16;291(5507):1284-911181991BMC Bioinformatics. 2010;11:60021167019Arch Med Res. 2011 Apr;42(3):226-3421722819Carcinogenesis. 2006 Mar;27(3):560-716195237J Natl Cancer Inst. 1959 Apr;22(4):719-4813655060Oncogene. 1998 Jun 11;16(23):3083-69662341J Prev Med Public Health. 2006 Mar;39(2):130-416615267Mutat Res. 2008 Mar 1;639(1-2):45-5418155253J Biol Chem. 2001 Jul 13;276(28):25639-4211371576BMJ. 1997 Sep 13;315(7109):629-349310563CA Cancer J Clin. 2011 Mar-Apr;61(2):69-9021296855J Natl Cancer Inst. 2005 Apr 20;97(8):567-7615840879Nature. 2003 Dec 18;426(6968):789-9614685227Carcinogenesis. 2004 Nov;25(11):2177-8115284179Oncogene. 2005 Jun 30;24(28):4496-50815856018Cancer Genet Cytogenet. 2009 Dec;195(2):143-919963114Amino Acid SubstitutionDNA GlycosylasesgeneticsmetabolismDatabases, GeneticGenetic Predisposition to DiseaseGenotypeHapMap ProjectHumansLung NeoplasmsgeneticsOdds RatioPolymorphism, Single NucleotideRNA, MessengermetabolismRisk Factors
2012011720120324201242860201242860201291160ppublish2254001310.1371/journal.pone.0035970PONE-D-12-01517PMC3335067
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1932-6203742012PloS onePLoS ONEThe DNA glycosylases Ogg1 and Nth1 do not contribute to Ig class switching in activated mouse splenic B cells.e3606110.1371/journal.pone.0036061During activation of B cells to undergo class switching, B cell metabolism is increased, and levels of reactive oxygen species (ROS) are increased. ROS can oxidize DNA bases resulting in substrates for the DNA glycosylases Ogg1 and Nth1. Ogg1 and Nth1 excise oxidized bases, and nick the resulting abasic sites, forming single-strand DNA breaks (SSBs) as intermediates during the repair process. In this study, we asked whether splenic B cells from mice deficient in these two enzymes would show altered class switching and decreased DNA breaks in comparison with wild-type mice. As the c-myc gene frequently recombines with the IgH S region in B cells induced to undergo class switching, we also analyzed the effect of deletion of these two glycosylases on DSBs in the c-myc gene. We did not detect a reduction in S region or c-myc DSBs or in class switching in splenic B cells from Ogg1- or Nth1-deficient mice or from mice deficient in both enzymes.UcherAnna JAJDepartment of Microbiology and Physiological Systems, Medical School, University of Massachusetts, Worcester, Massachusetts, United States of America.LinehanErin KEKTeeborGeorge WGWSchraderCarol ECEStavnezerJanetJengAI-R21-088578AINIAID NIH HHSUnited StatesAI-RO1-023283AINIAID NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20120420
United StatesPLoS One1012850811932-62030Immunoglobulin Heavy ChainsEC 3.1.25.1Deoxyribonuclease (Pyrimidine Dimer)EC 3.1.25.1Nth1 protein, mouseEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMProc Natl Acad Sci U S A. 1999 Nov 9;96(23):13300-510557315Mol Cell. 2011 Jan 21;41(2):232-4221255732J Immunol. 2003 Jun 1;170(11):5558-6212759433J Immunol. 2003 Sep 1;171(5):2504-912928399Nat Immunol. 2003 Oct;4(10):1023-812958596Int J Immunopharmacol. 1994 Jul;16(7):533-467928003Cell Immunol. 1999 Feb 25;192(1):41-710066345J Exp Med. 2005 Aug 15;202(4):561-816103411J Immunol. 2007 Jan 1;178(1):103-1017182545J Immunol. 2007 Nov 1;179(9):6064-7117947680DNA Repair (Amst). 2007 Dec 1;6(12):1764-7317681497J Exp Med. 2007 Nov 26;204(12):3017-2618025127Nature. 2008 Feb 14;451(7180):841-518273020Annu Rev Immunol. 2008;26:261-9218370922J Exp Med. 2008 Oct 27;205(11):2465-7218824584Cell. 2008 Dec 12;135(6):1028-3819070574DNA Repair (Amst). 2009 Jul 4;8(7):786-9419346169Mol Cell. 2009 Nov 25;36(4):631-4119941823J Immunol. 2010 Jun 1;184(11):6177-8720483782Nat Immunol. 2011 Jan;12(1):62-921113164Mol Cell Biol. 2002 Sep;22(17):6111-2112167705AnimalsB-LymphocytesenzymologyimmunologyCell ProliferationCells, CulturedDNA Breaks, Double-StrandedDNA GlycosylasesdeficiencygeneticsmetabolismDeoxyribonuclease (Pyrimidine Dimer)deficiencygeneticsGene Knockout TechniquesGenes, mycImmunoglobulin Class SwitchingImmunoglobulin Heavy ChainsgeneticsMiceMice, Inbred C57BLMice, KnockoutReal-Time Polymerase Chain ReactionRecombination, GeneticSpleencytologyTranscription, Genetic
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1096-092912812012JulToxicological sciences : an official journal of the Society of ToxicologyToxicol. Sci.Oxoguanine glycosylase 1 (OGG1) protects cells from DNA double-strand break damage following methylmercury (MeHg) exposure.272-8310.1093/toxsci/kfs138Methylmercury (MeHg) is a potent neurotoxin, teratogen, and probable carcinogen, but the underlying mechanisms of its actions remain unclear. Although MeHg causes several types of DNA damage, the toxicological consequences of this macromolecular damage are unknown. MeHg enhances oxidative stress, which can cause various oxidative DNA lesions that are primarily repaired by oxoguanine glycosylase 1 (OGG1). Herein, we compared the response of wild-type and OGG1 null (Ogg1(-/-)) murine embryonic fibroblasts to environmentally relevant, low micromolar concentrations of MeHg by measuring clonogenic efficiency, cell cycle arrest, DNA double-strand breaks (DSBs), and activation of the DNA damage response pathway.Ogg1(-/-) cells exhibited greater sensitivity to MeHg than wild-type controls, as measured by the clonogenic assay, and showed a greater propensity for MeHg-initiated apoptosis. Both wild-type and Ogg1(-/-) cells underwent cell cycle arrest when exposed to micromolar concentrations of MeHg; however, the extent of DSBs was exacerbated in Ogg1(-/-) cells compared with that in wild-type controls. Pretreatment with the antioxidative enzyme catalase reduced levels of DSBs in both wild-type and Ogg1(-/-) cells but failed to block MeHg-initiated apoptosis at micromolar concentrations. Our findings implicate reactive oxygen species mediated DNA damage in the mechanism of MeHg toxicity; and demonstrate for the first time that impaired DNA repair capacity enhances cellular sensitivity to MeHg. Accordingly, the genotoxic properties of MeHg may contribute to its neurotoxic and teratogenic effects, and an individual's response to oxidative stress and DNA damage may constitute an important determinant of risk.OndovcikStephanie LSLDepartment of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada.TamblynLauraLMcPhersonJohn PeterJPWellsPeter GPGengCanadian Institutes of Health ResearchCanadaJournal ArticleResearch Support, Non-U.S. Gov't20120420
United StatesToxicol Sci98054611096-09290Methylmercury CompoundsEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseIMAnimalsDNA DamageDNA GlycosylasesmetabolismFlow CytometryHumansMethylmercury CompoundstoxicityMiceMice, Knockout
2012424602012424602012111460ppublish22523232kfs13810.1093/toxsci/kfs138
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1097-45479062012JunJournal of neuroscience researchJ. Neurosci. Res.Proteomic study of amyloid beta (25-35) peptide exposure to neuronal cells: Impact on APE1/Ref-1's protein-protein interaction.1230-910.1002/jnr.23018The genotoxic, extracellular accumulation of amyloid β (Aβ) protein and subsequent neuronal cell death are associated with Alzheimer's disease (AD). APE1/Ref-1, the predominant apurinic/apyrimidinic (AP) endonuclease and essential in eukaryotic cells, plays a central role in the base excision repair (BER) pathway for repairing oxidized and alkylated bases and single-strand breaks (SSBs) in DNA. APE1/Ref-1 is also involved in the redox activation of several trans-acting factors (TFs) in various cell types, but little is known about its role in neuronal functions. There is emerging evidence for APE1/Ref-1's role in neuronal cells vulnerable in AD and other neurodegenerative disorders, as reflected in its nuclear accumulation in AD brains. An increase in APE1/Ref-1 has been shown to enhance neuronal survival after oxidative stress. To address whether APE1/Ref-1 level or its association with other proteins is responsible for this protective effect, we used 2-D proteomic analyses and identified cytoskeleton elements (i.e., tropomodulin 3, tropomyosin alpha-3 chain), enzymes involved in energy metabolism (i.e., pyruvate kinase M2, N-acetyl transferase, sulfotransferase 1c), proteins involved in stress response (i.e., leucine-rich and death domain, anti-NGF30), and heterogeneous nuclear ribonucleoprotien-H (hnRNP-H) as being associated with APE1/Ref-1 in Aβ(25-35)-treated rat pheochromocytoma PC12 and human neuroblastoma SH-SY5Y cell lines, two common neuronal precursor lines used in Aβ neurotoxicity studies. Because the levels of some of these proteins are affected in the brains of AD patients, our study suggests a neuroprotective role for APE1/Ref-1 via its association with those proteins and modulating their cellular functions during Aβ-mediated neurotoxicity.Copyright © 2012 Wiley Periodicals, Inc.ManthaAnil KAKDepartment of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas, USA. anilmantha@gmail.comDhimanMonishaMTaglialatelaGiulioGPerez-PoloRegino JRJMitraSankarSengP30 ES006676ESNIEHS NIH HHSUnited StatesR01 CA53791CANCI NIH HHSUnited StatesR01 ES08457ESNIEHS NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20120220
United StatesJ Neurosci Res76001110360-40120Amyloid beta-Peptides0Peptide Fragments0amyloid beta-protein (25-35)EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAmyloid beta-PeptidespharmacologyAnimalsCell LineDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismGene Expression Regulationdrug effectsHumansImmunoprecipitationMass SpectrometryNeuronsdrug effectsPeptide FragmentspharmacologyProteomicsRatsReproducibility of ResultsTransfection
201108112011112820111202201241160201241160201281160ppublish2248872710.1002/jnr.23018
