A Humanized Mouse Model of HPV-Associated Pathology Driven by E7 Expression
Publication Date
July 23, 2012
Journal
PLOS ONE
Authors
Águeda Buitrago Pérez, Mariam Hachimi, Marta Dueñas, Belén Lloveras, et al
Volume
7
Issue
7
Pages
e41743
DOI
https://dx.plos.org/10.1371/journal.pone.0041743
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0041743
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22911850
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402432
Europe PMC
http://europepmc.org/abstract/MED/22911850
Web of Science
000306687700145
Scopus
84864196455
Mendeley
http://www.mendeley.com/research/humanized-mouse-model-hpvassociated-pathology-driven-e7-expression
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"A humanized mouse model of HPV-associated pathology driven by E7 expression", "type"=>"journal", "authors"=>[{"first_name"=>"Águeda", "last_name"=>"Buitrago-Pérez", "scopus_author_id"=>"26632882500"}, {"first_name"=>"Mariam", "last_name"=>"Hachimi", "scopus_author_id"=>"55321235800"}, {"first_name"=>"Marta", "last_name"=>"Dueñas", "scopus_author_id"=>"7004115630"}, {"first_name"=>"Belén", "last_name"=>"Lloveras", "scopus_author_id"=>"6603788292"}, {"first_name"=>"Almudena", "last_name"=>"Santos", "scopus_author_id"=>"55320876300"}, {"first_name"=>"Almudena", "last_name"=>"Holguín", "scopus_author_id"=>"23060331400"}, {"first_name"=>"Blanca", "last_name"=>"Duarte", "scopus_author_id"=>"24279381700"}, {"first_name"=>"Juan Luis", "last_name"=>"Santiago", "scopus_author_id"=>"20735627400"}, {"first_name"=>"Baki", "last_name"=>"Akgül", "scopus_author_id"=>"55899250900"}, {"first_name"=>"José L.", "last_name"=>"Rodríguez-Peralto", "scopus_author_id"=>"7005762332"}, {"first_name"=>"Alan", "last_name"=>"Storey", "scopus_author_id"=>"7005179668"}, {"first_name"=>"Catalina", "last_name"=>"Ribas", "scopus_author_id"=>"7003400795"}, {"first_name"=>"Fernando", "last_name"=>"Larcher", "scopus_author_id"=>"57192273720"}, {"first_name"=>"Marcelal", "last_name"=>"de Rio", "scopus_author_id"=>"55320474100"}, {"first_name"=>"Jesús M.", "last_name"=>"Paramio", "scopus_author_id"=>"6701734556"}, {"first_name"=>"Ramón", "last_name"=>"García-Escudero", "scopus_author_id"=>"6602471179"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"365316159", "isbn"=>"10.1371/journal.pone.0041743", "sgr"=>"84864196455", "issn"=>"19326203", "pmid"=>"22911850", "scopus"=>"2-s2.0-84864196455", "doi"=>"10.1371/journal.pone.0041743"}, "id"=>"0c7e5c97-500f-39a3-bdf6-a6dfce237a4e", "abstract"=>"Human papillomavirus (HPV) is the causative agent of human cervical cancer and has been associated with oropharyngeal squamous cell carcinoma development. Although prophylactic vaccines have been developed, there is a need to develop new targeted therapies for individuals affected with malignant infected lesions in these locations, which must be tested in appropriate models. Cutaneous beta HPV types appear to be involved in skin carcinogenesis. Virus oncogenicity is partly achieved by inactivation of retinoblastoma protein family members by the viral E7 gene. Here we show that the E7 protein of cutaneous beta HPV5 binds pRb and promotes its degradation. In addition, we described an in vivo model of HPV-associated disease in which artificial human skin prepared using primary keratinocytes engineered to express the E7 protein is engrafted onto nude mice. Expression of E7 in the transplants was stably maintained for up to 6 months, inducing the appearance of lesions that, in the case of HPV16 E7, histologically resembled human anogenital lesions caused by oncogenic HPVs. Moreover, it was confirmed through biomarker expression analysis via immunodetection and/or quantitative PCR from mRNA and miRNA that the 16E7-modified engrafted skin shares molecular features with human HPV-associated pretumoral and tumoral lesions. Finally, our findings indicate a decrease of the in vitro capacity of HPV5 E7 to reduce pRb levels in vivo, possibly explaining the phenotypical differences when compared with 16E7-grafts. Our model seems to be a valuable platform for basic research into HPV oncogenesis and preclinical testing of HPV-associated antitumor therapies.", "link"=>"http://www.mendeley.com/research/humanized-mouse-model-hpvassociated-pathology-driven-e7-expression", "reader_count"=>47, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>4, "Other"=>4, "Student > Master"=>7, "Student > Bachelor"=>5, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>4, "Other"=>4, "Student > Master"=>7, "Student > Bachelor"=>5, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>8, "Agricultural and Biological Sciences"=>20, "Medicine and Dentistry"=>11, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Chemistry"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>20}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Italy"=>1, "Portugal"=>1}, "group_count"=>2}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84864196455"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84864196455?