c-Myc Accelerates S-Phase and Requires WRN to Avoid Replication Stress
Publication Date
June 18, 2009
Journal
PLOS ONE
Authors
Kristin Robinson, Nichaya Asawachaicharn, Denise A. Galloway & Carla Grandori
Volume
4
Issue
6
Pages
e5951
DOI
https://dx.plos.org/10.1371/journal.pone.0005951
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0005951
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/19554081
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694031
Europe PMC
http://europepmc.org/abstract/MED/19554081
Web of Science
000267079500002
Scopus
67650146183
Mendeley
http://www.mendeley.com/research/cmyc-accelerates-sphase-requires-wrn-avoid-replication-stress
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"c-Myc accelerates S-phase and requires WRN to avoid replication stress", "type"=>"journal", "authors"=>[{"first_name"=>"Kristin", "last_name"=>"Robinson", "scopus_author_id"=>"7403229212"}, {"first_name"=>"Nichaya", "last_name"=>"Asawachaicharn", "scopus_author_id"=>"26967596800"}, {"first_name"=>"Denise A.", "last_name"=>"Galloway", "scopus_author_id"=>"7102847305"}, {"first_name"=>"Carla", "last_name"=>"Grandori", "scopus_author_id"=>"6603682207"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-67650146183", "sgr"=>"67650146183", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0005951", "pmid"=>"19554081", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"354877164"}, "id"=>"d4c89d22-1628-315d-a897-235eed427ced", "abstract"=>"c-Myc interacts with components of the pre-replication complex and directly regulates DNA replication [1]. However the consequences of this novel c-Myc function on cell cycle dynamics and replication-associated damage are unknown. Here, we show that c-Myc overexpression in primary human fibroblasts markedly accelerates S-phase while c-Myc deficient fibroblasts exhibit a prolonged S-phase. We also show that the Werner DNA helicase protein (WRN) plays a critical role in supporting c-Myc-driven S-phase, as depletion of WRN in c-Myc overexpressing cells increases DNA damage specifically at sites of DNA synthesis. This excess DNA damage activates a \"replication stress\" pathway involving ATR, CHK1, CHK2, and p53, leading to rapid senescence of WRN deficient c-Myc overexpressing cells. Indeed, depletion of p53 rescues this senescence response. We propose that WRN functions to repair abnormal replication structures caused by the acceleration of DNA replication by c-Myc. This work provides an additional mechanistic explanation for c-Myc-induced DNA damage and senescence, and reveals a vulnerability of c-Myc overexpressing cells that could potentially be exploited in cancer therapy.", "link"=>"http://www.mendeley.com/research/cmyc-accelerates-sphase-requires-wrn-avoid-replication-stress", "reader_count"=>61, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Librarian"=>1, "Student > Doctoral Student"=>1, "Researcher"=>22, "Student > Ph. D. Student"=>16, "Student > Master"=>9, "Other"=>2, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Librarian"=>1, "Student > Doctoral Student"=>1, "Researcher"=>22, "Student > Ph. D. Student"=>16, "Student > Master"=>9, "Other"=>2, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>11, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>35, "Medicine and Dentistry"=>9, "Neuroscience"=>1, "Chemistry"=>2, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>35}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>11}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Japan"=>1, "United Kingdom"=>1, "Germany"=>2}, "group_count"=>2}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/67650146183"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/67650146183?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=67650146183&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=67650146183&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/67650146183", "dc:identifier"=>"SCOPUS_ID:67650146183", "eid"=>"2-s2.0-67650146183", "dc:title"=>"c-Myc accelerates S-phase and requires WRN to avoid replication stress", "dc:creator"=>"Robinson K.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"4", "prism:issueIdentifier"=>"6", "prism:pageRange"=>nil, "prism:coverDate"=>"2009-06-18", "prism:coverDisplayDate"=>"18 June 2009", "prism:doi"=>"10.1371/journal.pone.0005951", "citedby-count"=>"54", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Fred Hutchinson Cancer Research Center", "affiliation-city"=>"Seattle", "affiliation-country"=>"United States"}], "pubmed-id"=>"19554081", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e5951", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0005951", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"6", "year"=>"2009", "pdf_views"=>"98", "xml_views"=>"4", "html_views"=>"553"}
