Inhibitors of endopeptidase and angiotensin-converting enzyme lead to an amplification of the morphological changes and an upregulation of the substance P system in a muscle overuse model

PubMed Central

2014-01-01

Background We have previously observed, in studies on an experimental overuse model, that the tachykinin system may be involved in the processes of muscle inflammation (myositis) and other muscle tissue alterations. To further evaluate the significance of tachykinins in these processes, we have used inhibitors of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), substances which are known to terminate the activity of various endogenously produced substances, including tachykinins. Methods Injections of inhibitors of NEP and ACE, as well as the tachykinin substance P (SP), were given locally outside the tendon of the triceps surae muscle of rabbits subjected to marked overuse of this muscle. A control group was given NaCl injections. Evaluations were made at 1 week, a timepoint of overuse when only mild inflammation and limited changes in the muscle structure are noted in animals not treated with inhibitors. Both the soleus and gastrocnemius muscles were examined morphologically and with immunohistochemistry and enzyme immunoassay (EIA). Results A pronounced inflammation (myositis) and changes in the muscle fiber morphology, including muscle fiber necrosis, occurred in the overused muscles of animals given NEP and ACE inhibitors. The morphological changes were clearly more prominent than for animals subjected to overuse and NaCl injections (NaCl group). A marked SP-like expression, as well as a marked expression of the neurokinin-1 receptor (NK-1R) was found in the affected muscle tissue in response to injections of NEP and ACE inhibitors. The concentration of SP in the muscles was also higher than that for the NaCl group. Conclusions The observations show that the local injections of NEP and ACE inhibitors led to marked SP-like and NK-1R immunoreactions, increased SP concentrations, and an amplification of the morphological changes in the tissue. The injections of the inhibitors thus led to a more marked myositis process and an upregulation of the SP system. Endogenously produced substances, out of which the tachykinins conform to one substance family, may play a role in mediating effects in the tissue in a muscle that is subjected to pronounced overuse. PMID:24725470

Trichinella spiralis: nurse cell formation with emphasis on analogy to muscle cell repair

PubMed Central

Wu, Zhiliang; Sofronic-Milosavljevic, Lj; Nagano, Isao; Takahashi, Yuzo

2008-01-01

Trichinella infection results in formation of a capsule in infected muscles. The capsule is a residence of the parasite which is composed of the nurse cell and fibrous wall. The process of nurse cell formation is complex and includes infected muscle cell response (de-differentiation, cell cycle re-entry and arrest) and satellite cell responses (activation, proliferation and differentiation). Some events that occur during the nurse cell formation are analogous to those occurring during muscle cell regeneration/repair. This article reviews capsule formation with emphasis on this analogy. PMID:18710582

The effects of Capn1 gene inactivation on the differential expression of genes in skeletal muscle

USDA-ARS?s Scientific Manuscript database

Protein turnover is required for muscle growth and regeneration and several proteolytic enzymes, including the calpains, degrade myofibrillar proteins during this process. In a previous experiment, phenotypic differences were observed between µ-calpain knockout (KO) and wild type (WT) mice, includin...

The wasting continuum in heart failure: from sarcopenia to cachexia.

PubMed

von Haehling, Stephan

2015-11-01

Sarcopenia (muscle wasting) and cachexia share some pathophysiological aspects. Sarcopenia affects approximately 20 %, cachexia <10 % of ambulatory patients with heart failure (HF). Whilst sarcopenia means loss of skeletal muscle mass and strength that predominantly affects postural rather than non-postural muscles, cachexia means loss of muscle and fat tissue that leads to weight loss. The wasting continuum in HF implies that skeletal muscle is lost earlier than fat tissue and may lead from sarcopenia to cachexia. Both tissues require conservation, and therapies that stop the wasting process have tremendous therapeutic appeal. The present paper reviews the pathophysiology of muscle and fat wasting in HF and discusses potential treatments, including exercise training, appetite stimulants, essential amino acids, growth hormone, testosterone, electrical muscle stimulation, ghrelin and its analogues, ghrelin receptor agonists and myostatin antibodies.

The regulation of smooth muscle contractility by zipper-interacting protein kinase.

PubMed

Ihara, Eikichi; MacDonald, Justin A

2007-01-01

Smooth muscle contractility is mainly regulated by phosphorylation of the 20 kDa myosin light chains (LC20), a process that is controlled by the opposing activities of myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP). Recently, intensive research has revealed that various protein kinase networks including Rho-kinase, integrin-linked kinase, zipper-interacting protein kinase (ZIPK), and protein kinase C (PKC) are involved in the regulation of LC20 phosphorylation and have important roles in modulating smooth muscle contractile responses to Ca2+ (i.e., Ca2+ sensitization and Ca2+ desensitization). Here, we review the general background and structure of ZIPK and summarize our current understanding of its involvement in a number of cell processes including cell death (apoptosis), cell motility, and smooth muscle contraction. ZIPK has been found to induce the diphosphorylation of LC20 at Ser-19 and Thr-18 in a Ca2+-independent manner and to regulate MLCP activity directly through its phosphorylation of the myosin-targeting subunit of MLCP or indirectly through its phosphorylation of the PKC-potentiated inhibitory protein of MLCP. Future investigations of ZIPK function in smooth muscle will undoubtably focus on determining the mechanisms that regulate its cellular activity, including the identification of upstream signaling pathways, the characterization of autoinhibitory domains and regulatory phosphorylation sites, and the development of specific inhibitor compounds.

Muscle activity and spine load during pulling exercises: influence of stable and labile contact surfaces and technique coaching.

PubMed

McGill, Stuart M; Cannon, Jordan; Andersen, Jordan T

2014-10-01

This study examined pulling exercises performed on stable surfaces and unstable suspension straps. Specific questions included: which exercises challenged particular muscles, what was the magnitude of resulting spine load, and did technique coaching influence results. Fourteen males performed pulling tasks while muscle activity, external force, and 3D body segment motion were recorded. These data were processed and input to a sophisticated and anatomically detailed 3D model that used muscle activity and body segment kinematics to estimate muscle force, in this way the model was sensitive to each individual's choice of motor control for each task. Muscle forces and linked segment joint loads were used to calculate spine loads. There were gradations of muscle activity and spine load characteristics to every task. It appears that suspension straps alter muscle activity less in pulling exercises, compared to studies reporting on pushing exercises. The chin-up and pull-up exercises created the highest spine load as they required the highest muscle activation, despite the body "hanging" under tractioning gravitational load. Coaching shoulder centration through retraction increased spine loading but undoubtedly adds proximal stiffness. An exercise atlas of spine compression was constructed to help with the decision making process of exercise choice for an individual. Copyright © 2014 Elsevier Ltd. All rights reserved.

Small Heat Shock Protein 20 (HspB6) in Cardiac Hypertrophy and Failure

PubMed Central

Fan, Guo-Chang; Kranias, Evangelia G.

2010-01-01

Hsp20, referred to as HspB6, is constitutively expressed in various tissues. Specifically, HspB6 is most highly expressed in different types of muscle including vascular, airway, colonic, bladder, and uterine smooth muscle; cardiac muscle; and skeletal muscle. It can be phosphorylated at Ser-16 by both cAMP- and cGMP-dependent protein kinases (PKA/PKG). Recently, Hsp20 and its phosphorylation have been implicated in multiple physiological and pathophysiological processes including smooth muscle relaxation, platelet aggregation, exercise training, myocardial infarction, atherosclerosis, insulin resistance and Alzheimer’s disease. In the heart, key advances have been made in elucidating the significance of Hsp20 in contractile function and cardioprotection over the last decade. This mini-review highlights exciting findings in animal models and human patients, with special emphasis on the potential salutary effects of Hsp20 in heart disease. PMID:20869365

Reactive oxygen species and calcium signals in skeletal muscle: A crosstalk involved in both normal signaling and disease.

PubMed

Espinosa, Alejandra; Henríquez-Olguín, Carlos; Jaimovich, Enrique

2016-09-01

Reactive Oxygen Species (ROS) have been profusely studied as agents of potential damage to living cells and they have been related to a number of pathological processes. Increasing evidence points to a more positive role of ROS in cell signaling and the detailed mechanism that regulates the precise amount of ROS needed for cell functioning without the deleterious effects of excess ROS still needs to be resolved in detail. In skeletal muscle the main source of ROS during normal functioning appears to be NADPH oxidase 2 (NOX2), which is activated by electrical stimuli (or exercise) through a cascade of events that include ATP release through pannexin1 channels. NOX2 is a protein complex that assembles in the T-tubule membrane before activation and ROS production by NOX2 appears to be important for muscle adaptation through gene expression and mitochondrial biogenesis as well as for improving glucose transport after insulin action. Excess ROS production (or diminished antioxidant defenses) plays a role in a number of pathological processes in skeletal muscle. Together with increased reactive nitrogen species, an increase in ROS appears to have a deleterious role in a model of Duchenne muscular dystrophy as well as muscle wasting in other diseases such as aging sarcopenia and cancer cachexia. In addition, ROS is involved in obesity and muscle insulin resistance, both of which are causally related to type 2 diabetes. A detailed description of the fine-tuning of ROS (including all sources of ROS) in skeletal muscle in health and disease will significantly contribute to our knowledge of both muscle adaptation and muscle related pathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recent advances on the role of long non-coding RNA H19 in regulating mammalian muscle growth and development.

PubMed

Qin, Chen Yu; Cai, He; Qing, Han Rui; Li, Li; Zhang, Hong Ping

2017-12-20

As one of the first identified long non-coding RNAs (lncRNAs), H19 plays a wide range of roles in vivo, including not only as a tumor suppressor and oncogene involved in disease process, but also as a regulator of growth and development of multiple tissues in mammalian embryos. The function of H19 in muscles (both skeletal and cardiac muscle) draws widespread attention due to the following two reasons. On one hand, H19 promotes myogenic differentiation and myogenesis of skeletal muscle satellite cells (SMSCs) via regulating Igf2 in cis. On the other hand, H19 also modulates the target genes in trans, including sponging let-7, miR-106 or miR-29 to mediate myocyte glucose uptake, cardiomyocyte proliferation and tendon repair, as well as promote embryonic development and muscle regeneration through binding to MBD1 as a chromatin modifier. In this review, we summarize the role of H19 in mammalian muscles, which will provide a reference for further research to unveil the molecular mechanism of muscle growth and development.

Gene expression profiling of porcine skeletal muscle in the early recovery phase following acute physical activity.

PubMed

Jensen, Jeanette H; Conley, Lene N; Hedegaard, Jakob; Nielsen, Mathilde; Young, Jette F; Oksbjerg, Niels; Hornshøj, Henrik; Bendixen, Christian; Thomsen, Bo

2012-07-01

Acute physical activity elicits changes in gene expression in skeletal muscles to promote metabolic changes and to repair exercise-induced muscle injuries. In the present time-course study, pigs were submitted to an acute bout of treadmill running until near exhaustion to determine the impact of unaccustomed exercise on global transcriptional profiles in porcine skeletal muscles. Using a combined microarray and candidate gene approach, we identified a suite of genes that are differentially expressed in muscles during postexercise recovery. Several members of the heat shock protein family and proteins associated with proteolytic events, such as the muscle-specific E3 ubiquitin ligase atrogin-1, were significantly upregulated, suggesting that protein breakdown, prevention of protein aggregation and stabilization of unfolded proteins are important processes for restoration of cellular homeostasis. We also detected an upregulation of genes that are associated with muscle cell proliferation and differentiation, including MUSTN1, ASB5 and CSRP3, possibly reflecting activation, differentiation and fusion of satellite cells to facilitate repair of muscle damage. In addition, exercise increased expression of the orphan nuclear hormone receptor NR4A3, which regulates metabolic functions associated with lipid, carbohydrate and energy homeostasis. Finally, we observed an unanticipated induction of the long non-coding RNA transcript NEAT1, which has been implicated in RNA processing and nuclear retention of adenosine-to-inosine edited mRNAs in the ribonucleoprotein bodies called paraspeckles. These findings expand the complexity of pathways affected by acute contractile activity of skeletal muscle, contributing to a better understanding of the molecular processes that occur in muscle tissue in the recovery phase.

Myoblast fusion in Drosophila

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haralalka, Shruti; Abmayr, Susan M., E-mail: sma@stowers.org; Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, MO 66160

2010-11-01

The body wall musculature of a Drosophila larva is composed of an intricate pattern of 30 segmentally repeated muscle fibers in each abdominal hemisegment. Each muscle fiber has unique spatial and behavioral characteristics that include its location, orientation, epidermal attachment, size and pattern of innervation. Many, if not all, of these properties are dictated by founder cells, which determine the muscle pattern and seed the fusion process. Myofibers are then derived from fusion between a specific founder cell and several fusion competent myoblasts (FCMs) fusing with as few as 3-5 FCMs in the small muscles on the most ventral sidemore » of the embryo and as many as 30 FCMs in the larger muscles on the dorsal side of the embryo. The focus of the present review is the formation of the larval muscles in the developing embryo, summarizing the major issues and players in this process. We have attempted to emphasize experimentally-validated details of the mechanism of myoblast fusion and distinguish these from the theoretically possible details that have not yet been confirmed experimentally. We also direct the interested reader to other recent reviews that discuss myoblast fusion in Drosophila, each with their own perspective on the process . With apologies, we use gene nomenclature as specified by Flybase (http://flybase.org) but provide Table 1 with alternative names and references.« less

A fully resolved fluid-structure-muscle-activation model for esophageal transport

NASA Astrophysics Data System (ADS)

Kou, Wenjun; Bhalla, Amneet P. S.; Griffith, Boyce E.; Johnson, Mark; Patankar, Neelesh A.

2013-11-01

Esophageal transport is a mechanical and physiological process that transfers the ingested food bolus from the pharynx to the stomach through a multi-layered esophageal tube. The process involves interactions between the bolus, esophageal wall composed of mucosal, circular muscle (CM) and longitudinal muscle (LM) layers, and neurally coordinated muscle activation including CM contraction and LM shortening. In this work, we present a 3D fully-resolved model of esophageal transport based on the immersed boundary method. The model describes the bolus as a Newtonian fluid, the esophageal wall as a multi-layered elastic tube represented by springs and beams, and the muscle activation as a traveling wave of sequential actuation/relaxation of muscle fibers, represented by springs with dynamic rest lengths. Results on intraluminal pressure profile and bolus shape will be shown, which are qualitatively consistent with experimental observations. Effects of activating CM contraction only, LM shortening only or both, for the bolus transport, are studied. A comparison among them can help to identify the role of each type of muscle activation. The support of grant R01 DK56033 and R01 DK079902 from NIH is gratefully acknowledged.

Structure-function relationship of skeletal muscle provides inspiration for design of new artificial muscle

NASA Astrophysics Data System (ADS)

Gao, Yingxin; Zhang, Chi

2015-03-01

A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure-function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure-function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure-function relationship of skeletal muscle into the design of artificial muscle.

Skeletal muscle hypertrophy and regeneration: interplay between the myogenic regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways.

PubMed

Zanou, Nadège; Gailly, Philippe

2013-11-01

Adult skeletal muscle can regenerate in response to muscle damage. This ability is conferred by the presence of myogenic stem cells called satellite cells. In response to stimuli such as injury or exercise, these cells become activated and express myogenic regulatory factors (MRFs), i.e., transcription factors of the myogenic lineage including Myf5, MyoD, myogenin, and Mrf4 to proliferate and differentiate into myofibers. The MRF family of proteins controls the transcription of important muscle-specific proteins such as myosin heavy chain and muscle creatine kinase. Different growth factors are secreted during muscle repair among which insulin-like growth factors (IGFs) are the only ones that promote both muscle cell proliferation and differentiation and that play a key role in muscle regeneration and hypertrophy. Different isoforms of IGFs are expressed during muscle repair: IGF-IEa, IGF-IEb, or IGF-IEc (also known as mechano growth factor, MGF) and IGF-II. MGF is expressed first and is observed in satellite cells and in proliferating myoblasts whereas IGF-Ia and IGF-II expression occurs at the state of muscle fiber formation. Interestingly, several studies report the induction of MRFs in response to IGFs stimulation. Inversely, IGFs expression may also be regulated by MRFs. Various mechanisms are proposed to support these interactions. In this review, we describe the general process of muscle hypertrophy and regeneration and decipher the interactions between the two groups of factors involved in the process.

Emg Signal Analysis of Healthy and Neuropathic Individuals

NASA Astrophysics Data System (ADS)

Gupta, Ashutosh; Sayed, Tabassum; Garg, Ridhi; Shreyam, Richa

2017-08-01

Electromyography is a method to evaluate levels of muscle activity. When a muscle contracts, an action potential is generated and this circulates along the muscular fibers. In electromyography, electrodes are connected to the skin and the electrical activity of muscles is measured and graph is plotted. The surface EMG signals picked up during the muscular activity are interfaced with a system. The EMG signals from individual suffering from Neuropathy and healthy individual, so obtained, are processed and analyzed using signal processing techniques. This project includes the investigation and interpretation of EMG signals of healthy and Neuropathic individuals using MATLAB. The prospective use of this study is in developing the prosthetic device for the people with Neuropathic disability.

Genetic and environmental effects on the muscle structure response post-mortem.

PubMed

Thompson, J M; Perry, D; Daly, B; Gardner, G E; Johnston, D J; Pethick, D W

2006-09-01

This paper reviewed the mechanisms by which glycolytic rate and pre-rigor stretching of muscle impact on meat quality. If muscle is free to shorten during the rigor process extremes in glycolytic rate can impact negatively on meat quality by inducing either cold or rigor shortening. Factors that contribute to variation in glycolytic rate include the glycogen concentration at slaughter and fibre type of the muscle. Glycolysis is highly sensitive to temperature, which is an important factor in heavy grain fed carcasses. An alternative solution to controlling glycolysis is to stretch the muscle pre-rigor so that it cannot shorten, thus providing an insurance against extremes in processing conditions. Results are presented which show a large reduction in variance (both additive and phenotypic) in tenderness caused by pre-rigor stretching. Whilst this did not impact on the heritability of shear force, it did reduce genotype differences. The implications of these results on the magnitude of genotype effects on tenderness is discussed.

An image processing pipeline to detect and segment nuclei in muscle fiber microscopic images.

PubMed

Guo, Yanen; Xu, Xiaoyin; Wang, Yuanyuan; Wang, Yaming; Xia, Shunren; Yang, Zhong

2014-08-01

Muscle fiber images play an important role in the medical diagnosis and treatment of many muscular diseases. The number of nuclei in skeletal muscle fiber images is a key bio-marker of the diagnosis of muscular dystrophy. In nuclei segmentation one primary challenge is to correctly separate the clustered nuclei. In this article, we developed an image processing pipeline to automatically detect, segment, and analyze nuclei in microscopic image of muscle fibers. The pipeline consists of image pre-processing, identification of isolated nuclei, identification and segmentation of clustered nuclei, and quantitative analysis. Nuclei are initially extracted from background by using local Otsu's threshold. Based on analysis of morphological features of the isolated nuclei, including their areas, compactness, and major axis lengths, a Bayesian network is trained and applied to identify isolated nuclei from clustered nuclei and artifacts in all the images. Then a two-step refined watershed algorithm is applied to segment clustered nuclei. After segmentation, the nuclei can be quantified for statistical analysis. Comparing the segmented results with those of manual analysis and an existing technique, we find that our proposed image processing pipeline achieves good performance with high accuracy and precision. The presented image processing pipeline can therefore help biologists increase their throughput and objectivity in analyzing large numbers of nuclei in muscle fiber images. © 2014 Wiley Periodicals, Inc.

Muscles provide protection during microbial infection by activating innate immune response pathways in Drosophila and zebrafish.

PubMed

Chatterjee, Arunita; Roy, Debasish; Patnaik, Esha; Nongthomba, Upendra

2016-06-01

Muscle contraction brings about movement and locomotion in animals. However, muscles have also been implicated in several atypical physiological processes including immune response. The role of muscles in immunity and the mechanism involved has not yet been deciphered. In this paper, using Drosophila indirect flight muscles (IFMs) as a model, we show that muscles are immune-responsive tissues. Flies with defective IFMs are incapable of mounting a potent humoral immune response. Upon immune challenge, the IFMs produce anti-microbial peptides (AMPs) through the activation of canonical signaling pathways, and these IFM-synthesized AMPs are essential for survival upon infection. The trunk muscles of zebrafish, a vertebrate model system, also possess the capacity to mount an immune response against bacterial infections, thus establishing that immune responsiveness of muscles is evolutionarily conserved. Our results suggest that physiologically fit muscles might boost the innate immune response of an individual. © 2016. Published by The Company of Biologists Ltd.

Antisense long non-coding RNAs in rainbow trout: Discovery and potential role in muscle growth and quality traits

USDA-ARS?s Scientific Manuscript database

Endogenous mRNA-antisense transcripts are involved in regulation of a wide range of biological processes including muscle development and quality traits of farm animals. Standard RNA-Seq can be used to identify sense-antisense transcripts. However, strand-specific RNA-Seq is required to resolve ambi...

Methods for the Organogenesis of Skeletal Muscle in Tissue Culture

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman; Shansky, Janet; DelTatto, Michael; Chromiak, Joseph

1997-01-01

Skeletal muscle structure is regulated by many factors, including nutrition, hormones, electrical activity, and tension. The muscle cells are subjected to both passive and active mechanical forces at all stages of development and these forces play important but poorly understood roles in regulating muscle organogenesis and growth. For example, during embryogenesis, the rapidly growing skeleton places large passive mechanical forces on the attached muscle tissue. These forces not only help to organize the proliferating mononucleated myoblasts into the oriented, multinucleated myofibers of a functional muscle but also tightly couple the growth rate of muscle to that of bone. Postnatally, the actively contracting, innervated muscle fibers are subjected to different patterns of active and passive tensions which regulate longitudinal and cross sectional myofiber growth. These mechanically-induced organogenic processes have been difficult to study under normal tissue culture conditions, resulting in the development of numerous methods and specialized equipment to simulate the in vivo mechanical environment.These techniques have led to the "engineering" of bioartificial muscles (organoids) which display many of the characteristics of in vivo muscle including parallel arrays of postmitotic fibers organized into fascicle-like structures with tendon-like ends. They are contractile, express adult isoforms of contractile proteins, perform directed work, and can be maintained in culture for long periods. The in vivo-like characteristics and durability of these muscle organoids make them useful for long term in vitro studies on mechanotransduction mechanisms and on muscle atrophy induced by decreased tension. In this report, we described a simple method for generating muscle organoids from either primary embrionic avain or neonatal rodent myoblasts.

Voltage clamp methods for the study of membrane currents and SR Ca2+ release in adult skeletal muscle fibres

PubMed Central

Hernández-Ochoa, Erick O.; Schneider, Martin F.

2012-01-01

Skeletal muscle excitation-contraction (E-C)1 coupling is a process composed of multiple sequential stages, by which an action potential triggers sarcoplasmic reticulum (SR)2 Ca2+ release and subsequent contractile activation. The various steps in the E-C coupling process in skeletal muscle can be studied using different techniques. The simultaneous recordings of sarcolemmal electrical signals and the accompanying elevation in myoplasmic Ca2+, due to depolarization-initiated SR Ca2+ release in skeletal muscle fibres, have been useful to obtain a better understanding of muscle function. In studying the origin and mechanism of voltage dependency of E-C coupling a variety of different techniques have been used to control the voltage in adult skeletal fibres. Pioneering work in muscles isolated from amphibians or crustaceans used microelectrodes or ‘high resistance gap’ techniques to manipulate the voltage in the muscle fibres. The development of the patch clamp technique and its variant, the whole-cell clamp configuration that facilitates the manipulation of the intracellular environment, allowed the use of the voltage clamp techniques in different cell types, including skeletal muscle fibres. The aim of this article is to present an historical perspective of the voltage clamp methods used to study skeletal muscle E-C coupling as well as to describe the current status of using the whole-cell patch clamp technique in studies in which the electrical and Ca2+ signalling properties of mouse skeletal muscle membranes are being investigated. PMID:22306655

Skeletal muscle repair in a mouse model of nemaline myopathy

PubMed Central

Sanoudou, Despina; Corbett, Mark A.; Han, Mei; Ghoddusi, Majid; Nguyen, Mai-Anh T.; Vlahovich, Nicole; Hardeman, Edna C.; Beggs, Alan H.

2012-01-01

Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly understood. To address this question, we examined gene expression patterns in an NM mouse model carrying the human Met9Arg mutation of alpha-tropomyosin slow (Tpm3). We assessed five different skeletal muscles from affected mice, which are representative of muscles with differing fiber-type compositions, different physiological specializations and variable degrees of pathology. Although these same muscles in non-affected mice showed marked variation in patterns of gene expression, with diaphragm being the most dissimilar, the presence of the mutant protein in nemaline muscles resulted in a more similar pattern of gene expression among the muscles. This result suggests a common process or mechanism operating in nemaline muscles independent of the variable degrees of pathology. Transcriptional and protein expression data indicate the presence of a repair process and possibly delayed maturation in nemaline muscles. Markers indicative of satellite cell number, activated satellite cells and immature fibers including M-Cadherin, MyoD, desmin, Pax7 and Myf6 were elevated by western-blot analysis or immunohistochemistry. Evidence suggesting elevated focal repair was observed in nemaline muscle in electron micrographs. This analysis reveals that NM is characterized by a novel repair feature operating in multiple different muscles. PMID:16877500

Skeletal muscle repair in a mouse model of nemaline myopathy.

PubMed

Sanoudou, Despina; Corbett, Mark A; Han, Mei; Ghoddusi, Majid; Nguyen, Mai-Anh T; Vlahovich, Nicole; Hardeman, Edna C; Beggs, Alan H

2006-09-01

Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly understood. To address this question, we examined gene expression patterns in an NM mouse model carrying the human Met9Arg mutation of alpha-tropomyosin slow (Tpm3). We assessed five different skeletal muscles from affected mice, which are representative of muscles with differing fiber-type compositions, different physiological specializations and variable degrees of pathology. Although these same muscles in non-affected mice showed marked variation in patterns of gene expression, with diaphragm being the most dissimilar, the presence of the mutant protein in nemaline muscles resulted in a more similar pattern of gene expression among the muscles. This result suggests a common process or mechanism operating in nemaline muscles independent of the variable degrees of pathology. Transcriptional and protein expression data indicate the presence of a repair process and possibly delayed maturation in nemaline muscles. Markers indicative of satellite cell number, activated satellite cells and immature fibers including M-Cadherin, MyoD, desmin, Pax7 and Myf6 were elevated by western-blot analysis or immunohistochemistry. Evidence suggesting elevated focal repair was observed in nemaline muscle in electron micrographs. This analysis reveals that NM is characterized by a novel repair feature operating in multiple different muscles.

[Regulatory mechanism for lncRNAs in skeletal muscle development and progress on its research in domestic animals].

PubMed

Zhou, Rui; Wang, Yi Xin; Long, Ke Ren; Jiang, An An; Jin, Long

2018-04-20

Skeletal muscle is an essential tissue to maintain the normal functions of an organism. It is also closely associated with important economic performance, such as carcass weight, of domestic animals. In recent years, studies using high-throughput sequencing techniques have identified numerous long non-coding RNAs (lncRNAs) with myogenic functions involved in regulation of gene expression at multiple levels, including epigenetic, transcriptional and post-transcriptional regulation. These lncRNAs target myogenic factors, which participate in all processes of skeletal muscle development, including proliferation, migration and differentiation of skeletal muscle stem cells, proliferation, differentiation and fusion of myocytes, muscle hypertrophy and conversion of muscle fiber types. In this review, we summarize the functional roles of lncRNAs in regulation of myogenesis in humans and mice, describe the methods for the analysis of lncRNA function, discuss the progress of lncRNA research in domestic animals, and highlight the current problems and challenges in lncRNA research on livestock production. We hope to provide a useful reference for research on lncRNA in domestic animals, thereby further identifying the molecular regulatory mechanisms in skeletal muscle growth and development.

De novo transcriptome assembly and identification of genes associated with feed conversion ratio and breast muscle yield in domestic ducks.

PubMed

Zhu, Feng; Yuan, Jian-Ming; Zhang, Zhen-He; Hao, Jin-Ping; Yang, Yu-Ze; Hu, Shen-Qiang; Yang, Fang-Xi; Qu, Lu-Jiang; Hou, Zhuo-Cheng

2015-12-01

Breast muscle yield and feed conversion efficiency are the major breeding aims in duck breeding. Understanding the role of specific transcripts in the muscle and small intestine might lead to the elucidation of interrelated biological processes. In this study, we obtained jejunum and breast muscle samples from two strains of Peking ducks that were sorted by feed conversion ratio (FCR) and breast muscle percentage into two-tailed populations. Ten RNA-Seq libraries were developed from the pooled samples and sequenced using the Hiseq2000 platform. We created a reference duck transcript database using de novo assembly methods, which included 16 663 irredundant contigs with an N50 length of 1530 bp. This new duck reference cDNA dataset significantly improved the mapping rate for RNA-Seq data, from 50% to 70%. Mapping and annotation were followed by Gene Ontology analysis, which showed that numerous genes were differentially expressed between the low and high FCR groups. The differentially expressed genes in the jejunum were enriched in biological processes related to immune response and immune response activation, whereas those in the breast muscle were significantly enriched in biological processes related to muscle cell differentiation and organ development. We identified new candidate genes, that is, PCK1, for improving the FCR and breast muscle yield of ducks and obtained much better reference duck transcripts. This study suggested that de novo assembly is essential when applying transcriptome analysis to a species with an incomplete genome. © 2015 Stichting International Foundation for Animal Genetics.

Role of TGF-β signaling in inherited and acquired myopathies

PubMed Central

2011-01-01

The transforming growth factor-beta (TGF-β) superfamily consists of a variety of cytokines expressed in many different cell types including skeletal muscle. Members of this superfamily that are of particular importance in skeletal muscle are TGF-β1, mitogen-activated protein kinases (MAPKs), and myostatin. These signaling molecules play important roles in skeletal muscle homeostasis and in a variety of inherited and acquired neuromuscular disorders. Expression of these molecules is linked to normal processes in skeletal muscle such as growth, differentiation, regeneration, and stress response. However, chronic elevation of TGF-β1, MAPKs, and myostatin is linked to various features of muscle pathology, including impaired regeneration and atrophy. In this review, we focus on the aberrant signaling of TGF-β in various disorders such as Marfan syndrome, muscular dystrophies, sarcopenia, and critical illness myopathy. We also discuss how the inhibition of several members of the TGF-β signaling pathway has been implicated in ameliorating disease phenotypes, opening up novel therapeutic avenues for a large group of neuromuscular disorders. PMID:21798096

Effects of Geniposide from Gardenia Fruit Pomace on Skeletal-Muscle Fibrosis.

PubMed

Pan, Haiou; Li, Yan; Qian, Haifeng; Qi, Xiguang; Wu, Gangcheng; Zhang, Hui; Xu, Meijuan; Rao, Zhiming; Li, Jin-Long; Wang, Li; Ying, Hao

2018-05-30

Geniposide is the main bioactive constituent of gardenia fruit. Skeletal-muscle fibrosis is a common and irreversibly damaging process. Numerous studies have shown that geniposide could improve many chronic diseases, including metabolic syndrome and tumors. However, the effects of geniposide on skeletal-muscle fibrosis are still poorly understood. Here, we found that crude extracts of gardenia fruit pomace could significantly decrease the expression of profibrotic genes in vitro. Moreover, geniposide could also reverse profibrotic-gene expression induced by TGF-β and Smad4, a regulator of skeletal-muscle fibrosis. In addition, geniposide treatment could significantly downregulate profibrotic-gene expression and improve skeletal-muscle injuries in a mouse model of contusion. These results together suggest that geniposide has an antifibrotic effect on skeletal muscle through the suppression of the TGF-β-Smad4 signaling pathway.

Impact of oxidative stress on exercising skeletal muscle.

PubMed

Steinbacher, Peter; Eckl, Peter

2015-04-10

It is well established that muscle contractions during exercise lead to elevated levels of reactive oxygen species (ROS) in skeletal muscle. These highly reactive molecules have many deleterious effects, such as a reduction of force generation and increased muscle atrophy. Since the discovery of exercise-induced oxidative stress several decades ago, evidence has accumulated that ROS produced during exercise also have positive effects by influencing cellular processes that lead to increased expression of antioxidants. These molecules are particularly elevated in regularly exercising muscle to prevent the negative effects of ROS by neutralizing the free radicals. In addition, ROS also seem to be involved in the exercise-induced adaptation of the muscle phenotype. This review provides an overview of the evidences to date on the effects of ROS in exercising muscle. These aspects include the sources of ROS, their positive and negative cellular effects, the role of antioxidants, and the present evidence on ROS-dependent adaptations of muscle cells in response to physical exercise.

PABPN1-Dependent mRNA Processing Induces Muscle Wasting

PubMed Central

Raz, Yotam; van Putten, Maaike; Paniagua-Soriano, Guillem; Krom, Yvonne D.; Florea, Bogdan I.; Raz, Vered

2016-01-01

Poly(A) Binding Protein Nuclear 1 (PABPN1) is a multifunctional regulator of mRNA processing, and its expression levels specifically decline in aging muscles. An expansion mutation in PABPN1 is the genetic cause of oculopharyngeal muscle dystrophy (OPMD), a late onset and rare myopathy. Moreover, reduced PABPN1 expression correlates with symptom manifestation in OPMD. PABPN1 regulates alternative polyadenylation site (PAS) utilization. However, the impact of PAS utilization on cell and tissue function is poorly understood. We hypothesized that altered PABPN1 expression levels is an underlying cause of muscle wasting. To test this, we stably down-regulated PABPN1 in mouse tibialis anterior (TA) muscles by localized injection of adeno-associated viruses expressing shRNA to PABPN1 (shPab). We found that a mild reduction in PABPN1 levels causes muscle pathology including myofiber atrophy, thickening of extracellular matrix and myofiber-type transition. Moreover, reduced PABPN1 levels caused a consistent decline in distal PAS utilization in the 3’-UTR of a subset of OPMD-dysregulated genes. This alternative PAS utilization led to up-regulation of Atrogin-1, a key muscle atrophy regulator, but down regulation of proteasomal genes. Additionally reduced PABPN1 levels caused a reduction in proteasomal activity, and transition in MyHC isotope expression pattern in myofibers. We suggest that PABPN1-mediated alternative PAS utilization plays a central role in aging-associated muscle wasting. PMID:27152426

Ulk1-mediated autophagy plays an essential role in mitochondrial remodeling and functional regeneration of skeletal muscle

PubMed Central

Call, Jarrod A.; Wilson, Rebecca J.; Laker, Rhianna C.; Zhang, Mei; Kundu, Mondira

2017-01-01

Autophagy is a conserved cellular process for degrading aggregate proteins and dysfunctional organelle. It is still debatable if autophagy and mitophagy (a specific process of autophagy of mitochondria) play important roles in myogenic differentiation and functional regeneration of skeletal muscle. We tested the hypothesis that autophagy is critical for functional regeneration of skeletal muscle. We first observed time-dependent increases (3- to 6-fold) of autophagy-related proteins (Atgs), including Ulk1, Beclin1, and LC3, along with reduced p62 expression during C2C12 differentiation, suggesting increased autophagy capacity and flux during myogenic differentiation. We then used cardiotoxin (Ctx) or ischemia-reperfusion (I/R) to induce muscle injury and regeneration and observed increases in Atgs between days 2 and 7 in adult skeletal muscle followed by increased autophagy flux after day 7. Since Ulk1 has been shown to be essential for mitophagy, we asked if Ulk1 is critical for functional regeneration in skeletal muscle. We subjected skeletal muscle-specific Ulk1 knockout mice (MKO) to Ctx or I/R. MKO mice had significantly impaired recovery of muscle strength and mitochondrial protein content post-Ctx or I/R. Imaging analysis showed that MKO mice have significantly attenuated recovery of mitochondrial network at 7 and 14 days post-Ctx. These findings suggest that increased autophagy protein and flux occur during muscle regeneration and Ulk1-mediated mitophagy is critical for recovery for the mitochondrial network and hence functional regeneration. PMID:28356270

Nutritional strategies of physically active subjects with muscle dysmorphia.

PubMed

Contesini, Nadir; Adami, Fernando; Blake, Márcia de-Toledo; Monteiro, Carlos Bm; Abreu, Luiz C; Valenti, Vitor E; Almeida, Fernando S; Luciano, Alexandre P; Cardoso, Marco A; Benedet, Jucemar; de Assis Guedes de Vasconcelos, Francisco; Leone, Claudio; Frainer, Deivis Elton Schlickmann

2013-05-26

The aim of this study was to identify dietary strategies for physically active individuals with muscle dysmorphia based on a systematic literature review. References were included if the study population consisted of adults over 18 years old who were physically active in fitness centers. We identified reports through an electronic search ofScielo, Lilacs and Medline using the following keywords: muscle dysmorphia, vigorexia, distorted body image, and exercise. We found eight articles in Scielo, 17 in Medline and 12 in Lilacs. Among the total number of 37 articles, only 17 were eligible for inclusion in this review. The results indicated that the feeding strategies used by physically active individuals with muscle dysmorphia did not include planning or the supervision of a nutritionist. Diet included high protein and low fat foods and the ingestion of dietary and ergogenic supplements to reduce weight. Physically active subjects with muscle dysmorphia could benefit from the help of nutritional professionals to evaluate energy estimation, guide the diet and its distribution in macronutrient and consider the principle of nutrition to functional recovery of the digestive process, promote liver detoxification, balance and guide to organic adequate intake of supplemental nutrients and other substances.

Nutritional strategies of physically active subjects with muscle dysmorphia

PubMed Central

2013-01-01

Background The aim of this study was to identify dietary strategies for physically active individuals with muscle dysmorphia based on a systematic literature review. Method References were included if the study population consisted of adults over 18 years old who were physically active in fitness centers. We identified reports through an electronic search ofScielo, Lilacs and Medline using the following keywords: muscle dysmorphia, vigorexia, distorted body image, and exercise. We found eight articles in Scielo, 17 in Medline and 12 in Lilacs. Among the total number of 37 articles, only 17 were eligible for inclusion in this review. Results The results indicated that the feeding strategies used by physically active individuals with muscle dysmorphia did not include planning or the supervision of a nutritionist. Diet included high protein and low fat foods and the ingestion of dietary and ergogenic supplements to reduce weight. Conclusion Physically active subjects with muscle dysmorphia could benefit from the help of nutritional professionals to evaluate energy estimation, guide the diet and its distribution in macronutrient and consider the principle of nutrition to functional recovery of the digestive process, promote liver detoxification, balance and guide to organic adequate intake of supplemental nutrients and other substances. PMID:23706013

Thigh muscle segmentation of chemical shift encoding-based water-fat magnetic resonance images: The reference database MyoSegmenTUM.

PubMed

Schlaeger, Sarah; Freitag, Friedemann; Klupp, Elisabeth; Dieckmeyer, Michael; Weidlich, Dominik; Inhuber, Stephanie; Deschauer, Marcus; Schoser, Benedikt; Bublitz, Sarah; Montagnese, Federica; Zimmer, Claus; Rummeny, Ernst J; Karampinos, Dimitrios C; Kirschke, Jan S; Baum, Thomas

2018-01-01

Magnetic resonance imaging (MRI) can non-invasively assess muscle anatomy, exercise effects and pathologies with different underlying causes such as neuromuscular diseases (NMD). Quantitative MRI including fat fraction mapping using chemical shift encoding-based water-fat MRI has emerged for reliable determination of muscle volume and fat composition. The data analysis of water-fat images requires segmentation of the different muscles which has been mainly performed manually in the past and is a very time consuming process, currently limiting the clinical applicability. An automatization of the segmentation process would lead to a more time-efficient analysis. In the present work, the manually segmented thigh magnetic resonance imaging database MyoSegmenTUM is presented. It hosts water-fat MR images of both thighs of 15 healthy subjects and 4 patients with NMD with a voxel size of 3.2x2x4 mm3 with the corresponding segmentation masks for four functional muscle groups: quadriceps femoris, sartorius, gracilis, hamstrings. The database is freely accessible online at https://osf.io/svwa7/?view_only=c2c980c17b3a40fca35d088a3cdd83e2. The database is mainly meant as ground truth which can be used as training and test dataset for automatic muscle segmentation algorithms. The segmentation allows extraction of muscle cross sectional area (CSA) and volume. Proton density fat fraction (PDFF) of the defined muscle groups from the corresponding images and quadriceps muscle strength measurements/neurological muscle strength rating can be used for benchmarking purposes.

Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice.

PubMed

Camporez, João-Paulo G; Petersen, Max C; Abudukadier, Abulizi; Moreira, Gabriela V; Jurczak, Michael J; Friedman, Glenn; Haqq, Christopher M; Petersen, Kitt Falk; Shulman, Gerald I

2016-02-23

Sarcopenia, or skeletal muscle atrophy, is a debilitating comorbidity of many physiological and pathophysiological processes, including normal aging. There are no approved therapies for sarcopenia, but the antihypertrophic myokine myostatin is a potential therapeutic target. Here, we show that treatment of young and old mice with an anti-myostatin antibody (ATA 842) for 4 wk increased muscle mass and muscle strength in both groups. Furthermore, ATA 842 treatment also increased insulin-stimulated whole body glucose metabolism in old mice, which could be attributed to increased insulin-stimulated skeletal muscle glucose uptake as measured by a hyperinsulinemic-euglycemic clamp. Taken together, these studies provide support for pharmacological inhibition of myostatin as a potential therapeutic approach for age-related sarcopenia and metabolic disease.

[Muscle biopsy in children: Usefulness in 2012].

PubMed

Cuisset, J-M; Maurage, C-A; Carpentier, A; Briand, G; Thévenon, A; Rouaix, N; Vallée, L

2013-01-01

Muscle biopsy is a mainstay diagnostic tool for investigating neuromuscular disorders in children. We report the yield of pediatric muscle biopsy in a population of 415 children by a retrospective study of 419 biopsies performed between 1/01/2000 and 31/12/2009 in a neuropediatric department, including mitochondrial respiratory chain analysis for 87 children. Two hundred and fifty-five biopsies were from boys (61%) 164 from girls (39%). Their mean age at biopsy was 6.5years; 155 (37%) biopsies were obtained before the child was 5years old. Final histopathological diagnoses were: congenital myopathy (n=193, including 15 structural congenital myopathies); progressive muscular dystrophy (n=75 [18%] including 57 dystrophinopathies); congenital muscular dystrophy (n=17, including six primary merosinopathies); dermatomyositis (n=11); spinal muscular atrophy (n=9, including six atypical spinal muscular atrophies); metabolic myopathy (n=32, including 19 mitochondrial myopathies); encephalomyopathy (n=53 [13%], including 27 with a mitochondrial respiratory chain defect). Pathological diagnosis remained undetermined in 16 cases. In 184 patients (44%), the muscle biopsy revealed specific histopathological anomalies (dystrophic process; specific ultrastructural abnormalities; perifascicular atrophy; neurogenic atrophy; metabolic anomalies) enabling a precise etiological diagnosis. For 85% of progressive muscular dystrophies, the biopsy resulted in a genetic diagnosis after identification of the protein defect. In 15% of the congenital myopathies, histopathological anomalies focused attention on one or several genes. Concerning dystrophinopathies, quantification of dystrophin deficiency on the biopsy specimen contributed to the definition of the clinical phenotype: Duchenne, or Becker. In children with a myopathy, muscle biopsy is often indispensable to establish the etiological diagnosis. Based on the results from this series, muscle biopsy can provide a precise orientation in 45% of patients, leading to a genetic hypothesis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Fabrication and Properties of Composite Artificial Muscles Based on Nylon and a Shape Memory Alloy

NASA Astrophysics Data System (ADS)

Yin, Haibin; Zhou, Jia; Li, Junfeng; Joseph, Vincent S.

