Cyclosporin A Treatment of Leishmania donovani Reveals Stage-Specific Functions of Cyclophilins in Parasite Proliferation and Viability
Publication Date
June 29, 2010
Journal
PLOS Neglected Tropical Diseases
Authors
Wai Lok Yau, Thierry Blisnick, Jean François Taly, Manuela Helmer Citterich, et al
Volume
4
Issue
6
Pages
e729
DOI
https://dx.plos.org/10.1371/journal.pntd.0000729
Publisher URL
http://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0000729
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/20614016
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894131
Europe PMC
http://europepmc.org/abstract/MED/20614016
Web of Science
000279341300034
Scopus
77956997367
Mendeley
http://www.mendeley.com/research/cyclosporin-treatment-leishmania-donovani-reveals-stagespecific-functions-cyclophilins-parasite-prol
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Cyclosporin A treatment of Leishmania donovani reveals stage-specific functions of cyclophilins in parasite proliferation and viability", "type"=>"journal", "authors"=>[{"first_name"=>"Wai Lok", "last_name"=>"Yau", "scopus_author_id"=>"36547140700"}, {"first_name"=>"Thierry", "last_name"=>"Blisnick", "scopus_author_id"=>"6602353318"}, {"first_name"=>"Jean François", "last_name"=>"Taly", "scopus_author_id"=>"8846904000"}, {"first_name"=>"Manuela", "last_name"=>"Helmer-Citterich", "scopus_author_id"=>"6603748349"}, {"first_name"=>"Cordelia", "last_name"=>"Schiene-Fischer", "scopus_author_id"=>"55957075200"}, {"first_name"=>"Olivier", "last_name"=>"Leclercq", "scopus_author_id"=>"24503519500"}, {"first_name"=>"Jing", "last_name"=>"Li", "scopus_author_id"=>"36078695800"}, {"first_name"=>"Dirk", "last_name"=>"Schmidt-Arras", "scopus_author_id"=>"8786425400"}, {"first_name"=>"Miguel A.", "last_name"=>"Morales", "scopus_author_id"=>"35551605500"}, {"first_name"=>"Cedric", "last_name"=>"Notredame", "scopus_author_id"=>"6602109477"}, {"first_name"=>"Daniel", "last_name"=>"Romo", "scopus_author_id"=>"7004023555"}, {"first_name"=>"Philippe", "last_name"=>"Bastin", "scopus_author_id"=>"55917121900"}, {"first_name"=>"Gerald F.", "last_name"=>"Späth", "scopus_author_id"=>"7003643165"}], "year"=>2010, "source"=>"PLoS Neglected Tropical Diseases", "identifiers"=>{"issn"=>"1935-2735", "scopus"=>"2-s2.0-77956997367", "pui"=>"359899932", "doi"=>"10.1371/journal.pntd.0000729", "isbn"=>"1935-2735 (Electronic)\\r1935-2727 (Linking)", "sgr"=>"77956997367", "pmid"=>"20614016"}, "id"=>"b3292e00-5b0e-3eeb-b681-15116edd00cd", "abstract"=>"BACKGROUND: Cyclosporin A (CsA) has important anti-microbial activity against parasites of the genus Leishmania, suggesting CsA-binding cyclophilins (CyPs) as potential drug targets. However, no information is available on the genetic diversity of this important protein family, and the mechanisms underlying the cytotoxic effects of CsA on intracellular amastigotes are only poorly understood. Here, we performed a first genome-wide analysis of Leishmania CyPs and investigated the effects of CsA on host-free L. donovani amastigotes in order to elucidate the relevance of these parasite proteins for drug development.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Multiple sequence alignment and cluster analysis identified 17 Leishmania CyPs with significant sequence differences to human CyPs, but with highly conserved functional residues implicated in PPIase function and CsA binding. CsA treatment of promastigotes resulted in a dose-dependent inhibition of cell growth with an IC50 between 15 and 20 microM as demonstrated by proliferation assay and cell cycle analysis. Scanning electron microscopy revealed striking morphological changes in CsA treated promastigotes reminiscent to developing amastigotes, suggesting a role for parasite CyPs in Leishmania differentiation. In contrast to promastigotes, CsA was highly toxic to amastigotes with an IC50 between 5 and 10 microM, revealing for the first time a direct lethal effect of CsA on the pathogenic mammalian stage linked to parasite thermotolerance, independent from host CyPs. Structural modeling, enrichment of CsA-binding proteins from parasite extracts by FPLC, and PPIase activity assays revealed direct interaction of the inhibitor with LmaCyP40, a bifunctional cyclophilin with potential co-chaperone function.