The Hsp90 Co-Chaperone Sgt1 Governs Candida albicans Morphogenesis and Drug Resistance
Publication Date
September 06, 2012
Journal
PLOS ONE
Authors
Rebecca S. Shapiro, Aimee K. Zaas, Marisol Betancourt Quiroz, John R. Perfect, et al
Volume
7
Issue
9
Pages
e44734
DOI
https://dx.plos.org/10.1371/journal.pone.0044734
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0044734
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22970302
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435277
Europe PMC
http://europepmc.org/abstract/MED/22970302
Web of Science
000308458400116
Scopus
84866114557
Mendeley
http://www.mendeley.com/research/hsp90-cochaperone-sgt1-governs-candida-albicans-morphogenesis-drug-resistance
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"The Hsp90 Co-Chaperone Sgt1 Governs Candida albicans Morphogenesis and Drug Resistance", "type"=>"journal", "authors"=>[{"first_name"=>"Rebecca S.", "last_name"=>"Shapiro", "scopus_author_id"=>"26421390600"}, {"first_name"=>"Aimee K.", "last_name"=>"Zaas", "scopus_author_id"=>"6603264399"}, {"first_name"=>"Marisol", "last_name"=>"Betancourt-Quiroz", "scopus_author_id"=>"36571430600"}, {"first_name"=>"John R.", "last_name"=>"Perfect", "scopus_author_id"=>"7102729293"}, {"first_name"=>"Leah E.", "last_name"=>"Cowen", "scopus_author_id"=>"7003498523"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"365624325", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0044734", "scopus"=>"2-s2.0-84866114557", "pmid"=>"22970302", "sgr"=>"84866114557"}, "id"=>"39eac21a-89db-39a7-bf03-11e199d1332c", "abstract"=>"The molecular chaperone Hsp90 orchestrates regulatory circuitry governing fungal morphogenesis, biofilm development, drug resistance, and virulence. Hsp90 functions in concert with co-chaperones to regulate stability and activation of client proteins, many of which are signal transducers. Here, we characterize the first Hsp90 co-chaperone in the leading human fungal pathogen, Candida albicans. We demonstrate that Sgt1 physically interacts with Hsp90, and that it governs C. albicans morphogenesis and drug resistance. Genetic depletion of Sgt1 phenocopies depletion of Hsp90, inducing yeast to filament morphogenesis and invasive growth. Sgt1 governs these traits by bridging two morphogenetic regulators: Hsp90 and the adenylyl cyclase of the cAMP-PKA signaling cascade, Cyr1. Sgt1 physically interacts with Cyr1, and depletion of either Sgt1 or Hsp90 activates cAMP-PKA signaling, revealing the elusive link between Hsp90 and the PKA signaling cascade. Sgt1 also mediates tolerance and resistance to the two most widely deployed classes of antifungal drugs, azoles and echinocandins. Depletion of Sgt1 abrogates basal tolerance and acquired resistance to azoles, which target the cell membrane. Depletion of Sgt1 also abrogates tolerance and resistance to echinocandins, which target the cell wall, and renders echinocandins fungicidal. Though Sgt1 and Hsp90 have a conserved impact on drug resistance, the underlying mechanisms are distinct. Depletion of Hsp90 destabilizes the client protein calcineurin, thereby blocking crucial responses to drug-induced stress; in contrast, depletion of Sgt1 does not destabilize calcineurin, but blocks calcineurin activation in response to drug-induced stress. Sgt1 influences not only morphogenesis and drug resistance, but also virulence, as genetic depletion of C. albicans Sgt1 leads to reduced kidney fungal burden in a murine model of systemic infection. Thus, our characterization of the first Hsp90 co-chaperone in a fungal pathogen establishes C. albicans Sgt1 as a global regulator of morphogenesis and drug resistance, providing a new target for treatment of life-threatening fungal infections.", "link"=>"http://www.mendeley.com/research/hsp90-cochaperone-sgt1-governs-candida-albicans-morphogenesis-drug-resistance", "reader_count"=>38, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>5, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>5, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Nursing and Health Professions"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>27, "Medicine and Dentistry"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>5}}, "group_count"=>1}

CrossRef

