B1 SOX Coordinate Cell Specification with Patterning and Morphogenesis in the Early Zebrafish Embryo
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"B1 SOX coordinate cell specification with patterning and morphogenesis in the early zebrafish embryo", "type"=>"journal", "authors"=>[{"first_name"=>"Yuichi", "last_name"=>"Okuda", "scopus_author_id"=>"36239879100"}, {"first_name"=>"Eri", "last_name"=>"Ogura", "scopus_author_id"=>"7003780498"}, {"first_name"=>"Hisato", "last_name"=>"Kondoh", "scopus_author_id"=>"7101792028"}, {"first_name"=>"Yusuke", "last_name"=>"Kamachi", "scopus_author_id"=>"7004374984"}], "year"=>2010, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"358963188", "sgr"=>"77953184046", "pmid"=>"20463883", "scopus"=>"2-s2.0-77953184046", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "doi"=>"10.1371/journal.pgen.1000936", "issn"=>"15537390"}, "id"=>"06840c55-8def-3599-9fa1-3b1940e3c040", "abstract"=>"The B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 sox genes in zebrafish. Only the quadruple knockdown of the four B1 sox genes sox2/3/19a/19b resulted in very severe developmental abnormalities, confirming that the B1 sox genes are functionally redundant. We characterized the sox2/3/19a/19b quadruple knockdown embryos in detail by examining the changes in gene expression through in situ hybridization, RT-PCR, and microarray analyses. Importantly, these phenotypic analyses revealed that the B1 SOX proteins regulate the following distinct processes: (1) early dorsoventral patterning by controlling bmp2b/7; (2) gastrulation movements via the regulation of pcdh18a/18b and wnt11, a non-canonical Wnt ligand gene; (3) neural differentiation by regulating the Hes-class bHLH gene her3 and the proneural-class bHLH genes neurog1 (positively) and ascl1a (negatively), and regional transcription factor genes, e.g., hesx1, zic1, and rx3; and (4) neural patterning by regulating signaling pathway genes, cyp26a1 in RA signaling, oep in Nodal signaling, shh, and mdkb. Chromatin immunoprecipitation analysis of the her3, hesx1, neurog1, pcdh18a, and cyp26a1 genes further suggests a direct regulation of these genes by B1 SOX. We also found an interesting overlap between the early phenotypes of the B1 sox quadruple knockdown embryos and the maternal-zygotic spg embryos that are devoid of pou5f1 activity. These findings indicate that the B1 SOX proteins control a wide range of developmental regulators in the early embryo through partnering in part with Pou5f1 and possibly with other factors, and suggest that the B1 sox functions are central to coordinating cell fate specification with patterning and morphogenetic processes occurring in the early embryo.", "link"=>"http://www.mendeley.com/research/b1-sox-coordinate-cell-specification-patterning-morphogenesis-early-zebrafish-embryo", "reader_count"=>84, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>8, "Student > Doctoral Student"=>5, "Researcher"=>20, "Student > Ph. D. Student"=>21, "Student > Postgraduate"=>2, "Student > Master"=>10, "Other"=>1, "Student > Bachelor"=>12, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>8, "Student > Doctoral Student"=>5, "Researcher"=>20, "Student > Ph. D. Student"=>21, "Student > Postgraduate"=>2, "Student > Master"=>10, "Other"=>1, "Student > Bachelor"=>12, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>14, "Mathematics"=>1, "Agricultural and Biological Sciences"=>65, "Medicine and Dentistry"=>2, "Physics and Astronomy"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>65}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>14}, "Mathematics"=>{"Mathematics"=>1}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Argentina"=>1, "United States"=>2, "Brazil"=>1, "Italy"=>1, "United Kingdom"=>2, "Chile"=>3, "France"=>1, "Germany"=>1}, "group_count"=>1}

CrossRef

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/77953184046"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/77953184046?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77953184046&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=77953184046&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/77953184046", "dc:identifier"=>"SCOPUS_ID:77953184046", "eid"=>"2-s2.0-77953184046", "dc:title"=>"B1 SOX coordinate cell specification with patterning and morphogenesis in the early zebrafish embryo", "dc:creator"=>"Okuda Y.", "prism:publicationName"=>"PLoS Genetics", "prism:issn"=>"15537390", "prism:eIssn"=>"15537404", "prism:volume"=>"6", "prism:issueIdentifier"=>"5", "prism:pageRange"=>"36", "prism:coverDate"=>"2010-05-01", "prism:coverDisplayDate"=>"May 2010", "prism:doi"=>"10.1371/journal.pgen.1000936", "citedby-count"=>"63", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Osaka University", "affiliation-city"=>"Suita", "affiliation-country"=>"Japan"}], "pubmed-id"=>"20463883", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "source-id"=>"4000151808", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosgenetics%2Farticle%3Fid%3D10.1371%252Fjournal.pgen.1000936", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"5", "year"=>"2010", "pdf_views"=>"116", "xml_views"=>"5", "html_views"=>"390"}
