{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:23:53Z","timestamp":1792268633034,"version":"4.4.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37GM032443"],"award-info":[{"award-number":["R37GM032443"]}],"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":["R01AR064274"],"award-info":[{"award-number":["R01AR064274"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biophysical Journal"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.bpj.2020.12.033","type":"journal-article","created":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T06:32:40Z","timestamp":1611988360000},"page":"844-854","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prolonged myosin binding increases muscle stiffness in Drosophila models of Freeman-Sheldon syndrome"],"prefix":"10.1016","volume":"120","author":[{"given":"Kaylyn M.","family":"Bell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Kronert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanford I.","family":"Bernstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2552-4455","authenticated-orcid":false,"given":"Douglas M.","family":"Swank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Suppl 4","key":"10.1016\/j.bpj.2020.12.033_bib1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.2106\/JBJS.I.00281","article-title":"Arthrogryposis: a review and update","volume":"91","author":"Bamshad","year":"2009","journal-title":"J.\u00a0Bone Joint Surg. Am"},{"key":"10.1016\/j.bpj.2020.12.033_bib2","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/ng1775","article-title":"Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome","volume":"38","author":"Toydemir","year":"2006","journal-title":"Nat. Genet"},{"key":"10.1016\/j.bpj.2020.12.033_bib3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/(SICI)1096-8628(19980226)76:1<93::AID-AJMG17>3.0.CO;2-K","article-title":"Clinical analysis of a variant of Freeman-Sheldon syndrome (DA2B)","volume":"76","author":"Krakowiak","year":"1998","journal-title":"Am. J. Med. Genet"},{"key":"10.1016\/j.bpj.2020.12.033_bib4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/01.blo.0000157540.75191.1d","article-title":"The distal arthrogryposes: a new classification of peripheral contractures","volume":"435","author":"Beals","year":"2005","journal-title":"Clin. Orthop. Relat. Res"},{"key":"10.1016\/j.bpj.2020.12.033_bib5","doi-asserted-by":"crossref","DOI":"10.1136\/bcr-2015-212607","article-title":"Freeman-Sheldon syndrome in a 29-year-old woman presenting with rare and previously undescribed features","volume":"2015","author":"Chamberlain","year":"2015","journal-title":"BMJ Case Rep"},{"key":"10.1016\/j.bpj.2020.12.033_bib6","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1097\/SCS.0000000000002781","article-title":"Surgical approach, findings, and eight-year follow-up in a twenty-nine year old female with Freeman-Sheldon syndrome presenting with Blepharophimosis causing near-complete visual obstruction","volume":"27","author":"Portillo","year":"2016","journal-title":"J.\u00a0Craniofac. Surg"},{"key":"10.1016\/j.bpj.2020.12.033_bib7","doi-asserted-by":"crossref","first-page":"10318","DOI":"10.1074\/jbc.M115.707489","article-title":"The most prevalent Freeman-Sheldon syndrome mutations in the embryonic myosin motor share functional defects","volume":"291","author":"Walklate","year":"2016","journal-title":"J.\u00a0Biol. Chem"},{"key":"10.1016\/j.bpj.2020.12.033_bib8","doi-asserted-by":"crossref","first-page":"3348","DOI":"10.1093\/hmg\/ddv084","article-title":"The embryonic myosin R672C mutation that underlies Freeman-Sheldon syndrome impairs cross-bridge detachment and cycling in adult skeletal muscle","volume":"24","author":"Racca","year":"2015","journal-title":"Hum. Mol. Genet"},{"key":"10.1016\/j.bpj.2020.12.033_bib9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1091\/mbc.E18-08-0526","article-title":"Reductions in ATPase activity, actin sliding velocity, and myofibril stability yield muscle dysfunction in Drosophila models of myosin-based Freeman-Sheldon syndrome","volume":"30","author":"Rao","year":"2019","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.bpj.2020.12.033_bib10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ydbio.2019.02.017","article-title":"Myosin heavy chain mutations that cause Freeman-Sheldon syndrome lead to muscle structural and functional defects in Drosophila","volume":"449","author":"Das","year":"2019","journal-title":"Dev. Biol"},{"key":"10.1016\/j.bpj.2020.12.033_bib11","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1113\/JP277333","article-title":"The R249Q hypertrophic cardiomyopathy myosin mutation decreases contractility in Drosophila by impeding force production","volume":"597","author":"Bell","year":"2019","journal-title":"J.