{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:10:40Z","timestamp":1790665840176,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T00:00:00Z","timestamp":1458604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/N002768\/1"],"award-info":[{"award-number":["MR\/N002768\/1"]}]},{"DOI":"10.13039\/501100001728","name":"STINT","doi-asserted-by":"crossref","award":["1046782"],"award-info":[{"award-number":["1046782"]}],"id":[{"id":"10.13039\/501100001728","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Operational Infrastructure Support Program of the Victorian Government"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Nemaline myopathy, one of the most common congenital myopathies, is associated with mutations in various genes including\n                      <jats:italic>ACTA1<\/jats:italic>\n                      . This disease is also characterized by various forms\/degrees of muscle weakness, with most cases being severe and resulting in death in infancy. Recent findings have provided valuable insight into the underlying pathophysiological mechanisms. Mutations in\n                      <jats:italic>ACTA1<\/jats:italic>\n                      directly disrupt binding interactions between actin and myosin, and consequently the intrinsic force\u2010generating capacity of muscle fibers.\n                      <jats:italic>ACTA1<\/jats:italic>\n                      mutations are also associated with variations in myofiber size, the mechanisms of which have been unclear. In the present study, we sought to test the hypotheses that the compromised functional and morphological attributes of skeletal muscles bearing\n                      <jats:italic>ACTA1<\/jats:italic>\n                      mutations (1) would be directly due to the inefficient actomyosin complex and (2) could be restored by manipulating myosin expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used a knockin mouse model expressing the\n                      <jats:italic>ACTA1<\/jats:italic>\n                      His40Tyr actin mutation found in human patients. We then performed in vivo intramuscular injections of recombinant adeno\u2010associated viral vectors harboring a myosin transgene known to facilitate muscle contraction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed that in the presence of the transgene, the intrinsic force\u2010generating capacity was restored and myofiber size was normal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      This demonstrates a direct link between disrupted attachment of myosin molecules to actin monomers and muscle fiber atrophy. These data also suggest that further therapeutic interventions should primarily target myosin dysfunction to alleviate the pathology of\n                      <jats:italic>ACTA1<\/jats:italic>\n                      \u2010related nemaline myopathy. Ann Neurol 2016;79:717\u2013725\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24619","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T10:27:39Z","timestamp":1455791259000},"page":"717-725","source":"Crossref","is-referenced-by-count":30,"title":["Modulating myosin restores muscle function in a mouse model of nemaline myopathy"],"prefix":"10.1002","volume":"79","author":[{"given":"Johan","family":"Lindqvist","sequence":"first","affiliation":[{"name":"Department of Neuroscience Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yotam","family":"Levy","sequence":"additional","affiliation":[{"name":"Centre of Human and Aerospace Physiological Sciences, Faculty of Life Sciences &amp; Medicine King's College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha","family":"Pati\u2010Alam","sequence":"additional","affiliation":[{"name":"Centre of Human and Aerospace Physiological Sciences, Faculty of Life Sciences &amp; Medicine King's College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna C.","family":"Hardeman","sequence":"additional","affiliation":[{"name":"Neuromuscular and Regenerative Medicine Unit, School of Medical Sciences University of New South Wales Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gregorevic","sequence":"additional","affiliation":[{"name":"Baker IDI Heart and Diabetes Institute Melbourne Victoria Australia"},{"name":"Department of Biochemistry and Molecular Biology Monash University Melbourne Victoria Australia"},{"name":"Department of Physiology University of Melbourne Melbourne Victoria Australia"},{"name":"Department of Neurology University of Washington School of Medicine Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Ochala","sequence":"additional","affiliation":[{"name":"Centre of Human and Aerospace Physiological Sciences, Faculty of Life Sciences &amp; 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