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1464-38042742012JulMutagenesisMutagenesisRepair of oxidative DNA damage is delayed in the Ser326Cys polymorphic variant of the base excision repair protein OGG1.501-1010.1093/mutage/ges012Gene-environment interactions influence an individual's risk of disease development. A common human 8-oxoguanine DNA glycosylase 1 (OGG1) variant, Cys326-hOGG1, has been associated with increased cancer risk. Evidence suggests that this is due to reduced repair ability, particularly under oxidising conditions but the underlying mechanism is poorly understood. Oxidising conditions may arise due to internal cellular processes, such as inflammation or external chemical or radiation exposure. To investigate wild-type and variant OGG1 regulation and activity under oxidising conditions, we generated mOgg1 (-/-) null mouse embryonic fibroblasts cells stably expressing Ser326- and Cys326-hOGG1 and measured activity, gene expression, protein expression and localisation following treatment with the glutathione-depleting compound L-buthionine-S-sulfoximine (BSO). Assessment of OGG1 activity using a 7,8-dihydro-8-oxodeoxyguanine (8-oxo dG) containing molecular beacon demonstrated that the activity of both Ser326- and Cys326-hOGG1 was increased following oxidative treatment but with different kinetics. Peak activity of Ser326-hOGG1 occurred 12 h prior to that of Cys326-hOGG1. In both variants, the increased activity was not associated with any gene expression or protein increase or change in protein localisation. These findings suggest that up-regulation of OGG1 activity in response to BSO-induced oxidative stress is via post-transcriptional regulation and provide further evidence for impaired Cys326-hOGG1 repair ability under conditions of oxidative stress. This may have important implications for increased mutation frequency resulting from increased oxidative stress in individuals homozygous for the Cys326 hOGG1 allele.KershawRachael MRMSchool of Biosciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK.HodgesNikolas JNJengBiotechnology and Biological Sciences Research CouncilUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20120325
EnglandMutagenesis87078120267-83570Antimetabolites0Deoxyadenosines0RNA, Messenger0Reactive Oxygen Species452VLY9402Serine5072-26-4Buthionine Sulfoximine62471-63-02'-deoxy-7,8-dihydro-8-oxoadenosineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 3.2.2.-oxoguanine glycosylase 1, humanGAN16C9B8OGlutathioneK848JZ4886CysteineIMAnimalsAntimetabolitespharmacologyBlotting, WesternButhionine SulfoximinepharmacologyCells, CulturedCysteinechemistrygeneticsDNA DamagegeneticsDNA GlycosylasesgeneticsmetabolismphysiologyDNA RepairgeneticsDeoxyadenosinesmetabolismEmbryo, Mammaliancytologydrug effectsmetabolismFibroblastscytologydrug effectsmetabolismFlow CytometryGene-Environment InteractionGlutathionemetabolismHumansMiceMice, KnockoutMutation RateOxidative StressgeneticsPolymorphism, GeneticgeneticsRNA, MessengergeneticsReactive Oxygen SpeciesmetabolismReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionSerinechemistrygeneticsUp-Regulation
201232860201232860201211260ppublish22451681ges01210.1093/mutage/ges012
224503232012060120120416
1090-210442032012Apr13Biochemical and biophysical research communicationsBiochem. Biophys. Res. Commun.Apurinic/apyrimidinic endonuclease1/redox factor-1 (Ape1/Ref-1) is essential for IL-21-induced signal transduction through ERK1/2 pathway.628-3410.1016/j.bbrc.2012.03.051IL-21 is a pleiotropic cytokine that regulates T-cell and B-cell differentiation, NK-cell activation, and dendritic cell functions. IL-21 activates the JAK-STAT, ERK, and PI3K pathways. We report here that Ape1/Ref-1 has an essential role in IL-21-induced cell growth signal transduction. Overexpression of Ape1/Ref-1 enhances IL-21-induced cell proliferation, but it is suppressed by overexpressing an N-terminal deletion mutant of Ape1/Ref-1 that lacks the redox domain. Furthermore, knockdown of the Ape1/Ref-1 mRNA dramatically compromises IL-21-induced ERK1/2 activation and cell proliferation with increasing cell death. These impaired activities are recovered by the re-expression of Ape1/Ref-1 in the knockdown cells. Our findings are the first demonstration that Ape1/Ref-1 is an indispensable molecule for the IL-21-mediated signal transduction through ERK1/2 activation.Copyright © 2012 Elsevier Inc. All rights reserved.JulianaFarha MFMDepartment of Immunology, Yamagata University Faculty of Medicine, Yamagata, Japan.NaraHidetoshiHOnodaTadashiTRahmanMizanurMArakiAkemiAJinLianjinLFujiiHodakaHTanakaNobuyukiNHoshinoTomoakiTAsaoHironobuHengJournal ArticleResearch Support, Non-U.S. Gov't20120317
United StatesBiochem Biophys Res Commun03725160006-291X0Interleukins0interleukin-21EC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMAnimalsCell LineCell ProliferationCell SurvivalgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsmetabolismGene Knockdown TechniquesHumansInterleukinsbiosynthesisgeneticsMAP Kinase Signaling SystemgeneticsMiceSignal Transductiongenetics
201203092012031020123286020123286020126260ppublish22450323S0006-291X(12)00498-610.1016/j.bbrc.2012.03.051
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1473-55983052012MayJournal of hypertensionJ. Hypertens.Regulation of mouse-renin gene by apurinic/apyrimidinic-endonuclease 1 (APE1/Ref-1) via recruitment of histone deacetylase 1 corepressor complex.917-2510.1097/HJH.0b013e3283525124Apurinic/apyrimidinic-endonuclease 1 (APE1) heterozygous mice have chronically elevated blood pressure. Renin of the renin-angiotensin (ANG) system for blood pressure maintenance regulates production of ANG II, a vasoactive hormone. Renin expression and secretion from kidney juxtaglomerular cells are regulated by intracellular calcium. Our objective in this study is to investigate APE1's regulatory role in renin expression.Effect of APE1 on calcium-mediated modulation of renin expression was examined by real-time reverse transcriptase-PCR, Western analysis and renin promoter-dependent luciferase activity in APE1-knockdown, APE1-overexpressing or control mouse kidney As4.1 cells. Furthermore, coimmunoprecipitation and chromatin immunoprecipitation assays were utilized to examine the association of APE1 with histone deacetylase (HDAC)1 corepressor complex and their recruitment to renin enhancer. Finally, kidney renin mRNA level and plasma-renin activity were measured in wild-type and APE1-heterozygous mice.Here we show that APE1 is involved in calcium-mediated repression of renin gene. Our results further indicate that APE1 is a component of HDAC1 corepressor complex bound to renin-enhancer region. Increase in intracellular calcium ion concentration enhances the association of APE1 with HDAC1 corepressor complex and their recruitment to the enhancer region. Furthermore, APE1's N-terminal region is critical for formation and recruitment of the enhancer-bound corepressor complex. Increased renin expression in kidneys and higher plasma-renin activity in APE1 heterozygous mice further supports APE1's corepressor role in vivo.This study uncovers APE1's function as a novel negative regulator of renin expression, and thereby in blood pressure maintenance.SenguptaShiladityaSDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-1079, USA.ChattopadhyayRanajoyRManthaAnil KAKMitraSankarSBhakatKishor KKKengR01 CA148941CANCI NIH HHSUnited StatesR01 CA53791CANCI NIH HHSUnited StatesR01 ES008457ESNIEHS NIH HHSUnited StatesR01 CA053791CANCI NIH HHSUnited StatesR01 ESO8457PHS HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't
EnglandJ Hypertens83068820263-63520Chromatin0Co-Repressor Proteins0RNA, Small InterferingEC 1.13.12.-LuciferasesEC 3.4.23.15ReninEC 3.5.1.98Histone Deacetylase 1EC 4.2.99.18Apex1 protein, mouseEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMHypertension. 2009 Jun;53(6):1070-619433777J Biol Chem. 2007 Oct 12;282(41):29821-3017690094Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Am J Physiol Renal Physiol. 2010 Jan;298(1):F1-F1119640903Mol Endocrinol. 2010 Feb;24(2):391-40120032196Nucleic Acids Res. 2010 Jan;38(3):832-4519934257Nature. 2010 Nov 4;468(7320):46-721048758Oncogene. 2011 Jan 27;30(4):482-9320856196Hypertension. 2011 Mar;57(3):460-821282557Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Biochemistry. 1996 Nov 26;35(47):14679-838942627Cell. 1997 May 2;89(3):349-569150134Pflugers Arch. 1997 Jun;434(2):166-729136670Mol Cells. 1997 Jun 30;7(3):305-129264015Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-69560228J Biol Chem. 1998 Jun 5;273(23):14435-419603956Mutat Res. 1998 Oct 21;409(1):17-299806499Hypertension. 2005 Jan;45(1):3-815545507Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Physiol Rev. 2001 Jan;81(1):239-29711152759Cancer Res. 2001 Jul 15;61(14):5552-711454706EMBO J. 2001 Nov 15;20(22):6530-911707423J Biol Chem. 2001 Dec 7;276(49):45530-811564732J Cell Sci. 2002 Feb 15;115(Pt 4):689-9811865025Free Radic Biol Med. 2002 Jul 1;33(1):15-2812086678J Clin Invest. 2002 Jul;110(2):155-612122105Pflugers Arch. 2002 Jul;444(4):499-50512136269Am J Physiol Heart Circ Physiol. 2002 Dec;283(6):H2458-6512388321J Hypertens. 2003 Feb;21(2):327-3512569263Endocrinology. 2003 Jun;144(6):2179-8312746271Circ Res. 2003 May 16;92(9):1033-4012690040EMBO J. 2003 Dec 1;22(23):6299-30914633989Mol Cell Biol. 2004 Jan;24(1):306-1914673164Methods Enzymol. 2003;371:292-30014712709Nucleic Acids Res. 2004;32(10):3033-915175427Circ Res. 2004 Oct 29;95(9):902-1015472121Circ Res. 2004 Oct 29;95(9):849-5115514165Am J Physiol. 1977 Apr;232(4):F377-82851195J Physiol. 1977 Dec;273(3):745-64415132Kidney Int. 1979 Apr;15(4):427-44229303J Physiol. 1981 Jan;310:285-927014835Biochem Biophys Res Commun. 1984 Oct 30;124(2):359-666093795Am J Physiol. 1986 Apr;250(4 Pt 1):C563-713008566Mol Cell Endocrinol. 1986 Sep;47(1-2):1-122875004Physiol Rev. 1990 Oct;70(4):1067-1162217555J Biol Chem. 1990 Nov 15;265(32):19916-222174057Circulation. 1993 Jun;87(6):1816-288389259J Biol Chem. 1994 Nov 11;269(45):27855-627961715J Immunol. 1995 Jul 1;155(1):285-967602106Kidney Int. 1995 May;47(5):1266-737637256Physiol Genomics. 2008 Nov 12;35(3):243-5318780761Mol Cell Biol. 2008 Dec;28(23):7066-8018809583Mol Cell Biol. 2009 Apr;29(7):1834-5419188445J Biol Chem. 2005 Jul 1;280(26):24356-6215857826DNA Repair (Amst). 2005 Dec 8;4(12):1442-916199212Hypertension. 2005 Dec;46(6):1340-616286572Hypertension. 2006 Jul;48(1):14-2016754793Circ Res. 2006 Nov 24;99(11):1197-20617068292Endocrinology. 2007 Mar;148(3):1424-3017158202Circulation. 2007 May 29;115(21):2761-8817502569J Biol Chem. 2007 Sep 28;282(39):28474-8417686777Hypertension. 2009 Dec;54(6):1240-719822797AnimalsChromatinmetabolismCo-Repressor ProteinsmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismGene Expression RegulationHeterozygoteHistone Deacetylase 1metabolismHypertensiontherapyImmunoprecipitationKidneycytologyLuciferasesmetabolismMaleMiceMice, Inbred C57BLMice, TransgenicModels, BiologicalRNA, Small InterferingmetabolismReal-Time Polymerase Chain ReactionmethodsReninbiosynthesismetabolismReverse Transcriptase Polymerase Chain Reactionmethods
201232460201232460201281460ppublish2244134810.1097/HJH.0b013e3283525124PMC4108083NIHMS601365
