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{"title"=>"Dissemination of a Highly Virulent Pathogen: Tracking The Early Events That Define Infection", "type"=>"journal", "authors"=>[{"first_name"=>"Rodrigo J.", "last_name"=>"Gonzalez", "scopus_author_id"=>"26535995000"}, {"first_name"=>"M. Chelsea", "last_name"=>"Lane", "scopus_author_id"=>"9236802600"}, {"first_name"=>"Nikki J.", "last_name"=>"Wagner", "scopus_author_id"=>"55910156800"}, {"first_name"=>"Eric H.", "last_name"=>"Weening", "scopus_author_id"=>"6603135441"}, {"first_name"=>"Virginia L.", "last_name"=>"Miller", "scopus_author_id"=>"7201476879"}], "year"=>2015, "source"=>"PLoS Pathogens", "identifiers"=>{"scopus"=>"2-s2.0-84923834246", "sgr"=>"84923834246", "issn"=>"15537374", "doi"=>"10.1371/journal.ppat.1004587", "pmid"=>"25611317", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "pui"=>"602679678"}, "id"=>"b6682fd5-d3c3-30ab-97fb-cd771c3f7e69", "abstract"=>"The series of events that occurs immediately after pathogen entrance into the body is largely speculative. Key aspects of these events are pathogen dissemination and pathogen interactions with the immune response as the invader moves into deeper tissues. We sought to define major events that occur early during infection of a highly virulent pathogen. To this end, we tracked early dissemination of Yersinia pestis, a highly pathogenic bacterium that causes bubonic plague in mammals. Specifically, we addressed two fundamental questions: (1) do the bacteria encounter barriers in disseminating to draining lymph nodes (LN), and (2) what mechanism does this nonmotile bacterium use to reach the LN compartment, as the prevailing model predicts trafficking in association with host cells. Infection was followed through microscopy imaging in addition to assessing bacterial population dynamics during dissemination from the skin. We found and characterized an unexpected bottleneck that severely restricts bacterial dissemination to LNs. The bacteria that do not pass through this bottleneck are confined to the skin, where large numbers of neutrophils arrive and efficiently control bacterial proliferation. Notably, bottleneck formation is route dependent, as it is abrogated after subcutaneous inoculation. Using a combination of approaches, including microscopy imaging, we tested the prevailing model of bacterial dissemination from the skin into LNs and found no evidence of involvement of migrating phagocytes in dissemination. Thus, early stages of infection are defined by a bottleneck that restricts bacterial dissemination and by neutrophil-dependent control of bacterial proliferation in the skin. Furthermore, and as opposed to current models, our data indicate an intracellular stage is not required by Y. pestis to disseminate from the skin to draining LNs. Because our findings address events that occur during early encounters of pathogen with the immune response, this work can inform efforts to prevent or control infection.", "link"=>"http://www.mendeley.com/research/dissemination-highly-virulent-pathogen-tracking-early-events-define-infection", "reader_count"=>38, "reader_count_by_academic_status"=>{"Researcher"=>13, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Other"=>3, "Student > Master"=>4, "Student > Bachelor"=>4}, "reader_count_by_user_role"=>{"Researcher"=>13, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Other"=>3, "Student > Master"=>4, "Student > Bachelor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>20, "Chemistry"=>2, "Social Sciences"=>1, "Immunology and Microbiology"=>7, "Linguistics"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>7}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>20}, "Linguistics"=>{"Linguistics"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>1, "Madagascar"=>1}, "group_count"=>0}

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CrossRef

• http://doi.org/10.1038/icb.2015.46
• http://doi.org/10.1038/nrgastro.2017.79
• http://doi.org/10.1371/journal.ppat.1005222
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• http://doi.org/10.3389/fcimb.2018.00261
• http://doi.org/10.3390/pathogens9121039
• http://doi.org/10.1038/s41435-019-0065-0
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• http://doi.org/10.1128/IAI.00140-15
• http://doi.org/10.3390/biom10121637
• http://doi.org/10.1038/s41396-019-0475-z
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• http://doi.org/10.1371/journal.ppat.1005241
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• http://doi.org/10.1016/j.tim.2016.01.010
• http://doi.org/10.1093/femspd/ftaa001
• http://doi.org/10.1016/j.micpath.2015.07.012
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• http://doi.org/10.1371/journal.pone.0151788
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• http://doi.org/10.1128/IAI.00061-20
• http://doi.org/10.1128/mBio.01800-17

