The Borrelia burgdorferi RelA/SpoT Homolog and Stringent Response Regulate Survival in the Tick Vector and Global Gene Expression during Starvation
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"The Borrelia burgdorferi RelA/SpoT Homolog and Stringent Response Regulate Survival in the Tick Vector and Global Gene Expression during Starvation", "type"=>"journal", "authors"=>[{"first_name"=>"Dan", "last_name"=>"Drecktrah", "scopus_author_id"=>"57078835100"}, {"first_name"=>"Meghan", "last_name"=>"Lybecker", "scopus_author_id"=>"8781228600"}, {"first_name"=>"Niko", "last_name"=>"Popitsch", "scopus_author_id"=>"6504747482"}, {"first_name"=>"Philipp", "last_name"=>"Rescheneder", "scopus_author_id"=>"55246029700"}, {"first_name"=>"Laura S.", "last_name"=>"Hall", "scopus_author_id"=>"56053070200"}, {"first_name"=>"D. Scott", "last_name"=>"Samuels", "scopus_author_id"=>"6505697225"}], "year"=>2015, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"84943536036", "scopus"=>"2-s2.0-84943536036", "doi"=>"10.1371/journal.ppat.1005160", "pui"=>"606367767", "issn"=>"15537374", "pmid"=>"26371761"}, "id"=>"a8d1b9e3-ec5a-347b-983e-bfe713557d6b", "abstract"=>"As the Lyme disease bacterium Borrelia burgdorferi traverses its enzootic cycle, alternating between a tick vector and a vertebrate host, the spirochete must adapt and persist in the tick midgut under prolonged nutrient stress between blood meals. In this study, we examined the role of the stringent response in tick persistence and in regulation of gene expression during nutrient limitation. Nutritionally starving B. burgdorferi in vitro increased the levels of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), collectively referred to as (p)ppGpp, products of the bifunctional synthetase/hydrolase RelBbu (RelA/SpoT homolog). Conversely, returning B. burgdorferi to a nutrient-rich medium decreased (p)ppGpp levels. B. burgdorferi survival in ticks between the larval and nymph blood meals, and during starvation in vitro, was dependent on RelBbu. Furthermore, normal morphological conversion from a flat-wave shape to a condensed round body (RB) form during starvation was dependent on RelBbu; relBbu mutants more frequently formed RBs, but their membranes were compromised. By differential RNA sequencing analyses, we found that RelBbu regulates an extensive transcriptome, both dependent and independent of nutrient stress. The RelBbu regulon includes the glp operon, which is important for glycerol utilization and persistence in the tick, virulence factors and the late phage operon of the 32-kb circular plasmid (cp32) family. In summary, our data suggest that RelBbu globally modulates transcription in response to nutrient stress by increasing (p)ppGpp levels to facilitate B. burgdorferi persistence in the tick.", "link"=>"http://www.mendeley.com/research/borrelia-burgdorferi-relaspot-homolog-stringent-response-regulate-survival-tick-vector-global-gene-e", "reader_count"=>39, "reader_count_by_academic_status"=>{"Librarian"=>1, "Researcher"=>7, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>1, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Librarian"=>1, "Researcher"=>7, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>1, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>5, "Philosophy"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Philosophy"=>{"Philosophy"=>1}}, "reader_count_by_country"=>{"Austria"=>1, "Thailand"=>1, "India"=>1}, "group_count"=>2}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84943536036"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84943536036?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84943536036&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84943536036&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84943536036", "dc:identifier"=>"SCOPUS_ID:84943536036", "eid"=>"2-s2.0-84943536036", "dc:title"=>"The Borrelia burgdorferi RelA/SpoT Homolog and Stringent Response Regulate Survival in the Tick Vector and Global Gene Expression during Starvation", "dc:creator"=>"Drecktrah D.", "prism:publicationName"=>"PLoS Pathogens", "prism:issn"=>"15537366", "prism:eIssn"=>"15537374", "prism:volume"=>"11", "prism:issueIdentifier"=>"9", "prism:pageRange"=>nil, "prism:coverDate"=>"2015-01-01", "prism:coverDisplayDate"=>"2015", "prism:doi"=>"10.1371/journal.ppat.1005160", "citedby-count"=>"39", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University of Montana", "affiliation-city"=>"Missoula", "affiliation-country"=>"United States"}], "pubmed-id"=>"26371761", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e1005160", "source-id"=>"4000151809", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplospathogens%2Farticle%3Fid%3D10.1371%252Fjournal.ppat.1005160", "share_count"=>4, "like_count"=>19, "comment_count"=>2, "click_count"=>0, "total_count"=>25}

