CoChat
Sign Up
Cited by 371

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

Human Papillomaviruses Activate the ATM DNA Damage Pathway for Viral Genome Amplification upon Differentiation

Moody, Cary A., Laimins, Laimonis A.·2009·PLoS Pathogens
DOI 10.1371/journal.ppat.1000605PMC PMC2745661
Open this paper in CoChat — free account

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.ppat.1000605

Cites

12 of 12 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 HPV induces a cellular DNA damage response in infected cells. (A) DNA was harvested from undifferentiated (T0) HPV positive cells, as well as after 48 and 96 hours of differentiation in high calcium. Southern blot analysis was performed to examine amplification of viral genomes, represented by supercoiled (episomal) viral DNA. Standards of copies of HPV genomes per cell are indicated to the left of the gel. (B) Lysates harvested from undifferentiated (T0) HPV-31 positive HFKs (HFK-31) and from normal HFKs, as well as cells differentiated in high calcium medium for 48 and 96 hours, were analyzed by Western blot analysis for levels of the differentiation markers keratin 10 (K10) and involucrin. (C) Lysates were harvested from undifferentiated HFK-31 and from normal HFKs, as well as cells differentiated in high calcium medium for 48 and 96 hours. Western blot analysis was performed using the indicated phospho-specific antibodies, as well as antibodies to detect total protein levels. (D) HFK-31 cells were treated with DMSO as a vehicle control, or the indicated amounts of the ATM inhibitor KU-55933 for 48 and 96 in high calcium medium. Lysates were harvested at the indicated times and analyzed by Western blot analysis for the activation of CHK2 (Thr68), CHK1 (Ser317), and ATM (Ser1981), as well as antibodies to detect total protein levels. GAPDH served as a loading control. Ca = calcium.
Figure 1 HPV induces a cellular DNA damage response in infected cells. (A) DNA was harvested from undifferentiated (T0) HPV positive cells, as well as after 48 and 96 hours of differentiation in high calcium. Southern blot analysis was performed to examine amplification of viral genomes, represented by supercoiled (episomal) viral DNA. Standards of copies of HPV genomes per cell are indicated to the left of the gel. (B) Lysates harvested from undifferentiated (T0) HPV-31 positive HFKs (HFK-31) and from normal HFKs, as well as cells differentiated in high calcium medium for 48 and 96 hours, were analyzed by Western blot analysis for levels of the differentiation markers keratin 10 (K10) and involucrin. (C) Lysates were harvested from undifferentiated HFK-31 and from normal HFKs, as well as cells differentiated in high calcium medium for 48 and 96 hours. Western blot analysis was performed using the indicated phospho-specific antibodies, as well as antibodies to detect total protein levels. (D) HFK-31 cells were treated with DMSO as a vehicle control, or the indicated amounts of the ATM inhibitor KU-55933 for 48 and 96 in high calcium medium. Lysates were harvested at the indicated times and analyzed by Western blot analysis for the activation of CHK2 (Thr68), CHK1 (Ser317), and ATM (Ser1981), as well as antibodies to detect total protein levels. GAPDH served as a loading control. Ca = calcium.CC BY · PubMed Central
Figure 2 HPV does not affect the levels of the components of the MRN complex. Lysates were harvested from undifferentiated HFK-31 cells and normal HFKs, as well as from cells induced to differentiate in high calcium for 48 and 96 hours. Western blot analysis was performed using antibodies to NBS1, MRE11 and RAD50. Western blots were stripped and re-probed with an antibody to GAPDH as a loading control. Ca = calcium.
Figure 2 HPV does not affect the levels of the components of the MRN complex. Lysates were harvested from undifferentiated HFK-31 cells and normal HFKs, as well as from cells induced to differentiate in high calcium for 48 and 96 hours. Western blot analysis was performed using antibodies to NBS1, MRE11 and RAD50. Western blots were stripped and re-probed with an antibody to GAPDH as a loading control. Ca = calcium.CC BY · PubMed Central