  • {"month"=>"7", "year"=>"2009", "pdf_views"=>"52", "xml_views"=>"1", "html_views"=>"114"}
  • {"month"=>"8", "year"=>"2009", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"60"}
  • {"month"=>"9", "year"=>"2009", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"55"}
  • {"month"=>"10", "year"=>"2009", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"27"}
  • {"month"=>"11", "year"=>"2009", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"12", "year"=>"2009", "pdf_views"=>"25", "xml_views"=>"1", "html_views"=>"36"}
  • {"month"=>"1", "year"=>"2010", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"2", "year"=>"2010", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"3", "year"=>"2010", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"41"}
  • {"month"=>"4", "year"=>"2010", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"49"}
  • {"month"=>"5", "year"=>"2010", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"52"}
  • {"month"=>"6", "year"=>"2010", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"56"}
  • {"month"=>"7", "year"=>"2010", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"48"}
  • {"month"=>"8", "year"=>"2010", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"9", "year"=>"2010", "pdf_views"=>"15", "xml_views"=>"1", "html_views"=>"50"}
  • {"month"=>"10", "year"=>"2010", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"37"}
  • {"month"=>"11", "year"=>"2010", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"63"}
  • {"month"=>"12", "year"=>"2010", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"1", "year"=>"2011", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"29"}
  • {"month"=>"2", "year"=>"2011", "pdf_views"=>"27", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"3", "year"=>"2011", "pdf_views"=>"34", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"4", "year"=>"2011", "pdf_views"=>"43", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"5", "year"=>"2011", "pdf_views"=>"30", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"6", "year"=>"2011", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"7", "year"=>"2011", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"8", "year"=>"2011", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"9", "year"=>"2011", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"10", "year"=>"2011", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"11", "year"=>"2011", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"54"}
  • {"month"=>"12", "year"=>"2011", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"49"}
  • {"month"=>"1", "year"=>"2012", "pdf_views"=>"22", "xml_views"=>"1", "html_views"=>"55"}
  • {"month"=>"2", "year"=>"2012", "pdf_views"=>"24", "xml_views"=>"0", "html_views"=>"55"}
  • {"month"=>"3", "year"=>"2012", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"30"}
  • {"month"=>"4", "year"=>"2012", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"19"}
  • {"month"=>"5", "year"=>"2012", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"45"}
  • {"month"=>"6", "year"=>"2012", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"47"}
  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"40"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"11", "xml_views"=>"5", "html_views"=>"31"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"43"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"54"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"49"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"51"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"57"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"63"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"60"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"50"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"50"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"2", "html_views"=>"50"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"46"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"89"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"64"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"51"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"13"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"49"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"17"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"30"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"29"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"16"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"3", "html_views"=>"30"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"2", "html_views"=>"4"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"1"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/894341"], "description"=>"<p>a) c-Myc