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1932-6203722012PloS onePLoS ONEInvestigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: a molecular dynamics approach.e3167710.1371/journal.pone.0031677Elucidating the molecular dynamic behavior of Protein-DNA complex upon mutation is crucial in current genomics. Molecular dynamics approach reveals the changes on incorporation of variants that dictate the structure and function of Protein-DNA complexes. Deleterious mutations in APE1 protein modify the physicochemical property of amino acids that affect the protein stability and dynamic behavior. Further, these mutations disrupt the binding sites and prohibit the protein to form complexes with its interacting DNA.In this study, we developed a rapid and cost-effective method to analyze variants in APE1 gene that are associated with disease susceptibility and evaluated their impacts on APE1-DNA complex dynamic behavior. Initially, two different in silico approaches were used to identify deleterious variants in APE1 gene. Deleterious scores that overlap in these approaches were taken in concern and based on it, two nsSNPs with IDs rs61730854 (I64T) and rs1803120 (P311S) were taken further for structural analysis.Different parameters such as RMSD, RMSF, salt bridge, H-bonds and SASA applied in Molecular dynamic study reveals that predicted deleterious variants I64T and P311S alters the structure as well as affect the stability of APE1-DNA interacting functions. This study addresses such new methods for validating functional polymorphisms of human APE1 which is critically involved in causing deficit in repair capacity, which in turn leads to genetic instability and carcinogenesis.DossC George PriyaCGCentre for Nanobiotechnology, Medical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu, India. georgepriyadoss@vit.ac.inNagasundaramNNengJournal Article20120227
United StatesPLoS One1012850811932-62039007-49-2DNAEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Mol Biol. 1999 Nov 12;293(5):1241-5510547298J Mol Biol. 1983 Aug 25;168(4):867-856887253Biophys J. 2002 Sep;83(3):1595-61212202384Carcinogenesis. 2009 Jan;30(1):78-8719029194Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1513-3012496039Proteins. 2005 Sep 1;60(4):732-916021620Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1355-6315272157Structure. 1994 Aug 15;2(8):713-87994571Genome Res. 1998 Dec;8(12):1229-319872978Prog Biophys Mol Biol. 1984;44(2):97-1796385134BMC Bioinformatics. 2007 Aug 20;8:30117708757PLoS Comput Biol. 2008 Apr 25;4(4):e100006618437203Nucleic Acids Res. 2002 Sep 1;30(17):3894-90012202775Annu Rev Biophys Biomol Struct. 1993;22:381-4158347995Mutat Res. 2008 Dec 15;648(1-2):65-7218977234Biochemistry. 2011 Jan 18;50(2):266-7521121696Nucleic Acids Res. 1996 Jan 1;24(1):21-58594581J Mol Biol. 1997 Sep 19;272(2):276-909299354J Mol Biol. 2006 Mar 10;356(5):1263-7416412461Annu Rev Biochem. 1988;57:519-503052282DNA Repair (Amst). 2007 Apr 1;6(4):544-5917112792Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-99207062Biochemistry. 1992 Jan 28;31(3):725-321731929J Comput Chem. 2007 Sep;28(12):2075-8417405124Nucleic Acids Res. 2001 Jan 1;29(1):308-1111125122Mol Carcinog. 2005 Mar;42(3):127-4115584022Nucleic Acids Res. 2006 Jan 25;34(2):635-4616436800J Biomol Struct Dyn. 2000;17 Suppl 1:79-8522607409Proteins. 1991;11(4):271-801758882Hum Mutat. 2001 Aug;18(2):120-3111462236Hum Mutat. 2010 Sep;31(9):1043-920556796Nature. 2000 Jan 27;403(6768):451-610667800Biochemistry. 2010 May 11;49(18):3786-9620377204Annu Rev Biophys Biomol Struct. 1998;27:105-319646864Protein Eng. 1999 Jul;12(7):549-5510436080Infect Immun. 2008 May;76(5):2227-3418332206Int J Pept Protein Res. 1995 Mar;45(3):225-407775015BMC Bioinformatics. 2006;7:16616551372Nucleic Acids Res. 2007 Jan;35(Database issue):D247-5217130144Hum Mutat. 2001 Apr;17(4):263-7011295823Genomics. 2004 Jun;83(6):970-915177551Nucleic Acids Res. 2009 Feb;37(3):793-80319074953Genome Res. 2001 May;11(5):863-7411337480J Mol Biol. 1973 Sep 15;79(2):351-714760134Mutat Res. 2011 Jun 17;722(2):140-620633698Nucleic Acids Res. 2009 Jan;37(Database issue):D793-618842627Electrophoresis. 1997 Dec;18(15):2714-239504803Hum Mol Genet. 2001 Mar 15;10(6):591-711230178Nat Protoc. 2009;4(7):1073-8119561590Nucleic Acids Res. 2005 Jun 03;33(10):3193-915937195Nucleic Acids Res. 2006 Jan 1;34(Database issue):D302-516381872Nucleic Acids Res. 2004 Jan 1;32(Database issue):D520-214681472Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W635-4116845089Nucleic Acids Res. 2003 Jul 1;31(13):3812-412824425Hum Mutat. 2003 Jun;21(6):577-8112754702Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W306-1015980478Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W621-516845085Prog Biophys Mol Biol. 1992;58(3):203-241509093Bioinformatics. 2006 Sep 1;22(17):2183-516809394J Chem Theory Comput. 2008 Mar;4(3):435-4726620784Nucleic Acids Res. 2007 Jul;35(Web Server issue):W384-9217537826DNAgeneticsDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyasechemistrygeneticsGene DeletionGenetic VariationGenomicsHumansHydrogen BondingModels, MolecularMolecular ConformationMolecular Dynamics SimulationMutationPolymorphism, Single NucleotideProtein Conformation
20111120201201112012336020123360201282860ppublish2238405510.1371/journal.pone.0031677PONE-D-11-23191PMC3288039
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1549-471311952012MayOphthalmologyOphthalmologyGenetic polymorphisms in DNA repair genes OGG1, APE1, XRCC1, and XPD and the risk of age-related cataract.900-610.1016/j.ophtha.2011.11.004To analyze the association of the polymorphisms in 8-oxoguanine glycosylase-1 (OGG1), X-ray repair cross-complementing-1 (XRCC1), and AP endonuclease-1 (APE1) genes in the base excision repair pathway and xeroderma pigmentosum complementation group D (XPD) in the nucleotide excision repair pathway with the risk of cataract in a Chinese population.Case-control study.Subjects with cataract (n = 415) or no cataract (n = 386) in the Age Related Eye Disease Ancillary Study.The study included 415 cataract patients and 386 controls. Genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism method. Differences in the frequencies were estimated by the chi-square test, and risk was estimated by using unconditional logistic regression after adjusting for age and gender.Association of single nucleotide polymorphisms in OGG1-Ser326Cys with the development of age-related cataract.The OGG1 Cys/Cys genotype frequency was significantly higher in cataract patients (P = 0.014; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.171-3.624). The OGG1 Ser/Ser genotype (P = 0.003; OR, 0.647; 95% CI, 0.487-0.860) seems to have a protective role against cataract, and the Cys allele (P<0.001; OR, 1.517; 95% CI, 1.204-1.911) seems to have a deleterious role in the development of cataract. The genotype frequency of the Ser/Ser of OGG1-Ser326Cys was significantly different in the cortical and mixed-type cataract group (P = 0.014; OR, 0.591; 95% CI, 0.391-0.893; and P = 0.035; OR, 0.639; 95% CI, 0.425-0.960; respectively), and the Cys/Cys genotype of OGG1-Ser326Cys was significantly different in the mixed-type cataract group (P = 0.012; OR, 2.610; 95% CI, 1.284-5.306) compared with that of healthy controls. In XRCC1-Arg399Gln, APE1-Asp148Glu, and XPD-Lys751Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls.Results suggest that the Cys/Cys genotype of the OGG1-Ser326Cys polymorphism may be associated with increased risk of age-related cataract. However, in XRCC1-Arg399Gln, APE1-Asp148Glu, and XPD-Lys751Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls.Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.ZhangYiYHarbin Medical University, Harbin, China.ZhangLanLSongZhenZSunDong LinDLLiuHan RuoHRFuSong BinSBLiuDong RuiDRLiuPingPengJournal ArticleResearch Support, Non-U.S. Gov't20120204
United StatesOphthalmology78024430161-64200Codon0DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseEC 5.99.-ERCC2 protein, humanIMAgedAgingAsian Continental Ancestry GroupgeneticsCase-Control StudiesCataractgeneticsCodongeneticsDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-(Apurinic or Apyrimidinic Site) LyasegeneticsDNA-Binding ProteinsgeneticsFemaleGenotypeHumansMalePolymerase Chain ReactionPolymorphism, Restriction Fragment LengthPolymorphism, Single NucleotideRisk FactorsX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
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1530-68602652012MayFASEB journal : official publication of the Federation of American Societies for Experimental BiologyFASEB J.Nutrient deprivation regulates DNA damage repair in cardiomyocytes via loss of the base-excision repair enzyme OGG1.2117-2410.1096/fj.11-197525Oxidative stress contributes to the pathogenesis of many diseases, including heart failure, but the role and regulation of oxidative DNA damage in many cases have not been studied. Here, we set out to examine how oxidative DNA damage is regulated in cardiomyocytes. Compared to normal healthy controls, human hearts in end-stage cardiomyopathy (EsCM) showed a high degree of DNA damage by histological evidence of damage markers, including 8-oxoG and γH2AX (8-oxoG: 4.7±0.88 vs. 99.9±0.11%; γH2AX: 2.1±0.33 vs. 85.0±13.8%; P<0.01) This raised the possibility that defective DNA repair may be partly responsible. Indeed, nutrient deprivation led to impaired base-excision repair (BER) in cardiomyocytes in vitro, accompanied by loss of the BER enzyme OGG1, while BER activity was rescued by recombinant OGG1 (control vs. nutrient deprived vs. nutrient deprived+OGG1; 100±2.96 vs. 68.2±7.53 vs. 94.0±0.72%; ANOVA, P<0.01). Hearts from humans with EsCM and two murine models of myocardial stress also showed a loss of OGG1 protein. OGG1 loss was inhibited by the autophagy inhibitor bafilomycin and in autophagy-deficient Atg5(-/-) mouse embryonic fibroblasts. However, pharmacological activation of autophagy, itself, did not induce OGG1 loss, suggesting that autophagy is necessary but not sufficient for OGG1 turnover, and OGG1 loss requires concurrent nutrient deprivation. Finally, we found that the role of autophagy in nutrient starvation is complex, since it balanced the positive effects of ROS inhibition against the negative effect of OGG1 loss. Therefore, we have identified a central role for OGG1 in regulating DNA repair in cardiomyopathy. The manipulation of OGG1 may be used in future studies to examine the direct contribution of oxidative DNA damage to the progression of heart failure.SiggensLeeLDivision of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Centre of Clinical Investigation Building, Level 6, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.FiggNicholaNBennettMartinMFooRogerRengRG/08/009/25841British Heart FoundationUnited KingdomBritish Heart FoundationUnited KingdomG0800784Medical Research CouncilUnited Kingdom086797Wellcome TrustUnited KingdomG1000847Medical Research CouncilUnited KingdomWellcome TrustUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20120201
