{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:09:58Z","timestamp":1792670998713,"version":"4.5.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"7455","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2013,6]]},"DOI":"10.1038\/nature12216","type":"journal-article","created":{"date-parts":[[2013,6,4]],"date-time":"2013-06-04T12:21:11Z","timestamp":1370348471000},"page":"502-505","source":"Crossref","is-referenced-by-count":555,"title":["Severe malaria is associated with parasite binding to endothelial protein C receptor"],"prefix":"10.1038","volume":"498","author":[{"given":"Louise","family":"Turner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lavstsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne S.","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian W.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens E. V.","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Avril","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Brazier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Freeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob S.","family":"Jespersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten A.","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Magistrado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Lusingu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew K.","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor G.","family":"Theander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,6,5]]},"reference":[{"key":"BFnature12216_CR1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0140-6736(12)60034-8","volume":"379","author":"CJ Murray","year":"2012","unstructured":"Murray, C. J. et al. Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet 379, 413\u2013431 (2012)","journal-title":"Lancet"},{"key":"BFnature12216_CR2","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.mib.2006.06.006","volume":"9","author":"SM Kraemer","year":"2006","unstructured":"Kraemer, S. M. & Smith, J. D. A family affair: var genes, PfEMP1 binding, and malaria disease. Curr. Opin. Microbiol. 9, 374\u2013380 (2006)","journal-title":"Curr. Opin. Microbiol."},{"key":"BFnature12216_CR3","doi-asserted-by":"publisher","first-page":"E1791","DOI":"10.1073\/pnas.1120455109","volume":"109","author":"T Lavstsen","year":"2012","unstructured":"Lavstsen, T. et al. Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children. Proc. Natl Acad. Sci. USA 109, E1791\u2013E1800 (2012)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature12216_CR4","doi-asserted-by":"publisher","first-page":"E1782","DOI":"10.1073\/pnas.1120534109","volume":"109","author":"M Avril","year":"2012","unstructured":"Avril, M. et al. A restricted subset of var genes mediates adherence of Plasmodium falciparum-infected erythrocytes to brain endothelial cells. Proc. Natl Acad. Sci. USA 109, E1782\u2013E1790 (2012)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature12216_CR5","doi-asserted-by":"publisher","first-page":"E1772","DOI":"10.1073\/pnas.1120461109","volume":"109","author":"A Claessens","year":"2012","unstructured":"Claessens, A. et al. A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells. Proc. Natl Acad. Sci. USA 109, E1772\u2013E1781 (2012)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature12216_CR6","doi-asserted-by":"publisher","first-page":"3161","DOI":"10.1182\/blood-2006-09-003004","volume":"109","author":"LO Mosnier","year":"2007","unstructured":"Mosnier, L. O., Zlokovic, B. V. & Griffin, J. H. The cytoprotective protein C pathway. Blood 109, 3161\u20133172 (2007)","journal-title":"Blood"},{"key":"BFnature12216_CR7","doi-asserted-by":"crossref","unstructured":"Rask, T. S., Hansen, D. A., Theander, T. G., Gorm Pedersen, A. & Lavstsen, T. Plasmodium falciparum erythrocyte membrane protein 1 diversity in seven genomes\u2014divide and conquer. PLOS Comput. Biol. 6, (2010)","DOI":"10.1371\/journal.pcbi.1000933"},{"key":"BFnature12216_CR8","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1084\/jem.20041579","volume":"200","author":"A Salanti","year":"2004","unstructured":"Salanti, A. et al. Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. J. Exp. Med. 200, 1197\u20131203 (2004)","journal-title":"J. Exp. Med."},{"key":"BFnature12216_CR9","doi-asserted-by":"crossref","first-page":"26486","DOI":"10.1016\/S0021-9258(18)47220-1","volume":"269","author":"K Fukudome","year":"1994","unstructured":"Fukudome, K. & Esmon, C. T. Identification, cloning, and regulation of a novel endothelial cell protein C\/activated protein C receptor. J. Biol. Chem. 269, 26486\u201326491 (1994)","journal-title":"J. Biol. Chem."