  • {"month"=>"6", "year"=>"2010", "pdf_views"=>"49", "xml_views"=>"0", "html_views"=>"123"}
  • {"month"=>"7", "year"=>"2010", "pdf_views"=>"25", "xml_views"=>"0", "html_views"=>"62"}
  • {"month"=>"8", "year"=>"2010", "pdf_views"=>"27", "xml_views"=>"0", "html_views"=>"59"}
  • {"month"=>"9", "year"=>"2010", "pdf_views"=>"29", "xml_views"=>"1", "html_views"=>"89"}
  • {"month"=>"10", "year"=>"2010", "pdf_views"=>"23", "xml_views"=>"1", "html_views"=>"53"}
  • {"month"=>"11", "year"=>"2010", "pdf_views"=>"31", "xml_views"=>"0", "html_views"=>"62"}
  • {"month"=>"12", "year"=>"2010", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"1", "year"=>"2011", "pdf_views"=>"20", "xml_views"=>"2", "html_views"=>"44"}
  • {"month"=>"2", "year"=>"2011", "pdf_views"=>"16", "xml_views"=>"1", "html_views"=>"41"}
  • {"month"=>"3", "year"=>"2011", "pdf_views"=>"31", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"4", "year"=>"2011", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"5", "year"=>"2011", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"23"}
  • {"month"=>"6", "year"=>"2011", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"68"}
  • {"month"=>"7", "year"=>"2011", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"27"}
  • {"month"=>"8", "year"=>"2011", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"27"}
  • {"month"=>"9", "year"=>"2011", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"49"}
  • {"month"=>"10", "year"=>"2011", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"56"}
  • {"month"=>"11", "year"=>"2011", "pdf_views"=>"12", "xml_views"=>"2", "html_views"=>"32"}
  • {"month"=>"12", "year"=>"2011", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"49"}
  • {"month"=>"1", "year"=>"2012", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"2", "year"=>"2012", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"74"}
  • {"month"=>"3", "year"=>"2012", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"41"}
  • {"month"=>"4", "year"=>"2012", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"45"}
  • {"month"=>"5", "year"=>"2012", "pdf_views"=>"22", "xml_views"=>"1", "html_views"=>"47"}
  • {"month"=>"6", "year"=>"2012", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"36"}
  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"63"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"12", "xml_views"=>"6", "html_views"=>"71"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"53"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"43"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"15", "xml_views"=>"1", "html_views"=>"64"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"55"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"2", "html_views"=>"177"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"60"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"53"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"71", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"28", "xml_views"=>"0", "html_views"=>"62"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"49"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"51"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"15", "xml_views"=>"2", "html_views"=>"132"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"15", "xml_views"=>"1", "html_views"=>"185"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"78"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"127"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"2", "html_views"=>"223"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"190"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"170"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"200"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"262"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"198"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"258"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"2", "html_views"=>"253"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"15", "xml_views"=>"3", "html_views"=>"123"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"81"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"64"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"33"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"41"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"35"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"78"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"28", "xml_views"=>"1", "html_views"=>"80"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"60"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"52"