Counter

  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"176", "xml_views"=>"6", "html_views"=>"2080"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"85", "xml_views"=>"3", "html_views"=>"445"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"57", "xml_views"=>"1", "html_views"=>"170"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"31", "xml_views"=>"0", "html_views"=>"100"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"97"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"82"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"71"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"103"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"80"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"78"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"24", "xml_views"=>"0", "html_views"=>"76"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"80"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"70"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"28", "xml_views"=>"0", "html_views"=>"73"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"63"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"63"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"28", "xml_views"=>"1", "html_views"=>"74"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"62"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"54"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"69"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"66"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"46"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"24"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"26"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"22"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"3", "html_views"=>"17"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"18", "xml_views"=>"1", "html_views"=>"28"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"17"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2265881"], "description"=>"<p>(A) Temperature, growth phase and pH do not affect <i>rel</i><sub>Bbu</sub> transcript levels. <i>B</i>. <i>burgdorferi</i> strain B31-5A4 was grown in BSK + RS at 23°C or 35°C to log or stationary (stat) phase at pH 7.4 or 6.8 before RNA was isolated, cDNA synthesized and <i>rel</i><sub>Bbu</sub> transcript levels measured by qRT-PCR. (B) Starvation conditions reduce <i>rel</i><sub>Bbu</sub> transcript levels. <i>B</i>. <i>burgdorferi</i> strain B31-5A4 was grown in BSK + RS at 35°C to late log phase before cultures were collected and shifted to RPMI, RPMI without amino acids (aa) and glucose, RPMI without amino acids (aa) and phosphate (PO<sub>4</sub>), or returned to BSK + RS at 35°C. After 30 min, RNA was isolated, cDNA synthesized and <i>rel</i><sub>Bbu</sub> transcript levels measured by qRT-PCR. Values are normalized to <i>rel</i><sub>Bbu</sub> transcript levels at the beginning of each experiment (0 h). (C) <i>B</i>. <i>burgdorferi</i> strain B31-5A4 was grown in BSK + RS at 35°C (0 h), starved in RPMI for 6 h or starved in RPMI for 6 h, and then shifted back to BSK + RS for 2 h. At each time point, <i>rel</i><sub>Bbu</sub> transcript levels were measured as described above. Each value is the mean of three independent experiments and error bars represent the SEM.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544813, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_rel_Bbu_transcript_levels_change_in_response_to_nutrient_levels_/1544813", "title"=>"<i>rel</i><sub>Bbu</sub> transcript levels change in response to nutrient levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265880"], "description"=>"<p>(A) Analysis of radiolabeled nucleotides in wild-type strain B31-5A4 grown in <sup>32</sup>P-orthophosphate. Cultures were grown to late log phase in BSK + RS (lane 1) and then starved in RPMI culture medium for 30 min (lane 2) or 6 h (lane 3) and then shifted back to BSK + RS for 10 min (lane 4) or 2 h (lane 5). At each time point, nucleotides were extracted and separated by TLC. TLC plates were dried, exposed to a phosphor screen and visualized using a phosphorimager. (B) Quantification of (p)ppGpp levels by densitometry. Values represent the mean of three independent experiments, performed as described in A (lanes 1–5), expressed as (p)ppGpp normalized to (p)ppGpp + GTP. Error bars represent SEM. Asterisks indicate <i>P</i> < 0.05 as determined by one-way ANOVA and a Tukey’s <i>post-hoc</i> test.