The IkappaB Kinase Family Phosphorylates the Parkinson’s Disease Kinase LRRK2 at Ser935 and Ser910 during Toll-Like Receptor Signaling
Events
Loading … Spinner

CiteULike | Further Information

Mendeley | Further Information

{"title"=>"The IkappaB kinase family phosphorylates the Parkinson's disease kinase LRRK2 at Ser935 and Ser910 during Toll-Like Receptor signaling", "type"=>"journal", "authors"=>[{"first_name"=>"Nicolas", "last_name"=>"Dzamko", "scopus_author_id"=>"6507396486"}, {"first_name"=>"Francisco", "last_name"=>"Inesta-Vaquera", "scopus_author_id"=>"6504803503"}, {"first_name"=>"Jiazhen", "last_name"=>"Zhang", "scopus_author_id"=>"55255406500"}, {"first_name"=>"Chengsong", "last_name"=>"Xie", "scopus_author_id"=>"7401934728"}, {"first_name"=>"Huaibin", "last_name"=>"Cai", "scopus_author_id"=>"7202853130"}, {"first_name"=>"Simon", "last_name"=>"Arthur", "scopus_author_id"=>"7202382179"}, {"first_name"=>"Li", "last_name"=>"Tan", "scopus_author_id"=>"55236388100"}, {"first_name"=>"Hwanguen", "last_name"=>"Choi", "scopus_author_id"=>"55255235900"}, {"first_name"=>"Nathanael", "last_name"=>"Gray", "scopus_author_id"=>"7201699193"}, {"first_name"=>"Philip", "last_name"=>"Cohen", "scopus_author_id"=>"7402923816"}, {"first_name"=>"Patrick", "last_name"=>"Pedrioli", "scopus_author_id"=>"16402897200"}, {"first_name"=>"Kristopher", "last_name"=>"Clark", "scopus_author_id"=>"23972268100"}, {"first_name"=>"Dario R.", "last_name"=>"Alessi", "scopus_author_id"=>"7006548152"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"365023974", "sgr"=>"84862497413", "pmid"=>"22723946", "scopus"=>"2-s2.0-84862497413", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0039132", "issn"=>"19326203"}, "id"=>"0fccdac9-2193-3b8e-ba25-325ca7f2d00c", "abstract"=>"Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson's disease. LRRK2 is highly expressed in immune cells and recent work points towards a link between LRRK2 and innate immunity. Here we demonstrate that stimulation of the Toll-Like Receptor (TLR) pathway by MyD88-dependent agonists in bone marrow-derived macrophages (BMDMs) or RAW264.7 macrophages induces marked phosphorylation of LRRK2 at Ser910 and Ser935, the phosphorylation sites that regulate the binding of 14-3-3 to LRRK2. Phosphorylation of these residues is prevented by knock-out of MyD88 in BMDMs, but not the alternative TLR adaptor protein TRIF. Utilising both pharmacological inhibitors, including a new TAK1 inhibitor, NG25, and genetic models, we provide evidence that both the canonical (IKKα and IKKβ) and IKK-related (IKKε and TBK1) kinases mediate TLR agonist induced phosphorylation of LRRK2 in vivo. Moreover, all four IKK members directly phosphorylate LRRK2 at Ser910 and Ser935 in vitro. Consistent with previous work describing Ser910 and Ser935 as pharmacodynamic biomarkers of LRRK2 activity, we find that the TLR independent basal phosphorylation of LRRK2 at Ser910 and Ser935 is abolished following treatment of macrophages with LRRK2 kinase inhibitors. However, the increased phosphorylation of Ser910 and Ser935 induced by activation of the MyD88 pathway is insensitive to LRRK2 kinase inhibitors. Finally, employing LRRK2-deficient BMDMs, we present data indicating that LRRK2 does not play a major role in regulating the secretion of inflammatory cytokines induced by activation of the MyD88 pathway. Our findings provide the first direct link between LRRK2 and the IKKs that mediate many immune responses. Further work is required to uncover the physiological roles that phosphorylation of LRRK2 by IKKs play in controlling macrophage biology and to determine how phosphorylation of LRRK2 by IKKs impacts upon the use of Ser910 and Ser935 as pharmacodynamic biomarkers.", "link"=>"http://www.mendeley.com/research/ikappab-kinase-family-phosphorylates-parkinsons-disease-kinase-lrrk2-ser935-ser910-during-tolllike-r", "reader_count"=>90, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>5, "Librarian"=>1, "Researcher"=>22, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>4, "Student > Master"=>15, "Other"=>1, "Student > Bachelor"=>7, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>5, "Librarian"=>1, "Researcher"=>22, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>4, "Student > Master"=>15, "Other"=>1, "Student > Bachelor"=>7, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>10, "Agricultural and Biological Sciences"=>44, "Medicine and Dentistry"=>20, "Neuroscience"=>8, "Business, Management and Accounting"=>1, "Chemistry"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>20}, "Neuroscience"=>{"Neuroscience"=>8}, "Chemistry"=>{"Chemistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>44}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>10}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Republic of Singapore"=>1, "Belgium"=>1, "United States"=>2, "United Kingdom"=>3, "Australia"=>1}, "group_count"=>3}

CrossRef

