Receptor-Associated Protein (RAP) Plays a Central Role in Modulating Aβ Deposition in APP/PS1 Transgenic Mice
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{"title"=>"Receptor-associated protein (RAP) plays a central role in modulating Aβ deposition in APP/PS1 transgenic mice", "type"=>"journal", "authors"=>[{"first_name"=>"Guilian", "last_name"=>"Xu", "scopus_author_id"=>"7404264099"}, {"first_name"=>"Celeste", "last_name"=>"Karch", "scopus_author_id"=>"24460265800"}, {"first_name"=>"Ning", "last_name"=>"Li", "scopus_author_id"=>"55547128667"}, {"first_name"=>"Nianwei", "last_name"=>"Lin", "scopus_author_id"=>"24922057300"}, {"first_name"=>"David", "last_name"=>"Fromholt", "scopus_author_id"=>"9233688800"}, {"first_name"=>"Victoria", "last_name"=>"Gonzales", "scopus_author_id"=>"6603939767"}, {"first_name"=>"David R.", "last_name"=>"Borchelt", "scopus_author_id"=>"7005319619"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"52349094118", "doi"=>"10.1371/journal.pone.0003159", "pui"=>"352399784", "pmid"=>"18776935", "scopus"=>"2-s2.0-52349094118", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)"}, "id"=>"f00e91d0-3716-35eb-a066-5bf29ec3781e", "abstract"=>"BACKGROUND: Receptor associated protein (RAP) functions in the endoplasmic reticulum (ER) to assist in the maturation of several membrane receptor proteins, including low density lipoprotein receptor-related protein (LRP) and lipoprotein receptor 11 (SorLA/LR11). Previous studies in cell and mouse model systems have demonstrated that these proteins play roles in the metabolism of the amyloid precursor protein (APP), including processes involved in the generation, catabolism and deposition of beta-amyloid (Abeta) peptides.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Mice transgenic for mutant APPswe and mutant presenilin 1 (PS1dE9) were mated to mice with homozygous deletion of RAP. Unexpectedly, mice that were homozygous null for RAP and transgenic for APPswe/PS1dE9 showed high post-natal mortality, necessitating a shift in focus to examine the levels of amyloid deposition in APPswe/PS1dE9 that were hemizygous null for RAP. Immunoblot analysis confirmed 50% reductions in the levels of RAP with modest reductions in the levels of proteins dependent upon RAP for maturation [LRP trend towards a 20% reduction ; SorLA/LR11 statistically significant 15% reduction (p<0.05)]. Changes in the levels of these proteins in the brains of [APPswe/PS1dE9](+/-)/RAP(+/-) mice correlated with 30-40% increases in amyloid deposition by 9 months of age.\\n\\nCONCLUSIONS/SIGNIFICANCE: Partial reductions in the ER chaperone RAP enhance amyloid deposition in the APPswe/PS1dE9 model of Alzheimer amyloidosis. Partial reductions in RAP also affect the maturation of LRP and SorLA/LR11, which are each involved in several different aspects of APP processing and Abeta catabolism. Together, these findings suggest a central role for RAP in Alzheimer amyloidogenesis.", "link"=>"http://www.mendeley.com/research/receptorassociated-protein-rap-plays-central-role-modulating-a%CE%B2-deposition-appps1-transgenic-mice", "reader_count"=>9, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>3, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/922047"], "description"=>"<p>A). Silver staining reveals increased amyloid deposition in the brains of [APPswe/PS1dE9](+/−)/RAP(+/−) mice as compared to the parental APPswe/PS1dE9 line 85 mice. B). Plot of the results from counting amyloid plaques following procedures described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003159#s2\" target=\"_blank\">Methods</a>. Each dot indicates the number of amyloid plaques on a section. Six sections per animal were counted by two independent assessors that were blind to the genotype of the animals. Each section was counted 3 times by each assessor and averaged. Statistical analyses was conducted on the mean number of deposits for each animal [n = 6 for APPswe/PS1dE9 mice and n = 7 for the [APPswe/PS1dE9](+/−)/RAP(+/−) mice]. The statistical difference in amyloid burden between animals of the 2 genotypes was estimated by 2-tailed t-test with equal variance (p<0.05).</p>", "links"=>[], "tags"=>["reducing", "rap", "deposition", "brains"], "article_id"=>592486, "categories"=>["Neuroscience", "Genetics"], "users"=>["Guilian Xu", "Celeste Karch", "Ning Li", "Nianwei Lin", "David Fromholt", "Victoria Gonzales", "David R. Borchelt"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0003159.