United StatesFASEB J88044840892-66380DNA PrimersEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMNature. 2007 Jun 21;447(7147):941-5017581577Annu Rev Nutr. 2007;27:19-4017311494PLoS One. 2010;5(1):e856420084101Circ Res. 2007 Mar 30;100(6):914-2217332429FASEB J. 2003 Jul;17(10):1195-21412832285Circulation. 2005 Feb 8;111(5):591-715668342Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2979-849501201DNA Repair (Amst). 2010 Feb 4;9(2):144-5220042377N Engl J Med. 2007 Mar 15;356(11):1140-5117360992Nature. 2007 Mar 22;446(7134):444-817334357Circ Res. 1999 Sep 3;85(5):403-1410473670J Biol Chem. 2010 Jan 1;285(1):667-7419850931Mol Cancer Res. 2010 Jan;8(1):67-7920068071J Clin Invest. 2007 Jul;117(7):1782-9317607355Mutat Res. 2007 May 1;618(1-2):65-8017291544Annu Rev Physiol. 2001;63:391-42611181961Biol Chem. 2002 Mar-Apr;383(3-4):467-7512033436J Biol Chem. 2007 Feb 23;282(8):5529-3517142834Annu Rev Physiol. 2010;72:19-4420148665Nat Med. 2007 May;13(5):619-2417450150Cardiovasc Res. 2004 Nov 1;64(2):279-8815485687Autophagy. 2009 Oct;5(7):1034-619587530Cell. 2005 Sep 23;122(6):927-3916179260EMBO J. 2008 Jan 23;27(2):421-3218188152Cell. 2011 Apr 1;145(1):54-6621458667Annu Rev Physiol. 2010;72:45-5920148666J Clin Invest. 2005 Mar;115(3):500-815765131J Cell Physiol. 2006 Oct;209(1):1-716826603Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18877-8219020090Heart Fail Rev. 2010 Jul;15(4):331-4119363700Cardiovasc Res. 2001 Aug 1;51(2):304-1211470470Genome Med. 2010 Jun 14;2(6):3720546595Circ Res. 2001 Aug 3;89(3):198-20011485969J Clin Invest. 2003 May;111(10):1497-50412750399DNA Repair (Amst). 2008 Apr 2;7(4):648-5418294929Mol Biol Cell. 2004 Mar;15(3):1101-1114699058Nature. 2009 Oct 22;461(7267):1071-819847258Antioxid Redox Signal. 2007 Sep;9(9):1303-717627470AnimalsBase SequenceDNA DamageDNA GlycosylasesmetabolismDNA PrimersDNA RepairHumansImmunohistochemistryMiceMyocardiumenzymologymetabolismEMS52834
2012246020122460201263060ppublish22302830fj.11-19752510.1096/fj.11-197525PMC3630495EMS52834
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1568-78561132012Mar01DNA repairDNA Repair (Amst.)Lack of the DNA glycosylases MYH and OGG1 in the cancer prone double mutant mouse does not increase mitochondrial DNA mutagenesis.278-8510.1016/j.dnarep.2011.12.001Reactive oxygen species (ROS) are formed as natural byproducts during aerobic metabolism and readily induce premutagenic base lesions in the DNA. The 8-oxoguanine DNA glycosylase (OGG1) and MutY homolog 1 (MYH) synergistically prevent mutagenesis and cancer formation in mice. Their localization in the mitochondria as well as in the nucleus suggests that mutations in mitochondrial DNA (mtDNA) contribute to the carcinogenesis in the myh⁻/⁻/ogg1⁻/⁻ double knockout mouse. In order to test this hypothesis, we analyzed mtDNA mutagenesis and mitochondrial function in young (1month) and adult (6months) wt and myh⁻/⁻/ogg1⁻/⁻ mice. To our surprise, the absence of OGG1 and MYH had no impact on mtDNA mutation rates in these mice, even at the onset of cancer. This indicates that mtDNA mutagenesis is not responsible for the carcinogenesis of myh⁻/⁻/ogg1⁻/⁻ mice. In line with these results, mitochondrial function was unaffected in the cancerous tissues liver and lung, whereas a significant reduction in respiration capacity was observed in brain mitochondria from the adult myh⁻/⁻/ogg1⁻/⁻ mouse. The reduced respiration capacity correlated with a specific reduction (-25%) in complex I biochemical activity in brain mitochondria. Our results demonstrate that mtDNA mutations are not associated with cancer development in myh⁻/⁻/ogg1⁻/⁻ mice, and that impairment of mitochondrial function in brain could be linked to nuclear DNA mutations in this strain. OGG1 and MYH appear to be dispensable for antimutator function in mitochondria.Copyright © 2011 Elsevier B.V. All rights reserved.HalsneRuthRDepartment of Medical Biochemistry, University of Oslo and Oslo University Hospital, Norway.EsbensenYingYWangWeiWSchefflerKatjaKSuganthanRajikalaRBjøråsMagnarMEideLarsLengJournal ArticleResearch Support, Non-U.S. Gov't20111230
NetherlandsDNA Repair (Amst)1011391381568-78560DNA, MitochondrialEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-Ogg1 protein, mouseEC 3.2.2.-mutY adenine glycosylaseIMAnimalsCell RespirationgeneticsDNA DamagegeneticsDNA GlycosylasesdeficiencymetabolismDNA, MitochondrialgeneticsMiceMice, Inbred C57BLMice, Mutant StrainsMutagenesisgeneticsMutationgeneticsMutation RateNeoplasmsenzymologygeneticsOrgan Specificitygenetics
2011090220111104201112052012136020121360201291160ppublish22209780S1568-7864(11)00347-810.1016/j.dnarep.2011.12.001
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2476-762X13122012Asian Pacific journal of cancer prevention : APJCPAsian Pac. J. Cancer Prev.DNA repair gene polymorphisms at XRCC1, XRCC3, XPD, and OGG1 Loci in the hyderabad population of India.6469-74DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inherited SNPs of DNA repair genes may contribute to variation in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. India harbors enormous genetic and cultural diversity.In the present study we aimed to determine the genotypes and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 186 healthy individuals residing in the Hyderabad region of India and to compare them with HapMap and other populations.The genotype and allele frequency distribution at the four DNA repair gene loci among Hyderabad population of India revealed a characteristic pattern. Comparison of these gene polymorphisms with other populations revealed a distinctiveness of Hyderabad population from the Deccan region of India. To the best of our knowledge, this is the first report of such DNA repair gene polymorphisms in the Deccan Indian population.ParineNarasimha ReddyNRGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. reddyparine@gmail.comPathanAkbar Ali KhanAABobbaralaVaraprasadVAbduljaleelZainularifeenZKhanWajahatullahWAlanaziMohammedMengJournal ArticleResearch Support, Non-U.S. Gov't
ThailandAsian Pac J Cancer Prev1011306251513-73680DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10X-ray repair cross complementing protein 30XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanIMAdultAgedAsian Continental Ancestry GroupgeneticsDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-Binding ProteinsgeneticsGene FrequencygeneticsGenotypeHumansIndiaMiddle AgedPolymorphism, Single NucleotidegeneticsX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
20133860201211002014101060ppublish23464476
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1432-07388662012JunArchives of toxicologyArch. Toxicol.Elevated risk of hypertension induced by arsenic exposure in Taiwanese rural residents: possible effects of manganese superoxide dismutase (MnSOD) and 8-oxoguanine DNA glycosylase (OGG1) genes.869-7810.1007/s00204-011-0797-8Heavy metals, including arsenic and lead, may lead to cellular oxidative damage that is linked to hypertension. Manganese superoxide dismutase (MnSOD) is a scavenger of reactive oxygen species, and 8-oxoguanine DNA glycosylase (OGG1) is the major glycosylase that repairs DNA lesions. Interestingly, whether there is an elevated risk of hypertension with arsenic or lead exposure in individuals with genetic variations in MnSOD or OGG1 has not yet been investigated. Questionnaires were administered to 240 Taiwanese rural residents. Blood pressure and biochemical indicators were assessed in each subject. Urinary levels of arsenic and lead were measured with atomic absorption spectrometry; and MnSOD and OGG1 genotypes were identified via polymerase chain reaction. There was a dose-response relationship between urinary arsenic levels and risk of hypertension (P = 0.021, test for trend). However, there was no association between urinary lead levels and hypertension risk. Individuals with high urinary arsenic levels and the MnSOD Val-Ala/Ala-Ala genotypes had a greater risk of hypertension than those with low urinary arsenic levels and the MnSOD Val-Val genotype (odds ratio [OR] = 4.2, 95% confidence interval [CI] = 1.7-10.3). Subjects with a high urinary arsenic level and the OGG1 Cys-Cys genotype also had a greater risk of hypertension than those with a low urinary arsenic level and the OGG1 Ser-Ser/Ser-Cys genotypes (OR = 3.4, 95% CI = 1.1-10.7). Thus, both MnSOD and OGG1 genotypes may be prone to an increased risk of hypertension associated with arsenic exposure.ChenShiuan-ChihSCDepartment of Family and Community Medicine, Chung Shan Medical University Hospital, No. 110 Chien-Kuo N Rd, Sec. 1, Taichung 40242, Taiwan.ChenChun-ChiehCCKuoChung-YihCYHuangChun-HuangCHLinChin-HsiuCHLuZi-YunZYChenYi-YuYYLeeHong-ShenHSWongRuey-HongRHengComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't20111223
GermanyArch Toxicol04176150340-57612P299V784PLead5Z93L87A1RGuanine82014-86-68-oxyguanineEC 1.15.1.1Superoxide DismutaseEC 3.2.2.-DNA GlycosylasesN712M78A8GArsenicIMAdultAgedArsenictoxicityurineCross-Sectional StudiesDNA GlycosylasesgeneticsDose-Response Relationship, DrugFemaleGenetic Predisposition to DiseaseepidemiologyGenotypeGuanineanalogs & derivativesmetabolismHumansHypertensionchemically inducedepidemiologygeneticsurineLeadtoxicityurineMaleMiddle AgedOccupational Exposureadverse effectsstatistics & numerical dataOxidative StressgeneticsPolymorphism, GeneticRisk FactorsRural Populationstatistics & numerical dataSuperoxide DismutasegeneticsTaiwanepidemiology
