NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes
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{"title"=>"NLRP3 inflammasome is expressed and functional in mouse brain microglia but not in astrocytes", "type"=>"journal", "authors"=>[{"first_name"=>"Audrey", "last_name"=>"Gustin", "scopus_author_id"=>"55183471000"}, {"first_name"=>"Mélanie", "last_name"=>"Kirchmeyer", "scopus_author_id"=>"24923203400"}, {"first_name"=>"Eric", "last_name"=>"Koncina", "scopus_author_id"=>"23972703900"}, {"first_name"=>"Paul", "last_name"=>"Felten", "scopus_author_id"=>"56780309100"}, {"first_name"=>"Sophie", "last_name"=>"Losciuto", "scopus_author_id"=>"36135724200"}, {"first_name"=>"Tony", "last_name"=>"Heurtaux", "scopus_author_id"=>"6506824011"}, {"first_name"=>"Aubry", "last_name"=>"Tardivel", "scopus_author_id"=>"6602736420"}, {"first_name"=>"Paul", "last_name"=>"Heuschling", "scopus_author_id"=>"6603590386"}, {"first_name"=>"Catherine", "last_name"=>"Dostert", "scopus_author_id"=>"23033810800"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"26091541", "scopus"=>"2-s2.0-84938301985", "pui"=>"605586345", "doi"=>"10.1371/journal.pone.0130624", "sgr"=>"84938301985"}, "id"=>"890eb4fc-e460-34bd-aa3f-7d90a45ee9e6", "abstract"=>"Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1β plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization. Our results indicate that the capacity to form a functional NLRP3 inflammasome and secretion of IL-1β is limited to the microglial compartment in the mouse brain. We were not able to observe IL-1β secretion from astrocytes, nor do they express all NLRP3 inflammasome components. Microglia were able to produce IL-1β in response to different classical inflammasome activators, such as ATP, Nigericin or Alum. Similarly, microglia secreted IL-18 and IL-1α, two other inflammasome-linked pro-inflammatory factors. Cell stimulation with α-synuclein, a neurodegenerative disease-related peptide, did not result in the release of active IL-1β by microglia, despite a weak pro-inflammatory effect. Amyloid-β peptides were able to activate the NLRP3 inflammasome in microglia and IL-1β secretion occurred in a P2X7 receptor-independent manner. Thus microglia-dependent inflammasome activation can play an important role in the brain and especially in neuroinflammatory conditions.", "link"=>"http://www.mendeley.com/research/nlrp3-inflammasome-expressed-functional-mouse-brain-microglia-not-astrocytes", "reader_count"=>89, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>18, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>3, "Student > Master"=>15, "Other"=>2, "Student > Bachelor"=>18, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>18, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>3, "Student > Master"=>15, "Other"=>2, "Student > Bachelor"=>18, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>16, "Agricultural and Biological Sciences"=>32, "Medicine and Dentistry"=>7, "Neuroscience"=>24, "Philosophy"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>24}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>32}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>16}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Philosophy"=>{"Philosophy"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Spain"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2127222", "https://ndownloader.figshare.com/files/2127223"], "description"=>"<div><p>Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1β plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization. Our results indicate that the capacity to form a functional NLRP3 inflammasome and secretion of IL-1β is limited to the microglial compartment in the mouse brain. We were not able to observe IL-1β secretion from astrocytes, nor do they express all NLRP3 inflammasome components. Microglia were able to produce IL-1β in response to different classical inflammasome activators, such as ATP, Nigericin or Alum. Similarly, microglia secreted IL-18 and IL-1α, two other inflammasome-linked pro-inflammatory factors. Cell stimulation with α-synuclein, a neurodegenerative disease-related peptide, did not result in the release of active IL-1β by microglia, despite a weak pro-inflammatory effect. Amyloid-β peptides were able to activate the NLRP3 inflammasome in microglia and IL-1β secretion occurred in a P2X7 receptor-independent manner. Thus microglia-dependent inflammasome activation can play an important role in the brain and especially in neuroinflammatory conditions.