{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:38:21Z","timestamp":1785544701210,"version":"3.56.0"},"posted":{"date-parts":[[2025,6,12]]},"group-title":"Genetics","reference-count":84,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R00 HD097306"],"award-info":[{"award-number":["R00 HD097306"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000965","name":"American Federation for Aging Research","doi-asserted-by":"crossref","award":["AFAR Grant for Junior Faculty"],"award-info":[{"award-number":["AFAR Grant for Junior Faculty"]}],"id":[{"id":"10.13039\/100000965","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006772","name":"MAX AND MINNIE TOMERLIN VOELCKER FUND","doi-asserted-by":"crossref","award":["Voelcker Fund Young Investigator Award"],"award-info":[{"award-number":["Voelcker Fund Young Investigator Award"]}],"id":[{"id":"10.13039\/100006772","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Precise control of hormones is essential for animal development. Hormone bioavailability is regulated by their synthesis, transport, sequestration, natural turnover, and programmed degradation. Here, we use\n                  <jats:italic>Drosophila melanogaster<\/jats:italic>\n                  to investigate developmentally programmed degradation of the retinoid-like juvenile hormones (JHs). JHs promote juvenile growth and timely development by functionally opposing the steroid hormone, ecdysone. Despite well-characterized biochemistry, the developmental requirements for programmed JH degradation are poorly understood due to paralogue expansion. To close this knowledge gap, we generated double and triple knockout animals lacking one of two classes of JH degradation enzymes: JH esterases (JHEs) and JH epoxide hydrolases (JHEHs). We found that while both JHEs and JHEHs restrain JH signaling during\n                  <jats:italic>Drosophila<\/jats:italic>\n                  juvenile development, each has separate requirements in the regulation of developmental timing and growth. Strikingly, loss of all three JHEHs doubled the length of juvenile development, and the resulting pupae were smaller. Through targeted and genome-wide transcriptome analysis, measurements of hormone-producing glands, and rescue experiments, we uncovered both shared and unique dysregulated gene networks, some of which have established roles in the regulation of both body size and developmental timing. Our comparative analysis of both JH degradation pathways demonstrated that loss of JHEH, but not JHE, activates multiple levels of compensatory feedback to maintain homeostasis within JH and ecdysone axes. These data not only suggest that JHEH-mediated degradation is the dominant programmed JH degradation pathway in\n                  <jats:italic>D. melanogaster<\/jats:italic>\n                  development, but they also revealed new JH homeostatic mechanisms more generally. Together, this study provides new genetic tools and insights into programmed hormone degradation.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Article summary<\/jats:title>\n                  <jats:p>\n                    Hormones control the timing of developmental transitions and growth. As such, multiple mechanisms ensure precise amounts of a hormone are available at the right time and place. Here, we investigated the poorly understood process of developmentally programmed hormone degradation using juvenile hormones (JHs) in\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    as a model. We generated double and triple knockout strains to disrupt JH degradation and found an unexpected separation of requirements in regulating developmental growth and timing. Through phenotypic and transcriptomic analysis, this study provides insights into the mechanisms and complexities of programmed hormone degradation in animal development.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.06.09.657647","type":"posted-content","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T22:15:20Z","timestamp":1749766520000},"source":"Crossref","is-referenced-by-count":1,"title":["Juvenile hormone degradation enzymes have shared and unique requirements in\n                  <i>Drosophila<\/i>\n                  development"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6466-5333","authenticated-orcid":false,"given":"Rebecca","family":"Spokony","sequence":"first","affiliation":[{"name":"Department of Natural Sciences, Baruch College, City University of New York, New York, NY, 10010"},{"name":"Program in Molecular, Cellular, and Developmental Biology, Graduate Center, City University of New York, New York, NY, 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4013-4958","authenticated-orcid":false,"given":"Krystal","family":"Goyins","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6119-7836","authenticated-orcid":false,"given":"Harry","family":"Siegel","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249"},{"name":"Graduate School of Biomedical Sciences, The University of Texas