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1874-4702512012JanCurrent molecular pharmacologyCurr Mol PharmacolAPE1/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1.36-53The heterogeneity of most cancers diminishes the treatment effectiveness of many cancer-killing regimens. Thus, treatments that hold the most promise are ones that block multiple signaling pathways essential to cancer survival. One of the most promising proteins in that regard is APE1, whose reduction-oxidation activity influences multiple cancer survival mechanisms, including growth, proliferation, metastasis, angiogenesis, and stress responses. With the continued research using APE1 redox specific inhibitors alone or coupled with developing APE1 DNA repair inhibitors it will now be possible to further delineate the role of APE1 redox, repair and protein-protein interactions. Previously, use of siRNA or over expression approaches, while valuable, do not give a clear picture of the two major functions of APE1 since both techniques severely alter the cellular milieu. Additionally, use of the redox-specific APE1 inhibitor, APX3330, now makes it possible to study how inhibition of APE1's redox signaling can affect multiple tumor pathways and can potentiate the effectiveness of existing cancer regimens. Because APE1 is an upstream effector of VEGF, as well as other molecules that relate to angiogenesis and the tumor microenvironment, it is also being studied as a possible treatment for agerelated macular degeneration and diabetic retinopathy. This paper reviews all of APE1's functions, while heavily focusing on its redox activities. It also discusses APE1's altered expression in many cancers and the therapeutic potential of selective inhibition of redox regulation, which is the subject of intense preclinical studies.KelleyMark RMRDepartment of Pediatrics (Section of Hematology/Oncology), Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. mkelley@iupui.eduGeorgiadisMillie MMMFishelMelissa LMLengCA122298CANCI NIH HHSUnited StatesR21 CA122298CANCI NIH HHSUnited StatesR01 CA114571CANCI NIH HHSUnited StatesR01 CA121168-05CANCI NIH HHSUnited StatesR01 CA121168-02S1CANCI NIH HHSUnited StatesR41EY019784EYNEI NIH HHSUnited StatesCA106298CANCI NIH HHSUnited StatesCA114571CANCI NIH HHSUnited StatesCA121168CANCI NIH HHSUnited StatesCA121168-02S1CANCI NIH HHSUnited StatesR41 EY019784EYNEI NIH HHSUnited StatesR01 CA106298-05CANCI NIH HHSUnited StatesR01 CA114571-05CANCI NIH HHSUnited StatesR21 CA122298-02CANCI NIH HHSUnited StatesR41 EY019784-01EYNEI NIH HHSUnited StatesR01 CA121168CANCI NIH HHSUnited StatesR01 CA106298CANCI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tReview
United Arab EmiratesCurr Mol Pharmacol1014679971874-46720Antineoplastic Agents0Enzyme Inhibitors0Vascular Endothelial Growth Factor AEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMJ Biol Chem. 2000 Feb 18;275(7):4618-2710671489Clin Cancer Res. 2000 Feb;6(2):602-910690545J Pharmacol Exp Ther. 2000 Jun;293(3):912-2010869392Nat Biotechnol. 2000 Aug;18(8):877-8110932159J Biol Chem. 2000 Oct 6;275(40):31009-1510906132Mutat Res. 2000 Oct 16;461(2):83-10811018583J Biol Chem. 2000 Dec 1;275(48):37469-7310984493Cancer Res. 2001 Mar 1;61(5):2220-511280790J Mol Biol. 2001 Apr 6;307(4):1023-3411286553Oncogene. 2001 Feb 15;20(7):859-6811314019Int J Radiat Oncol Biol Phys. 2001 May 1;50(1):27-3611316543Clin Cancer Res. 2001 Aug;7(8):2387-9511489817Mutat Res. 2001 May 10;485(4):283-30711585362J Biol Chem. 2001 Oct 19;276(42):39368-7811483614Biochemistry. 2001 Oct 23;40(42):12639-4411601988Clin Cancer Res. 2001 Nov;7(11):3510-811705870Oncol Rep. 2002 Jan-Feb;9(1):11-711748448Nucleic Acids Res. 2002 Feb 1;30(3):823-911809897Nature. 2002 Feb 7;415(6872):655-911832948J Pediatr Hematol Oncol. 2001 May;23(4):234-911846302Mutagenesis. 2002 Mar;17(2):149-5611880544Anticancer Res. 2001 Nov-Dec;21(6A):4041-911911289Biol Chem. 2002 Mar-Apr;383(3-4):347-6412033427FASEB J. 2002 Jun;16(8):889-9012039869Biochem Biophys Res Commun. 2002 Sep 20;297(2):288-9312237116J Biol Chem. 2002 Nov 1;277(44):41715-2412200445Antioxid Redox Signal. 2002 Oct;4(5):805-1512470509Nat Immunol. 2003 Feb;4(2):145-5312524539Mol Cell Biol. 2003 May;23(9):3265-7312697826Science. 2003 Apr 25;300(5619):650-312714747J Biol Chem. 2003 May 16;278(20):18289-9612624104Oncogene. 2003 May 22;22(21):3243-5112761494Toxicology. 2003 Nov 15;193(1-2):3-3414599765EMBO J. 2003 Dec 1;22(23):6299-30914633989J Clin Invest. 2003 Dec;112(12):1793-514679175Carcinogenesis. 2004 Jan;25(1):11-914555612Nucleic Acids Res. 2004;32(1):73-8114704345Nucleic Acids Res. 2004;32(12):3531-615247342Mol Cancer. 2003 Jan 22;2:1212605718Mol Cell. 2004 Jul 23;15(2):209-2015260972Mol Cell Biol. 2004 Oct;24(19):8504-1815367671Br J Cancer. 2004 Sep 13;91(6):1166-7315316562Respir Res. 2004;5:1615450125Circ Res. 2004 Oct 29;95(9):902-1015472121J Biol Chem. 1989 Aug 25;264(24):13963-62668278Proc Natl Acad Sci U S A. 1990 Feb;87(3):1032-62105492Science. 1990 Sep 7;249(4973):1157-612118682EMBO J. 1992 Feb;11(2):653-651537340EMBO J. 1992 Sep;11(9):3323-351380454DNA Cell Biol. 1993 Apr;12(3):265-738466649Mol Cell Biol. 1993 Sep;13(9):5370-68355688Cancer Res. 1993 Oct 1;53(19):4469-738402615Mutat Res. 1994 Jul;315(1):55-637517011Gene. 1994 Aug 5;145(2):197-2038056331Ann N Y Acad Sci. 1994 Jul 29;726:306-87522424J Biol Chem. 1994 Nov 11;269(45):27855-627961715Proc Natl Acad Sci U S A. 1995 May 9;92(10):4497-5017753832Nucleic Acids Res. 1995 Aug 25;23(16):3224-307545284J Biol Chem. 1996 Apr 12;271(15):8593-88621488Oncogene. 1996 Feb 1;12(3):693-78637727J Biol Chem. 1996 Jul 26;271(30):17771-88663540Mol Cell Biol. 1996 Aug;16(8):4414-258754842Mol Cell Biol. 1996 Sep;16(9):4604-138756616Adv Exp Med Biol. 1996;387:69-758794196Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128J Biol Chem. 1996 Dec 13;271(50):32253-98943284Curr Opin Genet Dev. 1997 Feb;7(1):105-139024626Genes Dev. 1997 Mar 1;11(5):558-709119221Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-89108029J Biol Chem. 1997 Jun 6;272(23):14497-5009169404EMBO J. 1997 Nov 3;16(21):6548-589351835Anticancer Res. 1997 Sep-Oct;17(5B):3713-199427767J Immunol. 1998 Jan 15;160(2):810-99551916Br J Cancer. 1998 Apr;77(7):1169-739569057Mol Cell Biol. 1998 Nov;18(11):6191-2009774636Oncogene. 1998 Aug 20;17(7):845-519780001Mol Cell Biol. 1999 Jan;19(1):12-209858527EMBO J. 1999 Apr 1;18(7):1905-1410202154J Biol Chem. 1999 Sep 24;274(39):27891-710488136J Cell Sci. 2004 Dec 1;117(Pt 25):5965-7315564374DNA Repair (Amst). 2005 Mar 2;4(3):367-7915661660Nat Rev Mol Cell Biol. 2005 Jan;6(1):44-5515688066Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Oncogene. 2005 Feb 24;24(9):1641-715674341Oncogene. 2005 Mar 3;24(10):1738-4815674334Immunity. 2005 Mar;22(3):355-7015780992Mol Cell. 2005 Mar 18;17(6):793-80315780936Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4813-815781865Nat Rev Cancer. 2005 Apr;5(4):297-30915803156DNA Repair (Amst). 2005 Jul 12;4(7):826-3515927541Nucleic Acids Res. 2005;33(15):4711-2416113242Radiother Oncol. 2005 Aug;76(2):168-7616026872Trends Mol Med. 2005 Nov;11(11):503-1116214418Mol Cancer Ther. 2005 Dec;4(12):1923-3516373707Ann N Y Acad Sci. 2005 Nov;1059:184-9516382054EMBO Rep. 2006 Feb;7(2):219-2416322760J Biol Chem. 2006 May 19;281(20):14446-5616554306Cytokine Growth Factor Rev. 2006 Jun;17(3):147-5616516532J Biol Chem. 1999 Dec 10;274(50):35809-1510585464Nature. 2000 Jan 27;403(6768):451-610667800Nucleic Acids Res. 2000 Mar 1;28(5):1099-10510666449Toxicology. 2006 Jul 5;224(1-2):44-5516730871Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14140-516966602EMBO J. 2006 Oct 18;25(20):4784-9417024177Semin Cancer Biol. 2006 Dec;16(6):420-617092741Clin Cancer Res. 2007 Jan 1;13(1):260-717200364DNA Repair (Amst). 2007 Feb 4;6(2):254-6417118717Toxicol Lett. 2007 Feb 5;168(3):302-917207589Mol Cancer Res. 2007 Jan;5(1):61-7017259346Cell Cycle. 2007 Feb 1;6(3):318-2917297309DNA Repair (Amst). 2007 Mar 1;6(3):317-2817126083Clin Lymphoma Myeloma. 2007 Jan;7(4):296-30417324338J Cell Biochem. 2007 Mar 1;100(4):883-9617031865Cancer Res. 2007 Mar 1;67(5):2141-917332344DNA Repair (Amst). 2007 Apr 1;6(4):461-917166779Oncogene. 2007 Mar 29;26(14):2048-5717001309Nucleic Acids Res. 2007;35(5):1569-7717289756Cancer Lett. 2007 Jul 8;252(1):93-10317275176Mol Med. 2007 Jan-Feb;13(1-2):89-9617515960Cancer Metastasis Rev. 2007 Jun;26(2):249-6017415527Eur J Cancer. 2007 Aug;43(12):1791-80117588740Mol Aspects Med. 2007 Jun-Aug;28(3-4):375-9517560642Cancer Res. 2007 Sep 15;67(18):8952-917875738Invest Ophthalmol Vis Sci. 2008 Jan;49(1):407-1518172119DNA Repair (Amst). 2008 Feb 1;7(2):177-8617974506Nat Rev Cancer. 2008 Mar;8(3):180-9218273037Mol Immunol. 2008 Apr;45(8):2225-3518179823Nucleic Acids Res. 2008 Mar;36(5):1555-6618208837Anticancer Agents Med Chem. 2008 May;8(4):351-718473720Anticancer Agents Med Chem. 2008 May;8(4):417-2518473726Mol Cancer Ther. 2008 Jul;7(7):2012-2118645011Cancer Res. 2008 Aug 1;68(15):6425-3418676868Mutat Res. 2008 Aug 25;643(1-2):54-6318579163Antioxid Redox Signal. 2008 Nov;10(11):1853-6718627350DNA Repair (Amst). 2008 Dec 1;7(12):1927-3718773976Carcinogenesis. 2008 Dec;29(12):2267-7818791199Invest Ophthalmol Vis Sci. 2009 Feb;50(2):844-5018936153J Cell Physiol. 2009 Apr;219(1):209-1819097035Int J Cancer. 2009 Apr 1;124(7):1675-8419101986Proteomics. 2009 Feb;9(4):1058-7419180539Mol Cell Biol. 2009 Apr;29(7):1834-5419188445Cancer Res. 2009 Apr 15;69(8):3642-919351836J Nutr Biochem. 2009 Jun;20(6):443-5218789672Mol Cancer Res. 2009 May;7(5):745-5419435822Future Oncol. 2009 Jun;5(5):713-2619519210Vascul Pharmacol. 2009 Aug-Sep;51(2-3):133-919524065Mol Endocrinol. 2009 Sep;23(9):1346-5919460860DNA Repair (Amst). 2009 Nov 2;8(11):1273-8219726241Antioxid Redox Signal. 2009 Mar;11(3):651-6818715143Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Antioxid Redox Signal. 2009 Mar;11(3):639-5018715151Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Mol Endocrinol. 2010 Feb;24(2):391-40120032196J Med Chem. 2010 Feb 11;53(3):1200-1020067291Antioxid Redox Signal. 2010 Jun 1;12(11):1247-6919764832Breast Cancer Res. 2010;12(2):20320459590J Pharmacol Exp Ther. 2010 Sep 1;334(3):988-9820504914Exp Hematol. 2010 Dec;38(12):1178-8820826193Vision Res. 2011 Jan;51(1):93-10020937296Neurotoxicology. 2011 Jan;32(1):140-920932997Antioxid Redox Signal. 2011 Apr 15;14(8):1387-40120874257Mol Cancer Ther. 2011 Sep;10(9):1698-70821700832Neuron. 2004 Feb 19;41(4):549-6114980204Mol Cancer Ther. 2004 May;3(5):647-5415141023Mol Cancer Ther. 2004 Jun;3(6):679-8615210853Antineoplastic AgentschemistrypharmacologyDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsmetabolismEnzyme InhibitorschemistrypharmacologyHumansNeoplasmsdrug therapyenzymologyNeovascularization, PathologicOxidation-Reductiondrug effectsSignal Transductiondrug effectsTumor MicroenvironmentVascular Endothelial Growth Factor Ametabolism
