Porphyromonas gingivalis Peptidylarginine Deiminase, a Key Contributor in the Pathogenesis of Experimental Periodontal Disease and Experimental Arthritis
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{"title"=>"Porphyromonas gingivalis peptidylarginine deiminase, a key contributor in the pathogenesis of experimental periodontal disease and experimental arthritis", "type"=>"journal", "authors"=>[{"first_name"=>"Neville", "last_name"=>"Gully", "scopus_author_id"=>"6602505109"}, {"first_name"=>"Richard", "last_name"=>"Bright", "scopus_author_id"=>"56030714400"}, {"first_name"=>"Victor", "last_name"=>"Marino", "scopus_author_id"=>"14024664500"}, {"first_name"=>"Ceilidh", "last_name"=>"Marchant", "scopus_author_id"=>"35933418300"}, {"first_name"=>"Melissa", "last_name"=>"Cantley", "scopus_author_id"=>"26532372300"}, {"first_name"=>"David", "last_name"=>"Haynes", "scopus_author_id"=>"7102769050"}, {"first_name"=>"Catherine", "last_name"=>"Butler", "scopus_author_id"=>"8669571400"}, {"first_name"=>"Stuart", "last_name"=>"Dashper", "scopus_author_id"=>"6603692498"}, {"first_name"=>"Eric", "last_name"=>"Reynolds", "scopus_author_id"=>"35550178300"}, {"first_name"=>"Mark", "last_name"=>"Bartold", "scopus_author_id"=>"7007048712"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84903538710", "pmid"=>"24959715", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "pui"=>"373418878", "issn"=>"19326203", "scopus"=>"2-s2.0-84903538710", "doi"=>"10.1371/journal.pone.0100838"}, "id"=>"06472a02-e771-3da6-8cbb-e6362aeeeffa", "abstract"=>"OBJECTIVES: To investigate the suggested role of Porphyromonas gingivalis peptidylarginine deiminase (PAD) in the relationship between the aetiology of periodontal disease and experimentally induced arthritis and the possible association between these two conditions.\\n\\nMETHODS: A genetically modified PAD-deficient strain of P. gingivalis W50 was produced. The effect of this strain, compared to the wild type, in an established murine model for experimental periodontitis and experimental arthritis was assessed. Experimental periodontitis was induced following oral inoculation with the PAD-deficient and wild type strains of P. gingivalis. Experimental arthritis was induced via the collagen antibody induction process and was monitored by assessment of paw swelling and micro-CT analysis of the radio-carpal joints. Experimental periodontitis was monitored by micro CT scans of the mandible and histological assessment of the periodontal tissues around the mandibular molars. Serum levels of anti-citrullinated protein antibodies (ACPA) and P. gingivalis were assessed by ELISA.\\n\\nRESULTS: The development of experimental periodontitis was significantly reduced in the presence of the PAD-deficient P. gingivalis strain. When experimental arthritis was induced in the presence of the PAD-deficient strain there was less paw swelling, less erosive bone damage to the joints and reduced serum ACPA levels when compared to the wild type P. gingivalis inoculated group.\\n\\nCONCLUSION: This study has demonstrated that a PAD-deficient strain of P. gingivalis was associated with significantly reduced periodontal inflammation. In addition the extent of experimental arthritis was significantly reduced in animals exposed to prior induction of periodontal disease through oral inoculation of the PAD-deficient strain versus the wild type. This adds further evidence to the potential role for P. gingivalis and its PAD in the pathogenesis of periodontitis and exacerbation of arthritis. Further studies are now needed to elucidate the mechanisms which drive these processes.", "link"=>"http://www.mendeley.com/research/porphyromonas-gingivalis-peptidylarginine-deiminase-key-contributor-pathogenesis-experimental-period-1", "reader_count"=>43, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>9, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>9, "Student > Master"=>11, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>9, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>9, "Student > Master"=>11, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>14, "Medicine and Dentistry"=>19, "Design"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>19}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Poland"=>1, "United Kingdom"=>1, "Germany"=>1}, "group_count"=>8}