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"78"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"30"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"2", "html_views"=>"38"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"2", "html_views"=>"36"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"27", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"42"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"3", "html_views"=>"12"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"15"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"8"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/423193", "https://ndownloader.figshare.com/files/423230", "https://ndownloader.figshare.com/files/423272", "https://ndownloader.figshare.com/files/423298", "https://ndownloader.figshare.com/files/423332", "https://ndownloader.figshare.com/files/423357", "https://ndownloader.figshare.com/files/423380", "https://ndownloader.figshare.com/files/423403", "https://ndownloader.figshare.com/files/423511", "https://ndownloader.figshare.com/files/423526", "https://ndownloader.figshare.com/files/423542", "https://ndownloader.figshare.com/files/423623", "https://ndownloader.figshare.com/files/423675", "https://ndownloader.figshare.com/files/423732"], "description"=>"<div><p>The B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 <em>sox</em> genes in zebrafish. Only the quadruple knockdown of the four B1 <em>sox</em> genes <em>sox2/3/19a/19b</em> resulted in very severe developmental abnormalities, confirming that the B1 <em>sox</em> genes are functionally redundant. We characterized the <em>sox2/3/19a/19b</em> quadruple knockdown embryos in detail by examining the changes in gene expression through in situ hybridization, RT–PCR, and microarray analyses. Importantly, these phenotypic analyses revealed that the B1 SOX proteins regulate the following distinct processes: (1) early dorsoventral patterning by controlling <em>bmp2b/7</em>; (2) gastrulation movements via the regulation of <em>pcdh18a/18b</em> and <em>wnt11</em>, a non-canonical Wnt ligand gene; (3) neural differentiation by regulating the <em>Hes</em>-class bHLH gene <em>her3</em> and the proneural-class bHLH genes <em>neurog1</em> (positively) and <em>ascl1a</em> (negatively), and regional transcription factor genes, e.g., <em>hesx1</em>, <em>zic1</em>, and <em>rx3</em>; and (4) neural patterning by regulating signaling pathway genes, <em>cyp26a1</em> in RA signaling, <em>oep</em> in Nodal signaling, <em>shh</em>, and <em>mdkb</em>. Chromatin immunoprecipitation analysis of the <em>her3</em>, <em>hesx1</em>, <em>neurog1</em>, <em>pcdh18a</em>, and <em>cyp26a1</em> genes further suggests a direct regulation of these genes by B1 SOX. We also found an interesting overlap between the early phenotypes of the B1 <em>sox</em> quadruple knockdown embryos and the maternal-zygotic <em>spg</em> embryos that are devoid of <em>pou5f1</em> activity. These findings indicate that the B1 SOX proteins control a wide range of developmental regulators in the early embryo through partnering in part with Pou5f1 and possibly with other factors, and suggest that the B1 <em>sox</em> functions are central to coordinating cell fate specification with patterning and morphogenetic processes occurring in the early embryo.</p></div>", "links"=>[], "tags"=>["b1", "sox", "specification", "patterning", "morphogenesis", "zebrafish", "embryo"], "article_id"=>143578, "categories"=>["Genetics", "Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Yuichi Okuda", "Eri Ogura", "Hisato Kondoh", "Yusuke Kamachi"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000936.s001", "https://dx.doi.org/10.1371/journal.pgen.1000936.s002", "https://dx.doi.org/10.1371/journal.pgen.1000936.s003", "https://dx.doi.org/10.1371/journal.pgen.1000936.s004", "https://dx.doi.org/10.1371/journal.pgen.1000936.s005", "https://dx.doi.org/10.1371/journal.pgen.1000936.s006", "https://dx.doi.org/10.1371/journal.pgen.1000936.s007", "https://dx.doi.org/10.1371/journal.pgen.1000936.s008", "https://dx.doi.org/10.1371/journal.pgen.1000936.s009", "https://dx.doi.org/10.1371/journal.pgen.1000936.s010", "https://dx.doi.org/10.1371/journal.pgen.1000936.s011", "https://dx.doi.org/10.1371/journal.pgen.1000936.s012", "https://dx.doi.org/10.1371/journal.pgen.1000936.s013", "https://dx.doi.org/10.1371/journal.pgen.1000936.s014"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/B1_SOX_Coordinate_Cell_Specification_with_Patterning_and_Morphogenesis_in_the_Early_Zebrafish_Embryo/143578", "title"=>"B1 SOX Coordinate Cell Specification with Patterning and Morphogenesis in the Early Zebrafish Embryo", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-05-06 00:59:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/850135"], "description"=>"<p>Bright-field images of live embryos observed at the indicated time points. All are