Health at San Antonio, San Antonio, TX, 78299"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6039-077X","authenticated-orcid":false,"given":"Creehan","family":"Healy","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Alvarado","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1949-4656","authenticated-orcid":false,"given":"Amina","family":"Jumamyradova","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashfa","family":"Naseem","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Baruch College, City University of New York, New York, NY, 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-3470","authenticated-orcid":false,"given":"Alexey A.","family":"Soshnev","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-4946","authenticated-orcid":false,"given":"Lacy J","family":"Barton","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026073114401694000_2025.06.09.657647v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2011.09.003"},{"key":"2026073114401694000_2025.06.09.657647v2.2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.66.1.57"},{"key":"2026073114401694000_2025.06.09.657647v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2023.12.033"},{"key":"2026073114401694000_2025.06.09.657647v2.4","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.114.162941"},{"key":"2026073114401694000_2025.06.09.657647v2.5","doi-asserted-by":"crossref","unstructured":"Box, A. M. , N. A. Ramesh , S. Nandakumar , S. J. Church , D. Prasad et al., 2024 Cell cycle variants during Drosophila male accessory gland development. G3 (Bethesda) 14.","DOI":"10.1093\/g3journal\/jkae089"},{"key":"2026073114401694000_2025.06.09.657647v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2007.10.030"},{"key":"2026073114401694000_2025.06.09.657647v2.7","first-page":"1","article-title":"Juvenile Hormone Regulation and Action","volume":"2","year":"2019","journal-title":"Advances in Invertebrate (Neuro)Endocrinology"},{"key":"2026073114401694000_2025.06.09.657647v2.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0965-1748(01)00035-2"},{"key":"2026073114401694000_2025.06.09.657647v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/459927a"},{"key":"2026073114401694000_2025.06.09.657647v2.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2007.02.010"},{"key":"2026073114401694000_2025.06.09.657647v2.11","doi-asserted-by":"crossref","unstructured":"Danecek, P. , J. K. Bonfield , J. Liddle , J. Marshall , V. Ohan et al., 2021 Twelve years of SAMtools and BCFtools. Gigascience 10.","DOI":"10.1093\/gigascience\/giab008"},{"key":"2026073114401694000_2025.06.09.657647v2.12","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2012.0429"},{"key":"2026073114401694000_2025.06.09.657647v2.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28347-z"},{"key":"2026073114401694000_2025.06.09.657647v2.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2583.2004.00529.x"},{"key":"2026073114401694000_2025.06.09.657647v2.15","doi-asserted-by":"publisher","DOI":"10.1038\/srep06586"},{"key":"2026073114401694000_2025.06.09.657647v2.16","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw354"},{"key":"2026073114401694000_2025.06.09.657647v2.17","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ento.44.1.507"},{"key":"2026073114401694000_2025.06.09.657647v2.18","doi-asserted-by":"crossref","first-page":"104475","DOI":"10.1016\/j.ibmb.2025.104475","article-title":"Two cytochrome P450 epoxidases mediate juvenile hormone biosynthesis in Drosophila melanogaster","volume":"187","year":"2026","journal-title":"Insect Biochem Mol Biol"},{"key":"2026073114401694000_2025.06.09.657647v2.19","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.11.2365"},{"key":"2026073114401694000_2025.06.09.657647v2.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.10.012"},{"key":"2026073114401694000_2025.06.09.657647v2.21","doi-asserted-by":"crossref","unstructured":"Goodman, W. G. , and M. Cusson , 2012 8 - The Juvenile Hormones, pp. 310-365 in Insect Endocrinology, edited by L. I. Gilbert . Academic Press, San Diego.","DOI":"10.1016\/B978-0-12-384749-2.10008-1"},{"key":"2026073114401694000_2025.06.09.657647v2.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021139"},{"key":"2026073114401694000_2025.06.09.657647v2.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2019.01.001"},{"key":"2026073114401694000_2025.06.09.657647v2.24","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1093\/jee\/toaa041","article-title":"Effect of Treatment With 3-Octylthio-1,1,1- Trifluoropropan-2-One in the Diamondback Moth (Lepidoptera: Plutellidae) to the Toxicity of Diafenthiuron, Indoxacarb, and Bacillus thuringiensis","volume":"113","year":"2020","journal-title":"J Econ Entomol"},{"key":"2026073114401694000_2025.06.09.657647v2.25","doi-asserted-by":"crossref","unstructured":"Imura, E. , Y. Yoshinari , Y. Shimada-Niwa and R. Niwa , 2017 Protocols for Visualizing Steroidogenic Organs and Their Interactive Organs with Immunostaining in the Fruit Fly Drosophila melanogaster. J Vis Exp.","DOI":"10.3791\/55519-v"},{"key":"2026073114401694000_2025.06.09.657647v2.26","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6327(1998)37:4<305::AID-ARCH6>3.0.CO;2-P"},{"key":"2026073114401694000_2025.06.09.657647v2.27","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-024-01910-4"},{"issue":"04","key":"2026073114401694000_2025.06.09.657647v2.28","first-page":"138","article-title":"Juvenile hormone signaling","volume":"2","year":"2026","journal-title":"Comprehensive Molecular Insect Science"},{"key":"2026073114401694000_2025.06.09.657647v2.29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005394"},{"key":"2026073114401694000_2025.06.09.657647v2.