2018-05-01

This paper focuses on the design, fabrication and investigation of the mechanical properties of new artificial muscles formed by twisting and annealing. The artificial muscles designed by twisting nylon have become a popular topic in the field of smart materials due to their high mechanical performance with a large deformation and power density. However, the complexity of the heating and cooling system required to control the nylon muscle is a disadvantage, so we have proposed a composite artificial muscle for providing a direct electricity-driven actuation by integrating nylon and a shape memory alloy (SMA). In this paper, the design and fabrication process of these composite artificial muscles are introduced before their mechanical properties, which include the deformation, stiffness, load and response, are investigated. The results show that these composite artificial muscles that integrate nylon and a SMA provide better mechanical properties and yield up to a 44.1% deformation and 3.43 N driving forces. The good performance and direct electro-thermal actuation make these composite muscles ideal for driving robots in a method similar to human muscles.

The molecular signature of muscle stem cells is driven by nutrient availability and innate cell metabolism.

PubMed

Ryall, James G; Lynch, Gordon S

2018-07-01

To discuss how innate muscle stem-cell metabolism and nutrient availability can provide temporal regulation of chromatin accessibility and transcription. Fluorescence-activated cell sorting coupled with whole transcriptome sequencing revealed for the first time that quiescent and proliferating skeletal muscle stem cells exhibit a process of metabolic reprogramming, from fatty-acid oxidation during quiescence to glycolysis during proliferation. Using a combination of immunofluorescence and chromatin immunoprecipitation sequencing, this shift in metabolism has been linked to altered availability of key metabolites essential for histone (de)acetylation and (de)methylation, including acetyl-CoA, s-adenosylmethionine and α-ketoglutarate. Importantly, these changes in metabolite availability have been linked to muscle stem-cell function. Together, these results provide greater insight into how muscle stem cells interact with their local environment, with important implications for metabolic diseases, skeletal muscle regeneration and cell-transplantation therapies.

Novel Tyrosine Phosphorylation Sites in Rat Skeletal Muscle Revealed by Phosphopeptide Enrichment and HPLC-ESI-MS/MS

PubMed Central

Zhang, Xiangmin; Højlund, Kurt; Luo, Moulun; Meyer, Christian; Thangiah, Geetha; Yi, Zhengping

2012-01-01

Tyrosine phosphorylation plays a fundamental role in many cellular processes including differentiation, growth and insulin signaling. In insulin resistant muscle, aberrant tyrosine phosphorylation of several proteins has been detected. However, due to the low abundance of tyrosine phosphorylation (<1% of total protein phosphorylation), only a few tyrosine phosphorylation sites have been identified in mammalian skeletal muscle to date. Here, we used immunoprecipitation of phosphotyrosine peptides prior to HPLC-ESI-MS/MS analysis to improve the discovery of tyrosine phosphorylation in relatively small skeletal muscle biopsies from rats. This resulted in the identification of 87 distinctly localized tyrosine phosphorylation sites in 46 muscle proteins. Among them, 31 appear to be novel. The tyrosine phosphorylated proteins included major enzymes in the glycolytic pathway and glycogen metabolism, sarcomeric proteins, and proteins involved in Ca2+ homeostasis and phosphocreatine resynthesis. Among proteins regulated by insulin, we found tyrosine phosphorylation sites in glycogen synthase, and two of its inhibitors, GSK-3α and DYRK1A. Moreover, tyrosine phosphorylation sites were identified in several MAP kinases and a protein tyrosine phosphatase, SHPTP2. These results provide the largest catalogue of mammalian skeletal muscle tyrosine phosphorylation sites to date and provide novel targets for the investigation of human skeletal muscle phosphoproteins in various disease states. PMID:22609512

The use of transcranial magnetic stimulation to evaluate cortical excitability of lower limb musculature: Challenges and opportunities.

PubMed

Kesar, Trisha M; Stinear, James W; Wolf, Steven L

2018-05-05

Neuroplasticity is a fundamental yet relatively unexplored process that can impact rehabilitation of lower extremity (LE) movements. Transcranial magnetic stimulation (TMS) has gained widespread application as a non-invasive brain stimulation technique for evaluating neuroplasticity of the corticospinal pathway. However, a majority of TMS studies have been performed on hand muscles, with a paucity of TMS investigations focused on LE muscles. This perspective review paper proposes that there are unique methodological challenges associated with using TMS to evaluate corticospinal excitability of lower limb muscles. The challenges include: (1) the deeper location of the LE motor homunculus; (2) difficulty with targeting individual LE muscles during TMS; and (3) differences in corticospinal circuity controlling upper and lower limb muscles. We encourage future investigations that modify traditional methodological approaches to help address these challenges. Systematic TMS investigations are needed to determine the extent of overlap in corticomotor maps for different LE muscles. A simple, yet informative methodological solution involves simultaneous recordings from multiple LE muscles, which will provide the added benefit of observing how other relevant muscles co-vary in their responses during targeted TMS assessment directed toward a specific muscle. Furthermore, conventionally used TMS methods (e.g., determination of hot spot location and motor threshold) may need to be modified for TMS studies involving LE muscles. Additional investigations are necessary to determine the influence of testing posture as well as activation state of adjacent and distant LE muscles on TMS-elicited responses. An understanding of these challenges and solutions specific to LE TMS will improve the ability of neurorehabilitation clinicians to interpret TMS literature, and forge novel future directions for neuroscience research focused on elucidating neuroplasticity processes underlying locomotion and gait training.

Respiratory muscle function and exercise limitation in patients with chronic obstructive pulmonary disease: a review.

PubMed

Charususin, Noppawan; Dacha, Sauwaluk; Gosselink, Rik; Decramer, Marc; Von Leupoldt, Andreas; Reijnders, Thomas; Louvaris, Zafeiris; Langer, Daniel

2018-01-01

Respiratory muscle dysfunction is common and contributes to dyspnea and exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Improving dynamic function of respiratory muscles during exercise might help to reduce symptoms and improve exercise capacity. Areas covered: The aims of this review are to 1) summarize physiological mechanisms linking respiratory muscle dysfunction to dyspnea and exercise limitation; 2) provide an overview of available therapeutic approaches to better maintain load-capacity balance of respiratory muscles during exercise; and 3) to summarize current knowledge on potential mechanisms explaining effects of interventions aimed at optimizing dynamic respiratory muscle function with a special focus on inspiratory muscle training. Expert commentary: Several mechanisms which are potentially linking improvements in dynamic respiratory muscle function to symptomatic and functional benefits have not been studied so far in COPD patients. Examples of underexplored areas include the study of neural processes related to the relief of acute dyspnea and the competition between respiratory and peripheral muscles for limited energy supplies during exercise. Novel methodologies are available to non-invasively study these mechanisms. Better insights into the consequences of dynamic respiratory muscle dysfunction will hopefully contribute to further refine and individualize therapeutic approaches in patients with COPD.

Length adaptation of airway smooth muscle.

PubMed

Bossé, Ynuk; Sobieszek, Apolinary; Paré, Peter D; Seow, Chun Y

2008-01-01

Many types of smooth muscle, including airway smooth muscle (ASM), are capable of generating maximal force over a large length range due to length adaptation, which is a relatively rapid process in which smooth muscle regains contractility after experiencing a force decrease induced by length fluctuation. Although the underlying mechanism is unclear, it is believed that structural malleability of smooth muscle cells is essential for the adaptation to occur. The process is triggered by strain on the cell cytoskeleton that results in a series of yet undefined biochemical and biophysical events leading to restructuring of the cytoskeleton and contractile apparatus and consequently optimization of the overlap between the myosin and actin filaments. Although length adaptability is an intrinsic property of smooth muscle, maladaptation of ASM could result in excessive constriction of the airways and the inability of deep inspirations to dilate them. In this article, we describe the phenomenon of length adaptation in ASM and some possible underlying mechanisms that involve the myosin filament assembly and disassembly. We discuss a possible role of maladaptation of ASM in the pathogenesis of asthma. We believe that length adaptation in ASM is mediated by specific proteins and their posttranslational regulations involving covalent modifications, such as phosphorylation. The discovery of these molecules and the processes that regulate their activity will greatly enhance our understanding of the basic mechanisms of ASM contraction and will suggest molecular targets to alleviate asthma exacerbation related to excessive constriction of the airways.

Poorly Understood Aspects of Striated Muscle Contraction

PubMed Central

Månsson, Alf

2015-01-01

Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs. PMID:25961006

Poorly understood aspects of striated muscle contraction.

PubMed

Månsson, Alf; Rassier, Dilson; Tsiavaliaris, Georgios

2015-01-01

Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs.

Skeletal muscle plasticity: cellular and molecular responses to altered physical activity paradigms

NASA Technical Reports Server (NTRS)

Baldwin, Kenneth M.; Haddad, Fadia

2002-01-01

The goal of this article is to examine our current understanding of the chain of events known to be involved in the adaptive process whereby specific genes and their protein products undergo altered expression; specifically, skeletal muscle adaptation in response to altered loading states will be discussed, with a special focus on the regulation of the contractile protein, myosin heavy chain gene expression. This protein, which is both an important structural and regulatory protein comprising the contractile apparatus, can be expressed as different isoforms, thereby having an impact on the functional diversity of the muscle. Because the regulation of the myosin gene family is under the control of a complex set of processes including, but not limited to, activity, hormonal, and metabolic factors, this protein will serve as a cellular "marker" for studies of muscle plasticity in response to various mechanical perturbations in which the quantity and type of myosin isoform, along with other important cellular proteins, are altered in expression.

Mechanistic basis of manual therapy in myofascial injuries. Sonoelastographic evolution control.

PubMed

Martínez Rodríguez, Raúl; Galán del Río, Fernando

2013-04-01

The term myofascia is referred to the skeleton of muscle fibres organized as an interconnected 3D network that surrounds and connects the musculoskeletal system. Extracellular matrix muscle is relevant in tissue structural support and transmission of mechanical signals between fibres and tendons. Acute and chronic musculoskeletal injuries (muscle strain) are one of the major problems faced by those who practice any type of sport, regardless of whether they are professionals or amateurs. Therapeutic boarding is of uncertain value in most cases because there are many contributing factors such as type, severity, functional implication of the damaged tissue, progression or risk of relapse. Different studies suggest that the musculoskeletal cell matrix is essential for the development, maintenance and regeneration of skeletal muscle. In this article, we highlight the action of "non-contractile" structures, in particular the myofascial system or muscle fascia, which can be responsible for the pathophysiology and healing process of muscular injuries. Manual therapy plays a predominant role in the treatment of these types of injuries and is key in the process of obtaining a scar capable of transmitting mechanical information. The scientific basis of this process is described in this article. Through real-time sonoelastography we have accurate information regarding the current stage of the repair process and, thus, guide our treatment at all times. Some new concepts are introduced, including local elasticity, the relationship between fascial pretension and the different stages of the physiological myofascia repair process, scar modelling technique, and sonoelastographic evolution control. Copyright © 2012 Elsevier Ltd. All rights reserved.

Challenging the role of pH in skeletal muscle fatigue.

PubMed

Stackhouse, S K; Reisman, D S; Binder-Macleod, S A

2001-12-01

Muscle fatigue is frequently defined as a temporary loss in force- or torque-generating ability because of recent, repetitive muscle contraction (1). The development of this temporary loss of force is a complex process and results from the failure of a number of processes, including motor unit recruitment and firing rate, chemical transmission across the neuromuscular junction, propagation of the action potential along the muscle membrane and T tubules, Ca2+ release from the sarcoplasmic reticulum (SR), Ca2+ binding to troponin C, and cross-bridge cycling (for detailed reviews, see Bigland-Ritchie and Woods(1), McLester(2), and Favero(3)). Muscle fatigue may limit the time a person can stand, the distance a person can ambulate, or the number of stairs a person can ascend or descend. In practical terms, however, we cannot know what actually leads to a decline in function for a given patient. For a phenomenon that may have profound clinical implications, muscle fatigue often receives inadequate attention in physiology textbooks, many of which contain a page or less of information on the entire topic (4-8). In addition, many textbooks report that muscle fatigue is mainly the result of a decrease in pH within the muscle cell due to a rise in hydrogen ion concentration ([H+]) resulting from anaerobic metabolism and the accumulation of lactic acid (6-8). Recent literature, however, contradicts this assertion (9-10). The purpose of this update, therefore, is to provide a brief review of the role of pH in the development of muscle fatigue.

Ulk1-mediated autophagy plays an essential role in mitochondrial remodeling and functional regeneration of skeletal muscle.

PubMed

Call, Jarrod A; Wilson, Rebecca J; Laker, Rhianna C; Zhang, Mei; Kundu, Mondira; Yan, Zhen

2017-06-01

Autophagy is a conserved cellular process for degrading aggregate proteins and dysfunctional organelle. It is still debatable if autophagy and mitophagy (a specific process of autophagy of mitochondria) play important roles in myogenic differentiation and functional regeneration of skeletal muscle. We tested the hypothesis that autophagy is critical for functional regeneration of skeletal muscle. We first observed time-dependent increases (3- to 6-fold) of autophagy-related proteins (Atgs), including Ulk1, Beclin1, and LC3, along with reduced p62 expression during C2C12 differentiation, suggesting increased autophagy capacity and flux during myogenic differentiation. We then used cardiotoxin (Ctx) or ischemia-reperfusion (I/R) to induce muscle injury and regeneration and observed increases in Atgs between days 2 and 7 in adult skeletal muscle followed by increased autophagy flux after day 7 Since Ulk1 has been shown to be essential for mitophagy, we asked if Ulk1 is critical for functional regeneration in skeletal muscle. We subjected skeletal muscle-specific Ulk1 knockout mice (MKO) to Ctx or I/R. MKO mice had significantly impaired recovery of muscle strength and mitochondrial protein content post-Ctx or I/R. Imaging analysis showed that MKO mice have significantly attenuated recovery of mitochondrial network at 7 and 14 days post-Ctx. These findings suggest that increased autophagy protein and flux occur during muscle regeneration and Ulk1-mediated mitophagy is critical for recovery for the mitochondrial network and hence functional regeneration. Copyright © 2017 the American Physiological Society.

Myositis-specific autoantibodies are specific for myositis compared to genetic muscle disease.

PubMed

Mammen, Andrew L; Casciola-Rosen, Livia; Christopher-Stine, Lisa; Lloyd, Thomas E; Wagner, Kathryn R

2015-12-01

To determine the specificity of myositis-specific autoantibodies (MSAs) for autoimmune myopathy compared with inherited muscle diseases. Serum samples from 47 patients with genetically confirmed inherited muscle diseases were screened for the most common MSAs, including those recognizing TIF1γ, NXP2, Mi2, MDA5, Jo1, SRP, and HMGCR. We compared these results with the findings in a cohort of patients with dermatomyositis (DM) previously screened for anti-TIF1γ, -NXP2, -Mi2, -MDA5, and -Jo1. Overall, the presence of anti-TIF1γ, -NXP2, -Mi2, -MDA5, or -Jo1 was 96% specific and 67% sensitive for DM compared to patients with genetic muscle diseases. No patients with inherited muscle disease had anti-SRP or anti-HMGCR autoantibodies. Only 2 patients with genetic muscle disease had a MSA. One patient with anti-Mi2 autoantibodies had both genetically confirmed facioscapulohumeral dystrophy and dermatomyositis based on a typical skin rash and partial response to immunosuppressive medications. A second patient with anti-Jo-1 autoantibodies had both genetically defined limb-girdle muscular dystrophy type 2A (i.e., calpainopathy) and a systemic autoimmune process based on biopsy-confirmed lupus nephritis, sicca symptoms, and anti-Ro52 autoantibodies. The MSAs tested for in this study are highly specific for autoimmune muscle disease and are rarely, if ever, found in patients who only have genetic muscle disease. In patients with genetic muscle disease, the presence of a MSA should suggest the possibility of a coexisting autoimmune process.

Myositis-specific autoantibodies are specific for myositis compared to genetic muscle disease

PubMed Central

Casciola-Rosen, Livia; Christopher-Stine, Lisa; Lloyd, Thomas E.; Wagner, Kathryn R.

2015-01-01

Objective: To determine the specificity of myositis-specific autoantibodies (MSAs) for autoimmune myopathy compared with inherited muscle diseases. Methods: Serum samples from 47 patients with genetically confirmed inherited muscle diseases were screened for the most common MSAs, including those recognizing TIF1γ, NXP2, Mi2, MDA5, Jo1, SRP, and HMGCR. We compared these results with the findings in a cohort of patients with dermatomyositis (DM) previously screened for anti-TIF1γ, -NXP2, -Mi2, -MDA5, and -Jo1. Results: Overall, the presence of anti-TIF1γ, -NXP2, -Mi2, -MDA5, or -Jo1 was 96% specific and 67% sensitive for DM compared to patients with genetic muscle diseases. No patients with inherited muscle disease had anti-SRP or anti-HMGCR autoantibodies. Only 2 patients with genetic muscle disease had a MSA. One patient with anti-Mi2 autoantibodies had both genetically confirmed facioscapulohumeral dystrophy and dermatomyositis based on a typical skin rash and partial response to immunosuppressive medications. A second patient with anti-Jo-1 autoantibodies had both genetically defined limb-girdle muscular dystrophy type 2A (i.e., calpainopathy) and a systemic autoimmune process based on biopsy-confirmed lupus nephritis, sicca symptoms, and anti-Ro52 autoantibodies. Conclusions: The MSAs tested for in this study are highly specific for autoimmune muscle disease and are rarely, if ever, found in patients who only have genetic muscle disease. In patients with genetic muscle disease, the presence of a MSA should suggest the possibility of a coexisting autoimmune process. PMID:26668818

Systematic review of the synergist muscle ablation model for compensatory hypertrophy.

PubMed

Terena, Stella Maris Lins; Fernandes, Kristianne Porta Santos; Bussadori, Sandra Kalill; Deana, Alessandro Melo; Mesquita-Ferrari, Raquel Agnelli

2017-02-01

The aim was to evaluate the effectiveness of the experimental synergists muscle ablation model to promote muscle hypertrophy, determine the period of greatest hypertrophy and its influence on muscle fiber types and determine differences in bilateral and unilateral removal to reduce the number of animals used in this model. Following the application of the eligibility criteria for the mechanical overload of the plantar muscle in rats, nineteen papers were included in the review. The results reveal a greatest hypertrophy occurring between days 12 and 15, and based on the findings, synergist muscle ablation is an efficient model for achieving rapid hypertrophy and the contralateral limb can be used as there was no difference between unilateral and bilateral surgery, which reduces the number of animals used in this model. This model differs from other overload models (exercise and training) regarding the characteristics involved in the hypertrophy process (acute) and result in a chronic muscle adaptation with selective regulation and modification of fast-twitch fibers in skeletal muscle. This is an efficient and rapid model for compensatory hypertrophy.

Skeletal muscle wasting: new role of nonclassical renin-angiotensin system.

PubMed

Cabello-Verrugio, Claudio; Rivera, Juan C; Garcia, Dominga

2017-05-01

Skeletal muscle can be affected by many physiological and pathological conditions that contribute to the development of muscle weakness, including skeletal muscle loss, inflammatory processes, or fibrosis. Therefore, research into therapeutic treatment alternatives or alleviation of these effects on skeletal muscle is of great importance. Recent studies have shown that angiotensin (1-7) [Ang-(1-7)] - a vasoactive peptide of the nonclassical axis in the renin-angiotensin system (RAS) - and its Mas receptor are expressed in skeletal muscle. Ang-(1-7), through its Mas receptor, prevents or diminishes deleterious effects induced by skeletal muscle disease or injury. Specifically, the Ang-(1-7)-Mas receptor axis modulates molecular mechanisms involved in muscle mass regulation, such as the ubiquitin proteasome pathway, the insulin-like growth factor type 1/Akt (protein kinase B) pathway, or myonuclear apoptosis, and also inflammation and fibrosis pathways. Although further research into this topic and the possible side effects of Ang-(1-7) is necessary, these findings are promising, and suggest that the Ang-(1-7)-Mas axis can be considered a possible therapeutic target for treating patients with muscular disorders.

Genome-wide identification and characterization of long non-coding RNAs in developmental skeletal muscle of fetal goat.

PubMed

Zhan, Siyuan; Dong, Yao; Zhao, Wei; Guo, Jiazhong; Zhong, Tao; Wang, Linjie; Li, Li; Zhang, Hongping

2016-08-22

Long non-coding RNAs (lncRNAs) have been studied extensively over the past few years. Large numbers of lncRNAs have been identified in mouse, rat, and human, and some of them have been shown to play important roles in muscle development and myogenesis. However, there are few reports on the characterization of lncRNAs covering all the development stages of skeletal muscle in livestock. RNA libraries constructed from developing longissimus dorsi muscle of fetal (45, 60, and 105 days of gestation) and postnatal (3 days after birth) goat (Capra hircus) were sequenced. A total of 1,034,049,894 clean reads were generated. Among them, 3981 lncRNA transcripts corresponding to 2739 lncRNA genes were identified, including 3515 intergenic lncRNAs and 466 anti-sense lncRNAs. Notably, in pairwise comparisons between the libraries of skeletal muscle at the different development stages, a total of 577 transcripts were differentially expressed (P < 0.05) which were validated by qPCR using randomly selected six lncRNA genes. The identified goat lncRNAs shared some characteristics, such as fewer exons and shorter length, with the lncRNAs in other mammals. We also found 1153 lncRNAs genes were neighbored 1455 protein-coding genes (<10 kb upstream and downstream) and functionally enriched in transcriptional regulation and development-related processes, indicating they may be in cis-regulatory relationships. Additionally, Pearson's correlation coefficients of co-expression levels suggested 1737 lncRNAs and 19,422 mRNAs were possibly in trans-regulatory relationships (r > 0.95 or r < -0.95). These co-expressed mRNAs were enriched in development-related biological processes such as muscle system processes, regulation of cell growth, muscle cell development, regulation of transcription, and embryonic morphogenesis. This study provides a catalog of goat muscle-related lncRNAs, and will contribute to a fuller understanding of the molecular mechanism underpinning muscle development in mammals.

Identification of the essential protein domains for Mib2 function during the development of the Drosophila larval musculature and adult flight muscles.

PubMed

Domsch, Katrin; Acs, Andreas; Obermeier, Claudia; Nguyen, Hanh T; Reim, Ingolf

2017-01-01

The proper differentiation and maintenance of myofibers is fundamental to a functional musculature. Disruption of numerous mostly structural factors leads to perturbations of these processes. Among the limited number of known regulatory factors for these processes is Mind bomb2 (Mib2), a muscle-associated E3 ubiquitin ligase, which was previously established to be required for maintaining the integrity of larval muscles. In this study, we have examined the mechanistic aspects of Mib2 function by performing a detailed functional dissection of the Mib2 protein. We show that the ankyrin repeats, in its entirety, and the hitherto uncharacterized Mib-specific domains (MIB), are important for the major function of Mib2 in skeletal and visceral muscles in the Drosophila embryo. Furthermore, we characterize novel mib2 alleles that have arisen from a forward genetic screen aimed at identifying regulators of myogenesis. Two of these alleles are viable, but flightless hypomorphic mib2 mutants, and harbor missense mutations in the MIB domain and RING finger, respectively. Functional analysis of these new alleles, including in vivo imaging, demonstrates that Mib2 plays an additional important role in the development of adult thorax muscles, particularly in maintaining the larval templates for the dorsal longitudinal indirect flight muscles during metamorphosis.

Cancer cachexia-induced muscle atrophy: evidence for alterations in microRNAs important for muscle size.

PubMed

Lee, David E; Brown, Jacob L; Rosa-Caldwell, Megan E; Blackwell, Thomas A; Perry, Richard A; Brown, Lemuel A; Khatri, Bhuwan; Seo, Dongwon; Bottje, Walter G; Washington, Tyrone A; Wiggs, Michael P; Kong, Byung-Whi; Greene, Nicholas P

2017-05-01

Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy; however, less is known specifically on miRNAs in cancer cachexia. The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition. Phosphate-buffered saline (PBS) or Lewis lung carcinoma cells (LLC) were injected into C57BL/6J mice at 8 wk of age. LLC animals were allowed to develop tumors for 4 wk to induce cachexia. Tibialis anterior muscles were extracted and processed to isolate small RNAs, which were used for miRNA sequencing. Sequencing results were assembled with mature miRNAs, and functions of miRNAs were analyzed by Ingenuity Pathway Analysis. LLC animals developed tumors that contributed to significantly smaller tibialis anterior muscles (18.5%) and muscle cross-sectional area (40%) compared with PBS. We found 371 miRNAs to be present in the muscle above background levels. Of these, nine miRNAs were found to be differentially expressed. Significantly altered groups of miRNAs were categorized into primary functionalities including cancer, cell-to-cell signaling, and cellular development among others. Gene network analysis predicted specific alterations of factors contributing to muscle size including Akt, FOXO3, and others. These results create a foundation for future research into the sufficiency of targeting these genes to attenuate muscle loss in cancer cachexia. Copyright © 2017 the American Physiological Society.

SMASH - semi-automatic muscle analysis using segmentation of histology: a MATLAB application.

PubMed

Smith, Lucas R; Barton, Elisabeth R

2014-01-01

Histological assessment of skeletal muscle tissue is commonly applied to many areas of skeletal muscle physiological research. Histological parameters including fiber distribution, fiber type, centrally nucleated fibers, and capillary density are all frequently quantified measures of skeletal muscle. These parameters reflect functional properties of muscle and undergo adaptation in many muscle diseases and injuries. While standard operating procedures have been developed to guide analysis of many of these parameters, the software to freely, efficiently, and consistently analyze them is not readily available. In order to provide this service to the muscle research community we developed an open source MATLAB script to analyze immunofluorescent muscle sections incorporating user controls for muscle histological analysis. The software consists of multiple functions designed to provide tools for the analysis selected. Initial segmentation and fiber filter functions segment the image and remove non-fiber elements based on user-defined parameters to create a fiber mask. Establishing parameters set by the user, the software outputs data on fiber size and type, centrally nucleated fibers, and other structures. These functions were evaluated on stained soleus muscle sections from 1-year-old wild-type and mdx mice, a model of Duchenne muscular dystrophy. In accordance with previously published data, fiber size was not different between groups, but mdx muscles had much higher fiber size variability. The mdx muscle had a significantly greater proportion of type I fibers, but type I fibers did not change in size relative to type II fibers. Centrally nucleated fibers were highly prevalent in mdx muscle and were significantly larger than peripherally nucleated fibers. The MATLAB code described and provided along with this manuscript is designed for image processing of skeletal muscle immunofluorescent histological sections. The program allows for semi-automated fiber detection along with user correction. The output of the code provides data in accordance with established standards of practice. The results of the program have been validated using a small set of wild-type and mdx muscle sections. This program is the first freely available and open source image processing program designed to automate analysis of skeletal muscle histological sections.

A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice.

PubMed

Porter, John D; Khanna, Sangeeta; Kaminski, Henry J; Rao, J Sunil; Merriam, Anita P; Richmonds, Chelliah R; Leahy, Patrick; Li, Jingjin; Guo, Wei; Andrade, Francisco H

2002-02-01

Mutations in dystrophin cause Duchenne muscular dystrophy (DMD), but absent dystrophin does not invariably cause necrosis in all muscles, life stages and species. Using DNA microarray, we established a molecular signature of dystrophinopathy in the mdx mouse, with evidence that secondary mechanisms are key contributors to pathogenesis. We used variability controls, adequate replicates and stringent analytic tools, including significance analysis of microarrays to estimate and manage false positive rates. In leg muscle, we identified 242 differentially expressed genes, >75% of which have not been previously reported as altered in human or animal dystrophies. Data provide evidence for coordinated activity of numerous components of a chronic inflammatory response, including cytokine and chemokine signaling, leukocyte adhesion and diapedesis, invasive cell type-specific markers, and complement system activation. Selective chemokine upregulation was confirmed by RT-PCR and immunoblot, and may be a key determinant of the nature of the inflammatory response in dystrophic muscle. Up-regulation of secreted phosphoprotein 1 (minopontin, osteopontin) mRNA and protein in dystrophic muscle identified a novel linkage between inflammatory cells and repair processes. Extracellular matrix genes were up-regulated in mdx to levels similar to those in DMD. Since, unlike DMD, mdx exhibits little fibrosis, data suggest that collagen regulation at post-transcriptional stages mediates extensive fibrosis in DMD. Taken together, these data identify a relatively neglected aspect of DMD, suggest new treatment avenues, and highlight the value of genome-wide profiling in study of complex disease processes.

EMGD-FE: an open source graphical user interface for estimating isometric muscle forces in the lower limb using an EMG-driven model

PubMed Central

2014-01-01

Background This paper describes the “EMG Driven Force Estimator (EMGD-FE)”, a Matlab® graphical user interface (GUI) application that estimates skeletal muscle forces from electromyography (EMG) signals. Muscle forces are obtained by numerically integrating a system of ordinary differential equations (ODEs) that simulates Hill-type muscle dynamics and that utilises EMG signals as input. In the current version, the GUI can estimate the forces of lower limb muscles executing isometric contractions. Muscles from other parts of the body can be tested as well, although no default values for model parameters are provided. To achieve accurate evaluations, EMG collection is performed simultaneously with torque measurement from a dynamometer. The computer application guides the user, step-by-step, to pre-process the raw EMG signals, create inputs for the muscle model, numerically integrate the ODEs and analyse the results. Results An example of the application’s functions is presented using the quadriceps femoris muscle. Individual muscle force estimations for the four components as well the knee isometric torque are shown. Conclusions The proposed GUI can estimate individual muscle forces from EMG signals of skeletal muscles. The estimation accuracy depends on several factors, including signal collection and modelling hypothesis issues. PMID:24708668

EMGD-FE: an open source graphical user interface for estimating isometric muscle forces in the lower limb using an EMG-driven model.

PubMed

Menegaldo, Luciano Luporini; de Oliveira, Liliam Fernandes; Minato, Kin K

2014-04-04

This paper describes the "EMG Driven Force Estimator (EMGD-FE)", a Matlab® graphical user interface (GUI) application that estimates skeletal muscle forces from electromyography (EMG) signals. Muscle forces are obtained by numerically integrating a system of ordinary differential equations (ODEs) that simulates Hill-type muscle dynamics and that utilises EMG signals as input. In the current version, the GUI can estimate the forces of lower limb muscles executing isometric contractions. Muscles from other parts of the body can be tested as well, although no default values for model parameters are provided. To achieve accurate evaluations, EMG collection is performed simultaneously with torque measurement from a dynamometer. The computer application guides the user, step-by-step, to pre-process the raw EMG signals, create inputs for the muscle model, numerically integrate the ODEs and analyse the results. An example of the application's functions is presented using the quadriceps femoris muscle. Individual muscle force estimations for the four components as well the knee isometric torque are shown. The proposed GUI can estimate individual muscle forces from EMG signals of skeletal muscles. The estimation accuracy depends on several factors, including signal collection and modelling hypothesis issues.

Is back pain during childhood or adolescence associated with muscle strength, muscle endurance or aerobic capacity: three systematic literature reviews with one meta-analysis.

PubMed

Lardon, Arnaud; Leboeuf-Yde, Charlotte; Le Scanff, Christine

2015-01-01

Back pain is a common condition during childhood and adolescence. The causes of back pain are largely unknown but it seems plausible that some physical factors such as back muscle strength, back muscle endurance and aerobic capacity may play a role in its development, in particular in the early years. The objectives of this review were to investigate in childhood and adolescence 1) if muscular strength in trunk extension is associated with back pain, 2) if muscular endurance in trunk extension is associated with back pain and 3) if aerobic capacity is associated with back pain. Three systematic critical literature reviews with one meta-analysis. Systematic searches were made in June 2014 in PubMed, Embase and SportDiscus including longitudinal, retrospective or cross-sectional studies on back pain for subjects <20 years. Articles were accepted if they were written in French or English. The review process followed the AMSTAR recommendations. The possibility of conducting a meta-analysis was assessed for each research question. Four articles were included for the first objective, four for the second and three for the last. None of the included articles found an association between back muscle strength in extension and back pain. For the second objective, a protective association between back muscle endurance in extension and back pain was found, later confirmed in a meta-analysis (OR = 0.75, 95 % CI 0.58-0.98). The association between aerobic capacity and back pain is not clear. High back muscle endurance in extension appears protective of back pain in youngsters, but the roles of high back muscle strength in extension and aerobic capacity are less clear.

Tropomyosin 4 defines novel filaments in skeletal muscle associated with muscle remodelling/regeneration in normal and diseased muscle.

PubMed

Vlahovich, Nicole; Schevzov, Galina; Nair-Shaliker, Visalini; Ilkovski, Biljana; Artap, Stanley T; Joya, Josephine E; Kee, Anthony J; North, Kathryn N; Gunning, Peter W; Hardeman, Edna C

2008-01-01

The organisation of structural proteins in muscle into highly ordered sarcomeres occurs during development, regeneration and focal repair of skeletal muscle fibers. The involvement of cytoskeletal proteins in this process has been documented, with nonmuscle gamma-actin found to play a role in sarcomere assembly during muscle differentiation and also shown to be up-regulated in dystrophic muscles which undergo regeneration and repair [Lloyd et al.,2004; Hanft et al.,2006]. Here, we show that a cytoskeletal tropomyosin (Tm), Tm4, defines actin filaments in two novel compartments in muscle fibers: a Z-line associated cytoskeleton (Z-LAC), similar to a structure we have reported previously [Kee et al.,2004], and longitudinal filaments that are orientated parallel to the sarcomeric apparatus, present during myofiber growth and repair/regeneration. Tm4 is upregulated in paradigms of muscle repair including induced regeneration and focal repair and in muscle diseases with repair/regeneration features, muscular dystrophy and nemaline myopathy. Longitudinal Tm4-defined filaments also are present in diseased muscle. Transition of the Tm4-defined filaments from a longitudinal to a Z-LAC orientation is observed during the course of muscle regeneration. This Tm4-defined cytoskeleton is a marker of growth and repair/regeneration in response to injury, disease state and stress in skeletal muscle.

Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice.

PubMed

Bal, Naresh C; Singh, Sushant; Reis, Felipe C G; Maurya, Santosh K; Pani, Sunil; Rowland, Leslie A; Periasamy, Muthu

2017-10-06

Thermogenesis is an important homeostatic mechanism essential for survival and normal physiological functions in mammals. Both brown adipose tissue (BAT) ( i.e. uncoupling protein 1 (UCP1)-based) and skeletal muscle ( i.e. sarcolipin (SLN)-based) thermogenesis processes play important roles in temperature homeostasis, but their relative contributions differ from small to large mammals. In this study, we investigated the functional interplay between skeletal muscle- and BAT-based thermogenesis under mild versus severe cold adaptation by employing UCP1 -/- and SLN -/- mice. Interestingly, adaptation of SLN -/- mice to mild cold conditions (16 °C) significantly increased UCP1 expression, suggesting increased reliance on BAT-based thermogenesis. This was also evident from structural alterations in BAT morphology, including mitochondrial architecture, increased expression of electron transport chain proteins, and depletion of fat droplets. Similarly, UCP1 -/- mice adapted to mild cold up-regulated muscle-based thermogenesis, indicated by increases in muscle succinate dehydrogenase activity, SLN expression, mitochondrial content, and neovascularization, compared with WT mice. These results further confirm that SLN-based thermogenesis is a key player in muscle non-shivering thermogenesis (NST) and can compensate for loss of BAT activity. We also present evidence that the increased reliance on BAT-based NST depends on increased autonomic input, as indicated by abundant levels of tyrosine hydroxylase and neuropeptide Y. Our findings demonstrate that both BAT and muscle-based NST are equally recruited during mild and severe cold adaptation and that loss of heat production from one thermogenic pathway leads to increased recruitment of the other, indicating a functional interplay between these two thermogenic processes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Three dimensional digital reconstruction of the jaw adductor musculature of the extinct marsupial giant Diprotodon optatum

PubMed Central

2014-01-01

The morphology and arrangement of the jaw adductor muscles in vertebrates reflects masticatory style and feeding processes, diet and ecology. However, gross muscle anatomy is rarely preserved in fossils and is, therefore, heavily dependent on reconstructions. An undeformed skull of the extinct marsupial, Diprotodon optatum, recovered from Pleistocene sediments at Bacchus Marsh in Victoria, represents the most complete and best preserved specimen of the species offering a unique opportunity to investigate functional anatomy. Computed tomography (CT) scans and digital reconstructions make it possible to visualise internal cranial anatomy and predict location and morphology of soft tissues, including muscles. This study resulted in a 3D digital reconstruction of the jaw adductor musculature of Diprotodon, revealing that the arrangement of muscles is similar to that of kangaroos and that the muscle actions were predominantly vertical. 3D digital muscle reconstructions provide considerable advantages over 2D reconstructions for the visualisation of the spatial arrangement of the individual muscles and the measurement of muscle properties (length, force vectors and volume). Such digital models can further be used to estimate muscle loads and attachment sites for biomechanical analyses. PMID:25165628

Bioactive peptides from meat muscle and by-products: generation, functionality and application as functional ingredients.

PubMed

Lafarga, Tomas; Hayes, Maria

2014-10-01

Bioactive peptides are sequences of between 2-30 amino acids in length that impart a positive health effect to the consumer when ingested. They have been identified from a range of foods, including milk and muscle sources including beef, chicken, pork and marine muscles. The myriad of peptides identified from these sources have known antihypertensive, opioid, antioxidant, antithrombotic and other bioactivities. Indeed, bioactive peptides could play a role in the prevention of diseases associated with the development of metabolic syndrome and mental health diseases. The aim of this work is to present an overview of the bioactive peptides identified in muscle proteins and by-products generated during the processing of meat. The paper looks at the isolation, enrichment and characterisation strategies that have been employed to date to generate bioactive peptides and the potential future applications of these peptides in functional foods for the prevention of heart and mental health problems and obesity. Copyright © 2014 Elsevier Ltd. All rights reserved.

The mechanisms of cachexia underlying muscle dysfunction in COPD.

PubMed

Remels, A H V; Gosker, H R; Langen, R C J; Schols, A M W J

2013-05-01

Pulmonary cachexia is a prevalent, debilitating, and well-recognized feature of COPD associated with increased mortality and loss of peripheral and respiratory muscle function. The exact cause and underlying mechanisms of cachexia in COPD are still poorly understood. Increasing evidence, however, shows that pathological changes in intracellular mechanisms of muscle mass maintenance (i.e., protein turnover and myonuclear turnover) are likely involved. Potential factors triggering alterations in these mechanisms in COPD include oxidative stress, myostatin, and inflammation. In addition to muscle wasting, peripheral muscle in COPD is characterized by a fiber-type shift toward a more type II, glycolytic phenotype and an impaired oxidative capacity (collectively referred to as an impaired oxidative phenotype). Atrophied diaphragm muscle in COPD, however, displays an enhanced oxidative phenotype. Interestingly, intrinsic abnormalities in (lower limb) peripheral muscle seem more pronounced in either cachectic patients or weight loss-susceptible emphysema patients, suggesting that muscle wasting and intrinsic changes in peripheral muscle's oxidative phenotype are somehow intertwined. In this manuscript, we will review alterations in mechanisms of muscle mass maintenance in COPD and discuss the involvement of oxidative stress, inflammation, and myostatin as potential triggers of cachexia. Moreover, we postulate that an impaired muscle oxidative phenotype in COPD can accelerate the process of cachexia, as it renders muscle in COPD less energy efficient, thereby contributing to an energy deficit and weight loss when not dietary compensated. Furthermore, loss of peripheral muscle oxidative phenotype may increase the muscle's susceptibility to inflammation- and oxidative stress-induced muscle damage and wasting.

Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy.

PubMed

Carberry, Steven; Brinkmeier, Heinrich; Zhang, Yaxin; Winkler, Claudia K; Ohlendieck, Kay

2013-09-01

Duchenne muscular dystrophy is due to genetic abnormalities in the dystrophin gene and represents one of the most frequent genetic childhood diseases. In the X-linked muscular dystrophy (mdx) mouse model of dystrophinopathy, different subtypes of skeletal muscles are affected to a varying degree albeit the same single base substitution within exon 23 of the dystrophin gene. Thus, to determine potential muscle subtype-specific differences in secondary alterations due to a deficiency in dystrophin, in this study, we carried out a comparative histological and proteomic survey of mdx muscles. We intentionally included the skeletal muscles that are often used for studying the pathomechanism of muscular dystrophy. Histological examinations revealed a significantly higher degree of central nucleation in the soleus and extensor digitorum longus muscles compared with the flexor digitorum brevis and interosseus muscles. Muscular hypertrophy of 20-25% was likewise only observed in the soleus and extensor digitorum longus muscles from mdx mice, but not in the flexor digitorum brevis and interosseus muscles. For proteomic analysis, muscle protein extracts were separated by fluorescence two-dimensional (2D) gel electrophoresis. Proteins with a significant change in their expression were identified by mass spectrometry. Proteomic profiling established an altered abundance of 24, 17, 19 and 5 protein species in the dystrophin-deficient soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscle, respectively. The key proteomic findings were verified by immunoblot analysis. The identified proteins are involved in the contraction-relaxation cycle, metabolite transport, muscle metabolism and the cellular stress response. Thus, histological and proteomic profiling of muscle subtypes from mdx mice indicated that distinct skeletal muscles are differentially affected by the loss of the membrane cytoskeletal protein, dystrophin. Varying degrees of perturbed protein expression patterns in the muscle subtypes from mdx mice may be due to dissimilar downstream events, including differences in muscle structure or compensatory mechanisms that counteract pathophysiological processes. The interosseus muscle from mdx mice possibly represents a naturally protected phenotype.

Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy

PubMed Central

CARBERRY, STEVEN; BRINKMEIER, HEINRICH; ZHANG, YAXIN; WINKLER, CLAUDIA K.; OHLENDIECK, KAY

2013-01-01

Duchenne muscular dystrophy is due to genetic abnormalities in the dystrophin gene and represents one of the most frequent genetic childhood diseases. In the X-linked muscular dystrophy (mdx) mouse model of dystrophinopathy, different subtypes of skeletal muscles are affected to a varying degree albeit the same single base substitution within exon 23 of the dystrophin gene. Thus, to determine potential muscle subtype-specific differences in secondary alterations due to a deficiency in dystrophin, in this study, we carried out a comparative histological and proteomic survey of mdx muscles. We intentionally included the skeletal muscles that are often used for studying the pathomechanism of muscular dystrophy. Histological examinations revealed a significantly higher degree of central nucleation in the soleus and extensor digitorum longus muscles compared with the flexor digitorum brevis and interosseus muscles. Muscular hypertrophy of 20–25% was likewise only observed in the soleus and extensor digitorum longus muscles from mdx mice, but not in the flexor digitorum brevis and interosseus muscles. For proteomic analysis, muscle protein extracts were separated by fluorescence two-dimensional (2D) gel electrophoresis. Proteins with a significant change in their expression were identified by mass spectrometry. Proteomic profiling established an altered abundance of 24, 17, 19 and 5 protein species in the dystrophin-deficient soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscle, respectively. The key proteomic findings were verified by immunoblot analysis. The identified proteins are involved in the contraction-relaxation cycle, metabolite transport, muscle metabolism and the cellular stress response. Thus, histological and proteomic profiling of muscle subtypes from mdx mice indicated that distinct skeletal muscles are differentially affected by the loss of the membrane cytoskeletal protein, dystrophin. Varying degrees of perturbed protein expression patterns in the muscle subtypes from mdx mice may be due to dissimilar downstream events, including differences in muscle structure or compensatory mechanisms that counteract pathophysiological processes. The interosseus muscle from mdx mice possibly represents a naturally protected phenotype. PMID:23828267

Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells.