</p></div>", "links"=>[], "tags"=>["cell stimulation", "2x", "inflammasome activators", "NLRP 3 inflammasome components", "Astrocytes Neuroinflammation", "brain resident macrophages", "il", "Neurodegenerative diseases", "atp", "NLRP 3 inflammasome", "secretion", "microglial compartment", "protein aggregates", "neuroinflammatory conditions", "mouse brain", "Mouse Brain Microglia", "response"], "article_id"=>1455212, "categories"=>["Biological Sciences"], "users"=>["Audrey Gustin", "Mélanie Kirchmeyer", "Eric Koncina", "Paul Felten", "Sophie Losciuto", "Tony Heurtaux", "Aubry Tardivel", "Paul Heuschling", "Catherine Dostert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0130624.s001", "https://dx.doi.org/10.1371/journal.pone.0130624.s002"], "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NLRP3_Inflammasome_Is_Expressed_and_Functional_in_Mouse_Brain_Microglia_but_Not_in_Astrocytes_/1455212", "title"=>"NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-19 03:36:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/2127219"], "description"=>"<p>Microglia were stimulated with 5 μM α-synuclein (α-syn), either wild-type (α-syn WT) or mutant (α-syn A53T) (oligomeric form: olig. or fibrillated form: fib.) for 6 h. (<b>A</b>) RNA was extracted and analyzed for expression of <i>Nlrp3</i>, <i>Il1b</i> and <i>Tnf</i>, relative to <i>L27</i>, by Real-Time PCR. (<b>B</b>) After 6 h, 24 h or 48 h of stimulation with α-syn, or 6 h with LPS, cell lysates were analyzed by Western Blot for expression of pro-IL-1β and NLRP3. α-Tubulin was used as loading control. (<b>C</b>) LPS primed microglia were stimulated for 6 h with α-syn or for 30 min with ATP (1 mM) and IL-1β production in culture supernatants was assessed by ELISA. Data shown are the mean ± SD of at least three independent experiments. *p<0.05 compared to control (ctrl).</p>", "links"=>[], "tags"=>["cell stimulation", "2x", "inflammasome activators", "NLRP 3 inflammasome components", "Astrocytes Neuroinflammation", "brain resident macrophages", "il", "Neurodegenerative diseases", "atp", "NLRP 3 inflammasome", "secretion", "microglial compartment", "protein aggregates", "neuroinflammatory conditions", "mouse brain", "Mouse Brain Microglia", "response"], "article_id"=>1455209, "categories"=>["Biological Sciences"], "users"=>["Audrey Gustin", "Mélanie Kirchmeyer", "Eric Koncina", "Paul Felten", "Sophie Losciuto", "Tony Heurtaux", "Aubry Tardivel", "Paul Heuschling", "Catherine Dostert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130624.g004", "stats"=>{"downloads"=>1, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_945_synuclein_is_not_an_NLRP3_inflammasome_activator_/1455209", "title"=>"α-synuclein is not an NLRP3 inflammasome activator.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-19 03:36:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/2127218"], "description"=>"<p>Untreated or LPS primed microglia were stimulated with amyloid-β (Aβ)<sub><b>25–35</b></sub> (20 or 50 μM) or Aβ<sub><b>35–25</b></sub> (50 μM) for 5 h. (<b>A</b>) RNA was analyzed for expression of <i>Nlrp3</i>, <i>Il1b</i> and <i>Tnf</i>, relative to <i>L27</i>, by Real-Time PCR (<b>B)</b> Cell free culture supernatants (SN) and cell lysates (XT) were analyzed by Western Blot for expression of caspase-1 and IL-1β. α-Tubulin was used as loading control. (<b>C)</b> IL-1β production in culture supernatants was assessed by ELISA. (<b>D, E</b>) IL-1β production in culture supernatants was assessed by ELISA in wild type, <i>Nlrp3</i><sup><i>-/-</i></sup> and <i>Casp1</i><sup><i>-/-</i></sup> (<b>D</b>), or <i>P2rx7</i><sup><i>-/-</i></sup> (<b>E</b>) microglia. (<b>F)</b> ATP release was quantified in cell supernatant upon treatment. (<b>G</b>) Untreated or LPS primed microglia were stimulated with amyloid-β (Aβ) 1–42 (10μM) for 6h, 24h or 48h. IL-1β production in culture supernatants was assessed by ELISA. (<b>H)</b> Cell free culture supernatants (SN) and cell lysates (XT) were analyzed by Western Blot for expression IL-1β. α-Tubulin was used as loading control (<b>I)</b>. Data shown are mean ± SD of at least three independent experiments. *p<0.05 compared to control (ctrl), #p<0.05, KO compared to WT.