},{"key":"BFnature12216_CR10","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1182\/blood.V94.2.632","volume":"94","author":"RE Simmonds","year":"1999","unstructured":"Simmonds, R. E. & Lane, D. A. Structural and functional implications of the intron\/exon organization of the human endothelial cell protein C\/activated protein C receptor (EPCR) gene: comparison with the structure of CD1\/major histocompatibility complex \u03b11 and \u03b12 domains. Blood 94, 632\u2013641 (1999)","journal-title":"Blood"},{"key":"BFnature12216_CR11","doi-asserted-by":"publisher","first-page":"10212","DOI":"10.1073\/pnas.93.19.10212","volume":"93","author":"DJ Stearns-Kurosawa","year":"1996","unstructured":"Stearns-Kurosawa, D. J., Kurosawa, S., Mollica, J. S., Ferrell, G. L. & Esmon, C. T. The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc. Natl Acad. Sci. USA 93, 10212\u201310216 (1996)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature12216_CR12","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1160\/TH08-10-0632","volume":"101","author":"RA Schuepbach","year":"2009","unstructured":"Schuepbach, R. A., Feistritzer, C., Fernandez, J. A., Griffin, J. H. & Riewald, M. Protection of vascular barrier integrity by activated protein C in murine models depends on protease-activated receptor-1. Thromb. Haemost. 101, 724\u2013733 (2009)","journal-title":"Thromb. Haemost."},{"key":"BFnature12216_CR13","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s00018-011-0825-0","volume":"69","author":"EM Gleeson","year":"2012","unstructured":"Gleeson, E. M., O\u2019Donnell, J. S. & Preston, R. J. The endothelial cell protein C receptor: cell surface conductor of cytoprotective coagulation factor signaling. Cell. Mol. Life Sci. 69, 717\u2013726 (2012)","journal-title":"Cell. Mol. Life Sci."},{"key":"BFnature12216_CR14","doi-asserted-by":"publisher","first-page":"17491","DOI":"10.1074\/jbc.271.29.17491","volume":"271","author":"K Fukudome","year":"1996","unstructured":"Fukudome, K. et al. The endothelial cell protein C receptor. Cell surface expression and direct ligand binding by the soluble receptor. J. Biol. Chem. 271, 17491\u201317498 (1996)","journal-title":"J. Biol. Chem."},{"key":"BFnature12216_CR15","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1046\/j.1365-2958.2003.03378.x","volume":"47","author":"BA Robinson","year":"2003","unstructured":"Robinson, B. A., Welch, T. L. & Smith, J. D. Widespread functional specialization of Plasmodium falciparum erythrocyte membrane protein 1 family members to bind CD36 analysed across a parasite genome. Mol. Microbiol. 47, 1265\u20131278 (2003)","journal-title":"Mol. Microbiol."},{"key":"BFnature12216_CR16","doi-asserted-by":"publisher","first-page":"e1002665","DOI":"10.1371\/journal.ppat.1002665","volume":"8","author":"A Ghumra","year":"2012","unstructured":"Ghumra, A. et al. Induction of strain-transcending antibodies against Group A PfEMP1 surface antigens from virulent malaria parasites. PLoS Pathog. 8, e1002665 (2012)","journal-title":"PLoS Pathog."},{"key":"BFnature12216_CR17","doi-asserted-by":"publisher","first-page":"e14741","DOI":"10.1371\/journal.pone.0014741","volume":"6","author":"LB Ochola","year":"2011","unstructured":"Ochola, L. B. et al. Specific receptor usage in Plasmodium falciparum cytoadherence is associated with disease outcome. PLoS ONE 6, e14741 (2011)","journal-title":"PLoS ONE"},{"key":"BFnature12216_CR18","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1182\/blood-2002-12-3880","volume":"102","author":"DH Sturn","year":"2003","unstructured":"Sturn, D. H. et al. Expression and function of the endothelial protein C receptor in human neutrophils. Blood 102, 1499\u20131505 (2003)","journal-title":"Blood"},{"key":"BFnature12216_CR19","doi-asserted-by":"publisher","first-page":"6038","DOI":"10.1074\/jbc.275.8.6038","volume":"275","author":"J Xu","year":"2000","unstructured":"Xu, J., Qu, D., Esmon, N. L. & Esmon, C. T. Metalloproteolytic release of endothelial cell protein C receptor. J. Biol. Chem. 275, 6038\u20136044 (2000)","journal-title":"J. Biol. Chem."},{"key":"BFnature12216_CR20","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1111\/j.1538-7836.2011.04256.x","volume":"9","author":"MC Pintao","year":"2011","unstructured":"Pintao, M. C. et al. High levels of protein C are determined by PROCR haplotype 3. J. Thromb. Haemost. 