PubMed

Ma, Yun-Yun; Sun, Lin; Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

2016-01-01

Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification.

Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy.

PubMed

Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

2015-05-28

Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1.

Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy

PubMed Central

Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S.; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

2015-01-01

Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1. PMID:26018658

Circadian Rhythms, the Molecular Clock, and Skeletal Muscle

PubMed Central

Lefta, Mellani; Wolff, Gretchen; Esser, Karyn A.

2015-01-01

Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1−/− and ClockΔ19 mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle. PMID:21621073

CCL2 and CCR2 variants are associated with skeletal muscle strength and change in strength with resistance training.

PubMed

Harmon, Brennan T; Orkunoglu-Suer, E Funda; Adham, Kasra; Larkin, Justin S; Gordish-Dressman, Heather; Clarkson, Priscilla M; Thompson, Paul D; Angelopoulos, Theodore J; Gordon, Paul M; Moyna, Niall M; Pescatello, Linda S; Visich, Paul S; Zoeller, Robert F; Hubal, Monica J; Tosi, Laura L; Hoffman, Eric P; Devaney, Joseph M

2010-12-01

Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation. The present study hypothesizes that genetic variations in CCL2 and its receptor (CCR2) may help explain muscle trait variability. College-aged subjects [n = 874, Functional Single-Nucleotide Polymorphisms Associated With Muscle Size and Strength (FAMUSS) cohort] underwent a 12-wk supervised strength-training program for the upper arm muscles. Muscle size (via MR imaging) and elbow flexion strength (1 repetition maximum and isometric) measurements were taken before and after training. The study participants were then genotyped for 11 genetic variants in CCL2 and five variants in CCR2. Variants in the CCL2 and CCR2 genes show strong associations with several pretraining muscle strength traits, indicating that inflammatory genes in skeletal muscle contribute to the polygenic system that determines muscle phenotypes. These associations extend across both sexes, and several of these genetic variants have been shown to influence gene regulation.

Extracellular Potassium Homeostasis: Insights from Hypokalemic Periodic Paralysis

PubMed Central

Cheng, Chih-Jen; Kuo, Elizabeth; Huang, Chou-Long

2014-01-01

The extracellular potassium makes up only about 2% of the total body potassium store. The majority of the body potassium is distributed in the intracellular space, and of which about 80% is in skeletal muscle. Movement of potassium in and out of skeletal muscle thus plays a pivotal role in extracellular potassium homeostasis. The exchange of potassium between the extracellular space and skeletal muscle is mediated by specific membrane transporters. These include potassium uptake by Na+, K+-ATPase and release by inward rectifier K+ channels. These processes are regulated by circulating hormones, peptides, ions, and by physical activity of muscle as well as dietary potassium intake. Pharmaceutical agents, poisons and disease conditions also affect the exchange and alter extracellular potassium concentration. Here, we review extracellular potassium homeostasis focusing on factors and conditions that influence the balance of potassium movement in skeletal muscle. Recent findings that mutations of a skeletal muscle-specific inward rectifier K+ channel cause hypokalemic periodic paralysis provide interesting insights into the role of skeletal muscle in extracellular potassium homeostasis. These recent findings will be reviewed. PMID:23953801

Broad and Inconsistent Muscle Food Classification Is Problematic for Dietary Guidance in the U.S.

PubMed Central

O’Connor, Lauren E.; Campbell, Wayne W.; Woerner, Dale R.; Belk, Keith E.

2017-01-01

Dietary recommendations regarding consumption of muscle foods, such as red meat, processed meat, poultry or fish, largely rely on current dietary intake assessment methods. This narrative review summarizes how U.S. intake values for various types of muscle foods are grouped and estimated via methods that include: (1) food frequency questionnaires; (2) food disappearance data from the U.S. Department of Agriculture Economic Research Service; and (3) dietary recall information from the National Health and Nutrition Examination Survey data. These reported methods inconsistently classify muscle foods into groups, such as those previously listed, which creates discrepancies in estimated intakes. Researchers who classify muscle foods into these groups do not consistently considered nutrient content, in turn leading to implications of scientific conclusions and dietary recommendations. Consequentially, these factors demonstrate a need for a more universal muscle food classification system. Further specification to this system would improve accuracy and precision in which researchers can classify muscle foods in nutrition research. Future multidisciplinary collaboration is needed to develop a new classification system via systematic review protocol of current literature. PMID:28926963

Replication of Muscle Cell Using Bioimprint

NASA Astrophysics Data System (ADS)

Samsuri, Fahmi; Mitchell, John S.; Alkaisi, Maan M.; Evans, John J.

2009-07-01

In our earlier study a heat-curable PDMS or a UV curable elastomer, was used as the replicating material to introduce Bioimprint methodology to facilitate cell imaging [1-2] But, replicating conditions for thermal polymerization is known to cause cell dehydration during curing. In this study, a new type of polymer was developed for use in living cell replica formation, and it was tested on human muscle cells. The cells were incubated and cultured according to standard biological culturing procedures, and they were grown for about 10 days. The replicas were then separated from the muscle cells and taken for analysis under an Atomic Force Microscope (AFM). The new polymer was designed to be biocompatible with higher resolution and fast curing process compared to other types of silicon-based organic polymers such as polydimethylsiloxane (PDMS). Muscle cell imprints were achieved and higher resolution images were able to show the micro structures of the muscle cells, including the cellular fibers and cell membranes. The AFM is able to image features at nanoscale resolution. This capacity enables a number of characteristics of biological cells to be visualized in a unique manner. Polymer and muscle cells preparations were developed at Hamilton, in collaboration between Plant and Food Research and the Department of Electrical and Computer Engineering, University of Canterbury. Tapping mode was used for the AFM image analysis as it has low tip-sample forces and non-destructive imaging capability. We will be presenting the bioimprinting processes of muscle cells, their AFM imaging and characterization of the newly developed polymer.

Skeletal muscle regeneration and impact of aging and nutrition.

PubMed

Domingues-Faria, Carla; Vasson, Marie-Paule; Goncalves-Mendes, Nicolas; Boirie, Yves; Walrand, Stephane

2016-03-01

After skeletal muscle injury a regeneration process takes place to repair muscle. Skeletal muscle recovery is a highly coordinated process involving cross-talk between immune and muscle cells. It is well known that the physiological activities of both immune cells and muscle stem cells decline with advancing age, thereby blunting the capacity of skeletal muscle to regenerate. The age-related reduction in muscle repair efficiency contributes to the development of sarcopenia, one of the most important factors of disability in elderly people. Preserving muscle regeneration capacity may slow the development of this syndrome. In this context, nutrition has drawn much attention: studies have demonstrated that nutrients such as amino acids, n-3 polyunsaturated fatty acids, polyphenols and vitamin D can improve skeletal muscle regeneration by targeting key functions of immune cells, muscle cells or both. Here we review the process of skeletal muscle regeneration with a special focus on the cross-talk between immune and muscle cells. We address the effect of aging on immune and skeletal muscle cells involved in muscle regeneration. Finally, the mechanisms of nutrient action on muscle regeneration are described, showing that quality of nutrition may help to preserve the capacity for skeletal muscle regeneration with age. Copyright © 2015 Elsevier B.V. All rights reserved.

Nutrient-rich meat proteins in offsetting age-related muscle loss.

PubMed

Phillips, Stuart M

2012-11-01

From a health perspective, an underappreciated consequence of the normal aging process is the impacts that the gradual loss of skeletal muscle mass, termed sarcopenia, has on health beyond an effect on locomotion. Sarcopenia, refers to the loss of muscle mass, and associated muscle weakness, which occurs in aging and is thought to proceed at a rate of approximately 1% loss per year. However, periods of inactivity due to illness or recovery from orthopedic procedures such as hip or knee replacement are times of accelerated sarcopenic muscle loss from which it may be more difficult for older persons to recover. Some of the consequences of age-related sarcopenia are easy to appreciate such as weakness and, eventually, reduced mobility; however, other lesser recognized consequences include, due to the metabolic role the skeletal muscle plays, an increased risk for poor glucose control and a predisposition toward weight gain. What we currently know is that two stimuli can counter this age related muscle loss and these are physical activity, specifically resistance exercise (weightlifting), and nutrition. The focus of this paper is on the types of dietary protein that people might reasonably consume to offset sarcopenic muscle loss. Copyright © 2012 Elsevier Ltd. All rights reserved.

PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications.

PubMed

Barreiro, Esther; Gea, Joaquim

2018-01-26

Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia. Genetic inhibition of PARP activity attenuated the deleterious effects seen on depleted muscles in mouse models of oncologic cachexia. In the present minireview the mechanisms whereby PARP activity inhibition may improve muscle mass and performance in models of cancer-induced cachexia are discussed. Specifically, the beneficial effects of inhibition of PARP activity on attenuation of increased oxidative stress, protein catabolism, poor muscle anabolism and mitochondrial content and epigenetic modulation of muscle phenotype are reviewed in this article. Finally, the potential therapeutic strategies of pharmacological PARP activity inhibition for the treatment of cancer-induced cachexia are also being described in this review.

Identification of the essential protein domains for Mib2 function during the development of the Drosophila larval musculature and adult flight muscles

PubMed Central

Domsch, Katrin; Acs, Andreas; Obermeier, Claudia; Nguyen, Hanh T.

2017-01-01

The proper differentiation and maintenance of myofibers is fundamental to a functional musculature. Disruption of numerous mostly structural factors leads to perturbations of these processes. Among the limited number of known regulatory factors for these processes is Mind bomb2 (Mib2), a muscle-associated E3 ubiquitin ligase, which was previously established to be required for maintaining the integrity of larval muscles. In this study, we have examined the mechanistic aspects of Mib2 function by performing a detailed functional dissection of the Mib2 protein. We show that the ankyrin repeats, in its entirety, and the hitherto uncharacterized Mib-specific domains (MIB), are important for the major function of Mib2 in skeletal and visceral muscles in the Drosophila embryo. Furthermore, we characterize novel mib2 alleles that have arisen from a forward genetic screen aimed at identifying regulators of myogenesis. Two of these alleles are viable, but flightless hypomorphic mib2 mutants, and harbor missense mutations in the MIB domain and RING finger, respectively. Functional analysis of these new alleles, including in vivo imaging, demonstrates that Mib2 plays an additional important role in the development of adult thorax muscles, particularly in maintaining the larval templates for the dorsal longitudinal indirect flight muscles during metamorphosis. PMID:28282454

The involvement of transient receptor potential canonical type 1 in skeletal muscle regrowth after unloading-induced atrophy.

PubMed

Xia, Lu; Cheung, Kwok-Kuen; Yeung, Simon S; Yeung, Ella W

2016-06-01

Decreased mechanical loading results in skeletal muscle atrophy. The transient receptor potential canonical type 1 (TRPC1) protein is implicated in this process. Investigation of the regulation of TRPC1 in vivo has rarely been reported. In the present study, we employ the mouse hindlimb unloading and reloading model to examine the involvement of TRPC1 in the regulation of muscle atrophy and regrowth, respectively. We establish the physiological relevance of the concept that manipulation of TRPC1 could interfere with muscle regrowth processes following an atrophy-inducing event. Specifically, we show that suppressing TRPC1 expression during reloading impairs the recovery of the muscle mass and slow myosin heavy chain profile. Calcineurin appears to be part of the signalling pathway involved in the regulation of TRPC1 expression during muscle regrowth. These results provide new insights concerning the function of TRPC1. Interventions targeting TRPC1 or its downstream or upstream pathways could be useful for promoting muscle regeneration. Decreased mechanical loading, such as bed rest, results in skeletal muscle atrophy. The functional consequences of decreased mechanical loading include a loss of muscle mass and decreased muscle strength, particularly in anti-gravity muscles. The purpose of this investigation was to clarify the regulatory role of the transient receptor potential canonical type 1 (TRPC1) protein during muscle atrophy and regrowth. Mice were subjected to 14 days of hindlimb unloading followed by 3, 7, 14 and 28 days of reloading. Weight-bearing mice were used as controls. TRPC1 expression in the soleus muscle decreased significantly and persisted at 7 days of reloading. Small interfering RNA (siRNA)-mediated downregulation of TRPC1 in weight-bearing soleus muscles resulted in a reduced muscle mass and a reduced myofibre cross-sectional area (CSA). Microinjecting siRNA into soleus muscles in vivo after 7 days of reloading provided further evidence for the role of TRPC1 in regulating muscle regrowth. Myofibre CSA, as well as the percentage of slow myosin heavy chain-positive myofibres, was significantly lower in TRPC1-siRNA-expressing muscles than in control muscles after 14 days of reloading. Additionally, inhibition of calcineurin (CaN) activity downregulated TRPC1 expression in both weight-bearing and reloaded muscles, suggesting a possible association between CaN and TRPC1 during skeletal muscle regrowth. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The involvement of transient receptor potential canonical type 1 in skeletal muscle regrowth after unloading‐induced atrophy

PubMed Central

Xia, Lu; Cheung, Kwok‐Kuen; Yeung, Simon S.

2016-01-01

Key points Decreased mechanical loading results in skeletal muscle atrophy. The transient receptor potential canonical type 1 (TRPC1) protein is implicated in this process. Investigation of the regulation of TRPC1 in vivo has rarely been reported. In the present study, we employ the mouse hindlimb unloading and reloading model to examine the involvement of TRPC1 in the regulation of muscle atrophy and regrowth, respectively.We establish the physiological relevance of the concept that manipulation of TRPC1 could interfere with muscle regrowth processes following an atrophy‐inducing event. Specifically, we show that suppressing TRPC1 expression during reloading impairs the recovery of the muscle mass and slow myosin heavy chain profile. Calcineurin appears to be part of the signalling pathway involved in the regulation of TRPC1 expression during muscle regrowth.These results provide new insights concerning the function of TRPC1. Interventions targeting TRPC1 or its downstream or upstream pathways could be useful for promoting muscle regeneration. Abstract Decreased mechanical loading, such as bed rest, results in skeletal muscle atrophy. The functional consequences of decreased mechanical loading include a loss of muscle mass and decreased muscle strength, particularly in anti‐gravity muscles. The purpose of this investigation was to clarify the regulatory role of the transient receptor potential canonical type 1 (TRPC1) protein during muscle atrophy and regrowth. Mice were subjected to 14 days of hindlimb unloading followed by 3, 7, 14 and 28 days of reloading. Weight‐bearing mice were used as controls. TRPC1 expression in the soleus muscle decreased significantly and persisted at 7 days of reloading. Small interfering RNA (siRNA)‐mediated downregulation of TRPC1 in weight‐bearing soleus muscles resulted in a reduced muscle mass and a reduced myofibre cross‐sectional area (CSA). Microinjecting siRNA into soleus muscles in vivo after 7 days of reloading provided further evidence for the role of TRPC1 in regulating muscle regrowth. Myofibre CSA, as well as the percentage of slow myosin heavy chain‐positive myofibres, was significantly lower in TRPC1‐siRNA‐expressing muscles than in control muscles after 14 days of reloading. Additionally, inhibition of calcineurin (CaN) activity downregulated TRPC1 expression in both weight‐bearing and reloaded muscles, suggesting a possible association between CaN and TRPC1 during skeletal muscle regrowth. PMID:26752511

Effect of Aging Process and Time on Physicochemical and Sensory Evaluation of Raw Beef Top Round and Shank Muscles Using an Electronic Tongue.

PubMed

Kim, Ji-Han; Kim, Dong-Han; Ji, Da-Som; Lee, Hyun-Jin; Yoon, Dong-Kyu; Lee, Chi-Ho

2017-01-01

The objective of this study was to determine the effect of aging method (dry or wet) and time (20 d or 40 d) on physical, chemical, and sensory properties of two different muscles (top round and shank) from steers (n=12) using an electronic tongue (ET). Moisture content was not affected by muscle types and aging method ( p >0.05). Shear force of dry aged beef was significantly decreased compared to that of wet aged beef. Most fatty acids of dry aged beef were significantly lower than those of wet aged beef. Dry aged shank muscles had more abundant free amino acids than top round muscles. Dry-aging process enhanced tastes such as umami and saltiness compared to wet-aging process according to ET results. Dry-aging process could enhance the instrumental tenderness and umami taste of beef. In addition, the taste of shank muscle was more affected by dry-aging process than that of round muscle.

Effect of Aging Process and Time on Physicochemical and Sensory Evaluation of Raw Beef Top Round and Shank Muscles Using an Electronic Tongue

PubMed Central

2017-01-01

The objective of this study was to determine the effect of aging method (dry or wet) and time (20 d or 40 d) on physical, chemical, and sensory properties of two different muscles (top round and shank) from steers (n=12) using an electronic tongue (ET). Moisture content was not affected by muscle types and aging method (p>0.05). Shear force of dry aged beef was significantly decreased compared to that of wet aged beef. Most fatty acids of dry aged beef were significantly lower than those of wet aged beef. Dry aged shank muscles had more abundant free amino acids than top round muscles. Dry-aging process enhanced tastes such as umami and saltiness compared to wet-aging process according to ET results. Dry-aging process could enhance the instrumental tenderness and umami taste of beef. In addition, the taste of shank muscle was more affected by dry-aging process than that of round muscle. PMID:29725203

Why the chameleon has spiral-shaped muscle fibres in its tongue

PubMed Central

Leeuwen, J. L. van

1997-01-01

The intralingual accelerator muscle is the primary actuator for the remarkable ballistic tongue projection of the chameleon. At rest, this muscle envelopes the elongated entoglossal process, a cylindrically shaped bone with a tapering distal end. During tongue projection, the accelerator muscle elongates and slides forward along the entoglossal process until the entire muscle extends beyond the distal end of the process. The accelerator muscle fibres are arranged in transverse planes (small deviations are possible), and form (hitherto unexplained) spiral-shaped arcs from the peripheral to the internal boundary. To initiate tongue projection, the muscle fibres probably generate a high intramuscular pressure. The resulting negative pressure gradient (from base to tip) causes the muscle to elongate and to accelerate forward. Effective forward sliding is made possible by a lubricant and a relatively low normal stress exerted on the proximal cylindrical part of the entoglossal process. A relatively high normal stress is, however, probably required for an effective acceleration of muscle tissue over the tapered end of the process. For optimal performance, the fast extension movement should occur without significant (energy absorbing) torsional motion of the tongue. In addition, the tongue extension movement is aided by a close packing of the muscles fibres (required for a high power density) and a uniform strain and work output in every cross-section of the muscle. A quantitative model of the accelerator muscle was developed that predicts internal muscle fibre arrangements based on the functional requirements above and the physical principle of mechanical stability. The curved shapes and orientations of the muscle fibres typically found in the accelerator muscle were accurately predicted by the model. Furthermore, the model predicts that the reduction of the entoglossal radius towards the tip (and thus the internal radius of the muscle) tends to increase the normal stress on the entoglossal bone.

Effects of training and weight support on muscle activation in Parkinson's disease.

PubMed

Rose, Martin H; Løkkegaard, Annemette; Sonne-Holm, Stig; Jensen, Bente R

2013-12-01

The aim of this study was to investigate the effect of high-intensity locomotor training on knee extensor and flexor muscle activation and adaptability to increased body-weight (BW) support during walking in patients with Parkinson's disease (PD). Thirteen male patients with idiopathic PD and eight healthy participants were included. The PD patients completed an 8-week training program on a lower-body, positive-pressure treadmill. Knee extensor and flexor muscles activation during steady treadmill walking (3 km/h) were measured before, at the mid-point, and after training. Increasing BW support decreased knee extensor muscle activation (normalization) and increased knee flexor muscle activation (abnormal) in PD patients when compared to healthy participants. Training improved flexor peak muscle activation adaptability to increased (BW) support during walking in PD patients. During walking without BW support shorter knee extensor muscle off-activation time and increased relative peak muscle activation was observed in PD patients and did not improve with 8 weeks of training. In conclusion, patients with PD walked with excessive activation of the knee extensor and flexor muscles when compared to healthy participants. Specialized locomotor training may facilitate adaptive processes related to motor control of walking in PD patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Personality Typology in Relation to Muscle Strength

PubMed Central

Terracciano, Antonio; Milaneschi, Yuri; Metter, E. Jeffrey; Ferrucci, Luigi

2011-01-01

Background Physical inactivity plays a central role in the age-related decline in muscle strength, an important component in the process leading to disability. Personality, a significant determinant of health behaviors including physical activity, could therefore impact muscle strength throughout adulthood and affect the rate of muscle strength decline with aging. Personality typologies combining “high neuroticism” (N≥55), “low extraversion” (E<45), and “low conscientiousness” (C<45) have been associated with multiple risky health behaviors but have not been investigated with regards to muscle strength. Purpose The purpose of this study is to investigate associations between individual and combined typologies consisting of high N, low E, and low C and muscle strength, and whether physical activity and body mass index act as mediators. Method This cross-sectional study includes 1,220 participants from the Baltimore Longitudinal Study of Aging. Results High N was found among 18%, low E among 31%, and low C among 26% of the sample. High levels of N, particularly when combined with either low E or low C, were associated with lower muscle strength compared with having only one or none of these personality types. Facet analyses suggest an important role for the N components of depression and hostility. Physical activity level appears to partly explain some of these associations. Conclusion Findings provide support for the notion that the typological approach to personality may be useful in identifying specific personality types at risk of low muscle strength and offer the possibility for more targeted prevention and intervention programs. PMID:21614452

microRNA-133: expression, function and therapeutic potential in muscle diseases and cancer.

PubMed

Yu, Hao; Lu, Yinhui; Li, Zhaofa; Wang, Qizhao

2014-01-01

microRNAs (miRNAs) are a class of small non-coding RNAs that are 18-25 nucleotides (nt) in length and negatively regulate gene expression post-transcriptionally. miRNAs are known to mediate myriad processes and pathways. While many miRNAs are expressed ubiquitously, some are expressed in a tissue specific manner. miR-133 is one of the most studied and best characterized miRNAs to date. Specifically expressed in muscles, it has been classified as myomiRNAs and is necessary for proper skeletal and cardiac muscle development and function. Genes encoding miR-133 (miR-133a-1, miR-133a-2 and miR-133b) are transcribed as bicistronic transcripts together with miR-1-2, miR-1-1, and miR-206, respectively. However, they exhibit opposing impacts on muscle development. miR-133 gets involved in muscle development by targeting a lot of genes, including SFR, HDAC4, cyclin D2 and so on. Its aberrant expression has been linked to many diseases in skeletal muscle and cardiac muscle such as cardiac hypertrophy, muscular dystrophy, heart failure, cardiac arrhythmia. Beyond the study in muscle, miR-133 has been implicated in cancer and identified as a key factor in cancer development, including bladder cancer, prostate cancer and so on. Much more attention has been drawn to the versatile molecular functions of miR-133, making it a truly valuable therapeutic gene in miRNA-based gene therapy. In this review, we identified and summarized the results of studies of miR-133 with emphasis on its function in human diseases in muscle and cancer, and highlighted its therapeutic value. It might provide researchers a new insight into the biological significance of miR-133.

Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting

NASA Technical Reports Server (NTRS)

Wing, S. S.; Goldberg, A. L.; Goldberger, A. L. (Principal Investigator)

1993-01-01

Glucocorticoids are essential for the increase in protein breakdown in skeletal muscle normally seen during fasting. To determine which proteolytic pathway(s) are activated upon fasting, leg muscles from fed and fasted normal rats were incubated under conditions that block or activate different proteolytic systems. After food deprivation (1 day), the nonlysosomal ATP-dependent process increased by 250%, as shown in experiments involving depletion of muscle ATP. Also, the maximal capacity of the lysosomal process increased 60-100%, but no changes occurred in the Ca(2+)-dependent or the residual energy-independent proteolytic processes. In muscles from fasted normal and adrenalectomized (ADX) rats, the protein breakdown sensitive to inhibitors of the lysosomal or Ca(2+)-dependent pathways did not differ. However, the ATP-dependent process was 30% slower in muscles from fasted ADX rats. Administering dexamethasone to these animals or incubating their muscles with dexamethasone reversed this defect. During fasting, when the ATP-dependent process rises, muscles show a two- to threefold increase in levels of ubiquitin (Ub) mRNA. However, muscles of ADX animals failed to show this response. Injecting dexamethasone into the fasted ADX animals increased muscle Ub mRNA within 6 h. Thus glucocorticoids activate the ATP-Ub-dependent proteolytic pathway in fasting apparently by enhancing the expression of components of this system such as Ub.

In situ macrophage phenotypic transition is affected by altered cellular composition prior to acute sterile muscle injury.

PubMed

Patsalos, Andreas; Pap, Attila; Varga, Tamas; Trencsenyi, Gyorgy; Contreras, Gerardo Alvarado; Garai, Ildiko; Papp, Zoltan; Dezso, Balazs; Pintye, Eva; Nagy, Laszlo

2017-09-01

The in situ phenotypic switch of macrophages is delayed in acute injury following irradiation. The combination of bone marrow transplantation and local muscle radiation protection allows for the identification of a myeloid cell contribution to tissue repair. PET-MRI allows monitoring of myeloid cell invasion and metabolism. Altered cellular composition prior to acute sterile injury affects the in situ phenotypic transition of invading myeloid cells to repair macrophages. There is reciprocal intercellular communication between local muscle cell compartments, such as PAX7 positive cells, and recruited macrophages during skeletal muscle regeneration. Skeletal muscle regeneration is a complex interplay between various cell types including invading macrophages. Their recruitment to damaged tissues upon acute sterile injuries is necessary for clearance of necrotic debris and for coordination of tissue regeneration. This highly dynamic process is characterized by an in situ transition of infiltrating monocytes from an inflammatory (Ly6C high ) to a repair (Ly6C low ) macrophage phenotype. The importance of the macrophage phenotypic shift and the cross-talk of the local muscle tissue with the infiltrating macrophages during tissue regeneration upon injury are not fully understood and their study lacks adequate methodology. Here, using an acute sterile skeletal muscle injury model combined with irradiation, bone marrow transplantation and in vivo imaging, we show that preserved muscle integrity and cell composition prior to the injury is necessary for the repair macrophage phenotypic transition and subsequently for proper and complete tissue regeneration. Importantly, by using a model of in vivo ablation of PAX7 positive cells, we show that this radiosensitive skeletal muscle progenitor pool contributes to macrophage phenotypic transition following acute sterile muscle injury. In addition, local muscle tissue radioprotection by lead shielding during irradiation preserves normal macrophage transition dynamics and subsequently muscle tissue regeneration. Taken together, our data suggest the existence of a more extensive and reciprocal cross-talk between muscle tissue compartments, including satellite cells, and infiltrating myeloid cells upon tissue damage. These interactions shape the macrophage in situ phenotypic shift, which is indispensable for normal muscle tissue repair dynamics. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Eosinophilia of dystrophin-deficient muscle is promoted by perforin-mediated cytotoxicity by T cell effectors

NASA Technical Reports Server (NTRS)

Cai, B.; Spencer, M. J.; Nakamura, G.; Tseng-Ong, L.; Tidball, J. G.

2000-01-01

Previous investigations have shown that cytotoxic T lymphocytes (CTLs) contribute to muscle pathology in the dystrophin-null mutant mouse (mdx) model of Duchenne muscular dystrophy through perforin-dependent and perforin-independent mechanisms. We have assessed whether the CTL-mediated pathology includes the promotion of eosinophilia in dystrophic muscle, and thereby provides a secondary mechanism through which CTLs contribute to muscular dystrophy. Quantitative immunohistochemistry confirmed that eosinophilia is a component of the mdx dystrophy. In addition, electron microscopic observations show that eosinophils traverse the basement membrane of mdx muscle fibers and display sites of close apposition of eosinophil and muscle membranes. The close membrane apposition is characterized by impingement of eosinophilic rods of major basic protein into the muscle cell membrane. Transfer of mdx splenocytes and mdx muscle extracts to irradiated C57 mice by intraperitoneal injection resulted in muscle eosinophilia in the recipient mice. Double-mutant mice lacking dystrophin and perforin showed less eosinophilia than was displayed by mdx mice that expressed perforin. Finally, administration of prednisolone, which has been shown previously to reduce the concentration of CTLs in dystrophic muscle, produced a significant reduction in eosinophilia. These findings indicate that eosinophilia is a component of the mdx pathology that is promoted by perforin-dependent cytotoxicity of effector T cells. However, some eosinophilia of mdx muscle is independent of perforin-mediated processes.

Myostatin: expanding horizons.

PubMed

Sharma, Mridula; McFarlane, Craig; Kambadur, Ravi; Kukreti, Himani; Bonala, Sabeera; Srinivasan, Shruti

2015-08-01

Myostatin is a secreted growth and differentiation factor that belongs to the TGF-β superfamily. Myostatin is predominantly synthesized and expressed in skeletal muscle and thus exerts a huge impact on muscle growth and function. In keeping with its negative role in myogenesis, myostatin expression is tightly regulated at several levels including epigenetic, transcriptional, post-transcriptional, and post-translational. New revelations regarding myostatin regulation also offer mechanisms that could be exploited for developing myostatin antagonists. Increasingly, it is becoming clearer that besides its conventional role in muscle, myostatin plays a critical role in metabolism. Hence, molecular mechanisms by which myostatin regulates several key metabolic processes need to be further explored. © 2015 International Union of Biochemistry and Molecular Biology.

Laser Doppler vibrometry measurement of the mechanical myogram

NASA Astrophysics Data System (ADS)

Rohrbaugh, John W.; Sirevaag, Erik J.; Richter, Edward J.

2013-12-01

Contracting muscles show complex dimensional changes that include lateral expansion. Because this expansion process is intrinsically vibrational, driven by repetitive actions of multiple motor units, it can be sensed and quantified using the method of Laser Doppler Vibrometry (LDV). LDV has a number of advantages over more traditional mechanical methods based on microphones and accelerometers. The LDV mechanical myogram from a small hand muscle (the first dorsal interosseous) was studied under conditions of elastic loading applied to the tip of the abducted index finger. The LDV signal was shown to be related systematically to the level of force production, and to compare favorably with conventional methods for sensing the mechanical and electrical aspects of muscle contraction.

Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells

PubMed Central

Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

2016-01-01

Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification. PMID:27589055

Skeletal Muscle Mitochondria and Aging: A Review

PubMed Central

Peterson, Courtney M.; Johannsen, Darcy L.; Ravussin, Eric

2012-01-01

Aging is characterized by a progressive loss of muscle mass and muscle strength. Declines in skeletal muscle mitochondria are thought to play a primary role in this process. Mitochondria are the major producers of reactive oxygen species, which damage DNA, proteins, and lipids if not rapidly quenched. Animal and human studies typically show that skeletal muscle mitochondria are altered with aging, including increased mutations in mitochondrial DNA, decreased activity of some mitochondrial enzymes, altered respiration with reduced maximal capacity at least in sedentary individuals, and reduced total mitochondrial content with increased morphological changes. However, there has been much controversy over measurements of mitochondrial energy production, which may largely be explained by differences in approach and by whether physical activity is controlled for. These changes may in turn alter mitochondrial dynamics, such as fusion and fission rates, and mitochondrially induced apoptosis, which may also lead to net muscle fiber loss and age-related sarcopenia. Fortunately, strategies such as exercise and caloric restriction that reduce oxidative damage also improve mitochondrial function. While these strategies may not completely prevent the primary effects of aging, they may help to attenuate the rate of decline. PMID:22888430

Molecular events in skeletal muscle during disuse atrophy

NASA Technical Reports Server (NTRS)

Kandarian, Susan C.; Stevenson, Eric J.

2002-01-01

This review summarizes the current knowledge of the molecular processes underlying skeletal muscle atrophy due to disuse. Because the processes involved with muscle wasting due to illness are similar to disuse, this literature is used for comparison. Areas that are ripe for further study and that will advance our understanding of muscle atrophy are suggested.

Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures

PubMed Central

Gao, Yunfang; Arfat, Yasir; Wang, Huiping; Goswami, Nandu

2018-01-01

Prolonged periods of skeletal muscle inactivity or mechanical unloading (bed rest, hindlimb unloading, immobilization, spaceflight and reduced step) can result in a significant loss of musculoskeletal mass, size and strength which ultimately lead to muscle atrophy. With advancement in understanding of the molecular and cellular mechanisms involved in disuse skeletal muscle atrophy, several different signaling pathways have been studied to understand their regulatory role in this process. However, substantial gaps exist in our understanding of the regulatory mechanisms involved, as well as their functional significance. This review aims to update the current state of knowledge and the underlying cellular mechanisms related to skeletal muscle loss during a variety of unloading conditions, both in humans and animals. Recent advancements in understanding of cellular and molecular mechanisms, including IGF1-Akt-mTOR, MuRF1/MAFbx, FOXO, and potential triggers of disuse atrophy, such as calcium overload and ROS overproduction, as well as their role in skeletal muscle protein adaptation to disuse is emphasized. We have also elaborated potential therapeutic countermeasures that have shown promising results in preventing and restoring disuse-induced muscle loss. Finally, identified are the key challenges in this field as well as some future prospectives. PMID:29615929

Potential involvement of dietary advanced glycation end products in impairment of skeletal muscle growth and muscle contractile function in mice.

PubMed

Egawa, Tatsuro; Tsuda, Satoshi; Goto, Ayumi; Ohno, Yoshitaka; Yokoyama, Shingo; Goto, Katsumasa; Hayashi, Tatsuya

2017-01-01

Diets enriched with advanced glycation end products (AGE) have recently been related to muscle dysfunction processes. However, it remains unclear whether long-term exposure to an AGE-enriched diet impacts physiological characteristics of skeletal muscles. Therefore, we explored the differences in skeletal muscle mass, contractile function and molecular responses between mice receiving a diet high in AGE (H-AGE) and low in AGE (L-AGE) for 16 weeks. There were no significant differences between L-AGE and H-AGE mice with regard to body weight, food intake or epididymal fat pad weight. However, extensor digitorum longus (EDL) and plantaris (PLA) muscle weights in H-AGE mice were lower compared with L-AGE mice. Higher levels of N ε -(carboxymethyl)-l-lysine, a marker for AGE, in EDL muscles of H-AGE mice were observed compared with L-AGE mice. H-AGE mice showed lower muscle strength and endurance in vivo and lower muscle force production of PLA muscle in vitro. mRNA expression levels of myogenic factors including myogenic factor 5 and myogenic differentiation in EDL muscle were lower in H-AGE mice compared with L-AGE mice. The phosphorylation status of 70-kDa ribosomal protein S6 kinase Thr389, an indicator of protein synthesis signalling, was lower in EDL muscle of H-AGE mice than that of L-AGE mice. These findings suggest that long-term exposure to an AGE-enriched diet impairs skeletal muscle growth and muscle contractile function, and that these muscle dysfunctions may be attributed to the inhibition of myogenic potential and protein synthesis.

Differential apoptosis-related protein expression, mitochondrial properties, proteolytic enzyme activity, and DNA fragmentation between skeletal muscles.

PubMed

McMillan, Elliott M; Quadrilatero, Joe

2011-03-01

Increased skeletal muscle apoptosis has been associated with a number of conditions including aging, disuse, and cardiovascular disease. Skeletal muscle is a complex tissue comprised of several fiber types with unique properties. To date, no report has specifically examined apoptotic differences across muscles or fiber types. Therefore, we measured several apoptotic indices in healthy rat red (RG) and white gastrocnemius (WG) muscle, as well as examined the expression of several key proteins across fiber types in a mixed muscle (mixed gastrocnemius). The protein content of apoptosis-inducing factor (AIF), apoptosis repressor with caspase recruitment domain (ARC), Bax, Bcl-2, cytochrome c, heat shock protein 70 (Hsp70), and second mitochondria-derived activator of caspases (Smac) were significantly (P < 0.05) higher in RG vs. WG muscle. Cytosolic AIF, cytochrome c, and Smac as well as nuclear AIF were also significantly (P < 0.05) higher in RG compared with WG muscle. In addition, ARC protein expression was related to muscle fiber type and found to be highest (P < 0.001) in type I fibers. Similarly, AIF protein expression was differentially expressed across fibers; however, AIF was correlated to oxidative potential (P < 0.001). Caspase-3, -8, and -9 activity, calpain activity, and DNA fragmentation (a hallmark of apoptosis) were also significantly higher (P < 0.05) in RG compared with WG muscle. Furthermore, total muscle reactive oxygen species generation, as well as Ca(2+)-induced permeability transition pore opening and loss of membrane potential in isolated mitochondria were greater in RG muscle. Collectively, these data suggest that a number of apoptosis-related indices differ between muscles and fiber types. Given these findings, muscle and fiber-type differences in apoptotic protein expression, signaling, and susceptibility should be considered when studying cell death processes in skeletal muscle.

The 'sensory tolerance limit': A hypothetical construct determining exercise performance?

PubMed

Hureau, Thomas J; Romer, Lee M; Amann, Markus

2018-02-01

Neuromuscular fatigue compromises exercise performance and is determined by central and peripheral mechanisms. Interactions between the two components of fatigue can occur via neural pathways, including feedback and feedforward processes. This brief review discusses the influence of feedback and feedforward mechanisms on exercise limitation. In terms of feedback mechanisms, particular attention is given to group III/IV sensory neurons which link limb muscle with the central nervous system. Central corollary discharge, a copy of the neural drive from the brain to the working muscles, provides a signal from the motor system to sensory systems and is considered a feedforward mechanism that might influence fatigue and consequently exercise performance. We highlight findings from studies supporting the existence of a 'critical threshold of peripheral fatigue', a previously proposed hypothesis based on the idea that a negative feedback loop operates to protect the exercising limb muscle from severe threats to homeostasis during whole-body exercise. While the threshold theory remains to be disproven within a given task, it is not generalisable across different exercise modalities. The 'sensory tolerance limit', a more theoretical concept, may address this issue and explain exercise tolerance in more global terms and across exercise modalities. The 'sensory tolerance limit' can be viewed as a negative feedback loop which accounts for the sum of all feedback (locomotor muscles, respiratory muscles, organs, and muscles not directly involved in exercise) and feedforward signals processed within the central nervous system with the purpose of regulating the intensity of exercise to ensure that voluntary activity remains tolerable.

miR-182 attenuates atrophy-related gene expression by targeting FoxO3 in skeletal muscle

PubMed Central

Rahnert, Jill A.; Zheng, Bin; Woodworth-Hobbs, Myra E.; Franch, Harold A.; Russ Price, S.

2014-01-01

Skeletal muscle atrophy occurs in response to a variety of conditions including chronic kidney disease, diabetes, cancer, and elevated glucocorticoids. MicroRNAs (miR) may play a role in the wasting process. Activation of the forkhead box O3 (FoxO3) transcription factor causes skeletal muscle atrophy in patients, animals, and cultured cells by increasing the expression of components of the ubiquitin-proteasome and autophagy-lysosome proteolytic systems. To identify microRNAs that potentially modulate the atrophy process, an in silico target analysis was performed and miR-182 was predicted to target FoxO3 mRNA. Using a combination of immunoblot analysis, quantitative real-time RT-PCR, and FoxO3 3′-UTR luciferase reporter genes, miR-182 was confirmed to regulate FoxO3 expression in C2C12 myotubes. Transfection of miR-182 into muscle cells decreased FoxO3 mRNA 30% and FoxO3 protein 67% (P < 0.05) and also prevented a glucocorticoid-induced upregulation of multiple FoxO3 gene targets including MAFbx/atrogin-1, autophagy-related protein 12 (ATG12), cathepsin L, and microtubule-associated protein light chain 3 (LC3). Treatment of C2C12 myotubes with dexamethasone (Dex) (1 μM, 6 h) to induce muscle atrophy decreased miR-182 expression by 63% (P < 0.05). Similarly, miR-182 was decreased 44% (P < 0.05) in the gastrocnemius muscle of rats injected with streptozotocin to induce diabetes compared with controls. Finally, miR-182 was present in exosomes isolated from the media of C2C12 myotubes and Dex increased its abundance. These data identify miR-182 as an important regulator of FoxO3 expression that participates in the control of atrophy-inducing genes during catabolic diseases. PMID:24871856

Analysis of Muscle Contraction on Pottery Manufacturing Process Using Electromyography (EMG)

NASA Astrophysics Data System (ADS)

Soewardi, Hartomo; Azka Rahmayani, Amalia

2016-01-01

One of the most common problems in pottery manufacturing process is musculoskeletal disorders on workers. This disorder was caused by uncomfortable posture where the workers sit on the floor with one leg was folded and another was twisted for long duration. Back, waist, buttock, and right knee frequently experience the disorders. The objective of this research is to investigate the muscle contraction at such body part of workers in manufacturing process of pottery. Electromyography is used to investigate the muscle contraction based on the median frequency signal. Focus measurements is conducted on four muscles types. They are lower interscapular muscle on the right and left side, dorsal lumbar muscle, and lateral hamstring muscle. Statistical analysis is conducted to test differences of muscle contraction between female and male. The result of this research showed that the muscle which reached the highest contraction is dorsal lumbar muscle with the average of median frequency is 51,84 Hz. Then followed by lower interscapular muscle on the left side with the average of median frequency is 31,30 hz, lower interscapular muscle on the right side average of median frequency is 31,24 Hz, and lateral hamstring muscle average of median frequency is 21,77 Hz. Based on the statistic analysis result, there were no differences between male and female on left and right lower interscapular muscle and dorsal lumbar muscle but there were differences on lateral hamstring muscle with the significance level is 5%. Besides that, there were differences for all combination muscle types with the level of significance is 5%.

Relating speech production to tongue muscle compressions using tagged and high-resolution magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Xing, Fangxu; Ye, Chuyang; Woo, Jonghye; Stone, Maureen; Prince, Jerry

2015-03-01

The human tongue is composed of multiple internal muscles that work collaboratively during the production of speech. Assessment of muscle mechanics can help understand the creation of tongue motion, interpret clinical observations, and predict surgical outcomes. Although various methods have been proposed for computing the tongue's motion, associating motion with muscle activity in an interdigitated fiber framework has not been studied. In this work, we aim to develop a method that reveals different tongue muscles' activities in different time phases during speech. We use fourdimensional tagged magnetic resonance (MR) images and static high-resolution MR images to obtain tongue motion and muscle anatomy, respectively. Then we compute strain tensors and local tissue compression along the muscle fiber directions in order to reveal their shortening pattern. This process relies on the support from multiple image analysis methods, including super-resolution volume reconstruction from MR image slices, segmentation of internal muscles, tracking the incompressible motion of tissue points using tagged images, propagation of muscle fiber directions over time, and calculation of strain in the line of action, etc. We evaluated the method on a control subject and two postglossectomy patients in a controlled speech task. The normal subject's tongue muscle activity shows high correspondence with the production of speech in different time instants, while both patients' muscle activities show different patterns from the control due to their resected tongues. This method shows potential for relating overall tongue motion to particular muscle activity, which may provide novel information for future clinical and scientific studies.

Meat science: From proteomics to integrated omics towards system biology.