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  • {"files"=>["https://ndownloader.figshare.com/files/1562079", "https://ndownloader.figshare.com/files/1562080", "https://ndownloader.figshare.com/files/1562081", "https://ndownloader.figshare.com/files/1562082"], "description"=>"<div><p>Objectives</p><p>To investigate the suggested role of <i>Porphyromonas gingivalis</i> peptidylarginine deiminase (PAD) in the relationship between the aetiology of periodontal disease and experimentally induced arthritis and the possible association between these two conditions.</p><p>Methods</p><p>A genetically modified PAD-deficient strain of <i>P. gingivalis</i> W50 was produced. The effect of this strain, compared to the wild type, in an established murine model for experimental periodontitis and experimental arthritis was assessed. Experimental periodontitis was induced following oral inoculation with the PAD-deficient and wild type strains of <i>P. gingivalis</i>. Experimental arthritis was induced via the collagen antibody induction process and was monitored by assessment of paw swelling and micro-CT analysis of the radio-carpal joints. Experimental periodontitis was monitored by micro CT scans of the mandible and histological assessment of the periodontal tissues around the mandibular molars. Serum levels of anti-citrullinated protein antibodies (ACPA) and <i>P. gingivalis</i> were assessed by ELISA.</p><p>Results</p><p>The development of experimental periodontitis was significantly reduced in the presence of the PAD-deficient <i>P. gingivalis</i> strain. When experimental arthritis was induced in the presence of the PAD-deficient strain there was less paw swelling, less erosive bone damage to the joints and reduced serum ACPA levels when compared to the wild type <i>P. gingivalis</i> inoculated group.</p><p>Conclusion</p><p>This study has demonstrated that a PAD-deficient strain of <i>P. gingivalis</i> was associated with significantly reduced periodontal inflammation. In addition the extent of experimental arthritis was significantly reduced in animals exposed to prior induction of periodontal disease through oral inoculation of the PAD-deficient strain versus the wild type. This adds further evidence to the potential role for <i>P. gingivalis</i> and its PAD in the pathogenesis of periodontitis and exacerbation of arthritis. Further studies are now needed to elucidate the mechanisms which drive these processes.</p></div>", "links"=>[], "tags"=>["microbiology", "Animal models of infection", "Oral medicine", "dentistry", "Oral diseases", "Oral health", "rheumatology", "arthritis", "Animal studies", "Animal models of disease", "peptidylarginine", "pathogenesis", "periodontal"], "article_id"=>1081120, "categories"=>["Biological Sciences"], "users"=>["Neville Gully", "Richard Bright", "Victor Marino", "Ceilidh Marchant", "Melissa Cantley", "David Haynes", "Catherine Butler", "Stuart Dashper", "Eric Reynolds", "Mark Bartold"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0100838.s001", "https://dx.doi.org/10.1371/journal.pone.0100838.s002", "https://dx.doi.org/10.1371/journal.pone.0100838.s003", "https://dx.doi.org/10.1371/journal.pone.0100838.s004"], "stats"=>{"downloads"=>14, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Porphyromonas_gingivalis_Peptidylarginine_Deiminase_a_Key_Contributor_in_the_Pathogenesis_of_Experimental_Periodontal_Disease_and_Experimental_Arthritis/1081120", "title"=>"<i>Porphyromonas gingivalis</i> Peptidylarginine Deiminase, a Key Contributor in the Pathogenesis of Experimental Periodontal Disease and Experimental Arthritis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-06-24 03:01:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1562077"], "description"=>"<p>(+) Viable wild type (W50) and PAD-deficient (ECR527) <i>P. gingivalis strains</i> W50 and ECR527 were recovered from the gingiva of each group of mice inoculated separately with each strain at the three time points assayed. The colonies in both groups were black pigmented with gram negative staining organisms.</p><p>(−) No viable organisms were recovered from the control group receiving the vehicle (2% CMC).</p><p>(*) PPAD activity was only demonstrated in the group of mice where <i>P. gingivalis</i> W50 was recovered from gingival swabs.