Search results for "Muscle"
showing 10 items of 3397 documents
Redox-related biomarkers in physical exercise
2021
Research in redox biology of exercise has made considerable advances in the last 70 years. Since the seminal study of George Pake's group calculating the content of free radicals in skeletal muscle in resting conditions in 1954, many discoveries have been made in the field. The first section of this review is devoted to highlight the main research findings and fundamental changes in the exercise redox biology discipline. It includes: i) the first steps in free radical research, ii) the relation between exercise and oxidative damage, iii) the redox regulation of muscle fatigue, iv) the sources of free radicals during muscle contractions, and v) the role of reactive oxygen species as regulato…
Towards development of a statistical framework to evaluate myotonic dystrophy type 1 mRNA biomarkers in the context of a clinical trial
2020
AbstractMyotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 is caused by the expansion of a CTG repeat in the 3’-untranslated region of DMPK. Longer CTG expansions are associated with greater symptom severity and earlier age at onset. The primary mechanism of pathogenesis is thought to be mediated by a gain of function of the CUG-containing RNA, that leads to trans-dysregulation of RNA metabolism of many other genes. Specifically, the alternative splicing (AS) and alternative polyadenylation (APA) of many genes is known to be disrupted. In the context of clinical trials of emerging DM1 treatments, it is important…
The broad phenotypic spectrum of PPP2R1A -related neurodevelopmental disorders correlates with the degree of biochemical dysfunction
2021
PURPOSE: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. METHODS: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. RESULTS: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay …
rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences
2018
Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats. Interestingly, rbFOX1 competes with MBNL1 for binding to CCUG expanded repeats and overexpression of rbFOX1 partly releases MBNL1 from sequestration within CCUG RNA foci in DM2 muscle ce…
Simple Muscle Architecture Analysis (SMA): An ImageJ macro tool to automate measurements in B-mode ultrasound scans
2020
In vivo measurements of muscle architecture (i.e. the spatial arrangement of muscle fascicles) are routinely included in research and clinical settings to monitor muscle structure, function and plasticity. However, in most cases such measurements are performed manually, and more reliable and time-efficient automated methods are either lacking completely, or are inaccessible to those without expertise in image analysis. In this work, we propose an ImageJ script to automate the entire analysis process of muscle architecture in ultrasound images: Simple Muscle Architecture Analysis (SMA). Images are filtered in the spatial and frequency domains with built-in commands and external plugins to hi…
Influence of middle-distance running on muscular micro RNAs
2018
A specific subset of micro RNAs (miRs), including miR-133 and miR-206, is specifically expressed in muscle tissue, so that they are currently defined as muscular miRs (myomiRs). To further elucidate the role of myomiRs in muscle biology, we measured miR-133a and miR-206 in plasma of 28 middle-age recreational athletes. The study population consisted of 28 middle aged, recreation athletes (11 women and 17 men; mean age, 46 years) who completed a 21.1 km, half-marathon. The plasma concentration of miR-133a and miR-206, the serum concentration of creatine kinase (CK) and high-sensitivity (HS) cardiac troponin T (cTnT), as well as capillary lactate, were measured before and immediately after th…
Morphological Evidence of Telocytes in Skeletal Muscle Interstitium of Exercised and Sedentary Rodents
2021
Skeletal muscle atrophy, resulting from states of hypokinesis or immobilization, leads to morphological, metabolic, and functional changes within the muscle tissue, a large variety of which are supported by the stromal cells populating the interstitium. Telocytes represent a recently discovered population of stromal cells, which has been increasingly identified in several human organs and appears to participate in sustaining cross-talk, promoting regenerative mechanisms and supporting differentiation of local stem cell niche. The aim of this morphologic study was to investigate the presence of Telocytes in the tibialis anterior muscle of healthy rats undergoing an endurance training protoco…
Physiological and Molecular Adaptations to Strength Training
2018
High muscle contraction forces that lead to gains in muscle function, size, and strength characterize resistance exercise training. The purpose of this chapter is to outline the adaptations in myofiber size and metabolism that occur by stimuli of hormones and local growth factors, mechanical and metabolic stress of muscle tissue, and myofibrillar disruptions induced by a resistance exercise bout. The chapter will highlight the network of intracellular pathways (including mTOR signaling) that ultimately lead to increases in gene expression and protein synthesis. Accumulation of acute exercise responses by systematic training over time modulate the muscle proteome that can be observed as chan…
An siRNA-based screen in C2C12 myoblasts identifies novel genes involved in myogenic differentiation
2017
International audience; AbstractMyogenesis is a highly regulated multi-step process involving myoblast proliferation and differentiation. Although studies over the last decades have identified several factors governing these distinct major phases, many of them are not yet known. In order to identify novel genes, we took advantage of the C2C12 myoblastic line to establish a functional siRNA screen combined with quantitative-imaging analysis of a large amount of differentiated myoblasts. We knocked down 100 preselected mouse genes without a previously characterized role in muscle. Using image analysis, we tracked gene-silencing phenotypes by quantitative assessment of cellular density, myotub…
Arsenic promotes NF-Κb-mediated fibroblast dysfunction and matrix remodeling to impair muscle stem cell function
2016
Abstract Arsenic is a global health hazard that impacts over 140 million individuals worldwide. Epidemiological studies reveal prominent muscle dysfunction and mobility declines following arsenic exposure; yet, mechanisms underlying such declines are unknown. The objective of this study was to test the novel hypothesis that arsenic drives a maladaptive fibroblast phenotype to promote pathogenic myomatrix remodeling and compromise the muscle stem (satellite) cell (MuSC) niche. Mice were exposed to environmentally relevant levels of arsenic in drinking water before receiving a local muscle injury. Arsenic-exposed muscles displayed pathogenic matrix remodeling, defective myofiber regeneration …