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84866114557"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84866114557?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84866114557&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84866114557&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84866114557", "dc:identifier"=>"SCOPUS_ID:84866114557", "eid"=>"2-s2.0-84866114557", "dc:title"=>"The Hsp90 Co-Chaperone Sgt1 Governs Candida albicans Morphogenesis and Drug Resistance", "dc:creator"=>"Shapiro R.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"7", "prism:issueIdentifier"=>"9", "prism:pageRange"=>nil, "prism:coverDate"=>"2012-09-06", "prism:coverDisplayDate"=>"6 September 2012", "prism:doi"=>"10.1371/journal.pone.0044734", "citedby-count"=>"52", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University of Toronto", "affiliation-city"=>"Toronto", "affiliation-country"=>"Canada"}], "pubmed-id"=>"22970302", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e44734", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0044734", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"93", "xml_views"=>"4", "html_views"=>"430"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"33", "xml_views"=>"0", "html_views"=>"99"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"73"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"52"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"18", "xml_views"=>"1", "html_views"=>"69"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"53"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"47"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"56"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"55"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"13", "xml_views"=>"3", "html_views"=>"57"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"48"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"51"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"4", "html_views"=>"22"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"33"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"2", "html_views"=>"30"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"59"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"18", "xml_views"=>"1", "html_views"=>"65"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"14", "xml_views"=>"3", "html_views"=>"48"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"27"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"23"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"58"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"65"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"89"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"85"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"64"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"69"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"40"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"29"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"3", "html_views"=>"27"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"68"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"16"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"3", "html_views"=>"9"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"1"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"1", "year"=>"2020", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"2", "year"=>"2020", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"4"}
  • {"month"=>"3", "year"=>"2020", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"3"}
  • {"month"=>"4", "year"=>"2020", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"5", "year"=>"2020", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"2"}
  • {"month"=>"6", "year"=>"2020", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"7", "year"=>"2020", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"8", "year"=>"2020", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"0"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/581476"], "description"=>"<p>(A) Reduced levels of Sgt1 renders cells sensitive to fluconazole in minimum inhibitory concentration (MIC) assays. Assays were performed in YPD medium with a gradient of fluconazole from 0 to 256 µg/ml, in two-fold dilutions, with or without a fixed concentration of 20 µg/ml doxycycline (DOX), as indicated. Growth was measured by absorbance at 600 nm after 48 hours at 30°C. Optical densities were averaged for duplicate measurements and normalized relative to the no fluconazole control. Data was quantitatively displayed with colour using Treeview (see colour bar). (B) Reduced levels of Sgt1 renders azole-resistant <i>erg3</i> mutants sensitive to fluconazole in MIC assays. Assays were performed in YPD medium with a gradient of fluconazole from 0 to 256 µg/ml, in two-fold dilutions, with a fixed concentration of 20 µg/ml doxycycline, as indicated. Growth was measured after 72 hours at 30°C. Data was analyzed as in part A. (C) Cells with reduced levels of Sgt1 remain viable after exposure to fluconazole. MIC assays were performed in YPD medium with a gradient of fluconazole from 0 to 256 µg/ml, in two-fold dilutions, with or without a fixed concentration of 20 µg/ml doxycycline, as indicated. Assays were grown for 48 hours at 30°C, and cells from the MIC assays were spotted onto YPD medium and incubated at 30°C for 48 hours before plates were photographed.