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84862497413"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84862497413?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84862497413&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84862497413&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84862497413", "dc:identifier"=>"SCOPUS_ID:84862497413", "eid"=>"2-s2.0-84862497413", "dc:title"=>"The IkappaB kinase family phosphorylates the Parkinson's disease kinase LRRK2 at Ser935 and Ser910 during Toll-Like Receptor signaling", "dc:creator"=>"Dzamko N.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"7", "prism:issueIdentifier"=>"6", "prism:pageRange"=>nil, "prism:coverDate"=>"2012-06-18", "prism:coverDisplayDate"=>"18 June 2012", "prism:doi"=>"10.1371/journal.pone.0039132", "citedby-count"=>"111", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University of Dundee", "affiliation-city"=>"Dundee", "affiliation-country"=>"United Kingdom"}], "pubmed-id"=>"22723946", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e39132", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0039132", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"6", "year"=>"2012", "pdf_views"=>"167", "xml_views"=>"2", "html_views"=>"473"}
  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"113", "xml_views"=>"1", "html_views"=>"291"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"44", "xml_views"=>"4", "html_views"=>"152"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"45", "xml_views"=>"0", "html_views"=>"107"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"40", "xml_views"=>"0", "html_views"=>"142"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"116"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"30", "xml_views"=>"0", "html_views"=>"96"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"33", "xml_views"=>"0", "html_views"=>"180"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"41", "xml_views"=>"1", "html_views"=>"127"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"117"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"33", "xml_views"=>"1", "html_views"=>"111"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"142"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"27", "xml_views"=>"1", "html_views"=>"94"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"24", "xml_views"=>"0", "html_views"=>"85"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"58"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"23", "xml_views"=>"2", "html_views"=>"95"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"20", "xml_views"=>"2", "html_views"=>"186"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"266"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"20", "xml_views"=>"3", "html_views"=>"174"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"135"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"182"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"191"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"192"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"254"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"252"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"257"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"20", "xml_views"=>"2", "html_views"=>"253"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"251"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"24", "xml_views"=>"1", "html_views"=>"119"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"16", "xml_views"=>"1", "html_views"=>"67"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"17", "xml_views"=>"2", "html_views"=>"62"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"95"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"49"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"69"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"15", "xml_views"=>"1", "html_views"=>"34"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"68"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"52"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"54"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"62"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"60"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"59"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"40"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"47"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"48"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"53"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"3", "html_views"=>"61"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"51"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"2", "html_views"=>"40"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"33"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"37"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"74"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"26"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"2", "html_views"=>"32"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"10"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"19", "xml_views"=>"3", "html_views"=>"25"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"15", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"2", "html_views"=>"30"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"23"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"17"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"1", "year"=>"2020", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"2", "year"=>"2020", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"8"}