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PubMed Central | Further Information

• 4468559
• 4496611
• 4524221
• 4612776
• 4363629
• 4564194
• 4615631
• 4619670
• 4803270
• 4612776

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Article Coverage

• {"referral"=>"http://news.unchealthcare.org/news/2015/february/bubonic-bottleneck-unc-scientists-overturn-dogma-on-the-plague", "language"=>"", "title"=>"Bubonic Bottleneck: UNC scientists overturn dogma on the plague", "type"=>"Press Release", "publication"=>"UNC Health Care", "published_on"=>"2015-02-09T00:00:00Z", "link_state"=>"APPROVED"}
• {"referral"=>"http://www.united-academics.org/magazine/health-medicine/why-the-plague-is-so-deadly-still/", "language"=>"", "title"=>"Why the Plague is so Deadly Still", "type"=>"News", "publication"=>"United Academics", "published_on"=>"2015-02-09T00:00:00Z", "link_state"=>"APPROVED"}
• {"referral"=>"http://www.futurity.org/plague-yersinia-pestis-854072/", "language"=>"", "title"=>"Why we haven’t eradicated the plague", "type"=>"News", "publication"=>"Futurity", "published_on"=>"2015-02-11T00:00:00Z", "link_state"=>"APPROVED"}

Article Coverage Curated

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• {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplospathogens%2Farticle%3Fid%3D10.1371%252Fjournal.ppat.1004587", "share_count"=>10, "like_count"=>64, "comment_count"=>13, "click_count"=>0, "total_count"=>87}

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• {"id"=>"1070178738468401153", "text"=>"#PLOSPathogens: Dissemination of a Highly Virulent Pathogen: Tracking The Early Events That Define Infection https://t.co/bkV95qpN0J", "created_at"=>"2018-12-05T04:51:08Z", "user"=>"MoriartyLab", "user_name"=>"Moriarty Lab", "user_profile_image"=>"http://pbs.twimg.com/profile_images/839935232954421248/ffSO7gSS_normal.jpg"}
• {"id"=>"559897876353286146", "text"=>"Some surprising early events during Yersinia infection. @PLOSPathogens http://t.co/oC5RC1tNbB", "created_at"=>"2015-01-27T02:17:10Z", "user"=>"BoyleLab", "user_name"=>"Boyle Lab", "user_profile_image"=>"http://pbs.twimg.com/profile_images/548332296445898753/qMpMlqjV_normal.jpeg"}

Wikipedia | Further Information

• {"title"=>"File:Dissemination-of-a-Highly-Virulent-Pathogen-Tracking-The-Early-Events-That-Define-Infection-ppat.1004587.s010.ogv", "url"=>"http://commons.wikimedia.org/wiki/File:Dissemination-of-a-Highly-Virulent-Pathogen-Tracking-The-Early-Events-That-Define-Infection-ppat.1004587.s010.ogv", "timestamp"=>"2018-02-24T22:46:36Z"}