</p>", "links"=>[], "tags"=>["enables", "basal"], "article_id"=>251968, "categories"=>["Biochemistry", "Microbiology"], "users"=>["Rebecca S. Shapiro", "Aimee K. Zaas", "Marisol Betancourt-Quiroz", "John R. Perfect", "Leah E. Cowen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044734.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sgt1_enables_basal_tolerance_and_erg3_mediated_resistance_to_the_azoles_/251968", "title"=>"Sgt1 enables basal tolerance and <i>erg3</i>-mediated resistance to the azoles.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:32:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/581750"], "description"=>"<p>Genetic depletion of Sgt1 leads to reduced kidney fungal burden in a murine model of disseminated infection. CD1 mice were infected with 2.1×10<sup>6</sup> CFU/ml of the wild-type strain or <i>tetO-SGT1/sgt1</i>Δ strain and were treated with tetracycline, as indicated. * Indicates <i>P<</i>0.05, *** indicates <i>P<</i>0.0001, Kruskal-Wallis test.</p>", "links"=>[], "tags"=>["depletion", "sgt1", "leads", "reduced", "kidney", "fungal", "murine", "disseminated"], "article_id"=>252237, "categories"=>["Biochemistry", "Microbiology"], "users"=>["Rebecca S. Shapiro", "Aimee K. Zaas", "Marisol Betancourt-Quiroz", "John R. Perfect", "Leah E. Cowen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044734.g007", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_depletion_of_Sgt1_leads_to_reduced_kidney_fungal_burden_in_a_murine_model_of_disseminated_candidiasis_/252237", "title"=>"Genetic depletion of Sgt1 leads to reduced kidney fungal burden in a murine model of disseminated candidiasis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:37:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/581409"], "description"=>"<p>(A) Depletion of Sgt1 activates cAMP-PKA signaling. PKA activity was measured for cell extracts derived from the indicated strains. Sgt1 or Hsp90 levels were reduced by growth overnight in 20 µg/ml doxycycline, followed by subculture in fresh medium with 20 µg/ml doxycycline and growth until mid-log phase. Data are normalized against the level of PKA activity of wild type cell extracts, and are displayed as means ± standard deviations for triplicate samples. * Indicates <i>P<</i>0.01, ANOVA. (B) Sgt1 and Cyr1 physically interact as measured by reciprocal co-immunoprecipitation of epitope-tagged proteins. Left panel, immunoprecipitation of Sgt1-HA with anti-HA agarose co-purified 6x-His-FLAG-Myc (HFM)-Cyr1, while HFM-Cyr1 did not immunoprecipitate with anti-HA agarose in control cells harbouring only untagged Sgt1. Hsp90 also co-purified with Sgt1-HA, and was not purified in the controls with only untagged Sgt1. Right panel, immunoprecipitation of HFM-Cyr1 with anti-Nickel agarose co-purified Sgt1, while Sgt1 did not immunoprecipitate in control cells harbouring untagged Cyr1. Hsp90 was enriched in the immunoprecipitation of HFM-Cyr1 relative to the control immunoprecipiation with only untagged Cyr1.</p>", "links"=>[], "tags"=>["sgt1", "activates", "camp-pka", "interacts", "adenylyl", "cyclase"], "article_id"=>251902, "categories"=>["Biochemistry", "Microbiology"], "users"=>["Rebecca S. Shapiro", "Aimee K. Zaas", "Marisol Betancourt-Quiroz", "John R. Perfect", "Leah E. Cowen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044734.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Depletion_of_Sgt1_activates_cAMP_PKA_signaling_and_Sgt1_interacts_with_the_adenylyl_cyclase_Cyr1_/251902", "title"=>"Depletion of Sgt1 activates cAMP-PKA signaling, and Sgt1 interacts with the adenylyl cyclase Cyr1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:31:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/581585"], "description"=>"<p>(A) Reduced levels of Sgt1 enhances susceptibility to micafungin in minimum inhibitory concentration (MIC) assays. Assays were performed in YPD medium with a gradient of fluconazole from 0 to 2 µg/ml, in two-fold dilutions, with or without a fixed concentration of 20 µg/ml doxycycline (DOX), as indicated. Growth was measured after 72 hours at 30°C. Data was analyzed