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544812, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Starvation_of_B_burgdorferi_in_RPMI_increases_p_ppGpp_levels_/1544812", "title"=>"Starvation of <i>B</i>. <i>burgdorferi</i> in RPMI increases (p)ppGpp levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265889"], "description"=>"<p>The number of genes significantly Rel<sub>Bbu</sub>-downregulated (lower in wild type than <i>rel</i><sub>Bbu</sub><sup>-</sup>) greater than twofold as determined by RNA-seq in (A) stationary phase, (B) starvation and (C) recovery from starvation. Bars are color-coded based on the color scheme assigned in (D) for unique and overlapping conditions that downregulate genes. (D) Venn diagram of the number of genes Rel<sub>Bbu</sub>-downregulated in stationary phase, starvation and recovery from starvation. Functional gene category abbreviations are the same as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005160#ppat.1005160.g008\" target=\"_blank\">Fig 8</a>.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544821, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.g010", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rel_Bbu_downregulated_genes_during_nutrient_stress_/1544821", "title"=>"Rel<sub>Bbu</sub>-downregulated genes during nutrient stress.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265888"], "description"=>"<p>The number of genes significantly Rel<sub>Bbu</sub>-upregulated (higher in wild type than <i>rel</i><sub>Bbu</sub><sup>-</sup>) greater than twofold as determined by RNA-seq in (A) stationary phase, (B) starvation and (C) recovery from starvation. Bars are color-coded based on the color scheme assigned in (D) for unique and overlapping conditions that upregulate genes. (D) Venn diagram of the number of genes Rel<sub>Bbu</sub>-upregulated in stationary phase, starvation and recovery from starvation. Functional gene category abbreviations are the same as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005160#ppat.1005160.g008\" target=\"_blank\">Fig 8</a>.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544820, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.g009", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rel_Bbu_upregulated_genes_during_nutrient_stress_/1544820", "title"=>"Rel<sub>Bbu</sub>-upregulated genes during nutrient stress.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265885"], "description"=>"<p>(A) Live cell microscopy of wild-type (WT), <i>rel</i><sub>Bbu</sub> mutant (<i>rel</i><sub>Bbu</sub><sup>-</sup>) and <i>rel</i><sub>Bbu</sub><sup>-</sup> pBS-<i>flacp</i>-<i>rel</i><sub>Bbu</sub> (<i>rel</i><sub>Bbu</sub><sup>-</sup> comp) strains grown to late log phase or late stationary phase in BSK + RS before staining with WGA-Alexa Fluor 594. Scale bar = 10 μm. (B) RB quantification in log (gray bars) and stationary (black bars) phase. Each value represents the mean of three independent experiments; error bars represent SEM.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544817, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_rel_Bbu_affects_B_burgdorferi_morphology_in_stationary_phase_/1544817", "title"=>"<i>rel</i><sub>Bbu</sub> affects <i>B</i>. <i>burgdorferi</i> morphology in stationary phase.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265883"], "description"=>"<p>Strains were grown to late log phase in BSK + RS (0 h) before shifting to RPMI for 24 h or 72 h. Wild-type (WT), <i>rel</i><sub>Bbu</sub> mutant (<i>rel</i><sub>Bbu</sub><sup><i>-</i></sup>), and <i>rel</i><sub>Bbu</sub><sup><i>-</i></sup> pBS-<i>flacp</i>-<i>rel</i><sub>Bbu</sub> cells were stained with PI and visualized by DIC and fluorescence microscopy. Images are overlays of DIC and fluorescence images with PI shown in blue. Arrowheads are RBs that did not stain with PI and arrows point to PI-stained RBs. Scale bar = 10 μm. (B) The percentage of live spirochetes as quantified by PI staining following incubation in RPMI for various times (24 h to 96 h). Black squares represent WT in BSK + RS, black circles represent WT in RPMI, white squares represent <i>rel</i><sub>Bbu</sub><sup>-</sup> in BSK + RS, white circles represent <i>rel</i><sub>Bbu</sub><sup>-</sup> in RPMI, gray squares represent <i>rel</i><sub>Bbu</sub><sup><i>-</i></sup> pBS-<i>flacp</i>-<i>rel</i><sub>Bbu</sub> in BSK + RS, and gray circles represent <i>rel</i><sub>Bbu</sub><sup><i>-</i></sup> pBS-<i>flacp</i>-<i>rel</i><sub>Bbu</sub> in RPMI. Values are the means of three independent experiments with at least 100 spirochetes counted for each time point and error bars represent SEM. (C) Wild-type (black bars), <i>rel</i><sub>Bbu</sub><sup>-</sup> (hatched bars) and <i>rel</i><sub>Bbu</sub><sup>-</sup> pBS-<i>rel</i><sub>Bbu</sub> (gray bars) strains were grown in BSK + RS to late log phase before shifting to RPMI. To quantify the number of live <i>B</i>. <i>burgdorferi</i> at the time points indicated, samples of each culture were plated in semi-solid BSK, allowed to grow for two weeks and colonies enumerated to yield colony forming units (CFUs). Each value represents the mean of three independent experiments normalized to the initial number of colonies before shifting to RPMI (0 h). Error bars represent SEM.