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.002"},{"key":"2026073114401694000_2025.06.09.657647v2.31","doi-asserted-by":"publisher","DOI":"10.1584\/jpestics.R10-09"},{"key":"2026073114401694000_2025.06.09.657647v2.32","doi-asserted-by":"publisher","DOI":"10.1016\/S0965-1748(96)00043-4"},{"key":"2026073114401694000_2025.06.09.657647v2.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4"},{"key":"2026073114401694000_2025.06.09.657647v2.34","doi-asserted-by":"publisher","DOI":"10.1007\/BF00334868"},{"key":"2026073114401694000_2025.06.09.657647v2.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2018.06.016"},{"key":"2026073114401694000_2025.06.09.657647v2.36","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAD347"},{"key":"2026073114401694000_2025.06.09.657647v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/317555a0"},{"key":"2026073114401694000_2025.06.09.657647v2.38","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.genrep.2016.04.010","article-title":"Recent gene multiplication and evolution of a juvenile hormone esterase-related gene in a lepidopteran pest","volume":"4","year":"2016","journal-title":"Gene Reports"},{"key":"2026073114401694000_2025.06.09.657647v2.39","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.240315"},{"key":"2026073114401694000_2025.06.09.657647v2.40","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2660(08)60142-X"},{"key":"2026073114401694000_2025.06.09.657647v2.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36048-1"},{"key":"2026073114401694000_2025.06.09.657647v2.42","doi-asserted-by":"crossref","first-page":"104348","DOI":"10.1016\/j.ibmb.2025.104348","article-title":"Metabolic network remodeling through PxJHE modulates temperature adaptation in a cosmopolitan insect","volume":"182","year":"2025","journal-title":"Insect Biochem Mol Biol"},{"key":"2026073114401694000_2025.06.09.657647v2.43","doi-asserted-by":"crossref","unstructured":"Leyria, J. , S. Benrabaa , M. Nouzova , F. G. Noriega , L. V. Tose et al., 2022a Crosstalk between Nutrition, Insulin, Juvenile Hormone, and Ecdysteroid Signaling in the Classical Insect Model, Rhodnius prolixus. Int J Mol Sci 24.","DOI":"10.3390\/ijms24010007"},{"key":"2026073114401694000_2025.06.09.657647v2.44","doi-asserted-by":"crossref","unstructured":"Leyria, J. , I. Orchard and A. B. Lange , 2022b Impact of JH Signaling on Reproductive Physiology of the Classical Insect Model, Rhodnius prolixus. Int J Mol Sci 23.","DOI":"10.3390\/ijms232213832"},{"key":"2026073114401694000_2025.06.09.657647v2.45","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.877153"},{"key":"2026073114401694000_2025.06.09.657647v2.46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1716897115"},{"key":"2026073114401694000_2025.06.09.657647v2.47","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026073114401694000_2025.06.09.657647v2.48","doi-asserted-by":"publisher","DOI":"10.1111\/1744-7917.13084"},{"key":"2026073114401694000_2025.06.09.657647v2.49","unstructured":"Magee, M. , and R. Spokony , 2023 Effect of D. melanogaster larval density on pupal size. MicroPubl Biol 2023."},{"key":"2026073114401694000_2025.06.09.657647v2.50","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-10-r216"},{"key":"2026073114401694000_2025.06.09.657647v2.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2007.10.002"},{"key":"2026073114401694000_2025.06.09.657647v2.52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313058111"},{"key":"2026073114401694000_2025.06.09.657647v2.53","doi-asserted-by":"crossref","first-page":"102148","DOI":"10.1016\/j.gde.2023.102148","article-title":"Timing Drosophila development through steroid hormone action","volume":"84","year":"2024","journal-title":"Curr Opin Genet Dev"},{"key":"2026073114401694000_2025.06.09.657647v2.54","doi-asserted-by":"publisher","DOI":"10.1186\/jbiol43"},{"key":"2026073114401694000_2025.06.09.657647v2.55","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.61.2.493"},{"key":"2026073114401694000_2025.06.09.657647v2.