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• {"files"=>["https://ndownloader.figshare.com/files/1870846", "https://ndownloader.figshare.com/files/1870847", "https://ndownloader.figshare.com/files/1870849", "https://ndownloader.figshare.com/files/1870850", "https://ndownloader.figshare.com/files/1870851", "https://ndownloader.figshare.com/files/1870852", "https://ndownloader.figshare.com/files/1870853", "https://ndownloader.figshare.com/files/1870854", "https://ndownloader.figshare.com/files/1870856", "https://ndownloader.figshare.com/files/1870857"], "description"=>"<div><p>The series of events that occurs immediately after pathogen entrance into the body is largely speculative. Key aspects of these events are pathogen dissemination and pathogen interactions with the immune response as the invader moves into deeper tissues. We sought to define major events that occur early during infection of a highly virulent pathogen. To this end, we tracked early dissemination of <i>Yersinia pestis</i>, a highly pathogenic bacterium that causes bubonic plague in mammals. Specifically, we addressed two fundamental questions: (1) do the bacteria encounter barriers in disseminating to draining lymph nodes (LN), and (2) what mechanism does this nonmotile bacterium use to reach the LN compartment, as the prevailing model predicts trafficking in association with host cells. Infection was followed through microscopy imaging in addition to assessing bacterial population dynamics during dissemination from the skin. We found and characterized an unexpected bottleneck that severely restricts bacterial dissemination to LNs. The bacteria that do not pass through this bottleneck are confined to the skin, where large numbers of neutrophils arrive and efficiently control bacterial proliferation. Notably, bottleneck formation is route dependent, as it is abrogated after subcutaneous inoculation. Using a combination of approaches, including microscopy imaging, we tested the prevailing model of bacterial dissemination from the skin into LNs and found no evidence of involvement of migrating phagocytes in dissemination. Thus, early stages of infection are defined by a bottleneck that restricts bacterial dissemination and by neutrophil-dependent control of bacterial proliferation in the skin. Furthermore, and as opposed to current models, our data indicate an intracellular stage is not required by <i>Y. pestis</i> to disseminate from the skin to draining LNs. Because our findings address events that occur during early encounters of pathogen with the immune response, this work can inform efforts to prevent or control infection.</p></div>", "links"=>[], "tags"=>["nonmotile bacterium use", "microscopy imaging", "bottleneck", "causes bubonic plague", "pathogen", "findings address events", "infection", "bacteria encounter barriers", "dissemination", "ln", "model"], "article_id"=>1293280, "categories"=>["Biological Sciences"], "users"=>["Rodrigo J. Gonzalez", "M. Chelsea Lane", "Nikki J. Wagner", "Eric H. Weening", "Virginia L. Miller"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1004587.s001", "https://dx.doi.org/10.1371/journal.ppat.1004587.s002", "https://dx.doi.org/10.1371/journal.ppat.1004587.s003", "https://dx.doi.org/10.1371/journal.ppat.1004587.s004", "https://dx.doi.org/10.1371/journal.ppat.1004587.s005", "https://dx.doi.org/10.1371/journal.ppat.1004587.s006", "https://dx.doi.org/10.1371/journal.ppat.1004587.s007", "https://dx.doi.org/10.1371/journal.ppat.1004587.s008", "https://dx.doi.org/10.1371/journal.ppat.1004587.s009", "https://dx.doi.org/10.1371/journal.ppat.1004587.s010"], "stats"=>{"downloads"=>20, "page_views"=>43, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dissemination_of_a_Highly_Virulent_Pathogen_Tracking_The_Early_Events_That_Define_Infection_/1293280", "title"=>"Dissemination of a Highly Virulent Pathogen: Tracking The Early Events That Define Infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-01-22 02:44:42"}
• {"files"=>["https://ndownloader.figshare.com/files/1870759"], "description"=>"<p>Mice were inoculated with RFP-<i>Y. pestis</i> and the ear pinna was removed along with surrounding tissue, including draining LNs. (A) LN at 24 hpi, asterisk denotes the site of injection; (i) superimposed fluorescence of LN, (ii) microcolonies in LN, (iii) microcolony at the site where afferent lymphatic vessel (dotted lines) connects with LN; in the same panel, two sections of an afferent tube (red) with bacteria (green) are shown. (B) LN at 48 hpi; (i) superimposed fluorescence of LN, (ii) LN with two afferent vessels. (C-E) Bacteria in afferent vessels. (F) Bacteria associated with host cell in afferent vessel. (G-J) Bacteria in afferent lymphatic vessels at sites distant to LN. (G) bright field, (H) superimposed fluorescence showing a highly colonized LN. (I-J) detail of bacteria in vessels at sites distant to LN. C-J images from tissues harvested at 48 hpi. RFP-<i>Y. pestis</i> were used to image bacteria. In A, B, and G-J, signal was false-colored green for better visualization; DAPI was used to identify host cell nuclei; Antibodies to LYVE-1 and podoplanin were used to image lymphatic tissue. Experiments were performed a minimum of 3 times and representative pictures are shown.