Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans
Open accessAbstract
The study of regulatory networks in human pathogens such as Cryptococcus neoformans provides insights into host-pathogen interactions that may allow for correlation of gene expression patterns with clinical outcomes.In the present study, deletion of the cryptococcal copper-dependent transcription factor 1 (Cuf1) led to defects in growth and virulence factor expression in low copper conditions.In mouse models, cuf1Δ strains exhibited reduced dissemination to the brain, but no change in lung growth, suggesting copper is limiting in neurologic infections.To examine this further, a biologic probe of available copper was constructed using the cryptococcal CUF1-dependent copper transporter, CTR4.Fungal cells demonstrated high CTR4 expression levels after phagocytosis by macrophage-like J774.16 cells and during infection of mouse brains, but not lungs, consistent with limited copper availability during neurologic infection.This was extended to human brain infections by demonstrating CTR4 expression during C. neoformans infection of an AIDS patient.Moreover, high CTR4 expression by cryptococcal strains from 24 solid organ transplant patients was associated with dissemination to the CNS.Our results suggest that copper acquisition plays a central role in fungal pathogenesis during neurologic infection and that measurement of stable traits such as CTR4 expression may be useful for risk stratification of individuals with cryptococcosis. Results Identification of a copper-dependent transcription factor in C. neoformans.Complementation of one of a series of previously described lac-Nonstandard abbreviations used: BAL, bronchoalveolar lavage; BCS, bathocuproinedisulfonic acid; CSF, cerebrospinal fluid; Ctr4, copper transporter 4; Cuf1, copperdependent transcription factor 1; YPD, yeast extract/peptone/dextrose medium.
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.
Integrity signals
Registry
Cites
Statistics
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.
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?
Siderophore utilization might contribute toward the virulence of C. glabrata in both the Fe- and Cu-restricted mammalian host.
“This suggests that siderophore utilization might contribute toward the virulence of C. glabrata in both the Fe- and Cu-restricted mammalian host [49].”
From Host Iron Withholding Demands Siderophore Utilization for Candida glabrata to Survive Macrophage Killing (2011) · cites this paper as [49]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Infectious Diseases Society of America
Enders, J. F. (1969) · The Journal of Infectious Diseases · doi:10.1093/infdis/119.3.317 · Cited by 3,305 · see citing works
Applied Survival Analysis: Regression Modeling of Time-to-Event Data
Hosmer, D. W., Lemeshow, S. A., & May, S. J. (2008) · Cited by 3,030 · see citing works
Gralton, B. (2008) · Art monthly Australia · Cited by 3,001 · see citing works
Practice Guidelines for the Management of Cryptococcal Disease
Saag, M. S., Graybill, R. J., Larsen, R. A., Pappas, P. G., Perfect, J. R., Powderly, W. G., Sobel, J. D., Dismukes, W. E., & Mycoses Study Group Cryptococcal Subproject (2000) · Clinical Infectious Diseases · doi:10.1086/313757 · Cited by 1,101 · see citing works
Brodie, S. E. (1996) · Survey of Ophthalmology · doi:10.1016/s0039-6257(96)80075-0 · Cited by 770 · see citing works
Translational and Clinical Science — Time for a New Vision
Zerhouni, E. A. (2005) · New England Journal of Medicine · doi:10.1056/nejmsb053723 · Cited by 729 · see citing works
Casadevall, A., & Perfect, J. R. (1998) · ASM Press eBooks · doi:10.1128/9781555818241 · Cited by 673 · see citing works
The damage-response framework of microbial pathogenesis
Casadevall, A., & Pirofski, L. (2003) · Nature Reviews Microbiology · doi:10.1038/nrmicro732 · Cited by 662 · see citing works
Urease as a Virulence Factor in Experimental Cryptococcosis
Cox, G. M., Mukherjee, J., Cole, G. T., Casadevall, A., & Perfect, J. R. (2000) · Infection and Immunity · doi:10.1128/iai.68.2.443-448.2000 · Cited by 522 · see citing works
<i>Cryptococcus neoformans</i>Is a Facultative Intracellular Pathogen in Murine Pulmonary Infection
Feldmesser, M., Kress, Y., Novikoff, P., & Casadevall, A. (2000) · Infection and Immunity · doi:10.1128/iai.68.7.4225-4237.2000 · Cited by 423 · see citing works
Effect of the laccase gene CNLAC1, on virulence of Cryptococcus neoformans.