\\n\\nCONCLUSIONS/SIGNIFICANCE: The evolutionary expansion of the Leishmania CyP protein family and the toxicity of CsA on host-free amastigotes suggest important roles of PPIases in parasite biology and implicate Leishmania CyPs in key processes relevant for parasite proliferation and viability. The requirement of Leishmania CyP functions for intracellular parasite survival and their substantial divergence form host CyPs defines these proteins as prime drug targets.", "link"=>"http://www.mendeley.com/research/cyclosporin-treatment-leishmania-donovani-reveals-stagespecific-functions-cyclophilins-parasite-prol", "reader_count"=>46, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>10, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>10, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>24, "Business, Management and Accounting"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>4, "Computer Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Chemistry"=>{"Chemistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Computer Science"=>{"Computer Science"=>2}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Brazil"=>5, "United Kingdom"=>1, "India"=>2}, "group_count"=>1}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/77956997367"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/77956997367?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77956997367&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=77956997367&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/77956997367", "dc:identifier"=>"SCOPUS_ID:77956997367", "eid"=>"2-s2.0-77956997367", "dc:title"=>"Cyclosporin A treatment of Leishmania donovani reveals stage-specific functions of cyclophilins in parasite proliferation and viability", "dc:creator"=>"Yau W.", "prism:publicationName"=>"PLoS Neglected Tropical Diseases", "prism:volume"=>"4", "prism:issueIdentifier"=>"6", "prism:pageRange"=>nil, "prism:coverDate"=>"2010-06-01", "prism:coverDisplayDate"=>"June 2010", "prism:doi"=>"10.1371/journal.pntd.0000729", "citedby-count"=>"26", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Institut Pasteur, Paris", "affiliation-city"=>"Paris", "affiliation-country"=>"France"}], "pubmed-id"=>"20614016", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e729", "source-id"=>"11900154404", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosntds%2Farticle%3Fid%3D10.1371%252Fjournal.pntd.0000729", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"6", "year"=>"2010", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"59"}
  • {"month"=>"7", "year"=>"2010", "pdf_views"=>"70", "xml_views"=>"6", "html_views"=>"333"}
  • {"month"=>"8", "year"=>"2010", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"58"}
  • {"month"=>"9", "year"=>"2010", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"62"}
  • {"month"=>"10", "year"=>"2010", "pdf_views"=>"20", "xml_views"=>"2", "html_views"=>"68"}
  • {"month"=>"11", "year"=>"2010", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"89"}
  • {"month"=>"12", "year"=>"2010", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"1", "year"=>"2011", "pdf_views"=>"10", "xml_views"=>"3", "html_views"=>"51"}
  • {"month"=>"2", "year"=>"2011", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"53"}
  • {"month"=>"3", "year"=>"2011", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"59"}
  • {"month"=>"4", "year"=>"2011", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"40"}
  • {"month"=>"5", "year"=>"2011", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"6", "year"=>"2011", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"29"}
  • {"month"=>"7", "year"=>"2011", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"8", "year"=>"2011", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"36"}
  • {"month"=>"9", "year"=>"2011", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"82"}
  • {"month"=>"10", "year"=>"2011", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"73"}
  • {"month"=>"11", "year"=>"2011", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"65"}
  • {"month"=>"12", "year"=>"2011", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"64"}
  • {"month"=>"1", "year"=>"2012", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"82"}
  • {"month"=>"2", "year"=>"2012", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"3", "year"=>"2012", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"74"}
  • {"month"=>"4", "year"=>"2012", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"71"}
  • {"month"=>"5", "year"=>"2012", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"82"}
  • {"month"=>"6", "year"=>"2012", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"71"}