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84864196455&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84864196455&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84864196455", "dc:identifier"=>"SCOPUS_ID:84864196455", "eid"=>"2-s2.0-84864196455", "dc:title"=>"A humanized mouse model of HPV-associated pathology driven by E7 expression", "dc:creator"=>"Buitrago-Pérez A.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"7", "prism:issueIdentifier"=>"7", "prism:pageRange"=>nil, "prism:coverDate"=>"2012-07-23", "prism:coverDisplayDate"=>"23 July 2012", "prism:doi"=>"10.1371/journal.pone.0041743", "citedby-count"=>"16", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas", "affiliation-city"=>"Madrid", "affiliation-country"=>"Spain"}], "pubmed-id"=>"22911850", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e41743", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0041743", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"32", "xml_views"=>"4", "html_views"=>"268"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"38", "xml_views"=>"5", "html_views"=>"127"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"32", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"35", "xml_views"=>"0", "html_views"=>"76"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"74"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"63"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"74"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"52"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"25", "xml_views"=>"7", "html_views"=>"90"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"18", "xml_views"=>"2", "html_views"=>"69"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"107"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"3", "html_views"=>"60"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"43"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"12", "xml_views"=>"2", "html_views"=>"57"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"111"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"58"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"87"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"20", "xml_views"=>"2", "html_views"=>"170"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"14", "xml_views"=>"2", "html_views"=>"192"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"156"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"140"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"150"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"96"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"82"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"84"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"83"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"2", "html_views"=>"47"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"47"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"76"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"76"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"66"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"73"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"83"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"90"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"114"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"85"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"110"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"115"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"25", "xml_views"=>"0", "html_views"=>"102"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"53"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"62", "xml_views"=>"0", "html_views"=>"102"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"82"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"63"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"71"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"76"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"72"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"113"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"85"