lateral views. (A) Uninjected control (Ctr) embryos. (B) Single knockdowns of <i>sox2/3/19a/19b</i>. A 1∶1 mixture of two MOs (0.9 ng each) targeting one of the four B1 <i>sox</i> genes was injected for a single KD. The percentage of embryos in the same morphological class is indicated in each panel. (C) Triple knockdowns of <i>sox2/3/19a/19b</i>. A mixture of indicated combinations of MOs (i.e., a mixture of six MOs, 5.4 ng in total) was used to simultaneously knockdown three out of the four B1 <i>sox</i> genes. The major classes of morphological defects are shown with the percentage of occurrence. The remaining embryos showed either milder or more severe defects. (D) Uninjected control embryos (a–f) and <i>sox2/3/19a/19b</i> quadruple knockdown (QKD) embryos injected with a mixture of MOs targeting the four B1 <i>sox</i> genes (i.e., a mixture of eight MOs, 7.2 ng in total) (a’–f’). The QKD caused very severe developmental abnormalities: a delay in epiboly, a shortened anterior-posterior axis, and impairment of CNS development (61%). The remaining embryos showed either milder defects (7%), more severe defects (24%) or lethality (8%). The aberrant movement of the anterior prechordal plate (arrows in d and e’) suggests a decreased adhesion of ectodermal cells as well as defects in convergence and extension movements in the QKD embryos. The broken lines (e’ and f’) indicate the dorsal trunk regions where cell dissociation was observed. (g, h) Dose-dependent effects of the MOs used for QKD were examined by injecting reduced amounts of the mixture of MOs targeting the four B1 <i>sox</i> genes (3.6 ng in total [g] and 1.8 ng in total [h]). (i) As a negative control, a mixture of 5-base-mismatch control MOs (i.e., a mixture of eight 5mis-MOs, 7.2 ng in total) was injected. (j) The coinjection of a p53-MO (2 ng) had no impact on the neural defects in the QKD embryos.</p>", "links"=>[], "tags"=>["quadruple", "knockdowns"], "article_id"=>520580, "categories"=>["Genetics", "Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Yuichi Okuda", "Eri Ogura", "Hisato Kondoh", "Yusuke Kamachi"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000936.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Single_triple_and_quadruple_knockdowns_of_sox2_3_19a_19b_/520580", "title"=>"Single, triple, and quadruple knockdowns of <i>sox2/3/19a/19b</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:09:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/850323"], "description"=>"<p>(A, B) Uninjected control (Ctr) embryos (A) and the QKD embryos (B). Live embryos were observed at 10–11 (a), 15–16 (b) and 30–31 (c) hpf. Expression of <i>hesx1</i>, <i>pax2a</i> and <i>hoxb1b</i> (d), <i>dlx3b</i>, <i>hgg1</i> and <i>ntl</i> (e), and <i>neurog1</i> (f) was visualized by whole-mount in situ hybridization. Lateral views (a–c); dorsal views with anterior to the top (d–f). (C) The QKD phenotype is similarly rescued by an exogenous supply of any B1 <i>sox</i> mRNA. The MOs for QKD were coinjected with the indicated mRNAs. In the B1 <i>sox</i> mRNA-coinjected embryos, the expression of <i>hesx1</i>, <i>dlx3b</i> and <i>nuerog1</i> was recovered; patterning of the neural plate marked by <i>pax2a</i> and <i>hoxb1b</i> was normalized; and the expression patterns of <i>hgg1</i>, <i>ntl</i> and <i>dlx3b</i> reflecting C&E movements were also restored. Blue bracket, gap between the <i>hgg1</i> and <i>ntl</i> expression domains; white dotted line, neural plate border. (D) Recovery of the AP axis elongation in QKD embryos injected with one of the B1 <i>sox</i> mRNAs. The length of the embryos at 15–16 hpf along the AP axis between the arrowheads (Ab, Bb, Cb) was measured for the uninjected control (Ctr) (n = 7), the QKD (n = 9) and QKD with B1 <i>sox</i> mRNA injection (<i>sox2</i>, n = 9; <i>sox3</i>, n = 6; <i>sox19a</i>, n = 7; <i>sox19b</i>, n = 6). The average AP axis lengths with standard errors are shown.</p>", "links"=>[], "tags"=>["qkd", "phenotype", "exogenous", "b1"], "article_id"=>520774, "categories"=>["Genetics", "Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Yuichi Okuda", "Eri Ogura", "Hisato Kondoh", "Yusuke Kamachi"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000936.