PubMed

D'Alessandro, Angelo; Zolla, Lello

2013-01-14

Since the main ultimate goal of farm animal raising is the production of proteins for human consumption, research tools to investigate proteins play a major role in farm animal and meat science. Indeed, proteomics has been applied to the field of farm animal science to monitor in vivo performances of livestock animals (growth performances, fertility, milk quality etc.), but also to further our understanding of the molecular processes at the basis of meat quality, which are largely dependent on the post mortem biochemistry of the muscle, often in a species-specific way. Post mortem alterations to the muscle proteome reflect the biological complexity of the process of "muscle to meat conversion," a process that, despite decades of advancements, is all but fully understood. This is mainly due to the enormous amounts of variables affecting meat tenderness per se, including biological factors, such as animal species, breed specific-characteristic, muscle under investigation. However, it is rapidly emerging that the tender meat phenotype is not only tied to genetics (livestock breeding selection), but also to extrinsic factors, such as the rearing environment, feeding conditions, physical activity, administration of hormonal growth promotants, pre-slaughter handling and stress, post mortem handling. From this intricate scenario, biochemical approaches and systems-wide integrated investigations (metabolomics, transcriptomics, interactomics, phosphoproteomics, mathematical modeling), which have emerged as complementary tools to proteomics, have helped establishing a few milestones in our understanding of the events leading from muscle to meat conversion. The growing integration of omics disciplines in the field of systems biology will soon contribute to take further steps forward. Copyright © 2012 Elsevier B.V. All rights reserved.

CT Accuracy of Extrinsic Tongue Muscle Invasion in Oral Cavity Cancer.

PubMed

Junn, J C; Baugnon, K L; Lacayo, E A; Hudgins, P A; Patel, M R; Magliocca, K R; Corey, A S; El-Deiry, M; Wadsworth, J T; Beitler, J J; Saba, N F; Liu, Y; Aiken, A H

2017-02-01

Extrinsic tongue muscle invasion in oral cavity cancer upstages the primary tumor to a T4a. Despite this American Joint Committee on Cancer staging criterion, no studies have investigated the accuracy or prognostic importance of radiologic extrinsic tongue muscle invasion, the feasibility of standardizing extrinsic tongue muscle invasion reporting, or the degree of agreement across different disciplines: radiology, surgery, and pathology. The purpose of this study was to assess the agreement among radiology, surgery, and pathology for extrinsic tongue muscle invasion and to determine the imaging features most predictive of extrinsic tongue muscle invasion with surgical/pathologic confirmation. Thirty-three patients with untreated primary oral cavity cancer were included. Two head and neck radiologists, 3 otolaryngologists, and 1 pathologist prospectively evaluated extrinsic tongue muscle invasion. Fourteen of 33 patients had radiologic extrinsic tongue muscle invasion; however, only 8 extrinsic tongue muscle invasions were confirmed intraoperatively. Pathologists were unable to determine extrinsic tongue muscle invasion in post-formalin-fixed samples. Radiologic extrinsic tongue muscle invasion had 100% sensitivity, 76% specificity, 57% positive predictive value, and 100% negative predictive value with concurrent surgical-pathologic evaluation of extrinsic tongue muscle invasion as the criterion standard. On further evaluation, the imaging characteristic most consistent with surgical-pathologic evaluation positive for extrinsic tongue muscle invasion was masslike enhancement. Evaluation of extrinsic tongue muscle invasion is a subjective finding for all 3 disciplines. For radiology, masslike enhancement of extrinsic tongue muscle invasion most consistently corresponded to concurrent surgery/pathology evaluation positive for extrinsic tongue muscle invasion. Intraoperative surgical and pathologic evaluation should be encouraged to verify radiologic extrinsic tongue muscle invasion to minimize unnecessary upstaging. Because this process is not routine, imaging can add value by identifying those cases most suspicious for extrinsic tongue muscle invasion, thereby prompting this more detailed evaluation by surgeons and pathologists. © 2017 by American Journal of Neuroradiology.

Increased whole-body auditory startle reflex and autonomic reactivity in children with anxiety disorders

PubMed Central

Bakker, Mirte J.; Tijssen, Marina A.J.; van der Meer, Johan N.; Koelman, Johannes H.T.M.; Boer, Frits

2009-01-01

Background Young patients with anxiety disorders are thought to have a hypersensitive fear system, including alterations of the early sensorimotor processing of threatening information. However, there is equivocal support in auditory blink response studies for an enlarged auditory startle reflex (ASR) in such patients. We sought to investigate the ASR measured over multiple muscles (whole-body) in children and adolescents with anxiety disorders. Methods Between August and December 2006, we assessed ASRs (elicited by 8 consecutive tones of 104 dB, interstimulus interval of about 2 min) in 25 patients and 25 matched controls using a case–control design and in 9 nonaffected siblings. We recorded the electromyographic activity of 6 muscles and the sympathetic skin response. We investigated response occurrence (probability %) and response magnitude (area under the curve in μV × ms) of the combined response of 6 muscles and of the single blink response. Results In patients (17 girls, mean age 12 years; 13 social phobia, 9 generalized anxiety, 3 other), the combined response probability (p = 0.027) of all muscles, the combined area under the curve of all muscles (p = 0.011) and the sympathetic skin response (p = 0.006) were enlarged compared with matched controls. The response probability (p = 0.48) and area under the curve (p = 0.07) of the blink response were normal in patients compared with controls. The ASR pattern was normal with normal latencies in patients compared with controls. In nonaffected siblings, the sympathetic skin response (p = 0.038), but not the combined response probability of all muscles (p = 0.15), was enlarged compared with controls. Limitations Limitations are the sample size and restricted comparison to the psychophysiological ASR paradigm. Conclusion The results point toward a hypersensitive central nervous system (fear system), including early sensorimotor processing alterations and autonomic hyperreactivity. The multiple muscle (whole-body) ASR is suggested to be a better tool to detect ASR abnormalities in patients with anxiety disorders than the blink response alone. Abnormalities in ASR serve as a candidate endophenotype of anxiety disorders. PMID:19568483

Satellite Cells and the Muscle Stem Cell Niche

PubMed Central

Yin, Hang; Price, Feodor

2013-01-01

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration. PMID:23303905

The role of hormones, cytokines and heat shock proteins during age-related muscle loss.

PubMed

Lee, Claire E; McArdle, Anne; Griffiths, Richard D

2007-10-01

Ageing is associated with a progressive decline of muscle mass, strength, and quality, a condition known as sarcopenia. Due to the progressive ageing of western populations, age-related sarcopenia is a major public health problem. Several possible mechanisms for age-related muscle atrophy have been described; however the precise contribution of each is unknown. Age-related muscle loss is thought to be a multi-factoral process composed of events such as physical activity, nutritional intake, oxidative stress, inflammatory insults and hormonal changes. There is a need for a greater understanding of the loss of muscle mass with age as this could have a dramatic impact on the elderly and critically ill if this research leads to maintenance or improvement in functional ability. This review aims to outline the process of skeletal muscle degeneration with ageing, normal and aberrant skeletal muscle regeneration, and to address recent research on the effects of gender and sex steroid hormones during the process of age-related muscle loss.

Creatine Supplementation and Skeletal Muscle Metabolism for Building Muscle Mass- Review of the Potential Mechanisms of Action.

PubMed

Farshidfar, Farnaz; Pinder, Mark A; Myrie, Semone B

2017-01-01

Creatine, a very popular supplement among athletic populations, is of growing interest for clinical applications. Since over 90% of creatine is stored in skeletal muscle, the effect of creatine supplementation on muscle metabolism is a widely studied area. While numerous studies over the past few decades have shown that creatine supplementation has many favorable effects on skeletal muscle physiology and metabolism, including enhancing muscle mass (growth/hypertrophy); the underlying mechanisms are poorly understood. This report reviews studies addressing the mechanisms of action of creatine supplementation on skeletal muscle growth/hypertrophy. Early research proposed that the osmotic effect of creatine supplementation serves as a cellular stressor (osmosensing) that acts as an anabolic stimulus for protein synthesis signal pathways. Other reports indicated that creatine directly affects muscle protein synthesis via modulations of components in the mammalian target of rapamycin (mTOR) pathway. Creatine may also directly affect the myogenic process (formation of muscle tissue), by altering secretions of myokines, such as myostatin and insulin-like growth factor-1, and expressions of myogenic regulatory factors, resulting in enhanced satellite cells mitotic activities and differentiation into myofiber. Overall, there is still no clear understanding of the mechanisms of action regarding how creatine affects muscle mass/growth, but current evidence suggests it may exert its effects through multiple approaches, with converging impacts on protein synthesis and myogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Correlation of the Features of the Lumbar Multifidus Muscle With Facet Joint Osteoarthritis.

PubMed

Yu, Bo; Jiang, Kaibiao; Li, Xinfeng; Zhang, Jidong; Liu, Zude

2017-09-01

Facet joint osteoarthritis is considered a consequence of the aging process; however, there is evidence that it may be associated with degenerative changes of other structures. The goal of this study was to investigate the correlation between lumbar multifidus muscle features and facet joint osteoarthritis. This retrospective study included 160 patients who had acute or chronic low back pain and were diagnosed with facet joint osteoarthritis on computed tomography scan. Morphometric parameters, including cross-sectional area, muscle-fat index, and percentage of bilateral multifidus asymmetry at L3-L4, L4-L5, and L5-S1, were evaluated with T2-weighted magnetic resonance imaging. Patients with facet joint osteoarthritis had a smaller cross-sectional area and a higher muscle-fat index than those without facet joint osteoarthritis (P<.001). In multivariate regression analysis, older age and higher muscle-fat index were independently associated with facet joint osteoarthritis at all 3 spinal levels (P<.001). Smaller cross-sectional area was independently associated with facet joint osteoarthritis only at L4-L5 (P=.005). Asymmetry of the bilateral multifidus cross-sectional area was independently associated with facet joint osteoarthritis at L5-S1 (P=.009), but did not seem to be responsible for asymmetric degeneration of the bilateral facet joints. A higher multifidus muscle-fat index was independently associated with facet joint osteoarthritis, and bilateral multifidus size asymmetry was associated with the development of facet joint osteoarthritis at L5-S1. It seems more accurate to consider facet joint osteoarthritis a failure of the whole joint structure, including the paraspinal musculature, rather than simply a failure of the facet joint cartilage. [Orthopedics. 2017; 40(5):e793-e800.]. Copyright 2017, SLACK Incorporated.

Muscular anatomy of an entoproct creeping-type larva reveals extraordinary high complexity and potential shared characters with mollusks.

PubMed

Merkel, Julia; Lieb, Bernhard; Wanninger, Andreas

2015-07-03

Entoprocta (Kamptozoa) is an enigmatic, acoelomate, tentacle-bearing phylum with indirect development, either via a swimming- or a creeping-type larva and still debated phylogenetic position within Lophotrochozoa. Recent morphological and neuro-anatomical studies on the creeping-type larva support a close relationship of Entoprocta and Mollusca, with a number of shared apomorphies including a tetraneurous nervous system and a complex serotonin-expressing apical organ. However, many morphological traits of entoproct larvae, in particular of the putative basal creeping-type larva, remain elusive. Applying fluorescent markers and 3D modeling, we found that this larval type has the most complex musculature hitherto described for any lophotrochozoan larva. The muscle systems identified include numerous novel and most likely creeping-type larva-specific structures such as frontal organ retractors, several other muscle fibers originating from the frontal organ, and longitudinal prototroch muscles. Interestingly, we found distinct muscle sets that are also present in several mollusks. These include paired sets of dorso-ventral muscles that intercross ventrally above the foot sole and a paired enrolling muscle that is distinct from the musculature of the body wall. Our data add further morphological support for an entoproct-mollusk relationship (Tetraneuralia) and strongly argue for the presence of an enrolling musculature as well as seriality (but not segmentation) in the last common tetraneuralian ancestor. The evolutionary driving forces that have led to the emergence of the extraordinarily complex muscular architecture in this short-lived, non-feeding entoproct larval type remain unknown, as are the processes that give rise to the highly different and much simpler muscular bodyplan of the adult entoproct during metamorphosis.

Finger muscle attachments for an OpenSim upper-extremity model.

PubMed

Lee, Jong Hwa; Asakawa, Deanna S; Dennerlein, Jack T; Jindrich, Devin L

2015-01-01

We determined muscle attachment points for the index, middle, ring and little fingers in an OpenSim upper-extremity model. Attachment points were selected to match both experimentally measured locations and mechanical function (moment arms). Although experimental measurements of finger muscle attachments have been made, models differ from specimens in many respects such as bone segment ratio, joint kinematics and coordinate system. Likewise, moment arms are not available for all intrinsic finger muscles. Therefore, it was necessary to scale and translate muscle attachments from one experimental or model environment to another while preserving mechanical function. We used a two-step process. First, we estimated muscle function by calculating moment arms for all intrinsic and extrinsic muscles using the partial velocity method. Second, optimization using Simulated Annealing and Hooke-Jeeves algorithms found muscle-tendon paths that minimized root mean square (RMS) differences between experimental and modeled moment arms. The partial velocity method resulted in variance accounted for (VAF) between measured and calculated moment arms of 75.5% on average (range from 48.5% to 99.5%) for intrinsic and extrinsic index finger muscles where measured data were available. RMS error between experimental and optimized values was within one standard deviation (S.D) of measured moment arm (mean RMS error = 1.5 mm < measured S.D = 2.5 mm). Validation of both steps of the technique allowed for estimation of muscle attachment points for muscles whose moment arms have not been measured. Differences between modeled and experimentally measured muscle attachments, averaged over all finger joints, were less than 4.9 mm (within 7.1% of the average length of the muscle-tendon paths). The resulting non-proprietary musculoskeletal model of the human fingers could be useful for many applications, including better understanding of complex multi-touch and gestural movements.

Finger Muscle Attachments for an OpenSim Upper-Extremity Model

PubMed Central

Lee, Jong Hwa; Asakawa, Deanna S.; Dennerlein, Jack T.; Jindrich, Devin L.

2015-01-01

We determined muscle attachment points for the index, middle, ring and little fingers in an OpenSim upper-extremity model. Attachment points were selected to match both experimentally measured locations and mechanical function (moment arms). Although experimental measurements of finger muscle attachments have been made, models differ from specimens in many respects such as bone segment ratio, joint kinematics and coordinate system. Likewise, moment arms are not available for all intrinsic finger muscles. Therefore, it was necessary to scale and translate muscle attachments from one experimental or model environment to another while preserving mechanical function. We used a two-step process. First, we estimated muscle function by calculating moment arms for all intrinsic and extrinsic muscles using the partial velocity method. Second, optimization using Simulated Annealing and Hooke-Jeeves algorithms found muscle-tendon paths that minimized root mean square (RMS) differences between experimental and modeled moment arms. The partial velocity method resulted in variance accounted for (VAF) between measured and calculated moment arms of 75.5% on average (range from 48.5% to 99.5%) for intrinsic and extrinsic index finger muscles where measured data were available. RMS error between experimental and optimized values was within one standard deviation (S.D) of measured moment arm (mean RMS error = 1.5 mm < measured S.D = 2.5 mm). Validation of both steps of the technique allowed for estimation of muscle attachment points for muscles whose moment arms have not been measured. Differences between modeled and experimentally measured muscle attachments, averaged over all finger joints, were less than 4.9 mm (within 7.1% of the average length of the muscle-tendon paths). The resulting non-proprietary musculoskeletal model of the human fingers could be useful for many applications, including better understanding of complex multi-touch and gestural movements. PMID:25853869

Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice.

PubMed

Sayed, Ramy K A; de Leonardis, Erika Chacin; Guerrero-Martínez, José A; Rahim, Ibtissem; Mokhtar, Doaa M; Saleh, Abdelmohaimen M; Abdalla, Kamal E H; Pozo, María J; Escames, Germaine; López, Luis C; Acuña-Castroviejo, Darío

2016-10-01

The gastrocnemius muscle (GM) of young (3months) and aged (12months) female wild-type C57/BL6 mice was examined by light and electron microscopy, looking for the presence of structural changes at early stage of the aging process. Morphometrical parameters including body and gastrocnemius weights, number and type of muscle fibers, cross section area (CSA), perimeter, and Feret's diameter of single muscle fiber, were measured. Moreover, lengths of the sarcomere, A-band, I-band, H-zone, and number and CSA of intermyofibrillar mitochondria (IFM), were also determined. The results provide evidence that 12month-old mice had significant changes on skeletal muscle structure, beginning with the reduction of gastrocnemius weight to body weight ratio, compatible with an early loss of skeletal muscle function and strength. Moreover, light microscopy revealed increased muscle fibers size, with a significant increase on their CSA, perimeter, and diameter of both type I and type II muscle fibers, and a reduction in the percentage of muscle area occupied by type II fibers. Enhanced connective tissue infiltrations, and the presence of centrally nucleated muscle fibers, were also found in aged mice. These changes may underlie an attempt to compensate the loss of muscle mass and muscle fibers number. Furthermore, electron microscopy discovered a significant age-dependent increase in the length of sarcomeres, I and H bands, and reduction on the overlapped actin/myosin length, supporting contractile force loss with age. Electron microscopy also showed an increased number and CSA of IFM with age, which may reveal more endurance at 12months of age. Together, mice at early stage of aging already show significant changes in gastrocnemius muscle morphology and ultrastructure that are suggestive of the onset of sarcopenia. Copyright © 2016 Elsevier Inc. All rights reserved.

A Neuro-Mechanical Model Explaining the Physiological Role of Fast and Slow Muscle Fibres at Stop and Start of Stepping of an Insect Leg

PubMed Central

Toth, Tibor Istvan; Grabowska, Martyna; Schmidt, Joachim; Büschges, Ansgar; Daun-Gruhn, Silvia

2013-01-01

Stop and start of stepping are two basic actions of the musculo-skeletal system of a leg. Although they are basic phenomena, they require the coordinated activities of the leg muscles. However, little is known of the details of how these activities are generated by the interactions between the local neuronal networks controlling the fast and slow muscle fibres at the individual leg joints. In the present work, we aim at uncovering some of those details using a suitable neuro-mechanical model. It is an extension of the model in the accompanying paper and now includes all three antagonistic muscle pairs of the main joints of an insect leg, together with their dedicated neuronal control, as well as common inhibitory motoneurons and the residual stiffness of the slow muscles. This model enabled us to study putative processes of intra-leg coordination during stop and start of stepping. We also made use of the effects of sensory signals encoding the position and velocity of the leg joints. Where experimental observations are available, the corresponding simulation results are in good agreement with them. Our model makes detailed predictions as to the coordination processes of the individual muscle systems both at stop and start of stepping. In particular, it reveals a possible role of the slow muscle fibres at stop in accelerating the convergence of the leg to its steady-state position. These findings lend our model physiological relevance and can therefore be used to elucidate details of the stop and start of stepping in insects, and perhaps in other animals, too. PMID:24278108

Overexpression of NF90-NF45 Represses Myogenic MicroRNA Biogenesis, Resulting in Development of Skeletal Muscle Atrophy and Centronuclear Muscle Fibers

PubMed Central

Todaka, Hiroshi; Higuchi, Takuma; Yagyu, Ken-ichi; Sugiyama, Yasunori; Yamaguchi, Fumika; Morisawa, Keiko; Ono, Masafumi; Fukushima, Atsuki; Tsuda, Masayuki; Taniguchi, Taketoshi

2015-01-01

MicroRNAs (miRNAs) are involved in the progression and suppression of various diseases through translational inhibition of target mRNAs. Therefore, the alteration of miRNA biogenesis induces several diseases. The nuclear factor 90 (NF90)-NF45 complex is known as a negative regulator in miRNA biogenesis. Here, we showed that NF90-NF45 double-transgenic (dbTg) mice develop skeletal muscle atrophy and centronuclear muscle fibers in adulthood. Subsequently, we found that the levels of myogenic miRNAs, including miRNA 133a (miR-133a), which promote muscle maturation, were significantly decreased in the skeletal muscle of NF90-NF45 dbTg mice compared with those in wild-type mice. However, levels of primary transcripts of the miRNAs (pri-miRNAs) were clearly elevated in NF90-NF45 dbTg mice. This result indicated that the NF90-NF45 complex suppressed miRNA production through inhibition of pri-miRNA processing. This finding was supported by the fact that processing of pri-miRNA 133a-1 (pri-miR-133a-1) was inhibited via binding of NF90-NF45 to the pri-miRNA. Finally, the level of dynamin 2, a causative gene of centronuclear myopathy and concomitantly a target of miR-133a, was elevated in the skeletal muscle of NF90-NF45 dbTg mice. Taken together, we conclude that the NF90-NF45 complex induces centronuclear myopathy through increased dynamin 2 expression by an NF90-NF45-induced reduction of miR-133a expression in vivo. PMID:25918244

[Effect of weightlessness on the course of the reparative process in the muscles of the biosatellite Kosmos-2044 rats].

PubMed

Il'ina-Kakueva, E I; Burkovskaia, T E

1991-01-01

The repair process in the soleus and gastrocnemius muscles of SPF Wistar rats flown for 14 days on the biosatellite Cosmos-2044 was investigated. The muscles were injured 2 days before launch by means of clamp forceps. The exposure inhibited the process but did not impair its phasic development. As a result, the reparative field diminished and took the size of an atrophic muscle; thinner myofibers appeared that originated from the ends of injured atrophic fibers and fibers that underwent splitting. It is postulated that repair inhibition is caused by the same mechanisms that produce muscle atrophy in microgravity. It is suggested that both repair inhibition and muscle atrophy are induced by disorders in the neurotrophic regulation of metabolism due to partial disuse.

Development of a human body finite element model with multiple muscles and their controller for estimating occupant motions and impact responses in frontal crash situations.

PubMed

Iwamoto, Masami; Nakahira, Yuko; Kimpara, Hideyuki; Sugiyama, Takahiko; Min, Kyuengbo

2012-10-01

A few reports suggest differences in injury outcomes between cadaver tests and real-world accidents under almost similar conditions. This study hypothesized that muscle activity could primarily cause the differences, and then developed a human body finite element (FE) model with individual muscles. Each muscle was modeled as a hybrid model of bar elements with active properties and solid elements with passive properties. The model without muscle activation was firstly validated against five series of cadaver test data on impact responses in the anterior-posterior direction. The model with muscle activation levels estimated based on electromyography (EMG) data was secondly validated against four series of volunteer test data on bracing effects for stiffness and thickness of an upper arm muscle, and braced driver's responses under a static environment and a brake deceleration. A muscle controller using reinforcement learning (RL), which is a mathematical model of learning process in the basal ganglia associated with human postural controls, were newly proposed to estimate muscle activity in various occupant conditions including inattentive and attentive conditions. Control of individual muscles predicted by RL reproduced more human like head-neck motions than conventional control of two groups of agonist and antagonist muscles. The model and the controller demonstrated that head-neck motions of an occupant under an impact deceleration of frontal crash were different in between a bracing condition with maximal braking force and an occupant condition predicted by RL. The model and the controller have the potential to investigate muscular effects in various occupant conditions during frontal crashes.

Development of an Evidence-Based Clinical Algorithm for Practice in Hypotonia Assessment: A Proposal

PubMed Central

2014-01-01

Background Assessing muscle tone in children is essential during the neurological assessment and is often essential in ensuring a more accurate diagnosis for appropriate management. While there have been advances in child neurology, there remains much contention around the subjectivity of the clinical assessment of hypotonia, which is often the first step in the diagnostic process. Objective In response to this challenge, the objective of the study is to develop and validate a prototype of a decision making process in the form of a clinical algorithm that will guide clinicians during this assessment process. Methods Design research within a pragmatic stance will be employed in this study. Multi-phase stages of assessment, prototyping and evaluation will occur. These will include processes that include a systematic review, processes of reflection and action as well as validation methods. Given the mixed methods nature of this study, use of NVIVO or ATLAS-ti will be used in the analysis of qualitative data and SPSS for quantitative data. Results Initial results from the systematic review revealed a paucity of scientific literature that documented the objective assessment of hypotonia in children. The review identified the need for more studies with greater methodological rigor in order to determine best practice with respect to the methods used in the assessment of low muscle tone in the paediatric population. Conclusions It is envisaged that this proposal will contribute to a more accurate clinical diagnosis of children with low muscle tone in the absence of a gold standard. We anticipate that the use of this tool will ultimately assist clinicians towards moving to evidenced based practice whilst upholding best practice in the care of children with hypotonia. PMID:25485571

Powerful signals for weak muscles.

PubMed

Saini, Amarjit; Faulkner, Steve; Al-Shanti, Nasser; Stewart, Claire

2009-10-01

The aim of the present review is to summarise, evaluate and critique the different mechanisms involved in anabolic growth of skeletal muscle and the catabolic processes involved in cancer cachexia and sarcopenia of ageing. This is highly relevant, since they represent targets for future promising clinical investigations. Sarcopenia is an inevitable process associated with a gradual reduction in muscle mass and strength, associated with a reduction in motor unit number and atrophy of muscle fibres, especially the fast type IIa fibres. The loss of muscle mass with ageing is clinically important because it leads to diminished functional ability and associated complications. Cachexia is widely recognised as severe and rapid wasting accompanying disease states such as cancer or immunodeficiency disease. One of the main characteristics of cancer cachexia is asthenia or lack of strength, which is directly related to the muscle loss. Indeed, apart from the speed of loss, muscle wasting during cancer and ageing share many common metabolic pathways and mediators. In healthy young individuals, muscles maintain their mass and function because of a balance between protein synthesis and protein degradation associated with rates of anabolic and catabolic processes, respectively. Muscles grow (hypertrophy) when protein synthesis exceeds protein degradation. Conversely, muscles shrink (atrophy) when protein degradation dominates. These processes are not occurring independently of each other, but are finely coordinated by a web of intricate signalling networks. Such signalling networks are in charge of executing environmental and cellular cues that ultimately determine whether muscle proteins are synthesised or degraded. Increasing our understanding for the pathways involved in hypertrophy and atrophy and particularly the interaction of these pathways is essential in designing therapeutic strategies for both prevention and treatment of muscle wasting conditions with age and with disease.

Intermittent muscle activity in the feedback loop of postural control system during natural quiet standing.

PubMed

Tanabe, Hiroko; Fujii, Keisuke; Kouzaki, Motoki

2017-09-06

The origin of continual body oscillation during quiet standing is a neural-muscular-skeletal closed feedback loop system that includes insufficient joint stiffness and a time delay. Thus, muscle activity and joint oscillations are nonlinear during quiet standing, making it difficult to demonstrate the muscular-skeletal relationship experimentally. Here we experimentally revealed this relationship using intermittent control theory, in which non-actuation works to stabilize the skeletal system towards equilibrium. We found that leg muscles were activated/inactivated when the state point was located in the opposite/same direction as the direction of anatomical action, which was associated with joint torque actuating the body towards equilibrium. The derivative values of stability index defined in the phase space approximately 200 ms before muscle inactivation were also larger than those before activation for some muscles. These results indicate that bipedal standing might be achieved by monitoring the rate of change of stability/instability components and generating joint torque to stabilize the body. In conclusion, muscles are likely to activate in an event-driven manner during quiet standing and a possible metric for on/off switching is SI dot, and our methodology of EMG processing could allows us to extract such event-driven intermittent muscle activities.

Sarcocystis fayeri in skeletal muscle of horses with neuromuscular disease.

PubMed

Aleman, Monica; Shapiro, Karen; Sisó, Silvia; Williams, Diane C; Rejmanek, Daniel; Aguilar, Beatriz; Conrad, Patricia A

2016-01-01

Recent reports of Sarcocystis fayeri-induced toxicity in people consuming horse meat warrant investigation on the prevalence and molecular characterization of Sarcocystis spp. infection in horses. Sarcocysts in skeletal muscle of horses have been commonly regarded as an incidental finding. In this study, we investigated the prevalence of sarcocysts in skeletal muscle of horses with neuromuscular disease. Our findings indicated that S. fayeri infection was common in young mature horses with neuromuscular disease and could be associated with myopathic and neurogenic processes. The number of infected muscles and number of sarcocysts per muscle were significantly higher in diseased than in control horses. S. fayeri was predominantly found in low oxidative highly glycolytic myofibers. This pathogen had a high glycolytic metabolism. Common clinical signs of disease included muscle atrophy, weakness with or without apparent muscle pain, gait deficits, and dysphagia in horses with involvement of the tongue and esophagus. Horses with myositis were lethargic, apparently painful, stiff, and reluctant to move. Similar to humans, sarcocystosis and cardiomyopathy can occur in horses. This study did not establish causality but supported a possible association (8.9% of cases) with disease. The assumption of Sarcocysts spp. being an incidental finding in every case might be inaccurate. Copyright © 2015 Elsevier B.V. All rights reserved.

Analysis of EMG patterns of control subjects and subjects with ACL deficiency during an unanticipated walking cut task.

PubMed

Houck, Jeff R; Wilding, Gregory E; Gupta, Resmi; De Haven, Kenneth E; Maloney, Mike

2007-04-01

The purpose of this study was to describe the muscle activation patterns of the vastus lateralis (VL), medial hamstrings (MH) and lateral hamstrings (LH) associated with subjects that were anterior cruciate ligament (ACL) deficient and controls. A total of 54 subjects participated in this study including 25 ACL deficient subjects subdivided into copers (n=9) and non-copers (n=16) using clinical criteria. Muscle activation patterns were recorded at 1000 Hz during an unanticipated side step cut task. The root mean square processed data (time constant 11 ms) were ensemble averaged from 20% of stance before heel strike to toe off. Using the first five harmonics of the Fourier Coefficients as features, muscle activation patterns were divided using a cluster analysis algorithm. A majority (76-93%) of control subjects used three muscle activation patterns for each muscle. The coper group preferentially used a particular VL and MH activation pattern >2 times more frequently than controls. The non-coper group also preferentially used a MH activation pattern >2 times more frequently than controls and utilized a unique MH and LH activation pattern, distinct from the copers and controls. Specific muscle activation patterns distinguish subsets of subjects that are healthy and injured, suggesting possible patterns of muscle activation that contribute to coping status.

Development of low postural tone compensatory patterns in children - theoretical basis.

PubMed

Gogola, Anna; Saulicz, Edward; Kuszewski, Michał; Matyja, Małgorzata; Myśliwiec, Andrzej

2014-01-01

Neurological literature indicates the existence of children with low postural tone without association with central nervous system damage. This fact induces to think about mechanisms, which allow these children to maintain upright posture. There is a suspicion that compensatory mechanism included in this process, enables to achieve upright posture, but at expense of body posture quality. Observations of children's developmental stages caused determination of some postural tone area, which comprise both children with normotonia and with low postural tone without characteristics of central nervous system (CNS) damage. Set of specific qualities allows determination of two types of low postural tone: spastoidal and atetoidal type. Spastoidal type is characterized by deep trunk muscles (local) low postural tone compensated by excessive tension of superficial muscles (global). Atetoidal type includes children with low postural tone in both deep and superficial muscles. At inefficient active subsystem, verticalization proceeds at excessive use of passive subsystem qualities, that is meniscus, ligament, bone shape, and muscles passive features. From neurodevelopmental point of view compensatory mechanisms can be used in children with low postural tone in order to achieve upright posture, but at expense of body posture quality.

MRI-based quantification of Duchenne muscular dystrophy in a canine model

NASA Astrophysics Data System (ADS)

Wang, Jiahui; Fan, Zheng; Kornegay, Joe N.; Styner, Martin A.

2011-03-01

Duchenne muscular dystrophy (DMD) is a progressive and fatal X-linked disease caused by mutations in the DMD gene. Magnetic resonance imaging (MRI) has shown potential to provide non-invasive and objective biomarkers for monitoring disease progression and therapeutic effect in DMD. In this paper, we propose a semi-automated scheme to quantify MRI features of golden retriever muscular dystrophy (GRMD), a canine model of DMD. Our method was applied to a natural history data set and a hydrodynamic limb perfusion data set. The scheme is composed of three modules: pre-processing, muscle segmentation, and feature analysis. The pre-processing module includes: calculation of T2 maps, spatial registration of T2 weighted (T2WI) images, T2 weighted fat suppressed (T2FS) images, and T2 maps, and intensity calibration of T2WI and T2FS images. We then manually segment six pelvic limb muscles. For each of the segmented muscles, we finally automatically measure volume and intensity statistics of the T2FS images and T2 maps. For the natural history study, our results showed that four of six muscles in affected dogs had smaller volumes and all had higher mean intensities in T2 maps as compared to normal dogs. For the perfusion study, the muscle volumes and mean intensities in T2FS were increased in the post-perfusion MRI scans as compared to pre-perfusion MRI scans, as predicted. We conclude that our scheme successfully performs quantitative analysis of muscle MRI features of GRMD.

Contribution of the supplementary motor area and the cerebellum to the anticipatory postural adjustments and execution phases of human gait initiation.

PubMed

Richard, Aliénor; Van Hamme, Angèle; Drevelle, Xavier; Golmard, Jean-Louis; Meunier, Sabine; Welter, Marie-Laure

2017-09-01

Several brain structures including the brainstem, the cerebellum and the frontal cortico-basal ganglia network, with the primary and premotor areas have been shown to participate in the functional organization of gait initiation and postural control in humans, but their respective roles remain poorly understood. The aim of this study was to better understand the role of the supplementary motor area (SMA) and posterior cerebellum in the gait initiation process. Gait initiation parameters were recorded in 22 controls both before and after continuous theta burst transcranial stimulation (cTBS) of the SMA and cerebellum, and were compared to sham stimulation, using a randomized double-blind design study. The two phases of gait initiation process were analyzed: anticipatory postural adjustments (APAs) and execution, with recordings of soleus and tibialis anterior muscles. Functional inhibition of the SMA led to a shortened APA phase duration with advanced and increased muscle activity; during execution, it also advanced muscle co-activation and decreased the duration of stance soleus activity. Cerebellar functional inhibition did not influence the APA phase duration and amplitude but increased muscle co-activation, it decreased execution duration and showed a trend to increase velocity, with increased swing soleus muscle duration and activity. The results suggest that the SMA contributes to both the timing and amplitude of the APAs with no influence on step execution and the posterior cerebellum in the coupling between the APAs and execution phases and leg muscle activity pattern during gait initiation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Assessment of Muscle Fatigue Associated with Prolonged Standing in the Workplace

PubMed Central

Omar, Abdul Rahman; Saman, Alias Mohd; Othman, Ibrahim

2012-01-01

Objectives The objectives of this study were to determine the psychological fatigue and analyze muscle activity of production workers who are performing processes jobs while standing for prolonged time periods. Methods The psychological fatigue experienced by the workers was obtained through questionnaire surveys. Meanwhile, muscle activity has been analyzed using surface electromyography (sEMG) measurement. Lower extremities muscles include: erector spinae, tibialis anterior, and gastrocnemius were concurrently measured for more than five hours of standing. Twenty male production workers in a metal stamping company participated as subjects in this study. The subjects were required to undergo questionnaire surveys and sEMG measurement. Results Results of the questionnaire surveys found that all subjects experienced psychological fatigue due to prolonged standing jobs. Similarly, muscle fatigue has been identified through sEMG measurement. Based on the non-parametric statistical test using the Spearman's rank order correlation, the left erector spinae obtained a moderate positive correlation and statistically significant (rs = 0.552, p < 0.05) between the results of questionnaire surveys and sEMG measurement. Conclusion Based on this study, the authors concluded that prolonged standing was contributed to psychological fatigue and to muscle fatigue among the production workers. PMID:22953228

Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.

PubMed

Rønning, Sissel B; Carlson, Cathrine R; Stang, Espen; Kolset, Svein O; Hollung, Kristin; Pedersen, Mona E

2015-01-01

The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.

Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans.

PubMed

Hwang, Hyundoo; Barnes, Dawn E; Matsunaga, Yohei; Benian, Guy M; Ono, Shoichiro; Lu, Hang

2016-01-29

The sarcomere, the fundamental unit of muscle contraction, is a highly-ordered complex of hundreds of proteins. Despite decades of genetics work, the functional relationships and the roles of those sarcomeric proteins in animal behaviors remain unclear. In this paper, we demonstrate that optogenetic activation of the motor neurons that induce muscle contraction can facilitate quantitative studies of muscle kinetics in C. elegans. To increase the throughput of the study, we trapped multiple worms in parallel in a microfluidic device and illuminated for photoactivation of channelrhodopsin-2 to induce contractions in body wall muscles. Using image processing, the change in body size was quantified over time. A total of five parameters including rate constants for contraction and relaxation were extracted from the optogenetic assay as descriptors of sarcomere functions. To potentially relate the genes encoding the sarcomeric proteins functionally, a hierarchical clustering analysis was conducted on the basis of those parameters. Because it assesses physiological output different from conventional assays, this method provides a complement to the phenotypic analysis of C. elegans muscle mutants currently performed in many labs; the clusters may provide new insights and drive new hypotheses for functional relationships among the many sarcomere components.

Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Hwang, Hyundoo; Barnes, Dawn E.; Matsunaga, Yohei; Benian, Guy M.; Ono, Shoichiro; Lu, Hang

2016-01-01

The sarcomere, the fundamental unit of muscle contraction, is a highly-ordered complex of hundreds of proteins. Despite decades of genetics work, the functional relationships and the roles of those sarcomeric proteins in animal behaviors remain unclear. In this paper, we demonstrate that optogenetic activation of the motor neurons that induce muscle contraction can facilitate quantitative studies of muscle kinetics in C. elegans. To increase the throughput of the study, we trapped multiple worms in parallel in a microfluidic device and illuminated for photoactivation of channelrhodopsin-2 to induce contractions in body wall muscles. Using image processing, the change in body size was quantified over time. A total of five parameters including rate constants for contraction and relaxation were extracted from the optogenetic assay as descriptors of sarcomere functions. To potentially relate the genes encoding the sarcomeric proteins functionally, a hierarchical clustering analysis was conducted on the basis of those parameters. Because it assesses physiological output different from conventional assays, this method provides a complement to the phenotypic analysis of C. elegans muscle mutants currently performed in many labs; the clusters may provide new insights and drive new hypotheses for functional relationships among the many sarcomere components.

Effect of sex and RYR1 gene mutation on the muscle proteomic profile and main physiological biomarkers in pigs at slaughter.

PubMed

Oliván, Mamen; González, Joel; Bassols, Anna; Díaz, Fernando; Carreras, Ricard; Mainau, Eva; Arroyo, Laura; Peña, Raquel; Potes, Yaiza; Coto-Montes, Ana; Hollung, Kristin; Velarde, Antonio

2018-07-01

Gender and RYR1 gene mutation might have an effect on the muscle metabolic characteristics and on the animal's stress at slaughter, which could influence the process of muscle-to-meat conversion. Forty-eight pigs were distributed in a design including two factors: sex (male/female) and RYR1 genotype (NN/Nn). At slaughter, physiological blood biomarkers and muscle proteome were analyzed and carcass and meat quality traits were registered. Females had higher serum levels of glucose, urea, C-reactive protein "CRP", Pig-MAP and glutation-peroxidase "GPx" and lower levels of lactate, showed faster muscle pH decline and higher meat exudation. RYR1 mutation increased serum creatinine, creatine kinase and CRP and decreased GPx. The proteomic study highlighted significant effects of gender and RYR1 genotype on proteins related to fibre composition, antioxidant defense and post mortem glycolytic pathway, which correlate to differences of meat quality. This study provides interesting information on muscle biomarkers of the ultimate meat quality that are modulated by the animal's individual susceptibility to stress at slaughter. Copyright © 2018 Elsevier Ltd. All rights reserved.

Characterization of the Inflammatory Response in Dystrophic Muscle Using Flow Cytometry.

PubMed

Kastenschmidt, Jenna M; Avetyan, Ileen; Villalta, S A

2018-01-01

Although mutations of the dystrophin gene are the causative defect in Duchenne muscular dystrophy (DMD) patients, secondary disease processes such as inflammation contribute greatly to the pathogenesis of DMD. Genetic and histological studies have shown that distinct facets of the immune system promote muscle degeneration or regeneration during muscular dystrophy through mechanisms that are only beginning to be defined. Although histological methods have allowed the enumeration and localization of immune cells within dystrophic muscle, they are limited in their ability to assess the full spectrum of phenotypic states of an immune cell population and its functional characteristics. This chapter highlights flow cytometry methods for the isolation and functional study of immune cell populations from muscle of the mdx mouse model of DMD. We include a detailed description of preparing single-cell suspensions of dystrophic muscle that maintain the integrity of cell-surface markers used to identify macrophages, eosinophils, group 2 innate lymphoid cells, and regulatory T cells. This method complements the battery of histological assays that are currently used to study the role of inflammation in muscular dystrophy, and provides a platform capable of being integrated with multiple downstream methodologies for the mechanistic study of immunity in muscle degenerative diseases.

Estrogen-Related Receptor-α Coordinates Transcriptional Programs Essential for Exercise Tolerance and Muscle Fitness

PubMed Central

Perry, Marie-Claude; Dufour, Catherine R.; Tam, Ingrid S.; B'chir, Wafa

2014-01-01

Muscle fitness is an important determinant of health and disease. However, the molecular mechanisms involved in the coordinate regulation of the metabolic and structural determinants of muscle endurance are still poorly characterized. Herein, we demonstrate that estrogen-related receptor α (ERRα, NR3B1) is essential for skeletal muscle fitness. Notably, we show that ERRα-null animals are hypoactive and that genetic or therapeutic disruption of ERRα in mice results in reduced exercise tolerance. Mice lacking ERRα also exhibited lactatemia at exhaustion. Gene expression profiling demonstrates that ERRα plays a key role in various metabolic processes important for muscle function including energy substrate transport and use (Ldhd, Slc16a1, Hk2, and Glul), the tricarboxylic acid cycle (Cycs, and Idh3g), and oxidative metabolism (Pdha1, and Uqcrq). Metabolomics studies revealed impairment in replenishment of several amino acids (eg, glutamine) during recovery to exercise. Moreover, loss of ERRα was found to alter the expression of genes involved in oxidative stress response (Hmox1), maintenance of muscle fiber integrity (Trim63, and Hspa1b), and muscle plasticity and neovascularization (Vegfa). Taken together, our study shows that ERRα plays a key role in directing transcriptional programs required for optimal mitochondrial oxidative potential and muscle fitness, suggesting that modulation of ERRα activity could be used to manage metabolic myopathies and/or promote the adaptive response to physical exercise. PMID:25361393

Integrative Analysis of Porcine microRNAome during Skeletal Muscle Development

PubMed Central

Qin, Lijun; Chen, Yaosheng; Liu, Xiaohong; Ye, Sanxing; Yu, Kaifan; Huang, Zheng; Yu, Jingwei; Zhou, Xingyu; Chen, Hu; Mo, Delin

2013-01-01

Pig is an important agricultural animal for meat production and provides a valuable model for many human diseases. Functional studies have demonstrated that microRNAs (miRNAs) play critical roles in almost all aspects of skeletal muscle development and disease pathogenesis. To investigate the miRNAs involved in regulating different periods of skeletal muscle development, we herein performed a comprehensive research for porcine microRNAome (miRNAome) during 10 skeletal muscle developmental stages including 35, 49, 63, 77, 91 dpc (days post coitum) and 2, 28, 90, 120, 180 dpn (days postnatal) using Solexa sequencing technology. Our results extend the repertoire of pig miRNAome to 247 known miRNAs processed from 210 pre-miRNAs and 297 candidate novel miRNAs through comparison with known miRNAs in the miRBase. Expression analysis of the 15 most abundant miRNAs in every library indicated that functional miRNAome may be smaller and tend to be highly expressed. A series of muscle-related miRNAs summarized in our study present different patterns between myofibers formation phase and muscle maturation phase, providing valuable reference for investigation of functional miRNAs during skeletal muscle development. Analysis of temporal profiles of miRNA expression identifies 18 novel candidate myogenic miRNAs in pig, which might provide new insight into regulation mechanism mediated by miRNAs underlying muscle development. PMID:24039761

Research opportunities in muscle atrophy

NASA Technical Reports Server (NTRS)

Herbison, G. J. (Editor); Talbot, J. M. (Editor)

1984-01-01

Muscle atrophy in a weightless environment is studied. Topics of investigation include physiological factors of muscle atrophy in space flight, biochemistry, countermeasures, modelling of atrophied muscle tissue, and various methods of measurement of muscle strength and endurance. A review of the current literature and suggestions for future research are included.