Figure 3 HPV induces ATM activation and the accumulation of DNA repair proteins in nuclear foci. HFK-31 cells, as well as normal HFKs were harvested, fixed and permeabilized at either time 0 (undifferentiated cells), or after 48 hours of differentiation in high calcium medium containing DMSO, or 10 uM of the ATM inhibitor KU-55933. Samples were stained with (A) anti-pATM Ser1981 (red), anti-H2AX Ser139 (γ-H2AX) (green) antibodies; (B) anti-pCHK2 Thr68 (green), anti-γ-H2AX (red) antibodies; or (C) an anti-K10 antibody as a marker of differentiation. Samples were subsequently analyzed by confocal laser scanning microscopy using either a 60× objective lens (panels A and B), or a 40× objective lens (panel C). Cellular DNA was counterstained with DAPI. (D) Sections from organotypic raft cultures generated from HFK-31 cells, or normal HFKs were stained with an antibody to detect pCHK2-Thr68 (green). Cellular DNA was counterstained with DAPI. Images were visualized using confocal laser scanning microscopy. Ca = calcium.
Figure 3 HPV induces ATM activation and the accumulation of DNA repair proteins in nuclear foci. HFK-31 cells, as well as normal HFKs were harvested, fixed and permeabilized at either time 0 (undifferentiated cells), or after 48 hours of differentiation in high calcium medium containing DMSO, or 10 uM of the ATM inhibitor KU-55933. Samples were stained with (A) anti-pATM Ser1981 (red), anti-H2AX Ser139 (γ-H2AX) (green) antibodies; (B) anti-pCHK2 Thr68 (green), anti-γ-H2AX (red) antibodies; or (C) an anti-K10 antibody as a marker of differentiation. Samples were subsequently analyzed by confocal laser scanning microscopy using either a 60× objective lens (panels A and B), or a 40× objective lens (panel C). Cellular DNA was counterstained with DAPI. (D) Sections from organotypic raft cultures generated from HFK-31 cells, or normal HFKs were stained with an antibody to detect pCHK2-Thr68 (green). Cellular DNA was counterstained with DAPI. Images were visualized using confocal laser scanning microscopy. Ca = calcium.CC BY · PubMed Central
Figure 4 ATM activity is required for differentiation-dependent viral genome amplification, but not episomal maintenance. (A) DNA was isolated at the indicated passages from undifferentiated HPV-31 positive CIN612 cells grown in the presence of DMSO, or the ATM inhibitor KU-55933 and analyzed by Southern blot analysis for the presence of episomal (supercoiled) HPV DNA. (B, C) DNA was harvested from undifferentiated (0 hour) CIN612 cells, as well as cells differentiated in high calcium (48 and 96 hr) in the presence of DMSO, (B) 5 or 10 uM KU-55933, or (C) 5 uM CHK2 inhibitor (CHK2i) and analyzed for amplification of viral genomes by Southern blot analysis. (D) Lysates were harvested from undifferentiated (0 hour) CIN612 cells, as well as from CIN612 cells induced to differentiate in high calcium in the presence or absence of 5 or 10 uM KU-55933. Western blot analysis was performed using an antibody to keratin 10 (K10) and involucrin. (E) Lysates were harvested from undifferentiated (T0) HPV-31 positive cells, as well as from cells induced to differentiate in high calcium for 48 and 96 hours in the presence or absence of DMSO. Western blot analysis was performed using an antibody to K10. Blots were stripped and probed for GAPDH as a loading control. Ca = calcium.
Figure 4 ATM activity is required for differentiation-dependent viral genome amplification, but not episomal maintenance. (A) DNA was isolated at the indicated passages from undifferentiated HPV-31 positive CIN612 cells grown in the presence of DMSO, or the ATM inhibitor KU-55933 and analyzed by Southern blot analysis for the presence of episomal (supercoiled) HPV DNA. (B, C) DNA was harvested from undifferentiated (0 hour) CIN612 cells, as well as cells differentiated in high calcium (48 and 96 hr) in the presence of DMSO, (B) 5 or 10 uM KU-55933, or (C) 5 uM CHK2 inhibitor (CHK2i) and analyzed for amplification of viral genomes by Southern blot analysis. (D) Lysates were harvested from undifferentiated (0 hour) CIN612 cells, as well as from CIN612 cells induced to differentiate in high calcium in the presence or absence of 5 or 10 uM KU-55933. Western blot analysis was performed using an antibody to keratin 10 (K10) and involucrin. (E) Lysates were harvested from undifferentiated (T0) HPV-31 positive cells, as well as from cells induced to differentiate in high calcium for 48 and 96 hours in the presence or absence of DMSO. Western blot analysis was performed using an antibody to K10. Blots were stripped and probed for GAPDH as a loading control. Ca = calcium.CC BY · PubMed Central