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1874-4702512012JanCurrent molecular pharmacologyCurr Mol PharmacolSmall-molecule inhibitors of APE1 DNA repair function: an overview.14-35APE1 is a multifaceted protein that orchestrates multiple activities in the cell, one of which is the preservation of genomic integrity; a vital process that takes place in the context of the base excision repair (BER) pathway. Studies have implicated APE1 in rendering cancerous cells less vulnerable to the effects of DNA-damaging agents that are commonly used for the treatment of cancer. Furthermore, suppression of APE1 expression in cancer cell lines is accompanied by the potentiation of the activity of cytotoxic agents. As a result, major efforts have been directed towards the identification of small-molecule inhibitors of this DNA-repair enzyme. Herein, we review all patented small-molecule APE1 inhibitors reported prior to 2011. Unfortunately, the potency and selectivity of many of the reported inhibitors were not disclosed by the original authors, and at present it is unclear if APE1 is a bona fide target for many of the purported inhibitors. Moreover, cellular activity and toxicity of many inhibitors remain to be established. Since this is the first comprehensive review of small molecule APE1 inhibitors, we present all compounds reported to inhibit APE1 activity with an IC50 value ≤ 25 μM. Efforts towards a careful validation and optimization of these compounds are warranted. Furthermore, we explore potential allosteric drug-binding sites on the protein as an alternative approach for modulating the activity of this multifunctional protein. In addition, we give an overview of APE2, as well as other APE1 homologues in some disease-causing pathogens. Finally, given the universal importance of DNA repair, as well as the considerable conservation of repair proteins across all living organisms, we propose targeting the AP endonuclease activity of pathogens by the compounds discussed in this review, thereby expanding their therapeutic potential and application.Al-SafiRasha IRIDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA.OddeSrinivasSShabaikYumnaYNeamatiNouriNengJournal ArticleResearch Support, Non-U.S. Gov'tReview
United Arab EmiratesCurr Mol Pharmacol1014679971874-46720Enzyme Inhibitors0Small Molecule LibrariesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18APEX2 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCatalytic DomainDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) Lyaseantagonists & inhibitorsmetabolismEnzyme Inhibitorschemistrypharmacologytherapeutic useHumansNeoplasmsdrug therapyenzymologySmall Molecule Librarieschemistrytherapeutic useStructure-Activity Relationship
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1423-03803312012FebTumour biology : the journal of the International Society for Oncodevelopmental Biology and MedicineTumour Biol.Reduced expression of DNA repair genes (XRCC1, XPD, and OGG1) in squamous cell carcinoma of head and neck in North India.111-910.1007/s13277-011-0253-7Squamous cell carcinoma of head and neck (SCCHN) is the sixth most common cancer globally, and in India, it accounts for 30% of all cancer cases. Epidemiological studies have shown a positive association between defective DNA repair capacity and SCCHN. The underlying mechanism of their involvement is not well understood. In the present study, we have analyzed the relationship between SCCHN and the expression of DNA repair genes namely X-ray repair cross-complementing group 1 (XRCC1), xeroderma pigmentosum group D (XPD), and 8-oxoguanine DNA glycosylase (OGG1) in 75 SCCHN cases and equal number of matched healthy controls. Additionally, levels of DNA adduct [8-hydroxyguanine (8-OHdG)] in 45 SCCHN cases and 45 healthy controls were also determined, to ascertain a link between mRNA expression of these three genes and DNA adducts. The relative expression of XRCC1, XPD, and OGG1 in head and neck cancer patients was found to be significantly low as compared to controls. The percent difference of mean relative expression between cases and controls demonstrated maximum lowering in OGG1 (47.3%) > XPD (30.7%) > XRCC1 (25.2%). A negative Spearmen correlation between XRCC1 vs. 8-OHdG in cases was observed. In multivariate logistic regression analysis (adjusting for age, gender, smoking status, and alcohol use), low expression of XRCC1, XPD, and OGG1 was associated with a statistically significant increased risk of SCCHN [crude odds ratios (ORs) (95%CI) OR 2.10; (1.06-4.17), OR 2.76; (1.39-5.49), and 5.24 (2.38-11.52), respectively]. In conclusion, our study demonstrated that reduced expression of XRCC1, XPD, and OGG1 is associated with more than twofold increased risk in SCCHN.KumarAnilACSIR-Indian Institute of Toxicology Research, CSIR-IITR, PO Box 80, MG Marg, Lucknow 226001, India.PantMohan ChandMCSinghHirdya ShankerHSKhandelwalShashiSengJournal ArticleResearch Support, Non-U.S. Gov't20111115
United StatesTumour Biol84099221010-42830DNA-Binding Proteins0X-ray Repair Cross Complementing Protein 10XRCC1 protein, humanEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 3.6.4.12Xeroderma Pigmentosum Group D ProteinEC 5.99.-ERCC2 protein, humanIMInt J Cancer. 1994 Sep 15;58(6):825-97523311J Biol Chem. 2003 Dec 26;278(52):52914-814578343Biogerontology. 2010 Jun;11(3):287-9719707883Mutat Res. 2011 Dec 24;726(2):227-3321986195Mutat Res. 2002 Nov 30;509(1-2):165-7412427537Cancer Sci. 2009 Jul;100(7):1261-619432884Carcinogenesis. 2009 Jan;30(1):78-8719029194Carcinogenesis. 1999 Nov;20(11):2125-910545415Mol Carcinog. 1997 Apr;18(4):232-439142218DNA Repair (Amst). 2002 Mar 28;1(3):237-5012509255Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1614-88434025Cancer Epidemiol Biomarkers Prev. 1998 Apr;7(4):309-149568786Mutat Res. 2001 Aug 9;486(3):207-1611459633Mutat Res. 2008 Dec 15;648(1-2):65-7218977234Oncogene. 1990 Oct;5(10):1603-101979160Pharmacogenet Genomics. 2007 Nov;17(11):897-90518075460Cancer Epidemiol Biomarkers Prev. 1998 Jun;7(6):465-89641488Science. 1999 Dec 3;286(5446):1897-90510583946DNA Repair (Amst). 2007 Sep 1;6(9):1264-7017403617Biochimie. 1999 Jan-Feb;81(1-2):39-4410214908Cell Biol Toxicol. 2009 Oct;25(5):489-9718787964Mutat Res. 2006 Jan 29;593(1-2):88-9616054657J Invest Dermatol. 2005 Feb;124(2):435-4215675965Carcinogenesis. 2000 Aug;21(8):1527-3010910954Toxicol Sci. 2009 Jan;107(1):165-7018948301Cell Biol Int. 2009 Mar;33(3):357-6319385033Carcinogenesis. 2006 May;27(5):997-100716308313J Genet. 2008 Apr;87(1):3-2018560169FEBS Lett. 1994 Mar 14;341(1):59-648137923Carcinogenesis. 2007 Mar;28(3):657-6417028303J Psychosom Res. 2009 Mar;66(3):259-6619232240Carcinogenesis. 2003 Nov;24(11):1847-5212919962Int J Cancer. 2003 Apr 10;104(3):263-812569548Mutat Res. 2011 Mar 15;708(1-2):11-2021277872Mol Biol Rep. 2011 Feb;38(2):1251-6120571908Nature. 1991 Jan 31;349(6308):431-41992344Cancer Biomark. 2005;1(2-3):201-517192041DNA Repair (Amst). 2005 Jul 12;4(7):826-3515927541Am J Respir Cell Mol Biol. 2010 Nov;43(5):576-8420008282Science. 1989 Nov 3;246(4930):629-342683079Pharmacogenomics. 2006 Sep;7(6):843-5216981845J Toxicol Environ Health A. 2007 Jun;70(11):956-6317479411Free Radic Biol Med. 1999 Aug;27(3-4):401-1010468215Mutat Res. 2012 Jan 3;729(1-2):24-3421945240Oncogene. 1998 Jun 25;16(25):3219-259681819Free Radic Biol Med. 2010 Aug 15;49(4):587-9620483371Cancer Res. 1992 Feb 1;52(3):734-61310070Cancer Res. 2006 Dec 15;66(24):11683-917178863Carcinogenesis. 2000 May;21(5):965-7110783319Mol Gen Genet. 1997 Mar 26;254(2):171-89108279Mutat Res. 2008 Mar 1;639(1-2):45-5418155253Anticancer Res. 2011 Apr;31(4):1411-521508394Mol Cancer. 2009 Mar 05;8:1319265534Int J Cancer. 2002 Jul 1;100(1):9-1312115580Am J Hematol. 2005 Feb;78(2):100-715682421Annu Rev Genet. 1995;29:69-1058825469Cancer. 2002 Jan 15;94(2):393-711900225J Radiat Res. 2003 Mar;44(1):31-512841596J Natl Cancer Inst. 2003 Sep 3;95(17):1263-512953074Trends Genet. 1993 Jul;9(7):246-98379000Carcinogenesis. 2000 Dec;21(12):2219-2311133811Cancer Res. 2001 Feb 15;61(4):1354-711245433J Exp Clin Cancer Res. 2009 Mar 13;28:3719284666Cancer Epidemiol Biomarkers Prev. 1999 Sep;8(9):801-710498399Kidney Int. 2004 Aug;66(2):820-3115253739Free Radic Biol Med. 2011 Jul 15;51(2):417-2321569841AdultAgedCarcinoma, Squamous CellgeneticsDNA GlycosylasesgeneticsDNA RepairgeneticsDNA-Binding ProteinsgeneticsGene Expression Regulation, NeoplasticHead and Neck NeoplasmsgeneticsHumansMaleMiddle AgedX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Proteingenetics
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1873-45965212012Jan01Free radical biology & medicineFree Radic. Biol. Med.Influence of the OGG1 Ser326Cys polymorphism on oxidatively damaged DNA and repair activity.118-2510.1016/j.freeradbiomed.2011.09.038Oxidatively damaged DNA base lesions are considered to be mainly repaired by 8-oxoguanine DNA glycosylase (OGG1) mediated pathways. We investigated the effect of the OGG1 Ser326Cys polymorphism on the level and repair of oxidatively damaged DNA in mononuclear blood cells (MNBC) by means of the comet assay. We collected blood samples from 1,019 healthy subjects and genotyped for the OGG1 Ser326Cys polymorphism. We found 49 subjects homozygous for the variant genotype (Cys/Cys) and selected same numbers of age-matched subjects with the heterozygous (Ser/Cys) and homozygous wild-type genotype (Ser/Ser). Carriers of the Cys/Cys genotype had higher levels of formamidopyrimidine DNA glycosylase (FPG) sensitive sites in MNBC (0.31 ± 0.03 lesions/10(6)bp) compared to Ser/Ser (0.19 ± 0.02 lesions/10(6)bp, P<0.01). The level of hOGG1 sensitive sites in MNBC from the Ser326Cys carriers (0.19 ± 0.16 lesions/10(6) bp) was also higher compared to the Ser/Ser genotype (0.11 ± 0.09 lesions/10(6) bp, P<0.05). Still, there was no genotype-related difference in DNA repair incision activity of MNBC extracts on nucleoids with oxidatively damaged DNA induced by Ro19-8022/white light (P=0.20). In addition, there were no differences in the expression of OGG1 (P=0.69), ERCC1 (P=0.62), MUTYH (P=0.85), NEIL1 (P=0.17) or NUDT1 (P=0.48) in whole blood. Our results indicate that the OGG1 Ser326Cys polymorphism has limited influence on the DNA repair incisions by extracts of MNBC, whereas the apparent increased risk of cancer in subjects with the Cys/Cys genotype may be because of higher levels of oxidatively damaged DNA.Copyright © 2011 Elsevier Inc. All rights reserved.JensenAnnieADepartment of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.LøhrMilleMEriksenLouiseLGrønbækMortenMDorryEladELoftSteffenSMøllerPeterPengJournal ArticleResearch Support, Non-U.S. Gov't20111007
United StatesFree Radic Biol Med87091590891-58495614-64-28-hydroxyguanine5Z93L87A1RGuanineEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanAdenocarcinoma of lungIMAdenocarcinomaenzymologygeneticsAdultAgedCase-Control StudiesComet AssayDNA DamagegeneticsDNA GlycosylasesgeneticsmetabolismDNA RepairgeneticsDenmarkFemaleGenetic Predisposition to DiseaseGenotypeGuanineanalogs & derivativesmetabolismHomozygoteHumansLeukocytes, MononuclearcytologymetabolismLung NeoplasmsenzymologygeneticsMaleMiddle AgedOxidation-ReductionOxidative StressPolymorphism, Single Nucleotide