  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"75"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"9", "xml_views"=>"5", "html_views"=>"50"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"48"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"82"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"185"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"138"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"105"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"169"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"3", "html_views"=>"231"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"179"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"92"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"67"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"10", "xml_views"=>"2", "html_views"=>"64"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"76"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"2", "xml_views"=>"2", "html_views"=>"113"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"94"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"4", "xml_views"=>"2", "html_views"=>"82"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"47"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"31"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"52"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"53"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"2", "html_views"=>"23"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"24"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"16"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"14"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"16"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"3", "html_views"=>"16"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"0", "xml_views"=>"1", "html_views"=>"9"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"1"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"6"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"13"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"3"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"28", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"17", "xml_views"=>"2", "html_views"=>"7"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"1", "year"=>"2020", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"2", "year"=>"2020", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"3", "year"=>"2020", "pdf_views"=>"7", "xml_views"=>"3", "html_views"=>"3"}
  • {"month"=>"4", "year"=>"2020", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"2"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/842619"], "description"=>"<p>(<i>A</i>) Parasites were treated for up to 48 hours with CsA at the concentrations indicated at 26°C and pH 7.4 for promastigotes, or 37°C and pH 5.5 for amastigotes. Cell density of the samples was estimated using CASY cell counter and expressed in cell density per milliliter. (<i>B</i>) <i>Left panel, growth assessment</i>. Logarithmic promastigotes (pro, □) and axenic amastigotes (ama, ○) were incubated for 48 hours with CsA at the indicated concentrations. Cell density of the samples was estimated using hemocytometer and expressed in % of growth compared to solvent treated controls. <i>Right panel, cell proliferation and viability assay</i>. Promastigotes and axenic amastigotes were treated as detailed in (A). 20 µl of CellTiter-Blue solution was added to the cells after 48 hours of CsA treatment, and the assay was further incubated for 4 hours at 37°C. Resazurin reduction was expressed in % of fluorescence compared to solvent treated cells control. Results are representative of three quadruplicate experiments with mean ± S.D. indicated by the error bars.</p>", "links"=>[], "tags"=>["inhibits", "donovani"], "article_id"=>513063, "categories"=>["Medicine", "Physics", "Cell Biology", "Virology"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000729.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CsA_inhibits_L_donovani_in_vitro_growth_/513063", "title"=>"CsA inhibits <i>L. donovani in vitro</i> growth.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-29 00:51:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/419672", "https://ndownloader.figshare.com/files/419686"], "description"=>"<div><h3>Background</h3><p>Cyclosporin A (CsA) has important anti-microbial activity against parasites of the genus <em>Leishmania</em>, suggesting CsA-binding cyclophilins (CyPs) as potential drug targets. However, no information is available on the genetic diversity of this important protein family, and the mechanisms underlying the cytotoxic effects of CsA on intracellular amastigotes are only poorly understood. Here, we performed a first genome-wide analysis of <em>Leishmania</em> CyPs and investigated the effects of CsA on host-free <em>L. donovani</em> amastigotes in order to elucidate the relevance of these parasite proteins for drug development.