The quasi-parallel lives of satellite cells and atrophying muscle

PubMed Central

Biressi, Stefano; Gopinath, Suchitra D.

2015-01-01

Skeletal muscle atrophy or wasting accompanies various chronic illnesses and the aging process, thereby reducing muscle function. One of the most important components contributing to effective muscle repair in postnatal organisms, the satellite cells (SCs), have recently become the focus of several studies examining factors participating in the atrophic process. We critically examine here the experimental evidence linking SC function with muscle loss in connection with various diseases as well as aging, and in the subsequent recovery process. Several recent reports have investigated the changes in SCs in terms of their differentiation and proliferative capacity in response to various atrophic stimuli. In this regard, we review the molecular changes within SCs that contribute to their dysfunctional status in atrophy, with the intention of shedding light on novel potential pharmacological targets to counteract the loss of muscle mass. PMID:26257645

Effects of exercise on obesity-induced mitochondrial dysfunction in skeletal muscle

PubMed Central

Heo, Jun-Won; No, Mi-Hyun; Park, Dong-Ho; Kang, Ju-Hee; Seo, Dae Yun; Han, Jin; Neufer, P. Darrell

2017-01-01

Obesity is known to induce inhibition of glucose uptake, reduction of lipid metabolism, and progressive loss of skeletal muscle function, which are all associated with mitochondrial dysfunction in skeletal muscle. Mitochondria are dynamic organelles that regulate cellular metabolism and bioenergetics, including ATP production via oxidative phosphorylation. Due to these critical roles of mitochondria, mitochondrial dysfunction results in various diseases such as obesity and type 2 diabetes. Obesity is associated with impairment of mitochondrial function (e.g., decrease in O2 respiration and increase in oxidative stress) in skeletal muscle. The balance between mitochondrial fusion and fission is critical to maintain mitochondrial homeostasis in skeletal muscle. Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion and fission by favorably shifting fission or reducing fusion proteins. Mitophagy is the catabolic process of damaged or unnecessary mitochondria. Obesity reduces mitochondrial biogenesis in skeletal muscle and increases accumulation of dysfunctional cellular organelles, suggesting that mitophagy does not work properly in obesity. Mitochondrial dysfunction and oxidative stress are reported to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in skeletal muscle. It is well known that exercise is the most effective intervention to protect against obesity. Although the cellular and molecular mechanisms by which exercise protects against obesity-induced mitochondrial dysfunction in skeletal muscle are not clearly elucidated, exercise training attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in obese skeletal muscle. PMID:29200899

Org-1-dependent lineage reprogramming generates the ventral longitudinal musculature of the Drosophila heart.

PubMed

Schaub, Christoph; März, Johannes; Reim, Ingolf; Frasch, Manfred

2015-02-16

Only few examples of transdifferentiation, which denotes the conversion of one differentiated cell type to another, are known to occur during normal development, and more often, it is associated with regeneration processes. With respect to muscles, dedifferentiation/redifferentiation processes have been documented during post-traumatic muscle regeneration in blastema of newts as well as during myocardial regeneration. As shown herein, the ventral longitudinal muscles of the adult Drosophila heart arise from specific larval alary muscles in a process that represents the first known example of syncytial muscle transdifferentiation via dedifferentiation into mononucleate myoblasts during normal development. We demonstrate that this unique process depends on the reinitiation of a transcriptional program previously employed for embryonic alary muscle development, in which the factors Org-1 (Drosophila Tbx1) and Tailup (Drosophila Islet1) are key components. During metamorphosis, the action of these factors is combined with cell-autonomous inputs from the ecdysone steroid and the Hox gene Ultrabithorax, which provide temporal and spatial specificity to the transdifferentiation events. Following muscle dedifferentiation, inductive cues, particularly from the remodeling heart tube, are required for the redifferentiation of myoblasts into ventral longitudinal muscles. Our results provide new insights into mechanisms of lineage commitment and cell-fate plasticity during development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials

PubMed Central

Marzetti, Emanuele; Calvani, Riccardo; Cesari, Matteo; Buford, Thomas W.; Lorenzi, Maria; Behnke, Bradley J.; Leeuwenburgh, Christiaan

2013-01-01

Sarcopenia, the age-related loss of muscle mass and function, imposes a dramatic burden on individuals and society. The development of preventive and therapeutic strategies against sarcopenia is therefore perceived as an urgent need by health professionals and has instigated intensive research on the pathophysiology of this syndrome. The pathogenesis of sarcopenia is multifaceted and encompasses lifestyle habits, systemic factors (e.g., chronic inflammation and hormonal alterations), local environment perturbations (e.g., vascular dysfunction), and intramuscular specific processes. In this scenario, derangements in skeletal myocyte mitochondrial function are recognized as major factors contributing to the age-dependent muscle degeneration. In this review, we summarize prominent findings and controversial issues on the contribution of specific mitochondrial processes – including oxidative stress, quality control mechanisms and apoptotic signaling – on the development of sarcopenia. Extramuscular alterations accompanying the aging process with a potential impact on myocyte mitochondrial function are also discussed. We conclude with presenting methodological and safety considerations for the design of clinical trials targeting mitochondrial dysfunction to treat sarcopenia. Special emphasis is placed on the importance of monitoring the effects of an intervention on muscle mitochondrial function and identifying the optimal target population for the trial. PMID:23845738

Muscle Protein Profiles Used for Prediction of Texture of Farmed Salmon (Salmo salar L.).

PubMed

Ørnholt-Johansson, Gine; Frosch, Stina; Gudjónsdóttir, María; Wulff, Tune; Jessen, Flemming

2017-04-26

A soft texture is undesired in Atlantic salmon as it leads to downgrading and reduced yield, yet it is a factor for which the cause is not fully understood. This lack of understanding highlights the need for identifying the cause of the soft texture and developing solutions by which the processing industry can improve the yield. Changes in muscle protein profiles can occur both pre- and postharvest and constitute an overall characterization of the muscle properties including texture. The aim of this study was to investigate this relationship between specific muscle proteins and the texture of the salmon fillet. Samples for 2D-gel-based proteomics were taken from the fillet above the lateral line at the same position as where the texture had been measured. The resulting protein profiles were analyzed using multivariate data analysis. Sixteen proteins were found to correlate to the measured texture, showing that it is possible to predict peak force based on a small subset of proteins. Additionally, eight of the 16 proteins were identified by tandem mass spectrometry including serum albumin, dipeptidyl peptidase 3, heat shock protein 70, annexins, and a protein presumed to be a titin fragment. It is contemplated that the identification of these proteins and their significance for the measured texture will contribute to further understanding of the Atlantic salmon muscle texture.

Isolation and Quantitative Immunocytochemical Characterization of Primary Myogenic Cells and Fibroblasts from Human Skeletal Muscle

PubMed Central

Agley, Chibeza C.; Rowlerson, Anthea M.; Velloso, Cristiana P.; Lazarus, Norman L.; Harridge, Stephen D. R.

2015-01-01

The repair and regeneration of skeletal muscle requires the action of satellite cells, which are the resident muscle stem cells. These can be isolated from human muscle biopsy samples using enzymatic digestion and their myogenic properties studied in culture. Quantitatively, the two main adherent cell types obtained from enzymatic digestion are: (i) the satellite cells (termed myogenic cells or muscle precursor cells), identified initially as CD56+ and later as CD56+/desmin+ cells and (ii) muscle-derived fibroblasts, identified as CD56– and TE-7+. Fibroblasts proliferate very efficiently in culture and in mixed cell populations these cells may overrun myogenic cells to dominate the culture. The isolation and purification of different cell types from human muscle is thus an important methodological consideration when trying to investigate the innate behavior of either cell type in culture. Here we describe a system of sorting based on the gentle enzymatic digestion of cells using collagenase and dispase followed by magnetic activated cell sorting (MACS) which gives both a high purity (>95% myogenic cells) and good yield (~2.8 x 106 ± 8.87 x 105 cells/g tissue after 7 days in vitro) for experiments in culture. This approach is based on incubating the mixed muscle-derived cell population with magnetic microbeads beads conjugated to an antibody against CD56 and then passing cells though a magnetic field. CD56+ cells bound to microbeads are retained by the field whereas CD56– cells pass unimpeded through the column. Cell suspensions from any stage of the sorting process can be plated and cultured. Following a given intervention, cell morphology, and the expression and localization of proteins including nuclear transcription factors can be quantified using immunofluorescent labeling with specific antibodies and an image processing and analysis package. PMID:25650991

Proteomic analysis of laser capture microscopy purified myotendinous junction regions from muscle sections

PubMed Central

2014-01-01

The myotendinous junction is a specialized structure of the muscle fibre enriched in mechanosensing complexes, including costameric proteins and core elements of the z-disc. Here, laser capture microdissection was applied to purify membrane regions from the myotendinous junctions of mouse skeletal muscles, which were then processed for proteomic analysis. Sarcolemma sections from the longitudinal axis of the muscle fibre were used as control for the specificity of the junctional preparation. Gene ontology term analysis of the combined lists indicated a statistically significant enrichment in membrane-associated proteins. The myotendinous junction preparation contained previously uncharacterized proteins, a number of z-disc costameric ligands (e.g., actinins, capZ, αB cristallin, filamin C, cypher, calsarcin, desmin, FHL1, telethonin, nebulin, titin and an enigma-like protein) and other proposed players of sarcomeric stretch sensing and signalling, such as myotilin and the three myomesin homologs. A subset were confirmed by immunofluorescence analysis as enriched at the myotendinous junction, suggesting that laser capture microdissection from muscle sections is a valid approach to identify novel myotendinous junction players potentially involved in mechanotransduction pathways. PMID:25071420

Finite element analysis of the human mastication cycle.

PubMed

Commisso, Maria S; Martínez-Reina, Javier; Ojeda, Joaquín; Mayo, Juana

2015-01-01

The aim of this paper is to propose a biomechanical model that could serve as a tool to overcome some difficulties encountered in experimental studies of the mandible. One of these difficulties is the inaccessibility of the temporomandibular joint (TMJ) and the lateral pterygoid muscle. The focus of this model is to study the stresses in the joint and the influence of the lateral pterygoid muscle on the mandible movement. A finite element model of the mandible, including the TMJ, was built to simulate the process of unilateral mastication. Different activation patterns of the left and right pterygoid muscles were tried. The maximum stresses in the articular disc and in the whole mandible during a complete mastication cycle were reached during the instant of centric occlusion. The simulations show a great influence of the coordination of the right and left lateral pterygoid muscles on the movement of the jaw during mastication. An asynchronous activation of the lateral pterygoid muscles is needed to achieve a normal movement of the jaw during mastication. Copyright © 2014 Elsevier Ltd. All rights reserved.

Satellite cell proliferation in adult skeletal muscle

NASA Technical Reports Server (NTRS)

Morrison, Paul R. (Inventor); Thomason, Donald B. (Inventor); Stancel, George M. (Inventor); Booth, Frank W. (Inventor)

1995-01-01

Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

Dynamic changes in genes related to glucose uptake and utilization during pig skeletal and cardiac muscle development.

PubMed

Guo, Yanqin; Jin, Long; Wang, Fengjiao; He, Mengnan; Liu, Rui; Li, Mingzhou; Shuai, Surong

2014-01-01

Skeletal and cardiac muscle have important roles in glucose uptake and utilization. However, changes in expression of protein coding genes and miRNAs that participate in glucose metabolism during development are not fully understood. In this study, we investigated the expression of genes related to glucose metabolism during muscle development. We found an age-dependent increase in gene expression in cardiac muscle, with enrichment in heart development- and energy-related metabolic processes. A subset of genes that were up-regulated until 30 or 180 days postnatally, and then down-regulated in psoas major muscle was significantly enriched in mitochondrial oxidative-related processes, while genes that up-regulated in longissimus doris muscle was significantly enriched in glycolysis-related processes. Meanwhile, expression of energy-related microRNAs decreased with increasing age. In addition, we investigated the correlation between microRNAs and mRNAs in three muscle types across different stages of development and found many potential microRNA-mRNA pairs involved in regulating glucose metabolism.

Anatomy of the feeding apparatus of the nurse shark, Ginglymostoma cirratum.

PubMed

Motta; Wilga

1999-07-01

The anatomy of the feeding apparatus of the nurse shark, Ginglymostoma cirratum, was investigated by gross dissection and computer axial tomography. The labial cartilages, jaws, jaw suspension, muscles, and ligaments of the head are described. Palatoquadrate cartilages articulate with the chondrocranium caudally by short, laterally projecting hyomandibulae and rostrally by ethmoorbital articulations. Short orbital processes of the palatoquadrates are joined to the ethmoid region of the chondrocranium by short, thin ethmopalatine ligaments. In addition, various ligaments, muscles, and the integument contribute to the suspension of the jaws. When the mouth is closed and the palatoquadrate retracted, the palatine process of the palatoquadrate is braced against the ventral surface of the nasal capsule and the ascending process of the palatoquadrate is in contact with the rostrodorsal end of the suborbital shelf. When the mandible is depressed and the palatoquadrate protrudes slightly rostroventrally, the palatoquadrate moves away from the chondrocranium. A dual articulation of the quadratomandibular joint restricts lateral movement between the mandible and the palatoquadrate. The vertically oriented preorbitalis muscle spans the gape and is hypothesized to contribute to the generation of powerful crushing forces for its hard prey. The attachment of the preorbitalis to the prominent labial cartilages is also hypothesized to assist in the retraction of the labial cartilages during jaw closure. Separate levator palatoquadrati and spiracularis muscles, which are longitudinally oriented and attach the chondrocranium to the palatoquadrate, are hypothesized to assist in the retraction of the palatoquadrate during the recovery phase of feeding kinematics. Morphological specializations for suction feeding that contribute to large subambient suction pressures include hypertrophied coracohyoideus and coracobranchiales muscles to depress the hyoid and branchial arches, a small oral aperture with well-developed labial cartilages that occlude the gape laterally, and small teeth. Copyright 1999 Wiley-Liss, Inc.

Temporally distinct transcriptional regulation of myocyte dedifferentiation and Myofiber growth during muscle regeneration.

PubMed

Louie, Ke'ale W; Saera-Vila, Alfonso; Kish, Phillip E; Colacino, Justin A; Kahana, Alon

2017-11-09

Tissue regeneration requires a series of steps, beginning with generation of the necessary cell mass, followed by cell migration into damaged area, and ending with differentiation and integration with surrounding tissues. Temporal regulation of these steps lies at the heart of the regenerative process, yet its basis is not well understood. The ability of zebrafish to dedifferentiate mature "post-mitotic" myocytes into proliferating myoblasts that in turn regenerate lost muscle tissue provides an opportunity to probe the molecular mechanisms of regeneration. Following subtotal excision of adult zebrafish lateral rectus muscle, dedifferentiating residual myocytes were collected at two time points prior to cell cycle reentry and compared to uninjured muscles using RNA-seq. Functional annotation (GAGE or K-means clustering followed by GO enrichment) revealed a coordinated response encompassing epigenetic regulation of transcription, RNA processing, and DNA replication and repair, along with protein degradation and translation that would rewire the cellular proteome and metabolome. Selected candidate genes were phenotypically validated in vivo by morpholino knockdown. Rapidly induced gene products, such as the Polycomb group factors Ezh2 and Suz12a, were necessary for both efficient dedifferentiation (i.e. cell reprogramming leading to cell cycle reentry) and complete anatomic regeneration. In contrast, the late activated gene fibronectin was important for efficient anatomic muscle regeneration but not for the early step of myocyte cell cycle reentry. Reprogramming of a "post-mitotic" myocyte into a dedifferentiated myoblast requires a complex coordinated effort that reshapes the cellular proteome and rewires metabolic pathways mediated by heritable yet nuanced epigenetic alterations and molecular switches, including transcription factors and non-coding RNAs. Our studies show that temporal regulation of gene expression is programmatically linked to distinct steps in the regeneration process, with immediate early expression driving dedifferentiation and reprogramming, and later expression facilitating anatomical regeneration.

Differential expression of myogenic regulatory genes and Msx-1 during dedifferentiation and redifferentiation of regenerating amphibian limbs.

PubMed

Simon, H G; Nelson, C; Goff, D; Laufer, E; Morgan, B A; Tabin, C

1995-01-01

An amputated limb of an adult urodele amphibian is capable of undergoing regeneration. The new structures form from an undifferentiated mass of cells called the regenerative blastema. The cells of the blastema are believed to derive from differentiated tissues of the adult limb. However, the exact source of these cells and the process by which they undergo dedifferentiation are poorly understood. In order to elucidate the molecular and cellular basis for dedifferentiation we isolated a number of genes which are potential regulators of the process. These include Msx-1, which is believed to support the undifferentiated and proliferative state of cells in the embryonic limb bud; and two members of the myogenic regulatory gene family, MRF-4 and Myf-5, which are expressed in differentiated muscle and regulate muscle-specific gene activity. As anticipated, we find that Msx-1 is strongly up-regulated during the initiation of regeneration. It remains expressed throughout regeneration but is not found in the fully regenerated limb. The myogenic gene MRF-4 has the reverse expression pattern. It is expressed in adult limb muscle, is rapidly shut off in early regenerative blastemas, and is only reexpressed at the completion of regeneration. These kinetics are paralleled by those of a muscle-specific Myosin gene. In contrast Myf-5, a second member of the myogenic gene family, continues to be expressed throughout the regenerative process. Thus, MRF-4 and Myf-5 are likely to play distinct roles during regeneration. MRF-4 may directly regulate muscle phenotype and as such its repression may be a key event in dedifferentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals.

PubMed

Schwörer, Simon; Becker, Friedrich; Feller, Christian; Baig, Ali H; Köber, Ute; Henze, Henriette; Kraus, Johann M; Xin, Beibei; Lechel, André; Lipka, Daniel B; Varghese, Christy S; Schmidt, Manuel; Rohs, Remo; Aebersold, Ruedi; Medina, Kay L; Kestler, Hans A; Neri, Francesco; von Maltzahn, Julia; Tümpel, Stefan; Rudolph, K Lenhard

2016-12-15

The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing. Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice. The alteration includes aberrant global and site-specific induction of active chromatin marks in activated satellite cells from aged mice, resulting in the specific induction of Hoxa9 but not other Hox genes. Hoxa9 in turn activates several developmental pathways and represents a decisive factor that separates satellite cell gene expression in aged mice from that in young mice. The activated pathways include most of the currently known inhibitors of satellite cell function in ageing muscle, including Wnt, TGFβ, JAK/STAT and senescence signalling. Inhibition of aberrant chromatin activation or deletion of Hoxa9 improves satellite cell function and muscle regeneration in aged mice, whereas overexpression of Hoxa9 mimics ageing-associated defects in satellite cells from young mice, which can be rescued by the inhibition of Hoxa9-targeted developmental pathways. Together, these data delineate an altered epigenetic stress response in activated satellite cells from aged mice, which limits satellite cell function and muscle regeneration by Hoxa9-dependent activation of developmental pathways.

Vaginal cones or balls to improve pelvic floor muscle performance and urinary continence in women postpartum: a quantitative systematic review and meta-analysis protocol.

PubMed

Oblasser, Claudia; Christie, Janice; McCourt, Christine

2015-04-01

To identify, critically appraise and synthesize the best current evidence on the use of vaginal cones or balls to improve pelvic floor muscle performance and urinary continence in women post partum. The vaginal use of cones or balls is a pelvic floor muscle training method that aims to enhance muscle performance and thereby prevent or treat urinary incontinence. Nonetheless to date, no systematic review has focused on the effectiveness of these devices specifically during the postpartum period. Quantitative systematic review with potential meta-analysis. The review will be undertaken by searching 14 scientific databases (including PubMed and CINAHL, without date restriction) and the world-wide web; experts will also be contacted for published and unpublished data. Included studies must be randomized or quasi-randomized trials and have female participants until 1 year after childbirth. The intervention will be compared with no treatment, placebo, sham treatment or active controls. Outcome measures will relate to pelvic floor muscle performance or urinary incontinence. Studies will be selected, 'risk of bias' assessed and data extracted by two reviewers independently. Following inter-reviewer agreement of included studies, data will be checked after entry into systematic review processing software. If appropriate, data will be synthesized by meta-analysis; if this is not possible, a narrative review only will be undertaken. The information gained from this systematic review will help midwives, nurses, other health professionals and women after childbirth decide how to promote female pelvic floor health and in defining further areas of study. © 2014 John Wiley & Sons Ltd.

Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis

PubMed Central

2018-01-01

Muscle morphogenesis is tightly coupled with that of motor neurons (MNs). Both MNs and muscle progenitors simultaneously explore the surrounding tissues while exchanging reciprocal signals to tune their behaviors. We previously identified the Fat1 cadherin as a regulator of muscle morphogenesis and showed that it is required in the myogenic lineage to control the polarity of progenitor migration. To expand our knowledge on how Fat1 exerts its tissue-morphogenesis regulator activity, we dissected its functions by tissue-specific genetic ablation. An emblematic example of muscle under such morphogenetic control is the cutaneous maximus (CM) muscle, a flat subcutaneous muscle in which progenitor migration is physically separated from the process of myogenic differentiation but tightly associated with elongating axons of its partner MNs. Here, we show that constitutive Fat1 disruption interferes with expansion and differentiation of the CM muscle, with its motor innervation and with specification of its associated MN pool. Fat1 is expressed in muscle progenitors, in associated mesenchymal cells, and in MN subsets, including the CM-innervating pool. We identify mesenchyme-derived connective tissue (CT) as a cell type in which Fat1 activity is required for the non–cell-autonomous control of CM muscle progenitor spreading, myogenic differentiation, motor innervation, and for motor pool specification. In parallel, Fat1 is required in MNs to promote their axonal growth and specification, indirectly influencing muscle progenitor progression. These results illustrate how Fat1 coordinates the coupling of muscular and neuronal morphogenesis by playing distinct but complementary actions in several cell types. PMID:29768404

Functional morphology of the cranio-mandibular complex of the Guira cuckoo (Aves).

PubMed

Pestoni, Sofía; Degrange, Federico Javier; Tambussi, Claudia Patricia; Demmel Ferreira, María Manuela; Tirao, Germán Alfredo

2018-06-01

The cranio-mandibular complex is an important structure involved in food capture and processing. Its morphology is related to the nature of the food item. Jaw muscles enable the motion of this complex and their study is essential for functional and evolutionary analysis. The present study compares available behavioral and dietary data obtained from the literature with novel results from functional morphological analyses of the cranio-mandibular complex of the Guira cuckoo (Guira guira) to understand its relationship with the zoophagous trophic habit of this species. The bite force was estimated based on muscle dissections, measurements of the physiological cross-sectional area, and biomechanical modeling of the skull. The results were compared with the available functional morphological data for other birds. The standardized bite force of G. guira is higher than predicted for exclusively zoophagous birds, but lower than for granivorous and/or omnivorous birds. Guira guira possesses the generalized jaw muscular system of neognathous birds, but some features can be related to its trophic habit. The external adductor muscles act mainly during food item processing and multiple aspects of this muscle group are interpreted to increase bite force, that is, their high values of muscle mass, their mechanical advantage (MA), and their perpendicular orientation when the beak is closed. The m. depressor mandibulae and the m. pterygoideus dorsalis et ventralis are interpreted to prioritize speed of action (low MA values), being most important during prey capture. The supposed ecological significance of these traits is the potential to widen the range of prey size that can be processed and the possibility of rapidly capturing agile prey through changes in the leverage of the muscles involved in opening and closing of the bill. This contributes to the trophic versatility of the species and its ability to thrive in different habitats, including urban areas. © 2018 Wiley Periodicals, Inc.

Cardiovascular Aspects of Aging (Part 1 of 2).

ERIC Educational Resources Information Center

Van Camp, Steven P.; Boyer, John L.

1989-01-01

Reviews cardiovascular changes occurring during the aging process and the trainability of older persons. Although cardiovascular changes are part of life, activity levels need not decrease. Beneficial aspects of exercise include improvements in muscle strength, joint mobility, flexibility, coordination, and weight control. (SM)

Born to run: creating the muscle fiber.

PubMed

Schejter, Eyal D; Baylies, Mary K

2010-10-01

From the muscles that control the blink of your eye to those that allow you to walk, the basic architecture of muscle is the same: muscles consist of bundles of the unit muscle cell, the muscle fiber. The unique morphology of the individual muscle fiber is dictated by the functional demands necessary to generate and withstand the forces of contraction, which in turn leads to movement. Contractile muscle fibers are elongated, syncytial cells, which interact with both the nervous and skeletal systems to govern body motion. In this review, we focus on three key cell-cell and cell-matrix contact processes, that are necessary to create this exquisitely specialized cell: cell fusion, cell elongation, and establishment of a myotendinous junction. We address these processes by highlighting recent findings from the Drosophila model system. Copyright © 2010 Elsevier Ltd. All rights reserved.

Macrophage depletion impairs skeletal muscle regeneration: The roles of regulatory factors for muscle regeneration.

PubMed

Liu, Xiaoguang; Liu, Yu; Zhao, Linlin; Zeng, Zhigang; Xiao, Weihua; Chen, Peijie

2017-03-01

Though macrophages are essential for skeletal muscle regeneration, which is a complex process, the roles and mechanisms of the macrophages in the process of muscle regeneration are still not fully understood. The objective of this study is to explore the roles of macrophages and the mechanisms involved in the regeneration of injured skeletal muscle. One hundred and twelve C57BL/6 mice were randomly divided into muscle contusion and macrophages depleted groups. Their gastrocnemius muscles were harvested at the time points of 12 h, 1, 3, 5, 7, 14 d post-injury. The changes in skeletal muscle morphology were assessed by hematoxylin and eosin (HE) stain. The gene expression was analyzed by real-time polymerase chain reaction. The data showed that CL-liposomes treatment did affect the expression of myogenic regulatory factors (MyoD, myogenin) after injury. In addition, CL-liposomes treatment decreased the expression of regulatory factors of muscle regeneration (HGF, uPA, COX-2, IGF-1, MGF, FGF6) and increased the expression of inflammatory cytokines (TGF-β1, TNF-α, IL-1β, RANTES) in the late stage of regeneration. Moreover, there were significant correlations between macrophages and some regulatory factors (such as HGF, uPA) for muscle regeneration. These results suggested that macrophages depletion impairs skeletal muscle regeneration and that the regulatory factors for muscle regeneration may play important roles in this process. © 2017 International Federation for Cell Biology.

Genetics Home Reference: Sheldon-Hall syndrome

MedlinePlus

... proteins that are involved in muscle tensing (contraction). Muscle contraction occurs when thick filaments made of proteins called ... early development of the muscles. The process of muscle contraction is controlled (regulated) by other proteins called troponins ...

Inhibiting the Physiological Stress Effects of a Sustained Attention Task on Shoulder Muscle Activity.

PubMed

Wixted, Fiona; O'Riordan, Cliona; O'Sullivan, Leonard

2018-01-11

The objective of this study was to investigate if a breathing technique could counteract the effects of hyperventilation due to a sustained attention task on shoulder muscle activity. The trend towards higher levels of automation in industry is increasing. Consequently, manufacturing operators often monitor automated process for long periods of their work shift. Prolonged monitoring work requires sustained attention, which is a cognitive process that humans are typically poor at and find stressful. As sustained attention becomes an increasing requirement of manufacturing operators' job content, the resulting stress experienced could contribute to the onset of many health problems, including work related musculoskeletal disorders (WRMSDs). The SART attention test was completed by a group of participants before and after a breathing intervention exercise. The effects of the abdominal breathing intervention on breathing rate, upper trapezius muscle activity and end-tidal CO₂ were evaluated. The breathing intervention reduced the moderation effect of end-tidal CO₂ on upper trapezius muscle activity. Abdominal breathing could be a useful technique in reducing the effects of sustained attention work on muscular activity. This research can be applied to highly-automated manufacturing industries, where prolonged monitoring of work is widespread and could, in its role as a stressor, be a potential contributor to WRMSDs.

Ion implanted dielectric elastomer circuits

NASA Astrophysics Data System (ADS)

O'Brien, Benjamin M.; Rosset, Samuel; Anderson, Iain A.; Shea, Herbert R.

2013-06-01

Starfish and octopuses control their infinite degree-of-freedom arms with panache—capabilities typical of nature where the distribution of reflex-like intelligence throughout soft muscular networks greatly outperforms anything hard, heavy, and man-made. Dielectric elastomer actuators show great promise for soft artificial muscle networks. One way to make them smart is with piezo-resistive Dielectric Elastomer Switches (DES) that can be combined with artificial muscles to create arbitrary digital logic circuits. Unfortunately there are currently no reliable materials or fabrication process. Thus devices typically fail within a few thousand cycles. As a first step in the search for better materials we present a preliminary exploration of piezo-resistors made with filtered cathodic vacuum arc metal ion implantation. DES were formed on polydimethylsiloxane silicone membranes out of ion implanted gold nano-clusters. We propose that there are four distinct regimes (high dose, above percolation, on percolation, low dose) in which gold ion implanted piezo-resistors can operate and present experimental results on implanted piezo-resistors switching high voltages as well as a simple artificial muscle inverter. While gold ion implanted DES are limited by high hysteresis and low sensitivity, they already show promise for a range of applications including hysteretic oscillators and soft generators. With improvements to implanter process control the promise of artificial muscle circuitry for soft smart actuator networks could become a reality.

Aerobic Exercise Training in Post-Polio Syndrome: Process Evaluation of a Randomized Controlled Trial.

PubMed

Voorn, Eric L; Koopman, Fieke S; Brehm, Merel A; Beelen, Anita; de Haan, Arnold; Gerrits, Karin H L; Nollet, Frans

2016-01-01

To explore reasons for the lack of efficacy of a high intensity aerobic exercise program in post-polio syndrome (PPS) on cardiorespiratory fitness by evaluating adherence to the training program and effects on muscle function. A process evaluation using data from an RCT. Forty-four severely fatigued individuals with PPS were randomized to exercise therapy (n = 22) or usual care (n = 22). Participants in the exercise group were instructed to exercise 3 times weekly for 4 months on a bicycle ergometer (60-70% heart rate reserve). The attendance rate was high (median 89%). None of the participants trained within the target heart rate range during >75% of the designated time. Instead, participants exercised at lower intensities, though still around the anaerobic threshold (AT) most of the time. Muscle function did not improve in the exercise group. Our results suggest that severely fatigued individuals with PPS cannot adhere to a high intensity aerobic exercise program on a cycle ergometer. Despite exercise intensities around the AT, lower extremity muscle function nor cardiorespiratory fitness improved. Improving the aerobic capacity in PPS is difficult through exercise primarily focusing on the lower extremities, and may require a more individualized approach, including the use of other large muscle groups instead. Netherlands National Trial Register NTR1371.

Oral Supplementation of Melatonin Protects against Fibromyalgia-Related Skeletal Muscle Alterations in Reserpine-Induced Myalgia Rats.

PubMed

Favero, Gaia; Trapletti, Valentina; Bonomini, Francesca; Stacchiotti, Alessandra; Lavazza, Antonio; Rodella, Luigi Fabrizio; Rezzani, Rita

2017-06-29

Fibromyalgia is a chronic syndrome characterized by widespread musculoskeletal pain and an extensive array of other symptoms including disordered sleep, fatigue, depression and anxiety. Important factors involved in the pathogenic process of fibromyalgia are inflammation and oxidative stress, suggesting that ant-inflammatory and/or antioxidant supplementation might be effective in the management and modulation of this syndrome. Recent evidence suggests that melatonin may be suitable for this purpose due to its well known ant-inflammatory, antioxidant and analgesic effects. Thus, in the current study, the effects of the oral supplementation of melatonin against fibromyalgia-related skeletal muscle alterations were evaluated. In detail, 90 Sprague Dawley rats were randomly treated with reserpine, to reproduce the pathogenic process of fibromyalgia and thereafter they received melatonin. The animals treated with reserpine showed moderate alterations at hind limb skeletal muscles level and had difficulty in moving, together with significant morphological and ultrastructural alterations and expression of inflammatory and oxidative stress markers in the gastrocnemius muscle. Interestingly, melatonin, dose and/or time dependently, reduced the difficulties in spontaneous motor activity and the musculoskeletal morphostructural, inflammatory, and oxidative stress alterations. This study suggests that melatonin in vivo may be an effective tool in the management of fibromyalgia-related musculoskeletal morphofunctional damage.

Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation.

PubMed

Senesi, Pamela; Luzi, Livio; Montesano, Anna; Mazzocchi, Nausicaa; Terruzzi, Ileana

2013-07-19

Betaine (BET) is a component of many foods, including spinach and wheat. It is an essential osmolyte and a source of methyl groups. Recent studies have hypothesized that BET might play a role in athletic performance. However, BET effects on skeletal muscle differentiation and hypertrophy are still poorly understood. We examined BET action on neo myotubes maturation and on differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR array, Western blot and immunofluorescence analysis to study the BET effects on morphological features of C2C12 and on signaling pathways involved in muscle differentiation and hypertrophy. We performed a dose-response study, establishing that 10 mM BET was the dose able to stimulate morphological changes and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to identify the expression profile of genes encoding proteins involved in IGF-1 pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R) expression. Western blot and immunofluorescence analysis, performed in neo myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of Myosin Heavy Chain (MyHC) and neo myotubes length. Our findings provide the first evidence that BET could promote muscle fibers differentiation and increase myotubes size by IGF-1 pathway activation, suggesting that BET might represent a possible new drug/integrator strategy, not only in sport performance but also in clinical conditions characterized by muscle function impairment.

A Method for the Direct Identification of Differentiating Muscle Cells by a Fluorescent Mitochondrial Dye

PubMed Central

Miyake, Tetsuaki; McDermott, John C.; Gramolini, Anthony O.

2011-01-01

Identification of differentiating muscle cells generally requires fixation, antibodies directed against muscle specific proteins, and lengthy staining processes or, alternatively, transfection of muscle specific reporter genes driving GFP expression. In this study, we examined the possibility of using the robust mitochondrial network seen in maturing muscle cells as a marker of cellular differentiation. The mitochondrial fluorescent tracking dye, MitoTracker, which is a cell-permeable, low toxicity, fluorescent dye, allowed us to distinguish and track living differentiating muscle cells visually by epi-fluorescence microscopy. MitoTracker staining provides a robust and simple detection strategy for living differentiating cells in culture without the need for fixation or biochemical processing. PMID:22174849

A Special Population of Regulatory T Cells Potentiates Muscle Repair

PubMed Central

Burzyn, Dalia; Kuswanto, Wilson; Kolodin, Dmitriy; Shadrach, Jennifer L.; Cerletti, Massimiliano; Jang, Young; Sefik, Esen; Tan, Tze Guan; Wagers, Amy J.; Benoist, Christophe; Mathis, Diane

2014-01-01

SUMMARY Long recognized to be potent suppressors of immune responses, Foxp3+CD4+ regulatory T (Treg) cells are being rediscovered as regulators of nonimmunological processes. We describe a phenotypically and functionally distinct population of Treg cells that rapidly accumulated in the acutely injured skeletal muscle of mice, just as invading myeloidlineage cells switched from a proinflammatory to a proregenerative state. A Treg population of similar phenotype accumulated in muscles of genetically dystrophic mice. Punctual depletion of Treg cells during the repair process prolonged the proinflammatory infiltrate and impaired muscle repair, while treatments that increased or decreased Treg activities diminished or enhanced (respectively) muscle damage in a dystrophy model. Muscle Treg cells expressed the growth factor Amphiregulin, which acted directly on muscle satellite cells in vitro and improved muscle repair in vivo. Thus, Treg cells and their products may provide new therapeutic opportunities for wound repair and muscular dystrophies. PMID:24315098

Ca2+-Dependent Regulations and Signaling in Skeletal Muscle: From Electro-Mechanical Coupling to Adaptation

PubMed Central

Gehlert, Sebastian; Bloch, Wilhelm; Suhr, Frank

2015-01-01

Calcium (Ca2+) plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca2+ is critically involved in the innervation of skeletal muscle fibers that results in the exertion of an action potential along the muscle fiber membrane, the prerequisite for skeletal muscle contraction. Furthermore and among others, Ca2+ regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca2+-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca2+ ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca2+ ions in adult muscle but also highlight recent findings of critical Ca2+-dependent mechanisms essential for skeletal muscle-regulation and maintenance. PMID:25569087

Apoptosis in muscle-to-meat aging process: The omic witness.

PubMed

Longo, Valentina; Lana, Alessandro; Bottero, Maria Teresa; Zolla, Lello

2015-07-01

Meat derives from a muscle that undergoes a great number of biochemical and physiological changes. The anoxic condition established from the moment of animal sacrifice forces muscle cells to a sort of reaction, resulting in methodical programmed cell death to avoid necrosis. The duality autophagy and/or apoptosis is at the center of the scientific debate about the biological processes driving the muscle to meat conversion. Here we report an omic time course overview carried on proteome, phosphoproteome and metabolome of Piedmontese longissimus thoracis muscle searching for clues helping us to extricate through the dilemma. The survey depicts a progressive physiological impairing and our evidences push towards the apoptotic behavior: the proteomic time course trend of annexin A2, RKIP, HSPB6, αB crystalline, adenylate kinase, DJ-1 and 31kDa actin fragment; the 0-1day increased phosphorylation of myosin 2 and synaptopodin and the metabolomic time course trend of key metabolic indicators, like GSH/GSSG ratio, taurine and nitrotyrosine. The employed techniques provide strong indications about the likely apoptotic behavior of aging meat in muscle-to-meat conversion process. Our work underlines compelling evidences of the apoptotic behavior of Piedmontese beef muscle cells undergoing the muscle-to-meat process, whereas no autophagic clues are inferred from this omic investigation. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcriptome analysis reveals long intergenic non-coding RNAs involved in skeletal muscle growth and development in pig.

PubMed

Zou, Cheng; Li, Jingxuan; Luo, Wenzhe; Li, Long; Hu, An; Fu, Yuhua; Hou, Ye; Li, Changchun

2017-08-18

Long intergenic non-coding RNAs (lincRNAs) play essential roles in numerous biological processes and are widely studied. The skeletal muscle is an important tissue that plays an essential role in individual movement ability. However, lincRNAs in pig skeletal muscles are largely undiscovered and their biological functions remain elusive. In this study, we assembled transcriptomes using RNA-seq data published in previous studies of our laboratory group and identified 323 lincRNAs in porcine leg muscle. We found that these lincRNAs have shorter transcript length, fewer exons and lower expression level than protein-coding genes. Gene ontology and pathway analyses indicated that many potential target genes (PTGs) of lincRNAs were involved in skeletal-muscle-related processes, such as muscle contraction and muscle system process. Combined our previous studies, we found a potential regulatory mechanism in which the promoter methylation of lincRNAs can negatively regulate lincRNA expression and then positively regulate PTG expression, which can finally result in abnormal phenotypes of cloned piglets through a certain unknown pathway. This work detailed a number of lincRNAs and their target genes involved in skeletal muscle growth and development and can facilitate future studies on their roles in skeletal muscle growth and development.

The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis.

PubMed

Loeffler, Jean-Philippe; Picchiarelli, Gina; Dupuis, Luc; Gonzalez De Aguilar, Jose-Luis

2016-03-01

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease primarily characterized by upper and lower motor neuron degeneration, muscle wasting and paralysis. It is increasingly accepted that the pathological process leading to ALS is the result of multiple disease mechanisms that operate within motor neurons and other cell types both inside and outside the central nervous system. The implication of skeletal muscle has been the subject of a number of studies conducted on patients and related animal models. In this review, we describe the features of ALS muscle pathology and discuss on the contribution of muscle to the pathological process. We also give an overview of the therapeutic strategies proposed to alleviate muscle pathology or to deliver curative agents to motor neurons. ALS muscle mainly suffers from oxidative stress, mitochondrial dysfunction and bioenergetic disturbances. However, the way by which the disease affects different types of myofibers depends on their contractile and metabolic features. Although the implication of muscle in nourishing the degenerative process is still debated, there is compelling evidence suggesting that it may play a critical role. Detailed understanding of the muscle pathology in ALS could, therefore, lead to the identification of new therapeutic targets. © 2016 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

The role of skeletal-muscle-based thermogenic mechanisms in vertebrate endothermy

PubMed Central

Rowland, Leslie A.; Bal, Naresh C.; Periasamy, Muthu

2016-01-01

Thermogenesis is one of the most important homeostatic mechanisms that evolved during vertebrate evolution. Despite its importance for the survival of the organism, the mechanistic details behind various thermogenic processes remain incompletely understood. Although heat production from muscle has long been recognized as a thermogenic mechanism, whether muscle can produce heat independently of contraction remains controversial. Studies in birds and mammals suggest that skeletal muscle can be an important site of non-shivering thermogenesis (NST) and can be recruited during cold adaptation, although unequivocal evidence is lacking. Much research on thermogenesis during the last two decades has been focused on brown adipose tissue (BAT). These studies clearly implicate BAT as an important site of NST in mammals, in particular in newborns and rodents. However, BAT is either absent, as in birds and pigs, or is only a minor component, as in adult large mammals including humans, bringing into question the BAT-centric view of thermogenesis. This review focuses on the evolution and emergence of various thermogenic mechanisms in vertebrates from fish to man. A careful analysis of the existing data reveals that muscle was the earliest facultative thermogenic organ to emerge in vertebrates, long before the appearance of BAT in eutherian mammals. Additionally, these studies suggest that muscle-based thermogenesis is the dominant mechanism of heat production in many species including birds, marsupials, and certain mammals where BAT-mediated thermogenesis is absent or limited. We discuss the relevance of our recent findings showing that uncoupling of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by sarcolipin (SLN), resulting in futile cycling and increased heat production, could be the basis for NST in skeletal muscle. The overall goal of this review is to highlight the role of skeletal muscle as a thermogenic organ and provide a balanced view of thermogenesis in vertebrates. PMID:25424279

Zinc stimulates glucose oxidation and glycemic control by modulating the insulin signaling pathway in human and mouse skeletal muscle cell lines.