</p>", "links"=>[], "tags"=>["nonmotile bacterium use", "microscopy imaging", "bottleneck", "causes bubonic plague", "pathogen", "findings address events", "infection", "bacteria encounter barriers", "dissemination", "ln", "model"], "article_id"=>1293223, "categories"=>["Biological Sciences"], "users"=>["Rodrigo J. Gonzalez", "M. Chelsea Lane", "Nikki J. Wagner", "Eric H. Weening", "Virginia L. Miller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004587.g002", "stats"=>{"downloads"=>4, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Y_pestis_in_afferent_lymphatic_vessels_and_LNs_/1293223", "title"=>"<i>Y. pestis</i> in afferent lymphatic vessels and LNs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-01-22 02:44:42"}
• {"files"=>["https://ndownloader.figshare.com/files/1870781"], "description"=>"<p>(A) Bacterial burden in LN (circles) and ears (triangles) harvested at 24 hpi from mice inoculated with bacteria grown at 26°C (225 CFU, black) or 37°C (283 CFU, white). (B) Bacterial burden in LN (circles), spleens (squares) and ears (triangles) harvested at 48 hpi from mice inoculated with bacteria grown at 26°C (453 CFU, black) or 37°C (290 CFU, white). For (A) and (B), each symbol represents bacterial burden from a single mouse. Horizontal bars are the median of the group. The dotted line represents the limit of detection. Statistical significance was determined using the Mann Whitney test and the p value is shown. Differences between groups were considered to be statistically significant when p < 0.05. (C) Bacterial burden in LNs at different time points after inoculation with 337 CFU. Each bar represents the value from an individual LN (18 LNs were analyzed). A representative experiment is shown. (D) Bacterium associated with lymphatic vessel (green) at 15 min post inoculation. Maximum intensity projection (left) and xz slice (right). (E) Maximum intensity projection of bacteria associated with lymphatic vessel (green) at 20 min after inoculation. Scale bar is 10 μm. RFP-<i>Y. pestis</i> were used to image bacteria; DAPI was used to identify host cell nuclei; fluorescently labeled antibody against LYVE-1 was used to image lymphatic vessels. See <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004587#ppat.1004587.s010\" target=\"_blank\">S1 Video</a>. Experiments were performed a minimum of 2 times and data from representative experiments are shown.</p>", "links"=>[], "tags"=>["nonmotile bacterium use", "microscopy imaging", "bottleneck", "causes bubonic plague", "pathogen", "findings address events", "infection", "bacteria encounter barriers", "dissemination", "ln", "model"], "article_id"=>1293245, "categories"=>["Biological Sciences"], "users"=>["Rodrigo J. Gonzalez", "M. Chelsea Lane", "Nikki J. Wagner", "Eric H. Weening", "Virginia L. Miller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004587.g005", "stats"=>{"downloads"=>3, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bacterial_dissemination_from_the_ear_to_the_draining_LN_/1293245", "title"=>"Bacterial dissemination from the ear to the draining LN.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-01-22 02:44:42"}
• {"files"=>["https://ndownloader.figshare.com/files/1870763"], "description"=>"<p>(A and B) Southern dot blot analysis of DNA from bacteria from (A) LNs harvested at 12 hpi and (B) LNs and spleens at 48 hpi. Each row shows results from a single mouse (identified with a number). The number of CFU obtained from each tissue and from which DNA was extracted is also shown. Representative blots are shown for A and B. A dose of 211 CFU was used. Plates that were completely covered with a layer of bacteria (as opposed to isolated colonies) are identified as “lawn”. (C) Number of tagged strains in LNs after ID (black) or SC (white) inoculation at 48 hpi. A dose of 303 CFU and 331 CFU were used for the ID and SC inoculations, respectively. Each symbol represents a value from an individual mouse. Bars indicate medians per group. Results from two combined experiments are shown. (D) Number of tagged strains in ears (triangles) and LNs [circles at 12 hpi (black) and 48 hpi (white)]. A dose of 226 CFU was used. (E) Bacterial burden from LNs 48 h after the first of two consecutive inoculations. Mice were inoculated first with carbenicillin resistant <i>Y. pestis</i> (652 CFU) and, 24 h later, with kanamycin resistant <i>Y. pestis</i> (<i>Yp/Yp</i>, 449 CFU). Another group of mice was mock inoculated with PBS and, 24 h later, inoculated with kanamycin resistant <i>Y. pestis</i> (PBS/<i>Yp</i>, 449 CFU). The dotted line represents the limit of detection. Each symbol represents a value from an individual mouse. Bars indicate medians per group. The Wilcoxon matched-pairs signed-rank test (D) or the Mann Whitney test (C) and (E) was used to determine statistical significance and the p value is shown. Differences between groups were considered to be statistically significant when p < 0.05. Experiments were performed a minimum of 3 times and data from representative experiments are shown.