</p><h3>Methodology/Principal Findings</h3><p>Multiple sequence alignment and cluster analysis identified 17 <em>Leishmania</em> CyPs with significant sequence differences to human CyPs, but with highly conserved functional residues implicated in PPIase function and CsA binding. CsA treatment of promastigotes resulted in a dose-dependent inhibition of cell growth with an IC50 between 15 and 20 µM as demonstrated by proliferation assay and cell cycle analysis. Scanning electron microscopy revealed striking morphological changes in CsA treated promastigotes reminiscent to developing amastigotes, suggesting a role for parasite CyPs in <em>Leishmania</em> differentiation. In contrast to promastigotes, CsA was highly toxic to amastigotes with an IC50 between 5 and 10 µM, revealing for the first time a direct lethal effect of CsA on the pathogenic mammalian stage linked to parasite thermotolerance, independent from host CyPs. Structural modeling, enrichment of CsA-binding proteins from parasite extracts by FPLC, and PPIase activity assays revealed direct interaction of the inhibitor with LmaCyP40, a bifunctional cyclophilin with potential co-chaperone function.</p><h3>Conclusions/Significance</h3><p>The evolutionary expansion of the <em>Leishmania</em> CyP protein family and the toxicity of CsA on host-free amastigotes suggest important roles of PPIases in parasite biology and implicate <em>Leishmania</em> CyPs in key processes relevant for parasite proliferation and viability. The requirement of <em>Leishmania</em> CyP functions for intracellular parasite survival and their substantial divergence form host CyPs defines these proteins as prime drug targets.</p></div>", "links"=>[], "tags"=>["cyclosporin", "reveals", "stage-specific", "functions", "cyclophilins", "parasite", "proliferation", "viability"], "article_id"=>142858, "categories"=>["Medicine", "Physics", "Cell Biology", "Cancer"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000729.s001", "https://dx.doi.org/10.1371/journal.pntd.0000729.s002"], "stats"=>{"downloads"=>3, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Cyclosporin_A_Treatment_of_Leishmania_donovani_Reveals_Stage_Specific_Functions_of_Cyclophilins_in_Parasite_Proliferation_and_Viability/142858", "title"=>"Cyclosporin A Treatment of <em>Leishmania donovani</em> Reveals Stage-Specific Functions of Cyclophilins in Parasite Proliferation and Viability", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-06-29 00:47:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/843296"], "description"=>"<p><b>Footnote.</b> PPIase like proteins were retrieved by Blast analysis of the PPIase signature sequences in GeneDB (<a href=\"http://www.genedb.org\" target=\"_blank\">www.genedb.org</a>). Prosite accession numbers of the domains are: CSA_PPIASE: PS50072; FKBP_PPIASE: PS50059; PPIC_PPIASE: PS01096; PROKAR_LIPOPR: PS51257; TPR: PS50005; FHA: PS50006. Sequences flanking the PPIase domain were analyzed by Blast search in NCBI (blast.ncbi.nlm.nih.gov/Blast.cgi). 1, a single PPIase domain without any significant N- or C-terminal sequence extensions; 2, presence of parasite-specific N-terminal (N), C-terminal (C), or both extensions; 3, presence of additional functional domains;</p><p>*, represents the extension is unique to <i>Leishmania</i>;</p><p>#, Protein function with experimental support published <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000729#pntd.0000729-Rascher1\" target=\"_blank\">[60]</a>, <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000729#pntd.0000729-Dutta1\" target=\"_blank\">[61]</a>.</p>", "links"=>[], "tags"=>["containing", "proteins"], "article_id"=>513744, "categories"=>["Medicine", "Physics", "Cell Biology", "Virology"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000729.t001", "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PPIase_domain_containing_proteins_in_Leishmania_major_/513744", "title"=>"PPIase domain containing proteins in <i>Leishmania major</i>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-06-29 01:02:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/843143"], "description"=>"<p>(<i>A</i>) <i>Structural modelling</i>. Cyclosporin (CsA) binding pockets of <i>L. donovani</i> cyclophilin CyP2 (PDB code: 3eov, left upper panel) and <i>L. major</i> CyP40 in the presence of the CsA ligand (model complex, right upper panel) are shown. Cyclophilin residues are coloured in yellow and CsA is coloured by atom