PubMed

Norouzi, Shaghayegh; Adulcikas, John; Sohal, Sukhwinder Singh; Myers, Stephen

2018-01-01

Zinc is a metal ion that is an essential cell signaling molecule. Highlighting this, zinc is an insulin mimetic, activating cellular pathways that regulate cellular homeostasis and physiological responses. Previous studies have linked dysfunctional zinc signaling with several disease states including cancer, obesity, cardiovascular disease and type 2 diabetes. The present study evaluated the insulin-like effects of zinc on cell signaling molecules including tyrosine, PRSA40, Akt, ERK1/2, SHP-2, GSK-3β and p38, and glucose oxidation in human and mouse skeletal muscle cells. Insulin and zinc independently led to the phosphorylation of these proteins over a 60-minute time course in both mouse and human skeletal muscle cells. Similarly, utilizing a protein array we identified that zinc could active the phosphorylation of p38, ERK1/2 and GSK-3B in human and ERK1/2 and GSK-3B in mouse skeletal muscle cells. Glucose oxidation assays were performed on skeletal muscle cells treated with insulin, zinc, or a combination of both and resulted in a significant induction of glucose consumption in mouse (p<0.01) and human (p<0.05) skeletal muscle cells when treated with zinc alone. Insulin, as expected, increased glucose oxidation in mouse (p<0.001) and human (0.001) skeletal muscle cells, however the combination of zinc and insulin did not augment glucose consumption in these cells. Zinc acts as an insulin mimetic, activating key molecules implicated in cell signaling to maintain glucose homeostasis in mouse and human skeletal muscle cells. Zinc is an important metal ion implicated in several biological processes. The role of zinc as an insulin memetic in activating key signaling molecules involved in glucose homeostasis could provide opportunities to utilize this ion therapeutically in treating disorders associated with dysfunctional zinc signaling.

A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle.

PubMed

Spletter, Maria L; Barz, Christiane; Yeroslaviz, Assa; Zhang, Xu; Lemke, Sandra B; Bonnard, Adrien; Brunner, Erich; Cardone, Giovanni; Basler, Konrad; Habermann, Bianca H; Schnorrer, Frank

2018-05-30

Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing sarcomeres. To study sarcomerogenesis, we have generated a transcriptomics resource of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, most sarcomeric components group in two clusters, which are strongly induced after all myofibrils have been assembled, indicating a transcriptional transition during myofibrillogenesis. Following myofibril assembly, many short sarcomeres are added to each myofibril. Subsequently, all sarcomeres mature, reaching 1.5 µm diameter and 3.2 µm length and acquiring stretch-sensitivity. The efficient induction of the transcriptional transition during myofibrillogenesis, including the transcriptional boost of sarcomeric components, requires in part the transcriptional regulator Spalt major. As a consequence of Spalt knock-down, sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. Together, this defines an ordered sarcomere morphogenesis process under precise transcriptional control - a concept that may also apply to vertebrate muscle or heart development. © 2018, Spletter et al.

Levator claviculae muscle discovered during physical examination for cervical lymphadenopathy.

PubMed

Rosenheimer, J L; Loewy, J; Lozanoff, S

2000-01-01

During a routine physical examination of an adult female with a history of breast cancer and cervical lymphadenopathy, a mass was noted in the right supraclavicular region. The mass was unilateral and easily palpable along the superior border near the median aspect of the clavicle. Plain film radiography, performed to determine whether the mass represented an enlarged jugulo-omohyoid lymph node, revealed an elongated opaque mass in this region. Computed tomographic (CT) and magnetic resonance (MR) images were subsequently obtained. Sequential axial CT scans revealed a cylindrical mass that appeared to be independent of contiguous muscles, including the sternocleidomastoid, anterior, and middle scalene muscles. This mass attached inferiorly to the clavicle and superiorly to the transverse process of the sixth cervical vertebra. Sagittal, coronal, and axial MR scans confirmed the presence of a well-defined superficial mass. It is concluded that the mass represents a levator claviculae (cleidocervical) muscle. This observation underscores the importance of understanding soft tissue variants that may be encountered during a routine physical examination. Copyright 2000 Wiley-Liss, Inc.

AHNAK1 and AHNAK2 are costameric proteins: AHNAK1 affects transverse skeletal muscle fiber stiffness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marg, Andreas, E-mail: andreas.marg@mdc-berlin.de; Haase, Hannelore; Neumann, Tanja

2010-10-08

Research highlights: {yields} AHNAK1 and AHNAK2 are costameric proteins. {yields} Intact membrane repair in AHNAK1-deficient mice. {yields} AHNAK1{sup -/-} single fibers have a higher transverse stiffness. -- Abstract: The AHNAK scaffold PDZ-protein family is implicated in various cellular processes including membrane repair; however, AHNAK function and subcellular localization in skeletal muscle are unclear. We used specific AHNAK1 and AHNAK2 antibodies to analyzed the detailed localization of both proteins in mouse skeletal muscle. Co-localization of AHNAK1 and AHNAK2 with vinculin clearly demonstrates that both proteins are components of the costameric network. In contrast, no AHNAK expression was detected in the T-tubulemore » system. A laser wounding assay with AHNAK1-deficient fibers suggests that AHNAK1 is not involved in membrane repair. Using atomic force microscopy (AFM), we observed a significantly higher transverse stiffness of AHNAK1{sup -/-} fibers. These findings suggest novel functions of AHNAK proteins in skeletal muscle.« less

Exercise alters myostatin protein expression in sedentary and exercised streptozotocin-diabetic rats.

PubMed

Bassi, Daniela; Bueno, Patricia de Godoy; Nonaka, Keico Okino; Selistre-Araujo, Heloisa Sobreiro; Leal, Angela Merice de Oliveira

2015-04-01

The aim of this study was to analyze the effect of exercise on the pattern of muscle myostatin (MSTN) protein expression in two important metabolic disorders, i.e., obesity and diabetes mellitus. MSTN, is a negative regulator of skeletal muscle mass. We evaluated the effect of exercise on MSTN protein expression in diabetes mellitus and high fat diet-induced obesity. MSTN protein expression in gastrocnemius muscle was analyzed by Western Blot. P < 0.05 was assumed. Exercise induced a significant decrease in glycemia in both diabetic and obese animals. The expression of precursor and processed protein forms of MSTN and the weight of gastrocnemius muscle did not vary in sedentary or exercised obese animals. Diabetes reduced gastrocnemius muscle weight in sedentary animals. However, gastrocnemius muscle weight increased in diabetic exercised animals. Both the precursor and processed forms of muscle MSTN protein were significantly higher in sedentary diabetic rats than in control rats. The precursor form was significantly lower in diabetic exercised animals than in diabetic sedentary animals. However, the processed form did not change. These results demonstrate that exercise can modulate the muscle expression of MSTN protein in diabetic rats and suggest that MSTN may be involved in energy homeostasis.

Effects of altered loading states on muscle plasticity: what have we learned from rodents?

NASA Technical Reports Server (NTRS)

Baldwin, K. M.

1996-01-01

This paper summarizes the key findings concerning the adaptive properties of rodent muscle in response to altered loading states. When the mechanical stress on the muscle is chronically increased, the muscle adapts by hypertrophying its fibers. This response is regulated by processes resulting in contractile protein expression reflecting slower phenotypes, thereby enabling the muscle to better support load-hearing activity. In contrast, reducing the load-bearing activity induces an opposite response whereby muscles used for both antigravity function and locomotion atrophy while transforming some of the slow fibers into faster contractile phenotypes. Accompanying the atrophy is both a reduced power generating and activity sustaining capability. These adaptive processes are regulated by both transcriptional and translational processes. Available evidence further suggests that the interaction of heavy resistance activity and hormonal/growth factors (insulin-like growth factor, growth hormone, glucocorticoids, etc.) are critical in the maintenance of muscle mass and function. Also resistance training, in contrast to other activities such as endurance running, provides a more economical form of stress because less mechanical activity is required to maintain muscle homeostasis in the context of chronic states of weightlessness.

The value of mechanistic biophysical information for systems-level understanding of complex biological processes such as cytokinesis.

PubMed

Pollard, Thomas D

2014-12-02

This review illustrates the value of quantitative information including concentrations, kinetic constants and equilibrium constants in modeling and simulating complex biological processes. Although much has been learned about some biological systems without these parameter values, they greatly strengthen mechanistic accounts of dynamical systems. The analysis of muscle contraction is a classic example of the value of combining an inventory of the molecules, atomic structures of the molecules, kinetic constants for the reactions, reconstitutions with purified proteins and theoretical modeling to account for the contraction of whole muscles. A similar strategy is now being used to understand the mechanism of cytokinesis using fission yeast as a favorable model system. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Muscle segmentation in time series images of Drosophila metamorphosis.

PubMed

Yadav, Kuleesha; Lin, Feng; Wasser, Martin

2015-01-01

In order to study genes associated with muscular disorders, we characterize the phenotypic changes in Drosophila muscle cells during metamorphosis caused by genetic perturbations. We collect in vivo images of muscle fibers during remodeling of larval to adult muscles. In this paper, we focus on the new image processing pipeline designed to quantify the changes in shape and size of muscles. We propose a new two-step approach to muscle segmentation in time series images. First, we implement a watershed algorithm to divide the image into edge-preserving regions, and then, we classify these regions into muscle and non-muscle classes on the basis of shape and intensity. The advantage of our method is two-fold: First, better results are obtained because classification of regions is constrained by the shape of muscle cell from previous time point; and secondly, minimal user intervention results in faster processing time. The segmentation results are used to compare the changes in cell size between controls and reduction of the autophagy related gene Atg 9 during Drosophila metamorphosis.

Functional classification of skeletal muscle networks. I. Normal physiology

PubMed Central

Wang, Yu; Winters, Jack

2012-01-01

Extensive measurements of the parts list of human skeletal muscle through transcriptomics and other phenotypic assays offer the opportunity to reconstruct detailed functional models. Through integration of vast amounts of data present in databases and extant knowledge of muscle function combined with robust analyses that include a clustering approach, we present both a protein parts list and network models for skeletal muscle function. The model comprises the four key functional family networks that coexist within a functional space; namely, excitation-activation family (forward pathways that transmit a motoneuronal command signal into the spatial volume of the cell and then use Ca2+ fluxes to bind Ca2+ to troponin C sites on F-actin filaments, plus transmembrane pumps that maintain transmission capacity); mechanical transmission family (a sophisticated three-dimensional mechanical apparatus that bidirectionally couples the millions of actin-myosin nanomotors with external axial tensile forces at insertion sites); metabolic and bioenergetics family (pathways that supply energy for the skeletal muscle function under widely varying demands and provide for other cellular processes); and signaling-production family (which represents various sensing, signal transduction, and nuclear infrastructure that controls the turn over and structural integrity and regulates the maintenance, regeneration, and remodeling of the muscle). Within each family, we identify subfamilies that function as a unit through analysis of large-scale transcription profiles of muscle and other tissues. This comprehensive network model provides a framework for exploring functional mechanisms of the skeletal muscle in normal and pathophysiology, as well as for quantitative modeling. PMID:23085959

Expression and functional characterization of Smyd1a in myofibril organization of skeletal muscles.

PubMed

Gao, Jie; Li, Junling; Li, Bao-Jun; Yagil, Ezra; Zhang, Jianshe; Du, Shao Jun

2014-01-01

Smyd1, the founding member of the Smyd family including Smyd-1, 2, 3, 4 and 5, is a SET and MYND domain containing protein that plays a key role in myofibril assembly in skeletal and cardiac muscles. Bioinformatic analysis revealed that zebrafish genome contains two highly related smyd1 genes, smyd1a and smyd1b. Although Smyd1b function is well characterized in skeletal and cardiac muscles, the function of Smyd1a is, however, unknown. To investigate the function of Smyd1a in muscle development, we isolated smyd1a from zebrafish, and characterized its expression and function during muscle development via gene knockdown and transgenic expression approaches. The results showed that smyd1a was strongly expressed in skeletal muscles of zebrafish embryos. Functional analysis revealed that knockdown of smyd1a alone had no significant effect on myofibril assembly in zebrafish skeletal muscles. However, knockdown of smyd1a and smyd1b together resulted in a complete disruption of myofibril organization in skeletal muscles, a phenotype stronger than knockdown of smyd1a or smyd1b alone. Moreover, ectopic expression of zebrafish smyd1a or mouse Smyd1 transgene could rescue the myofibril defects from the smyd1b knockdown in zebrafish embryos. Collectively, these data indicate that Smyd1a and Smyd1b share similar biological activity in myofibril assembly in zebrafish embryos. However, Smyd1b appears to play a major role in this process.

The role of microRNAs in skeletal muscle health and disease

PubMed Central

Kirby, Tyler J.; Chaillou, Thomas; McCarthy, John J.

2016-01-01

Over the last decade non-coding RNAs have emerged as importance regulators of gene expression. In particular, microRNAs are a class of small RNAs of ~ 22 nucleotides that repress gene expression through a post-transcriptional mechanism. MicroRNAs have been shown to be involved in a broader range of biological processes, both physiological and pathological, including myogenesis, adaptation to exercise and various myopathies. The purpose of this review is to provide a comprehensive summary of what is currently known about the role of microRNAs in skeletal muscle health and disease. PMID:25553440

[Ultrasound diagnostics of muscle and tendon injuries].

PubMed

Stević, Ruza; Masulović, Dragan

2009-01-01

Sonography is a useful technique for the investigation of a number of musculoskeletal disorders. The most common indication for ultrasonography of muscles and tendons is the diagnosis of traumatic lesions, distinguishing them from other disorders and follow- up of healing process. The purpose of this paper is to show the importance of ultrasound in the diagnosis of muscle and tendon injuries. The study included 170 patients (148 male and 22 female), mean age 29.6 years (range 14-60 years). All examinations were performed by linear transducer of 7.5-10 MHz, with longitudinal and transverse scanning. Ultrasound examination followed physical examination. Traumatic lesions of muscles were diagnosed in 113 patients (66.7%) and tendon injuries in 57 cases (33.2%). The muscle changes detected by ultrasonography were the following: 70 (61.9%) partial and two (1.76%) complete ruptures, 22 (19.46%) haematoma, 9 (7.96%) strains grade I, 4 fibroses and 4 ossifying myositis 4 (3.5%, respectively). Complications of muscle injuries were diagnosed in two cases, a muscular hernia and an arteriovenous fistula. Among tendon injuries, 21 (33.8%) ruptures and 36 (66.1%) tendinitis were diagnosed. Accompanying effusion in the bursa of patients with tendon injuries was found in 9 cases. Ultrasonography allowed visualization and objective assessment of the type and the extent of traumatic pathomorphological changes of muscles and tendons. Such diagnostic possibilities of ultrasonography are especially important in the choice of appropriate therapy.

Post-transcriptional regulation of Pabpn1 by the RNA binding protein HuR.

PubMed

Phillips, Brittany L; Banerjee, Ayan; Sanchez, Brenda J; Di Marco, Sergio; Gallouzi, Imed-Eddine; Pavlath, Grace K; Corbett, Anita H

2018-06-25

RNA processing is critical for proper spatial and temporal control of gene expression. The ubiquitous nuclear polyadenosine RNA binding protein, PABPN1, post-transcriptionally regulates multiple steps of gene expression. Mutations in the PABPN1 gene expanding an N-terminal alanine tract in the PABPN1 protein from 10 alanines to 11-18 alanines cause the muscle-specific disease oculopharyngeal muscular dystrophy (OPMD), which affects eyelid, pharynx, and proximal limb muscles. Previous work revealed that the Pabpn1 transcript is unstable, contributing to low steady-state Pabpn1 mRNA and protein levels in vivo, specifically in skeletal muscle, with even lower levels in muscles affected in OPMD. Thus, low levels of PABPN1 protein could predispose specific tissues to pathology in OPMD. However, no studies have defined the mechanisms that regulate Pabpn1 expression. Here, we define multiple cis-regulatory elements and a trans-acting factor, HuR, which regulate Pabpn1 expression specifically in mature muscle in vitro and in vivo. We exploit multiple models including C2C12 myotubes, primary muscle cells, and mice to determine that HuR decreases Pabpn1 expression. Overall, we have uncovered a mechanism in mature muscle that negatively regulates Pabpn1 expression in vitro and in vivo, which could provide insight to future studies investigating therapeutic strategies for OPMD treatment.

Urological cancer care pathways: development and use in the context of systematic reviews and clinical practice guidelines.

PubMed

Maclennan, Sara Jane; Maclennan, Steven J; Imamura, Mari; Omar, Muhammad Imran; Vale, Luke; Lam, Thomas; Royle, Pamela; Royle, Justine; Swami, Satchi; Pickard, Rob; McClinton, Sam; Griffiths, T R Leyshon; Dahm, Philipp; N'dow, James

2011-06-01

Making healthcare treatment decisions is a complex process involving a broad stakeholder base including patients, their families, health professionals, clinical practice guideline developers and funders of healthcare. This paper presents a review of a methodology for the development of urological cancer care pathways (UCAN care pathways), which reflects an appreciation of this broad stakeholder base. The methods section includes an overview of the steps in the development of the UCAN care pathways and engagement with clinical content experts and patient groups. The development process is outlined, the uses of the urological cancer care pathways discussed and the implications for clinical practice highlighted. The full set of UCAN care pathways is published in this paper. These include care pathways on localised prostate cancer, locally advanced prostate cancer, metastatic prostate cancer, hormone-resistant prostate cancer, localised renal cell cancer, advanced renal cell cancer, testicular cancer, penile cancer, muscle invasive and metastatic bladder cancer and non-muscle invasive bladder cancer. The process provides a useful framework for improving urological cancer care through evidence synthesis, research prioritisation, stakeholder involvement and international collaboration. Although the focus of this work is urological cancers, the methodology can be applied to all aspects of urology and is transferable to other clinical specialties.

Transcriptome profiling of claw muscle of the mud crab (Scylla paramamosain) at different fattening stages

PubMed Central

Jiang, Qingling; Bao, Chenchang; Yang, Ya’nan; Liu, An; Liu, Fang; Huang, Huiyang; Ye, Haihui

2017-01-01

In crustaceans, muscle growth and development is complicated, and to date substantial knowledge gaps exist. In this study, the claw muscle, hepatopancreas and nervous tissue of the mud crab (Scylla paramamosain) were collected at three fattening stages for sequence by the Illumina sequencing. A total of 127.87 Gb clean data with no less than 3.94 Gb generated for each sample and the cycleQ30 percentages were more than 86.13% for all samples. De Bruijn assembly of these clean data produced 94,853 unigenes, thereinto, 50,059 unigenes were found in claw muscle. A total of 121 differentially expressed genes (DEGs) were revealed in claw muscle from the three fattening stages with a Padj value < 0.01, including 63 genes with annotation. Functional annotation and enrichment analysis showed that the DEGs clusters represented the predominant gene catalog with roles in biochemical processes (glycolysis, phosphorylation and regulation of transcription), molecular function (ATP binding, 6-phosphofructokinase activity, and sequence-specific DNA binding) and cellular component (6-phosphofructokinase complex, plasma membrane, and integral component of membrane). qRT-PCR was employed to further validate certain DEGs. Single nucleotide polymorphism (SNP) analysis obtained 159,322, 125,963 and 166,279 potential SNPs from the muscle transcriptome at stage B, stage C and stage D, respectively. In addition, there were sixteen neuropeptide transcripts being predicted in the claw muscle. The present study provides a comprehensive transcriptome of claw muscle of S. paramamosain during fattening, providing a basis for screening the functional genes that may affect muscle growth of S. paramamosain. PMID:29141033

PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.

PubMed

Hatazawa, Yukino; Tadaishi, Miki; Nagaike, Yuta; Morita, Akihito; Ogawa, Yoshihiro; Ezaki, Osamu; Takai-Igarashi, Takako; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Kamei, Yasutomi; Miura, Shinji

2014-01-01

Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain α-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.

PGC-1α-Mediated Branched-Chain Amino Acid Metabolism in the Skeletal Muscle

PubMed Central

Nagaike, Yuta; Morita, Akihito; Ogawa, Yoshihiro; Ezaki, Osamu; Takai-Igarashi, Takako; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Kamei, Yasutomi; Miura, Shinji

2014-01-01

Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain α-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism. PMID:24638054

Artificial Muscles Based on Electroactive Polymers as an Enabling Tool in Biomimetics

NASA Technical Reports Server (NTRS)

Bar-Cohen, Y.

2007-01-01

Evolution has resolved many of nature's challenges leading to working and lasting solutions that employ principles of physics, chemistry, mechanical engineering, materials science, and many other fields of science and engineering. Nature's inventions have always inspired human achievements leading to effective materials, structures, tools, mechanisms, processes, algorithms, methods, systems, and many other benefits. Some of the technologies that have emerged include artificial intelligence, artificial vision, and artificial muscles, where the latter is the moniker for electroactive polymers (EAPs). To take advantage of these materials and make them practical actuators, efforts are made worldwide to develop capabilities that are critical to the field infrastructure. Researchers are developing analytical model and comprehensive understanding of EAP materials response mechanism as well as effective processing and characterization techniques. The field is still in its emerging state and robust materials are still not readily available; however, in recent years, significant progress has been made and commercial products have already started to appear. In the current paper, the state-of-the-art and challenges to artificial muscles as well as their potential application to biomimetic mechanisms and devices are described and discussed.

Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T.

We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation,more » myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through mechanisms involving its adhesive and signaling functions.« less

Glucocorticoids and 11β-HSD1 are major regulators of intramyocellular protein metabolism

PubMed Central

Hassan-Smith, Zaki K; Doig, Craig L; Sherlock, Mark; Stewart, Paul M; Lavery, Gareth G

2016-01-01

The adverse metabolic effects of prescribed and endogenous glucocorticoid excess, ‘Cushing’s syndrome’, create a significant health burden. While skeletal muscle atrophy and resultant myopathy is a clinical feature, the molecular mechanisms underpinning these changes are not fully defined. We have characterized the impact of glucocorticoids upon key metabolic pathways and processes regulating muscle size and mass including: protein synthesis, protein degradation, and myoblast proliferation in both murine C2C12 and human primary myotube cultures. Furthermore, we have investigated the role of pre-receptor modulation of glucocorticoid availability by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in these processes. Corticosterone (CORT) decreased myotube area, decreased protein synthesis, and increased protein degradation in murine myotubes. This was supported by decreased mRNA expression of insulin-like growth factor (IGF1), decreased activating phosphorylation of mammalian target of rapamycin (mTOR), decreased phosphorylation of 4E binding protein 1 (4E-BP1), and increased mRNA expression of key atrophy markers including: atrogin-1, forkhead box O3a (FOXO3a), myostatin (MSTN), and muscle-ring finger protein-1 (MuRF1). These findings were endorsed in human primary myotubes, where cortisol also decreased protein synthesis and increased protein degradation. The effects of 11-dehydrocorticosterone (11DHC) (in murine myotubes) and cortisone (in human myotubes) on protein metabolism were indistinguishable from that of CORT/cortisol treatments. Selective 11β-HSD1 inhibition blocked the decrease in protein synthesis, increase in protein degradation, and reduction in myotube area induced by 11DHC/cortisone. Furthermore, CORT/cortisol, but not 11DHC/cortisone, decreased murine and human myoblast proliferative capacity. Glucocorticoids are potent regulators of skeletal muscle protein homeostasis and myoblast proliferation. Our data underscores the potential use of selective 11β-HSD1 inhibitors to ameliorate muscle-wasting effects associated with glucocorticoid excess. PMID:27048233

A muscle-specific knockout implicates nuclear receptor coactivator MED1 in the regulation of glucose and energy metabolism.

PubMed

Chen, Wei; Zhang, Xiaoting; Birsoy, Kivanc; Roeder, Robert G

2010-06-01

As conventional transcriptional factors that are activated in diverse signaling pathways, nuclear receptors play important roles in many physiological processes that include energy homeostasis. The MED1 subunit of the Mediator coactivator complex plays a broad role in nuclear receptor-mediated transcription by anchoring the Mediator complex to diverse promoter-bound nuclear receptors. Given the significant role of skeletal muscle, in part through the action of nuclear receptors, in glucose and fatty acid metabolism, we generated skeletal muscle-specific Med1 knockout mice. Importantly, these mice show enhanced insulin sensitivity and improved glucose tolerance as well as resistance to high-fat diet-induced obesity. Furthermore, the white muscle of these mice exhibits increased mitochondrial density and expression of genes specific to type I and type IIA fibers, indicating a fast-to-slow fiber switch, as well as markedly increased expression of the brown adipose tissue-specific UCP-1 and Cidea genes that are involved in respiratory uncoupling. These dramatic results implicate MED1 as a powerful suppressor in skeletal muscle of genetic programs implicated in energy expenditure and raise the significant possibility of therapeutical approaches for metabolic syndromes and muscle diseases through modulation of MED1-nuclear receptor interactions.

Application of biospeckles for assessment of structural and cellular changes in muscle tissue

NASA Astrophysics Data System (ADS)

Maksymenko, Oleksandr P.; Muravsky, Leonid I.; Berezyuk, Mykola I.

2015-09-01

A modified spatial-temporal speckle correlation technique for operational assessment of structural changes in muscle tissues after slaughtering is considered. Coefficient of biological activity as a quantitative indicator of structural changes of biochemical processes in biological tissues is proposed. The experimental results have shown that this coefficient properly evaluates the biological activity of pig and chicken muscle tissue samples. Studying the degradation processes in muscle tissue during long-time storage in a refrigerator by measuring the spatial-temporal dynamics of biospeckle patterns is carried out. The reduction of the bioactivity level of refrigerated muscle tissue samples connected with the initiation of muscle fiber cracks and ruptures, reduction of sarcomeres, nuclei deformation, nuclear chromatin diminishing, and destruction of mitochondria is analyzed.

Recommendations for the Avoidance of Delayed-Onset Muscle Soreness.

ERIC Educational Resources Information Center

Szymanski, David J.

2001-01-01

Describes the possible causes of delayed-onset muscle soreness (DOMS), which include buildup of lactic acid in muscle, increased intracellular calcium concentration, increased intramuscular inflammation, and muscle fiber and connective tissue damage. Proposed methods to reduce DOMS include warming up before exercise and performing repeated bouts…

A Review of Antioxidant Peptides Derived from Meat Muscle and By-Products.

PubMed

Liu, Rui; Xing, Lujuan; Fu, Qingquan; Zhou, Guang-Hong; Zhang, Wan-Gang

2016-09-20

Antioxidant peptides are gradually being accepted as food ingredients, supplemented in functional food and nutraceuticals, to positively regulate oxidative stress in the human body against lipid and protein oxidation. Meat muscle and meat by-products are rich sources of proteins and can be regarded as good materials for the production of bioactive peptides by use of enzymatic hydrolysis or direct solvent extraction. In recent years, there has been a growing number of studies conducted to characterize antioxidant peptides or hydrolysates derived from meat muscle and by-products as well as processed meat products, including dry-cured hams. Antioxidant peptides obtained from animal sources could exert not only nutritional value but also bioavailability to benefit human health. This paper reviews the antioxidant peptides or protein hydrolysates identified in muscle protein and by-products. We focus on the procedure for the generation of peptides with antioxidant capacity including the acquisition of crude peptides, the assessment of antioxidant activity, and the purification and identification of the active fraction. It remains critical to perform validation experiments with a cell model, animal model or clinical trial to eliminate safety concerns before final application in the food system. In addition, some of the common characteristics on structure-activity relationship are also reviewed based on the identified antioxidant peptides.

A Review of Antioxidant Peptides Derived from Meat Muscle and By-Products

PubMed Central

Liu, Rui; Xing, Lujuan; Fu, Qingquan; Zhou, Guang-hong; Zhang, Wan-gang

2016-01-01

Antioxidant peptides are gradually being accepted as food ingredients, supplemented in functional food and nutraceuticals, to positively regulate oxidative stress in the human body against lipid and protein oxidation. Meat muscle and meat by-products are rich sources of proteins and can be regarded as good materials for the production of bioactive peptides by use of enzymatic hydrolysis or direct solvent extraction. In recent years, there has been a growing number of studies conducted to characterize antioxidant peptides or hydrolysates derived from meat muscle and by-products as well as processed meat products, including dry-cured hams. Antioxidant peptides obtained from animal sources could exert not only nutritional value but also bioavailability to benefit human health. This paper reviews the antioxidant peptides or protein hydrolysates identified in muscle protein and by-products. We focus on the procedure for the generation of peptides with antioxidant capacity including the acquisition of crude peptides, the assessment of antioxidant activity, and the purification and identification of the active fraction. It remains critical to perform validation experiments with a cell model, animal model or clinical trial to eliminate safety concerns before final application in the food system. In addition, some of the common characteristics on structure-activity relationship are also reviewed based on the identified antioxidant peptides. PMID:27657142

Sensitivity of estimated muscle force in forward simulation of normal walking

PubMed Central

Xiao, Ming; Higginson, Jill

2009-01-01

Generic muscle parameters are often used in muscle-driven simulations of human movement estimate individual muscle forces and function. The results may not be valid since muscle properties vary from subject to subject. This study investigated the effect of using generic parameters in a muscle-driven forward simulation on muscle force estimation. We generated a normal walking simulation in OpenSim and examined the sensitivity of individual muscle to perturbations in muscle parameters, including the number of muscles, maximum isometric force, optimal fiber length and tendon slack length. We found that when changing the number muscles included in the model, only magnitude of the estimated muscle forces was affected. Our results also suggest it is especially important to use accurate values of tendon slack length and optimal fiber length for ankle plantarflexors and knee extensors. Changes in force production one muscle were typically compensated for by changes in force production by muscles in the same functional muscle group, or the antagonistic muscle group. Conclusions regarding muscle function based on simulations with generic musculoskeletal parameters should be interpreted with caution. PMID:20498485

Histopathological Evaluation of Skeletal Muscle with Specific Reference to Mouse Models of Muscular Dystrophy.

PubMed

Terry, Rebecca L; Wells, Dominic J

2016-12-01

The muscular dystrophies are a diverse group of degenerative diseases for which many mouse models are available. These models are frequently used to assess potential therapeutic interventions and histological evaluation of multiple muscles is an important part of this assessment. Histological evaluation is especially useful when combined with tests of muscle function. This unit describes a protocol for necropsy, processing, cryosectioning, and histopathological evaluation of murine skeletal muscles, which is applicable to both models of muscular dystrophy and other neuromuscular conditions. Key histopathological features of dystrophic muscle are discussed using the mdx mouse (a model of Duchenne muscular dystrophy) as an example. Optimal handling during dissection, processing and sectioning is vital to avoid artifacts that can confound or prevent future analyses. Muscles carefully processed using this protocol are suitable for further evaluation using immunohistochemistry, immunofluorescence, special histochemical stains, and immuoblotting. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Temporal analysis of reciprocal miRNA-mRNA expression patterns predicts regulatory networks during differentiation in human skeletal muscle cells

PubMed Central

Sjögren, Rasmus J. O.; Egan, Brendan; Katayama, Mutsumi; Zierath, Juleen R.

2014-01-01

microRNAs (miRNAs) are short noncoding RNAs that regulate gene expression through posttranscriptional repression of target genes. miRNAs exert a fundamental level of control over many developmental processes, but their role in the differentiation and development of skeletal muscle from myogenic progenitor cells in humans remains incompletely understood. Using primary cultures established from human skeletal muscle satellite cells, we performed microarray profiling of miRNA expression during differentiation of myoblasts (day 0) into myotubes at 48 h intervals (day 2, 4, 6, 8, and 10). Based on a time-course analysis, we identified 44 miRNAs with altered expression [false discovery rate (FDR) < 5%, fold change > ±1.2] during differentiation, including the marked upregulation of the canonical myogenic miRNAs miR-1, miR-133a, miR-133b, and miR-206. Microarray profiling of mRNA expression at day 0, 4, and 10 identified 842 and 949 genes differentially expressed (FDR < 10%) at day 4 and 10, respectively. At day 10, 42% of altered transcripts demonstrated reciprocal expression patterns in relation to the directional change of their in silico predicted regulatory miRNAs based on analysis using Ingenuity Pathway Analysis microRNA Target Filter. Bioinformatic analysis predicted networks of regulation during differentiation including myomiRs miR-1/206 and miR-133a/b, miRNAs previously established in differentiation including miR-26 and miR-30, and novel miRNAs regulated during differentiation of human skeletal muscle cells such as miR-138-5p and miR-20a. These reciprocal expression patterns may represent new regulatory nodes in human skeletal muscle cell differentiation. This analysis serves as a reference point for future studies of human skeletal muscle differentiation and development in healthy and disease states. PMID:25547110

Activation of Pax7-Positive Cells in a Non-Contractile Tissue Contributes to Regeneration of Myogenic Tissues in the Electric Fish S. macrurus

PubMed Central

Weber, Christopher M.; Martindale, Mark Q.; Tapscott, Stephen J.; Unguez, Graciela A.

2012-01-01

The ability to regenerate tissues is shared across many metazoan taxa, yet the type and extent to which multiple cellular mechanisms come into play can differ across species. For example, urodele amphibians can completely regenerate all lost tissues, including skeletal muscles after limb amputation. This remarkable ability of urodeles to restore entire limbs has been largely linked to a dedifferentiation-dependent mechanism of regeneration. However, whether cell dedifferentiation is the fundamental factor that triggers a robust regeneration capacity, and whether the loss or inhibition of this process explains the limited regeneration potential in other vertebrates is not known. Here, we studied the cellular mechanisms underlying the repetitive regeneration of myogenic tissues in the electric fish S. macrurus. Our in vivo microinjection studies of high molecular weight cell lineage tracers into single identified adult myogenic cells (muscle or noncontractile muscle-derived electrocytes) revealed no fragmentation or cellularization proximal to the amputation plane. In contrast, ultrastructural and immunolabeling studies verified the presence of myogenic stem cells that express the satellite cell marker Pax7 in mature muscle fibers and electrocytes of S. macrurus. These data provide the first example of Pax-7 positive muscle stem cells localized within a non-contractile electrogenic tissue. Moreover, upon amputation, Pax-7 positive cells underwent a robust replication and were detected exclusively in regions that give rise to myogenic cells and dorsal spinal cord components revealing a regeneration process in S. macrurus that is dependent on the activation of myogenic stem cells for the renewal of both skeletal muscle and the muscle-derived electric organ. These data are consistent with the emergent concept in vertebrate regeneration that different tissues provide a distinct progenitor cell population to the regeneration blastema, and these progenitor cells subsequently restore the original tissue. PMID:22685526

Autophagy during beef aging

PubMed Central

García-Macia, Marina; Sierra, Verónica; Palanca, Ana; Vega-Naredo, Ignacio; de Gonzalo-Calvo, David; Rodríguez-González, Susana; Oliván, Mamen; Coto-Montes, Ana

2013-01-01

The conversion of muscle into meat is a complex process of major concern for meat scientists due to its influence on the final meat quality. The aim of this study was to investigate the occurrence of autophagic processes in the conversion of muscle into meat. Our findings demonstrated, for the first time, the occurrence of autophagic processes in the muscle tissue at early postmortem period (2 h to 24 h) in both beef breeds studied (Asturiana de los Valles and Asturiana de la Montaña) showing significant time-scale differences between breeds, which could indicate a role of this process in meat maturation. These breeds have different physiological features: while Asturiana de los Valles is a meat-specialized breed showing high growth rate, an elevated proportion of white fibers in the muscle and low intramuscular fat level, Asturiana de la Montaña is a small- to medium-sized rustic breed adapted to less-favored areas, showing more red fibers in the muscle and a high intramuscular fat content. PMID:24225649

Vibroacoustic processes and structural variations in muscular tissue

NASA Astrophysics Data System (ADS)

Antonets, V. A.; Klochkov, B. N.; Kovaleva, E. P.

1995-03-01

This paper reviews the problems and results obtained in the course of experimental and theoretical investigations of the vibroacoustic activity of contracting muscles. Two types of such processes are examined: (1) acoustic vibrations due to the macromolecular recombinations of muscle proteins, which are responsible for the muscle contraction, and (2) acoustic vibrations associated with the finite accuracy and speed of the receptor-effector system that controls the muscle contraction. By investigating the acoustic vibrations, we examine structural recombinations (conformation variations) in macromolecules during mechanochemical reactions. Since chemical reactions of macromolecules are always accompanied by conformational recombinations, the generation mechanism, which is responsible for the contraction processes in a muscular tissue, can also be extended to other macromolecular media. Investigation of infrasound vibrations makes it possible to explore the quality and error of control for the processes in the muscle under different types of loading. Since a living body is controlled via perceptions, the latter can be quantitatively estimated by the parametess of infrasound vibrations.

Influence of type of muscle on volatile compounds throughout the manufacture of Celta dry-cured ham.

PubMed

Bermúdez, Roberto; Franco, Daniel; Carballo, Javier; Lorenzo, José M

2015-12-01

The effect of muscle type on volatile compounds throughout the manufacture of Celta dry-cured ham was studied. Thirty Celta ham were taken from the fresh pieces, after the end of the salting stage, after 120 days of post-salting, after the end of drying-ripening stage, and after 165 and 330 days of "bodega" step. The volatile compounds from semimembranosus (SM) and biceps femoris (BF) muscles were extracted by using headspace-solid phase microextraction (SPME) and analysed by gas chromatographic/mass spectrometry (GC/MS). Fifty-five volatile compounds were identified and quantified. The number of volatile compounds increased during the different steps of the process, reaching at 550 days of process 39 and 40 volatile compounds in SM and BF muscles, respectively. Results indicated that the most abundant chemical family in flavour at the end of the manufacturing process were esters in the two muscles studied, followed by aliphatic hydrocarbons and aldehydes. During the manufacturing process, an increase in the total amount of volatile compounds was observed, being this increase more marked in samples from BF muscle (from 550.7 to 1118.9 × 10(6) area units) than in samples from SM muscle (from 459.3 to 760.4 × 10(6) area units). Finally, muscle type displayed significant (P < 0.05) differences for four esters, two alcohols, one aldehyde, one ketone and four aliphatic hydrocarbons. © The Author(s) 2014.

[Application of the xenogenic acellular dermal matrix membrane application used in the postoperative tissue shortage repair].

PubMed

Bai, Yanxia; Yan, Liying; Zhang, Shaoqiang; Shao, Yuan; Yao, Xiaobao; Li, Honghui; Zhao, Ruimin; Zhao, Qian; Zhang, Pengfei; Yang, Qi

2014-09-01

To observe the short-term and long-term curative effect of the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer) application used in the 82 cases postoperative tissue shortage repair that after the head neck carcinoma resection. To held the 82 cases head neck carcinoma postoperative mucosa shortage repaired after resection by the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer), 65 cases mucosa shortage wound be directly covered by the repair membrane and the other 17 cases mucosa shortage wound be repaired by the tranfered muscle tissue flap with the repair membrane covered; 53 cases underwent additional postoperative radiotherapy between 2-4 weeks and follow-up in 1, 3, 6, 12, 18, 24, 30, 36, 48, 60 months and observed the operation site repair process through the electronic laryngoscope, observed the patients respiration, swallow, phonation function. Seventy-seven cases patients operation incision reached I phase healing standard, another 5 cases patients operation incision reached II phase healing standard because of the wound infection and fully-recovered through the local wound drainage,dressing process. All the patients tracheal cannula,the stomach tube be extubated successfully and without the local cicatricial constriction occurred. Seventy-eight cases follow up period reached 1 year including 53 cases who underwent postoperative radiotherapy, 49 cases follow up period reached 3 years including 32 cases who underwent postoperative radiotherapy, 14 cases follow up period reached 5 years including 12 cases who underwent postoperative radiotherapy. The patients with static local lesions discovered no reaction such as exclusion, allergy. The application of xenogenic acellular dermal matrix membrane (or joint muscle flap transfer used in in the postoperative tissue shortage repair that after the head neck carcinoma resection have several advantage such as comparatively easily implementation, operation safety edge enough,well preserved organ function, comparatively low incidence about the laryngeal stenosis, the short-term and long-term repair effect are all exact.

Sensory training with vibration-induced kinesthetic illusions improves proprioceptive integration in patients with Parkinson's disease.

PubMed

Ribot-Ciscar, Edith; Aimonetti, Jean-Marc; Azulay, Jean-Philippe

2017-12-15

The present study investigates whether proprioceptive training, based on kinesthetic illusions, can help in re-educating the processing of muscle proprioceptive input, which is impaired in patients with Parkinson's disease (PD). The processing of proprioceptive input before and after training was evaluated by determining the error in the amplitude of voluntary dorsiflexion ankle movement (20°), induced by applying a vibration on the tendon of the gastrocnemius-soleus muscle (a vibration-induced movement error). The training consisted of the subjects focusing their attention upon a series of illusory movements of the ankle. Eleven PD patients and eleven age-matched control subjects were tested. Before training, vibration reduced dorsiflexion amplitude in controls by 4.3° (P<0.001); conversely, vibration was inefficient in PD's movement amplitude (reduction of 2.1°, P=0.20). After training, vibration significantly reduced the estimated movement amplitude in PD patients by 5.3° (P=0.01). This re-emergence of a vibration-induced error leads us to conclude that proprioceptive training, based on kinesthetic illusions, is a simple means for re-educating the processing of muscle proprioceptive input in PD patients. Such complementary training should be included in rehabilitation programs that presently focus on improving balance and motor performance. Copyright © 2017 Elsevier B.V. All rights reserved.

Gait post-stroke: Pathophysiology and rehabilitation strategies.

PubMed

Beyaert, C; Vasa, R; Frykberg, G E

2015-11-01

We reviewed neural control and biomechanical description of gait in both non-disabled and post-stroke subjects. In addition, we reviewed most of the gait rehabilitation strategies currently in use or in development and observed their principles in relation to recent pathophysiology of post-stroke gait. In both non-disabled and post-stroke subjects, motor control is organized on a task-oriented basis using a common set of a few muscle modules to simultaneously achieve body support, balance control, and forward progression during gait. Hemiparesis following stroke is due to disruption of descending neural pathways, usually with no direct lesion of the brainstem and cerebellar structures involved in motor automatic processes. Post-stroke, improvements of motor activities including standing and locomotion are variable but are typically characterized by a common postural behaviour which involves the unaffected side more for body support and balance control, likely in response to initial muscle weakness of the affected side. Various rehabilitation strategies are regularly used or in development, targeting muscle activity, postural and gait tasks, using more or less high-technology equipment. Reduced walking speed often improves with time and with various rehabilitation strategies, but asymmetric postural behaviour during standing and walking is often reinforced, maintained, or only transitorily decreased. This asymmetric compensatory postural behaviour appears to be robust, driven by support and balance tasks maintaining the predominant use of the unaffected side over the initially impaired affected side. Based on these elements, stroke rehabilitation including affected muscle strengthening and often stretching would first need to correct the postural asymmetric pattern by exploiting postural automatic processes in various particular motor tasks secondarily beneficial to gait. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Muscle fatigue evaluation of astronaut upper limb based on sEMG and subjective assessment

NASA Astrophysics Data System (ADS)

Zu, Xiaoqi; Zhou, Qianxiang; Li, Yun

2012-07-01

All movements are driven by muscle contraction, and it is easy to cause muscle fatigue. Evaluation of muscle fatigue is a hot topic in the area of astronaut life support training and rehabilitation. If muscle gets into fatigue condition, it may reduce work efficiency and has an impact on psychological performance. Therefore it is necessary to develop an accurate and usable method on muscle fatigue evaluation of astronaut upper limb. In this study, we developed a method based on surface electromyography (sEMG) and subjective assessment (Borg scale) to evaluate local muscle fatigue. Fifteen healthy young male subjects participated in the experiment. They performed isometric muscle contractions of the upper limb. sEMG of the biceps brachii were recorded during the entire process of isotonic muscle contraction and Borg scales of muscle fatigue were collected in certain times. sEMG were divided into several parts, and then mean energy of each parts were calculated by the one-twelfth band octave method. Equations were derived based on the relationship between the mean energy of sEMG and Borg scale. The results showed that cubic curve could describe the degree of local muscle fatigue, and could be used to evaluate and monitor local muscle fatigue during the entire process.

Microwave sensing for meat and fish structure evaluation

NASA Astrophysics Data System (ADS)

Clerjon, S.; Damez, J. L.