  • {"month"=>"3", "year"=>"2020", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"9"}
  • {"month"=>"4", "year"=>"2020", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"3"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/623120"], "description"=>"<p>(<b>A</b>) Primary bone marrow derived macrophages were treated with 100 ng/ml TNFα for the indicated time points before cell lysis and immunoblot with the indicated antibodies. (<b>B & C</b>) As in <b>A</b> except 200 µg/ml zymosan was used. (<b>D and E</b>) as in <b>A</b> except that 100 µg/ml curdlan was used. Immunoblots are representative of at least two independent experiments.</p>", "links"=>[], "tags"=>["agonists", "lrrk2"], "article_id"=>293609, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Non_TLR_immune_agonists_fail_to_increase_LRRK2_phosphorylation_/293609", "title"=>"Non-TLR immune agonists fail to increase LRRK2 phosphorylation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-18 01:00:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/623289"], "description"=>"<p>(<b>A</b>) Primary bone marrow derived macrophages were generated from MYD88 knock-out mice and wild type littermate controls. Macrophages were stimulated with either 1 µg/ml Pam<sub>3</sub>CSK<sub>4</sub>, 100 ng/ml LPS, 1 µg/ml FSL1 or 2.5 µM ODN1826 for 1 h. Cell lysates were prepared and subjected to immunoblot with the indicated antibodies. (<b>B</b>) As in <b>A</b> except that macrophages were generated from TRIF knock-out mice and wild type littermate controls. All immunoblots are representative of at least two independent experiments.</p>", "links"=>[], "tags"=>["induced", "lrrk2", "ser935", "phosphorylation"], "article_id"=>293772, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.g004", "stats"=>{"downloads"=>1, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TLR_induced_LRRK2_Ser935_phosphorylation_is_MYD88_dependent_/293772", "title"=>"TLR induced LRRK2 Ser935 phosphorylation is MYD88-dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-18 01:02:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/623386"], "description"=>"<p>(<b>A</b>) Primary bone marrow derived macrophages were treated with indicated concentrations of LRRK2-IN1 or CZC25146 or DMSO as control for 1 h. Cell lysates were prepared and subjected to immunoblot with the indicated antibodies. (<b>B</b>) Primary bone marrow derived macrophages were pre-treated with indicated concentrations of LRRK2-IN1 or CZC25146 or DMSO as control for 1 h before stimulation with 100 ng/ml LPS for 1h. Cell lysates were prepared and subjected to immunoblot with the indicated antibodies. (<b>C</b>) As in <b>B</b> except 1 µg/ml Pam<sub>3</sub>CSK<sub>4</sub> was used. (<b>D</b>) RAW264.7 cells were treated with 100 ng/ml LPS or 1 µg/ml Pam<sub>3</sub>CSK<sub>4</sub> for 1 h before cell lysis. Endogenous LRRK2 was immunoprecipitated from 3 mg RAW264.7 cell lysate with 3 µg rabbit monoclonal LRRK2 100–500 antibody. Kinase activity was measured using 20 µM Nictide with n = 4 in duplicate. Kinase activity is reported as pmol of ATP incorporated into Nictide per minute per mg of lystate immunoprecipitated from. A parallel set of immunoprecipitations was used to measure 14-3-3 binding by overlay assay. All results are representative of at least two independent experiments.</p>", "links"=>[], "tags"=>["phosphorylation", "tlr", "signaling", "lrrk2", "kinase"], "article_id"=>293865, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.g005", "stats"=>{"downloads"=>2, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ser935_phosphorylation_during_TLR_signaling_does_not_require_LRRK2_kinase_activity_/293865", "title"=>"Ser935 phosphorylation during TLR signaling does not require LRRK2 kinase activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-18 01:04:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/624118"], "description"=>"<p>Bone marrow derived macrophages from LRRK2 knockout mice and wild type littermate controls were plated at a density of 1×10<sup>6</sup> in 2 ml of tissue culture media. Cells were treated with 100 ng/ml LPS 24 h after plating and RNA collected at the indicated time points. Gene expression was normalized to GAPDH and the fold increase in mRNA expression compared to wild type macrophages at time 0 was calculated by the comparative Ct method (2<sup>−ddct</sup>). Data is presented as mean fold increase in expression ± S.E.M. Experiments were performed with n = 4 in duplicate.