Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy

Blood biochemistry analysis and serum analysis were performed by the Easter Bush Pathology Department, University of Edinburgh. Animal husbandry was performed by Centre for Integrative Physiology bio-research restructure technical staff, University of Edinburgh. Assistance with intravenous injections was provided by Ian Coldicott (University of Sheffield) and Hannah Shorrock (University of Edinburgh). Human blood cDNA was a gift to GH from Kathy Evans, University of Edinburgh. Imaging was performed at the IMPACT imaging facility, University of Edinburgh, with technical assistance from Anisha Kubasik-Thayil. The authors would also like to thank Lyndsay Murray for technical discussions relating to qRT-PCR analysis. This work was supported by funding from the SMA Trust and the Anatomical Society (via grants to THG); the Euan MacDonald Centre for Motor Neurone Disease Research (via grants to THG and SHP); the Wellcome Trust (via grants to EJNG and THG); Muscular Dystrophy UK (via grants to THG and CGB); a Elphinstone Scholarship from the University of Aberdeen (to SHP); and The French Muscular Dystrophy Association (via grants to CM and JC).

Vascular defects and spinal cord hypoxia in spinal muscular atrophy

© 2015 American Neurological Association. Funded by The Euan MacDonald Center for Motor Neurone Disease Research The SMA Trust Muscular Dystrophy UK The SMA Trust The SMA Trust Motor Neurone Disease Association National Institute for Health Research Great Ormond Street Hospital Biomedical Research Center Medical Research Council Great Ormond Street Hospital Charity

Cognitive dysfunction in Duchenne muscular dystrophy: a possible role for neuromodulatory immune molecules

Duchenne muscular dystrophy (DMD) is an X chromosome-linked disease characterized by progressive physical disability, immobility, and premature death in affected boys. Underlying the devastating symptoms of DMD is the loss of dystrophin, a structural protein that connects the extracellular matrix to the cell cytoskeleton and provides protection against contraction-induced damage in muscle cells, leading to chronic peripheral inflammation. However, dystrophin is also expressed in neurons within specific brain regions, including the hippocampus, a structure associated with learning and memory formation. Linked to this, a subset of boys with DMD exhibit nonprogressing cognitive dysfunction, with deficits in verbal, short-term, and working memory. Furthermore, in the genetically comparable dystrophin-deficient mdx mouse model of DMD, some, but not all, types of learning and memory are deficient, and specific deficits in synaptogenesis and channel clustering at synapses has been noted. Little consideration has been devoted to the cognitive deficits associated with DMD compared with the research conducted into the peripheral effects of dystrophin deficiency. Therefore, this review focuses on what is known about the role of full-length dystrophin (Dp427) in hippocampal neurons. The importance of dystrophin in learning and memory is assessed, and the potential importance that inflammatory mediators, which are chronically elevated in dystrophinopathies, may have on hippocampal function is also evaluated.

Assisted standing for Duchenne muscular dystrophy

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of standing devices and orthoses on musculoskeletal impairments (such as pain, contracture, scoliosis development and bone density) in people with DMD, and secondarily to determine their effect on quality of life, participation in activities, and patient experience.

Influencia del polimorfismo del receptor de andrógenos en la masa ósea, masa muscular y condición física en niños y niñas

Programa de doctorado: Actividad Física, Salud y Rendimiento Deportivo

Muscular anatomy of the pectoral and forelimb of caiman crocodilus crocodilus (linnaeus, 1758) (crocodylia: alligatoridae)

v. 17, n. 2, p. 285-295, abr./jun. 2016.

Modellazione 3D e analisi dello stato tenso-deformativo di una calandra per la produzione di tubi di acciaio a saldatura elicoidale

Il lavoro di indagine che è stato sviluppato nella presente tesi è volto a valutare, attraverso metodi FEM, ossia tecniche numeriche computazionali, le sollecitazioni e le deformazioni che agiscono sul telaio di uno "Stampo", macchina che realizza l'operazione di calandratura della lamiera nella produzione di tubi di acciaio a saldatura elicoidale. In particolare l’analisi riportata in questo documento può ritenersi uno studio preliminare che ha lo scopo di creare un simulatore tenso-deformativo che permetta di realizzare un futuro lavoro di validazione del modello, quindi esso è stato realizzato nel modo più flessibile possibile, in modo che sia agevole, anche in un secondo tempo, introdurvi delle modifiche. Il Software utilizzato per la realizzazione dell'analisi FEM è Salomé-Meca accompagnato dal risolutore Code Aster. Oltre all'analisi sul Telaio dello Stampo si è effettuato uno studio preliminare, di validità generale, in cui si riportano in dettaglio le operazioni da effettuare per lo studio degli Assembly. In particolare è stato utilizzato il software Efficient per la creazione del file di comando.