accelerates S-phase in human foreskin fibroblasts (HFFs). BrdU pulse-chase experiment in HFFs transduced with pB-Myc retrovirus or empty vector, pBabe. Cells were synchronized by thymidine block and released in BrdU for one hour, then chased in BrdU-free media for the indicated time. Progression of early labeled BrdU cells through S and G2 was monitored by FACS analysis. The BrdU positive HFF-Myc cells accumulated in G2 between three to four hours after release, while the control cells HFF-pB accumulated in G2 beginning at five hours. Propidium iodide staining at the time of release, prior to BrdU addition to verify the G1/S arrest of HFF-Myc cells is shown in supplementary <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005951#pone.0005951.s003\" target=\"_blank\">Figure S1</a>. b) Knockout of <i>c-myc</i> lengthens S-phase. Propidium iodide profiles of the rat cell line TGR, its derivatives <i>c-myc</i>−/− <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005951#pone.0005951-Mateyak1\" target=\"_blank\">[22]</a> and the reconstituted <i>c-myc</i>−/−;+pB-Myc upon release from thymidine block is shown. While TGR cells completed S-phase between eight and eleven hours, <i>c-myc</i>−/− cells were still in S-phase at eleven hours. Reconstituted <i>c-myc</i>−/−;+pB-Myc cells showed a dramatic acceleration of S-phase (six hrs). c) Expression of c-Myc was analyzed by western blot. Actin is shown as loading control.</p>", "links"=>[], "tags"=>["levels"], "article_id"=>564801, "categories"=>["Molecular Biology", "Cell Biology", "Biochemistry", "Cancer", "Genetics"], "users"=>["Kristin Robinson", "Nichaya Asawachaicharn", "Denise A. Galloway", "Carla Grandori"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005951.g001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_c_Myc_levels_determine_the_rate_of_S_phase_/564801", "title"=>"c-Myc levels determine the rate of S-phase.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-18 01:20:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/443388", "https://ndownloader.figshare.com/files/443466", "https://ndownloader.figshare.com/files/443562"], "description"=>"<div><p>c-Myc interacts with components of the pre-replication complex and directly regulates DNA replication <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005951#pone.0005951-DominguezSola1\">[1]</a>. However the consequences of this novel c-Myc function on cell cycle dynamics and replication-associated damage are unknown. Here, we show that c-Myc overexpression in primary human fibroblasts markedly accelerates S-phase while c-Myc deficient fibroblasts exhibit a prolonged S-phase. We also show that the Werner DNA helicase protein (WRN) plays a critical role in supporting c-Myc-driven S-phase, as depletion of WRN in c-Myc overexpressing cells increases DNA damage specifically at sites of DNA synthesis. This excess DNA damage activates a “replication stress” pathway involving ATR, CHK1, CHK2, and p53, leading to rapid senescence of WRN deficient c-Myc overexpressing cells. Indeed, depletion of p53 rescues this senescence response. We propose that WRN functions to repair abnormal replication structures caused by the acceleration of DNA replication by c-Myc. This work provides an additional mechanistic explanation for c-Myc-induced DNA damage and senescence, and reveals a vulnerability of c-Myc overexpressing cells that could potentially be exploited in cancer therapy.</p></div>", "links"=>[], "tags"=>["c-myc", "accelerates", "s-phase", "requires", "wrn", "replication"], "article_id"=>147398, "categories"=>["Molecular Biology", "Cell Biology", "Biochemistry", "Cancer", "Genetics"], "users"=>["Kristin Robinson", "Nichaya Asawachaicharn", "Denise A. Galloway", "Carla Grandori"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0005951.s001", "https://dx.doi.org/10.1371/journal.pone.0005951.s002", "https://dx.doi.org/10.1371/journal.pone.0005951.s003"], "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/c_Myc_Accelerates_S_Phase_and_Requires_WRN_to_Avoid_Replication_Stress/147398", "title"=>"c-Myc Accelerates S-Phase and Requires WRN to Avoid Replication Stress", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-06-18 02:03:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/894710"], "description"=>"<p>a) <i>hTERT</i>-WRN<sup>−/−</sup> cells