\u00a0Physiol"},{"key":"10.1016\/j.bpj.2020.12.033_bib12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.38064","article-title":"Prolonged cross-bridge binding triggers muscle dysfunction in a Drosophila model of myosin-based hypertrophic cardiomyopathy","volume":"7","author":"Kronert","year":"2018","journal-title":"eLife"},{"key":"10.1016\/j.bpj.2020.12.033_bib13","first-page":"2957","article-title":"Functional domains of the Drosophila melanogaster muscle myosin heavy-chain gene are encoded by alternatively spliced exons","volume":"9","author":"George","year":"1989","journal-title":"Mol. Cell. Biol"},{"key":"10.1016\/j.bpj.2020.12.033_bib14","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1101\/gad.4.6.885","article-title":"Alternative myosin hinge regions are utilized in a tissue-specific fashion that correlates with muscle contraction speed","volume":"4","author":"Collier","year":"1990","journal-title":"Genes Dev"},{"key":"10.1016\/j.bpj.2020.12.033_bib15","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1002\/ajmg.a.36762","article-title":"Genotype-phenotype relationships in Freeman-Sheldon syndrome","volume":"164A","author":"Beck","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"10.1016\/j.bpj.2020.12.033_bib16","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/1097-0029(20000915)50:6<430::AID-JEMT2>3.0.CO;2-E","article-title":"Determining structure\/function relationships for sarcomeric myosin heavy chain by genetic and transgenic manipulation of Drosophila","volume":"50","author":"Swank","year":"2000","journal-title":"Microsc. Res. Tech"},{"key":"10.1016\/j.bpj.2020.12.033_bib17","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1083\/jcb.107.6.2601","article-title":"Molecular and ultrastructural defects in a Drosophila myosin heavy chain mutant: differential effects on muscle function produced by similar thick filament abnormalities","volume":"107","author":"O\u2019Donnell","year":"1988","journal-title":"J.\u00a0Cell Biol"},{"key":"10.1016\/j.bpj.2020.12.033_bib18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ymeth.2011.10.015","article-title":"Mechanical analysis of Drosophila indirect flight and jump muscles","volume":"56","author":"Swank","year":"2012","journal-title":"Methods"},{"key":"10.1016\/j.bpj.2020.12.033_bib19","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/BF01843574","article-title":"Physiological properties of the dorsal longitudinal flight muscle and the tergal depressor of the trochanter muscle of Drosophila melanogaster","volume":"11","author":"Peckham","year":"1990","journal-title":"J.\u00a0Muscle Res. Cell Motil"},{"key":"10.1016\/j.bpj.2020.12.033_bib20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/BF00711932","article-title":"Sinusoidal analysis: a high resolution method for correlating biochemical reactions with physiological processes in activated skeletal muscles of rabbit, frog and crayfish","volume":"1","author":"Kawai","year":"1980","journal-title":"J.\u00a0Muscle Res. Cell Motil"},{"key":"10.1016\/j.bpj.2020.12.033_bib21","doi-asserted-by":"crossref","first-page":"17543","DOI":"10.1073\/pnas.0604972103","article-title":"An exceptionally fast actomyosin reaction powers insect flight muscle","volume":"103","author":"Swank","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bpj.2020.12.033_bib22","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1242\/jeb.117.1.357","article-title":"The mechanical power output of a tettigoniid wing muscle during singing and flight","volume":"117","author":"Josephson","year":"1985","journal-title":"J.