Salas, S. D., Bennett, J. E., Kwon-Chung, K. J., Perfect, J. R., & Williamson, P. R. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.2.377 · Cited by 405 · see citing works
Self-citationWilliamson, P. R. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.3.656-664.1994 · Cited by 371 · see citing works
Self-citationVisualization of nitric oxide in living cells by a copper-based fluorescent probe
Lim, M. H., Dong, X., & Lippard, S. J. (2006) · Nature Chemical Biology · doi:10.1038/nchembio794 · Cited by 353 · see citing works
Tucker, S. C., & Casadevall, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052702799 · Cited by 306 · see citing works
Jungmann, J., Reins, H., Lee, J., Romeo, A. M., Hassett, R. F., Kosman, D. J., & Jentsch, S. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06198.x · Cited by 283 · see citing works
Chang, Y. C., Stins, M. F., McCaffery, M. J., Miller, G., Pare, D. R., Dam, T., Paul-Satyasee, M., Kim, K. S., & Kwon-Chung, K. J. (2004) · Infection and Immunity · doi:10.1128/iai.72.9.4985-4995.2004 · Cited by 275 · see citing works
Cox, G. M., Harrison, T. S., McDade, H. C., Taborda, C. P., Heinrich, G., Casadevall, A., & Perfect, J. R. (2002) · Infection and Immunity · doi:10.1128/iai.71.1.173-180.2003 · Cited by 267 · see citing works
Singh, N. R., Lortholary, O., Alexander, B. D., Gupta, K. L., John, G. T., Pursell, K. J., Munoz, P., Klintmalm, G. B. G., Stosor, V., Busto, R. D., et al. (2005) · Clinical Infectious Diseases · doi:10.1086/430606 · Cited by 249 · see citing works
Self-citationTransition Metal Transport in Yeast
Ho, A. V., Ward, D. M., & Kaplan, J. (2002) · Annual Review of Microbiology · doi:10.1146/annurev.micro.56.012302.160847 · Cited by 225 · see citing works
Jenny-Avital, E. R., & Abadi, M. A. (2002) · Clinical Infectious Diseases · doi:10.1086/344467 · Cited by 186 · see citing works
Introduction to Probability and Statistics
Finney, D. J., & Mendenhall, W. M. (1977) · International Statistical Review · doi:10.2307/1403018 · Cited by 182 · see citing works
Pukkila-Worley, R., Gerrald, Q. D., Kraus, P. R., Boily, M.-J., Davis, M. J., Giles, S. S., Cox, G. M., Heitman, J., & Alspaugh, J. A. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.1.190-201.2005 · Cited by 181 · see citing works
Hmama, Z., Sendide, K., Talal, A., García, R., Dobos, K. M., & Reiner, N. E. (2004) · Journal of Cell Science · doi:10.1242/jcs.01072 · Cited by 151 · see citing works
Cruz, M. C., Fox, D. S., & Heitman, J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.5.1020 · Cited by 150 · see citing works
Introduction Probability And Statistics
Mendenhall, W. 1. (1967) · Andalas University Repository (Andalas University) · Cited by 149 · see citing works
Kaslow, D. C., & Shiloach, J. (1994) · Nature Biotechnology · doi:10.1038/nbt0594-494 · Cited by 131 · see citing works
A Copper-sensing Transcription Factor Regulates Iron Uptake Genes in Schizosaccharomyces pombe
Labbé, S., Peña, M. M. O., Fernandes, A. R., & Thiele, D. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.51.36252 · Cited by 120 · see citing works
Davis-Kaplan, S. R., Askwith, C. C., Bengtzen, A. C., Radisky, D. C., & Kaplan, J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.23.13641 · Cited by 120 · see citing works
Noverr, M. C., Williamson, P. R., Fajardo, R. S., & Huffnagle, G. B. (2004) · Infection and Immunity · doi:10.1128/iai.72.3.1693-1699.2004 · Cited by 112 · see citing works
Self-citationMultiple virulence factors of Cryptococcus neoformans are dependent on VPH1
Erickson, T., Liu, L., Gueyikian, A., Zhu, X., Gibbons, J. T., & Williamson, P. R. (2001) · Molecular Microbiology · doi:10.1046/j.1365-2958.2001.02712.x · Cited by 109 · see citing works
Self-citationCryptococcaemia: clinical features and prognostic factors
Jean, S. (2002) · QJM · doi:10.1093/qjmed/95.8.511 · Cited by 109 · see citing works
Evolution of protein fold in the presence of functional constraints
Andreeva, A. E., & Murzin, A. G. (2006) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2006.04.003 · Cited by 105 · see citing works