type. H-bonds are displayed as green dotted lines. The lower panel shows a multiple sequence alignment of the CsA binding regions of <i>L. donovani</i> CyP2 (PDB code: 3eov) and the six <i>L. major</i> cyclophilins analyzed. The residues in close proximity to the ligand are shown in bold. Yellow and orange filling identifies residues forming respectively one or two hydrogen bonds with CsA atoms. (<i>B</i>) <i>Affinity chromatography and Western blotting</i>. Total protein extracts obtained from logarithmic <i>L. donovani</i> promastigote cultures were incubated with resin alone (−), or resin coupled with CsA (+), bound proteins were analyzed by SDS-PAGE and SyproRuby staining, and identified by MS analysis (left panel, CyP2), or Western blotting using polyclonal anti-LmaCyP40 antibody (right panel). In, input; Ft, flow through; El, eluate. (<i>C</i>) <i>PPIase assay</i>. The <i>cis/trans</i> isomerization activity of recombinant <i>Leishmania major</i> GST::Strep::CyP40 was performed using Abz-Ala-Ala-Pro-Phe-pNA as substrate. Determination of k<sub>cat</sub>/K<sub>m</sub> (upper panel) was performed by evaluation of the linear dependency of k<sub>enz</sub> from the concentration of GST::Strep::CyP40. Each data point represents the mean of three independent measurements. The lower panel shows inhibition of <i>Leishmania major</i> GST::Strep::CyP40 peptidyl prolyl <i>cis/trans</i> isomerase activity by CsA. PPIase activity was measured at increasing amounts of CsA using the substrate Abz-Ala-Ala-Pro-Phe-pNA.</p>", "links"=>[], "tags"=>["cyclophilin", "40"], "article_id"=>513585, "categories"=>["Medicine", "Physics", "Cell Biology", "Virology"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000729.g008", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Leishmania_cyclophilin_40_is_a_target_for_CsA_/513585", "title"=>"<i>Leishmania</i> cyclophilin 40 is a target for CsA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-29 00:59:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/842951"], "description"=>"<p>Parasites were treated for 48 hours with either CsA or FK506 at the concentrations indicated at 26°C and pH 7.4 for promastigotes, or 37°C and pH 5.5 for amastigotes. (<i>A</i>) Cell density of the samples was estimated using CASY cell counter and expressed in cell number per milliliter, after 24 to 48 hours treatment. (<i>B</i>) Cell proliferation was measured using CellTiter-Blue cell viability assay by following resazurin reduction, which is expressed in % of fluorescence compared to solvent treated cells control. (<i>C</i>) Cell death was measured by propidium iodide staining and FACS analysis as detailed in legend of <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000729#pntd-0000729-g003\" target=\"_blank\">Fig. 3</a>. Results of (<i>A</i>) are representative of three quadruplicate experiments with mean ± S.D represented by the error bars. Three independent experiments were performed for (B) with the error bars representing ±S.D.</p>", "links"=>[], "tags"=>["stage-specific", "csa"], "article_id"=>513397, "categories"=>["Medicine", "Physics", "Cell Biology", "Virology"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000729.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_stage_specific_effects_of_CsA_occur_through_distinct_mechanisms_/513397", "title"=>"The stage-specific effects of CsA occur through distinct mechanisms.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-29 00:56:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/842409"], "description"=>"<p>17 CyP-like proteins are annotated in the <i>L. major</i> genome database (LmaCyPs). The cyclophilin-like domain (CLD) and other domains were identified with ScanProsite. Most LmaCyPs are characterized by parasite-specific N- and C-terminal extensions. Additional functional domains are identified in two LmaCyPs, LmjF31.0050 (LmaCyP5) and LmjF35.4770 (LmaCyP40), containing a prokaryotic lipid attachment domain (PLD) and tetratricopeptide repeat domains (TPR), respectively. The bar represents 100 amino acids.