\u00a0Exp. Biol"},{"key":"10.1016\/j.bpj.2020.12.033_bib23","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1242\/jeb.199.12.2767","article-title":"In\u00a0vivo length oscillations of indirect flight muscles in the fruit fly Drosophila virilis","volume":"199","author":"Chan","year":"1996","journal-title":"J.\u00a0Exp. Biol"},{"key":"10.1016\/j.bpj.2020.12.033_bib24","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.bpj.2011.07.045","article-title":"Disrupting the myosin converter-relay interface impairs Drosophila indirect flight muscle performance","volume":"101","author":"Ramanath","year":"2011","journal-title":"Biophys. J"},{"key":"10.1016\/j.bpj.2020.12.033_bib25","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.bpj.2009.11.051","article-title":"The mechanical properties of Drosophila jump muscle expressing wild-type and embryonic myosin isoforms","volume":"98","author":"Eldred","year":"2010","journal-title":"Biophys. J"},{"key":"10.1016\/j.bpj.2020.12.033_bib26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/BF00273589","article-title":"Characterisation of missense mutations in the Act88F gene of Drosophila melanogaster","volume":"226","author":"Drummond","year":"1991","journal-title":"Mol. Gen. Genet"},{"key":"10.1016\/j.bpj.2020.12.033_bib27","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/374650a0","article-title":"Impairment of muscle function caused by mutations of phosphorylation sites in myosin regulatory light chain","volume":"374","author":"Tohtong","year":"1995","journal-title":"Nature"},{"key":"10.1016\/j.bpj.2020.12.033_bib28","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13395-020-00241-6","article-title":"Drosophila myosin mutants model the disparate severity of type 1 and type 2B distal arthrogryposis and indicate an enhanced actin affinity mechanism","volume":"10","author":"Guo","year":"2020","journal-title":"Skelet. Muscle"},{"key":"10.1016\/j.bpj.2020.12.033_bib29","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nsmb.3408","article-title":"The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations","volume":"24","author":"Nag","year":"2017","journal-title":"Nat. Struct. Mol. Biol"},{"key":"10.1016\/j.bpj.2020.12.033_bib30","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.bpj.2009.05.023","article-title":"Cardiomyopathy mutations reveal variable region of myosin converter as major element of cross-bridge compliance","volume":"97","author":"Seebohm","year":"2009","journal-title":"Biophys. J"},{"key":"10.1016\/j.bpj.2020.12.033_bib31","doi-asserted-by":"crossref","first-page":"eaao2267","DOI":"10.1126\/sciadv.aao2267","article-title":"A mixed-kinetic model describes unloaded velocities of smooth, skeletal, and cardiac muscle myosin filaments in\u00a0vitro","volume":"3","author":"Brizendine","year":"2017","journal-title":"Sci. Adv"},{"key":"10.1016\/j.bpj.2020.12.033_bib32","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1083\/jcb.134.4.895","article-title":"Glycine 699 is pivotal for the motor activity of skeletal muscle myosin","volume":"134","author":"Kinose","year":"1996","journal-title":"J.\u00a0Cell Biol"},{"key":"10.1016\/j.bpj.2020.12.033_bib33","doi-asserted-by":"crossref","first-page":"e12356","DOI":"10.15252\/emmm.202012356","article-title":"MYH3-associated distal arthrogryposis zebrafish model is normalized with para-aminoblebbistatin","volume":"12","author":"Whittle","year":"2020","journal-title":"EMBO Mol. Med"},{"key":"10.1016\/j.bpj.2020.12.033_bib34","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1038\/s41467-020-15922-5","article-title":"A role for actin flexibility in thin filament-mediated contractile regulation and myopathy","volume":"11","author":"Viswanathan","year":"2020","journal-title":"Nat. Commun"},{"key":"10.1016\/j.bpj.2020.12.033_bib35","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1016\/j.jmb.2016.04.021","article-title":"A restrictive cardiomyopathy mutation in an invariant proline at the myosin head\/rod junction enhances head flexibility and function, yielding muscle defects in Drosophila","volume":"428","author":"Achal","year":"2016","journal-title":"J.