Figure 5 Formation of replication foci is impaired in the absence of ATM activity. FISH analysis was performed using undifferentiated (T0), as well as differentiated (48 hr high calcium) HPV-31 positive HFKs using a HPV-31 nick translated probe (green). FISH analysis was also performed on HPV positive cells grown in high calcium for 48 hr in the presence of 10 uM KU-55933. Cellular DNA was counterstained with DAPI, and images were visualized using confocal laser scanning microscopy. Ca = calcium.
Figure 5 Formation of replication foci is impaired in the absence of ATM activity. FISH analysis was performed using undifferentiated (T0), as well as differentiated (48 hr high calcium) HPV-31 positive HFKs using a HPV-31 nick translated probe (green). FISH analysis was also performed on HPV positive cells grown in high calcium for 48 hr in the presence of 10 uM KU-55933. Cellular DNA was counterstained with DAPI, and images were visualized using confocal laser scanning microscopy. Ca = calcium.CC BY · PubMed Central
Figure 6 HPV-mediated caspase activation requires CHK2 kinase activity. Lysates were harvested from undifferentiated (0 hour) HPV-31 positive CIN612 cells, as well as from HPV-31 cells induced to differentiate in high calcium in the presence of DMSO or 5 uM of the CHK2 inhibitor (CHK2i) for the indicated times. Western blot analysis was performed using antibodies to detect the cleaved (active) form of caspase-7, as well as an antibody to detect pro-caspase-7. GAPDH served as a loading control. Ca = calcium.
Figure 6 HPV-mediated caspase activation requires CHK2 kinase activity. Lysates were harvested from undifferentiated (0 hour) HPV-31 positive CIN612 cells, as well as from HPV-31 cells induced to differentiate in high calcium in the presence of DMSO or 5 uM of the CHK2 inhibitor (CHK2i) for the indicated times. Western blot analysis was performed using antibodies to detect the cleaved (active) form of caspase-7, as well as an antibody to detect pro-caspase-7. GAPDH served as a loading control. Ca = calcium.CC BY · PubMed Central
Figure 7 E7 induces CHK2 phosphorylation upon differentiation and interacts with the phosphorylated form of ATM. (A) Lysates were harvested from HFKs transduced with the retroviral vector pLXSN alone, or pLXSN-HPV-31 E7 at 0 hr (undifferentiated cells), as well as after differentiation in high calcium for 48 and 96 hours. Western blot analysis was performed using a phospho-specific antibody to pCHK2 Thr68, as well as an antibody to total CHK2. GAPDH served as a loading control. Ca = calcium. (B) Lysates were prepared from U2OS cells transiently transfected with vectors expressing HA, wild-type HA-31E7, HA-31E7 ΔLHCYE or HA-31E7 L67R. Immunoprecipitations were performed using an antibody to endogenous ATM, followed by Western blot analysis using an antibody to HA. (C) Immunoprecipitations were performed on lysates harvested from U2OS cells transfected with HA alone, HA-E7, HA-E7 DLHCYE or HA-E7 L67R using an antibody to HA followed by Western blot analysis to detect precipitated pATM Ser1981. (D) Lysates were prepared from transfected U20S cells treated with DMSO or 10 uM KU-55933 for 12 hours. Immunoprecipitatations were performed using an antibody to ATM, followed by Western blot analysis using an antibody to HA. IP = Immunoprecipitation, IB = Immunoblot. No Ab = No antibody (control).
Figure 7 E7 induces CHK2 phosphorylation upon differentiation and interacts with the phosphorylated form of ATM. (A) Lysates were harvested from HFKs transduced with the retroviral vector pLXSN alone, or pLXSN-HPV-31 E7 at 0 hr (undifferentiated cells), as well as after differentiation in high calcium for 48 and 96 hours. Western blot analysis was performed using a phospho-specific antibody to pCHK2 Thr68, as well as an antibody to total CHK2. GAPDH served as a loading control. Ca = calcium. (B) Lysates were prepared from U2OS cells transiently transfected with vectors expressing HA, wild-type HA-31E7, HA-31E7 ΔLHCYE or HA-31E7 L67R. Immunoprecipitations were performed using an antibody to endogenous ATM, followed by Western blot analysis using an antibody to HA. (C) Immunoprecipitations were performed on lysates harvested from U2OS cells transfected with HA alone, HA-E7, HA-E7 DLHCYE or HA-E7 L67R using an antibody to HA followed by Western blot analysis to detect precipitated pATM Ser1981. (D) Lysates were prepared from transfected U20S cells treated with DMSO or 10 uM KU-55933 for 12 hours. Immunoprecipitatations were performed using an antibody to ATM, followed by Western blot analysis using an antibody to HA. IP = Immunoprecipitation, IB = Immunoblot. No Ab = No antibody (control).CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 12 references

