{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T19:40:01Z","timestamp":1783021201678,"version":"3.54.6"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS111041"],"award-info":[{"award-number":["R01NS111041"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007270","name":"University of Michigan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007270","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dystrophin links the actin cytoskeleton to the extracellular matrix through the dystrophin\u2013glycoprotein complex (DGC), providing structural stability to muscle fibers. In mdx mice, which lack dystrophin, neuromuscular junctions (NMJs) remain largely structurally and functionally intact despite extensive muscle pathology. Here, using single- and double-mutant mice deficient in dystrophin and \u03b1-syntrophin (\u03b1-syn), we investigated how utrophin upregulation contributes to NMJ maintenance in dystrophic muscle. During early postnatal development, when dystrophic muscles are transiently resistant to degeneration, the DGC proteins \u03b1-dystrobrevin, \u03b1-syn, and \u03b2-dystroglycan are broadly distributed along both synaptic and extra-synaptic regions of the sarcolemma, although their overall levels are reduced compared with wild-type (WT) muscle. In contrast, in WT mice, utrophin is restricted to NMJs, whereas in dystrophic muscles from both mutants, it is distributed along both synaptic and extra-synaptic regions of the sarcolemma, particularly within the innervated zone of muscle fibers. As muscles mature and degeneration begins, these DGC components become highly restricted to NMJs while being markedly reduced or absent from the extra-synaptic sarcolemma in many muscle cells. Although utrophin remains highly enriched at synaptic sites in mdx:\u03b1-syn\u2212\/\u2212 muscles, their NMJs display severe structural abnormalities compared with those of mdx mice. These include a dramatic reduction in synaptic fold depth and density, a decrease in presynaptic vesicle density, retraction of nerve terminals, and axonal thinning. These findings demonstrate that utrophin localization at the NMJ is not sufficient to preserve synaptic integrity and that functional interactions between utrophin and \u03b1-syn are required to maintain the NMJ in dystrophic muscle.<\/jats:p>","DOI":"10.1093\/hmg\/ddag060","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:58:45Z","timestamp":1782863925000},"source":"Crossref","is-referenced-by-count":0,"title":["Utrophin requires \u03b1-Syntrophin to maintain neuromuscular junction integrity in\n                    <i>mdx<\/i>\n                    mice"],"prefix":"10.1093","volume":"35","author":[{"given":"Alissa","family":"Wierenga","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology , 1105 N. University Avenue, Ann Arbor, Michigan, 48109,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology , 1105 N. University Avenue, Ann Arbor, Michigan, 48109,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad O","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology , 1105 N. University Avenue, Ann Arbor, Michigan, 48109,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology , 1105 N. University Avenue, Ann Arbor, Michigan, 48109,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Reda","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology , 1105 N. University Avenue, Ann Arbor, Michigan, 48109,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Maag","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology , 1105 N. University Avenue, Ann Arbor, Michigan, 48109,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameen","family":"Abou-Rjaily","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology , 1105 N. University Avenue, Ann Arbor, Michigan, 48109,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenlang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology , 1105 N. University Avenue, Ann Arbor, Michigan, 48109,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1991-0963","authenticated-orcid":false,"given":"Mohammed","family":"Akaaboune","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology , 1105 N. University Avenue, Ann Arbor, Michigan, 48109,","place":["USA"]},{"name":"Michigan Neuroscience Institute, University of Michigan , 2800 Plymouth Road, NCRC B25-1793, Ann Arbor, MI 48109 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"2026070214505714200_ref1","doi-asserted-by":"publisher","first-page":"134833","DOI":"10.1016\/j.neulet.2020.134833","article-title":"The role of the dystrophin glycoprotein complex on the neuromuscular system","volume":"722","author":"Belhasan","year":"2020","journal-title":"Neurosci Lett"},{"key":"2026070214505714200_ref2","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1152\/physrev.00028.2001","article-title":"Function and genetics of dystrophin and dystrophin-related proteins in muscle","volume":"82","author":"Blake","year":"2002","journal-title":"Physiol