or control <i>hTERT</i>-immortalized fibroblasts were transduced with LXSN-Myc and stained with anti-RPA (subunit 32) antibodies. Images were collected with a 40X oil–immersion objective. WRN<sup>−/−</sup> cells expressing c-Myc showed prominent RPA nuclear staining. b) Cells as in (a) were subjected to a Triton extraction prior to fixation and stained for p-ATR (Ser428) to reveal the p-ATR associated with the chromatin resistant fraction. Images were collected with a 100X oil–immersion objective. Specific staining occurred in WRN<sup>−/−</sup> cells upon c-Myc overexpression and was not detectable in the control <i>hTERT</i>–immortalized normal fibroblasts. c) Increased p-ATR (Ser428) and RPA (subunit 70) in WRN<sup>−/−</sup> cells upon c-Myc overexpression was confirmed by Western analysis. In addition increased levels of p-CHK1, p-CHK2, and p-p53 by c-Myc were detected in WRN<sup>−/−</sup> cells. HFFs exposed to UV are shown as positive control of DNA damage response.</p>", "links"=>[], "tags"=>["induced", "wrn", "deficient", "cells", "c-myc"], "article_id"=>565158, "categories"=>["Molecular Biology", "Cell Biology", "Biochemistry", "Cancer", "Genetics"], "users"=>["Kristin Robinson", "Nichaya Asawachaicharn", "Denise A. Galloway", "Carla Grandori"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005951.g004", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_stress_induced_in_WRN_deficient_cells_by_c_Myc_overexpression_/565158", "title"=>"Replication stress induced in WRN deficient cells by c-Myc overexpression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-18 01:25:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/894839"], "description"=>"<p>a) Western analysis of <i>hTERT</i>-WRN<sup>−/−</sup> cells simultaneously transduced with c-Myc and sip53 retroviral vectors indicates p53 knockdown and c-Myc overexpression. b) A representative field of cells as in (a) stained for senescence associated β-Gal. Knockdown of p53 rescues senescence and decreases the percentage of senescent cells. c) Quantitation of cells as in (a) that stained positive for SA-β-Gal at passage 2 and 4 after viral transduction and selection.</p>", "links"=>[], "tags"=>["p53", "rescues", "senescence", "cells", "c-myc"], "article_id"=>565289, "categories"=>["Molecular Biology", "Cell Biology", "Biochemistry", "Cancer", "Genetics"], "users"=>["Kristin Robinson", "Nichaya Asawachaicharn", "Denise A. Galloway", "Carla Grandori"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005951.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Knockdown_of_p53_rescues_senescence_in_WRN_8722_8722_cells_in_response_to_c_Myc_overexpression_/565289", "title"=>"Knockdown of p53 rescues senescence in WRN<sup>−/−</sup> cells in response to c-Myc overexpression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-18 01:28:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/894590"], "description"=>"<p>a) <i>hTERT</i>-immortalized WRN<sup>−/−</sup> fibroblasts and normal <i>hTERT</i>-control fibroblasts were transduced with LXSN-Myc expressing retrovirus and labeled with BrdU for 30 minutes during S-phase. Cells were stained with anti-BrdU (red) and anti-γ-H2AX (green). Images were collected with a 100X oil–immersion objective. Note the increased appearance of γ-H2AX and BrdU spots (yellow) in WRN<sup>−/−</sup> cells expressing c-Myc versus vector, LXSN, transduced WRN<sup>−/−</sup> cells or WRN<sup>+/+</sup> cells also expressing c-Myc. b) BrdU and γ -H2AX co-localized foci from (a) were counted in 10 cells/condition (Imaris software). c) HFF-Myc and HFF-pB cells were transduced with retroviruses encoding two different short hairpins to WRN, siWRN I and II, or scrambled control and labeled with BrdU at the first passage after infection. Knockdown using either siWRN virus caused increased co-localization of γ -H2AX (green) and BrdU (red). d) Quantitation of γ -H2AX and BrdU of experiment shown in (c). e) Western analysis of a parallel transduction of HFFs indicating the WRN knockdown achieved with siWRN I and II. Actin is shown as loading control.</p>", "links"=>[], "tags"=>["accumulates", "replication", "sites", "wrn", "deficient", "cells", "c-myc"], "article_id"=>565036, "categories"=>["Molecular Biology", "Cell Biology", "Biochemistry", "Cancer", "Genetics"], "users"=>["Kristin Robinson", "Nichaya Asawachaicharn", "Denise A. Galloway", "Carla Grandori"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005951.