Research works printed but not linked: 50

  1. H zur Hausen, 2002, Papillomaviruses and cancer: from basic studies to clinical application., Nat Rev Cancer, 2, 342, 10.1038/nrc798 · DOI
  2. JM Walboomers, 1999, Human papillomavirus is a necessary cause of invasive cervical cancer worldwide., J Pathol, 189, 12, 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F · DOI
  3. MA Bedell, 1991, Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation., J Virol, 65, 2254, 10.1128/JVI.65.5.2254-2260.1991 · DOI
  4. M Hummel, 1992, Differentiation-induced and constitutive transcription of human papillomavirus type 31b in cell lines containing viral episomes., J Virol, 66, 6070, 10.1128/JVI.66.10.6070-6080.1992 · DOI
  5. S Cheng, 1995, Differentiation-dependent up-regulation of the human papillomavirus E7 gene reactivates cellular DNA replication in suprabasal differentiated keratinocytes., Genes Dev, 9, 2335, 10.1101/gad.9.19.2335 · DOI
  6. CA Moody, 2007, Human papillomaviruses activate caspases upon epithelial differentiation to induce viral genome amplification., Proc Natl Acad Sci U S A, 104, 19541, 10.1073/pnas.0707947104 · DOI
  7. CE Lilley, 2007, Using or abusing: viruses and the cellular DNA damage response., Trends Microbiol, 15, 119, 10.1016/j.tim.2007.01.003 · DOI
  8. N Shirata, 2005, Activation of ataxia telangiectasia-mutated DNA damage checkpoint signal transduction elicited by herpes simplex virus infection., J Biol Chem, 280, 30336, 10.1074/jbc.M500976200 · DOI
  9. CE Lilley, 2005, DNA repair proteins affect the lifecycle of herpes simplex virus 1., Proc Natl Acad Sci U S A, 102, 5844, 10.1073/pnas.0501916102 · DOI
  10. HA Rogoff, 2004, Apoptosis associated with deregulated E2F activity is dependent on E2F1 and Atm/Nbs1/Chk2., Mol Cell Biol, 24, 2968, 10.1128/MCB.24.7.2968-2977.2004 · DOI
  11. S Matsuoka, 2007, ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage., Science, 316, 1160, 10.1126/science.1140321 · DOI · Paper page
  12. S Banin, 1998, Enhanced phosphorylation of p53 by ATM in response to DNA damage., Science, 281, 1674, 10.1126/science.281.5383.1674 · DOI · Paper page
  13. CE Canman, 1998, Activation of the ATM kinase by ionizing radiation and phosphorylation of p53., Science, 281, 1677, 10.1126/science.281.5383.1677 · DOI · Paper page
  14. S Matsuoka, 1998, Linkage of ATM to cell cycle regulation by the Chk2 protein kinase., Science, 282, 1893, 10.1126/science.282.5395.1893 · DOI
  15. JY Ahn, 2000, Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation., Cancer Res, 60, 5934
  16. M Gatei, 2001, Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment using phospho-specific antibodies., J Biol Chem, 276, 17276, 10.1074/jbc.M011681200 · DOI
  17. PT Yazdi, 2002, SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint., Genes Dev, 16, 571, 10.1101/gad.970702 · DOI
  18. R Kitagawa, 2004, Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway., Genes Dev, 18, 1423, 10.1101/gad.1200304 · DOI