Rev"},{"key":"2026070214505714200_ref3","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1161\/01.RES.0000126574.61061.25","article-title":"The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma","volume":"94","author":"Lapidos","year":"2004","journal-title":"Circ Res"},{"key":"2026070214505714200_ref4","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.bbadis.2006.05.010","article-title":"Dystrophin, its interactions with other proteins, and implications for muscular dystrophy","volume":"1772","author":"Ervasti","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"2026070214505714200_ref5","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1083\/jcb.122.4.809","article-title":"A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin","volume":"122","author":"Ervasti","year":"1993","journal-title":"J Cell Biol"},{"key":"2026070214505714200_ref6","doi-asserted-by":"publisher","first-page":"3710","DOI":"10.1073\/pnas.90.8.3710","article-title":"Dystrophin protects the sarcolemma from stresses developed during muscle contraction","volume":"90","author":"Petrof","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026070214505714200_ref7","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1126\/science.2662404","article-title":"The molecular basis of muscular dystrophy in the mdx mouse: a point mutation","volume":"244","author":"Sicinski","year":"1989","journal-title":"Science"},{"key":"2026070214505714200_ref8","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/0022-510X(87)90219-X","article-title":"Muscular dystrophy in the mdx mouse: histopathology of the soleus and extensor digitorum longus muscles","volume":"80","author":"Carnwath","year":"1987","journal-title":"J Neurol Sci"},{"key":"2026070214505714200_ref9","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/j.1365-2990.1988.tb00866.x","article-title":"The mdx mouse skeletal muscle myopathy: I. A histological, morphometric and biochemical investigation","volume":"14","author":"Coulton","year":"1988","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2026070214505714200_ref10","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0022-510X(94)00276-T","article-title":"mdx mice show progressive weakness and muscle deterioration with age","volume":"129","author":"Pastoret","year":"1995","journal-title":"J Neurol Sci"},{"key":"2026070214505714200_ref11","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1093\/brain\/110.2.269","article-title":"The mutant mdx: inherited myopathy in the mouse. Morphological studies of nerves, muscles and end-plates","volume":"110","author":"Torres","year":"1987","journal-title":"Brain"},{"key":"2026070214505714200_ref12","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1073\/pnas.81.4.1189","article-title":"X chromosome-linked muscular dystrophy (mdx) in the mouse","volume":"81","author":"Bulfield","year":"1984","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026070214505714200_ref13","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1083\/jcb.128.3.355","article-title":"Mechanical function of dystrophin in muscle cells","volume":"128","author":"Pasternak","year":"1995","journal-title":"J Cell Biol"},{"key":"2026070214505714200_ref14","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/j.1750-3639.1996.tb00781.x","article-title":"Utrophin: a structural and functional comparison to dystrophin","volume":"6","author":"Blake","year":"1996","journal-title":"Brain Pathol"},{"key":"2026070214505714200_ref15","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1083\/jcb.136.4.871","article-title":"Subtle neuromuscular defects in utrophin-deficient mice","volume":"136","author":"Grady","year":"1997","journal-title":"J Cell Biol"},{"key":"2026070214505714200_ref16","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/S0092-8674(00)80533-4","article-title":"Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy","volume":"90","author":"Grady","year":"1997","journal-title":"Cell"},{"key":"2026070214505714200_ref17","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1083\/jcb.136.4.883","article-title":"Postsynaptic abnormalities at the neuromuscular junctions of utrophin-deficient mice","volume":"136","author":"Deconinck","year":"1997","journal-title":"J Cell Biol"},{"key":"2026070214505714200_ref18","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/S0092-8674(00)80532-2","article-title":"Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy","volume":"90","author":"Deconinck","year":"1997","journal-title":"Cell"},{"key":"2026070214505714200_ref19","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s40259-024-00693-y","article-title":"Correction: dystrophin- and Utrophin-based therapeutic approaches for treatment of Duchenne muscular dystrophy: a comparative review","volume":"39","author":"Szwec","year":"2025","journal-title":"Bio Drugs"},{"key":"2026070214505714200_ref20","doi-asserted-by":"publisher","first-page":"e0205926","DOI":"10.1371\/journal.pone.0205926","article-title":"Cycles