Globotriaosylsphingosine Accumulation and Not Alpha-Galactosidase-A Deficiency Causes Endothelial Dysfunction in Fabry Disease
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Globotriaosylsphingosine accumulation and not alpha-galactosidase-a deficiency causes endothelial dysfunction in fabry disease", "type"=>"journal", "authors"=>[{"first_name"=>"Mehdi", "last_name"=>"Namdar", "scopus_author_id"=>"15052261200"}, {"first_name"=>"Catherine", "last_name"=>"Gebhard", "scopus_author_id"=>"55145526500"}, {"first_name"=>"Rafael", "last_name"=>"Studiger", "scopus_author_id"=>"55203545700"}, {"first_name"=>"Yi", "last_name"=>"Shi", "scopus_author_id"=>"40661803200"}, {"first_name"=>"Pavani", "last_name"=>"Mocharla", "scopus_author_id"=>"25922895000"}, {"first_name"=>"Christian", "last_name"=>"Schmied", "scopus_author_id"=>"36966677300"}, {"first_name"=>"Pedro", "last_name"=>"Brugada", "scopus_author_id"=>"56580593700"}, {"first_name"=>"Thomas F.", "last_name"=>"Lüscher", "scopus_author_id"=>"55956533700"}, {"first_name"=>"Giovanni G.", "last_name"=>"Camici", "scopus_author_id"=>"7005597818"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84860425284", "sgr"=>"84860425284", "pui"=>"364721034", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"22558451", "doi"=>"10.1371/journal.pone.0036373"}, "id"=>"5348d4a3-8003-3b51-ae85-0027e2194c53", "abstract"=>"BACKGROUND: Fabry disease (FD) is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA) resulting in the accumulation of globotriaosylsphingosine (Gb3) in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. METHODS AND RESULTS: In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs) were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs. CONCLUSIONS: Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.", "link"=>"http://www.mendeley.com/research/globotriaosylsphingosine-accumulation-not-alphagalactosidasea-deficiency-causes-endothelial-dysfunct", "reader_count"=>27, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>1, "Researcher"=>7, "Student > Ph. D. Student"=>6, "Other"=>4, "Student > Master"=>1, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>1, "Researcher"=>7, "Student > Ph. D. Student"=>6, "Other"=>4, "Student > Master"=>1, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>7, "Neuroscience"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Neuroscience"=>{"Neuroscience"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "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"=>{"Germany"=>1}, "group_count"=>2}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84860425284"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84860425284?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84860425284&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84860425284&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84860425284", "dc:identifier"=>"SCOPUS_ID:84860425284", "eid"=>"2-s2.0-84860425284", "dc:title"=>"Globotriaosylsphingosine accumulation and not alpha-galactosidase-a deficiency causes endothelial dysfunction in fabry disease", "dc:creator"=>"Namdar M.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"7", "prism:issueIdentifier"=>"4", "prism:pageRange"=>nil, "prism:coverDate"=>"2012-04-30", "prism:coverDisplayDate"=>"30 April 2012", "prism:doi"=>"10.1371/journal.pone.0036373", "citedby-count"=>"31", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"UniversitatsSpital Zurich", "affiliation-city"=>"Zurich", "affiliation-country"=>"Switzerland"}, {"@_fa"=>"true", "affilname"=>"Heart Rhythm Management Centre UZB", "affiliation-city"=>"Brussels", "affiliation-country"=>"Belgium"}], "pubmed-id"=>"22558451", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e36373", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0036373", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Journal Comments | Further Information

Counter

  • {"month"=>"4", "year"=>"2012", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"5", "year"=>"2012", "pdf_views"=>"81", "xml_views"=>"3", "html_views"=>"211"}
  • {"month"=>"6", "year"=>"2012", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"14", "xml_views"=>"4", "html_views"=>"34"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"47"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"32", "xml_views"=>"0", "html_views"=>"70"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"39"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"22"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"2", "html_views"=>"42"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"72"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"11", "xml_views"=>"3", "html_views"=>"41"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"11", "xml_views"=>"2", "html_views"=>"47"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"42"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"43"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"2", "html_views"=>"37"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"47"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"38"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"60"