  19. O Fernandez-Capetillo, 2004, H2AX: the histone guardian of the genome., DNA Repair (Amst), 3, 959, 10.1016/j.dnarep.2004.03.024 · DOI
  20. TT Paull, 2000, A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage., Curr Biol, 10, 886, 10.1016/S0960-9822(00)00610-2 · DOI · Paper page
  21. MN Ruesch, 1998, Activation of papillomavirus late gene transcription and genome amplification upon differentiation in semisolid medium is coincident with expression of involucrin and transglutaminase but not keratin-10., J Virol, 72, 5016, 10.1128/JVI.72.6.5016-5024.1998 · DOI
  22. M Gatei, 2000, ATM-dependent phosphorylation of nibrin in response to radiation exposure., Nat Genet, 25, 115, 10.1038/75508 · DOI · Paper page
  23. DS Lim, 2000, ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway., Nature, 404, 613, 10.1038/35007091 · DOI · Paper page
  24. B Xu, 2001, Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation., Mol Cell Biol, 21, 3445, 10.1128/MCB.21.10.3445-3450.2001 · DOI
  25. XQ Wang, 2006, ATR dependent activation of Chk2., J Cell Physiol, 208, 613, 10.1002/jcp.20700 · DOI
  26. JH Lee, 2004, Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex., Science, 304, 93, 10.1126/science.1091496 · DOI · Paper page
  27. J Falck, 2005, Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage., Nature, 434, 605, 10.1038/nature03442 · DOI
  28. CT Carson, 2003, The Mre11 complex is required for ATM activation and the G2/M checkpoint., Embo J, 22, 6610, 10.1093/emboj/cdg630 · DOI · Paper page
  29. E Fuchs, 1990, Epidermal differentiation: the bare essentials., J Cell Biol, 111, 2807, 10.1083/jcb.111.6.2807 · DOI
  30. C Stevens, 2003, Chk2 activates E2F-1 in response to DNA damage., Nat Cell Biol, 5, 401, 10.1038/ncb974 · DOI
  31. MT Jack, 2004, DNA-dependent protein kinase and checkpoint kinase 2 synergistically activate a latent population of p53 upon DNA damage., J Biol Chem, 279, 15269, 10.1074/jbc.M309917200 · DOI
  32. JT Powers, 2004, E2F1 uses the ATM signaling pathway to induce p53 and Chk2 phosphorylation and apoptosis., Mol Cancer Res, 2, 203, 10.1158/1541-7786.203.2.4 · DOI
  33. ME McLaughlin-Drubin, 2009, The human papillomavirus E7 oncoprotein., Virology, 384, 335, 10.1016/j.virol.2008.10.006 · DOI
  34. MS Longworth, 2004, The binding of histone deacetylases and the integrity of zinc finger-like motifs of the E7 protein are essential for the life cycle of human papillomavirus type 31., J Virol, 78, 3533, 10.1128/JVI.78.7.3533-3541.2004 · DOI
  35. ER Flores, 1997, Evidence for a switch in the mode of human papillomavirus type 16 DNA replication during the viral life cycle., J Virol, 71, 7167, 10.1128/JVI.71.10.7167-7179.1997 · DOI
  36. DE Wilkinson, 2004, Recruitment of cellular recombination and repair proteins to sites of herpes simplex virus type 1 DNA replication is dependent on the composition of viral proteins within prereplicative sites and correlates with the induction of the DNA damage response., J Virol, 78, 4783, 10.1128/JVI.78.9.4783-4796.2004 · DOI