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"70"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"68"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"59"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"2", "html_views"=>"71"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"113"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"61"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"14", "xml_views"=>"2", "html_views"=>"34"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"58"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"3", "html_views"=>"43"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"15", "xml_views"=>"2", "html_views"=>"29"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"15"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/316355", "https://ndownloader.figshare.com/files/316373", "https://ndownloader.figshare.com/files/316380", "https://ndownloader.figshare.com/files/316390", "https://ndownloader.figshare.com/files/316399", "https://ndownloader.figshare.com/files/316406", "https://ndownloader.figshare.com/files/316413", "https://ndownloader.figshare.com/files/316421", "https://ndownloader.figshare.com/files/316440", "https://ndownloader.figshare.com/files/316446", "https://ndownloader.figshare.com/files/316448"], "description"=>"<div><p>Human papillomavirus (HPV) is the causative agent of human cervical cancer and has been associated with oropharyngeal squamous cell carcinoma development. Although prophylactic vaccines have been developed, there is a need to develop new targeted therapies for individuals affected with malignant infected lesions in these locations, which must be tested in appropriate models. Cutaneous beta HPV types appear to be involved in skin carcinogenesis. Virus oncogenicity is partly achieved by inactivation of retinoblastoma protein family members by the viral E7 gene. Here we show that the E7 protein of cutaneous beta HPV5 binds pRb and promotes its degradation. In addition, we described an <em>in vivo</em> model of HPV-associated disease in which artificial human skin prepared using primary keratinocytes engineered to express the E7 protein is engrafted onto nude mice. Expression of E7 in the transplants was stably maintained for up to 6 months, inducing the appearance of lesions that, in the case of HPV16 E7, histologically resembled human anogenital lesions caused by oncogenic HPVs. Moreover, it was confirmed through biomarker expression analysis via immunodetection and/or quantitative PCR from mRNA and miRNA that the 16E7-modified engrafted skin shares molecular features with human HPV-associated pretumoral and tumoral lesions. Finally, our findings indicate a decrease of the <em>in vitro</em> capacity of HPV5 E7 to reduce pRb levels <em>in vivo</em>, possibly explaining the phenotypical differences when compared with 16E7-grafts. Our model seems to be a valuable platform for basic research into HPV oncogenesis and preclinical testing of HPV-associated antitumor therapies.</p> </div>", "links"=>[], "tags"=>["humanized", "hpv-associated", "pathology", "driven", "e7"], "article_id"=>122417, "categories"=>["Cancer", "Cell Biology"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.s001", "https://dx.doi.org/10.1371/journal.pone.0041743.s002", "https://dx.doi.org/10.1371/journal.pone.0041743.s003", "https://dx.doi.org/10.1371/journal.pone.0041743.s004", "https://dx.doi.org/10.1371/journal.pone.0041743.s005", "https://dx.doi.org/10.1371/journal.pone.0041743.s006", "https://dx.doi.org/10.1371/journal.pone.0041743.s007", "https://dx.doi.org/10.1371/journal.pone.0041743.s008", "https://dx.doi.org/10.1371/journal.pone.0041743.s009", "https://dx.doi.org/10.1371/journal.pone.0041743.s010", "https://dx.doi.org/10.1371/journal.pone.0041743.s011"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Humanized_Mouse_Model_of_HPV_Associated_Pathology_Driven_by_E7_Expression/122417", "title"=>"A Humanized Mouse Model of HPV-Associated Pathology Driven by E7 Expression", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-07-23 00:40:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/605567"], "description"=>"<p>(<b>A</b>) Immunoblots of Saos2 lysates cotransfected with either pcDNA3.1(−)-FLAG (<b>Vector</b>), pcDNA3.1(−)-10E7FLAG (<b>10E7</b>), pcDNA3.1(−)-5E7FLAG (<b>5E7</b>), or pcDNA3.1(−)-16E7FLAG (<b>16E7</b>) plasmids. The effect on pRb expression levels was tested upon cotransfection with the pcDNA-mycRb vector in all cases. Transfection efficiencies were assesed using pcDNA-eGFP. Note that both 5E7 