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DNA_damage_accumulates_at_replication_sites_in_WRN_deficient_cells_in_response_to_c_Myc_overexpression_/565036", "title"=>"DNA damage accumulates at replication sites in WRN deficient cells in response to c-Myc overexpression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-18 01:23:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/894472"], "description"=>"<p>HFF-pB (a) and HFF-Myc (b) were synchronized by thymidine block, labeled at the indicated times for 30 minutes with BrdU, and fixed for staining. Cells were stained for WRN (green) and BrdU (red), and DNA was stained with Hoechst (blue). Images were collected with a 100X oil–immersion objective. An increased co-localization of WRN with BrdU foci (yellow) is detectable at the 1.5 and 2.5 hr time point in HFF-Myc cells. This indicates recruitment of WRN at sites of newly replicated DNA caused by c-Myc overexpression. A 3-D movie reconstructed from this experiment can be seen as supplemental data (Supplementary <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005951#pone.0005951.s001\" target=\"_blank\">Movies S1</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005951#pone.0005951.s002\" target=\"_blank\">S2</a>). c) Higher magnification of HFF-pB (top) and HFF-Myc (bottom) cells at 1–1.5 hr time point to better visualize WRN and BrdU co-localized foci. d), e) Percentage of cells in early, intermediate, and late S-phase determined by the BrdU patterns. HFF-Myc (e) progressed faster than HFF-pB (d) and only “late” patterns were present at 3.5 hrs post-release, similar to the result obtained by the pulse-chase experiment (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005951#pone-0005951-g001\" target=\"_blank\">Fig. 1</a>).</p>", "links"=>[], "tags"=>["wrn", "replication", "sites", "c-myc", "overexpressing"], "article_id"=>564926, "categories"=>["Molecular Biology", "Cell Biology", "Biochemistry", "Cancer", "Genetics"], "users"=>["Kristin Robinson", "Nichaya Asawachaicharn", "Denise A. Galloway", "Carla Grandori"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005951.g002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_presence_of_WRN_at_replication_sites_in_c_Myc_overexpressing_HFFs_/564926", "title"=>"Increased presence of WRN at replication sites in c-Myc overexpressing HFFs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-18 01:22:06"}

PMC Usage Stats | Further Information

  • {"month"=>"1", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"33", "year"=>"2010", "pdf"=>"6", "unique-ip"=>"35", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"2", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"15", "unique-ip"=>"26", "pdf"=>"2", "year"=>"2010", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"3", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"16", "year"=>"2010", "pdf"=>"4", "unique-ip"=>"24", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"4", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"16", "unique-ip"=>"14", "pdf"=>"7", "year"=>"2010", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"5", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"10", "year"=>"2010", "pdf"=>"8", "unique-ip"=>"12", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"6", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"14", "unique-ip"=>"15", "pdf"=>"8", "year"=>"2010", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"7", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"12", "year"=>"2010", "pdf"=>"4", "unique-ip"=>"15", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"8", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"17", "unique-ip"=>"19", "pdf"=>"5", "year"=>"2010", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"9", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"12", "year"=>"2010", "pdf"=>"4", "unique-ip"=>"12", "figure"=>"16", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"10", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"11", "unique-ip"=>"13", "pdf"=>"16", "year"=>"2010", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"11", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"21", "year"=>"2010", "pdf"=>"13", "unique-ip"=>"23", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"12", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"15", "unique-ip"=>"16", "pdf"=>"18", "year"=>"2010", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"1", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"11", "year"=>"2011", "pdf"=>"6", "unique-ip"=>"21", "figure"=>"14", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"2", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"8", "unique-ip"=>"14", "pdf"=>"2", "year"=>"2011", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"3", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"15", "year"=>"2011", "pdf"=>"4", "unique-ip"=>"22", "figure"=>"14", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"4", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"10", "unique-ip"=>"13", "pdf"=>"7", "year"=>"2011", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"5", "scanned-page-browse"=>"0", "cited-by"=>"1", "abstract"=>"2", "full-text"=>"14", "year"=>"2011", "pdf"=>"9", "unique-ip"=>"18", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"6", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"8", "unique-ip"=>"10", "pdf"=>"2", "year"=>"2011", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"7", "scanned-page-browse"=>"0", "cited-by"=>"1", "abstract"=>"0", "full-text"=>"16", "year"=>"2011", "pdf"=>"5", "unique-ip"=>"16", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"8", "cited-by"=>"1", "abstract"=>"0", "full-text"=>"10", "unique-ip"=>"11", "pdf"=>"6", "year"=>"2011", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"9", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"10", "year"=>"2011", "pdf"=>"5", "unique-ip"=>"9", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"10", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"16", "unique-ip"=>"13", "pdf"=>"4", "year"=>"2011", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"11", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"13", "year"=>"2011", "pdf"=>"5", "unique-ip"=>"8", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"12", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"19", "unique-ip"=>"12", "pdf"=>"8", "year"=>"2011", "figure"=>"33", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"1", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"15", "year"=>"2012", "pdf"=>"8", "unique-ip"=>"13", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"2", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"6", "unique-ip"=>"7", "pdf"=>"2", "year"=>"2012", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"3", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"6", "year"=>"2012", "pdf"=>"4", "unique-ip"=>"10", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"4", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"4", "unique-ip"=>"6", "pdf"=>"2", "year"=>"2012", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"5", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"13", "year"=>"2012", "pdf"=>"4", "unique-ip"=>"14", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"6", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"31", "unique-ip"=>"25", "pdf"=>"27", "year"=>"2009", "figure"=>"16", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"7", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"101", "year"=>"2009", "pdf"=>"69", "unique-ip"=>"91", "figure"=>"21", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"8", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"28", "unique-ip"=>"26", "pdf"=>"20", "year"=>"2009", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"9", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"27", "year"=>"2009", "pdf"=>"14", "unique-ip"=>"28", "figure"=>"18", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"10", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"13", "unique-ip"=>"12", "pdf"=>"8", "year"=>"2009", "figure"=>"11", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"11", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"39", "year"=>"2009", "pdf"=>"6", "unique-ip"=>"39", "figure"=>"18", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"12", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"31", "unique-ip"=>"26", "pdf"=>"7", "year"=>"2009", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"11", "year"=>"2012", "pdf"=>"5", "unique-ip"=>"10", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"16", "full-text"=>"33", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"31", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"11", "full-text"=>"17", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"8", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"13", "full-text"=>"6", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"3", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"7", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"23", "full-text"=>"9", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"14", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"16", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"12", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"18", "full-text"=>"16", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"8", "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"=>"13", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"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"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"16", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"24", "full-text"=>"25", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2009-01-01T00:00:00Z", "end_date"=>"2009-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[349, 