</p>", "links"=>[], "tags"=>["microbiology", "Animal models of infection", "Oral medicine", "dentistry", "Oral diseases", "Oral health", "rheumatology", "arthritis", "Animal studies", "Animal models of disease", "viable", "swabs"], "article_id"=>1081118, "categories"=>["Biological Sciences"], "users"=>["Neville Gully", "Richard Bright", "Victor Marino", "Ceilidh Marchant", "Melissa Cantley", "David Haynes", "Catherine Butler", "Stuart Dashper", "Eric Reynolds", "Mark Bartold"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100838.t002", "stats"=>{"downloads"=>1, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Recovery_of_viable_P_gingivalis_from_oral_swabs_after_final_inoculation_/1081118", "title"=>"Recovery of viable <i>P. gingivalis</i> from oral swabs after final inoculation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-24 03:01:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1562059"], "description"=>"<p>A. Appearance of front and rear paws for CMC control group at day 7 post EA induction. B. Appearance of front and rear paws for ECR527 & EA group at day 7 post EA induction. C. Appearance of front and rear paws for W50 & EA group at day 7 post EA induction. D. Total paw score grade out of a 60 including front and back paws. Data represent mean (± SEM). The number of animals in each group was 6 and measurements were performed once daily per animal Statistical analysis was done by two way ANOVA and Tukey multiple comparisons. Raw data for data points are shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100838#pone.0100838.s001\" target=\"_blank\">Figure S1</a>. <i>Abbreviations:</i> CMC = carboxymethyl cellulose; ECR527 = PAD-deficient <i>P. gingivalis</i>; W50 = wild type <i>P. Gingivalis</i>; EA = experimental arthritis</p>", "links"=>[], "tags"=>["microbiology", "Animal models of infection", "Oral medicine", "dentistry", "Oral diseases", "Oral health", "rheumatology", "arthritis", "Animal studies", "Animal models of disease", "scoring", "paw"], "article_id"=>1081100, "categories"=>["Biological Sciences"], "users"=>["Neville Gully", "Richard Bright", "Victor Marino", "Ceilidh Marchant", "Melissa Cantley", "David Haynes", "Catherine Butler", "Stuart Dashper", "Eric Reynolds", "Mark Bartold"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100838.g004", "stats"=>{"downloads"=>1, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Visual_appearance_and_scoring_of_paw_swelling_/1081100", "title"=>"Visual appearance and scoring of paw swelling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-24 03:01:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1562056"], "description"=>"<p>A. Histology of mouse jaw for CMC control group at day 63. B. Histology of mouse jaw for ECR527 & EA group at day 63. C. Histology of mouse jaw for W50 & EA group at day 63. Arrow indicates increased inflammatory reaction in supra-crestal alveolar bone gingival tissue. D. Histological scores (mean ± SEM) for the presence of osteoclasts and evidence of bone erosion around the first and second upper molars for all groups in the study. Original magnification of A–C = 100X. The number of animals in each group was 6 and measurements were performed in triplicate. Statistical analysis was done by one way ANOVA and Tukey multiple comparisons. <i>Abbreviations:</i> CMC = carboxymethyl cellulose; ECR527 = PAD-deficient <i>P. gingivalis</i>; W50 = wild type <i>P. Gingivalis</i>; EA = experimental arthritis.</p>", "links"=>[], "tags"=>["microbiology", "Animal models of infection", "Oral medicine", "dentistry", "Oral diseases", "Oral health", "rheumatology", "arthritis", "Animal studies", "Animal models of disease", "maxillary", "periodontal"], "article_id"=>1081097, "categories"=>["Biological Sciences"], "users"=>["Neville Gully", "Richard Bright", "Victor Marino", "Ceilidh Marchant", "Melissa Cantley", "David Haynes", "Catherine Butler", "Stuart Dashper", "Eric Reynolds", "Mark Bartold"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100838.g002", "stats"=>{"downloads"=>2, "page_views"=>44, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histological_analysis_of_maxillary_periodontal_tissues_/1081097", "title"=>"Histological analysis of maxillary periodontal tissues.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-24 03:01:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1562073"], "description"=>"<p>A. Histology of the radio-carpal joint for CMC control group at day 63. B. Histology of the radio-carpal joint for ECR527 & EA group at day 63. C. Histology of the radio-carpal joint for W50 & EA group at day 63. Arows indicate increased inflamaotry reaction in joint. D. Histological scores (mean ± SEM) for (a) inflammation and (b) bone and cartilage destruction for both front and rear paws combined. Original magnification of A–C = 100X. The number of animals in each group was 6 and measurements were performed in triplicate. Statistical analysis was done by One way ANOVA and Bonferroni multiple comparisons. <i>Abbreviations:</i> CMC = carboxymethyl cellulose; ECR527 = PAD-deficient <i>P. gingivalis</i>; W50 = wild type <i>P. Gingivalis</i>; EA = experimental arthritis</p>", "links"=>[], "tags"=>["microbiology", "Animal models of infection", "Oral medicine", "dentistry", "Oral diseases", "Oral health", "rheumatology", "arthritis", "Animal studies", "Animal models of disease"], "article_id"=>1081114, "categories"=>["Biological Sciences"], "users"=>["Neville Gully", "Richard Bright", "Victor Marino", "Ceilidh Marchant", "Melissa Cantley", "David Haynes", "Catherine Butler", "Stuart Dashper", "Eric Reynolds", "Mark Bartold"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100838.g005", "stats"=>{"downloads"=>2, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histological_assessment_of_joint_inflammation_/1081114", "title"=>"Histological assessment of joint inflammation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-24 03:01:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1562076"], "description"=>"<p>The mean (± SEM) titre of anti-<i>P.gingivalis</i> detected in the sera of mice over 9 week time course. Raw data for data points are shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100838#pone.0100838.s003\" target=\"_blank\">Figure S3</a>. The number in each group was 6 and measurements were performed in duplicate. Statistical analysis was done by one way ANOVA and Tukey multiple comparisons. <i>Abbreviations:</i> CMC = carboxymethyl cellulose; ECR527 = PAD-deficient <i>P. gingivalis</i>; W50 = wild type <i>P. Gingivalis</i>; EA = experimental arthritis</p>", "links"=>[], "tags"=>["microbiology", "Animal models of infection", "Oral medicine", "dentistry", "Oral diseases", "Oral health", "rheumatology", "arthritis", "Animal studies", "Animal models of disease"], "article_id"=>1081117, "categories"=>["Biological Sciences"], "users"=>["Neville Gully", "Richard Bright", "Victor Marino", "Ceilidh Marchant", "Melissa Cantley", "David Haynes", "Catherine Butler", "Stuart Dashper", "Eric Reynolds", "Mark Bartold"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100838.g007", "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_anti_P_gingivalis_levels_/1081117", "title"=>"Serum anti-<i>P. gingivalis</i> levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-24 03:01:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1562075"], "description"=>"<p>The mean (± SEM) titre of anti-CCP antibodies detected in the sera of mice at week 9 from each of the 6 treatment groups. Raw data for data points are shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100838#pone.0100838.s002\" target=\"_blank\">Figure S2</a>. The number in each group was 6 and measurements were performed in duplicate. Statistical analysis was done by one way ANOVA and Tukey multiple comparisons. <i>Abbreviations:</i> CMC = carboxymethyl cellulose; ECR527 = PAD-deficient <i>P. gingivalis</i>; W50 = wild type <i>P. Gingivalis</i>; EA = experimental arthritis</p>", "links"=>[], "tags"=>["microbiology", "Animal models of infection", "Oral medicine", "dentistry", "Oral diseases", "Oral health", "rheumatology", "arthritis", "Animal studies", "Animal models of disease", "anti-ccp", "antibody"], "article_id"=>1081116, "categories"=>["Biological Sciences"], "users"=>["Neville Gully", "Richard Bright", "Victor Marino", "Ceilidh Marchant", "Melissa Cantley", "David Haynes", "Catherine Butler", "Stuart Dashper", "Eric Reynolds", "Mark Bartold"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100838.g006", "stats"=>{"downloads"=>0, "page_views"=>33, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_anti_CCP_antibody_levels_/1081116", "title"=>"Serum anti-CCP antibody levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-24 03:01:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1562057"], "description"=>"<p>A. Micro CT appearance of paw for CMC control group at day 63. B. Micro CT appearance of paw for ECR527 & EA group at day 63. C. Micro CT appearance of paw for W50 & EA group at day 63. D. The front paws (left and right combined), were processed to determine bone loss/growth between the two scanned time points in the radio-carpal joint. Data represent mean (± SEM). The number of animals in each group was 6 and measurements were performed in duplicate. Statistical analysis was done by one way ANOVA and Bonferroni multiple comparisons. <i>Abbreviations:</i> CMC = carboxymethyl cellulose; ECR527 = PAD-deficient <i>P. gingivalis</i>; W50 = wild type <i>P. Gingivalis</i>; EA = experimental arthritis</p>", "links"=>[], "tags"=>["microbiology", "Animal models of infection", "Oral medicine", "dentistry", "Oral diseases", "Oral health", "rheumatology", "arthritis", "Animal studies", "Animal models of disease", "ct", "erosion", "paw", "radio-carpal"], "article_id"=>1081098, "categories"=>["Biological Sciences"], "users"=>["Neville Gully", "Richard Bright", "Victor Marino", "Ceilidh Marchant", "Melissa Cantley", "David Haynes", "Catherine Butler", "Stuart Dashper", "Eric Reynolds", "Mark Bartold"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100838.g003", "stats"=>{"downloads"=>0, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Micro_CT_appearance_and_analysis_of_bone_erosion_in_front_paw_radio_carpal_joint_/1081098", "title"=>"Micro CT appearance and analysis of bone erosion in front paw radio-carpal joint.