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544815, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.g004", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Survival_of_B_burgdorferi_during_starvation_conditions_in_vitro_depends_on_rel_Bbu_/1544815", "title"=>"Survival of <i>B</i>. <i>burgdorferi</i> during starvation conditions <i>in vitro</i> depends on <i>rel</i><sub>Bbu</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265884"], "description"=>"<p>Fluorescence microscopy of live <i>B</i>. <i>burgdorferi</i> wild-type (WT), <i>rel</i><sub>Bbu</sub> mutant (<i>rel</i><sub>Bbu</sub><sup><i>-</i></sup>), and <i>rel</i><sub>Bbu</sub><sup><i>-</i></sup> pBS-<i>rel</i><sub>Bbu</sub> strains grown in BSK + RS to late log phase (A-C) or shifted to RPMI for 2 days (D-F) and stained with WGA-Alexa Fluor 594. Scale bar = 10 μm. Scanning electron microscopy of <i>rel</i><sub>Bbu</sub><sup><i>-</i></sup> strains after shifting to RPMI for 2 days (G-J). Arrows indicate folded and disrupted membranes and arrowheads indicate membrane beading. Scale bar = 600 nm.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544816, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.g005", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_rel_Bbu_regulates_round_body_formation_under_starvation_conditions_in_vitro_/1544816", "title"=>"<i>rel</i><sub>Bbu</sub> regulates round body formation under starvation conditions <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265882"], "description"=>"<p>(A) The <i>rel</i><sub>Bbu</sub> mutant (<i>rel</i><sub>Bbu</sub><sup>-</sup>) was constructed by replacing the <i>rel</i><sub>Bbu</sub> gene in strain B31-5A4 with the streptomycin resistance gene <i>aadA</i> fused to the <i>B</i>. <i>burgdorferi flgB</i> promoter and the <i>B</i>. <i>subtilis trpL</i> terminator. The <i>rel</i><sub>Bbu</sub> mutant was complemented in <i>trans</i> by transformation with the <i>Borrelia</i> shuttle vector pBSV2 containing the <i>rel</i><sub>Bbu</sub> gene fused to either the <i>flacp</i> inducible promoter (pBS-<i>flacp</i>-<i>rel</i><sub>Bbu</sub>) or its native promoter (pBS-<i>rel</i><sub>Bbu</sub>). (B) RT-PCR analysis of RNA isolated from wild-type (lane 1), <i>rel</i><sub>Bbu</sub><sup>-</sup> (lane 2), <i>rel</i><sub>Bbu</sub><sup>-</sup> pBS-<i>flacp</i>-<i>rel</i><sub>Bbu</sub> (lane 3), or <i>rel</i><sub>Bbu</sub><sup>-</sup> pBS-<i>rel</i><sub>Bbu</sub> (lane 4) strains. Samples were incubated with (+RT) or without (-RT) reverse transcriptase, and <i>rel</i><sub>Bbu</sub> and <i>flaB</i> transcripts were detected by PCR using primer pairs rsh 981F/rsh 1984R and flaB 423F/flaB 542R, respectively. Products were separated on 1% (<i>rel</i><sub>Bbu</sub>) or 2% (<i>flaB</i>) agarose gels and stained with ethidium bromide. ntc = no template control. (C) Production of (p)ppGpp in the wild-type (WT), <i>rel</i><sub>Bbu</sub><sup><i>-</i></sup> and <i>rel</i><sub>Bbu</sub><sup><i>-</i></sup> pBS-<i>rel</i><sub>Bbu</sub> (<i>rel</i><sub>Bbu</sub><sup>-</sup> comp) strains. <sup>32</sup>P-labeled cultures were grown to log phase, shifted to RPMI for 6 h and nucleotides were extracted and analyzed by TLC.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544814, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutation_and_complementation_of_rel_Bbu_in_B_burgdorferi_/1544814", "title"=>"Mutation and complementation of <i>rel</i><sub>Bbu</sub> in <i>B</i>. <i>burgdorferi</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265891", "https://ndownloader.figshare.com/files/2265892", "https://ndownloader.figshare.com/files/2265893", "https://ndownloader.figshare.com/files/2265894", "https://ndownloader.figshare.com/files/2265895", "https://ndownloader.figshare.com/files/2265896", "https://ndownloader.figshare.com/files/2265897", "https://ndownloader.figshare.com/files/2265898", "https://ndownloader.figshare.com/files/2265899", "https://ndownloader.figshare.com/files/2265900", "https://ndownloader.figshare.com/files/2265901", "https://ndownloader.figshare.com/files/2265902", "https://ndownloader.figshare.com/files/2265903", "https://ndownloader.figshare.com/files/2265904", "https://ndownloader.figshare.com/files/2265905", "https://ndownloader.figshare.com/files/2265906", "https://ndownloader.figshare.com/files/2265907"], "description"=>"<div><p>As the Lyme disease bacterium <i>Borrelia burgdorferi</i> traverses its enzootic cycle, alternating between a tick vector and a