as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044734#pone-0044734-g004\" target=\"_blank\">Figure 4</a>. (B) Reduced levels of Sgt1 renders echinocandin-resistant <i>FKS1</i> mutants susceptible to micafungin in MIC assays. Assays were performed in YPD medium with a gradient of fluconazole from 0 to 8 µg/ml, in two-fold dilutions, with or without a fixed concentration of 20 µg/ml doxycycline, as indicated. Growth was measured after 72 hours at 30°C. Data was analyzed as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044734#pone-0044734-g004\" target=\"_blank\">Figure 4</a>. (C) Reduction of Sgt1 levels creates a fungicidal combination with micafungin. MIC assays were performed in YPD medium with a gradient of fluconazole from 0 to 2 µg/ml, in two-fold dilutions, with or without a fixed concentration of 20 µg/ml doxycycline, as indicated. Assays were grown for 72 hours at 30°C, and cells from the MIC assays were spotted onto YPD medium and incubated at 30°C for 48 hours before plates were photographed.</p>", "links"=>[], "tags"=>["sgt1", "levels", "enhances", "susceptibility", "echinocandins", "creates", "fungicidal"], "article_id"=>252073, "categories"=>["Biochemistry", "Microbiology"], "users"=>["Rebecca S. Shapiro", "Aimee K. Zaas", "Marisol Betancourt-Quiroz", "John R. Perfect", "Leah E. Cowen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044734.g005", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reduction_of_Sgt1_levels_enhances_susceptibility_to_echinocandins_and_creates_a_fungicidal_combination_/252073", "title"=>"Reduction of Sgt1 levels enhances susceptibility to echinocandins and creates a fungicidal combination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:34:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/581266"], "description"=>"<p>(A) Genetic depletion of Sgt1 induces filamentation. Sgt1 levels were reduced by growth overnight in 20 µg/ml doxycycline, followed by subculture in fresh medium with 20 µg/ml doxycycline. (B) Genetic depletion of Sgt1 in <i>the tetO-SGT1/sgt1</i>Δ strain leads to wrinkly colony morphology and invasive growth. Cells were plated on YPD agar and grown at 37°C for 3 days. Colonies were washed from the plates with H<sub>2</sub>O. (C) The <i>tetO-SGT1/sgt1</i>Δ strain has lower <i>SGT1</i> transcript levels compared to wild type in the absence of doxycycline (** indicates <i>P<</i>0.01, ANOVA), and <i>SGT1</i> levels are completely depleted upon treatment with doxycycline (* indicates <i>P<</i>0.05, ANOVA). Wild type, <i>SGT1/sgt11</i>Δ, or <i>tetO-SGT1/sgt1</i>Δ cells grown overnight in 20 µg/ml doxycycline, followed by subculture in fresh medium with 20 µg/ml doxycycline and grown until mid-log phase, as indicated. <i>SGT1</i> transcript levels were normalized to <i>GPD1</i>. Data are means ± standard deviations for triplicate samples.</p>", "links"=>[], "tags"=>["depletion", "sgt1", "induces", "wrinkly", "morphology", "invasive"], "article_id"=>251752, "categories"=>["Biochemistry", "Microbiology"], "users"=>["Rebecca S. Shapiro", "Aimee K. Zaas", "Marisol Betancourt-Quiroz", "John R. Perfect", "Leah E. Cowen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044734.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_depletion_of_Sgt1_induces_filamentation_wrinkly_colony_morphology_and_invasive_growth_/251752", "title"=>"Genetic depletion of Sgt1 induces filamentation, wrinkly colony morphology and invasive growth.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:29:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/581699"], "description"=>"<p>(A) Cna1 retains stability upon depletion of Sgt1. Sgt1 levels were reduced by growth overnight in 20 µg/ml doxycycline, followed by subculture in fresh medium with 20 µg/ml doxycycline and growth until mid-log phase. First panel, immune blot analysis of Sgt1 levels (50 µg protein loaded per well); and second panel, immune blot analysis of Cna1-TAP levels (50 µg protein loaded per well). Actin was used as a loading control. (B) Sgt1 is required for Cna1 activation in response to fluconazole or micafungin. Transcript levels of a Cna1-dependent gene, <i>UTR2</i>, were measured for the wild-type (<i>SGT1/SGT1</i>) or <i>tetO-SGT1/sgt1</i>Δ strains by quantitative RT-PCR after growth in rich medium at 30°C with or without 20 µg/ml doxycycline (DOX), 16 µg/ml fluconazole (FL), and 30 ng/ml micafungin (MF), as indicated. <i>UTR2</i> transcript levels were normalized to <i>GPD1</i>. Data are means ± standard deviations for triplicate samples.