</p>", "links"=>[], "tags"=>["cell stimulation", "2x", "inflammasome activators", "NLRP 3 inflammasome components", "Astrocytes Neuroinflammation", "brain resident macrophages", "il", "Neurodegenerative diseases", "atp", "NLRP 3 inflammasome", "secretion", "microglial compartment", "protein aggregates", "neuroinflammatory conditions", "mouse brain", "Mouse Brain Microglia", "response"], "article_id"=>1455208, "categories"=>["Biological Sciences"], "users"=>["Audrey Gustin", "Mélanie Kirchmeyer", "Eric Koncina", "Paul Felten", "Sophie Losciuto", "Tony Heurtaux", "Aubry Tardivel", "Paul Heuschling", "Catherine Dostert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130624.g003", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Amyloid_25_8211_35_activates_microglia_to_secrete_IL_1_946_independently_from_P2X7_signaling_/1455208", "title"=>"Amyloid-β<sub>25–35</sub> activates microglia to secrete IL-1β independently from P2X7 signaling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-19 03:36:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/2127216"], "description"=>"<p>LPS primed microglia were stimulated with ATP (1 mM, 30 min), Nigericin (Nig, 1.34 μM, 2 h), Monosodium urate (MSU, 100 μg/ml, 5 h) or Aluminium hydroxide (Alum, 300 μg/ml, 5 h). IL-1β production and caspase-1 cleavage were assessed by Western blot (<b>A</b>). Secretion of IL-1β (<b>B</b>), IL-18 (<b>C</b>) and IL-1α(<b>D</b>) in supernatants of wild-type (WT), <i>Nlrp3</i><sup><i>-/-</i></sup> and <i>Casp1</i><sup><i>-/-</i></sup> microglia was assessed by ELISA. IL-1β secretion was assessed by ELISA in WT and <i>P2rx7</i><sup><i>-/-</i></sup> microglia (<b>E</b>) and after treatment with different inhibitors (<b>F-H</b>) (± KCl (25 mM), N-acetyl cystein (NAC, 5 mM), Ca-074Me (10 μM) and cytochalasinD (cytoD, 2 μM)). Inhibitors were added for 30 min prior to inflammasome activation. Data shown are the mean ± SD of at least three independent experiments. *p<0.05, ns = not significant, compared to control (ctrl) (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130624#pone.0130624.g003\" target=\"_blank\">Fig 3B–3E</a>) or compared to no treatment (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130624#pone.0130624.g003\" target=\"_blank\">Fig 3F–3H</a>), #p<0.05, KO compared to WT.</p>", "links"=>[], "tags"=>["cell stimulation", "2x", "inflammasome activators", "NLRP 3 inflammasome components", "Astrocytes Neuroinflammation", "brain resident macrophages", "il", "Neurodegenerative diseases", "atp", "NLRP 3 inflammasome", "secretion", "microglial compartment", "protein aggregates", "neuroinflammatory conditions", "mouse brain", "Mouse Brain Microglia", "response"], "article_id"=>1455206, "categories"=>["Biological Sciences"], "users"=>["Audrey Gustin", "Mélanie Kirchmeyer", "Eric Koncina", "Paul Felten", "Sophie Losciuto", "Tony Heurtaux", "Aubry Tardivel", "Paul Heuschling", "Catherine Dostert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130624.g002", "stats"=>{"downloads"=>1, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NLRP3_inflammasome_activation_mechanism_in_microglia_/1455206", "title"=>"NLRP3 inflammasome activation mechanism in microglia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-19 03:36:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/2127220"], "description"=>"<p>Astrocytes were treated for 6h with LPS, P3C, IL-1β, TNFα, IFNγ or CCM and RNA was extracted and analyzed for expression of <i>Il6</i>, <i>Nos2</i>, <i>Cxcl10</i> (<b>A</b>), <i>Il1b</i>, <i>Nlrp3 and IL18</i><b>(B)</b> relative to <i>L27</i>, by Real-Time PCR. CXCL10 secretion was assessed after 6h or 24h of CCM treatment <b>(C)</b>. Mouse astrocyte-enriched cultures (AEC-M2) and microglia were primed with Complete Cytokine Mix for (24h) or LPS (6h), respectively, prior to stimulation with ATP (1 mM, 30 min), Nig (1,34 μM, 2h), Aβ<sub><b>25–35</b></sub> (20 μM, 5h), WT and mutant α-synuclein (5 μM, 5h) or poly(dA:dT) (1 or 2,5 μg/mL, 5h). Levels of IL-1β(<b>D, E and F</b>) and IL-18 (<b>G</b>) in culture supernatants were assessed by ELISA. Data shown are the mean ± SD of at least three independent experiments *p<0.05 compared to control (ctrl).