Singh, N., Lortholary, O., Alexander, B. D., Gupta, K. L., John, G. T., Pursell, K. J., Muñóz, P., Klintmalm, G. B. G., Stosor, V., Delbusto, R., et al. (2005) · Transplantation · doi:10.1097/01.tp.0000180530.17683.02 · Cited by 102 · see citing works
Self-citationPanepinto, J. C., Liu, L., Ramos, J., Zhu, X., Vályi-Nagy, T., Ekşi, S., Fu, J., Jaffe, H. A., Wickes, B. L., & Williamson, P. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200523048 · Cited by 99 · see citing works
Self-citationMolecular and genetic analysis of URA5 transformants of Cryptococcus neoformans
Varma, A., Edman, J. C., & Kwon-Chung, K. J. (1992) · Infection and Immunity · doi:10.1128/iai.60.3.1101-1108.1992 · Cited by 93 · see citing works
Singh, N., Lortholary, O., Alexander, B. D., et al. (2005) · Transplantation · doi:10.1097/01.tp.0000173774.74388.49 · Cited by 81 · see citing works
Self-citationRees, E. M., & Thiele, D. J. (2004) · Current Opinion in Microbiology · doi:10.1016/j.mib.2004.02.004 · Cited by 78 · see citing works
Trace metal regulation of neuronal apoptosis: From genes to behavior
Levenson, C. W. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.08.010 · Cited by 77 · see citing works
An efficiently regulated promoter system for Cryptococcus neoformans utilizing the CTR4 promoter
Ory, J. J., Griffith, C. L., & Doering, T. L. (2004) · Yeast · doi:10.1002/yea.1139 · Cited by 77 · see citing works
Zhu, X., & Williamson, P. R. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03752.x · Cited by 76 · see citing works
Self-citationBeaudoin, J., & Labbé, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011256200 · Cited by 73 · see citing works
Liu, L., Wakamatsu, K., Ito, S., & Williamson, P. R. (1999) · Infection and Immunity · doi:10.1128/iai.67.1.108-112.1999 · Cited by 71 · see citing works
Self-citationDominant selection system for use inCryptococcus neoformans
Cox, G. M., Toffaletti, D. L., & Perfect, J. R. (1996) · Medical Mycology · doi:10.1080/02681219680000691 · Cited by 70 · see citing works
Vilchez, R. A., Irish, W. D., Lacomis, J. M., Costello, P., Fung, J. J., & Kusne, S. (2001) · Medicine · doi:10.1097/00005792-200109000-00004 · Cited by 63 · see citing works
Marvin, M. E., Mason, R. P., & Cashmore, A. M. (2004) · Microbiology · doi:10.1099/mic.0.27004-0 · Cited by 60 · see citing works
Beaudoin, J., Mercier, A., Langlois, R., & Labbé, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300861200 · Cited by 55 · see citing works
Copper-induced ferroportin-1 expression in J774 macrophages is associated with increased iron efflux
Chung, J., Haile, D. J., & Wessling‐Resnick, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306622101 · Cited by 54 · see citing works
Cryptococcus neoformansvar.gattiican exploitAcanthamoeba castellaniifor growth
Malliaris, S. D., Steenbergen, J. N., & Casadevall, A. (2004) · Medical Mycology · doi:10.1080/13693786310001616500 · Cited by 53 · see citing works
Panepinto, J. C., Liu, L., Ramos, J., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23048 · Cited by 50 · see citing works
Self-citationMelanin-deficient mutants ofCryptococcus neoformans
Torres-Guererro, H., & Edman, J. C. (1994) · Medical Mycology · doi:10.1080/02681219480000381 · Cited by 49 · see citing works
Fungal CNS infections in patients with hematologic malignancy
Pagano, L., Caira, M., Falcucci, P., & Fianchi, L. (2005) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.3.5.775 · Cited by 48 · see citing works
Liu, X., Hu, G., Panepinto, J. C., & Williamson, P. R. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05299.x · Cited by 45 · see citing works
Self-citationLiver transplantation: the Italian experience
FAGIUOLI, S., Mirante, V. G., Pompili, M., et al. (2002) · Digestive and Liver Disease · doi:10.1016/s1590-8658(02)80207-9 · Cited by 38 · see citing works
Intersection of fungal fitness and virulence inCryptococcus neoformans
Panepinto, J. C., & Williamson, P. R. (2006) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2006.00078.x · Cited by 38 · see citing works
Self-citationToffaletti, D. L., Poeta, M. D., Rude, T. H., Dietrich, F. S., & Perfect, J. R. (2003) · Microbiology · doi:10.1099/mic.0.26021-0 · Cited by 37 · see citing works