</p>", "links"=>[], "tags"=>["lrrk2", "ko", "lps"], "article_id"=>294603, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.t003", "stats"=>{"downloads"=>0, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_mRNA_expression_in_wild_type_and_LRRK2_KO_BMDM_8217_s_following_LPS_stimulation_/294603", "title"=>"mRNA expression in wild type and LRRK2 KO BMDM’s following LPS stimulation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-18 01:16:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/623589"], "description"=>"<p>) Schematic of SILAC experiment. <b>B-E</b>) Extracted Ion Current for phosphopeptides encompassing Ser935 (<b>B</b>), Ser910 (<b>C</b>) and Ser955 (<b>D</b>) of LRRK2 and Ser177 of optineurin (<b>E</b>). The results for unstimulated RAW264.7 macrophages are presented in blue, results for RAW264.7 macrophages stimulated for 60 min with Pam<sub>3</sub>CSK<sub>4</sub> (1 µg/ml) are in green and the results from RAW264.7 macrophages pre-treated with 2 µM MRT67307 prior to stimulation with Pam<sub>3</sub>CSK<sub>4</sub> (1 µg/ml) for 60 min are depicted in red. (<b>F</b>) Table summarizing the results of the phosphopeptides from LRRK2 identified in the phosphoproteomics screen. <b>G</b>) Primary bone marrow derived macrophages were pre-treated with 2 µM MRT67307 or DMSO control for 1 h before stimulation with 100 ng/ml LPS for the indicated time points. Immunoblots are representative of at least two independent experiments.</p>", "links"=>[], "tags"=>["lrrk2", "ser935", "phosphorylation", "tlr"], "article_id"=>294068, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.g006", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TBK1_and_IKK_949_regulate_LRRK2_Ser935_phosphorylation_following_TLR_activation_A_/294068", "title"=>"TBK1 and IKKε regulate LRRK2 Ser935 phosphorylation following TLR activation. A", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-18 01:07:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/622999"], "description"=>"<p>(<b>A & B</b>)<b>.</b> Primary bone marrow derived macrophages were treated with 100 ng/ml LPS for the indicated time points before cell lysis and immunoblot with indicated antibodies. (<b>C & D</b>) Primary bone marrow derived macrophages were treated with 1 µg/ml Pam<sub>3</sub>CSK<sub>4</sub> for the indicated time points before cell lysis and immunoblot with indicated antibodies. (<b>E</b>) Primary bone marrow derived macrophages were treated with the following TLR agonists for 1 h. 1 µg/ml Pam<sub>3</sub>CSK<sub>4</sub>, 10<sup>8</sup> cells HKLM, 10 µg/ml LMW and HMW Poly(I:C), 100 ng/ml LPS, 10 µg/ml Flagellin, 1 µg/ml FSL1, 1 µM CLO97 and 2.5 µM ODN1826. (<b>F & G</b>) Primary bone marrow derived macrophages were treated with 10 µg/ml Poly(I:C) for the indicated time points before cell lysis and immunoblot with indicated antibodies. All immunoblots are representative of at least two independent experiments.</p>", "links"=>[], "tags"=>["agonists", "lrrk2", "phosphorylation"], "article_id"=>293474, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.g002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TLR_agonists_increase_LRRK2_phosphorylation_at_Ser935_/293474", "title"=>"TLR agonists increase LRRK2 phosphorylation at Ser935.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-18 00:57:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/624026"], "description"=>"<p>Bone marrow derived macrophages from LRRK2 knockout mice and wild type littermate controls were plated at a density of 1×10<sup>6</sup> in 2 ml of tissue culture media. Cells were treated with 1 µg/ml Pam<sub>3</sub>CSK<sub>4</sub> 24 h after plating and RNA collected at the indicated time points. Gene expression was normalized to GAPDH and the fold increase in mRNA expression compared to wild type macrophages at time 0 was calculated by the comparative Ct method (2<sup>-ddct</sup>). Data is presented as mean fold increase in expression ± S.E.M. Experiments were performed with n = 4 in duplicate.</p>", "links"=>[], "tags"=>["lrrk2", "ko", "pam3csk4"], "article_id"=>294507, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.t004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_mRNA_expression_in_wild_type_and_LRRK2_KO_BMDM_8217_s_following_PAM3CSK4_stimulation_/294507", "title"=>"mRNA expression in wild type and LRRK2 KO BMDM’s following PAM3CSK4 stimulation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-18 01:15:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/623885"], "description"=>"<p>Bone marrow derived macrophages were prepared from LRRK2 knock-out mice and littermate controls. BMDMs were treated with 100 ng/ml LPS for the indicated time points. Cells lysates were subjected to immunoblot with the indicated antibodies. Results are representative of two independent experiments performed in duplicate.</p>", "links"=>[], "tags"=>["ikk", "signalling", "impaired", "lrrk2", "knock-out"], "article_id"=>294364, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.g008", "stats"=>{"downloads"=>1, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Acute_IKK_signalling_is_not_impaired_in_LRRK2_knock_out_macrophages_/294364", "title"=>"Acute IKK signalling is not impaired in LRRK2 knock-out macrophages.