</p>", "links"=>[], "tags"=>["nonmotile bacterium use", "microscopy imaging", "bottleneck", "causes bubonic plague", "pathogen", "findings address events", "infection", "bacteria encounter barriers", "dissemination", "ln", "model"], "article_id"=>1293227, "categories"=>["Biological Sciences"], "users"=>["Rodrigo J. Gonzalez", "M. Chelsea Lane", "Nikki J. Wagner", "Eric H. Weening", "Virginia L. Miller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004587.g003", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_bottleneck_limits_dissemination_of_Y_pestis_to_the_draining_LN_/1293227", "title"=>"A bottleneck limits dissemination of <i>Y. pestis</i> to the draining LN.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-01-22 02:44:42"}
• {"files"=>["https://ndownloader.figshare.com/files/1870775"], "description"=>"<p>(A) Neutrophils at the IS at different time points. A diagram summarizing the events per time point is shown (left). At 0.5 hpi (i) neutrophil extravasation and (ii) cluster of neutrophils. Bacteria are distant from neutrophils at this time point and are not detected in the same field with neutrophils. At 7 hpi (i) bacteria close to neutrophil and (ii) bacteria inside a neutrophil. At 24 hpi (i) large cluster of neutrophils and (ii) bacteria close to neutrophils. RFP-<i>Y. pestis</i> was used to image bacteria; fluorescently labeled antibody to Ly6G was used to image neutrophils (green), and DAPI was used to stain host cell nuclei. At least four ears per time point were analyzed and images shown here belong to representative experiments. The images show maximum intensity projections from z-stacks. Scale bar is 10 μm. (B) Bacterial burden in LN (circles) or (C) ears (triangles) harvested at 12 hpi from mice injected with PBS (black) or with neutrophil depleting antibody to Ly6G (white). For (B) and (C) the doses used were 189 CFU and 206 CFU, respectively. Each symbol represents bacterial burden from a single mouse. Horizontal bars are the median of the group. The dotted line represents the limit of detection. All values obtained from ears were higher than the limit of detection. Statistical significance was determined using the Mann Whitney test and the p value is shown. Differences between groups were considered to be statistically significant when p < 0.05. Experiments were performed a minimum of 2 times and data from one representative experiment are shown.</p>", "links"=>[], "tags"=>["nonmotile bacterium use", "microscopy imaging", "bottleneck", "causes bubonic plague", "pathogen", "findings address events", "infection", "bacteria encounter barriers", "dissemination", "ln", "model"], "article_id"=>1293239, "categories"=>["Biological Sciences"], "users"=>["Rodrigo J. Gonzalez", "M. Chelsea Lane", "Nikki J. Wagner", "Eric H. Weening", "Virginia L. Miller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004587.g004", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Role_of_neutrophils_during_infection_/1293239", "title"=>"Role of neutrophils during infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-01-22 02:44:42"}
• {"files"=>["https://ndownloader.figshare.com/files/1870739"], "description"=>"<p>(A) RFP-<i>Y. pestis</i> in the skin 5 minutes post inoculation (mpi). (B) GFP-<i>Y. pestis</i> in tube-like structures at the base of a mouse ear. Signal from the ear tissue derives from autofluorescence and was false-colored blue. (C) GFP-<i>Y. pestis</i> in tubes located at the base of the ear (arrowheads indicate regions enlarged in D and E). (D-E) <i>Y. pestis</i> inside the tubes. (F) RFP-<i>Y. pestis</i> associated with host cells (nuclei stained with DAPI) inside tubes. (B-F) taken at 48 hpi. A, C, and F show maximum intensity projections from z-stacks. Experiments were performed a minimum of 3 times and representative pictures are shown.</p>", "links"=>[], "tags"=>["nonmotile bacterium use", "microscopy imaging", "bottleneck", "causes bubonic plague", "pathogen", "findings address events", "infection", "bacteria encounter barriers", "dissemination", "ln", "model"], "article_id"=>1293203, "categories"=>["Biological Sciences"], "users"=>["Rodrigo J. Gonzalez", "M. Chelsea Lane", "Nikki J. Wagner", "Eric H. Weening", "Virginia L. Miller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004587.g001", "stats"=>{"downloads"=>2, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Y_pestis_in_the_skin_and_in_afferent_lymphatic_vessels_/1293203", "title"=>"<i>Y. pestis</i> in the skin and in afferent lymphatic vessels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-01-22 02:44:42"}