</p>", "links"=>[], "tags"=>["cyp-like"], "article_id"=>512855, "categories"=>["Medicine", "Physics", "Cell Biology", "Virology"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000729.g001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Diagram_representing_the_L_major_CyP_like_proteins_/512855", "title"=>"Diagram representing the <i>L. major</i> CyP-like proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-29 00:47:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/842696"], "description"=>"<p><i>(A) FACS analysis</i>. Logarithmic promastigotes (black bars) and axenic amastigotes (grey bars) were incubated for 48 hours with the indicated CsA concentrations. The cells were then washed once with PBS, stained with 2 µg/ml of PI and analyzed by FACS. Proportion of dead parasites is expressed in % of PI positive (+) stained cells after subtracting the background of solvent treated cells control. The error bars represent the mean±S.D. of four independent experiments. <i>(B) Cell cycle analysis</i>. CsA-treated promastigotes were fixed in cold 90% methanol and stained with propidium iodide for cell cycle analysis. The stained cells were subjected to FACS analysis (exλ = 488 nm/emλ = 617 nm). 10,000 events were analyzed and cell cycle distribution was calculated with the model Dean-Jett-Fox using the FlowJo Software package (Tree Star, Inc.). At least two independent experiments were performed and representative results are shown.</p>", "links"=>[], "tags"=>["affects", "viability"], "article_id"=>513144, "categories"=>["Medicine", "Physics", "Cell Biology", "Virology"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000729.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CsA_affects_L_donovani_viability_and_proliferation_/513144", "title"=>"CsA affects <i>L. donovani</i> viability and proliferation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-29 00:52:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/843052"], "description"=>"<p>Axenic amastigotes and promastigotes were either treated with solvent or 15 µM CsA, and incubated at either 26°C or 37°C. At the time points indicated, aliquots of the cells were stained with propidium iodide and analyzed by FACS. The proportion of dead parasites is expressed in % of PI positive (+) cells. Three independent experiments were performed, and one representative triplicate experiment is shown. The error bars represent ±S.D.</p>", "links"=>[], "tags"=>["affects"], "article_id"=>513498, "categories"=>["Medicine", "Physics", "Cell Biology", "Virology"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000729.g007", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CsA_affects_L_donovani_thermotolerance_/513498", "title"=>"CsA affects <i>L. donovani</i> thermotolerance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-29 00:58:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/842835"], "description"=>"<p>Promastigotes were incubated with 0.15% ethanol or 15 µM (B, C) or 20 µM (A) CsA at 26°C, pH 7.4 for 72 hours. Axenic amastigotes were prepared as described in experimental procedure. 10<sup>7</sup> cells were fixed with either methanol for Giemsa staining (<i>A</i>), or 2.5% glutaraldehyde for scanning electron microscopy (<i>B</i>). The bar corresponds to 1 µm (B) and 5 µm (A). Two independent experiments were performed and representative fields are shown. (<i>C</i>) <i>Flagellum length measurement</i>. CsA-treated and solvent treated cells <i>L. donovani</i> promastigotes were fixed in methanol and stained with anti-tubulin monoclonal antibody. Flagellum length was measured from a total of 180 cells each for control and CsA-treated samples. Only cells with a single flagellum that was completely visible and fully in focus were taken into account. Samples were observed with a DMR Leica microscope and images were captured with a Cool Snap HQ camera (Roper Scientific). Images were analysed using the IPLab Spectrum 3.9 software (Scanalytics & BD Biosciences) and flagellum length was measured using ImageJ (NIH). (<i>D</i>) <i>Immunoblot analysis of CsA treated parasites</i>. Parasites were treated with solvent or 15 µM CsA for 72 hours, lysed in 1× Laemmli buffer, and lysates equal to 2×10<sup>7</sup> cells were analyzed by immunoblotting. Promastigote specific marker LPG (upper), amastigote specific marker A2 (middle) and α-tubulin (lower) were analyzed. Two independent experiments which gave identical results were performed.</p>", "links"=>[], "tags"=>["promastigotes", "altered"], "article_id"=>513277, "categories"=>["Medicine", "Physics", "Cell Biology", "Virology"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000729.g005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CsA_treated_L_donovani_promastigotes_show_altered_morphology_/513277", "title"=>"CsA-treated <i>L. donovani</i> promastigotes show altered morphology.