and 16E7, but not 10E7, induced a significant decrease in transiently expressed pRb protein. (<b>B</b>) Immunoblots of Saos2 lysates cotransfected with pcDNA3.1(−)-FLAG (<b>Vector</b>) or with increasing amounts of either pcDNA3.1(−)-5E7FLAG (<b>5E7</b>) or pcDNA3.1(−)-16E7FLAG (<b>16E7</b>) plasmids in the presence of similar amounts of pcDNA-mycRb. Lower panel shows the relative quantification of pRb with respect to eGFP. Note that both 5E7 and 16E7 reduced pRb levels in a dose-dependent manner. (<b>C</b>) Immunoblots of Saos2 lysates cotransfected with either pcDNA3.1(−)-FLAG (<b>Vector</b>), pcDNA3.1(−)-5E7FLAG (<b>5E7</b>), pcDNA3.1(−)-ΔDLFC_5E7FLAG (<b>mut_5E7</b>) pcDNA3.1(−)-ΔDLYC_16E7FLAG (<b>mut_16E7</b>) or pcDNA3.1(−)-16E7FLAG (<b>16E7</b>) plasmids in the presence of pcDNA-mycRb. (<b>D</b>) Immunoblots of Saos2 lysates cotransfected with either pcDNA3.1(−)-FLAG (<b>Vector</b>), pcDNA3.1(−)-5E7FLAG (<b>5E7</b>) or pcDNA3.1(−)-16E7FLAG (<b>16E7</b>) plasmids in the presence of pcDNA-mycRb and increasing concentrations of the proteasome inhibitor MG132. Lower panel shows the relative quantification of pRb with respect to eGFP. Note that MG132 inhibits pRb reduction mediated by 5E7 and 16E7. (<b>E</b>) Foreskin PHK cells were infected with retroviruses generated by pLZRS-E7-IRES-GFP vectors. Immunoblots prepared using specific antibodies showed reduced protein levels of pRb, p107 and p130 upon transduction with E7 from both HPV5 and 16. 5E7 was visualized with an anti-FLAG antibody, and 16E7 with an anti-16E7 antibody. E7 induced the expression of proliferation markers (PCNA and cyclin A), tumor suppressor p53, the proapoptotic effector Bax and the cell cycle inhibitor p21. No increase in the cell cycle inhibitor p16 was observed.</p>", "links"=>[], "tags"=>["hpv5", "e7", "proteins"], "article_id"=>276039, "categories"=>["Cancer", "Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cutaneous_HPV5_E7_protein_reduces_pocket_proteins_levels_/276039", "title"=>"Cutaneous HPV5 E7 protein reduces pocket proteins levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-23 01:40:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/605813"], "description"=>"<p>H&E staining of representative samples of control vector, HPV5 E7 and HPV16 E7 transplants [<b>Skin grafts:</b> upper images (<b>A</b> to <b>F</b>)], as well as CIN1 and bowenoid papulosis (BP) human HR-HPV-infected samples [<b>Human pathology samples</b>: lower images (<b>G</b> to <b>J</b>)]. The histology of vector and 5E7 samples is similar to that of normal skin, with basal, spinous, granulous and cornified layers properly assembled in a mature, differentiated squamous epidermal epithelium of normal thickness (<b>A</b> and <b>B</b>). All 16E7-grafts display epidermal acanthosis (<b>C</b>). Features observed in human HR-HPV-infected lesions are present in HPV16 E7-grafts including suprabasal mitosis (white arrows in <b>D</b>), nuclear atypia (black arrowheads in <b>D, </b><b>G</b> and <b>H</b>), hyperkeratosis (black circles in <b>C</b>, <b>E</b>, <b>F</b>, and <b>J</b>), parakeratosis (black arrows in <b>E</b> and <b>I</b>), papillomatosis (<b>F</b>), hypergranulosis (asterisks in <b>C</b> and <b>D</b>) and capillaries (white arrowheads in <b>F</b> and <b>J</b>).</p>", "links"=>[], "tags"=>["e7-grafts", "hpv-infected", "pathology"], "article_id"=>276290, "categories"=>["Cancer", "Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathology_of_E7_grafts_and_human_HPV_infected_pathology_samples_/276290", "title"=>"Histopathology of E7-grafts and human HPV-infected pathology samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-23 01:44:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/606093"], "description"=>"<p>Sections of paraffin-embedded grafts were processed for immunofluorescence staining with antibodies to epithelial differentiation markers (basal cytokeratin 5, early suprabasal cytokeratin 1 and 10, and late suprabasal involucrin) and proliferation markers (BrdU, PCNA). As in normal skin, cytokeratin 5 (K5) is expressed in the basal layer, cytokeratin 10 (K10) and 1 (K1) in early suprabasal cells, and involucrin (Inv) in late differentiated cells in control vector samples (<b>A</b>, <b>D</b> and <b>G</b>). A similar phenotype was observed in the HPV5 E7 samples (<b>B</b>, <b>E</b> and <b>H</b>). An expansion of involucrin positive cells downwards was observed in HPV16 E7-transplants (<b>C</b> and <b>K</b>). BrdU and PCNA, normally present in some basal cells (<b>D</b> and <b>G</b>), are ectopically present in suprabasal cells of HPV16 E7 samples (<b>F</b> and <b>I</b>). Focal areas of suprabasal PCNA positive cells occur in HPV5 E7 samples (<b>H</b>). Importantly, suprabasal K5/K10 positive (<b>J</b>) or K5/involucrin positive cells (<b>K</b>) were observed in 16E7-grafts. Where indicated, DAPI staining was used to visualize cellular nuclei. <b>K5Inv</b>: staining with both K5 and involucrin antibodies; <b>K5K10BrdU</b>: staining with K5, K10 and BrdU antibodies; <b>K1PCNADAPI</b>: staining with K1, PCNA and DAPI. Dashed line indicates the location of the basal membrane.