vertebrate host, the spirochete must adapt and persist in the tick midgut under prolonged nutrient stress between blood meals. In this study, we examined the role of the stringent response in tick persistence and in regulation of gene expression during nutrient limitation. Nutritionally starving <i>B</i>. <i>burgdorferi in vitro</i> increased the levels of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), collectively referred to as (p)ppGpp, products of the bifunctional synthetase/hydrolase Rel<sub>Bbu</sub> (RelA/SpoT homolog). Conversely, returning <i>B</i>. <i>burgdorferi</i> to a nutrient-rich medium decreased (p)ppGpp levels. <i>B</i>. <i>burgdorferi</i> survival in ticks between the larval and nymph blood meals, and during starvation <i>in vitro</i>, was dependent on Rel<sub>Bbu</sub>. Furthermore, normal morphological conversion from a flat-wave shape to a condensed round body (RB) form during starvation was dependent on Rel<sub>Bbu</sub>; <i>rel</i><sub>Bbu</sub> mutants more frequently formed RBs, but their membranes were compromised. By differential RNA sequencing analyses, we found that Rel<sub>Bbu</sub> regulates an extensive transcriptome, both dependent and independent of nutrient stress. The Rel<sub>Bbu</sub> regulon includes the <i>glp</i> operon, which is important for glycerol utilization and persistence in the tick, virulence factors and the late phage operon of the 32-kb circular plasmid (cp32) family. In summary, our data suggest that Rel<sub>Bbu</sub> globally modulates transcription in response to nutrient stress by increasing (p)ppGpp levels to facilitate <i>B</i>. <i>burgdorferi</i> persistence in the tick.</p></div>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544823, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005160.s001", "https://dx.doi.org/10.1371/journal.ppat.1005160.s002", "https://dx.doi.org/10.1371/journal.ppat.1005160.s003", "https://dx.doi.org/10.1371/journal.ppat.1005160.s004", "https://dx.doi.org/10.1371/journal.ppat.1005160.s005", "https://dx.doi.org/10.1371/journal.ppat.1005160.s006", "https://dx.doi.org/10.1371/journal.ppat.1005160.s007", "https://dx.doi.org/10.1371/journal.ppat.1005160.s008", "https://dx.doi.org/10.1371/journal.ppat.1005160.s009", "https://dx.doi.org/10.1371/journal.ppat.1005160.s010", "https://dx.doi.org/10.1371/journal.ppat.1005160.s011", "https://dx.doi.org/10.1371/journal.ppat.1005160.s012", "https://dx.doi.org/10.1371/journal.ppat.1005160.s013", "https://dx.doi.org/10.1371/journal.ppat.1005160.s014", "https://dx.doi.org/10.1371/journal.ppat.1005160.s015", "https://dx.doi.org/10.1371/journal.ppat.1005160.s016", "https://dx.doi.org/10.1371/journal.ppat.1005160.s017"], "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Borrelia_burgdorferi_RelA_SpoT_Homolog_and_Stringent_Response_Regulate_Survival_in_the_Tick_Vector_and_Global_Gene_Expression_during_Starvation/1544823", "title"=>"The <i>Borrelia burgdorferi</i> RelA/SpoT Homolog and Stringent Response Regulate Survival in the Tick Vector and Global Gene Expression during Starvation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265890"], "description"=>"<p><sup>a</sup> Intradermal injection with 10<sup>5</sup> cells.</p><p><sup>b</sup> Tissues collected five weeks post-injection or post nymph feeding and cultured in BSK medium. Figures are the number of infected mice/number of mice tested.</p><p><sup>c</sup> Five nymphs infected with the indicated strains were allowed to feed to repletion on naïve mice.</p><p>Mouse infectivity of the <i>B</i>. <i>burgdorferi rel</i><sub>Bbu</sub> mutant.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544822, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mouse_infectivity_of_the_B_burgdorferi_rel_Bbu_mutant_/1544822", "title"=>"Mouse infectivity of the <i>B</i>. <i>burgdorferi rel</i><sub>Bbu</sub> mutant.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265887"], "description"=>"<p>Genes significantly differentially expressed more than twofold as determined by RNA-seq of wild-type B31-5A4 (A) shifted from stationary phase to starvation (6 h RPMI) and (B) in recovery (2 h BSK + RS) from starvation. The number of genes upregulated (black bars) and downregulated (gray bars) are divided by functional category using the following abbreviations: BP, bacteriophage; CD, cell division; CE, cell envelope; CM, chemotaxis and motility; MT, metabolism; PD, protein degradation; RR, DNA replication and repair; SR, stress response; TL, translation; TP, transporter proteins; TR, transcription and transcriptional regulation; and U, unknown.