of myofiber degeneration and regeneration lead to remodeling of the neuromuscular junction in two mammalian models of Duchenne muscular dystrophy","volume":"13","author":"Haddix","year":"2018","journal-title":"PLoS One"},{"key":"2026070214505714200_ref21","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1007\/BF01187915","article-title":"Structure and function of the neuromuscular junction in young adult mdx mice","volume":"20","author":"Lyons","year":"1991","journal-title":"J Neurocytol"},{"key":"2026070214505714200_ref22","doi-asserted-by":"publisher","first-page":"252","DOI":"10.3389\/fphys.2015.00252","article-title":"Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice","volume":"6","author":"Pratt","year":"2015","journal-title":"Front Physiol"},{"key":"2026070214505714200_ref23","doi-asserted-by":"publisher","first-page":"7108","DOI":"10.1038\/s41467-022-34831-3","article-title":"Pharmacological inhibition of HDAC6 improves muscle phenotypes in dystrophin-deficient mice by downregulating TGF-beta via Smad3 acetylation","volume":"13","author":"Osseni","year":"2022","journal-title":"Nat Commun"},{"key":"2026070214505714200_ref24","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1023\/B:NEUR.0000020619.24681.2b","article-title":"The postsynaptic submembrane machinery at the neuromuscular junction: requirement for rapsyn and the utrophin\/dystrophin-associated complex","volume":"32","author":"Banks","year":"2003","journal-title":"J Neurocytol"},{"key":"2026070214505714200_ref25","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1083\/jcb.150.6.1385","article-title":"Absence of alpha-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin","volume":"150","author":"Adams","year":"2000","journal-title":"J Cell Biol"},{"key":"2026070214505714200_ref26","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1242\/jcs.198358","article-title":"Spatial distribution and molecular dynamics of dystrophin glycoprotein components at the neuromuscular junction in vivo","volume":"130","author":"Aittaleb","year":"2017","journal-title":"J Cell Sci"},{"key":"2026070214505714200_ref27","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0896-6273(00)80894-6","article-title":"Maturation and maintenance of the neuromuscular synapse: genetic evidence for roles of the dystrophin--glycoprotein complex","volume":"25","author":"Grady","year":"2000","journal-title":"Neuron"},{"key":"2026070214505714200_ref28","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/0012-1606(91)90340-9","article-title":"Fiber regeneration is not persistent in dystrophic (MDX) mouse skeletal muscle","volume":"148","author":"DiMario","year":"1991","journal-title":"Dev Biol"},{"key":"2026070214505714200_ref29","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/0896-6273(91)90301-F","article-title":"Dystrophin-related protein is localized to neuromuscular junctions of adult skeletal muscle","volume":"7","author":"Ohlendieck","year":"1991","journal-title":"Neuron"},{"key":"2026070214505714200_ref30","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1093\/hmg\/ddac041","article-title":"Distinct roles of the dystrophin-glycoprotein complex: alpha-dystrobrevin and alpha-syntrophin in the maintenance of the postsynaptic apparatus of the neuromuscular synapse","volume":"31","author":"Valenzuela","year":"2022","journal-title":"Hum Mol Genet"},{"key":"2026070214505714200_ref31","doi-asserted-by":"publisher","first-page":"11004","DOI":"10.1523\/JNEUROSCI.1930-10.2010","article-title":"The alpha-syntrophin PH and PDZ domains scaffold acetylcholine receptors, utrophin, and neuronal nitric oxide synthase at the neuromuscular junction","volume":"30","author":"Adams","year":"2010","journal-title":"J Neurosci"},{"key":"2026070214505714200_ref32","doi-asserted-by":"publisher","first-page":"2978","DOI":"10.1093\/hmg\/ddy197","article-title":"Syntrophin binds directly to multiple spectrin-like repeats in dystrophin and mediates binding of nNOS to repeats 16-17","volume":"27","author":"Adams","year":"2018","journal-title":"Hum Mol Genet"},{"key":"2026070214505714200_ref33","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1083\/jcb.138.1.81","article-title":"Differential association of syntrophin pairs with the dystrophin complex","volume":"138","author":"Peters","year":"1997","journal-title":"J Cell Biol"},{"key":"2026070214505714200_ref34","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.bbamem.2013.08.023","article-title":"Dystrophin complex functions as a scaffold for signalling proteins","volume":"1838","author":"Constantin","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"2026070214505714200_ref35","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.3390\/ijms12031660","article-title":"The role of alpha-dystrobrevin in striated muscle","volume":"12","author":"Nakamori","year":"2011","journal-title":"Int J Mol Sci"},{"key":"2026070214505714200_ref36","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1002\/aja.1001980403","article-title":"Expression