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Partially_reducing_RAP_increases_A_946_deposition_in_the_brains_of_APPswe_PS1dE9_mice_/592486", "title"=>"Partially reducing RAP increases Aβ deposition in the brains of APPswe/PS1dE9 mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:33:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/922156"], "description"=>"<p>A). Filter trap assays of tissue homogenates from 6 parental line 85 mice and 6 offspring that were APPswe/PS1dE9 positive and hemizygous for RAP was performed as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003159#s2\" target=\"_blank\">Methods</a>. Each column contains a serial dilution of the sample. 300 µg total protein was loaded in the first well, followed by serial 2-fold dilutions. The [APPswe/PS1dE9](+/−)/RAP(+/−) mice have about twice the amount of high molecular weight Aβ burden as the parental line 85 mice at the same age (9 months). B). Quantification of signal intensity was measured as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003159#s2\" target=\"_blank\">Methods</a> across the entire range of dilutions for each group of mice. The amount of high molecular weight “aggregated” Aβ was found to be significantly higher in [APPswe/PS1dE9](+/−)/RAP(+/−) mice at 9 months as compared to the parental APPswe/PS1dE9 animals of the same age (p values noted on graph).</p>", "links"=>[], "tags"=>["assay", "amyloid"], "article_id"=>592603, "categories"=>["Neuroscience", "Genetics"], "users"=>["Guilian Xu", "Celeste Karch", "Ning Li", "Nianwei Lin", "David Fromholt", "Victoria Gonzales", "David R. Borchelt"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0003159.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Filter_assay_of_amyloid_burden_in_APPswe_PS1dE9_8722_RAP_8722_mice_/592603", "title"=>"Filter assay of amyloid burden in [APPswe/PS1dE9](+/−)/RAP(+/−) mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:34:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/922344"], "description"=>"<p>A). Immunoblots were probed with polyclonal antibody 4109 to RAP (1∶1000), 377 to LRP (1∶1000) and monoclonal antibody anti-LR11 (1∶1000; BD Biosciences, San Jose, CA). Protein concentration was determined by BCA. Each lane contains 100 µg total protein. Genotypes of the mice are marked on the figure. B). Quantification of the intensity of the bands in panel A, using a Fuji LAS-3000 imaging device and software provided by the manufacturer. Statistical comparisons of each protein in the two genotypes of interest ([APPswe/PS1dE9](+/−)/RAP(+/+) and [APPswe/PS1dE9](+/−)/RAP(+/−) were conducted on the raw quantitative data, which consisted of pixel values for each protein band quantified. Two-tailed student t-Test with equal variance was used to estimate the probability that differences in the levels of each protein, between genotypes, resulted from random chance (p values for each comparison are noted on the figure). Because the levels of each protein were measured as lower in mice lacking one RAP allele, we chose to graph the data by setting the mean value for each protein in the [APPswe/PS1dE9](+/−)/RAP(+/+) mice to 100, designated controls, and then graphing the values of mice lacking one RAP allele as a percent of the controls. The data represent measures from 6 [APPswe/PS1dE9](+/−)/RAP(+/+) mice compared to 7 [APPswe/PS1dE9] (+/−)/RAP(+/−) mice (except for measures of LR11 n = 6 as one lane was unmeasurable). The two mice without APPswe/PS1dE9 transgenes were not included in measurements so that the only difference between the two groups of animals analyzed was the number of functional RAP alleles.</p>", "links"=>[], "tags"=>["lrp"], "article_id"=>592788, "categories"=>["Neuroscience", "Genetics"], "users"=>["Guilian Xu", "Celeste Karch", "Ning Li", "Nianwei Lin", "David Fromholt", "Victoria Gonzales", "David R. Borchelt"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0003159.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_RAP_LRP_and_SorLA_LR11_levels_/592788", "title"=>"Analysis of RAP, LRP and SorLA/LR11 levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:35:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/922443"], "description"=>"<p>Five [APPswe/PS1dE9](+/−)/RAP(+/−) mice (lanes 2, 4, 8, 9), one [APPswe/PS1dE9](−)/RAP(+/+) mouse (lane 1), one [APPswe/PS1dE9](−)/RAP(+/−) mouse (lane 3), one [APPswe/PS1dE9](+/−)RAP(+/+) mouse (lane 5) and two [APPswe/PS1dE9](−)/RAP(−/−) mice (lanes 6, 7) were used in this experiment. 