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-18 01:12:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/323207", "https://ndownloader.figshare.com/files/323252", "https://ndownloader.figshare.com/files/323294", "https://ndownloader.figshare.com/files/323379", "https://ndownloader.figshare.com/files/323405", "https://ndownloader.figshare.com/files/323427", "https://ndownloader.figshare.com/files/323435"], "description"=>"<div><p>Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson's disease. LRRK2 is highly expressed in immune cells and recent work points towards a link between LRRK2 and innate immunity. Here we demonstrate that stimulation of the Toll-Like Receptor (TLR) pathway by MyD88-dependent agonists in bone marrow-derived macrophages (BMDMs) or RAW264.7 macrophages induces marked phosphorylation of LRRK2 at Ser910 and Ser935, the phosphorylation sites that regulate the binding of 14-3-3 to LRRK2. Phosphorylation of these residues is prevented by knock-out of MyD88 in BMDMs, but not the alternative TLR adaptor protein TRIF. Utilising both pharmacological inhibitors, including a new TAK1 inhibitor, NG25, and genetic models, we provide evidence that both the canonical (IKKα and IKKβ) and IKK-related (IKKε and TBK1) kinases mediate TLR agonist induced phosphorylation of LRRK2 in vivo. Moreover, all four IKK members directly phosphorylate LRRK2 at Ser910 and Ser935 in vitro. Consistent with previous work describing Ser910 and Ser935 as pharmacodynamic biomarkers of LRRK2 activity, we find that the TLR independent basal phosphorylation of LRRK2 at Ser910 and Ser935 is abolished following treatment of macrophages with LRRK2 kinase inhibitors. However, the increased phosphorylation of Ser910 and Ser935 induced by activation of the MyD88 pathway is insensitive to LRRK2 kinase inhibitors. Finally, employing LRRK2-deficient BMDMs, we present data indicating that LRRK2 does not play a major role in regulating the secretion of inflammatory cytokines induced by activation of the MyD88 pathway. Our findings provide the first direct link between LRRK2 and the IKKs that mediate many immune responses. Further work is required to uncover the physiological roles that phosphorylation of LRRK2 by IKKs play in controlling macrophage biology and to determine how phosphorylation of LRRK2 by IKKs impacts upon the use of Ser910 and Ser935 as pharmacodynamic biomarkers.</p> </div>", "links"=>[], "tags"=>["ikappab", "kinase", "phosphorylates", "lrrk2", "ser935", "ser910", "toll-like", "receptor", "signaling"], "article_id"=>123786, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039132.s001", "https://dx.doi.org/10.1371/journal.pone.0039132.s002", "https://dx.doi.org/10.1371/journal.pone.0039132.s003", "https://dx.doi.org/10.1371/journal.pone.0039132.s004", "https://dx.doi.org/10.1371/journal.pone.0039132.s005", "https://dx.doi.org/10.1371/journal.pone.0039132.s006", "https://dx.doi.org/10.1371/journal.pone.0039132.s007"], "stats"=>{"downloads"=>12, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_IkappaB_Kinase_Family_Phosphorylates_the_Parkinson_s_Disease_Kinase_LRRK2_at_Ser935_and_Ser910_during_Toll_Like_Receptor_Signaling/123786", "title"=>"The IkappaB Kinase Family Phosphorylates the Parkinson’s Disease Kinase LRRK2 at Ser935 and Ser910 during Toll-Like Receptor Signaling", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-06-18 01:03:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/622873"], "description"=>"<p>(<b>A</b>) Purified rabbit monoclonal antibody raised against residues 100–500 of human LRRK2 was used to immunoblot 5 µg HEK293 cell lysate containing overexpressed GFP-LRRK2 variants, 30 µg LRRK2 wild type and knock-out mouse embryonic fibroblast (MEF) lysate and 30 µg human lymphoblastoid cell lysate. Lymphoblast and MEF cells were treated plus or minus 1 µM LRRK2-IN1 for 2 h. A longer exposure was required for the MEF LRRK2 signal. (<b>B</b>) As in <b>A</b> except a rabbit monoclonal antibody to LRRK2 phosphorylated at Ser935 was used.</p>", "links"=>[], "tags"=>["monoclonal", "lrrk2"], "article_id"=>293349, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_rabbit_monoclonal_LRRK2_antibodies_/293349", "title"=>"Generation of rabbit monoclonal LRRK2 antibodies.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-18 00:55:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/624166"], "description"=>"<p>Bone marrow derived macrophages from LRRK2 knockout mice and wild type littermate controls were plated at a density of 1×10<sup>6</sup> in 2 ml of tissue culture media. Cells were treated with 100 ng/ml LPS 24 h after plating and media collected at the indicated time points. Cytokines were measured with an antibody based multiplex assay and concentrations determined by standard curve. Data is presented as mean concentration in pg/ml ± S.E.M. Experiments were performed with n = 4 in duplicate.