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rescue_of_the_QKD_phenotype_by_exogenous_B1_sox_mRNAs_/520774", "title"=>"Rescue of the QKD phenotype by exogenous B1 <i>sox</i> mRNAs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:12:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/850537"], "description"=>"<p>Comparison of the gene expression profiles between uninjected control (Ctr) and QKD embryos. (A) Ventral expansion of early neural gene expression (<i>otx2</i> [a], <i>zic2b</i> [b] and <i>sox2/3/19a/19b</i> [e–h]), and reduced expression of non-neural ectoderm marker genes (<i>foxi1</i> [c] and <i>dlx3b</i> [d]) at 75%E. (B) Altered expression patterns of neural genes at the tailbud and 3-somite stages. The expression domains of <i>gbx1</i> (c–e), <i>eng2a</i> (f) and <i>hoxb1b</i> (g, h) were anterolaterally shifted, which encompass the <i>otx2</i> expression domain (a, b). (C) Defective neural development revealed by the loss of expression of neural marker genes, <i>hesx1</i> (a), <i>zic1</i> (b), <i>rx3</i> (c), <i>nkx1.2la</i> (d) and <i>krox20</i> (e). Residual expression of <i>krox20</i> was observed in r5-derived neural crest cells. (D) Wider mesoderm structures with a shortened axis revealed by mesodermal marker genes, <i>ntl</i> (a) and <i>myod1</i> (b). The stages and embryo orientations are shown in each panel: E, epiboly stage; S, somite stage; L, lateral view with dorsal to the right; D, dorsal view with anterior to the top.</p>", "links"=>[], "tags"=>["embryo", "neural", "movements", "qkd"], "article_id"=>520983, "categories"=>["Genetics", "Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Yuichi Okuda", "Eri Ogura", "Hisato Kondoh", "Yusuke Kamachi"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000936.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Defects_in_embryo_patterning_early_neural_development_and_C_amp_E_movements_in_the_QKD_embryos_/520983", "title"=>"Defects in embryo patterning, early neural development, and C&E movements in the QKD embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:16:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/850732"], "description"=>"<p>(A) DV patterning defects involving the reduced expression of <i>bmp</i> genes. Expression of <i>bmp2b/7/4</i> (a–g) and the Bmp downstream genes <i>gata2</i>, <i>szl</i> and <i>eve1</i> (h–j) is reduced in the QKD embryos. (k–s) Expression of the Bmp antagonist genes, <i>chd</i> and <i>nog1</i>, and the organizer gene <i>gsc</i>. All are lateral views with dorsal to the right. (B) The BMP downstream genes are restored by an exogenous supply of <i>bmp2b/7</i>. Embryos were injected together with the MOs for QKD and a mixture of <i>bmp2b/7</i> mRNAs (20 or 40 pg each) and subjected to RT-PCR analysis at the shield stage. <i>bactin1</i> was used as an RT-PCR control. (C) Decreased expression of genes regulating C&E movements in the QKD embryos. Temporal expression profiles of the indicated genes in the uninjected control and QKD embryos from the sphere to 3-somite stages were determined by RT-PCR. Expression of non-canonical <i>wnt</i> genes is reduced in the QKD embryos. Expression of <i>pcdh18a</i>/<i>18b</i> is also reduced in the QKD embryos, whereas <i>cdh1</i>, which is known to be involved in epiboly, is expressed at normal levels. <i>bactin1</i> was used as an RT-PCR control.</p>", "links"=>[], "tags"=>["dv", "patterning", "gastrulation", "movements", "qkd"], "article_id"=>521180, "categories"=>["Genetics", "Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Yuichi Okuda", "Eri Ogura", "Hisato Kondoh", "Yusuke Kamachi"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000936.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Defects_in_DV_patterning_and_gastrulation_movements_in_the_QKD_embryos_/521180", "title"=>"Defects in DV patterning and gastrulation movements in the QKD embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:19:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/850917"], "description"=>"<p>(A) Altered expression of genes involved in neural differentiation. RT-PCR analysis of the indicated genes was performed as described in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000936#pgen-1000936-g004\" target=\"_blank\">Figure 4C</a>. (B) Effects of B1 <i>sox</i> QKD on neural bHLH gene expression. The <i>her3</i> expression is totally lost in the QKD embryos (a–c), whereas <i>ascl1a</i> is transiently upregulated at 75%E in a broad area of the neuroectoderm (d–f). (C) The loss of <i>cyp26a1</i> expression in the anterior neuroectoderm (a, b) and evidence of hindbrain patterning defects: expansion of <i>hoxb1a</i> expression (c) and a severe reduction of <i>mafba</i> expression (d). (D) The loss of expression of <i>oep</i> and <i>shha/b</i> in the neuroectoderm of the QKD embryos. (a–d) In the QKD embryos, the expression of <i>oep</i> is lost in the ectoderm at the shield stage (b) and the neuroectoderm at the 75%E and tailbud stages (c, d) (marked by open arrowheads in b’–d’), whereas its initial zygotic expression (a) and mesodermal expression (b–d) are maintained (closed arrowheads in a’–d’). (e) <i>ndr2</i> is also expressed in the QKD mesoderm at normal levels. (f–i) The expression of <i>shha/b</i> in the neuroectoderm is lost (marked by open arrowheads in f’–i’), whereas that in the mesoderm is retained (closed arrowheads in f’–i’). (E) The loss of <i>mdkb</i> expression in the neuroectoderm and severe reduction of <i>foxd3</i> expression in the neural crest cells of QKD embryos.