{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T07:16:59Z","timestamp":1789197419055,"version":"build-2803163510"},"reference-count":49,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI105856"],"award-info":[{"award-number":["AI105856"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM141088"],"award-info":[{"award-number":["GM141088"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI050886"],"award-info":[{"award-number":["AI050886"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["I-1275"],"award-info":[{"award-number":["I-1275"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["I-1558"],"award-info":[{"award-number":["I-1558"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["I-2010-20190330"],"award-info":[{"award-number":["I-2010-20190330"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,11,12]]},"abstract":"<jats:p>\n                    A prevalent feature of\n                    <jats:italic>Strongyloides stercoralis<\/jats:italic>\n                    is a life-long and potentially lethal infection that is due to the nematode parasite\u2019s ability to autoinfect and, thereby, self-replicate within its host. Here, we investigated the role of the parasite\u2019s nuclear receptor,\n                    <jats:italic>Ss-<\/jats:italic>\n                    DAF-12, in governing infection. We identified \u03947-DA as the endogenous\n                    <jats:italic>Ss-<\/jats:italic>\n                    DAF-12 ligand and elucidated the hormone\u2019s biosynthetic pathway. Genetic loss of function of the ligand\u2019s rate-limiting enzyme demonstrated that \u03947-DA synthesis is necessary for parasite reproduction, whereas its absence is required for the development of infectious larvae. Availability of the ligand permits\n                    <jats:italic>Ss-<\/jats:italic>\n                    DAF-12 to function as an on\/off switch governing autoinfection, making it vulnerable to therapeutic intervention. In a preclinical model of hyperinfection, pharmacologic activation of DAF-12 suppressed autoinfection and markedly reduced lethality. Moreover, when \u03947-DA was administered with ivermectin, the current but limited drug of choice for treating strongyloidiasis, the combinatorial effects of the two drugs resulted in a near cure of the disease.\n                  <\/jats:p>","DOI":"10.7554\/elife.73535","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T08:15:11Z","timestamp":1636704911000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.73535","source":"Crossref","is-referenced-by-count":21,"title":["Characterization of the endogenous DAF-12 ligand and its use as an anthelmintic agent in Strongyloides stercoralis"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0768-0988","authenticated-orcid":true,"given":"Zhu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Texas Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Cheong","family":"Cheong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Texas Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2052-8051","authenticated-orcid":true,"given":"Jet","family":"Tsien","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heping","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, 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States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B","family":"Lok","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania","place":["Philadelphia, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-641X","authenticated-orcid":true,"given":"Steven A","family":"Kliewer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Texas Southwestern Medical Center","place":["Dallas, United States"]},{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4355-0796","authenticated-orcid":true,"given":"David J","family":"Mangelsdorf","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Texas 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