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-29 00:54:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/842512"], "description"=>"<p>(<i>A</i>) <i>Neighbor-Joining tree (500 bootstrap replicates) of the 118 CyP-like proteins</i>. CyP proteins were identified by PSI-Blasting Human PPIaseA against Human, <i>L. major</i>, <i>L. infantum</i>, <i>L. braziliensis</i>, <i>T. brucei</i>, and <i>T. cruzi</i> genomes. Multiple sequence alignment was performed with T-Coffee and fed into the MEGA4 software package. Numbers on nodes indicate bootstrap support. (<i>B</i>) <i>UPGMA clustering of CyP functional residues</i>. Positions corresponding to the CsA binding sites (as defined on the Human PPIaseA) are displayed on the figure along with the CyP-like protein they originate from. The UPGMA clustering shows groups of putatively identical binding sites.</p>", "links"=>[], "tags"=>["cyp-like"], "article_id"=>512958, "categories"=>["Medicine", "Physics", "Cell Biology", "Virology"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000729.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bioinformatics_analysis_of_the_L_major_CyP_like_protein_family_/512958", "title"=>"Bioinformatics analysis of the <i>L. major</i> CyP-like protein family.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-29 00:49:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/843255"], "description"=>"<p><b>Footnote</b>. The functional amino acid residues implicated in PPIase catalytic activity and CsA binding of human CyPA (HsCyPA) (NCBI accession no. NP_066953) are shown <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000729#pntd.0000729-Zydowsky1\" target=\"_blank\">[73]</a>, <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000729#pntd.0000729-Pflugl1\" target=\"_blank\">[74]</a>. LmaCyPs were aligned against the human CyPA domain by ClustalX 2.0 with matrix Blosum62. Amino acid changes of LmaCyPs compared to human CyPA are shown.</p>", "links"=>[], "tags"=>["lmacyp", "sites", "compared"], "article_id"=>513695, "categories"=>["Medicine", "Physics", "Cell Biology", "Virology"], "users"=>["Wai-Lok Yau", "Thierry Blisnick", "Jean-François Taly", "Manuela Helmer-Citterich", "Cordelia Schiene-Fischer", "Olivier Leclercq", "Jing Li", "Dirk Schmidt-Arras", "Miguel A. Morales", "Cedric Notredame", "Daniel Romo", "Philippe Bastin", "Gerald F. Späth"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000729.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Conservation_of_LmaCyP_functional_sites_compared_to_human_CyPA_/513695", "title"=>"Conservation of LmaCyP functional sites compared to human CyPA.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-06-29 01:01:35"}

PMC Usage Stats | Further Information

  • {"scanned-page-browse"=>"0", "month"=>"7", "cited-by"=>"0", "abstract"=>"11", "full-text"=>"28", "unique-ip"=>"32", "pdf"=>"18", "year"=>"2010", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"8", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"5", "full-text"=>"34", "year"=>"2010", "pdf"=>"28", "unique-ip"=>"40", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"4"}
  • {"scanned-page-browse"=>"0", "month"=>"9", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"22", "unique-ip"=>"24", "pdf"=>"16", "year"=>"2010", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"10", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"25", "year"=>"2010", "pdf"=>"24", "unique-ip"=>"33", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"11", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"18", "unique-ip"=>"26", "pdf"=>"18", "year"=>"2010", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"14", "year"=>"2010", "pdf"=>"10", "unique-ip"=>"15", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"14", "unique-ip"=>"17", "pdf"=>"9", "year"=>"2011", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"23", "year"=>"2011", "pdf"=>"13", "unique-ip"=>"24", "figure"=>"11", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"5", "full-text"=>"29", "unique-ip"=>"34", "pdf"=>"14", "year"=>"2011", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"6", "full-text"=>"13", "year"=>"2011", "pdf"=>"8", "unique-ip"=>"18", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"4", "full-text"=>"17", "unique-ip"=>"21", "pdf"=>"10", "year"=>"2011", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"26", "year"=>"2011", "pdf"=>"6", "unique-ip"=>"19", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"7", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"29", "unique-ip"=>"21", "pdf"=>"8", "year"=>"2011", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"8", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"4", "year"=>"2011", "pdf"=>"4", "unique-ip"=>"4", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"9", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"9", "unique-ip"=>"8", "pdf"=>"5", "