  37. X Zhao, 2008, Ataxia telangiectasia-mutated damage-signaling kinase- and proteasome-dependent destruction of Mre11-Rad50-Nbs1 subunits in Simian virus 40-infected primate cells., J Virol, 82, 5316, 10.1128/JVI.02677-07 · DOI
  38. L Antoni, 2007, CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin?, Nat Rev Cancer, 7, 925, 10.1038/nrc2251 · DOI
  39. C Karlsson-Rosenthal, 2006, Cdc25: mechanisms of checkpoint inhibition and recovery., Trends Cell Biol, 16, 285, 10.1016/j.tcb.2006.04.002 · DOI
  40. HK Wang, 2009, Robust production and passaging of infectious HPV in squamous epithelium of primary human keratinocytes., Genes Dev, 23, 181, 10.1101/gad.1735109 · DOI
  41. RS Maser, 2001, Mre11 complex and DNA replication: linkage to E2F and sites of DNA synthesis., Mol Cell Biol, 21, 6006, 10.1128/MCB.21.17.6006-6016.2001 · DOI
  42. MS Longworth, 2005, HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs., Embo J, 24, 1821, 10.1038/sj.emboj.7600651 · DOI · Paper page
  43. TR Wooldridge, 2008, Regulation of human papillomavirus type 31 gene expression during the differentiation-dependent life cycle through histone modifications and transcription factor binding., Virology, 374, 371, 10.1016/j.virol.2007.12.011 · DOI
  44. DJ Klumpp, 1999, Differentiation-induced changes in promoter usage for transcripts encoding the human papillomavirus type 31 replication protein E1., Virology, 257, 239, 10.1006/viro.1999.9636 · DOI
  45. M Kadaja, 2007, Genomic instability of the host cell induced by the human papillomavirus replication machinery., Embo J, 26, 2180, 10.1038/sj.emboj.7601665 · DOI
  46. CL Halbert, 1992, The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells., J Virol, 66, 2125, 10.1128/JVI.66.4.2125-2134.1992 · DOI · Paper page
  47. WG Hubert, 2002, Human papillomavirus type 31 replication modes during the early phases of the viral life cycle depend on transcriptional and posttranscriptional regulation of E1 and E2 expression., J Virol, 76, 2263, 10.1128/jvi.76.5.2263-2273.2002 · DOI
  48. F Fehrmann, 2005, Human papillomavirus type 31 life cycle: methods for study using tissue culture models., Methods Mol Biol, 292, 317
  49. F Fehrmann, 2003, Human papillomavirus type 31 E5 protein supports cell cycle progression and activates late viral functions upon epithelial differentiation., J Virol, 77, 2819, 10.1128/JVI.77.5.2819-2831.2003 · DOI
  50. BA Van Tine, 2005, Simultaneous in situ detection of RNA, DNA, and protein using tyramide-coupled immunofluorescence., Methods Mol Biol, 292, 215

Cited by

Metadata

Authors
Moody, C. A., & Laimins, L. A.
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2009-10-02
Volume
5
Issue
10
Pages
e1000605
ISSN
1553-7374
DOI
10.1371/journal.ppat.1000605
PMC
PMC2745661
Cited by
371
References
12
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review