</p>", "links"=>[], "tags"=>["cna1", "retains", "depletion", "sgt1"], "article_id"=>252190, "categories"=>["Biochemistry", "Microbiology"], "users"=>["Rebecca S. Shapiro", "Aimee K. Zaas", "Marisol Betancourt-Quiroz", "John R. Perfect", "Leah E. Cowen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044734.g006", "stats"=>{"downloads"=>3, "page_views"=>74, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hsp90_client_protein_Cna1_retains_stability_upon_depletion_of_Sgt1_though_Sgt1_is_required_for_Cna1_activation_/252190", "title"=>"Hsp90 client protein Cna1 retains stability upon depletion of Sgt1, though Sgt1 is required for Cna1 activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:36:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/581337"], "description"=>"<p>Hsp90 and Sgt1 physically interact as measured by reciprocal co-immunoprecipitation of epitope-tagged proteins. Left panel, immunoprecipitation of Hsp90-TAP with anti-IgG agarose co-purified Sgt1-HA, while Sgt1-HA did not immunoprecipitate with anti-IgG agarose in control cells harbouring only untagged Hsp90. Right panel, immunoprecipitation of Sgt1-HA with anti-HA agarose co-purified Hsp90, while Hsp90 did not immunoprecipitate in control cells harbouring only untagged Sgt1.</p>", "links"=>[], "tags"=>["interacts", "hsp90"], "article_id"=>251831, "categories"=>["Biochemistry", "Microbiology"], "users"=>["Rebecca S. Shapiro", "Aimee K. Zaas", "Marisol Betancourt-Quiroz", "John R. Perfect", "Leah E. Cowen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044734.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sgt1_physically_interacts_with_Hsp90_in_C_albicans_/251831", "title"=>"Sgt1 physically interacts with Hsp90 in <i>C. albicans</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:30:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/306167", "https://ndownloader.figshare.com/files/306229", "https://ndownloader.figshare.com/files/306287", "https://ndownloader.figshare.com/files/306338", "https://ndownloader.figshare.com/files/306422", "https://ndownloader.figshare.com/files/306470", "https://ndownloader.figshare.com/files/306566"], "description"=>"<div><p>The molecular chaperone Hsp90 orchestrates regulatory circuitry governing fungal morphogenesis, biofilm development, drug resistance, and virulence. Hsp90 functions in concert with co-chaperones to regulate stability and activation of client proteins, many of which are signal transducers. Here, we characterize the first Hsp90 co-chaperone in the leading human fungal pathogen, <em>Candida albicans</em>. We demonstrate that Sgt1 physically interacts with Hsp90, and that it governs <em>C. albicans</em> morphogenesis and drug resistance. Genetic depletion of Sgt1 phenocopies depletion of Hsp90, inducing yeast to filament morphogenesis and invasive growth. Sgt1 governs these traits by bridging two morphogenetic regulators: Hsp90 and the adenylyl cyclase of the cAMP-PKA signaling cascade, Cyr1. Sgt1 physically interacts with Cyr1, and depletion of either Sgt1 or Hsp90 activates cAMP-PKA signaling, revealing the elusive link between Hsp90 and the PKA signaling cascade. Sgt1 also mediates tolerance and resistance to the two most widely deployed classes of antifungal drugs, azoles and echinocandins. Depletion of Sgt1 abrogates basal tolerance and acquired resistance to azoles, which target the cell membrane. Depletion of Sgt1 also abrogates tolerance and resistance to echinocandins, which target the cell wall, and renders echinocandins fungicidal. Though Sgt1 and Hsp90 have a conserved impact on drug resistance, the underlying mechanisms are distinct. Depletion of Hsp90 destabilizes the client protein calcineurin, thereby blocking crucial responses to drug-induced stress; in contrast, depletion of Sgt1 does not destabilize calcineurin, but blocks calcineurin activation in response to drug-induced stress. Sgt1 influences not only morphogenesis and drug resistance, but also virulence, as genetic depletion of <em>C. albicans</em> Sgt1 leads to reduced kidney fungal burden in a murine model of systemic infection. Thus, our characterization of the first Hsp90 co-chaperone in a fungal pathogen establishes <em>C. albicans</em> Sgt1 as a global regulator of morphogenesis and drug resistance, providing a new target for treatment of life-threatening fungal infections.