</p>", "links"=>[], "tags"=>["neural", "qkd"], "article_id"=>521368, "categories"=>["Genetics", "Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Yuichi Okuda", "Eri Ogura", "Hisato Kondoh", "Yusuke Kamachi"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000936.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impairment_of_neural_development_in_the_QKD_embryos_/521368", "title"=>"Impairment of neural development in the QKD embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:22:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/851075"], "description"=>"<p>(A) Schematic representation of the protein structures of SOX3, SOX3-VP16 and SOX3-EnR. Dominant activator and repressor forms of SOX3 were constructed by fusing the VP16 activation and Engrailed repression (EnR) domains, respectively, to truncated SOX3(1–156 aa). (B) Gene expression responses to SOX3, SOX3-VP16 or SOX3-EnR under QKD conditions. mRNAs of <i>sox3</i>, <i>sox3-VP16</i> and <i>sox3-EnR</i> (20 pg) were individually injected with the MOs for QKD and gene expression responses were examined by RT-PCR. The exogenous supply of either SOX3 or SOX3-VP16 but not by SOX3-EnR recovered expression of genes that were downregulated (<i>bmp2b/7</i>, <i>pcdh18a/18b</i>, <i>her3</i>, <i>hesx1</i> and <i>zic1</i>) in the QKD embryos and also suppressed expression of genes that were upregulated (<i>stmn2a</i> and <i>ascl1a</i>). <i>bactin1</i> was used as an RT-PCR control. (C) Partial rescue by SOX3-VP16 and strengthening by SOX3-EnR of the morphological phenotypes of the QKD embryos. Live embryo images at 10–11, 15–16, and 30–31 hpf were observed. SOX3-VP16-injected embryos showed a rather ventralized phenotype. Embryos coinjected with SOX3-EnR died during late segmentation stages. All are lateral views.</p>", "links"=>[], "tags"=>["actions", "b1", "sox"], "article_id"=>521529, "categories"=>["Genetics", "Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Yuichi Okuda", "Eri Ogura", "Hisato Kondoh", "Yusuke Kamachi"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000936.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regulatory_actions_of_the_B1_SOX_proteins_/521529", "title"=>"Regulatory actions of the B1 SOX proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:25:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/851208"], "description"=>"<p>(A) ChIP analysis showing direct association of B1 SOX with regulatory sequences of the downstream genes. (a) Potential binding sites for SOX and POU within the analyzed genomic regions are schematically shown. (b) ChIP-PCR analysis using anti-SOX2 antibody. ChIP experiments were performed using zebrafish embryos at the 70–80%E and tailbud to 2-somite stages. ChIP-PCR analysis using anti-SOX2 antibody that weakly cross-reacts with SOX3/19A/19B revealed specific binding of B1 SOX to the regulatory sequences of the <i>hesx1</i>, <i>her3</i>, <i>pcdh18a</i>, <i>cyp26a1</i> and <i>neurog1</i> genes in the zebrafish embryo. <i>bactin2</i> was used as a negative control. (B) B1 SOX-dependent activities of the regulatory sequences of <i>hesx1</i>, <i>cyp26a1</i> and <i>pcdh18a</i>. (a) The Venusluc fusion reporter (Venus plus firefly luciferase) constructs containing either of the promoters for <i>hesx1</i> or <i>cyp26a1</i> or the upstream conserved sequence of <i>pcdh18a</i> with the HSV TK promoter are schematically shown. (b) The Venusluc reporters were injected into embryos with or without the MOs for QKD together with the reference vector TK-<i>Renilla</i> luciferase. More than 20 injected embryos per sample were collected at the tailbud stage, and luciferase assays were performed. The normalized luciferase activity generated by TK-Venusluc was arbitrarily assigned a value of 1. Data are shown as the average values of four independent injection experiments with standard errors.</p>", "links"=>[], "tags"=>["targets", "b1", "sox", "proteins", "zebrafish"], "article_id"=>521651, "categories"=>["Genetics", "Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Yuichi Okuda", "Eri Ogura", "Hisato Kondoh", "Yusuke Kamachi"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000936.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Direct_regulatory_targets_of_the_B1_SOX_proteins_in_the_zebrafish_embryo_/521651", "title"=>"Direct regulatory targets of the B1 SOX proteins in the zebrafish embryo.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:27:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/851312"], "description"=>"<p>The B1 <i>sox</i> expression domains are schematically illustrated at the top. The B1 SOX-downstream genes that were identified in this study are shown with possible time windows for regulation. The major downstream genes of B1 SOX were found to be developmental transcription factor genes (indicated in blue), signaling pathway genes (red) and cell adhesion molecule genes (green). Our data indicate that, in these regulations, B1 SOX primarily act as activators and appear to indirectly repress several target genes through the activation of hypothetical repressors. A direct regulation of the <i>pcdh18a</i>, <i>her3</i>, <i>hesx1</i>, <i>cyp26a1</i> and <i>neurog1</i> genes by B1 SOX is suggested by our ChIP analysis (indicated by blue arrows). The developmental effects of the regulation by B1 SOX are indicated on the right.