</p>", "links"=>[], "tags"=>["differentiation", "proliferation", "markers"], "article_id"=>276571, "categories"=>["Cancer", "Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Epidermal_differentiation_and_proliferation_markers_in_E7_grafts_/276571", "title"=>"Epidermal differentiation and proliferation markers in E7-grafts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-23 01:49:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/606362"], "description"=>"<p>Sections of paraffin-embedded grafts were processed for immunohistochemistry staining with antibodies to cell cycle inhibitor p21 and cell cycle regulator cyclin A. With respect to control vector grafts (<b>A</b> and <b>D</b>), both p21 and cyclin A proteins are induced in suprabasal cells of HPV16 E7 transplants (<b>C</b> and <b>F</b>) and in focal HPV5 E7 areas (<b>B</b> and <b>E</b>). In the inserts, dotted lines indicate the location of the basal membrane.</p>", "links"=>[], "tags"=>["p21", "cyclin"], "article_id"=>276842, "categories"=>["Cancer", "Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_p21_and_cyclin_A_in_E7_grafts_/276842", "title"=>"Induction of p21 and cyclin A in E7-grafts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-23 01:54:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/606566"], "description"=>"<p>Sections of paraffin-embedded grafts were processed for immunofluorescence staining with antibodies to the apoptosis markers caspase-3 active and p53. Caspase-3 active is not expressed in control vector samples (<b>A</b>), but some scattered positive cells are observed in HPV5 E7 (<b>B</b>) and HPV16 E7 grafts (<b>C</b> and <b>D</b>). No p53 staining was observed in control and HPV5 E7 samples (not shown), but eventual, p53-positive cells were observed in the HPV16 E7-transplants (<b>D</b>). Dotted line indicates the location of the basal membrane. Inserts in panels <b>B</b>–<b>D</b> show magnified areas of staining. DAPI was used to visualize cell nuclei.</p>", "links"=>[], "tags"=>["showed"], "article_id"=>277046, "categories"=>["Cancer", "Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_E7_grafts_showed_no_significant_apoptosis_/277046", "title"=>"E7-grafts showed no significant apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-23 01:57:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/606712"], "description"=>"<p>(<b>A</b>) Pocket protein and eGFP expression was analyzed by immunoblotting with specific antibodies using graft protein lysates from control vector, 5E7 and 16E7 samples. (<b>B</b>) Pocket protein and eGFP protein expression bands were quantified and relative (pocket protein/eGFP) values plotted. Horizontal green lines represents mean relative values. According to Student’s t-test, significant differences were only detected in pRb/eGFP expression values between vector and 16E7 samples (threshold p-val<0.05). *: p-val<0.05.</p>", "links"=>[], "tags"=>["proteins"], "article_id"=>277193, "categories"=>["Cancer", "Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pocket_proteins_expression_in_skin_grafts_/277193", "title"=>"Pocket proteins expression in skin grafts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-23 01:59:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/606885"], "description"=>"<p>Sections of paraffin-embedded grafts were processed for immunofluorescence staining with antibodies to MCM7. MCM7 is normally confined to the basal layer as in control vector transplants (<b>A</b>). Suprabasal expression is eventually observed in HPV5 E7-samples (<b>B</b>). Importantly, MCM7 is expressed in HPV16 E7-grafts in most suprabasal cells, reaching the uppermost spinous cells. Representative images of different 16E7-grafts are shown (<b>C, C’, C’’, C’’’</b>).