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1532-045615522012MarComparative biochemistry and physiology. Toxicology & pharmacology : CBPComp. Biochem. Physiol. C Toxicol. Pharmacol.8-Oxoguanine DNA glycosylase 1 (OGG1) from the copepod Tigriopus japonicus: molecular characterization and its expression in response to UV-B and heavy metals.290-910.1016/j.cbpc.2011.09.0108-Oxoguanine DNA glycosylase 1 (EC 3.2.2.23) is encoded by OGG1 gene and plays a key role in removing 8-oxo-7,8-dihydroguanine (8-oxoG) base in DNA lesion by reactive oxygen species (ROS). To identify and characterize OGG1 gene (TJ-OGG1) in the copepod Tigriopus japonicus, the full-length cDNA sequence, genomic structure, and promoter region was analyzed. In addition, to investigate transcriptional change of TJ-OGG1 mRNA under oxidative stress conditions, T. japonicus were exposed to environmental oxidative inducers, H(2)O(2), UV-B, and heavy metals (Cd, Cu, and Zn), respectively. The full-length cDNA of TJ-OGG1 gene was 1708 bp in length, encoding 343 amino acid residues. The deduced amino acid sequences of TJ-OGG1 showed a 56% similarity with human. Two conserved motifs (HhH and PVD loop) and two conserved residues (lysine and aspartic acid) in active sites were also observed. TJ-OGG1 genome structure contained six exons and five introns and putative transcription factor binding sites such as Nrf-2, p53, ERE-half sites, and XRE were detected on the promoter region. TJ-OGG1 mRNA level was increased at approximately three-fold (P<0.05) at 1mM and approximately 4-fold (P<0.01) at 10mM of H(2)O(2), respectively. UV-B enhanced the expression of TJ-OGG1 mRNA at 15kJ/m(2) (P<0.05) and more (P<0.001). In a time-course experiment, TJ-OGG1 gene was highly transcribed within 12h after exposure of 10 kJ/m(2) (P<0.01) and 20 kJ/m(2) (P<0.001). The expression of TJ-OGG1 mRNA after exposure to Cu and Cd for 96 h was significantly up-regulated at 0.1 μg/L and then remarkably reduced in a dose-dependent manner. Their transcript levels did not change at low dose (0.1 and 1 μg/L) but were dose-dependently down-regulated at high dose (10 and 100 μg/L). These findings suggest that H(2)O(2), UV-B, and heavy metals induce oxidative stress and generate oxidatively damaged DNA. Consequently, the enhanced TJ-OGG1 gene expression would be associated with active involvement of TJ-OGG1 gene in DNA repair process as a cellular protection mechanism. This is the first report on the cloning and characterization of OGG1 gene in aquatic animals. This study is helpful for a better understanding of the molecular mechanisms of cellular protection against various environmental oxidative stress inducers such as UV-B and heavy metals in aquatic invertebrates.Copyright © 2011 Elsevier Inc. All rights reserved.KimBo-MiBMDepartment of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791, South Korea.RheeJae-SungJSSeoJung SooJSKimIl-ChanICLeeYoung-MiYMLeeJae-SeongJSengGENBANKJN090125Journal ArticleResearch Support, Non-U.S. Gov't20111001
United StatesComp Biochem Physiol C Toxicol Pharmacol1009595001532-04560DNA, Complementary0Oxidants0Transcription Factors00BH33GNGHCadmium5614-64-28-hydroxyguanine5Z93L87A1RGuanine789U1901C5CopperBBX060AN9VHydrogen PeroxideEC 3.2.2.-DNA GlycosylasesIMAmino Acid SequenceAnimalsBase SequenceBinding SitesgeneticsCadmiumpharmacologyCloning, MolecularCopepodaenzymologygeneticsmetabolismCopperpharmacologyDNA GlycosylasesclassificationgeneticsmetabolismDNA, ComplementarychemistrygeneticsDose-Response Relationship, DrugGene Expression Regulation, Enzymologicdrug effectsradiation effectsGuanineanalogs & derivativesmetabolismHydrogen PeroxidepharmacologyMolecular Sequence DataOxidantspharmacologyPhylogenyPromoter Regions, GeneticgeneticsReverse Transcriptase Polymerase Chain ReactionSequence Analysis, DNASequence Homology, Amino AcidTranscription FactorsmetabolismUltraviolet Rays
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1362-49624022012JanNucleic acids researchNucleic Acids Res.Ubiquitin ligase UBR3 regulates cellular levels of the essential DNA repair protein APE1 and is required for genome stability.701-1110.1093/nar/gkr744APE1 (Ref-1) is an essential human protein involved in DNA damage repair and regulation of transcription. Although the cellular functions and biochemical properties of APE1 are well characterized, the mechanism involved in regulation of the cellular levels of this important DNA repair/transcriptional regulation enzyme, remains poorly understood. Using an in vitro ubiquitylation assay, we have now purified the human E3 ubiquitin ligase UBR3 as a major activity that polyubiquitylates APE1 at multiple lysine residues clustered on the N-terminal tail. We further show that a knockout of the Ubr3 gene in mouse embryonic fibroblasts leads to an up-regulation of the cellular levels of APE1 protein and subsequent genomic instability. These data propose an important role for UBR3 in the control of the steady state levels of APE1 and consequently error free DNA repair.MeisenbergCorneliaCGray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.TaitPhillip SPSDianovaIrina IIIWrightKatherineKEdelmannMariola JMJTernetteNicolaNTasakiTakafumiTKesslerBenedikt MBMParsonsJason LJLKwonYong TaeYTDianovGrigory LGLengUL1 TR000005TRNCATS NIH HHSUnited StatesMedical Research CouncilUnited KingdomG0700730Medical Research CouncilUnited KingdomR01 HL083365HLNHLBI NIH HHSUnited StatesCancer Research UKUnited KingdomGM074000GMNIGMS NIH HHSUnited StatesHL083365HLNHLBI NIH HHSUnited StatesG0501068Medical Research CouncilUnited KingdomJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20110920
EnglandNucleic Acids Res04110110305-1048EC 2.3.2.27UBR3 protein, mouseEC 2.3.2.27Ubiquitin-Protein LigasesEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseK3Z4F929H6LysineIMNucleic Acids Res. 1994 May 25;22(10):1866-737516064Nat Cell Biol. 2010 Jun;12(6):563-7120473298Eur J Biochem. 2000 Apr;267(8):2135-4910759836Carcinogenesis. 2000 Jul;21(7):1329-3410874010Mutat Res. 2000 Oct 16;461(2):83-10811018583Am J Pathol. 2001 Jan;158(1):199-20611141493Cancer Res. 2001 Jul 15;61(14):5552-711454706Mutat Res. 2001 May 10;485(4):283-30711585362Biochemistry. 2001 Oct 23;40(42):12639-4411601988Clin Cancer Res. 2003 Oct 15;9(13):4689-9414581338Mutat Res. 2003 Oct 29;531(1-2):157-6314637252J Clin Invest. 2003 Dec;112(12):1887-9414679184Nucleic Acids Res. 2004;32(12):3531-615247342Mol Cell Biol. 2004 Sep;24(18):8145-5315340075Biochemistry. 1972 Sep 12;11(19):3610-84626532Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-41722334Cell. 1992 Feb 21;68(4):755-671739980Nucleic Acids Res. 1992 Sep 11;20(17):4417-211383925Nature. 1993 Apr 22;362(6422):709-158469282J Biol Chem. 2007 Jun 22;282(25):18510-2017462990Trends Biochem Sci. 2007 Nov;32(11):520-817962019Mol Cell. 2008 Feb 29;29(4):477-8718313385Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-238799128Nucleic Acids Res. 1997 Jun 15;25(12):2495-5009171104Anticancer Res. 1997 Sep-Oct;17(5B):3713-199427767Mutat Res. 1998 Oct 21;409(1):17-299806499Nucleic Acids Res. 2005;33(1):298-30615647512Mol Cell. 2005 Feb 4;17(3):463-7015694346Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325FEBS J. 2005 Jul;272(13):3231-4015978030Mol Cell Biol. 2005 Aug;25(16):7120-3616055722Clin Cancer Res. 2005 Sep 1;11(17):6205-1116144922Nucleic Acids Res. 2008 Mar;36(5):1555-6618208837DNA Repair (Amst). 2008 Jun 1;7(6):932-4018472309J Biol Chem. 2009 Jan 16;284(3):1884-9519008229Oncogene. 2009 Apr 2;28(13):1616-2519219073Free Radic Biol Med. 2009 Jun 1;46(11):1488-9919268524EMBO J. 2009 Oct 21;28(20):3207-1519713937Neurosci Lett. 2009 Dec 11;466(3):124-719782121Antioxid Redox Signal. 2009 Mar;11(3):621-3818715144Nucleic Acids Res. 2010 Jan;38(3):832-4519934257Clin Cancer Res. 2000 Feb;6(2):602-910690545AnimalsDNA-(Apurinic or Apyrimidinic Site) LyasechemistrymetabolismGene Knockout TechniquesGenomic InstabilityHeLa CellsHumansLysinemetabolismMiceUbiquitin-Protein LigasesgeneticsmetabolismUbiquitination
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0027-51077361-22012Aug01Mutation researchMutat. Res.Impact of cadmium on hOGG1 and APE1 as a function of the cellular p53 status.56-6310.1016/j.mrfmmm.2011.05.006The tumor suppressor protein p53, often called the guardian of the genome, is involved in important cellular processes, such as cell cycle control, apoptosis and DNA repair. With respect to BER, p53 might physically interact with and affect the transcription of different BER proteins such as hOGG1, APE1 or Polβ. In studies in HCT116 p53(-/-) cells previously published, activity and mRNA expression of hOGG1 were found to be significantly decreased, while down-regulation of APE1 mRNA and protein levels in response to genotoxic stress were only described in HCT116 p53(+/+) cells, but not in the isogenic p53 knockout cell line. The predominantly indirect genotoxic carcinogen cadmium inhibits the BER pathway and potentially interferes with zinc binding proteins such as p53. Therefore, this study was accomplished to investigate whether p53 is involved in the cadmium-induced inhibition of BER activity. To address this issue we applied a non-radioactive cleavage test system based on a Cy5-labeled oligonucleotide. We present evidence that p53 is not essential for hOGG1 and APE1 gene expression as well as OGG and APE activity in unstressed HCT116 cells; however, it plays an important role in the cellular response to cadmium treatment. Here, a direct involvement of p53 was only observed with respect to APE1 gene expression contributing to an altered APE activity, while OGG activity was presumably affected indirectly due to a stronger accumulation of cadmium in HCT116 p53(+/+) cells. In summary, p53 indeed affects the BER pathway directly and indirectly in response to cadmium treatment.Copyright © 2011 Elsevier B.V. All rights reserved.HamannIngritIInstitut für Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut für Technologie, 76131 Karlsruhe, Germany.KönigCharlotteCRichterConstanzeCJahnkeGunnarGHartwigAndreaAengJournal ArticleResearch Support, Non-U.S. Gov't20110513
NetherlandsMutat Res04007630027-510700BH33GNGHCadmiumEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanEC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMCadmiumtoxicityDNA GlycosylasesmetabolismDNA Repairdrug effectsDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismGenes, p53HCT116 CellsHumans