MORENO, T., Artacho, R., Navarro, M., et al. (1998) · The Science of The Total Environment · doi:10.1016/s0048-9697(98)00158-2 · Cited by 35 · see citing works
Copper Induces Cytoplasmic Retention of Fission Yeast Transcription Factor Cuf1
Beaudoin, J., & Labbé, S. (2006) · Eukaryotic Cell · doi:10.1128/ec.5.2.277-292.2006 · Cited by 35 · see citing works
Zhang, S., Varma, A., & Williamson, P. R. (1999) · Gene · doi:10.1016/s0378-1119(98)00590-3 · Cited by 31 · see citing works
Self-citationAugmented metalloproteinase activity and acute lung injury in copper-deficient rats
Lentsch, A. B., Kato, A., Saari, J. T., et al. (2001) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2001.281.2.l387 · Cited by 28 · see citing works
Pulmonary fungal infection with yeasts andpneumocystisin patients with hematological malignancy
Pagano, L., Caira, M., & Fianchi, L. (2005) · Annals of Medicine · doi:10.1080/07853890510037374 · Cited by 27 · see citing works
Srikantha, T., Zhao, R., Daniels, K. J., Radke, J. B., & Soll, D. R. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.8.1434-1445.2005 · Cited by 27 · see citing works
Blankenship, J. R., Singh, N., Alexander, B. D., & Heitman, J. (2005) · Journal of Clinical Microbiology · doi:10.1128/jcm.43.1.464-467.2005 · Cited by 25 · see citing works
Self-citationHuang, G., Nie, X., & Chen, J. (2006) · Acta Biochimica et Biophysica Sinica · doi:10.1111/j.1745-7270.2006.00146.x · Cited by 16 · see citing works
Study ofCryptococcus neoformansactin gene regulation with a β-galactosidase-actin fusion
Toffaletti, D. L., & Perfect, J. R. (1997) · Medical Mycology · doi:10.1080/02681219780001351 · Cited by 13 · see citing works
Study of Cryptococcus neoformans actin gene regulation with a beta-galactosidase-actin fusion.
Toffaletti, D. L., & Perfect, J. R. (1998) · PubMed · Cited by 11 · see citing works
Jimenez‐Exposito, M., Bonet, M. B., Alonso‐Villaverde, C., et al. (2002) · Medicina Clínica · doi:10.1016/s0025-7753(02)73574-4 · Cited by 6 · see citing works
γδ+ T cells in Wilson's diseaseT cells in Wilson's disease
Fiszer, U., Korczak-Kowalska, G., Gajda, J., et al. (1996) · International Journal of Clinical & Laboratory Research · doi:10.1007/bf02644775 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis
Kwon-Chung, K. J., Fraser, J. A., Doering, T. L., Wang, Z. A., Janbon, G., Idnurm, A., & Bahn, Y.-S. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019760 · Cited by 531 · see citing works
Copper in Microbial Pathogenesis: Meddling with the Metal
Samanovic, M. I., Ding, C., Thiele, D. J., & Darwin, K. H. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.01.009 · Cited by 278 · see citing works
The Yin and Yang of copper during infection
Besold, A. N., Culbertson, E. M., & Culotta, V. C. (2016) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-016-1335-1 · Cited by 215 · see citing works
Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence
Ding, C., Festa, R. A., Chen, Y.-L., Espart, A., Palacios, Ò., Espín, J., Capdevila, M., Atrian, S., Heitman, J., & Thiele, D. J. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.02.002 · Cited by 179 · see citing works
Molecular mechanisms of cryptococcal meningitis
Liu, T.-B., Perlin, D. S., & Xue, C. (2012) · Virulence · doi:10.4161/viru.18685 · Cited by 131 · see citing works
The Role of Copper Homeostasis at the Host-Pathogen Axis: From Bacteria to Fungi
Li, C., Li, Y., & Ding, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20010175 · Cited by 107 · see citing works
Wiemann, P., Perevitsky, A., Lim, F. Y., Shadkchan, Y., Knox, B. P., Landero Figueora, J. A., Choera, T., Niu, M., Steinberger, A. J., Wüthrich, M., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.019 · Cited by 104 · see citing works
Sun, T.-S., Ju, X., Gao, H.-L., Wang, T., Thiele, D. J., Li, J.-Y., Wang, Z.-Y., & Ding, C. (2014) · Nature Communications · doi:10.1038/ncomms6550 · Cited by 94 · see citing works
Nevitt, T., & Thiele, D. J. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1001322 · Cited by 95 · see citing works
“glabrata in both the Fe- and Cu-restricted mammalian host [49].”