\u00a0Mol. Biol"},{"key":"10.1016\/j.bpj.2020.12.033_bib36","doi-asserted-by":"crossref","first-page":"12092","DOI":"10.1016\/S0021-9258(20)71324-4","article-title":"A monoclonal antibody to the embryonic myosin heavy chain of rat skeletal muscle","volume":"259","author":"Gambke","year":"1984","journal-title":"J.\u00a0Biol. Chem"},{"key":"10.1016\/j.bpj.2020.12.033_bib37","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/0092-8674(88)90463-1","article-title":"Fast muscle fibers are preferentially affected in Duchenne muscular dystrophy","volume":"52","author":"Webster","year":"1988","journal-title":"Cell"},{"key":"10.1016\/j.bpj.2020.12.033_bib38","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/0092-8674(86)90707-5","article-title":"Developmental progression of myosin gene expression in cultured muscle cells","volume":"46","author":"Silberstein","year":"1986","journal-title":"Cell"},{"key":"10.1016\/j.bpj.2020.12.033_bib39","doi-asserted-by":"crossref","first-page":"6167","DOI":"10.1093\/nar\/17.15.6167","article-title":"Expression and DNA sequence analysis of a human embryonic skeletal muscle myosin heavy chain gene","volume":"17","author":"Karsch-Mizrachi","year":"1989","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.bpj.2020.12.033_bib40","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1001\/archneur.65.8.1083","article-title":"Embryonic myosin heavy-chain mutations cause distal arthrogryposis and developmental myosin myopathy that persists postnatally","volume":"65","author":"Tajsharghi","year":"2008","journal-title":"Arch. Neurol"},{"key":"10.1016\/j.bpj.2020.12.033_bib41","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/aja.1001980306","article-title":"Modulation of contractile protein gene expression in fetal murine crural muscles: emergence of muscle diversity","volume":"198","author":"Ontell","year":"1993","journal-title":"Dev. Dyn"},{"key":"10.1016\/j.bpj.2020.12.033_bib42","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1083\/jcb.108.5.1791","article-title":"Molecular genetic characterization of a developmentally regulated human perinatal myosin heavy chain","volume":"108","author":"Feghali","year":"1989","journal-title":"J.\u00a0Cell Biol"},{"key":"10.1016\/j.bpj.2020.12.033_bib43","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13395-015-0046-6","article-title":"Developmental myosins: expression patterns and functional significance","volume":"5","author":"Schiaffino","year":"2015","journal-title":"Skelet. Muscle"},{"key":"10.1016\/j.bpj.2020.12.033_bib44","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/ncb734","article-title":"A small-molecule inhibitor of skeletal muscle myosin II","volume":"4","author":"Cheung","year":"2002","journal-title":"Nat. Cell Biol"},{"key":"10.1016\/j.bpj.2020.12.033_bib45","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.bpj.2014.07.075","article-title":"The myosin inhibitor blebbistatin stabilizes the super-relaxed state in skeletal muscle","volume":"107","author":"Wilson","year":"2014","journal-title":"Biophys. J"},{"key":"10.1016\/j.bpj.2020.12.033_bib46","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/cm.10113","article-title":"Skeletal muscle myosin cross-bridge cycling is necessary for myofibrillogenesis","volume":"55","author":"Ramachandran","year":"2003","journal-title":"Cell Motil. Cytoskeleton"}],"container-title":["Biophysical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349521000758?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349521000758?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:10:26Z","timestamp":1778631026000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006349521000758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["S0006349521000758"],"URL":"https:\/\/doi.org\/10.1016\/j.bpj.2020.12.033","relation":{},"ISSN":["0006-3495"],"issn-type":[{"value":"0006-3495","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Prolonged myosin binding increases muscle stiffness in Drosophila models of Freeman-Sheldon syndrome","name":"articletitle","label":"Article Title"},{"value":"Biophysical Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bpj.2020.12.033","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Biophysical Society.","name":"copyright","label":"Copyright"}]}}