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1559-131X2922012JunMedical oncology (Northwood, London, England)Med. Oncol.Prognostic significance of APE1 cytoplasmic localization in human epithelial ovarian cancer.1265-7110.1007/s12032-011-9931-yCytoplasmic localization of apurinic/apyrimidinic endonuclease 1 (APE1) correlates with different tumorigenic processes and poor prognosis in several cancer types. However, rare investigation into the prognosis value of cytoplasmic localization of APE1 was provided in ovarian cancer. The present study examined for the first time the cytoplasmic localization of APE1 in epithelial ovarian cancer (EOC) by immunohistochemistry. The relationship between cytoplasmic localization of APE1 and clinicopathological parameters, as well as the correlation between cytoplasmic localization of APE1 and prognosis, was investigated. We found that cytoplasmic positivity was significantly higher in EOCs with low tumor differentiation (P = 0.002) and was significantly higher in advanced Federation International of Gynecology and Obstetrics (FIGO) stage (III + IV) patients compared to that in early FIGO stage (I + II) patients (40.7% vs. 11.8%; P = 0.002). No significant difference was observed in APE1 pattern referring to age, tumor size, family history, histological type, ascites, and lymphatic metastasis (P > 0.05). In addition, a lower survival rate was found in patients with cytoplasmic positive localization of APE1 compared to that in patients with cytoplasmic negative localization (P < 0.05). All these findings suggest that cytoplasmic localization of APE1 is associated with tumor progression and might be a valuable prognostic marker for EOC.ShengQingsongQDepartment of Gynecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, People's Republic of China.ZhangYingYWangRuiRZhangJianfangJChenBiliangBWangJianJZhangWeiWXinXiaoyanXengJournal Article20110410
United StatesMed Oncol94355121357-0560EC 4.2.99.18APEX1 protein, humanEC 4.2.99.18DNA-(Apurinic or Apyrimidinic Site) LyaseIMMutat Res. 2001 Mar 7;485(2):143-5211182545Antioxid Redox Signal. 2009 Mar;11(3):601-2018976116Endocr Rev. 2001 Apr;22(2):255-8811294827Cancer Treat Rev. 2010 Aug;36(5):425-3520056333Mutat Res. 2003 Oct 29;531(1-2):157-6314637252Br J Cancer. 2010 Feb 16;102(4):704-920087352Biochem Biophys Res Commun. 1999 Aug 11;261(3):859-6310441516Anticancer Res. 2001 Nov-Dec;21(6A):4041-911911289Mutat Res. 2000 Oct 16;461(2):83-10811018583Cancer Res. 1998 Jan 15;58(2):189-949443389CA Cancer J Clin. 2002 Jan-Feb;52(1):23-4711814064Cancer Sci. 2003 Jul;94(7):582-812841865Br J Cancer. 1998 Apr;77(7):1169-739569057Nat Immunol. 2003 Feb;4(2):145-5312524539Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):367-8415706084Hum Pathol. 2008 Feb;39(2):201-817949784Cancer Res. 1995 Dec 15;55(24):6097-1028521399Mol Cell Biol. 2002 Apr;22(8):2810-2011909973Clin Cancer Res. 2004 Dec 1;10(23):7875-8315585620J Endocrinol Invest. 2001 Mar;24(3):RC10-211314755Mol Med. 2007 Jan-Feb;13(1-2):89-9617515960Int J Oncol. 2009 Nov;35(5):1069-7919787261Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Jan;40(1):125-819292061Mol Cell Biol. 2009 Apr;29(7):1834-5419188445J Biol Chem. 1999 Jun 11;274(24):16959-6410358044Mol Cell Biol. 2010 Jan;30(2):366-7119901076Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-89108029Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-4315824325Nucleic Acids Res. 2009 Jul;37(12):3946-5819401441J Biol Chem. 2001 Jan 12;276(2):1335-4411035035Oncol Rep. 2002 Jan-Feb;9(1):11-711748448Front Biosci. 2007 Sep 01;12:5166-7417569638Cell Mol Life Sci. 2010 Nov;67(21):3589-60820706766Cystadenocarcinoma, MucinousmetabolismmortalityCystadenocarcinoma, SerousmetabolismmortalityCytoplasmmetabolismDNA-(Apurinic or Apyrimidinic Site) LyasemetabolismEndometrial NeoplasmsmetabolismmortalityFemaleHumansImmunoenzyme TechniquesLymphatic MetastasisMiddle AgedNeoplasm StagingOvarian NeoplasmsmetabolismmortalityPrognosisSurvival Rate
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1522-727827102012OctEnvironmental toxicologyEnviron. Toxicol.Oxidative damage and OGG1 expression induced by a combined effect of titanium dioxide nanoparticles and lead acetate in human hepatocytes.590-710.1002/tox.20682Titanium dioxide (TiO(2)) is a widely used nanomaterial that can cause biological damage through oxidative stress. At low concentrations, TiO(2) can interact with lead acetate (PbAc) to produce different toxic responses, compared with TiO(2) or PbAc alone. In this study, we utilized the following as indicators of toxic responses in human embryo hepatocytes (L02): reactive oxygen species (ROS), reduced glutathione (GSH), superoxide dismutase (SOD), and the DNA adducts 8-hydroxydeoxyguanosine (8-OHdG) and 8-oxoguanine DNA glycosylase homolog 1 (OGG1). These were used to evaluate the oxidative stress of TiO(2) (at 0.001, 0.01, 0.1, 1, and 10 μg mL(-1)) mixed with PbAc (1 μg mL(-1)) on L02 cells without photoactivation. Compared with the negative control (1‰ dimethyl sulfoxide), TiO(2) mixed with PbAc induced increased release of ROS (at 0.001, 0.01, 0.1, 1, 10 μg mL(-1) TiO(2)), intracellular SOD activity (at 0.1 and 0.01 μg mL(-1) TiO(2)), GSH levels (at 0.01-1 μg mL(-1) TiO(2)), 8-OHdG levels (at 1 and 10 μg mL(-1) TiO(2)), OGG1 expression (at 0.001-1 μg mL(-1) TiO(2)), and cytotoxicity (at 0.1, 1, and 10 μg mL(-1) TiO(2)) in L02 cells. There were no significant changes in ROS, GSH, SOD, 8-OHdG, or OGG1 levels when L02 cells were treated with TiO(2) alone or PbAc alone. These findings indicate that TiO(2) and PbAc in combination induce cytotoxicity and oxidative stress in L02 cells in the absence of photoactivation.Copyright © 2011 Wiley Periodicals, Inc.DuHairongHMOE Key Lab of Environment and Health, Institute of Environmental Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.ZhuXiaolingXFanChuangangCXuSongSWangYoujieYZhouYikaiYengJournal ArticleResearch Support, Non-U.S. Gov't20110120
United StatesEnviron Toxicol1008853571520-40810Organometallic Compounds0Reactive Oxygen Species15FIX9V2JPtitanium dioxide88847-89-68-oxo-7-hydrodeoxyguanosineD1JT611TNETitaniumEC 1.15.1.1Superoxide DismutaseEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanG9481N71RODeoxyguanosineGAN16C9B8OGlutathioneRX077P88RYlead acetateIMCell LineCell SurvivalDNA GlycosylasesmetabolismDeoxyguanosineanalogs & derivativesanalysisGlutathionemetabolismHepatocytesdrug effectsmetabolismHumansNanoparticlestoxicityOrganometallic CompoundstoxicityOxidative Stressdrug effectsReactive Oxygen SpeciesmetabolismSuperoxide DismutasemetabolismTitaniumtoxicity
20100706201010272010110420111226020111226020135260ppublish2125432310.1002/tox.20682
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1437-160X3252012MayRheumatology internationalRheumatol. Int.Association of the C-285T and A5954G polymorphisms in the DNA repair gene OGG1 with the susceptibility of rheumatoid arthritis.1165-910.1007/s00296-010-1738-1Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. Previous study indicated that DNA repair system was involved in the pathology of RA. In this study, we investigated the association of two 8-oxoguanine glycosylase 1 (OGG1) gene polymorphisms (rs159153 and rs3219008) with the susceptibility to RA in 384 Taiwanese individuals (192 patients with RA and 192 controls). Our data showed that statistically significant difference in genotype frequency distributions was found at rs3219008 SNP between patients with RA and control groups (P = 5.6E-0.5). Our data also indicated that individuals with the AG genotype at rs3219008 SNP may have a higher risk of developing RA. We did not observe any statistically significant association of OGG1 haplotype frequencies (rs159153 and rs3219008) with RA progression. The study suggested that OGG1 polymorphisms (rs159153 and rs3219008) are associated with RA progression and that these may be used as molecular markers of RA.ChenShih-YinSYGenetic Center, Department of Medical Research, China Medical University Hospital, Graduate Institute of Chinese Medical Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan.WanLeiLHuangChung-MingCMHuangYu-ChuenYCSheuJim Jinn-ChyuanJJLinYing-JuYJLiuShih-PingSPLanYu-ChingYCLaiChih-HoCHLinCheng-WenCWTsaiChang-HaiCHTsaiFuu-JenFJengJournal ArticleResearch Support, Non-U.S. Gov't20110121
GermanyRheumatol Int82068850172-81720Genetic MarkersEC 3.2.2.-DNA GlycosylasesEC 3.2.2.-oxoguanine glycosylase 1, humanIMJ Hum Genet. 2001;46(8):471-711501945Arthritis Rheum. 1991 Jul;34(7):822-302059230J Clin Invest. 2008 Jul;118(7):2516-2518521188FASEB J. 2003 Jul;17(10):1195-21412832285N Engl J Med. 1990 May 3;322(18):1277-892271017Nat Genet. 2002 Dec;32(4):650-412426569FASEB J. 2005 Feb;19(2):290-215677345J Rheumatol. 1995 Aug;22(8):1450-47473464Clin Exp Rheumatol. 2008 Jul-Aug;26(4):632-718799095J Exp Med. 2009 Jun 8;206(6):1435-4919451263Hum Genet. 2003 Jan;112(1):34-4112483297Arthritis Rheum. 1997 Feb;40(2):341-519041946Bioinformatics. 2005 Jan 15;21(2):263-515297300Nat Genet. 2003 Aug;34(4):395-40212833157J Rheumatol. 2008 Nov;35(11):2113-819004052J Rheumatol. 1990 Feb;17(2):127-332181124Hum Genet. 2007 Apr;121(2):233-4217203305Trends Mol Med. 2003 Oct;9(10):405-714557050Arthritis Rheum. 1988 Mar;31(3):315-243358796DNA Cell Biol. 2009 Nov;28(11):579-8819630534Cell. 1996 May 3;85(3):307-108616886Springer Semin Immunopathol. 1998;20(1-2):5-229836366Clin Exp Rheumatol. 2004 Mar-Apr;22(2):219-2215083890Am J Hum Genet. 1995 Jul;57(1):150-97611283Mutat Res. 2005 Jun 3;573(1-2):136-5115829243Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):811-516614128Arthritis, RheumatoidenzymologygeneticsmortalityCase-Control StudiesChi-Square DistributionDNA GlycosylasesgeneticsDNA RepairDisease ProgressionGene FrequencyGenetic MarkersGenetic Predisposition to DiseaseHaplotypesHumansKaplan-Meier EstimateLogistic ModelsOdds RatioPhenotypePolymorphism, Single NucleotideRisk AssessmentRisk FactorsTaiwan
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diff --git a/retracted pathology articles b/retracted pathology articles index 23c45b6..143e41a 100644 --- a/retracted pathology articles +++ b/retracted pathology articles @@ -1 +1,12 @@ -retracted pathology articles \ No newline at end of file +retracted pathology articles + + +Retraction Watch Database User Guide + +https://retractionwatch.com/retraction-watch-database-user-guide/ + + +National Library of Medicine (NLM) and Retracted Publications + + +https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0027066/ \ No newline at end of file