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544819, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.g008", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_transcript_levels_in_wild_type_B_burgdorferi_during_nutrient_stress_/1544819", "title"=>"Changes in transcript levels in wild-type <i>B</i>. <i>burgdorferi</i> during nutrient stress.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-15 02:51:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/2265886"], "description"=>"<p>(A) Immunofluorescence microscopy of ticks allowed to feed on mice infected with wild-type (WT), <i>rel</i><sub>Bbu</sub> mutant (<i>rel</i><sub>Bbu</sub><sup>-</sup>) or <i>rel</i><sub>Bbu</sub><sup>-</sup> pBS-<i>rel</i><sub>Bbu</sub> strains. Ticks were dissected and fixed on slides one week after naïve larvae had fed to repletion (fed larvae) or after larvae had molted to nymphs (unfed nymph) or one week after nymphs had fed to repletion on uninfected mice (fed nymph). Samples were processed for IF microscopy using rabbit polyclonal anti-<i>B</i>. <i>burgdorferi</i> antibodies followed by goat anti-rabbit Alexa Fluor 488 antibodies to visualize spirochetes (green). Tick cells were visualized by staining with WGA-Alexa Fluor 594 (red). Scale bar = 10 μm. (B) Quantification of <i>Borrelia</i> in ticks that had fed on mice infected with wild-type (black circles), <i>rel</i><sub>Bbu</sub><sup>-</sup> (white circles) or <i>rel</i><sub>Bbu</sub><sup>-</sup> pBS-<i>rel</i><sub>Bbu</sub> (gray circles) strains. Total DNA was isolated from larvae that had fed to repletion (fed larvae) or after larvae had molted to nymphs (unfed nymph) or one week after nymphs had fed to repletion on uninfected mice (fed nymph). The number of <i>B</i>. <i>burgdorferi</i> genome equivalents per tick was determined by qPCR using TaqMan primers/probe to <i>flaB</i>. The difference between the number of WT and <i>rel</i><sub>Bbu</sub><sup>-</sup> in fed nymphs was statistically significant (<i>P</i> = 0.018) by a one-way ANOVA with a Tukey’s <i>post hoc</i> test.</p>", "links"=>[], "tags"=>["glycerol utilization", "nymph blood meals", "RNA sequencing analyses", "rb", "relBbu mutants", "Virulence factors", "burgdorferi persistence", "glp operon", "phage operon", "guanosine pentaphosphate", "gene expression", "Tick Vector", "RelBbu regulon", "Stringent Response Regulate Survival", "burgdorferi survival", "round body", "Global Gene Expression", "Lyme disease bacterium Borrelia burgdorferi traverses", "modulates transcription", "blood meals", "enzootic cycle", "guanosine tetraphosphate", "stress"], "article_id"=>1544818, "categories"=>["Biological Sciences"], "users"=>["Dan Drecktrah", "Meghan Lybecker", "Niko Popitsch", "Philipp Rescheneder", "Laura S. Hall", "D. Scott Samuels"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005160.g007", "stats"=>{"downloads"=>13, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tick_persistence_depends_on_rel_Bbu_/1544818", "title"=>"Tick persistence depends on <i>rel</i><sub>Bbu</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-09-15 02:51:13"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"27", "full-text"=>"36", "pdf"=>"21", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"72", "full-text"=>"68", "pdf"=>"33", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"20", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"52", "full-text"=>"52", "pdf"=>"26", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"2", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"50", "full-text"=>"27", "pdf"=>"25", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"19", "full-text"=>"16", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"14", "full-text"=>"17", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"28", "full-text"=>"18", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"10", "cited-by"=>"1", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"22", "full-text"=>"17", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"23", "full-text"=>"20", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"16", "full-text"=>"14", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"14", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"17", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"9", "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"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"22", "full-text"=>"17", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"7", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "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"=>"16", "full-text"=>"18", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"21", "full-text"=>"18", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"7", "cited-by"=>"1", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"19", "full-text"=>"15", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
Loading … Spinner
There are currently no alerts