100 µg total protein was loaded per lane. Upper panel - Immunoblot of tissue extract probed with antibody 4109 to RAP (1∶1000). Lower panel - Immunoblot of tissue extract probed with antibody 377 to LRP (1∶1000). The upper band (∼600 kDa) is the full length LRP, the lower band is an 85 kDa fragment of mature, endoproteolytically cleaved, LRP.</p>", "links"=>[], "tags"=>["lrp", "rap", "transgenic"], "article_id"=>592889, "categories"=>["Neuroscience", "Genetics"], "users"=>["Guilian Xu", "Celeste Karch", "Ning Li", "Nianwei Lin", "David Fromholt", "Victoria Gonzales", "David R. Borchelt"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0003159.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_LRP_and_RAP_levels_in_transgenic_animals_/592889", "title"=>"Analysis of LRP and RAP levels in transgenic animals.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:35:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/922555"], "description"=>"<p>The tissue samples used in this experiment were from the same preparation as those in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003159#pone-0003159-g004\" target=\"_blank\">Figure 4</a>. Immunoblots were probed with monoclonal antibody, 6E10, which is specific for human Aβ 1–17 amino acids contained within the transgene product. Each lane contains 50 µg total protein. Lanes 1–3 were male APPswe/PS1dE9(+/−) mice with RAP(+/+), Lane 4–7 were female APPswe/PS1dE9(+/−) mice with RAP(+/−), Lane 8 and 9 were male APPswe /PS1dE9 mice with RAP(+/−). No obvious difference of the levels of full-length APPswe protein was noted.</p>", "links"=>[], "tags"=>["app", "transgenic"], "article_id"=>593003, "categories"=>["Neuroscience", "Genetics"], "users"=>["Guilian Xu", "Celeste Karch", "Ning Li", "Nianwei Lin", "David Fromholt", "Victoria Gonzales", "David R. Borchelt"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0003159.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_APP_levels_in_transgenic_mice_/593003", "title"=>"Analysis of APP levels in transgenic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:36:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/922624"], "description"=>"*<p>Both animals died before 3 months of age.</p>", "links"=>[], "tags"=>["offsprings", "crosses", "mice", "rap"], "article_id"=>593069, "categories"=>["Neuroscience", "Genetics"], "users"=>["Guilian Xu", "Celeste Karch", "Ning Li", "Nianwei Lin", "David Fromholt", "Victoria Gonzales", "David R. Borchelt"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0003159.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genotypes_of_offsprings_between_crosses_of_APPswe_PS1dE9_RAP_8722_mice_and_RAP_8722_8722_mice_/593069", "title"=>"Genotypes of offsprings between crosses of APPswe/PS1dE9(+)/RAP(+/−) mice and RAP (−/−) mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 09:36:51"}

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  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
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  • {"unique-ip"=>"5", "full-text"=>"2", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"1", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
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  • {"unique-ip"=>"6", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"2", "full-text"=>"1", "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"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
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  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"2", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
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  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
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  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
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  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"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"=>"6"}
  • {"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"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"28", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"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"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
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  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"20", "full-text"=>"23", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"22", "full-text"=>"22", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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Relative Metric

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