</p> </div>", "links"=>[], "tags"=>["hsp90", "co-chaperone", "sgt1", "governs", "morphogenesis"], "article_id"=>120403, "categories"=>["Biochemistry", "Microbiology"], "users"=>["Rebecca S. Shapiro", "Aimee K. Zaas", "Marisol Betancourt-Quiroz", "John R. Perfect", "Leah E. Cowen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0044734.s001", "https://dx.doi.org/10.1371/journal.pone.0044734.s002", "https://dx.doi.org/10.1371/journal.pone.0044734.s003", "https://dx.doi.org/10.1371/journal.pone.0044734.s004", "https://dx.doi.org/10.1371/journal.pone.0044734.s005", "https://dx.doi.org/10.1371/journal.pone.0044734.s006", "https://dx.doi.org/10.1371/journal.pone.0044734.s007"], "stats"=>{"downloads"=>7, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Hsp90_Co_Chaperone_Sgt1_Governs_Candida_albicans_Morphogenesis_and_Drug_Resistance/120403", "title"=>"The Hsp90 Co-Chaperone Sgt1 Governs <em>Candida albicans</em> Morphogenesis and Drug Resistance", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-06 00:06:43"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"73", "full-text"=>"83", "pdf"=>"42", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"46", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"61", "full-text"=>"63", "pdf"=>"41", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"28", "supp-data"=>"9", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"39", "full-text"=>"41", "pdf"=>"22", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"24", "full-text"=>"24", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"23", "full-text"=>"24", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"19", "full-text"=>"14", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"45", "full-text"=>"44", "pdf"=>"33", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"23", "full-text"=>"27", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"19", "full-text"=>"16", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"16", "full-text"=>"18", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"18", "full-text"=>"22", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"22", "full-text"=>"22", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"15", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"383", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"221", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"6", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"6", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"12", "full-text"=>"6", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"21", "full-text"=>"13", "pdf"=>"10", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"4", "cited-by"=>"1", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"16", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"19", "full-text"=>"18", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"27", "full-text"=>"24", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"20", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"5", "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"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"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"=>"10"}
  • {"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"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"2", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"11", "full-text"=>"15", "pdf"=>"1", "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"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"3", "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"=>"10", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"18", "full-text"=>"9", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"1", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"2", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"4", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"5", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"7", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"22", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Microbiology", "average_usage"=>[339, 580, 709, 814, 907, 1003, 1095, 1190, 1286, 1375, 1466, 1546, 1622, 1694, 1765, 1830, 1902, 1978, 2054, 2122, 2194, 2269, 2330, 2388, 2460]}, {"subject_area"=>"/Biology and life sciences/Mycology", "average_usage"=>[375, 602, 746, 847, 942, 1060, 1162, 1258, 1358, 1453, 1528, 1646, 1768, 1830, 1928, 1980, 2060, 2153, 2240, 2316, 2380, 2453, 2540, 2617, 2695]}, {"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[331, 557, 677, 777, 868, 960, 1050, 1136, 1223, 1307, 1390, 1466, 1536, 1603, 1673, 1741, 1814, 1889, 1954, 2028, 2096, 2164, 2233, 2305, 2362]}, {"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/Pathology and laboratory medicine", "average_usage"=>[321, 553, 683, 785, 880, 973, 1072, 1162, 1249, 1336, 1425, 1504, 1574, 1642, 1711, 1785, 1852, 1923, 1987, 2050, 2129, 2192, 2259, 2325, 2393]}]}
Loading … Spinner
There are currently no alerts