PMC Usage Stats | Further Information

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• {"unique-ip"=>"50", "full-text"=>"56", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"12"}
• {"unique-ip"=>"62", "full-text"=>"68", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2021", "month"=>"1"}

Relative Metric

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

F1000Prime | Further Information

• {"year"=>2019, "month"=>7, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2019-07-29T08:41:36Z"}
• {"year"=>2019, "month"=>8, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2019-08-26T08:41:22Z"}
• {"year"=>2019, "month"=>9, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2019-09-30T08:41:21Z"}
• {"year"=>2019, "month"=>10, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2019-10-28T08:41:20Z"}
• {"year"=>2019, "month"=>11, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2019-11-25T09:41:29Z"}
• {"year"=>2019, "month"=>12, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2019-12-30T09:41:44Z"}
• {"year"=>2020, "month"=>1, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-01-27T09:41:15Z"}
• {"year"=>2020, "month"=>2, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-02-24T09:41:24Z"}
• {"year"=>2020, "month"=>3, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-03-30T08:41:27Z"}
• {"year"=>2020, "month"=>4, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-04-27T08:41:18Z"}
• {"year"=>2020, "month"=>5, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-05-25T08:41:21Z"}
• {"year"=>2020, "month"=>6, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-06-29T08:41:21Z"}
• {"year"=>2020, "month"=>7, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-07-27T08:41:20Z"}
• {"year"=>2020, "month"=>8, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-08-31T08:41:28Z"}
• {"year"=>2020, "month"=>9, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-09-28T08:41:24Z"}
• {"year"=>2020, "month"=>10, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-10-26T08:41:22Z"}
• {"year"=>2020, "month"=>11, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-11-30T09:41:27Z"}
• {"year"=>2020, "month"=>12, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2020-12-28T09:41:26Z"}
• {"year"=>2021, "month"=>1, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2021-01-25T09:41:30Z"}
• {"year"=>2021, "month"=>2, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2021-02-22T09:41:27Z"}
• {"year"=>2021, "month"=>3, "doi"=>"10.1371/journal.ppat.1004587", "f1000_id"=>"725321978", "url"=>"https://f1000.com/prime/725321978", "score"=>3, "classifications"=>["good_for_teaching", "new_finding"], "updated_at"=>"2021-03-01T09:41:17Z"}