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"51", "xml_views"=>"1", "html_views"=>"48"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"13"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"43"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"71"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"60"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"72"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"54"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"60"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"62"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"55"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"40"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"2", "html_views"=>"23"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"55"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"17"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"3", "html_views"=>"16"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"3", "html_views"=>"9"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"16"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"2", "html_views"=>"18"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"10"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"1", "year"=>"2020", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"2", "year"=>"2020", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"11"}
  • {"month"=>"3", "year"=>"2020", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"4", "year"=>"2020", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"5", "year"=>"2020", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"6", "year"=>"2020", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"7", "year"=>"2020", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"8", "year"=>"2020", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"9", "year"=>"2020", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"19"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/644744"], "description"=>"<p><b>A.</b> TNF-α enhances VCAM-1 expression in HMiVECs. Values are indicated as percent of unstimulated control. *p<0.05 vs unstimulated control; Values are representative of at least 4 different experiments; all blots are normalized to GAPDH expression. <b>B.</b> Gb3 enhances VCAM-1 expression in TNF-α stimulated HMaVECs and under basal conditions. Values are indicated as percent of unstimulated control. *p<0.05 vs unstimulated control; **p<0.05 vs TNF-α alone. <b>C./D.</b> GLA gene silencing did not affect expression of VCAM-1.</p>", "links"=>[], "tags"=>["enhances", "vcam-1", "stimulated"], "article_id"=>315227, "categories"=>["Biochemistry", "Cell Biology", "Genetics"], "users"=>["Mehdi Namdar", "Catherine Gebhard", "Rafael Studiger", "Yi Shi", "Pavani Mocharla", "Christian Schmied", "Pedro Brugada", "Thomas F. Lüscher", "Giovanni G. Camici"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036373.g005", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gb3_enhances_VCAM_1_expression_in_TNF_945_stimulated_HMiVECs_/315227", "title"=>"Gb3 enhances VCAM-1 expression in TNF-α stimulated HMiVECs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-30 01:27:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/644380"], "description"=>"<p><b>A.</b> Gb3 inhibits total eNOS expression in TNF-α stimulated HMiVECs and under basal conditions. Values are indicated as percent of unstimulated control. *p<0.05 vs unstimulated control; **p<0.05 vs TNF-α alone. <b>B.</b> Gb3 inhibits Ser<sub>1177</sub> pho eNOS expression in TNF-α stimulated HMiVECs and under basal conditions. Values are indicated as percent of unstimulated control. *p<0.05 vs unstimulated control; **p<0.05 vs TNF-α alone. Values are representative of at least 4 different experiments; all blots are normalized to GAPDH expression. <b>C./D.</b> In all cases expression remained unchanged following GLA gene silencing.</p>", "links"=>[], "tags"=>["impairs", "enos"], "article_id"=>314868, "categories"=>["Biochemistry", "Cell Biology", "Genetics"], "users"=>["Mehdi Namdar", "Catherine Gebhard", "Rafael Studiger", "Yi Shi", "Pavani Mocharla", "Christian Schmied", "Pedro Brugada", "Thomas F. Lüscher", "Giovanni G. Camici"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036373.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gb3_impairs_eNOS_expression_in_HMiVECs_/314868", "title"=>"Gb3 impairs eNOS expression in HMiVECs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-30 01:21:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/333863", "https://ndownloader.figshare.com/files/333887", "https://ndownloader.figshare.com/files/333924", "https://ndownloader.figshare.com/files/333963", "https://ndownloader.figshare.com/files/334003", "https://ndownloader.figshare.com/files/334044"], "description"=>"<div><h3>Background</h3><p>Fabry disease (FD) is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA) resulting in the accumulation of globotriaosylsphingosine (Gb3) in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known.</p> <h3>Methods and Results</h3><p>In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs) were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs.</p> <h3>Conclusions</h3><p>Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.</p> </div>", "links"=>[], "tags"=>["globotriaosylsphingosine", "accumulation", "alpha-galactosidase-a", "deficiency", "causes", "endothelial", "dysfunction", "fabry"], "article_id"=>125940, "categories"=>["Biochemistry", "Cell Biology", "Genetics"], "users"=>["Mehdi Namdar", "Catherine Gebhard", "Rafael Studiger", "Yi Shi", "Pavani Mocharla", "Christian Schmied", "Pedro Brugada", "Thomas F. Lüscher", "Giovanni G. Camici"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0036373.s001", "https://dx.doi.org/10.1371/journal.pone.0036373.s002", "https://dx.doi.org/10.1371/journal.pone.0036373.s003", "https://dx.doi.org/10.1371/journal.pone.0036373.s004", "https://dx.doi.org/10.1371/journal.pone.0036373.s005", "https://dx.doi.org/10.1371/journal.pone.0036373.s006"], "stats"=>{"downloads"=>7, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Globotriaosylsphingosine_Accumulation_and_Not_Alpha_Galactosidase_A_Deficiency_Causes_Endothelial_Dysfunction_in_Fabry_Disease/125940", "title"=>"Globotriaosylsphingosine Accumulation and Not Alpha-Galactosidase-A Deficiency Causes Endothelial Dysfunction in Fabry Disease", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-04-30 01:39:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/644509"], "description"=>"<p><b>A.</b> Gb3 enhances iNOS expression in HMiVECs under basal conditions. TNF-α enhances iNOS expression in HMiVECs. Values are indicated as percent of unstimulated control. *p<0.05 vs unstimulated control. <b>B.</b> TNF-α enhances iNOS expression in HMaVECs. Values are indicated as percent of unstimulated control. *p<0.05 vs unstimulated control; Values are representative of at least 4 different experiments; all blots are normalized to GAPDH expression. <b>C./D.</b> GLA gene silencing had no effect on expression of iNOS.</p>", "links"=>[], "tags"=>["enhances", "inos"], "article_id"=>314996, "categories"=>["Biochemistry", "Cell Biology", "Genetics"], "users"=>["Mehdi Namdar", "Catherine Gebhard", "Rafael Studiger", "Yi Shi", "Pavani Mocharla", "Christian Schmied", "Pedro Brugada", "Thomas F. Lüscher", "Giovanni G. Camici"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036373.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gb3_enhances_iNOS_expression_in_HMiVECs_/314996", "title"=>"Gb3 enhances iNOS expression in HMiVECs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-30 01:23:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/644265"], "description"=>"<p><b>A.</b> Incubation with Gb3 increased intracellular concentration of Gb3, as measured by ELISA, by 2-folds in HMaVECs and HMiVECs (n = 4, p = 0.03 and p = 0.04, respectively, versus untreated control, <b>B.</b> Maximal a-Gal A protein silencing of 70% occurred 48 hrs after transfection of HMaVECs with siRNA 3. Transfection of HMaVECs with Non-targeting (NT)-RNA did not alter endothelial a-Gal A expression. Values are representative of at least 4 different experiments; all blots are normalized to GAPDH expression. <b>C.</b> Intracellular Gb3 concentrations 2 days following siRNA transfection remained unchanged compared to untreated cells.</p>", "links"=>[], "tags"=>["loading", "alpha-galactosidase"], "article_id"=>314749, "categories"=>["Biochemistry", "Cell Biology", "Genetics"], "users"=>["Mehdi Namdar", "Catherine Gebhard", "Rafael Studiger", "Yi Shi", "Pavani Mocharla", "Christian Schmied", "Pedro Brugada", "Thomas F. Lüscher", "Giovanni G. Camici"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036373.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gb3_loading_and_alpha_Galactosidase_A_gene_silencing_/314749", "title"=>"Gb3 loading and alpha-Galactosidase A gene silencing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-30 01:19:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/644620"], "description"=>"<p><b>A.</b> Gb3 enhances COX-2 expression in HMiVECs under basal conditions. TNF-α enhances COX-2 expression in HMiVECs. Values are indicated as percent of unstimulated control. *p<0.05 vs unstimulated control. <b>B.</b> TNF-α enhanced COX-1 expression in both HMiVECs and HMaVECs by 1.5-fold and 1.4-fold, respectively. Values are representative of at least 4 different experiments; all blots are normalized to GAPDH expression. <b>C.</b> GLA gene silencing had no effect on expression of COX-2.</p>", "links"=>[], "tags"=>["enhances", "cox-2"], "article_id"=>315103, "categories"=>["Biochemistry", "Cell Biology", "Genetics"], "users"=>["Mehdi Namdar", "Catherine Gebhard", "Rafael Studiger", "Yi Shi", "Pavani Mocharla", "Christian Schmied", "Pedro Brugada", "Thomas F. Lüscher", "Giovanni G. Camici"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036373.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gb3_enhances_COX_2_expression_in_HMiVECs_/315103", "title"=>"Gb3 enhances COX-2 expression in HMiVECs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-30 01:25:03"}

PMC Usage Stats | Further Information