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2008.04.003"},{"key":"2026073114401694000_2025.06.09.657647v2.57","doi-asserted-by":"publisher","DOI":"10.47665\/tb.38.3.066"},{"key":"2026073114401694000_2025.06.09.657647v2.58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006583"},{"key":"2026073114401694000_2025.06.09.657647v2.59","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTAC166"},{"key":"2026073114401694000_2025.06.09.657647v2.60","doi-asserted-by":"crossref","unstructured":"Qu, X. , H. Lu , X. Zhang , L. Xin and X. Chen , 2026 TITIN Regulates Body Size via the JH-JHE Pathway in Honeybees (Apis mellifera). Int J Mol Sci 27.","DOI":"10.3390\/ijms27104501"},{"key":"2026073114401694000_2025.06.09.657647v2.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2024.12.010"},{"key":"2026073114401694000_2025.06.09.657647v2.62","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw257"},{"key":"2026073114401694000_2025.06.09.657647v2.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.151313"},{"key":"2026073114401694000_2025.06.09.657647v2.64","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cois.2018.07.010","article-title":"Juvenile hormone signaling in insect oogenesis","volume":"31","year":"2019","journal-title":"Curr Opin Insect Sci"},{"issue":"Pt 5","key":"2026073114401694000_2025.06.09.657647v2.65","first-page":"515","article-title":"Gene-environment interaction for body size and larval density in Drosophila melanogaster: an investigation of effects on development time, thorax length and adult sex ratio","volume":"72","year":"1994","journal-title":"Heredity (Edinb"},{"key":"2026073114401694000_2025.06.09.657647v2.66","doi-asserted-by":"crossref","unstructured":"Shinoda, T. , T. Kotaki and H. E. Numata , 2026 Juvenile Hormone: Structure, Synthesis and Function. Springer Singapore.","DOI":"10.1007\/978-981-95-8605-9"},{"key":"2026073114401694000_2025.06.09.657647v2.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinsphys.2023.104487"},{"key":"2026073114401694000_2025.06.09.657647v2.68","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13015-w"},{"key":"2026073114401694000_2025.06.09.657647v2.69","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.22.12884"},{"key":"2026073114401694000_2025.06.09.657647v2.70","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1046\/j.1432-1033.2003.03868.x","article-title":"Characterization and cDNA cloning of a clofibrate-inducible microsomal epoxide hydrolase in Drosophila melanogaster","volume":"270","year":"2003","journal-title":"Eur J Biochem"},{"key":"2026073114401694000_2025.06.09.657647v2.71","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.cbpc.2013.05.004","article-title":"The glutathione-related detoxication responses to juvenile and ecdysone hormones in Galleria mellonella","volume":"158","year":"2013","journal-title":"Comp Biochem Physiol C Toxicol Pharmacol"},{"key":"2026073114401694000_2025.06.09.657647v2.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2018.12.002"},{"key":"2026073114401694000_2025.06.09.657647v2.73","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/s41598-017-00907-0","article-title":"Juvenile Hormone Epoxide Hydrolase: a Promising Target for Hemipteran Pest Management","volume":"7","year":"2017","journal-title":"Sci Rep"},{"key":"2026073114401694000_2025.06.09.657647v2.74","doi-asserted-by":"crossref","first-page":"1073721","DOI":"10.3389\/fmolb.2023.1073721","article-title":"Simultaneous silencing of juvenile hormone metabolism genes through RNAi interrupts metamorphosis in the cotton boll weevil","volume":"10","year":"2023","journal-title":"Front Mol Biosci"},{"key":"2026073114401694000_2025.06.09.657647v2.75","unstructured":"Venkatesh, R. M. R. a. K. , 1990 Metabolism of Juvenile Hormones: Degradation and Titer Regulation. Morphogenetic hormones of arthropods: 126\u2013179."},{"key":"2026073114401694000_2025.06.09.657647v2.76","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.761387"},{"key":"2026073114401694000_2025.06.09.657647v2.77","doi-asserted-by":"publisher","DOI":"10.1126\/science.213.4505.361"},{"key":"2026073114401694000_2025.06.09.657647v2.78","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2003.06.007"},{"key":"2026073114401694000_2025.06.09.657647v2.79","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007318"},{"key":"2026073114401694000_2025.06.09.657647v2.80","doi-asserted-by":"publisher","DOI":"10.1002\/arch.20257"},{"key":"2026073114401694000_2025.06.09.657647v2.81","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-11-85"},{"key":"2026073114401694000_2025.06.09.657647v2.82","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1800435115"},{"key":"2026073114401694000_2025.06.09.657647v2.83","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2017.01.001"},{"key":"2026073114401694000_2025.06.09.657647v2.84","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2583.2006.00675.x"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.06.09.657647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T21:40:29Z","timestamp":1785534029000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.06.09.657647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,12]]},"references-count":84,"URL":"https:\/\/doi.org\/10.1101\/2025.06.09.657647","relation":{},"subject":[],"published":{"date-parts":[[2025,6,12]]},"subtype":"preprint"}}