</p>", "links"=>[], "tags"=>["cell stimulation", "2x", "inflammasome activators", "NLRP 3 inflammasome components", "Astrocytes Neuroinflammation", "brain resident macrophages", "il", "Neurodegenerative diseases", "atp", "NLRP 3 inflammasome", "secretion", "microglial compartment", "protein aggregates", "neuroinflammatory conditions", "mouse brain", "Mouse Brain Microglia", "response"], "article_id"=>1455210, "categories"=>["Biological Sciences"], "users"=>["Audrey Gustin", "Mélanie Kirchmeyer", "Eric Koncina", "Paul Felten", "Sophie Losciuto", "Tony Heurtaux", "Aubry Tardivel", "Paul Heuschling", "Catherine Dostert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130624.g005", "stats"=>{"downloads"=>6, "page_views"=>102, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Astrocytes_are_not_able_to_secrete_inflammasome_substrates_IL_1_946_and_IL_18_/1455210", "title"=>"Astrocytes are not able to secrete inflammasome substrates IL-1β and IL-18.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-19 03:36:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/2127215"], "description"=>"<p>mRNA and/or protein expression of inflammasome components and substrates NLRP1, NLRP3, NLRC4, ASC (Pycard), Aim-2, Caspase-1, Caspase-4, IL-1α, IL-1β, IL-18 and HMGB1, were studied in mouse microglia, astrocytes, or bone-marrow derived macrophages (BMDM) after 6 hours of stimulation with LPS or Complete Cytokine Mix. RNA was extracted and analyzed for gene expression, relative to <i>L27</i>, by Real-Time PCR (<b>A, C, D</b>). Bar graphs shown represent the mean ± SD. (<b>B</b>) NLRP3, ASC and Caspase-1 expression were analyzed by Western Blot and α-Tubulin was used as loading control. (<b>E</b>) Microglia were analyzed by immunofluorescence for the expression of Iba1, NLRP3, ASC, Caspase-1, HMGB1 and IL-1β, nuclei are stained by DAPI, scale bar: 50μm. Data shown are the mean ± SD of at least three independent experiments. *p<0.05 compared to control (ctrl).</p>", "links"=>[], "tags"=>["cell stimulation", "2x", "inflammasome activators", "NLRP 3 inflammasome components", "Astrocytes Neuroinflammation", "brain resident macrophages", "il", "Neurodegenerative diseases", "atp", "NLRP 3 inflammasome", "secretion", "microglial compartment", "protein aggregates", "neuroinflammatory conditions", "mouse brain", "Mouse Brain Microglia", "response"], "article_id"=>1455205, "categories"=>["Biological Sciences"], "users"=>["Audrey Gustin", "Mélanie Kirchmeyer", "Eric Koncina", "Paul Felten", "Sophie Losciuto", "Tony Heurtaux", "Aubry Tardivel", "Paul Heuschling", "Catherine Dostert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130624.g001", "stats"=>{"downloads"=>2, "page_views"=>64, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inflammasome_components_NLRP3_ASC_and_caspase_1_are_expressed_in_microglia_but_not_in_astrocytes_/1455205", "title"=>"Inflammasome components NLRP3, ASC and caspase-1 are expressed in microglia, but not in astrocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-19 03:36:37"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"52", "full-text"=>"63", "pdf"=>"20", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
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  • {"unique-ip"=>"56", "full-text"=>"74", "pdf"=>"14", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"36", "full-text"=>"37", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"43", "full-text"=>"42", "pdf"=>"14", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"37", "full-text"=>"41", "pdf"=>"14", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"47", "full-text"=>"58", "pdf"=>"17", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"88", "full-text"=>"109", "pdf"=>"37", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"75", "full-text"=>"88", "pdf"=>"32", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"66", "full-text"=>"104", "pdf"=>"18", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"63", "full-text"=>"68", "pdf"=>"23", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"54", "full-text"=>"60", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"55", "full-text"=>"56", "pdf"=>"16", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"34", "full-text"=>"42", "pdf"=>"16", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"50", "full-text"=>"52", "pdf"=>"16", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}
  • {"unique-ip"=>"54", "full-text"=>"59", "pdf"=>"16", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}
  • {"unique-ip"=>"56", "full-text"=>"65", "pdf"=>"13", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"11"}
  • {"unique-ip"=>"50", "full-text"=>"56", "pdf"=>"14", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"12"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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