9, 969\u2013976 (2011)","journal-title":"J. Thromb. Haemost."},{"key":"BFnature12216_CR21","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1182\/blood-2011-10-383448","volume":"119","author":"J Dennis","year":"2012","unstructured":"Dennis, J. et al. The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies. Blood 119, 2392\u20132400 (2012)","journal-title":"Blood"},{"key":"BFnature12216_CR22","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.1017\/S1462399409001082","volume":"11","author":"JA Rowe","year":"2009","unstructured":"Rowe, J. A., Claessens, A., Corrigan, R. A. & Arman, M. Adhesion of Plasmodium falciparum-infected erythrocytes to human cells: molecular mechanisms and therapeutic implications. Expert Rev. Mol. Med. 11, e16 (2009)","journal-title":"Expert Rev. Mol. Med."},{"key":"BFnature12216_CR23","doi-asserted-by":"publisher","first-page":"3356","DOI":"10.4049\/jimmunol.0901331","volume":"183","author":"GK Cham","year":"2009","unstructured":"Cham, G. K. et al. Sequential, ordered acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 domains. J. Immunol. 183, 3356\u20133363 (2009)","journal-title":"J. Immunol."},{"key":"BFnature12216_CR24","doi-asserted-by":"publisher","first-page":"4653","DOI":"10.1128\/IAI.00593-10","volume":"78","author":"GK Cham","year":"2010","unstructured":"Cham, G. K. et al. Hierarchical, domain type-specific acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 in Tanzanian children. Infect. Immun. 78, 4653\u20134659 (2010)","journal-title":"Infect. Immun."},{"key":"BFnature12216_CR25","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1111\/j.1365-2044.2006.04752.x","volume":"61","author":"BJ Kendrick","year":"2006","unstructured":"Kendrick, B. J., Gray, A. G., Pickworth, A. & Watters, M. P. Drotrecogin alfa (activated) in severe falciparum malaria. Anaesthesia 61, 899\u2013902 (2006)","journal-title":"Anaesthesia"},{"key":"BFnature12216_CR26","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1177\/0310057X0703500320","volume":"35","author":"LG Rankin","year":"2007","unstructured":"Rankin, L. G. & Austin, D. L. The use of activated protein C in severe Plasmodium falciparum malaria. Anaesth. Intensive Care 35, 428\u2013432 (2007)","journal-title":"Anaesth. Intensive Care"},{"key":"BFnature12216_CR27","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1177\/0310057X1003800421","volume":"38","author":"O Robak","year":"2010","unstructured":"Robak, O. et al. The use of drotrecogin alfa in severe falciparum malaria. Anaesth. Intensive Care 38, 751\u2013754 (2010)","journal-title":"Anaesth. Intensive Care"},{"key":"BFnature12216_CR28","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/1475-2875-11-129","volume":"11","author":"CW Wang","year":"2012","unstructured":"Wang, C. W. et al. Evidence for in vitro and in vivo expression of the conserved VAR3 (type 3) Plasmodium falciparum erythrocyte membrane protein 1. Malar. J. 11, 129 (2012)","journal-title":"Malar. J."},{"key":"BFnature12216_CR29","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S0165-5728(97)00036-2","volume":"76","author":"MF Stins","year":"1997","unstructured":"Stins, M. F., Gilles, F. & Kim, K. S. Selective expression of adhesion molecules on human brain microvascular endothelial cells. J. Neuroimmunol. 76, 81\u201390 (1997)","journal-title":"J. Neuroimmunol."},{"key":"BFnature12216_CR30","doi-asserted-by":"publisher","first-page":"e29025","DOI":"10.1371\/journal.pone.0029025","volume":"6","author":"L Turner","year":"2011","unstructured":"Turner, L. et al. Antibodies against PfEMP1, RIFIN, MSP3 and GLURP are acquired during controlled Plasmodium falciparum malaria infections in naive volunteers. PLoS ONE 6, e29025 (2011)","journal-title":"PLoS ONE"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature12216.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature12216","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature12216.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:11:59Z","timestamp":1684419119000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature12216"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6]]},"references-count":30,"journal-issue":{"issue":"7455","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["BFnature12216"],"URL":"https:\/\/doi.org\/10.1038\/nature12216","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718017789.793479639","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6]]}}}