  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"71", "unique-ip"=>"64", "pdf"=>"50", "year"=>"2012", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"37", "year"=>"2012", "pdf"=>"23", "unique-ip"=>"34", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"unique-ip"=>"30", "full-text"=>"38", "pdf"=>"25", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
  • {"unique-ip"=>"22", "full-text"=>"21", "pdf"=>"16", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"35", "full-text"=>"34", "pdf"=>"28", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"38", "full-text"=>"37", "pdf"=>"24", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"37", "full-text"=>"40", "pdf"=>"22", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"41", "full-text"=>"51", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"47", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"10", "full-text"=>"17", "pdf"=>"9", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"37", "full-text"=>"43", "pdf"=>"29", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"16", "full-text"=>"20", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"13", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"4", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"5", "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"=>"2"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"3", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"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"=>"7", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"15", "full-text"=>"10", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"31", "full-text"=>"41", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"16", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"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"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"35", "full-text"=>"42", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"35", "full-text"=>"41", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"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"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"37", "full-text"=>"51", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"42", "full-text"=>"47", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"19", "full-text"=>"60", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"44", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"42", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"18", "full-text"=>"52", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"40", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"14", "full-text"=>"49", "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"=>"15", "full-text"=>"39", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"21", "full-text"=>"24", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"26", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"19", "full-text"=>"19", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"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"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"21", "full-text"=>"19", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"15", "full-text"=>"17", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"4", "full-text"=>"4", "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"=>"11", "full-text"=>"11", "pdf"=>"4", "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"=>"10", "pdf"=>"2", "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"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"12", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"16", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"13", "full-text"=>"11", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"17", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"17", "full-text"=>"18", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Anatomy and physiology", "average_usage"=>[307, 540, 660, 756, 847, 936, 1025, 1111, 1199, 1282, 1361, 1432]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[316, 541, 663, 766, 856, 950, 1041, 1128, 1218, 1302, 1382, 1456, 1526, 1593, 1657, 1729, 1796, 1862, 1930, 1999, 2065, 2132, 2202, 2261, 2319]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[319, 556, 679, 785, 881, 970, 1062, 1149, 1236, 1323, 1402, 1474, 1545, 1617, 1681, 1754, 1822, 1892, 1963, 2031, 2099, 2165, 2233, 2299, 2359]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[333, 576, 707, 814, 908, 1004, 1104, 1197, 1280, 1370, 1449, 1531, 1603, 1673, 1742, 1817, 1886, 1954, 2025, 2098, 2171, 2234, 2304, 2365, 2431]}, {"subject_area"=>"/Biology and life sciences/Physiology", "average_usage"=>[307, 536, 653, 753, 839, 926, 1017, 1103, 1189, 1268, 1348, 1425, 1492, 1557, 1620, 1686, 1759, 1825, 1891, 1950, 2014, 2079, 2141, 2200, 2255]}, {"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/Hematology", "average_usage"=>[300, 532, 651, 749, 842, 929, 1022, 1106, 1192, 1267, 1351, 1423, 1489, 1553, 1631, 1694, 1764, 1835, 1899, 1964, 2027, 2087, 2159, 2228, 2280]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[308, 535, 653, 754, 847, 930, 1020, 1103, 1188, 1268, 1351, 1420, 1487, 1550, 1614, 1679, 1757, 1830, 1898, 1961, 2024, 2086, 2150, 2216, 2266]}]}
Loading … Spinner
There are currently no alerts