</p>", "links"=>[], "tags"=>["surrogate", "mcm7", "ectopically"], "article_id"=>277369, "categories"=>["Cancer", "Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HPV_surrogate_marker_MCM7_is_ectopically_expressed_in_E7_transplants_/277369", "title"=>"HPV surrogate marker MCM7 is ectopically expressed in E7-transplants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-23 02:02:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/607161"], "description"=>"<p>(<b>A</b>) Both PCNA and MCM7 displayed similar ectopic expression in most suprabasal cells of 16E7-grafts. In the basal layer, areas of expression coexisted with expression-free areas. (<b>B</b>) The same patterns were observed in tumor areas of cervical carcinoma samples where p16 was also present. PCNA and MCM7 expression expands progressively upwards in CIN1 and CIN3 (<b>C</b>), while most basal and subrabasal cells were stained in different cases of bowenoid papulosis (<b>D</b>). Middle panels in <b>C</b> and inserts in <b>D</b> highlight areas of basal cells showing negative staining for MCM7, PCNA and p16 (the latter, in CIN1). Dotted lines indicate the location of the basal membrane.</p>", "links"=>[], "tags"=>["16e7-grafts", "hpv-infected", "anogenital", "neoplasias"], "article_id"=>277637, "categories"=>["Cancer", "Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Similarities_between_16E7_grafts_and_HPV_infected_anogenital_neoplasias_identified_by_immunohistochemistry_/277637", "title"=>"Similarities between 16E7-grafts and HPV-infected anogenital neoplasias identified by immunohistochemistry.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-23 02:07:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/607316"], "description"=>"<p>mRNA quantification of E2F1, CENPF, MELK and RFC4 genes was conducted by qRT-PCR using RNA purified from PHK cells or grafts, or obtained from reported microarray experiments for CC or VIN. Each dot represents an individual sample. Horizontal lines represent mean values in each sample group. (<b>A</b>) All genes were induced in E7-transduced PHKs, though not significantly (Student’s t-test threshold p-val<0.05). Significant overexpression was also observed for all genes in HPV16 E7-transplants, but only for E2F1 in HPV5 E7. Shown are log<sub>2</sub>-based, z-values of expression relative to housekeeping GUSB in PHK cells and transplants (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041743#s2\" target=\"_blank\">Materials and Methods</a>). (<b>B</b>) Microarray expression patterns of each gene in CC and VIN infected with HR-HPVs are shown as log<sub>2</sub>-based, z-values (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041743#s2\" target=\"_blank\">Materials and Methods</a>). All genes display significant overexpression in CC with respect to cervix uteri (N), and in VIN with respect to normal vulva (N). Horizontal lines represent mean values in each sample group. *: p-val <0.05, **: p-val <0.005, ***: p-val <0.0005, ****: p-val <0.00005. <b>V</b>: control vector; <b>5</b>: HPV5 E7; <b>16</b>: HPV16 E7. (<b>C</b>) miRNA was quantified by qRT-PCR for miR-146a, miR-21 and miR-200a, using RNA purified from skin grafts. Shown are log<sub>2</sub>-based, z-values of expression relative to housekeeping U6B. Each dot represents an individual sample value. All miRNAs were overexpressed in HPV16 E7-grafts. Only miR-21 displayed significant deregulation in transplants expressing HPV5 E7. Horizontal lines represent mean values in each sample group. *: p-val <0.05, **: p-val <0.005, ***: p-val <0.0005, ****: p-val <0.00005. <b>V</b>: control vector; <b>5</b>: HPV5 E7; <b>16</b>: HPV16 E7.</p>", "links"=>[], "tags"=>["quantification", "oncogenic", "hpv", "biomarker", "genes"], "article_id"=>277792, "categories"=>["Cancer", "Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RNA_expression_quantification_of_oncogenic_HPV_biomarker_genes_and_miRNAs_/277792", "title"=>"RNA expression quantification of oncogenic HPV biomarker genes and miRNAs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-23 02:09:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/607463"], "description"=>"<p>Histopathology of skin transplants.</p>", "links"=>[], "tags"=>["Virology", "Infectious diseases", "oncology", "pathology"], "article_id"=>277939, "categories"=>["Cancer", "Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Águeda Buitrago-Pérez", "Mariam Hachimi", "Marta Dueñas", "Belén Lloveras", "Almudena Santos", "Almudena Holguín", "Blanca Duarte", "Juan Luis Santiago", "Baki Akgül", "José L. Rodríguez-Peralto", "Alan Storey", "Catalina Ribas", "Fernando Larcher", "Marcela del Rio", "Jesús M. Paramio", "Ramon Garcia-Escudero"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041743.