year"=>"2011", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"10", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"14", "year"=>"2011", "pdf"=>"3", "unique-ip"=>"15", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"11", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"11", "unique-ip"=>"11", "pdf"=>"10", "year"=>"2011", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"13", "year"=>"2011", "pdf"=>"6", "unique-ip"=>"13", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"15", "unique-ip"=>"12", "pdf"=>"5", "year"=>"2012", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"8", "year"=>"2012", "pdf"=>"4", "unique-ip"=>"10", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"23", "unique-ip"=>"22", "pdf"=>"18", "year"=>"2012", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"13", "year"=>"2012", "pdf"=>"12", "unique-ip"=>"16", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"15", "unique-ip"=>"11", "pdf"=>"5", "year"=>"2012", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"11", "year"=>"2012", "pdf"=>"4", "unique-ip"=>"10", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"unique-ip"=>"19", "full-text"=>"18", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"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"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"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"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"1", "full-text"=>"0", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"12", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"11", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"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"=>"5"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"3", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"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"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"3", "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"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"1", "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"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"4", "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"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "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"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"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"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "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"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"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"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}

Relative Metric

{"start_date"=>"2010-01-01T00:00:00Z", "end_date"=>"2010-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[283, 565, 720, 852, 970, 1070, 1168, 1258, 1336, 1411, 1487, 1571, 1640, 1709, 1776, 1843, 1906, 1969, 2031, 2086, 2152, 2221, 2286, 2361, 2419, 2480, 2543, 2598, 2665, 2731, 2802, 2868, 2932, 2996, 3053, 3114, 3169, 3232, 3289, 3355, 3413, 3473, 3530, 3595, 3648, 3711, 3764, 3810, 3863]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[265, 560, 722, 863, 978, 1083, 1172, 1261, 1345, 1428, 1488, 1559, 1630, 1701, 1764, 1840, 1899, 1965, 2028, 2088, 2150, 2211, 2270, 2348, 2410, 2461, 2531, 2598, 2645, 2719, 2793, 2870, 2923, 2974, 3020, 3080, 3142, 3198, 3259, 3351, 3418, 3471, 3527, 3581, 3637, 3706, 3761, 3817, 3872]}, {"subject_area"=>"/Biology and life sciences/Microbiology", "average_usage"=>[306, 616, 785, 930, 1062, 1178, 1267, 1361, 1440, 1545, 1627, 1690, 1764, 1825, 1903, 1965, 2043, 2099, 2172, 2232, 2313, 2376, 2451, 2524, 2595, 2661, 2729, 2781, 2848, 2911, 2974, 3059, 3138, 3196, 3272, 3342, 3408, 3471, 3530, 3601, 3661, 3734, 3803, 3862, 3922, 3966, 4035, 4092, 4165]}, {"subject_area"=>"/Biology and life sciences/Parasitology", "average_usage"=>[277, 573, 714, 825, 931, 1032, 1126, 1207, 1278, 1351, 1422, 1495, 1558, 1626, 1696, 1747, 1811, 1888, 1954, 2005, 2095, 2149, 2214, 2277, 2318, 2389, 2436, 2493, 2567, 2666, 2727, 2784, 2871, 2936, 2984, 3058, 3116, 3178, 3223, 3295, 3360, 3423, 3504, 3579, 3645, 3716, 3757, 3826, 3873]}, {"subject_area"=>"/Medicine and health sciences/Pathology and laboratory medicine", "average_usage"=>[274, 546, 703, 837, 951, 1058, 1152, 1234, 1323, 1387, 1453, 1538, 1606, 1694, 1753, 1814, 1873, 1941, 2011, 2079, 2137, 2193, 2260, 2325, 2386, 2459, 2528, 2598, 2651, 2728, 2788, 2859, 2931, 2999, 3068, 3131, 3209, 3258, 3321, 3372, 3426, 3500, 3561, 3613, 3685, 3743, 3805, 3839]}]}
Loading … Spinner
There are currently no alerts