Considerations in the use of high intensity leg cycle ergometry as a test of muscular performance

High intensity leg cycle ergometry is a widely used method of measuring muscular performance during maximal exercise. Until recently, it was deemed to be a predominantly lower body activity; however, there is now evidence to suggest that the upper body could be making a significant contribution to power output, as demonstrated by the intense electrical activity of the forearm musculature. As high intensity cycle ergometry often is used to measure performance in untrained cyclists it is important they are given at least two familiarisation trials to ensure results are both reliable and reproducible. In addition, diurnal variations exist during a single high intensity bout of exercise. It is likely these daily fluctuations are influenced by a number of biochemical and physiological variables. The purpose of this article is to outline factors that contribute to our interpretation of data following high intensity cycle ergometry.

The role of intracellular calcium perturbations in muscle damage and dysfunction in mouse models of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the dystrophin gene. DMD is clinically characterized by severe, progressive and irreversible loss of muscle function, in which most patients lose the ability to walk by their early teens and die by their early 20’s. Impaired intracellular calcium (Ca2+) regulation and activation of cell degradation pathways have been proposed as key contributors to DMD disease progression. This dissertation research consists of three studies investigating the role of intracellular Ca2+ in skeletal muscle dysfunction in different mouse models of DMD. Study one evaluated the role of Ca2+-activated enzymes (proteases) that activate protein degradation in excitation-contraction (E-C) coupling failure following repeated contractions in mdx and dystrophin-utrophin null (mdx/utr-/-) mice. Single muscle fibers from mdx/utr-/- mice had greater E-C coupling failure following repeated contractions compared to fibers from mdx mice. Moreover, protease inhibition during these contractions was sufficient to attenuate E-C coupling failure in muscle fibers from both mdx and mdx/utr-/- mice. Study two evaluated the effects of overexpressing the Ca2+ buffering protein sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1 (SERCA1) in skeletal muscles from mdx and mdx/utr-/- mice. Overall, SERCA1 overexpression decreased muscle damage and protected the muscle from contraction-induced injury in mdx and mdx/utr-/- mice. In study three, the cellular mechanisms underlying the beneficial effects of SERCA1 overexpression in mdx and mdx/utr-/- mice were investigated. SERCA1 overexpression attenuated calpain activation in mdx muscle only, while partially attenuating the degradation of the calpain target desmin in mdx/utr-/- mice. Additionally, SERCA1 overexpression decreased the SERCA-inhibitory protein sarcolipin in mdx muscle but did not alter levels of Ca2+ regulatory proteins (parvalbumin and calsequestrin) in either dystrophic model. Lastly, SERCA1 overexpression blunted the increase in endoplasmic reticulum stress markers Grp78/BiP in mdx mice and C/EBP homologous protein (CHOP) in mdx and mdx/utr-/- mice. Overall, findings from the studies presented in this dissertation provide new insight into the role of Ca2+ in muscle dysfunction and damage in different dystrophic mouse models. Further, these findings support the overall strategy for improving intracellular Ca2+ control for the development of novel therapies for DMD.

Best Practice Guidelines on molecular diagnostics in Duchenne/Becker muscular dystrophies

Meeting participants: Rosário dos Santos, Porto, Portugal

Sistema de armazenamento de energia com base em baterias e no ondulador de tensão trifásico

Dissertação para obtenção do grau de Mestre em Engenharia Electrotécnica Ramo de Automação e Eletrotécnica Ramo de Automação e Eletrónica Industrial

Comparación de la evolución en pacientes con diagnóstico de espasmo muscular en región cervical, dorsal y lumbar, atendidos con masaje manual y pacientes tratados con vibroterapia en las edades de 20 a 70 años de ambos sexos, atendidos en el Hospital Nacional de San Francisco Gotera, departamento de Morazán, en el período de julio a septiembre de 2007.

La investigación se realizó en pacientes con diagnóstico de Espasmo Muscular en región Cervical, Dorsal y Lumbar entre las edades de 20 a 70 años de ambos sexos, atendidos en el Hospital Nacional de San Francisco Gotera, en el período de Julio a Septiembre de 2007, con el objetivo de establecer la comparación de la evolución entre los pacientes atendidos con Masaje Manual y los tratados con Vibroterapia. La muestra estuvo constituida por un total de 12 pacientes, la cual se dividió en dos grupos de 6 pacientes cada uno, en donde se atendió a un grupo con Masaje manual y el otro fue tratado con Vibroterapia. El tipo de estudio aplicado fue prospectivo y comparativo, las técnicas de obtención de información empleadas fueron la Documental como la bibliografía y la de Campo como la entrevista; la primera permitió realizar una amplia revisión de libros y diccionarios y la segunda fue destinada a la población en estudio con el fin de obtener información del estado real del paciente.