</p>", "links"=>[], "tags"=>["secretion", "lrrk2", "ko", "lps"], "article_id"=>294643, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.t001", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokine_secretion_in_wild_type_and_LRRK2_KO_BMDM_8217_s_following_LPS_stimulation_/294643", "title"=>"Cytokine secretion in wild type and LRRK2 KO BMDM’s following LPS stimulation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-18 01:17:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/623719"], "description"=>"<p>(<b>A</b>) Primary bone marrow derived macrophages were treated with either DMSO, 1 µM 5z-7-Oxozeanol (TAK1 inhibitor), 2 µM NG25 (TAK1 inhibitor), 2 µM MRT67307 (TBK1/IKKε inhibitor) or 10 µM B1605906 (IKKβ inhibitor) alone or in the indicated combinations for 1 h before stimulation with 100 ng/ml LPS for 1 h. Cell lysates were subjected to immunoblot analysis with the indicated antibodies. (<b>B</b>) Bone marrow derived macrophages were generated from kinase inactive IKKα double Ser176A and Ser180A knock-in mice or littermate wild type controls. Macrophages were treated with either DMSO, 2 µM MRT67307 (TBK1/IKKε inhibitor) or 10 µM B1605906 (IKKβ inhibitor) as indicated for 1 h before stimulation with 100 ng/ml LPS for 1 h. Cell lysates were subjected to immunoblot analysis with the indicated antibodies. (<b>C</b>) As in <b>A</b> except that BMDMs were treated with DMSO, 1 µM 5z-7-Oxozeanol (TAK1 inhibitor), 2 µM MRT67307 (TBK1/IKKε inhibitor) alone or in combination for 1 h before stimulation with 1 µg/ml Pam<sub>3</sub>CSK4 or 200 µg/ml zymosan. (<b>D</b>) Ha tagged wild type and kinase inactive variants of IKKα IKKβ IKKε and TBK1 were expressed by transfection into HEK293 cells then immunoprecipitated by Ha-agarose. Kinases were used to phosphorylate bacterially expressed substrates GST-LRRK2 (882-1300), GST-IκBα (2-54) and GST-IRF3 (1-427) at 30°C for 30 min before reaction termination with sample buffer. 10% of the in vitro phosphorylation reaction was used for immunoblot analysis with the indicated antibodies. <b>E</b>) Baculovirus expressed TAK1 and IKKε were used to phosphorylate bacterially expressed substrates GST-LRRK2 (882-1300), GST-MKK6 (2-334) and GST-IRF3 (1-427) at 30°C for 30 min before reaction termination with sample buffer. 10% of the in vitro phosphorylation reaction was used for immunoblot analysis with the indicated antibodies or for autoradiograph.</p>", "links"=>[], "tags"=>["lrrk2", "ser935", "phosphorylation", "tlr"], "article_id"=>294194, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.g007", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IKK_945_and_IKK_946_contribute_to_LRRK2_Ser935_phosphorylation_following_TLR_activation_/294194", "title"=>"IKKα and IKKβ contribute to LRRK2 Ser935 phosphorylation following TLR activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-18 01:09:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/624079"], "description"=>"<p>Bone marrow derived macrophages from LRRK2 knockout mice and wild type littermate controls were plated at a density of 1×10<sup>6</sup> in 2 ml of tissue culture media. Cells were treated with 1 µg/ml Pam<sub>3</sub>CSK<sub>4</sub> 24 h after plating and media collected at the indicated time points. Cytokines were measured with an antibody based multiplex assay and concentrations determined by standard curve. Data is presented as mean concentration in pg/ml ± S.E.M. Experiments were performed with n = 4 in duplicate.</p>", "links"=>[], "tags"=>["secretion", "lrrk2", "ko", "pam3csk4"], "article_id"=>294559, "categories"=>["Molecular Biology", "Biochemistry", "Immunology"], "users"=>["Nicolas Dzamko", "Francisco Inesta-Vaquera", "Jiazhen Zhang", "Chengsong Xie", "Huaibin Cai", "Simon Arthur", "Li Tan", "Hwanguen Choi", "Nathanael Gray", "Philip Cohen", "Patrick Pedrioli", "Kristopher Clark", "Dario R. Alessi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039132.t002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokine_secretion_in_wild_type_and_LRRK2_KO_BMDM_8217_s_following_PAM3CSK4_stimulation_/294559", "title"=>"Cytokine secretion in wild type and LRRK2 KO BMDM’s following PAM3CSK4 stimulation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-18 01:15:59"}

PMC Usage Stats | Further Information

  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"6", "year"=>"2012", "pdf"=>"4", "unique-ip"=>"9", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"unique-ip"=>"109", "full-text"=>"123", "pdf"=>"72", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"70", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
  • {"unique-ip"=>"48", "full-text"=>"51", "pdf"=>"23", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"23", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"49", "full-text"=>"43", "pdf"=>"33", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"33", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"56", "full-text"=>"66", "pdf"=>"46", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"28", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"34", "full-text"=>"37", "pdf"=>"18", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"21", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"49", "full-text"=>"48", "pdf"=>"15", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"24", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"37", "full-text"=>"37", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"40", "full-text"=>"44", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"24", "full-text"=>"19", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"36", "full-text"=>"31", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"42", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"23", "full-text"=>"18", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"11", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"29", "full-text"=>"31", "pdf"=>"29", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"22", "supp-data"=>"13", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"24", "full-text"=>"24", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"21", "full-text"=>"36", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"28", "full-text"=>"30", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"19", "full-text"=>"29", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"15", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"20", "full-text"=>"13", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"24", "full-text"=>"21", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"25", "full-text"=>"26", "pdf"=>"18", "abstract"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"3", "pdf"=>"2", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"24", "full-text"=>"25", "pdf"=>"35", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"20", "full-text"=>"25", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"21", "full-text"=>"16", "pdf"=>"24", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"23", "full-text"=>"26", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"21", "full-text"=>"16", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"18", "full-text"=>"15", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"22", "full-text"=>"25", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"11", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"5", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"25", "full-text"=>"18", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"14", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"20", "full-text"=>"20", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"23", "full-text"=>"24", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"3", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"21", "full-text"=>"23", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"17", "full-text"=>"17", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"15", "full-text"=>"19", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"23", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"19", "full-text"=>"18", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"21", "full-text"=>"19", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"18", "full-text"=>"21", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"16", "full-text"=>"11", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"5", "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"=>"14", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"14", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"2", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"10", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"7", "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"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"33", "full-text"=>"44", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"19", "full-text"=>"17", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"15", "full-text"=>"21", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"17", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"11", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"19", "full-text"=>"25", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"24", "full-text"=>"35", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"16", "full-text"=>"30", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"15", "full-text"=>"24", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"1", "cited-by"=>"2", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"23", "full-text"=>"36", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"23", "full-text"=>"34", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"22", "full-text"=>"23", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"4", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"24", "full-text"=>"23", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"15", "full-text"=>"9", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"17", "full-text"=>"13", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"12", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}

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/Developmental biology", "average_usage"=>[313, 562, 690, 796, 893, 986, 1079, 1173, 1257, 1349, 1429, 1506, 1586, 1661, 1730, 1803, 1876, 1945, 2017, 2091, 2163, 2225, 2294, 2362, 2430]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[324, 551, 679, 782, 879, 971, 1064, 1154, 1245, 1328, 1406, 1476, 1541, 1617, 1683, 1754, 1818, 1893, 1962, 2025, 2092, 2164, 2227, 2294, 2355]}, {"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/Immunology", "average_usage"=>[307, 545, 668, 765, 855, 943, 1029, 1113, 1202, 1285, 1361, 1439, 1506, 1571, 1636, 1706, 1772, 1837, 1901, 1969, 2031, 2096, 2160, 2228, 2287]}]}
Loading … Spinner
There are currently no alerts