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathology_of_skin_transplants_/277939", "title"=>"Histopathology of skin transplants.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-23 02:12:19"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"46", "full-text"=>"51", "pdf"=>"19", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"69", "full-text"=>"70", "pdf"=>"51", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"60", "full-text"=>"70", "pdf"=>"51", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"23", "full-text"=>"22", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"17", "full-text"=>"18", "pdf"=>"4", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"28", "full-text"=>"29", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"31", "full-text"=>"31", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"45", "full-text"=>"53", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"47", "full-text"=>"49", "pdf"=>"30", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"25", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"17", "full-text"=>"17", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"20", "full-text"=>"16", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"12", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"20", "full-text"=>"15", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"8", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"19", "full-text"=>"18", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"18", "full-text"=>"17", "pdf"=>"11", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"10", "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"=>"13", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"7", "abstract"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"16", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"9", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"20", "full-text"=>"18", "pdf"=>"20", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"20", "full-text"=>"18", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"12", "full-text"=>"7", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"15", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"22", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"14", "full-text"=>"8", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"20", "full-text"=>"14", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"15", "pdf"=>"7", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"21", "full-text"=>"33", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"15", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"20", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"11", "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"=>"12", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"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"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"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"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"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"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"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"=>"11"}
  • {"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"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"16", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"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"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"19", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[322, 550, 671, 773, 864, 955, 1048, 1135, 1223, 1308, 1387, 1465, 1534, 1602, 1673, 1744, 1813, 1885, 1955, 2026, 2093, 2160, 2228, 2290, 2349]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[333, 576, 707, 814, 908, 1004, 1104, 1197, 1280, 1370, 1449, 1531, 1603, 1673, 1742, 1817, 1886, 1954, 2025, 2098, 2171, 2234, 2304, 2365, 2431]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[312, 547, 668, 769, 861, 953, 1046, 1135, 1224, 1307, 1388, 1464, 1536, 1606, 1676, 1744, 1812, 1882, 1954, 2020, 2089, 2155, 2218, 2282, 2344]}, {"subject_area"=>"/Medicine and health sciences/Surgical and invasive medical procedures", "average_usage"=>[286, 511, 637, 736, 826, 907, 995, 1071, 1150, 1221, 1293, 1366, 1437, 1507, 1560, 1637, 1698, 1755, 1815, 1860, 1939, 2007, 2062, 2121, 2162]}, {"subject_area"=>"/Medicine and health sciences/Urology", "average_usage"=>[354, 588, 721, 835, 935, 1015, 1103, 1217, 1309, 1400, 1505, 1594, 1662, 1738, 1799, 1873, 1937, 2016, 2085, 2151, 2234, 2302, 2401, 2443, 2500]}]}
Loading … Spinner
There are currently no alerts