of the dystrophin-related protein (utrophin) gene during mouse embryogenesis","volume":"198","author":"Schofield","year":"1993","journal-title":"Dev Dyn"},{"key":"2026070214505714200_ref37","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/0022-510X(94)90295-X","article-title":"Does utrophin expression in muscles of mdx mice during postnatal development functionally compensate for dystrophin deficiency?","volume":"122","author":"Pons","year":"1994","journal-title":"J Neurol Sci"},{"key":"2026070214505714200_ref38","doi-asserted-by":"publisher","first-page":"4975","DOI":"10.1074\/jbc.270.10.4975","article-title":"Identification of alpha-syntrophin binding to syntrophin triplet, dystrophin, and utrophin","volume":"270","author":"Yang","year":"1995","journal-title":"J Biol Chem"},{"key":"2026070214505714200_ref39","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1002\/j.2040-4603.2015.tb00638.x","article-title":"The dystrophin complex: structure, function, and implications for therapy","volume":"5","author":"Gao","year":"2015","journal-title":"Compr Physiol"},{"key":"2026070214505714200_ref40","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1152\/jappl.1999.86.3.924","article-title":"Hindlimb immobilization applied to 21-day-old mdx mice prevents the occurrence of muscle degeneration","volume":"86","author":"Mokhtarian","year":"1999","journal-title":"J Appl Physiol (1985)"},{"key":"2026070214505714200_ref41","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/BF00687043","article-title":"Skeletal muscle pathology in X chromosome-linked muscular dystrophy (mdx) mouse","volume":"69","author":"Tanabe","year":"1986","journal-title":"Acta Neuropathol"},{"key":"2026070214505714200_ref42","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.nmd.2003.09.004","article-title":"A-utrophin up-regulation in mdx skeletal muscle is independent of regeneration","volume":"14","author":"Weir","year":"2004","journal-title":"Neuromuscul Disord"},{"key":"2026070214505714200_ref43","doi-asserted-by":"publisher","first-page":"19106","DOI":"10.1074\/jbc.M109642200","article-title":"The utrophin gene is transcriptionally up-regulated in regenerating muscle","volume":"277","author":"Galvagni","year":"2002","journal-title":"J Biol Chem"},{"key":"2026070214505714200_ref44","doi-asserted-by":"publisher","first-page":"C1300","DOI":"10.1152\/ajpcell.2001.281.4.C1300","article-title":"Increased expression of utrophin in a slow vs. a fast muscle involves posttranscriptional events","volume":"281","author":"Gramolini","year":"2001","journal-title":"Am J Physiol-Cell Ph"},{"key":"2026070214505714200_ref45","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1002\/mus.880130813","article-title":"Neuromuscular transmission in the mdx mouse","volume":"13","author":"Nagel","year":"1990","journal-title":"Muscle Nerve"},{"key":"2026070214505714200_ref46","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1083\/jcb.142.5.1269","article-title":"Differential membrane localization and intermolecular associations of alpha-dystrobrevin isoforms in skeletal muscle","volume":"142","author":"Peters","year":"1998","journal-title":"J Cell Biol"},{"key":"2026070214505714200_ref47","doi-asserted-by":"publisher","first-page":"10302","DOI":"10.1523\/JNEUROSCI.3408-04.2004","article-title":"Structural abnormalities at neuromuscular synapses lacking multiple syntrophin isoforms","volume":"24","author":"Adams","year":"2004","journal-title":"J Neurosci"},{"key":"2026070214505714200_ref48","doi-asserted-by":"publisher","first-page":"15586","DOI":"10.1523\/JNEUROSCI.4038-11.2011","article-title":"Nicotinic acetylcholine receptor stability at the NMJ deficient in \u03b1-Syntrophin","volume":"31","author":"Valenzuela","year":"2011","journal-title":"J Neurosci"},{"key":"2026070214505714200_ref49","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1002\/mus.21873","article-title":"Genotyping, and mice by primer competition polymerase chain reaction","volume":"43","author":"Shin","year":"2011","journal-title":"Muscle Nerve"},{"key":"2026070214505714200_ref50","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s41592-020-01018-x","article-title":"Cellpose: a generalist algorithm for cellular segmentation","volume":"18","author":"Stringer","year":"2021","journal-title":"Nat Methods"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/35\/13\/ddag060\/68684618\/ddag060.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/35\/13\/ddag060\/68684618\/ddag060.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:51:04Z","timestamp":1783018264000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/doi\/10.1093\/hmg\/ddag060\/8723826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":50,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2026,6,26]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddag060","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"ddag060"}}