614, 744, 851, 955, 1059, 1167, 1262, 1352, 1431, 1516, 1593, 1668, 1746, 1817, 1883, 1950, 2017, 2075, 2141, 2198, 2254, 2313, 2368, 2424, 2474, 2534, 2591, 2651, 2710, 2776, 2837, 2892, 2953, 3014, 3072, 3130, 3186, 3251, 3307, 3366, 3427, 3500, 3561, 3627, 3688, 3759, 3821, 3888, 3950, 4010, 4070, 4131, 4189, 4242, 4307, 4370, 4431, 4491, 4549, 4608]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[336, 588, 721, 826, 931, 1029, 1138, 1224, 1311, 1395, 1477, 1555, 1632, 1704, 1774, 1847, 1919, 1987, 2039, 2089, 2149, 2204, 2264, 2319, 2370, 2424, 2481, 2535, 2593, 2645, 2702, 2765, 2816, 2865, 2932, 2992, 3045, 3105, 3159, 3208, 3259, 3316, 3374, 3430, 3490, 3542, 3602, 3654, 3720, 3783, 3851, 3919, 3981, 4038, 4096, 4151, 4197, 4235, 4297, 4372, 4437]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[315, 570, 717, 826, 931, 1027, 1137, 1224, 1308, 1379, 1458, 1542, 1613, 1694, 1768, 1841, 1909, 1957, 2019, 2082, 2127, 2182, 2232, 2290, 2352, 2419, 2476, 2525, 2572, 2627, 2670, 2722, 2800, 2846, 2901, 2963, 3017, 3078, 3136, 3210, 3253, 3303, 3366, 3431, 3486, 3538, 3600, 3663, 3723, 3776, 3815, 3880, 3966, 4036, 4103, 4145, 4193, 4232, 4304, 4369, 4426]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[366, 637, 775, 896, 999, 1118, 1230, 1322, 1416, 1516, 1602, 1685, 1767, 1849, 1914, 1982, 2049, 2120, 2185, 2246, 2303, 2363, 2409, 2473, 2535, 2599, 2655, 2717, 2777, 2842, 2906, 2977, 3021, 3088, 3144, 3199, 3253, 3317, 3379, 3456, 3508, 3567, 3634, 3716, 3781, 3853, 3911, 3974, 4040, 4118, 4170, 4218, 4285, 4341, 4404, 4467, 4527, 4584, 4631, 4689, 4725]}, {"subject_area"=>"/Biology and life sciences/Physiology", "average_usage"=>[306, 556, 687, 796, 910, 1010, 1116, 1207, 1291, 1370, 1458, 1539, 1613, 1694, 1768, 1842, 1905, 1965, 2034, 2097, 2148, 2198, 2253, 2307, 2349, 2409, 2462, 2516, 2562, 2614, 2666, 2723, 2779, 2833, 2895, 2961, 3009, 3061, 3119, 3183, 3232, 3303, 3367, 3414, 3464, 3516, 3588, 3648, 3713, 3774, 3827, 3880, 3953, 4012, 4070, 4125, 4187, 4230, 4291, 4339, 4393]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[332, 584, 719, 824, 927, 1030, 1139, 1233, 1322, 1402, 1483, 1570, 1649, 1730, 1806, 1873, 1939, 2003, 2068, 2130, 2191, 2248, 2302, 2362, 2427, 2485, 2544, 2599, 2653, 2709, 2778, 2840, 2896, 2950, 3013, 3073, 3137, 3189, 3253, 3305, 3364, 3423, 3489, 3557, 3606, 3668, 3742, 3797, 3852, 3907, 3962, 4027, 4072, 4132, 4193, 4256, 4308, 4366, 4427, 4493, 4556]}, {"subject_area"=>"/Medicine and health sciences/Anatomy", "average_usage"=>[339, 580, 713, 827, 926, 1032, 1153, 1258, 1348, 1429, 1522, 1603, 1687, 1772, 1834, 1905, 1972, 2029, 2098, 2151, 2214, 2275, 2335, 2388, 2446, 2496, 2553, 2604, 2653, 2705, 2780, 2822, 2890, 2947, 3020, 3070, 3114, 3162, 3226, 3285, 3353, 3433, 3500, 3547, 3592, 3639, 3700, 3769, 3858, 3922, 3967, 4028, 4069, 4137, 4191, 4246, 4302, 4372, 4436, 4498, 4579]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[321, 578, 720, 834, 929, 1032, 1139, 1230, 1314, 1399, 1483, 1569, 1645, 1719, 1793, 1864, 1941, 2002, 2063, 2129, 2189, 2232, 2285, 2336, 2395, 2448, 2515, 2581, 2637, 2681, 2747, 2800, 2854, 2920, 2974, 3039, 3088, 3143, 3202, 3258, 3299, 3389, 3447, 3510, 3573, 3643, 3713, 3771, 3845, 3907, 3956, 4020, 4074, 4127, 4187, 4251, 4316, 4354, 4401, 4472, 4518]}, {"subject_area"=>"/Physical sciences", "average_usage"=>[340, 575, 698, 803, 889, 974, 1077, 1169, 1245, 1318, 1398, 1468, 1540, 1608, 1679, 1748, 1819, 1877, 1937, 1999, 2044, 2100, 2148, 2198, 2250, 2306, 2357, 2414, 2458, 2517, 2572, 2636, 2690, 2749, 2799, 2861, 2914, 2970, 3026, 3102, 3143, 3237, 3303, 3373, 3441, 3500, 3553, 3608, 3679, 3733, 3791, 3856, 3908, 3962, 4033, 4096, 4149, 4187, 4229, 4281, 4336]}, {"subject_area"=>"/Physical sciences/Chemistry", "average_usage"=>[303, 516, 651, 762, 853, 944, 1048, 1140, 1218, 1291, 1366, 1449, 1509, 1593, 1663, 1726, 1797, 1856, 1906, 1958, 2018, 2083, 2128, 2175, 2235, 2294, 2354, 2403, 2452, 2502, 2558, 2617, 2672, 2730, 2794, 2857, 2913, 2970, 3036, 3087, 3155, 3216, 3270, 3336, 3390, 3450, 3508, 3568, 3623, 3705, 3762, 3812, 3895, 3938, 4026, 4083, 4137, 4187, 4235, 4292, 4348]}]}
Loading … Spinner
There are currently no alerts