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-24 03:01:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1562049"], "description"=>"<p>A. Micro CT of mouse jaw for CMC control group. B. Micro CT of mouse jaw for ECR527 & EA group. C. Micro CT of mouse jaw W50 & EA group. D. Measurements of bone changes in the jaw were calculated by measuring the cemento-enamel junction-alveolar bone crest on three slices for each mouse using CTAn sagital sections. Data represent mean (± SEM). The number of animals in each group was 6 and measurements were performed in triplicate. Statistical analysis was done by one way ANOVA and Tukey multiple comparisons. White bars represent CEJ/ABC distance measurements. <i>Abbreviations:</i> CMC = carboxymethyl cellulose; ECR527 = PAD-deficient <i>P. gingivalis</i>; W50 = wild type <i>P. Gingivalis</i>; EA = experimental arthritis</p>", "links"=>[], "tags"=>["microbiology", "Animal models of infection", "Oral medicine", "dentistry", "Oral diseases", "Oral health", "rheumatology", "arthritis", "Animal studies", "Animal models of disease", "ct", "periodontal"], "article_id"=>1081092, "categories"=>["Biological Sciences"], "users"=>["Neville Gully", "Richard Bright", "Victor Marino", "Ceilidh Marchant", "Melissa Cantley", "David Haynes", "Catherine Butler", "Stuart Dashper", "Eric Reynolds", "Mark Bartold"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100838.g001", "stats"=>{"downloads"=>3, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Micro_CT_appearance_and_analysis_of_periodontal_bone_loss_/1081092", "title"=>"Micro CT appearance and analysis of periodontal bone loss.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-24 03:01:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1562078"], "description"=>"a<p>Underlined sequence of SOE primers indicates the part of the primer that is not complementary to the target sequence, but provides complementarity with a second PCR product for splicing.</p>", "links"=>[], "tags"=>["microbiology", "Animal models of infection", "Oral medicine", "dentistry", "Oral diseases", "Oral health", "rheumatology", "arthritis", "Animal studies", "Animal models of disease", "primers"], "article_id"=>1081119, "categories"=>["Biological Sciences"], "users"=>["Neville Gully", "Richard Bright", "Victor Marino", "Ceilidh Marchant", "Melissa Cantley", "David Haynes", "Catherine Butler", "Stuart Dashper", "Eric Reynolds", "Mark Bartold"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100838.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Oligonucleotide_primers_used_in_this_study_/1081119", "title"=>"Oligonucleotide primers used in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-24 03:01:04"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"11", "full-text"=>"5", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"25", "full-text"=>"28", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"20", "full-text"=>"26", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"46", "full-text"=>"42", "pdf"=>"24", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"23", "full-text"=>"30", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"23", "full-text"=>"21", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"28", "full-text"=>"26", "pdf"=>"15", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"17", "full-text"=>"12", "pdf"=>"8", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"31", "full-text"=>"25", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"24", "full-text"=>"25", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"25", "full-text"=>"18", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"19", "full-text"=>"27", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"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"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
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Relative Metric

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