</p>", "links"=>[], "tags"=>["embryonic", "stage-dependent", "b1"], "article_id"=>521757, "categories"=>["Genetics", "Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Yuichi Okuda", "Eri Ogura", "Hisato Kondoh", "Yusuke Kamachi"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000936.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_embryonic_stage_dependent_target_gene_regulation_by_B1_SOX_/521757", "title"=>"Summary of embryonic stage-dependent target gene regulation by B1 SOX.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:29:17"}

PMC Usage Stats | Further Information

  • {"month"=>"5", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"65", "year"=>"2010", "pdf"=>"35", "unique-ip"=>"56", "figure"=>"28", "scanned-summary"=>"0", "supp-data"=>"11"}
  • {"scanned-page-browse"=>"0", "month"=>"6", "cited-by"=>"0", "abstract"=>"4", "full-text"=>"53", "unique-ip"=>"52", "pdf"=>"29", "year"=>"2010", "figure"=>"21", "scanned-summary"=>"0", "supp-data"=>"29"}
  • {"month"=>"7", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"30", "year"=>"2010", "pdf"=>"14", "unique-ip"=>"24", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"scanned-page-browse"=>"0", "month"=>"8", "cited-by"=>"0", "abstract"=>"4", "full-text"=>"39", "unique-ip"=>"40", "pdf"=>"35", "year"=>"2010", "figure"=>"15", "scanned-summary"=>"0", "supp-data"=>"6"}
  • {"month"=>"9", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"53", "year"=>"2010", "pdf"=>"34", "unique-ip"=>"44", "figure"=>"15", "scanned-summary"=>"0", "supp-data"=>"1"}
  • {"scanned-page-browse"=>"0", "month"=>"10", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"49", "unique-ip"=>"506", "pdf"=>"1684", "year"=>"2010", "figure"=>"22", "scanned-summary"=>"0", "supp-data"=>"9"}
  • {"month"=>"11", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"29", "year"=>"2010", "pdf"=>"13", "unique-ip"=>"35", "figure"=>"12", "scanned-summary"=>"0", "supp-data"=>"4"}
  • {"scanned-page-browse"=>"0", "month"=>"12", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"22", "unique-ip"=>"24", "pdf"=>"9", "year"=>"2010", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"3"}
  • {"month"=>"1", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"34", "year"=>"2011", "pdf"=>"24", "unique-ip"=>"28", "figure"=>"20", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"scanned-page-browse"=>"0", "month"=>"2", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"21", "unique-ip"=>"29", "pdf"=>"8", "year"=>"2011", "figure"=>"17", "scanned-summary"=>"0", "supp-data"=>"1"}
  • {"month"=>"3", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"17", "year"=>"2011", "pdf"=>"9", "unique-ip"=>"21", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"4", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"15", "unique-ip"=>"24", "pdf"=>"12", "year"=>"2011", "figure"=>"19", "scanned-summary"=>"0", "supp-data"=>"3"}
  • {"month"=>"5", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"28", "year"=>"2011", "pdf"=>"11", "unique-ip"=>"28", "figure"=>"20", "scanned-summary"=>"0", "supp-data"=>"3"}
  • {"scanned-page-browse"=>"0", "month"=>"6", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"16", "unique-ip"=>"19", "pdf"=>"7", "year"=>"2011", "figure"=>"14", "scanned-summary"=>"0", "supp-data"=>"1"}
  • {"month"=>"7", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"19", "year"=>"2011", "pdf"=>"6", "unique-ip"=>"16", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"8", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"20", "unique-ip"=>"23", "pdf"=>"5", "year"=>"2011", "figure"=>"18", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"9", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"16", "year"=>"2011", "pdf"=>"6", "unique-ip"=>"18", "figure"=>"11", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"10", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"12", "unique-ip"=>"17", "pdf"=>"6", "year"=>"2011", "figure"=>"21", "scanned-summary"=>"0", "supp-data"=>"4"}