BackgroundLiu, T.-B., Kim, J.-C., Wang, Y., Toffaletti, D. L., Eugenin, E., Perfect, J. R., Kim, K. J., & Xue, C. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003247 · Cited by 89 · see citing works
Efficacy of Oral Encochleated Amphotericin B in a Mouse Model of Cryptococcal Meningoencephalitis
Lu, R., Hollingsworth, C., Qiu, J., Wang, A., Hughes, E., Xin, X., Konrath, K. M., Elsegeiny, W., Park, Y.-D., Atakulu, L., et al. (2019) · mBio · doi:10.1128/mbio.00724-19 · Cited by 67 · see citing works
Self-citationChayakulkeeree, M., Rude, T. H., Toffaletti, D. L., & Perfect, J. R. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00442-07 · Cited by 56 · see citing works
Cai, Z., Du, W., Zeng, Q., Long, N., Dai, C., & Lu, L. (2017) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2017.08.003 · Cited by 49 · see citing works
Khemiri, I., Tebbji, F., & Sellam, A. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00935 · Cited by 40 · see citing works
Transcription factor Afmac1 controls copper import machinery in Aspergillus fumigatus
Kusuya, Y., Hagiwara, D., Sakai, K., Yaguchi, T., Gonoi, T., & Takahashi, H. (2017) · Current Genetics · doi:10.1007/s00294-017-0681-z · Cited by 34 · see citing works
A High-Throughput Screening Assay for Fungicidal Compounds against Cryptococcus neoformans
Rabjohns, J. L. A., Park, Y.-D., Dehdashti, J., Sun, W., Henderson, C., Zelazny, A., Metallo, S. J., Zheng, W., & Williamson, P. R. (2014) · SLAS Discovery · doi:10.1177/1087057113496847 · Cited by 33 · see citing works
Self-citationPark, Y.-S., Kim, T.-H., & Yun, C.-W. (2017) · Biochemical Journal · doi:10.1042/bcj20170191 · Cited by 30 · see citing works
Self-citation
- Authors
- Waterman, S. R., Hacham, M., Hu, G., Zhu, X., Park, Y.-D., Shin, S., Panepinto, J., Valyi-Nagy, T., Beam, C., Husain, S., Singh, N., & Williamson, P. R.
- Affiliations
- University of Illinois Chicago (US)
- University of Pittsburgh (US)
- Corresponding author
- Williamson, Peter R.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-03-01
- Volume
- 117
- Issue
- 3
- Pages
- 794-802
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1784002
- OpenAlex
- W1997557971
- Cited by
- 134
- References
- 67
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 7 · 2020: 8 · 2019: 6 · 2018: 8 · 2017: 13 · 2016: 8 · 2015: 4 · 2014: 9 · 2013: 6 · 2012: 11
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5u01ai047087-03)
- National Institute of Allergy and Infectious Diseases (R01AI049371, R01AI045995, AI45995, AI47087, AI 49371)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- Cryptococcus neoformans, copper uptake, fungal virulence, central nervous system infection, cryptococcosis, macrophage phagocytosis, solid organ transplant recipients, AIDS, risk stratification, host-pathogen interaction
- MeSH terms
- Adult, Animals, Brain, Copper, Cryptococcosis, Cryptococcus neoformans, Disease Models, Animal, Fungal Proteins, Humans, Lung, Macrophages, Middle Aged, Transcription Factors, Virulence, Gene Expression Regulation, Fungal, Cation Transport Proteins, Mice
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