  • {"month"=>"11", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"21", "year"=>"2011", "pdf"=>"14", "unique-ip"=>"17", "figure"=>"12", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"12", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"13", "unique-ip"=>"13", "pdf"=>"6", "year"=>"2011", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"4"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"13", "unique-ip"=>"18", "pdf"=>"19", "year"=>"2012", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"1"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"22", "year"=>"2012", "pdf"=>"4", "unique-ip"=>"16", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"8"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"15", "unique-ip"=>"22", "pdf"=>"17", "year"=>"2012", "figure"=>"17", "scanned-summary"=>"0", "supp-data"=>"14"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"14", "year"=>"2012", "pdf"=>"7", "unique-ip"=>"17", "figure"=>"15", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"15", "unique-ip"=>"13", "pdf"=>"5", "year"=>"2012", "figure"=>"11", "scanned-summary"=>"0", "supp-data"=>"1"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"11", "year"=>"2012", "pdf"=>"2", "unique-ip"=>"15", "figure"=>"10", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"3", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
  • {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"0", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"20", "full-text"=>"24", "pdf"=>"11", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"8", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"8", "pdf"=>"2", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"18", "full-text"=>"22", "pdf"=>"7", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"17", "full-text"=>"10", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"14", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"10", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"13", "full-text"=>"9", "pdf"=>"5", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"22", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"23", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"10", "cited-by"=>"1", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"11", "full-text"=>"7", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"16", "full-text"=>"18", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"14", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"10", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"2", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"11", "full-text"=>"15", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"5", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"13", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}

Relative Metric

{"start_date"=>"2010-01-01T00:00:00Z", "end_date"=>"2010-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[288, 576, 733, 867, 984, 1087, 1182, 1267, 1346, 1424, 1501, 1577, 1646, 1711, 1778, 1841, 1908, 1970, 2034, 2102, 2162, 2227, 2296, 2359, 2422, 2482, 2550, 2610, 2679, 2747, 2820, 2887, 2955, 3009, 3067, 3130, 3200, 3257, 3322, 3379, 3443, 3507, 3571, 3632, 3683, 3753, 3822, 3877]}, {"subject_area"=>"/Biology and life sciences/Anatomy", "average_usage"=>[275, 532, 682, 800, 904, 1008, 1103, 1194, 1265, 1340, 1412, 1479, 1546, 1610, 1672, 1736, 1793, 1861, 1922, 1978, 2032, 2094, 2155, 2220, 2279, 2333, 2395, 2481, 2543, 2601, 2669, 2722, 2767, 2826, 2882, 2942, 3006, 3054, 3110, 3176, 3253, 3313, 3367, 3422, 3472, 3539, 3593, 3655, 3703]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[265, 560, 722, 863, 978, 1083, 1172, 1261, 1345, 1428, 1488, 1559, 1630, 1701, 1764, 1840, 1899, 1965, 2028, 2088, 2150, 2211, 2270, 2348, 2410, 2461, 2531, 2598, 2645, 2719, 2793, 2870, 2923, 2974, 3020, 3080, 3142, 3198, 3259, 3351, 3418, 3471, 3527, 3581, 3637, 3706, 3761, 3817, 3872]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[306, 610, 768, 915, 1043, 1164, 1255, 1349, 1432, 1511, 1592, 1674, 1744, 1817, 1889, 1950, 2028, 2087, 2153, 2217, 2274, 2349, 2418, 2488, 2558, 2616, 2686, 2745, 2809, 2869, 2938, 3008, 3071, 3131, 3189, 3258, 3320, 3389, 3446, 3503, 3552, 3613, 3677, 3744, 3788, 3842, 3907, 3966, 4015]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[286, 573, 735, 872, 989, 1096, 1185, 1277, 1365, 1449, 1520, 1597, 1668, 1729, 1799, 1852, 1917, 1984, 2054, 2108, 2169, 2234, 2303, 2374, 2436, 2501, 2560, 2620, 2683, 2742, 2830, 2909, 2981, 3032, 3089, 3148, 3210, 3266, 3323, 3379, 3448, 3512, 3576, 3635, 3693, 3747, 3827, 3876, 3938]}, {"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[290, 557, 702, 824, 930, 1032, 1119, 1197, 1276, 1347, 1410, 1477, 1539, 1603, 1678, 1741, 1801, 1866, 1930, 1988, 2060, 2117, 2185, 2239, 2300, 2358, 2429, 2486, 2548, 2613, 2693, 2758, 2824, 2891, 2950, 3019, 3093, 3163, 3224, 3284, 3355, 3421, 3486, 3552, 3622, 3684, 3749, 3799, 3859]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[277, 558, 715, 845, 963, 1070, 1166, 1258, 1336, 1410, 1485, 1561, 1638, 1707, 1767, 1834, 1896, 1960, 2030, 2096, 2165, 2229, 2300, 2368, 2425, 2489, 2553, 2617, 2679, 2743, 2814, 2873, 2941, 2995, 3050, 3111, 3169, 3235, 3300, 3363, 3428, 3487, 3548, 3605, 3670, 3726, 3785, 3844]}]}
Loading … Spinner
There are currently no alerts