2007-04-01

Monitoring changes in muscle structure during the ageing of bovine meat and quality loss due to fish freezing are major industrial challenges. During ageing, bovine muscle becomes tender through muscle fibre deterioration, and full control of this process is essential. Conversely, degradation of fish muscle, often due to long storage or a freezing cycle, lowers quality. To improve competitiveness, and to respond to consumer quality demand, muscle structure needs to be evaluated in-line. We present here a polarimetric microwave method (10-24 GHz) consisting in free space and contact reflection coefficient measurements using a horn antenna and rectangular probes, respectively. This method is based on the measurement of dielectric properties of tissues parallel and perpendicular to muscle fibre directions. The dielectric properties of structured tissues such as muscles are anisotropic, but during processing structural disorganization reduces this anisotropy. The method is illustrated by the discrimination of fresh and frozen-thawed fish fillets and by monitoring of meat ageing.

Skeletal muscle

USDA-ARS?s Scientific Manuscript database

There are approximately 650-850 muscles in the human body these include skeletal (striated), smooth and cardiac muscle. The approximation is based on what some anatomists consider separate muscle or muscle systems. Muscles are classified based on their anatomy (striated vs. smooth) and if they are v...

Magnetic resonance imaging of live freshwater mussels (Unionidae)

USGS Publications Warehouse

Michael, Holliman F.; Davis, Denise; Bogan, Arthur E.; Kwak, Thomas J.; Cope, W. Gregory; Levine, Jay F.

2008-01-01

We examined the soft tissues of live freshwater mussels, Eastern elliptio Elliptio complanata, via magnetic resonance imaging (MRI), acquiring data with a widely available human whole-body MRI system. Anatomical features depicted in the profile images included the foot, stomach, intestine, anterior and posterior adductor muscles, and pericardial cavity. Noteworthy observations on soft tissue morphology included a concentration of lipids at the most posterior aspect of the foot, the presence of hemolymph-filled fissures in the posterior adductor muscle, the presence of a relatively large hemolymph-filled sinus adjacent to the posterior adductor muscle (at the ventral-anterior aspect), and segmentation of the intestine (a diagnostic description not reported previously in Unionidae). Relatively little is known about the basic biology and ecological physiology of freshwater mussels. Traditional approaches for studying anatomy and tissue processes, and for measuring sub-lethal physiological stress, are destructive or invasive. Our study, the first to evaluate freshwater mussel soft tissues by MRI, clarifies the body plan of unionid mussels and demonstrates the efficacy of this technology for in vivoevaluation of the structure, function, and integrity of mussel soft tissues.

Aging human body: changes in bone, muscle and body fat with consequent changes in nutrient intake.

PubMed

JafariNasabian, Pegah; Inglis, Julia E; Reilly, Wendimere; Kelly, Owen J; Ilich, Jasminka Z

2017-07-01

Aging affects almost all physiological processes, but changes in body composition and body phenotype are most observable. In this review, we focus on these changes, including loss of bone and muscle and increase in body fat or redistribution of the latter, possibly leading to osteosarcopenic obesity syndrome. We also address low-grade chronic inflammation, prevalent in aging adults and a cause of many disorders including those associated with body composition. Changes in dietary intake and nutritional requirements of older individuals, that all may lead to some disturbances on tissue and organ levels, are discussed as well. Finally, we discuss the hormonal changes in the aging body, considering each of the tissues, bone, muscle and fat as separate endocrine organs, but yet in the continuous interface and communication with each other. Although there are still many unanswered questions in this field, this review will enable the readers to better understand the aging human body and measures needing to be implemented toward reducing impaired health and disability in older individuals. © 2017 Society for Endocrinology.

Growth factor involvement in tension-induced skeletal muscle growth

NASA Technical Reports Server (NTRS)

Vandenburgh, H. H.

1987-01-01

Muscle tissue culture techniques were developed to grow skeletal myofibers which differentiate into more adult-like myofibers. Mechanical simulation studies of these muscle cells in a newly developed mechanical cell simulator can now be performed to study growth processes in skeletal muscle. Conditions in the mechanical cell simulator were defined where mechanical activity can either prevent muscle wasting or stimulate muscle growth. The role of endogenous and exogenous growth factors in tension-induced muscle growth is being investigated under the defined conditions of tissue culture.

Tensiomygraphic Measurement of Atrophy Related Processes During Bed Rest and Recovery

NASA Astrophysics Data System (ADS)

Simunic, B. ostjan; Degens, Hans; Rittweger, Jorn; Narici, Marcco; Pisot, Venceslav; Mekjavic, Igor B.; Pisot, Rado

2013-02-01

Tensiomyographic (TMG) parameters were recently proposed for a non-invasive estimation of MHC distribution in human vastus lateralis muscle. However, TMG potential is even higher, offers additional insight into the skeletal muscle physiology, especially in the field of atrophy and hypertrophy. The purpose of this study is in developing time dynamics of TMG-measured contraction time (Tc) and maximal response amplitude (Dm), together with muscle belly thickness, measure thoroughly during 35-day bed rest and followed in 30-day recovery (N = 10 males; age 24.3 ± 2.6 years). Measurements were performed in two postural muscles (vastus medialis and lateralis) and one non-postural muscle (biceps femoris). During bed rest period we found different dynamics of muscle thickness decrease and Dm increase. Tc was unchanged in postural muscles, but in non-postural muscle increased significantly and stayed as such even at the end of recovery. We could conclude that TMG related parameters are more sensitive in measuring muscle atrophic and hypertrophic processes than biomedical imaging technique. However, a mechanism that regulates Dm still needs to be identified.

Force encoding in muscle spindles during stretch of passive muscle

PubMed Central

Blum, Kyle P.; Zytnicki, Daniel

2017-01-01

Muscle spindle proprioceptive receptors play a primary role in encoding the effects of external mechanical perturbations to the body. During externally-imposed stretches of passive, i.e. electrically-quiescent, muscles, the instantaneous firing rates (IFRs) of muscle spindles are associated with characteristics of stretch such as length and velocity. However, even in passive muscle, there are history-dependent transients of muscle spindle firing that are not uniquely related to muscle length and velocity, nor reproduced by current muscle spindle models. These include acceleration-dependent initial bursts, increased dynamic response to stretch velocity if a muscle has been isometric, and rate relaxation, i.e., a decrease in tonic IFR when a muscle is held at a constant length after being stretched. We collected muscle spindle spike trains across a variety of muscle stretch kinematic conditions, including systematic changes in peak length, velocity, and acceleration. We demonstrate that muscle spindle primary afferents in passive muscle fire in direct relationship to muscle force-related variables, rather than length-related variables. Linear combinations of whole muscle-tendon force and the first time derivative of force (dF/dt) predict the entire time course of transient IFRs in muscle spindle Ia afferents during stretch (i.e., lengthening) of passive muscle, including the initial burst, the dynamic response to lengthening, and rate relaxation following lengthening. Similar to acceleration scaling found previously in postural responses to perturbations, initial burst amplitude scaled equally well to initial stretch acceleration or dF/dt, though later transients were only described by dF/dt. The transient increase in dF/dt at the onset of lengthening reflects muscle short-range stiffness due to cross-bridge dynamics. Our work demonstrates a critical role of muscle cross-bridge dynamics in history-dependent muscle spindle IFRs in passive muscle lengthening conditions relevant to the detection and sensorimotor response to mechanical perturbations to the body, and to previously-described history-dependence in perception of limb position. PMID:28945740

Force encoding in muscle spindles during stretch of passive muscle.

PubMed

Blum, Kyle P; Lamotte D'Incamps, Boris; Zytnicki, Daniel; Ting, Lena H

2017-09-01

Muscle spindle proprioceptive receptors play a primary role in encoding the effects of external mechanical perturbations to the body. During externally-imposed stretches of passive, i.e. electrically-quiescent, muscles, the instantaneous firing rates (IFRs) of muscle spindles are associated with characteristics of stretch such as length and velocity. However, even in passive muscle, there are history-dependent transients of muscle spindle firing that are not uniquely related to muscle length and velocity, nor reproduced by current muscle spindle models. These include acceleration-dependent initial bursts, increased dynamic response to stretch velocity if a muscle has been isometric, and rate relaxation, i.e., a decrease in tonic IFR when a muscle is held at a constant length after being stretched. We collected muscle spindle spike trains across a variety of muscle stretch kinematic conditions, including systematic changes in peak length, velocity, and acceleration. We demonstrate that muscle spindle primary afferents in passive muscle fire in direct relationship to muscle force-related variables, rather than length-related variables. Linear combinations of whole muscle-tendon force and the first time derivative of force (dF/dt) predict the entire time course of transient IFRs in muscle spindle Ia afferents during stretch (i.e., lengthening) of passive muscle, including the initial burst, the dynamic response to lengthening, and rate relaxation following lengthening. Similar to acceleration scaling found previously in postural responses to perturbations, initial burst amplitude scaled equally well to initial stretch acceleration or dF/dt, though later transients were only described by dF/dt. The transient increase in dF/dt at the onset of lengthening reflects muscle short-range stiffness due to cross-bridge dynamics. Our work demonstrates a critical role of muscle cross-bridge dynamics in history-dependent muscle spindle IFRs in passive muscle lengthening conditions relevant to the detection and sensorimotor response to mechanical perturbations to the body, and to previously-described history-dependence in perception of limb position.

The relationship between blood and muscle samples to monitor for residues of the antibiotic enrofloxacin in chickens.

PubMed

Reyes-Herrera, I; Schneider, M J; Blore, P J; Donoghue, D J

2011-02-01

In 2005, the US Food and Drug Administration withdrew approval for use of enrofloxacin in poultry, thus effectively imposing zero tolerance for residues of this antibiotic in poultry. Conventional residue monitoring for most antibiotics, including enrofloxacin, involves removing poultry carcasses from the processing line and collecting muscle tissues for analysis. Because of the loss of valuable edible products and the difficulties and expense of sampling all the carcasses, only a small portion of carcasses are tested for violative residues. Unlike muscle tissue, blood is readily available from all birds at the beginning of processing and may be used to screen for illegal residues in all poultry carcasses. It is unknown, however, if enrofloxacin concentrations in blood are predictive of muscle concentrations. In an effort to evaluate this relationship, 156 broiler chickens, 5 wk of age, were dosed with either 25 or 50 µg/mL of enrofloxacin for 3 or 7 d, respectively, in the drinking water. Blood and muscle samples were collected at 0, 1, 3, 6, 12, and 24 h (n = 6 birds/group) during the first dosing day, every 48 h during the dosing period, and every 12 h during the withdrawal period for up to 60 h after withdrawal. Enrofloxacin residues were determined in all blood and tissue samples during the dosing periods and in most of the withdrawal period for both doses. These results support the potential to use blood to screen for illegal enrofloxacin residues in edible poultry tissues in an effort to protect the human food supply.

Redox Control of Skeletal Muscle Regeneration.

PubMed

Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan; Groussard, Carole; Zouhal, Hassane; Chazaud, Bénédicte; Mounier, Rémi

2017-08-10

Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276-310.

Redox Control of Skeletal Muscle Regeneration

PubMed Central

Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan; Groussard, Carole; Zouhal, Hassane

2017-01-01

Abstract Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276–310. PMID:28027662

Sarcospan: a small protein with large potential for Duchenne muscular dystrophy

PubMed Central

2013-01-01

Purification of the proteins associated with dystrophin, the gene product responsible for Duchenne muscular dystrophy, led to the discovery of the dystrophin-glycoprotein complex. Sarcospan, a 25-kDa transmembrane protein, was the last component to be identified and its function in skeletal muscle has been elusive. This review will focus on progress over the last decade revealing that sarcospan is an important regulator of muscle cell adhesion, strength, and regeneration. Investigations using several transgenic mouse models demonstrate that overexpression of sarcospan in the mouse model for Duchenne muscular dystrophy ameliorates pathology and restores muscle cell binding to laminin. Sarcospan improves cell surface expression of the dystrophin- and utrophin-glycoprotein complexes as well as α7β1 integrin, which are the three major laminin-binding complexes in muscle. Utrophin and α7β1 integrin compensate for the loss of dystrophin and the finding that sarcospan increases their abundance at the extra-synaptic sarcolemma supports the use of sarcospan as a therapeutic target. Newly discovered phenotypes in sarcospan-deficient mice, including a reduction in specific force output and increased drop in force in the diaphragm muscle, result from decreased utrophin and dystrophin expression and further reveal sarcospan’s role in determining abundance of these complexes. Dystrophin protein levels and the specific force output of the diaphragm muscle are further reduced upon genetic removal of α7 integrin (Itga7) in SSPN-deficient mice, demonstrating that interactions between integrin and sarcospan are critical for maintenance of the dystrophin-glycoprotein complex and force production of the diaphragm muscle. Sarcospan is a major regulator of Akt signaling pathways and sarcospan-deficiency significantly impairs muscle regeneration, a process that is dependent on Akt activation. Intriguingly, sarcospan regulates glycosylation of a specific subpopulation of α-dystroglycan, the laminin-binding receptor associated with dystrophin and utrophin, localized to the neuromuscular junction. Understanding the basic mechanisms responsible for assembly and trafficking of the dystrophin- and utrophin-glycoprotein complexes to the cell surface is lacking and recent studies suggest that sarcospan plays a role in these essential processes. PMID:23282144

Biologically inspired technologies using artificial muscles

NASA Astrophysics Data System (ADS)

Bar-Cohen, Yoseph

2005-01-01

After billions of years of evolution, nature developed inventions that work, which are appropriate for the intended tasks and that last. The evolution of nature led to the introduction of highly effective and power efficient biological mechanisms that are scalable from micron to many meters in size. Imitating these mechanisms offers enormous potentials for the improvement of our life and the tools we use. Humans have always made efforts to imitate nature and we are increasingly reaching levels of advancement where it becomes significantly easier to imitate, copy, and adapt biological methods, processes and systems. Some of the biomimetic technologies that have emerged include artificial muscles, artificial intelligence, and artificial vision to which significant advances in materials science, mechanics, electronics, and computer science have contributed greatly. One of the newest fields of biomimetics is the electroactive polymers (EAP) that are also known as artificial muscles. To take advantage of these materials, efforts are made worldwide to establish a strong infrastructure addressing the need for comprehensive analytical modeling of their operation mechanism and develop effective processing and characterization techniques. The field is still in its emerging state and robust materials are not readily available however in recent years significant progress has been made and commercial products have already started to appear. This paper covers the state-of-the-art and challenges to making artificial muscles and their potential biomimetic applications.

Real time estimation of generation, extinction and flow of muscle fibre action potentials in high density surface EMG.

PubMed

Mesin, Luca

2015-02-01

Developing a real time method to estimate generation, extinction and propagation of muscle fibre action potentials from bi-dimensional and high density surface electromyogram (EMG). A multi-frame generalization of an optical flow technique including a source term is considered. A model describing generation, extinction and propagation of action potentials is fit to epochs of surface EMG. The algorithm is tested on simulations of high density surface EMG (inter-electrode distance equal to 5mm) from finite length fibres generated using a multi-layer volume conductor model. The flow and source term estimated from interference EMG reflect the anatomy of the muscle, i.e. the direction of the fibres (2° of average estimation error) and the positions of innervation zone and tendons under the electrode grid (mean errors of about 1 and 2mm, respectively). The global conduction velocity of the action potentials from motor units under the detection system is also obtained from the estimated flow. The processing time is about 1 ms per channel for an epoch of EMG of duration 150 ms. A new real time image processing algorithm is proposed to investigate muscle anatomy and activity. Potential applications are proposed in prosthesis control, automatic detection of optimal channels for EMG index extraction and biofeedback. Copyright © 2014 Elsevier Ltd. All rights reserved.

Automated unsupervised multi-parametric classification of adipose tissue depots in skeletal muscle

PubMed Central

Valentinitsch, Alexander; Karampinos, Dimitrios C.; Alizai, Hamza; Subburaj, Karupppasamy; Kumar, Deepak; Link, Thomas M.; Majumdar, Sharmila

2012-01-01

Purpose To introduce and validate an automated unsupervised multi-parametric method for segmentation of the subcutaneous fat and muscle regions in order to determine subcutaneous adipose tissue (SAT) and intermuscular adipose tissue (IMAT) areas based on data from a quantitative chemical shift-based water-fat separation approach. Materials and Methods Unsupervised standard k-means clustering was employed to define sets of similar features (k = 2) within the whole multi-modal image after the water-fat separation. The automated image processing chain was composed of three primary stages including tissue, muscle and bone region segmentation. The algorithm was applied on calf and thigh datasets to compute SAT and IMAT areas and was compared to a manual segmentation. Results The IMAT area using the automatic segmentation had excellent agreement with the IMAT area using the manual segmentation for all the cases in the thigh (R2: 0.96) and for cases with up to moderate IMAT area in the calf (R2: 0.92). The group with the highest grade of muscle fat infiltration in the calf had the highest error in the inner SAT contour calculation. Conclusion The proposed multi-parametric segmentation approach combined with quantitative water-fat imaging provides an accurate and reliable method for an automated calculation of the SAT and IMAT areas reducing considerably the total post-processing time. PMID:23097409

Aerobic Exercise Training in Post-Polio Syndrome: Process Evaluation of a Randomized Controlled Trial

PubMed Central

Voorn, Eric L.; Koopman, Fieke S.; Brehm, Merel A.; Beelen, Anita; de Haan, Arnold; Gerrits, Karin H. L.; Nollet, Frans

2016-01-01

Objective To explore reasons for the lack of efficacy of a high intensity aerobic exercise program in post-polio syndrome (PPS) on cardiorespiratory fitness by evaluating adherence to the training program and effects on muscle function. Design A process evaluation using data from an RCT. Patients Forty-four severely fatigued individuals with PPS were randomized to exercise therapy (n = 22) or usual care (n = 22). Methods Participants in the exercise group were instructed to exercise 3 times weekly for 4 months on a bicycle ergometer (60–70% heart rate reserve). Results The attendance rate was high (median 89%). None of the participants trained within the target heart rate range during >75% of the designated time. Instead, participants exercised at lower intensities, though still around the anaerobic threshold (AT) most of the time. Muscle function did not improve in the exercise group. Conclusion Our results suggest that severely fatigued individuals with PPS cannot adhere to a high intensity aerobic exercise program on a cycle ergometer. Despite exercise intensities around the AT, lower extremity muscle function nor cardiorespiratory fitness improved. Improving the aerobic capacity in PPS is difficult through exercise primarily focusing on the lower extremities, and may require a more individualized approach, including the use of other large muscle groups instead. Trial Registration Netherlands National Trial Register NTR1371 PMID:27419388

Evaluation of Augmented Reality Feedback in Surgical Training Environment.

PubMed

Zahiri, Mohsen; Nelson, Carl A; Oleynikov, Dmitry; Siu, Ka-Chun

2018-02-01

Providing computer-based laparoscopic surgical training has several advantages that enhance the training process. Self-evaluation and real-time performance feedback are 2 of these advantages, which avoid dependency of trainees on expert feedback. The goal of this study was to investigate the use of a visual time indicator as real-time feedback correlated with the laparoscopic surgical training. Twenty novices participated in this study working with (and without) different presentations of time indicators. They performed a standard peg transfer task, and their completion times and muscle activity were recorded and compared. Also of interest was whether the use of this type of feedback induced any side effect in terms of motivation or muscle fatigue. Of the 20 participants, 15 (75%) preferred using a time indicator in the training process rather than having no feedback. However, time to task completion showed no significant difference in performance with the time indicator; furthermore, no significant differences in muscle activity or muscle fatigue were detected with/without time feedback. The absence of significant difference between task performance with/without time feedback shows that using visual real-time feedback can be included in surgical training based on user preference. Trainees may benefit from this type of feedback in the form of increased motivation. The extent to which this can influence training frequency leading to performance improvement is a question for further study.

Macrophage Depletion Impairs Skeletal Muscle Regeneration: the Roles of Pro-fibrotic Factors, Inflammation, and Oxidative Stress.

PubMed

Xiao, Weihua; Liu, Yu; Chen, Peijie

2016-12-01

Muscle contusion is one of the most common muscle injuries in sports medicine. Macrophages play complex roles in the regeneration of skeletal muscle. However, the roles of macrophages, especially the mechanisms involved, in the regeneration of muscle contusion are still not fully understood. We hypothesize that the depletion of macrophages impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may be involved in the process. To test these hypotheses, we constructed a muscle contusion injury and a macrophage depletion model and followed it up with morphological and gene expression analyses. The data showed that fibrotic scars were formed in the muscle of contusion injury, and they deteriorated in the mice of macrophage depletion. Furthermore, the sizes of regenerating myofibers were significantly reduced by macrophage depletion. Pro-fibrotic factors, inflammatory cytokines, chemokines, and oxidative stress-related enzymes increased significantly after muscle injury. Moreover, the expression of these factors was delayed by macrophage depletion. Most of them were still significantly higher in the later stage of regeneration. These results suggest that macrophage depletion impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may play important roles in the process.

Increased adipogenic conversion of muscle satellite cells in obese Zucker rats.

PubMed

Scarda, A; Franzin, C; Milan, G; Sanna, M; Dal Prà, C; Pagano, C; Boldrin, L; Piccoli, M; Trevellin, E; Granzotto, M; Gamba, P; Federspil, G; De Coppi, P; Vettor, R

2010-08-01

Visceral and intermuscular adipose tissue (IMAT) depots account for most obesity-related metabolic and cardiovascular complications. Muscle satellite cells (SCs) are mesenchymal stem cells giving rise to myotubes and also to adipocytes, suggesting their possible contribution to IMAT origin and expansion. We investigated the myogenic differentiation of SCs and the adipogenic potential of both preadipocytes and SCs from genetically obese Zucker rats (fa/fa), focusing on the role of Wnt signaling in these differentiation processes. SCs were isolated by single-fiber technique from flexor digitorum brevis muscle and preadipocytes were extracted from subcutaneous adipose tissue (AT). Morphological features and gene expression profile were evaluated during in vitro myogenesis and adipogenesis. Wingless-type MMTV integration site family member 10b (Wnt10b) expression was quantified by quantitative PCR in skeletal muscle and AT. We did not observe any difference in the proliferation rate and in the myogenic differentiation of SCs from obese and lean rats. However, a decreased insulin-induced glucose uptake was present in myotubes originating from fa/fa rats. Under adipogenic conditions, preadipocytes and SCs of obese animals displayed an enhanced adipogenesis. Wnt10b expression was reduced in obese rats in both muscle and AT. Our data suggest that the increase in different fat depots including IMAT and the reduced muscle insulin sensitivity, the major phenotypical alteration of obese Zucker rats, could be ascribed to an intrinsic defect, either genetically determined or acquired, still present in both muscle and fat precursors. The involvement of Wnt10b as a regulator of both adipogenesis and muscle-to-fat conversion is suggested.

Ageing influence in the evolution of strength and muscle mass in women with fibromyalgia: the al-Ándalus project.

PubMed

Latorre-Román, Pedro Ángel; Segura-Jiménez, Víctor; Aparicio, Virginia A; Santos E Campos, María Aparecida; García-Pinillos, Felipe; Herrador-Colmenero, Manuel; Álvarez-Gallardo, Inmaculada C; Delgado-Fernández, Manuel

2015-07-01

Fibromyalgia is associated with physical disabilities in daily activities. Moreover, patients with fibromyalgia present similar levels of functional capacity and physical condition than elderly people. The aim of this study was to analyse the evolution of strength and muscle mass in women with fibromyalgia along ageing. A total sample of 492 fibromyalgia patients and 279 healthy control women were included in the study. Participants in each group were further divided into four age subgroups: subgroup 1: 30-39 years old, subgroup 2: 40-49 years old, subgroup 3: 50-59 years old and subgroup 4: 60-69 years old. Standardized field-based fitness tests were used to assess muscle strength (30-s chair stand, handgrip strength and arm curl tests). Fibromyalgia patients did not show impairment on muscle mass along ageing, without values of skeletal muscle mass index below 6.76 kg/m(2) in any group. However, in all variables of muscle strength, the fibromyalgia group showed less strength than the healthy group (p < 0.05) for all age groups. As expected, handgrip strength test showed differences along ageing only in the fibromyalgia group (p < 0.001). Age was inversely associated with skeletal muscle mass (r = -0.155, p < 0.01) and handgrip strength (r = -0.230, p < 0.001) in the FM group. Women with fibromyalgia showed a reduction in muscle strength along ageing process, with significantly lower scores than healthy women for each age group, representing a risk of dynapenia.

Wnt Protein-mediated Satellite Cell Conversion in Adult and Aged Mice Following Voluntary Wheel Running

PubMed Central

Fujimaki, Shin; Hidaka, Ryo; Asashima, Makoto; Takemasa, Tohru; Kuwabara, Tomoko

2014-01-01

Muscle represents an abundant, accessible, and replenishable source of adult stem cells. Skeletal muscle-derived stem cells, called satellite cells, play essential roles in regeneration after muscle injury in adult skeletal muscle. Although the molecular mechanism of muscle regeneration process after an injury has been extensively investigated, the regulation of satellite cells under steady state during the adult stage, including the reaction to exercise stimuli, is relatively unknown. Here, we show that voluntary wheel running exercise, which is a low stress exercise, converts satellite cells to the activated state due to accelerated Wnt signaling. Our analysis showed that up-regulated canonical Wnt/β-catenin signaling directly modulated chromatin structures of both MyoD and Myf5 genes, resulting in increases in the mRNA expression of Myf5 and MyoD and the number of proliferative Pax7+Myf5+ and Pax7+ MyoD+ cells in skeletal muscle. The effect of Wnt signaling on the activation of satellite cells, rather than Wnt-mediated fibrosis, was observed in both adult and aged mice. The association of β-catenin, T-cell factor, and lymphoid enhancer transcription factors of multiple T-cell factor/lymphoid enhancer factor regulatory elements, conserved in mouse, rat, and human species, with the promoters of both the Myf5 and MyoD genes drives the de novo myogenesis in satellite cells even in aged muscle. These results indicate that exercise-stimulated extracellular Wnts play a critical role in the regulation of satellite cells in adult and aged skeletal muscle. PMID:24482229

Comparison of foot muscle morphology and foot kinematics between recreational runners with normal feet and with asymptomatic over-pronated feet.

PubMed

Zhang, Xianyi; Aeles, Jeroen; Vanwanseele, Benedicte

2017-05-01

Over-pronated feet are common in adults and are associated with lower limb injuries. Studying the foot muscle morphology and foot kinematic patterns is important for understanding the mechanism of over-pronation related injuries. The aim of this study is to compare the foot muscle morphology and foot inter-segmental kinematics between recreational runners with normal feet and those with asymptomatic over-pronated feet. A total of 26 recreational runners (17 had normal feet and 9 had over-pronated feet) participated in this study and their foot type was assessed using the 6-item Foot Posture Index. Selected foot muscles were scanned using an ultrasound device and the scanned images were processed to measure the thickness and cross-sectional area of the muscles. Muscles of interest include abductor hallucis, abductor digiti minimi, flexor digitorum brevis and longus, tibialis anterior and peroneus muscles. Foot kinematic data during walking was collected using a 3D motion capture system incorporating the Oxford Foot Model. The results show that individuals with over-pronated feet have larger size of abductor hallucis, flexor digitorum brevis and longus and smaller abductor digiti minimi than controls. Higher rearfoot peak eversion and forefoot peak supination during walking were observed in individuals with over-pronated feet. However, during gait the forefoot peak abduction was comparable. These findings indicate that in active asymptomatic individuals with over-pronated feet, the foot muscle morphology is adapted to increase control of the foot motion. The morphological characteristics of the foot muscles in asymptomatic individuals with over-pronated feet may affect their foot kinematics and benefit prevention from injuries. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of the adapter protein Abi1 in actin-associated signaling and smooth muscle contraction.

PubMed

Wang, Tao; Cleary, Rachel A; Wang, Ruping; Tang, Dale D

2013-07-12

Actin filament polymerization plays a critical role in the regulation of smooth muscle contraction. However, our knowledge regarding modulation of the actin cytoskeleton in smooth muscle just begins to accumulate. In this study, stimulation with acetylcholine (ACh) induced an increase in the association of the adapter protein c-Abl interactor 1 (Abi1) with neuronal Wiskott-Aldrich syndrome protein (N-WASP) (an actin-regulatory protein) in smooth muscle cells/tissues. Furthermore, contractile stimulation activated N-WASP in live smooth muscle cells as evidenced by changes in fluorescence resonance energy transfer efficiency of an N-WASP sensor. Abi1 knockdown by lentivirus-mediated RNAi inhibited N-WASP activation, actin polymerization, and contraction in smooth muscle. However, Abi1 silencing did not affect myosin regulatory light chain phosphorylation at Ser-19 in smooth muscle. In addition, c-Abl tyrosine kinase and Crk-associated substrate (CAS) have been shown to regulate smooth muscle contraction. The interaction of Abi1 with c-Abl and CAS has not been investigated. Here, contractile activation induced formation of a multiprotein complex including c-Abl, CAS, and Abi1. Knockdown of c-Abl and CAS attenuated the activation of Abi1 during contractile activation. More importantly, Abi1 knockdown inhibited c-Abl phosphorylation at Tyr-412 and the interaction of c-Abl with CAS. These results suggest that Abi1 is an important component of the cellular process that regulates N-WASP activation, actin dynamics, and contraction in smooth muscle. Abi1 is activated by the c-Abl-CAS pathway, and Abi1 reciprocally controls the activation of its upstream regulator c-Abl.

Role of the Adapter Protein Abi1 in Actin-associated Signaling and Smooth Muscle Contraction*

PubMed Central

Wang, Tao; Cleary, Rachel A.; Wang, Ruping; Tang, Dale D.

2013-01-01

Actin filament polymerization plays a critical role in the regulation of smooth muscle contraction. However, our knowledge regarding modulation of the actin cytoskeleton in smooth muscle just begins to accumulate. In this study, stimulation with acetylcholine (ACh) induced an increase in the association of the adapter protein c-Abl interactor 1 (Abi1) with neuronal Wiskott-Aldrich syndrome protein (N-WASP) (an actin-regulatory protein) in smooth muscle cells/tissues. Furthermore, contractile stimulation activated N-WASP in live smooth muscle cells as evidenced by changes in fluorescence resonance energy transfer efficiency of an N-WASP sensor. Abi1 knockdown by lentivirus-mediated RNAi inhibited N-WASP activation, actin polymerization, and contraction in smooth muscle. However, Abi1 silencing did not affect myosin regulatory light chain phosphorylation at Ser-19 in smooth muscle. In addition, c-Abl tyrosine kinase and Crk-associated substrate (CAS) have been shown to regulate smooth muscle contraction. The interaction of Abi1 with c-Abl and CAS has not been investigated. Here, contractile activation induced formation of a multiprotein complex including c-Abl, CAS, and Abi1. Knockdown of c-Abl and CAS attenuated the activation of Abi1 during contractile activation. More importantly, Abi1 knockdown inhibited c-Abl phosphorylation at Tyr-412 and the interaction of c-Abl with CAS. These results suggest that Abi1 is an important component of the cellular process that regulates N-WASP activation, actin dynamics, and contraction in smooth muscle. Abi1 is activated by the c-Abl-CAS pathway, and Abi1 reciprocally controls the activation of its upstream regulator c-Abl. PMID:23740246

Scapulothoracic muscle activity and recruitment timing in patients with shoulder impingement symptoms and glenohumeral instability.

PubMed

Struyf, Filip; Cagnie, Barbara; Cools, Ann; Baert, Isabel; Brempt, Jolien Van; Struyf, Pieter; Meeus, Mira

2014-04-01

Various studies have investigated scapulothoracic muscle activity and recruitment patterns in relation to shoulder complaints in different populations, but a consensus review is lacking. To systematically review the state of the art regarding scapulothoracic muscle activity and recruitment timing in subjects with shoulder pain compared to pain free controls. Systematic review. The search for relevant articles was performed in Pubmed and Web of Science, including Web of Knowledge, using key words related to shoulder pain, scapulothoracic muscle activity or recruitment timing. Articles were included till November 2012. Case-control studies concerning the scapulothoracic region and muscle recruitment using electromyography (EMG) were included. Articles regarding rotator cuff muscles or neck-shoulder pathologies or studies handling a treatment outcome, were excluded. The methodological quality of the articles was assessed using appropriate risk of bias criteria for case-control studies. A total of 12 articles were included in the systematic review, containing patients with Shoulder Impingement Syndrome (SIS) or glenohumeral instability. In patients with SIS 3 out of 6 articles showed increased upper trapezius muscle (UT) activity, 3 out of 5 studies showed decreased lower trapezius muscle (LT) activity and 3 out of 5 articles showed decreased serratus anterior muscle (SA) activity. Patients with glenohumeral instability showed contradictory results on scapulothoracic muscle activity patterns. In both SIS and glenohumeral instability patients, no consensus was found on muscle recruitment timing. Patients with SIS and glenohumeral instability display numerous variations in scapulothoracic muscle activity compared to healthy controls. In the SIS-group, the LT and SA muscle activity is decreased. In addition, the UT muscle activity is increased among the SIS patients, whereas no clear change is seen among patients with glenohumeral instability. Although the scapulothoracic muscle activity changed, no consensus could be made regarding muscle recruitment timing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Robust generation and expansion of skeletal muscle progenitors and myocytes from human pluripotent stem cells.

PubMed

Shelton, Michael; Kocharyan, Avetik; Liu, Jun; Skerjanc, Ilona S; Stanford, William L

2016-05-15

Human pluripotent stem cells provide a developmental model to study early embryonic and tissue development, tease apart human disease processes, perform drug screens to identify potential molecular effectors of in situ regeneration, and provide a source for cell and tissue based transplantation. Highly efficient differentiation protocols have been established for many cell types and tissues; however, until very recently robust differentiation into skeletal muscle cells had not been possible unless driven by transgenic expression of master regulators of myogenesis. Nevertheless, several breakthrough protocols have been published in the past two years that efficiently generate cells of the skeletal muscle lineage from pluripotent stem cells. Here, we present an updated version of our recently described 50-day protocol in detail, whereby chemically defined media are used to drive and support muscle lineage development from initial CHIR99021-induced mesoderm through to PAX7-expressing skeletal muscle progenitors and mature skeletal myocytes. Furthermore, we report an optional method to passage and expand differentiating skeletal muscle progenitors approximately 3-fold every 2weeks using Collagenase IV and continued FGF2 supplementation. Both protocols have been optimized using a variety of human pluripotent stem cell lines including patient-derived induced pluripotent stem cells. Taken together, our differentiation and expansion protocols provide sufficient quantities of skeletal muscle progenitors and myocytes that could be used for a variety of studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Mechanomyographic Parameter Extraction Methods: An Appraisal for Clinical Applications

PubMed Central

Ibitoye, Morufu Olusola; Hamzaid, Nur Azah; Zuniga, Jorge M.; Hasnan, Nazirah; Wahab, Ahmad Khairi Abdul

2014-01-01

The research conducted in the last three decades has collectively demonstrated that the skeletal muscle performance can be alternatively assessed by mechanomyographic signal (MMG) parameters. Indices of muscle performance, not limited to force, power, work, endurance and the related physiological processes underlying muscle activities during contraction have been evaluated in the light of the signal features. As a non-stationary signal that reflects several distinctive patterns of muscle actions, the illustrations obtained from the literature support the reliability of MMG in the analysis of muscles under voluntary and stimulus evoked contractions. An appraisal of the standard practice including the measurement theories of the methods used to extract parameters of the signal is vital to the application of the signal during experimental and clinical practices, especially in areas where electromyograms are contraindicated or have limited application. As we highlight the underpinning technical guidelines and domains where each method is well-suited, the limitations of the methods are also presented to position the state of the art in MMG parameters extraction, thus providing the theoretical framework for improvement on the current practices to widen the opportunity for new insights and discoveries. Since the signal modality has not been widely deployed due partly to the limited information extractable from the signals when compared with other classical techniques used to assess muscle performance, this survey is particularly relevant to the projected future of MMG applications in the realm of musculoskeletal assessments and in the real time detection of muscle activity. PMID:25479326

Endoplasmic Reticulum Stress, Calcium Dysregulation and Altered Protein Translation: Intersection of Processes That Contribute to Cancer Cachexia Induced Skeletal Muscle Wasting.

PubMed

Isaac, Stephanie T; Tan, Timothy C; Polly, Patsie

2016-01-01

Cancer cachexia is a debilitating paraneoplastic wasting syndrome characterized by skeletal muscle depletion and unintentional weight loss. It affects up to 50-80% of patients with cancer and directly accounts for one-quarter of cancer-related deaths due to cardio-respiratory failure. Muscle weakness, one of the hallmarks of this syndrome, has been postulated to be due to a combination of muscle breakdown, dysfunction and decrease in the ability to repair, with effective treatment strategies presently limited. Excessive inflammatory cytokine levels due to the host-tumor interaction, such as Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α, are hypothesised to drive this pathological process but the specific mechanisms by which these cytokines produce skeletal muscle dysfunction in cancer cachexia remain undefined. Endoplasmic Reticulum (ER) stress and the associated disruptions in calcium signaling have been implicated in cytokine-mediated disruptions in skeletal muscle and function. Disrupted ER stress-related processes such as the Unfolded Protein Response (UPR), calcium homeostasis and altered muscle protein synthesis have been reported in clinical and experimental cachexia and other inflammation-driven muscle diseases such as myositis, potentially suggesting a link between increased IL-6 and TNF-α and ER stress in skeletal muscle cells. As the concept of upregulated ER stress in skeletal muscle cells due to elevated cytokines is novel and potentially very relevant to our understanding of cancer cachexia, this review aims to examine the potential relationship between inflammatory cytokine mediated muscle breakdown and ER stress, in the context of cancer cachexia, and to discuss the molecular signaling pathways underpinning this pathology.

Cardiac function in muscular dystrophy associates with abdominal muscle pathology.

PubMed

Gardner, Brandon B; Swaggart, Kayleigh A; Kim, Gene; Watson, Sydeaka; McNally, Elizabeth M

The muscular dystrophies target muscle groups differentially. In mouse models of muscular dystrophy, notably the mdx model of Duchenne Muscular Dystrophy, the diaphragm muscle shows marked fibrosis and at an earlier age than other muscle groups, more reflective of the histopathology seen in human muscular dystrophy. Using a mouse model of limb girdle muscular dystrophy, the Sgcg mouse, we compared muscle pathology across different muscle groups and heart. A cohort of nearly 200 Sgcg mice were studied using multiple measures of pathology including echocardiography, Evans blue dye uptake and hydroxyproline content in multiple muscle groups. Spearman rank correlations were determined among echocardiographic and pathological parameters. The abdominal muscles were found to have more fibrosis than other muscle groups, including the diaphragm muscle. The abdominal muscles also had more Evans blue dye uptake than other muscle groups. The amount of diaphragm fibrosis was found to correlate positively with fibrosis in the left ventricle, and abdominal muscle fibrosis correlated with impaired left ventricular function. Fibrosis in the abdominal muscles negatively correlated with fibrosis in the diaphragm and right ventricles. Together these data reflect the recruitment of abdominal muscles as respiratory muscles in muscular dystrophy, a finding consistent with data from human patients.

Muscle twitching

MedlinePlus

... Some are common and normal. Others are signs of a nervous system disorder. Causes Causes may include: Autoimmune disorders , such ... muscle Spinal muscular atrophy Weak muscles (myopathy) Symptoms of a nervous system disorder include: Loss of, or change in, sensation ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juberg, D.R.; Loch-Caruso, R.

Elevated levels of DDT and other organochlorine pesticides have been associated with spontaneous abortion and preterm birth in several species, including humans. Despite the prevalence of organochlorine pesticides in the environment, a mechanistic basis for this association has not been explored. Furthermore, while DDT has been associated with inhibition of calcium ATPases, altered gap junctional communication and electrophysiological changes, all of which could affect the excitation-contraction process characteristic of smooth muscle, direct effects of DDT on uterine smooth muscle have not been reported. This study was initiated to assess the direct effects of o,p{prime}-DDT (an estrogenic isomer present in themore » technical grade preparation) on pregnant rat uterine tissue.« less

Biomimetic actuators using electroactive polymers (EAP) as artificial muscles

NASA Technical Reports Server (NTRS)

Bar-Cohen, Yoseph

2006-01-01

Evolution has resolved many of nature's challenges leading to lasting solutions with maximal performance and effective use of resources. Nature's inventions have always inspired human achievements leading to effective materials, structures, tools, mechanisms, processes, algorithms, methods, systems and many other benefits. The field of mimicking nature is known as Biomimetics and one of its topics includes electroactive polymers that gain the moniker artificial muscles. Integrating EAP with embedded sensors, self-repair and many other capabilities that are used in composite materials can add greatly to the capability of smart biomimetic systems. Such development would enable fascinating possibilities potentially turning science fiction ideas into engineering reality.

Simultaneous prediction of muscle and contact forces in the knee during gait.

PubMed

Lin, Yi-Chung; Walter, Jonathan P; Banks, Scott A; Pandy, Marcus G; Fregly, Benjamin J

2010-03-22

Musculoskeletal models are currently the primary means for estimating in vivo muscle and contact forces in the knee during gait. These models typically couple a dynamic skeletal model with individual muscle models but rarely include articular contact models due to their high computational cost. This study evaluates a novel method for predicting muscle and contact forces simultaneously in the knee during gait. The method utilizes a 12 degree-of-freedom knee model (femur, tibia, and patella) combining muscle, articular contact, and dynamic skeletal models. Eight static optimization problems were formulated using two cost functions (one based on muscle activations and one based on contact forces) and four constraints sets (each composed of different combinations of inverse dynamic loads). The estimated muscle and contact forces were evaluated using in vivo tibial contact force data collected from a patient with a force-measuring knee implant. When the eight optimization problems were solved with added constraints to match the in vivo contact force measurements, root-mean-square errors in predicted contact forces were less than 10 N. Furthermore, muscle and patellar contact forces predicted by the two cost functions became more similar as more inverse dynamic loads were used as constraints. When the contact force constraints were removed, estimated medial contact forces were similar and lateral contact forces lower in magnitude compared to measured contact forces, with estimated muscle forces being sensitive and estimated patellar contact forces relatively insensitive to the choice of cost function and constraint set. These results suggest that optimization problem formulation coupled with knee model complexity can significantly affect predicted muscle and contact forces in the knee during gait. Further research using a complete lower limb model is needed to assess the importance of this finding to the muscle and contact force estimation process. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Regulation of phosphorylase kinase by low concentrations of Ca ions upon muscle contraction: the connection between metabolism and muscle contraction and the connection between muscle physiology and Ca-dependent signal transduction.

PubMed

Ozawa, Eijiro

2011-01-01

It had long been one of the crucial questions in muscle physiology how glycogenolysis is regulated in connection with muscle contraction, when we found the answer to this question in the last half of the 1960s. By that time, the two principal currents of muscle physiology, namely, the metabolic flow starting from glycogen and the mechanisms of muscle contraction, had already been clarified at the molecular level thanks to our senior researchers. Thus, the final question we had to answer was how to connect these two currents. We found that low concentrations of Ca ions (10(-7)-10(-4) M) released from the sarcoplasmic reticulum for the regulation of muscle contraction simultaneously reversibly activate phosphorylase kinase, the enzyme regulating glycogenolysis. Moreover, we found that adenosine 3',5'-monophosphate (cyclic AMP), which is already known to activate muscle phosphorylase kinase, is not effective in the absence of such concentrations of Ca ions. Thus, cyclic AMP is not effective by itself alone and only modifies the activation process in the presence of Ca ions (at that time, cyclic AMP-dependent protein kinase had not yet been identified). After a while, it turned out that our works have not only provided the solution to the above problem on muscle physiology, but have also been considered as the first report of Ca-dependent protein phosphorylation, which is one of the central problems in current cell biology. Phosphorylase kinase is the first protein kinase to phosphorylate a protein resulting in the change in the function of the phosphorylated protein, as shown by Krebs and Fischer. Our works further showed that this protein kinase is regulated in a Ca-dependent manner. Accordingly, our works introduced the concept of low concentrations of Ca ions, which were first identified as the regulatory substance of muscle contraction, to the vast field of Ca biology including signal transduction.

Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

PubMed

Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

2016-01-04

The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

New Advances in Molecular Therapy for Muscle Repair after Diseases and Injuries

DTIC Science & Technology

2008-04-01

frequently disabling injuries sustained by athletes and soldiers. Although injured muscles heal naturally, the regeneration is very slow and often...yields incomplete functional recovery. In injured muscle, regeneration begins shortly after injury, but the healing process is rather inefficient and is...skin disorders), can reduce muscle fibrosis and consequently improve muscle healing , resulting in nearly complete recovery after laceration or strain

[Muscle regeneration in mdx mouse, and a trial of normal myoblast transfer into regenerating dystrophic muscle].

PubMed

Takemitsu, M; Arahata, K; Nonaka, I

1990-10-01

The most ideal therapeutic trial on Duchenne muscular dystrophy (DMD) is a transfer of normal myoblasts into dystrophic muscle which has been attempted on animal models in several institutes. In the process of muscle regeneration, the transferred normal myoblasts are expected to incorporate into the regenerating fibers in host dystrophic mouse. To know the capacity of muscle regeneration in dystrophic muscle, we compared the regenerating process of the normal muscle with that of the dystrophic muscle after myonecrosis induced by 0.25% bupivacaine hydrochloride (BPVC) chronologically. In the present study, C57BL/10ScSn-mdx (mdx) mouse was used as an animal model of DMD and C57BL/10ScSn (B10) mouse as a control. There was no definite difference in the behavior of muscle fiber regeneration between normal and dystrophic muscles. The dystrophic muscle regenerated rapidly at the similar tempo to the normal as to their size and fiber type differentiation. The variation in fiber size diameter of dystrophic muscle, however, was more obvious than that of normal. To promote successful myoblast transfer from B10 mouse into dystrophic mdx mouse at higher ratio, cultured normal myoblasts were transferred into the regenerating dystrophic muscle on the first and the second day after myonecrosis induced by BPVC. Two weeks after the myoblast injection, the muscles were examined with immunohistochemical stain using anti dystrophin antibody. Although dystrophin-positive fibers appeared in dystrophic muscle, the positive fibers were unexpectedly small in number (3.86 +/- 1.50%).(ABSTRACT TRUNCATED AT 250 WORDS)

Distinct muscle apoptotic pathways are activated in muscles with different fiber types in a rat model of critical illness myopathy.

PubMed

Barnes, Benjamin T; Confides, Amy L; Rich, Mark M; Dupont-Versteegden, Esther E

2015-06-01

Critical illness myopathy (CIM) is associated with severe muscle atrophy and fatigue in affected patients. Apoptotic signaling is involved in atrophy and is elevated in muscles from patients with CIM. In this study we investigated underlying mechanisms of apoptosis-related pathways in muscles with different fiber type composition in a rat model of CIM using denervation and glucocorticoid administration (denervation and steroid-induced myopathy, DSIM). Soleus and tibialis anterior (TA) muscles showed severe muscle atrophy (40-60% of control muscle weight) and significant apoptosis in interstitial as well as myofiber nuclei that was similar between the two muscles with DSIM. Caspase-3 and -8 activities, but not caspase-9 and -12, were elevated in TA and not in soleus muscle, while the caspase-independent proteins endonuclease G (EndoG) and apoptosis inducing factor (AIF) were not changed in abundance nor differentially localized in either muscle. Anti-apoptotic proteins HSP70, -27, and apoptosis repressor with a caspase recruitment domain (ARC) were elevated in soleus compared to TA muscle and ARC was significantly decreased with induction of DSIM in soleus. Results indicate that apoptosis is a significant process associated with DSIM in both soleus and TA muscles, and that apoptosis-associated processes are differentially regulated in muscles of different function and fiber type undergoing atrophy due to DSIM. We conclude that interventions combating apoptosis with CIM may need to be directed towards inhibiting caspase-dependent as well as -independent mechanisms to be able to affect muscles of all fiber types.

Mechanical forces and their second messengers in stimulating cell growth in vitro

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.

1992-01-01

Mechanical forces play an important role in modulating the growth of a number of different tissues including skeletal muscle, smooth muscle, cardiac muscle, bone, endothelium, epithelium, and lung. As interest increases in the molecular mechanisms by which mechanical forces are transduced into growth alterations, model systems are being developed to study these processes in tissue culture. This paper reviews the current methods available for mechanically stimulating tissue cultured cells. It then outlines some of the putative 'mechanogenic' second messengers involved in altering cell growth. Not surprisingly, many mechanogenic second messengers are the same as those involved in growth factor-induced cell growth. It is hypothesized that from an evolutionary standpoint, some second messenger systems may have initially evolved for unicellular organisms to respond to physical forces such as gravity and mechanical perturbation in their environment. As multicellular organisms came into existence, they appropriated these mechanogenic second messenger cascades for cellular regulation by growth factors.

Neural Contributions to Muscle Fatigue: From the Brain to the Muscle and Back Again

PubMed Central

Taylor, Janet L.; Amann, Markus; Duchateau, Jacques; Meeusen, Romain; Rice, Charles L.

2016-01-01

During exercise, there is a progressive reduction in the ability to produce muscle forces. Processes within the nervous system, as well as within the muscles contribute to this fatigue. In addition to impaired function of the motor system, sensations associated with fatigue, and impairment of homeostasis can contribute to impairment of performance during exercise. This review discusses some of the neural changes that accompany exercise and the development of fatigue. The role of brain monoaminergic neurotransmitter systems in whole-body endurance performance is discussed, particularly with regard to exercise in hot environments. Next, fatigue-related alterations in the neuromuscular pathway are discussed in terms of changes in motor unit firing, motoneuron excitability and motor cortical excitability. These changes have mostly been investigated during single-limb isometric contractions. Finally, the small-diameter muscle afferents that increase firing with exercise and fatigue are discussed. These afferents have roles in cardiovascular and respiratory responses to exercise, and in impairment of exercise performance through interaction with the motor pathway, as well as providing sensations of muscle discomfort. Thus, changes at all levels of the nervous system including the brain, spinal cord, motor output, sensory input and autonomic function occur during exercise and fatigue. The mix of influences and the importance of their contribution varies with the type of exercise being performed. PMID:27003703

Precision of MRI-based body composition measurements of postmenopausal women

PubMed Central

Romu, Thobias; Thorell, Sofia; Lindblom, Hanna; Berin, Emilia; Holm, Anna-Clara Spetz; Åstrand, Lotta Lindh; Karlsson, Anette; Borga, Magnus; Hammar, Mats; Leinhard, Olof Dahlqvist

2018-01-01

Objectives To determine precision of magnetic resonance imaging (MRI) based fat and muscle quantification in a group of postmenopausal women. Furthermore, to extend the method to individual muscles relevant to upper-body exercise. Materials and methods This was a sub-study to a randomized control trial investigating effects of resistance training to decrease hot flushes in postmenopausal women. Thirty-six women were included, mean age 56 ± 6 years. Each subject was scanned twice with a 3.0T MR-scanner using a whole-body Dixon protocol. Water and fat images were calculated using a 6-peak lipid model including R2*-correction. Body composition analyses were performed to measure visceral and subcutaneous fat volumes, lean volumes and muscle fat infiltration (MFI) of the muscle groups’ thigh muscles, lower leg muscles, and abdominal muscles, as well as the three individual muscles pectoralis, latissimus, and rhomboideus. Analysis was performed using a multi-atlas, calibrated water-fat separated quantification method. Liver-fat was measured as average proton density fat-fraction (PDFF) of three regions-of-interest. Precision was determined with Bland-Altman analysis, repeatability, and coefficient of variation. Results All of the 36 included women were successfully scanned and analysed. The coefficient of variation was 1.1% to 1.5% for abdominal fat compartments (visceral and subcutaneous), 0.8% to 1.9% for volumes of muscle groups (thigh, lower leg, and abdomen), and 2.3% to 7.0% for individual muscle volumes (pectoralis, latissimus, and rhomboideus). Limits of agreement for MFI was within ± 2.06% for muscle groups and within ± 5.13% for individual muscles. The limits of agreement for liver PDFF was within ± 1.9%. Conclusion Whole-body Dixon MRI could characterize a range of different fat and muscle compartments with high precision, including individual muscles, in the study-group of postmenopausal women. The inclusion of individual muscles, calculated from the same scan, enables analysis for specific intervention programs and studies. PMID:29415060

Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis.

PubMed

Goh, Qingnian; Dearth, Christopher L; Corbett, Jacob T; Pierre, Philippe; Chadee, Deborah N; Pizza, Francis X

2015-02-15

We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast-myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube-myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube-myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. Copyright © 2014 Elsevier Inc. All rights reserved.

Intercellular Adhesion Molecule-1 Expression by Skeletal Muscle Cells Augments Myogenesis

PubMed Central

Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T.; Pierre, Philippe; Chadee, Deborah N.; Pizza, Francis X.

2014-01-01

We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast-myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube-myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube-myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. PMID:25281303

Pharmacologic effects of grain weevil extract on isolated guinea pig tracheal smooth muscle.

PubMed

Schachter, E Neil; Zuskin, Eugenija; Arumugam, Uma; Goswami, Satindra; Castranova, Vincent; Whitmer, Mike; Chiarelli, Angelo

2008-01-01

The grain weevil, an insect (pest) that infects grain, is a frequent contaminant of processed wheat, and its presence may contribute to respiratory abnormalities in grain workers. We studied the in vitro effects of an extract of grain weevil (GWE) on airway smooth muscle. Pharmacologic studies included in vitro challenge of guinea pig trachea with GWE, in parallel organ baths, pretreated with mediator-modifying agents or a control solution. Dose-related contractions of nonsensitized guinea pig trachea (GPT) were demonstrated using this extract. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with drugs known to modulate smooth muscle contraction: atropine, indomethacin, pyrilamine, acivicin, NDGA, BPB, TMB8, captopril, and capsaicin. Atropine, pyrilamine, BPB, and capsaicin significantly reduced the contractile effects of the extract at most of the challenge doses (p < 0.01 or p < 0.05). Inhibition of GWE-induced contraction by blocking of other mediators was less complete. We suggest that GWE causes dose-related airway smooth muscle constriction of the GPT by nonimmunologic mechanisms involving a variety of airway mediators and possibly cholinergic receptors.

Notch Signaling in Vascular Smooth Muscle Cells

PubMed Central

Baeten, J.T.; Lilly, B.

2018-01-01

The Notch signaling pathway is a highly conserved pathway involved in cell fate determination in embryonic development and also functions in the regulation of physiological processes in several systems. It plays an especially important role in vascular development and physiology by influencing angiogenesis, vessel patterning, arterial/venous specification, and vascular smooth muscle biology. Aberrant or dysregulated Notch signaling is the cause of or a contributing factor to many vascular disorders, including inherited vascular diseases, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, associated with degeneration of the smooth muscle layer in cerebral arteries. Like most signaling pathways, the Notch signaling axis is influenced by complex interactions with mediators of other signaling pathways. This complexity is also compounded by different members of the Notch family having both overlapping and unique functions. Thus, it is vital to fully understand the roles and interactions of each Notch family member in order to effectively and specifically target their exact contributions to vascular disease. In this chapter, we will review the Notch signaling pathway in vascular smooth muscle cells as it relates to vascular development and human disease. PMID:28212801

A 12-week randomized double-blind parallel pilot trial of Sinetrol XPur on body weight, abdominal fat, waist circumference, and muscle metabolism in overweight men.

PubMed

Cases, Julien; Romain, Cindy; Dallas, Constantin; Gerbi, Alain; Rouanet, Jean Max

2015-01-01

Overweight and obesity are associated to increased risk of developing non-communicable diseases that might dramatically affect life expectancy according World Health Organization. Overweight, obesity, and decline in physical activity are correlated to a significant propensity to lose skeletal muscle mass as a result of prolonged inflammation and oxidative stress whereas cohort surveys and clinical investigations have demonstrated health benefits of Citrus-based polyphenols to reverse such regression. Overweight men were included in a double-blind, randomized, parallel pilot trial where they received daily for a 12-week period 900 mg of a Citrus-based polyphenol extract, Sinetrol® XPur. Body composition, anthropometric, and blood parameters were assessed before and at the end of the intervention period. After 12 weeks, while the silhouette slimmed down, metabolic parameters were significantly improved and skeletal muscle catabolism held back. These data suggest that over a 12-week period, the efficacy of the supplement improve both overweight process and correlated skeletal muscle mass metabolism.

Targeting mitochondrial function and proteostasis to mitigate dynapenia.

PubMed

Musci, Robert V; Hamilton, Karyn L; Miller, Benjamin F

2018-01-01

Traditionally, interventions to treat skeletal muscle aging have largely targeted sarcopenia-the age-related loss of skeletal muscle mass. Dynapenia refers to the age-related loss in skeletal muscle function due to factors outside of muscle mass, which helps to inform treatment strategies for aging skeletal muscle. There is evidence that mechanisms to maintain protein homeostasis and proteostasis, deteriorate with age. One key mechanism to maintain proteostasis is protein turnover, which is an energetically costly process. When there is a mismatch between cellular energy demands and energy provision, inelastic processes related to metabolism are maintained, but there is competition for the remaining energy between the elastic processes of somatic maintenance and growth. With aging, mitochondrial dysfunction reduces ATP generation capacity, constraining the instantaneous supply of energy, thus compromising growth and somatic maintenance processes. Further, with age the need for somatic maintenance increases because of the accumulation of protein damage. In this review, we highlight the significant role mitochondria have in maintaining skeletal muscle proteostasis through increased energy provision, protein turnover, and substrate flux. In addition, we provide evidence that improving mitochondrial function could promote a cellular environment that is conducive to somatic maintenance, and consequently for mitigating dynapenia. Finally, we highlight interventions, such as aerobic exercise, that could be used to improve mitochondrial function and improve outcomes related to dynapenia.

Meat and fermented meat products as a source of bioactive peptides.

PubMed

Stadnik, Joanna; Kęska, Paulina

2015-01-01

Bioactive peptides are short amino acid sequences, that upon release from the parent protein may play different physiological roles, including antioxidant, antihypertensive, antimicrobial, and other bioactivities. They have been identified from a range of foods, including those of animal origin, e.g., milk and muscle sources (with pork, beef, or chicken and various species of fish and marine organism). Bioactive peptides are encrypted within the sequence of the parent protein molecule and latent until released and activated by enzymatic proteolysis, e.g. during gastrointestinal digestion or food processing. Bioactive peptides derived from food sources have the potential for incorporation into functional foods and nutraceuticals. The aim of this paper is to present an overview of the muscle-derived bioactive peptides, especially those of fermented meats and the potential benefits of these bioactive compounds to human health.

Muscle Research and Gene Ontology: New standards for improved data integration

PubMed Central

Feltrin, Erika; Campanaro, Stefano; Diehl, Alexander D; Ehler, Elisabeth; Faulkner, Georgine; Fordham, Jennifer; Gardin, Chiara; Harris, Midori; Hill, David; Knoell, Ralph; Laveder, Paolo; Mittempergher, Lorenza; Nori, Alessandra; Reggiani, Carlo; Sorrentino, Vincenzo; Volpe, Pompeo; Zara, Ivano; Valle, Giorgio; Deegan née Clark, Jennifer

2009-01-01

Background The Gene Ontology Project provides structured controlled vocabularies for molecular biology that can be used for the functional annotation of genes and gene products. In a collaboration between the Gene Ontology (GO) Consortium and the muscle biology community, we have made large-scale additions to the GO biological process and cellular component ontologies. The main focus of this ontology development work concerns skeletal muscle, with specific consideration given to the processes of muscle contraction, plasticity, development, and regeneration, and to the sarcomere and membrane-delimited compartments. Our aims were to update the existing structure to reflect current knowledge, and to resolve, in an accommodating manner, the ambiguity in the language used by the community. Results The updated muscle terminologies have been incorporated into the GO. There are now 159 new terms covering critical research areas, and 57 existing terms have been improved and reorganized to follow their usage in muscle literature. Conclusion The revised GO structure should improve the interpretation of data from high-throughput (e.g. microarray and proteomic) experiments in the area of muscle science and muscle disease. We actively encourage community feedback on, and gene product annotation with these new terms. Please visit the Muscle Community Annotation Wiki . PMID:19178689

Impedance Alterations in Healthy and Diseased Mice During Electrically Induced Muscle Contraction.

PubMed

Sanchez, Benjamin; Li, Jia; Geisbush, Tom; Bardia, Ramon Bragos; Rutkove, Seward B

2016-08-01

Alterations in the health of muscles can be evaluated through the use of electrical impedance myography (EIM). To date, however, nearly all work in this field has relied upon the measurement of muscle at rest. To provide an insight into the contractile mechanisms of healthy and disease muscle, we evaluated the alterations in the spectroscopic impedance behavior of muscle during the active process of muscle contraction. The gastrocnemii from a total of 13 mice were studied (five wild type, four muscular dystrophy animals, and four amyotrophic lateral sclerosis animals). Muscle contraction was induced via monophasic current pulse stimulation of the sciatic nerve. Simultaneously, multisine EIM (1 kHz to 1 MHz) and force measurements of the muscle were performed. Stimulation was applied at three different rates to produce mild, moderate, and strong contractions. We identified changes in both single and multifrequency data, as assessed by the Cole impedance model parameters. The processes of contraction and relaxation were clearly identified in the impedance spectra and quantified via derivative plots. Reductions in the center frequency fc were observed during the contraction consistent with the increasing muscle fiber diameter. Different EIM stimulation rate-dependencies were also detected across the three groups of animals.

Muscle Research and Gene Ontology: New standards for improved data integration.

PubMed

Feltrin, Erika; Campanaro, Stefano; Diehl, Alexander D; Ehler, Elisabeth; Faulkner, Georgine; Fordham, Jennifer; Gardin, Chiara; Harris, Midori; Hill, David; Knoell, Ralph; Laveder, Paolo; Mittempergher, Lorenza; Nori, Alessandra; Reggiani, Carlo; Sorrentino, Vincenzo; Volpe, Pompeo; Zara, Ivano; Valle, Giorgio; Deegan, Jennifer

2009-01-29

The Gene Ontology Project provides structured controlled vocabularies for molecular biology that can be used for the functional annotation of genes and gene products. In a collaboration between the Gene Ontology (GO) Consortium and the muscle biology community, we have made large-scale additions to the GO biological process and cellular component ontologies. The main focus of this ontology development work concerns skeletal muscle, with specific consideration given to the processes of muscle contraction, plasticity, development, and regeneration, and to the sarcomere and membrane-delimited compartments. Our aims were to update the existing structure to reflect current knowledge, and to resolve, in an accommodating manner, the ambiguity in the language used by the community. The updated muscle terminologies have been incorporated into the GO. There are now 159 new terms covering critical research areas, and 57 existing terms have been improved and reorganized to follow their usage in muscle literature. The revised GO structure should improve the interpretation of data from high-throughput (e.g. microarray and proteomic) experiments in the area of muscle science and muscle disease. We actively encourage community feedback on, and gene product annotation with these new terms. Please visit the Muscle Community Annotation Wiki http://wiki.geneontology.org/index.php/Muscle_Biology.

Autophagy and Mis-targeting of Therapeutic Enzyme in Skeletal Muscle in Pompe Disease

PubMed Central

Fukuda, Tokiko; Ahearn, Meghan; Roberts, Ashley; Mattaliano, Robert J.; Zaal, Kristien; Ralston, Evelyn; Plotz, Paul H.; Raben, Nina

2009-01-01

Enzyme replacement therapy (ERT) became a reality for patients with Pompe disease, a fatal cardiomyopathy and skeletal muscle myopathy caused by a deficiency of glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA). The therapy, which relies on receptor-mediated endocytosis of recombinant human GAA (rhGAA), appears to be effective in cardiac muscle, but less so in skeletal muscle. We have previously shown a profound disturbance of the lysosomal degradative pathway (autophagy) in therapy-resistant muscle of GAA knockout mice (KO). Our findings here demonstrate a progressive age-dependent autophagic build-up in addition to enlargement of glycogen-filled lysosomes in multiple muscle groups in the KO. Trafficking and processing of the therapeutic enzyme along the endocytic pathway appear to be affected by the autophagy. Confocal microscopy of live single muscle fibers exposed to fluorescently labeled rhGAA indicates that a significant portion of the endocytosed enzyme in the KO was trapped as a partially processed form in the autophagic areas instead of reaching its target – the lysosomes. A fluid-phase endocytic marker was similarly mis-targeted and accumulated in vesicular structures within the autophagic areas. These findings may explain why ERT often falls short of reversing the disease process, and point to new avenues for the development of pharmacological intervention. PMID:17008131

Dynamic Analysis of the Abnormal Isometric Strength Movement Pattern between Shoulder and Elbow Joint in Patients with Hemiplegia.

PubMed

Liu, Yali; Hong, Yuezhen; Ji, Linhong

2018-01-01

Patients with hemiplegia usually have weak muscle selectivity and usually perform strength at a secondary joint (secondary strength) during performing a strength at one joint (primary strength). The abnormal strength pattern between shoulder and elbow joint has been analyzed by the maximum value while the performing process with strength changing from 0 to maximum then to 0 was a dynamic process. The objective of this study was to develop a method to dynamically analyze the strength changing process. Ten patients were asked to perform four group asks (maximum and 50% maximum voluntary strength in shoulder abduction, shoulder adduction, elbow flexion, and elbow extension). Strength and activities from seven muscles were measured. The changes of secondary strength had significant correlation with those of primary strength in all tasks ( R > 0.76, p < 0.01). The antagonistic muscles were moderately influenced by the primary strength ( R > 0.4, p < 0.01). Deltoid muscles, biceps brachii, triceps brachii, and brachioradialis had significant influences on the abnormal strength pattern (all p < 0.01). The dynamic method was proved to be efficient to analyze the different influences of muscles on the abnormal strength pattern. The muscles, deltoid muscles, biceps brachii, triceps brachii, and brachioradialis, much influenced the stereotyped movement pattern between shoulder and elbow joint.

Dynamic Analysis of the Abnormal Isometric Strength Movement Pattern between Shoulder and Elbow Joint in Patients with Hemiplegia

PubMed Central

2018-01-01

Patients with hemiplegia usually have weak muscle selectivity and usually perform strength at a secondary joint (secondary strength) during performing a strength at one joint (primary strength). The abnormal strength pattern between shoulder and elbow joint has been analyzed by the maximum value while the performing process with strength changing from 0 to maximum then to 0 was a dynamic process. The objective of this study was to develop a method to dynamically analyze the strength changing process. Ten patients were asked to perform four group asks (maximum and 50% maximum voluntary strength in shoulder abduction, shoulder adduction, elbow flexion, and elbow extension). Strength and activities from seven muscles were measured. The changes of secondary strength had significant correlation with those of primary strength in all tasks (R > 0.76, p < 0.01). The antagonistic muscles were moderately influenced by the primary strength (R > 0.4, p < 0.01). Deltoid muscles, biceps brachii, triceps brachii, and brachioradialis had significant influences on the abnormal strength pattern (all p < 0.01). The dynamic method was proved to be efficient to analyze the different influences of muscles on the abnormal strength pattern. The muscles, deltoid muscles, biceps brachii, triceps brachii, and brachioradialis, much influenced the stereotyped movement pattern between shoulder and elbow joint. PMID:29610654

Muscle contraction controls skeletal morphogenesis through regulation of chondrocyte convergent extension.

PubMed

Shwartz, Yulia; Farkas, Zsuzsanna; Stern, Tomer; Aszódi, Attila; Zelzer, Elazar

2012-10-01

Convergent extension driven by mediolateral intercalation of chondrocytes is a key process that contributes to skeletal growth and morphogenesis. While progress has been made in deciphering the molecular mechanism that underlies this process, the involvement of mechanical load exerted by muscle contraction in its regulation has not been studied. Using the zebrafish as a model system, we found abnormal pharyngeal cartilage morphology in both chemically and genetically paralyzed embryos, demonstrating the importance of muscle contraction for zebrafish skeletal development. The shortening of skeletal elements was accompanied by prominent changes in cell morphology and organization. While in control the cells were elongated, chondrocytes in paralyzed zebrafish were smaller and exhibited a more rounded shape, confirmed by a reduction in their length-to-width ratio. The typical columnar organization of cells was affected too, as chondrocytes in various skeletal elements exhibited abnormal stacking patterns, indicating aberrant intercalation. Finally, we demonstrate impaired chondrocyte intercalation in growth plates of muscle-less Sp(d) mouse embryos, implying the evolutionary conservation of muscle force regulation of this essential morphogenetic process.Our findings provide a new perspective on the regulatory interaction between muscle contraction and skeletal morphogenesis by uncovering the role of muscle-induced mechanical loads in regulating chondrocyte intercalation in two different vertebrate models. Copyright © 2012 Elsevier Inc. All rights reserved.

Myomaker is a membrane activator of myoblast fusion and muscle formation.

PubMed

Millay, Douglas P; O'Rourke, Jason R; Sutherland, Lillian B; Bezprozvannaya, Svetlana; Shelton, John M; Bassel-Duby, Rhonda; Olson, Eric N

2013-07-18

Fusion of myoblasts is essential for the formation of multi-nucleated muscle fibres. However, the identity of muscle-specific proteins that directly govern this fusion process in mammals has remained elusive. Here we identify a muscle-specific membrane protein, named myomaker, that controls myoblast fusion. Myomaker is expressed on the cell surface of myoblasts during fusion and is downregulated thereafter. Overexpression of myomaker in myoblasts markedly enhances fusion, and genetic disruption of myomaker in mice causes perinatal death due to an absence of multi-nucleated muscle fibres. Remarkably, forced expression of myomaker in fibroblasts promotes fusion with myoblasts, demonstrating the direct participation of this protein in the fusion process. Pharmacological perturbation of the actin cytoskeleton abolishes the activity of myomaker, consistent with previous studies implicating actin dynamics in myoblast fusion. These findings reveal a long-sought myogenic fusion protein that controls mammalian myoblast fusion and provide new insights into the molecular underpinnings of muscle formation.

Sex steroids do not affect muscle weight, oxidative metabolism or cytosolic androgen reception binding of functionally overloaded rat Plantaris muscles

NASA Technical Reports Server (NTRS)

Max, S. R.; Rance, N.

1983-01-01

The effects of sex steroids on muscle weight and oxidative capacity of rat planaris muscles subjected to functional overload by removal of synergistic muscles were investigated. Ten weeks after bilateral synergist removal, plantaris muscles were significantly hypertrophic compared with unoperated controls. After this period, the ability of the muscles to oxide three substrates of oxidative metabolism was assessed. Experimental procedures are discussed and results are presented herein. Results suggest a lack of beneficial effect of sex hormone status on the process of hypertrophy and on biochemical changes in overloaded muscle. Such findings are not consistent with the idea of synergistic effects of sex steroids and muscle usage.

Common cellular events occur during wound healing and organ regeneration in the sea cucumber Holothuria glaberrima.

PubMed

San Miguel-Ruiz, José E; García-Arrarás, José E

2007-10-18

All animals possess some type of tissue repair mechanism. In some species, the capacity to repair tissues is limited to the healing of wounds. Other species, such as echinoderms, posses a striking repair capability that can include the replacement of entire organs. It has been reported that some mechanisms, namely extracellular matrix remodeling, appear to occur in most repair processes. However, it remains unclear to what extent the process of organ regeneration, particularly in animals where loss and regeneration of complex structures is a programmed natural event, is similar to wound healing. We have now used the sea cucumber Holothuria glaberrima to address this question. Animals were lesioned by making a 3-5 mm transverse incision between one of the longitudinal muscle pairs along the bodywall. Lesioned tissues included muscle, nerve, water canal and dermis. Animals were allowed to heal for up to four weeks (2, 6, 12, 20, and 28 days post-injury) before sacrificed. Tissues were sectioned in a cryostat and changes in cellular and tissue elements during repair were evaluated using classical dyes, immmuohistochemistry and phalloidin labeling. In addition, the temporal and spatial distribution of cell proliferation in the animals was assayed using BrdU incorporation. We found that cellular events associated with wound healing in H. glaberrima correspond to those previously shown to occur during intestinal regeneration. These include: (1) an increase in the number of spherule-containing cells, (2) remodeling of the extracellular matrix, (3) formation of spindle-like structures that signal dedifferentiation of muscle cells in the area flanking the lesion site and (4) intense cellular division occurring mainly in the coelomic epithelium after the first week of regeneration. Our data indicate that H. glaberrima employs analogous cellular mechanisms during wound healing and organ regeneration. Thus, it is possible that regenerative limitations in some organisms are due either to the absence of particular mechanisms associated with repair or the inability of activating the repair process in some tissues or stages.

Engineered skeletal muscle tissue for soft robotics: fabrication strategies, current applications, and future challenges.

PubMed

Duffy, Rebecca M; Feinberg, Adam W

2014-01-01

Skeletal muscle is a scalable actuator system used throughout nature from the millimeter to meter length scales and over a wide range of frequencies and force regimes. This adaptability has spurred interest in using engineered skeletal muscle to power soft robotics devices and in biotechnology and medical applications. However, the challenges to doing this are similar to those facing the tissue engineering and regenerative medicine fields; specifically, how do we translate our understanding of myogenesis in vivo to the engineering of muscle constructs in vitro to achieve functional integration with devices. To do this researchers are developing a number of ways to engineer the cellular microenvironment to guide skeletal muscle tissue formation. This includes understanding the role of substrate stiffness and the mechanical environment, engineering the spatial organization of biochemical and physical cues to guide muscle alignment, and developing bioreactors for mechanical and electrical conditioning. Examples of engineered skeletal muscle that can potentially be used in soft robotics include 2D cantilever-based skeletal muscle actuators and 3D skeletal muscle tissues engineered using scaffolds or directed self-organization. Integration into devices has led to basic muscle-powered devices such as grippers and pumps as well as more sophisticated muscle-powered soft robots that walk and swim. Looking forward, current, and future challenges include identifying the best source of muscle precursor cells to expand and differentiate into myotubes, replacing cardiomyocytes with skeletal muscle tissue as the bio-actuator of choice for soft robots, and vascularization and innervation to enable control and nourishment of larger muscle tissue constructs. © 2013 Wiley Periodicals, Inc.

Assessment of muscle fatigue using electromygraphm sensing

NASA Astrophysics Data System (ADS)

Helmi, Muhammad Hazimin Bin; Ping, Chew Sue; Ishak, Nur Elliza Binti; Saad, Mohd Alimi Bin Mohd; Mokhtar, Anis Shahida Niza Binti

2017-08-01

Muscle fatigue is condition of muscle decline in ability after undergoing any physical activity. Observation of the muscle condition of an athlete during training is crucial to prevent or minimize injury and able to achieve optimum performance in actual competition. The aim of this project is to develop a muscle monitoring system to detect muscle fatigue in swimming athlete. This device is capable to measure muscle stress level of the swimmer and at the same time provide indication of muscle fatigue level to trainer. Electromyography signal was recorded from the muscle movement while practicing the front crawl stroke repetitively. The time domain data was processed to frequency spectra in order to study the effect of muscle fatigue. The results show that the recorded EMG signal is able to sense muscle fatigue.

The Biochemistry of the Muscle Contraction Process: An Undergraduate Laboratory Experiment Using Viscosity to Follow the Progress of a Reaction.

ERIC Educational Resources Information Center

Belliveau, James F.; And Others

1981-01-01

Describes an undergraduate laboratory experiment using viscosity to follow the progress of the contractile process in muscles. This simple, short experiment illustrates the action of ATP as the source of energy in the contractile process and the catalytic effect of calcium ions as a control in the energy producing process. (CS)

Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

ERIC Educational Resources Information Center

Ianuzzo, C. D.; Chen, V.

1977-01-01

Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

Metabolic Dysregulation in Amyotrophic Lateral Sclerosis: Challenges and Opportunities

PubMed Central

Joardar, Archi; Manzo, Ernesto

2017-01-01

Purpose of Review Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease for which there is no cure and treatments are at best palliative. Several genes have been linked to ALS, which highlight defects in multiple cellular processes including RNA processing, proteostasis and metabolism. Clinical observations have identified glucose intolerance and dyslipidemia as key features of ALS however the causes of these metabolic alterations remain elusive. Recent Findings Recent studies reveal that motor neurons and muscle cells may undergo cell type specific metabolic changes that lead to utilization of alternate fuels. For example, ALS patients’ muscles exhibit reduced glycolysis and increased reliance on fatty acids. In contrast, ALS motor neurons contain damaged mitochondria and exhibit impaired lipid beta oxidation, potentially leading to increased glycolysis as a compensatory mechanism. Summary These findings highlight the complexities of metabolic alterations in ALS and provide new opportunities for designing therapeutic strategies based on restoring cellular energetics. PMID:29057168

Metabolic Dysregulation in Amyotrophic Lateral Sclerosis: Challenges and Opportunities.

PubMed

Joardar, Archi; Manzo, Ernesto; Zarnescu, Daniela C

2017-06-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease for which there is no cure and treatments are at best palliative. Several genes have been linked to ALS, which highlight defects in multiple cellular processes including RNA processing, proteostasis and metabolism. Clinical observations have identified glucose intolerance and dyslipidemia as key features of ALS however the causes of these metabolic alterations remain elusive. Recent studies reveal that motor neurons and muscle cells may undergo cell type specific metabolic changes that lead to utilization of alternate fuels. For example, ALS patients' muscles exhibit reduced glycolysis and increased reliance on fatty acids. In contrast, ALS motor neurons contain damaged mitochondria and exhibit impaired lipid beta oxidation, potentially leading to increased glycolysis as a compensatory mechanism. These findings highlight the complexities of metabolic alterations in ALS and provide new opportunities for designing therapeutic strategies based on restoring cellular energetics.

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD.

PubMed

Roshanravan, Baback; Gamboa, Jorge; Wilund, Kenneth

2017-06-01

Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high risk for mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment that includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle, and physical performance in chronic kidney disease. Kidney health providers need to identify patient and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can use in clinical practice to prevent functional decline and disability. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Genome-Wide Mapping of Collier In Vivo Binding Sites Highlights Its Hierarchical Position in Different Transcription Regulatory Networks

PubMed Central

Dubois, Laurence; Bataillé, Laetitia; Painset, Anaïs; Le Gras, Stéphanie; Jost, Bernard; Crozatier, Michèle; Vincent, Alain

2015-01-01

Collier, the single Drosophila COE (Collier/EBF/Olf-1) transcription factor, is required in several developmental processes, including head patterning and specification of muscle and neuron identity during embryogenesis. To identify direct Collier (Col) targets in different cell types, we used ChIP-seq to map Col binding sites throughout the genome, at mid-embryogenesis. In vivo Col binding peaks were associated to 415 potential direct target genes. Gene Ontology analysis revealed a strong enrichment in proteins with DNA binding and/or transcription-regulatory properties. Characterization of a selection of candidates, using transgenic CRM-reporter assays, identified direct Col targets in dorso-lateral somatic muscles and specific neuron types in the central nervous system. These data brought new evidence that Col direct control of the expression of the transcription regulators apterous and eyes-absent (eya) is critical to specifying neuronal identities. They also showed that cross-regulation between col and eya in muscle progenitor cells is required for specification of muscle identity, revealing a new parallel between the myogenic regulatory networks operating in Drosophila and vertebrates. Col regulation of eya, both in specific muscle and neuronal lineages, may illustrate one mechanism behind the evolutionary diversification of Col biological roles. PMID:26204530

Characterization of microRNAs from goat (Capra hircus) by Solexa deep-sequencing technology.

PubMed

Ling, Y H; Ding, J P; Zhang, X D; Wang, L J; Zhang, Y H; Li, Y S; Zhang, Z J; Zhang, X R

2013-06-13

MicroRNAs (miRNAs) are an important class of small noncoding RNAs that are highly conserved in plants and animals. Many miRNAs are known to mediate a myriad of cell processes, including proliferation and differentiation, via the regulation of some transcription and signaling factors, which are closely related to muscle development and disease. In this study, small RNA cDNA libraries of Boer goats were constructed. In addition, we obtained the goat muscle miRNAs by using Solexa deep-sequencing technology and analyzed these miRNA characteristics by combining it with the bioinformatics technology. Based on Solexa sequencing and bioinformatics analysis, 562 species-conserved and 5 goat genome-specific miRNAs were identified, 322 of which exceeded 100 in the expression levels. The results of real-time quantitative polymerase chain reaction from 8 randomly selected miRNAs showed that the 8 miRNAs were expressed in goat muscle, and the expression patterns were consistent with the Solexa sequencing results. The identification and characterization of miRNAs in goat muscle provide important information on the role of miRNA regulation in muscle growth and development. These data will help to facilitate studies on the regulatory roles played by miRNAs during goat growth and development.

Time-dependent changes in protein expression in rainbow trout muscle following hypoxia.

PubMed

Wulff, Tune; Jokumsen, Alfred; Højrup, Peter; Jessen, Flemming

2012-04-18

Adaptation to hypoxia is a complex process, and individual proteins will be up- or down-regulated in order to address the main challenges at any given time. To investigate the dynamics of the adaptation, rainbow trout (Oncorhynchus mykiss) was exposed to 30% of normal oxygen tension for 1, 2, 5 and 24 h respectively, after which muscle samples were taken. The successful investigation of numerous proteins in a single study was achieved by selectively separating the sarcoplasmic proteins using 2-DE. In total 46 protein spots were identified as changing in abundance in response to hypoxia using one-way ANOVA and multivariate data analysis. Proteins of interest were subsequently identified by MS/MS following tryptic digestion. The observed regulation following hypoxia in skeletal muscle was determined to be time specific, as only a limited number of proteins were regulated in response to more than one time point. The cellular response to hypoxia included regulation of proteins involved in maintaining iron homeostasis, energy levels and muscle structure. In conclusion, this proteome-based study presents a comprehensive investigation of the expression profiles of numerous proteins at four different time points. This increases our understanding of timed changes in protein expression in rainbow trout muscle following hypoxia. Copyright © 2012 Elsevier B.V. All rights reserved.

The bHLH transcription factor Hand is regulated by Alk in the Drosophila embryonic gut

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varshney, Gaurav K.; Palmer, Ruth H.

2006-12-29

During embryonic development the midgut visceral muscle is formed by fusion of cells within the visceral mesoderm, a process initiated by the specification of a specialised cell type, the founder cell, within this tissue. Activation of the receptor tyrosine kinase Anaplastic lymphoma kinase (Alk) in the developing visceral muscle of Drosophila melanogaster initiates a signal transduction pathway required for muscle fusion. In this paper, we have investigated downstream components which are regulated by this novel signalling pathway. Here we show that Alk-mediated signal transduction drives the expression of the bHLH transcription factor Hand in vivo. Loss of Alk function resultsmore » in a complete lack of Hand expression in this tissue, whereas Alk gain of function results in an expansion of Hand expression. Finally, we have investigated the process of muscle fusion in the gut of Hand mutant animals and can find no obvious defects in this process, suggesting that Hand is not critical for visceral muscle fusion per se.« less

Towards human exploration of space: the THESEUS review series on muscle and bone research priorities.

PubMed

Lang, Thomas; Van Loon, Jack J W A; Bloomfield, Susan; Vico, Laurence; Chopard, Angele; Rittweger, Joern; Kyparos, Antonios; Blottner, Dieter; Vuori, Ilkka; Gerzer, Rupert; Cavanagh, Peter R

2017-01-01

Without effective countermeasures, the musculoskeletal system is altered by the microgravity environment of long-duration spaceflight, resulting in atrophy of bone and muscle tissue, as well as in deficits in the function of cartilage, tendons, and vertebral disks. While inflight countermeasures implemented on the International Space Station have evidenced reduction of bone and muscle loss on low-Earth orbit missions of several months in length, important knowledge gaps must be addressed in order to develop effective strategies for managing human musculoskeletal health on exploration class missions well beyond Earth orbit. Analog environments, such as bed rest and/or isolation environments, may be employed in conjunction with large sample sizes to understand sex differences in countermeasure effectiveness, as well as interaction of exercise with pharmacologic, nutritional, immune system, sleep and psychological countermeasures. Studies of musculoskeletal biomechanics, involving both human subject and computer simulation studies, are essential to developing strategies to avoid bone fractures or other injuries to connective tissue during exercise and extravehicular activities. Animal models may be employed to understand effects of the space environment that cannot be modeled using human analog studies. These include studies of radiation effects on bone and muscle, unraveling the effects of genetics on bone and muscle loss, and characterizing the process of fracture healing in the mechanically unloaded and immuno-compromised spaceflight environment. In addition to setting the stage for evidence-based management of musculoskeletal health in long-duration space missions, the body of knowledge acquired in the process of addressing this array of scientific problems will lend insight into the understanding of terrestrial health conditions such as age-related osteoporosis and sarcopenia.

[Metabolic processes in rat skeletal muscle after a flight on the Kosmos-936 biosatellite].

PubMed

Nosova, E A; Veresotskaia, N A; Kolchina, E V; Kurkina, L M; Belitskaia, R A

1981-01-01

The study of skeletal muscles of rats flown on Cosmos-936 demonstrated different metabolic reactions in muscle fibers of different function and type to weightlessness and Earth gravity. The data obtained gave evidence that artificial gravity may considerably prevent metabolic changes in muscles developing in response to specific effects of weightlessness.

Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in insect muscle.

PubMed

Ferdinandus; Arai, Satoshi; Ishiwata, Shin'ichi; Suzuki, Madoka; Sato, Hirotaka

2015-01-01

This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action) and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing). A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects.

Oral Dosing of Chemical Indicators for In Vivo Monitoring of Ca2+ Dynamics in Insect Muscle

PubMed Central

Ferdinandus; Arai, Satoshi; Ishiwata, Shin’ichi; Suzuki, Madoka; Sato, Hirotaka

2015-01-01

This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action) and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing). A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects. PMID:25590329

A systematic review of surface electromyography analyses of the bench press movement task.

PubMed

Stastny, Petr; Gołaś, Artur; Blazek, Dusan; Maszczyk, Adam; Wilk, Michał; Pietraszewski, Przemysław; Petr, Miroslav; Uhlir, Petr; Zając, Adam

2017-01-01

The bench press exercise (BP) plays an important role in recreational and professional training, in which muscle activity is an important multifactorial phenomenon. The objective of this paper is to systematically review electromyography (EMG) studies performed on the barbell BP exercise to answer the following research questions: Which muscles show the greatest activity during the flat BP? Which changes in muscle activity are related to specific conditions under which the BP movement is performed? PubMed, Scopus, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library were searched through June 10, 2016. A combination of the following search terms was used: bench press, chest press, board press, test, measure, assessment, dynamometer, kinematics and biomechanics. Only original, full-text articles were considered. The search process resulted in 14 relevant studies that were included in the discussion. The triceps brachii (TB) and pectoralis major (PM) muscles were found to have similar activity during the BP, which was significantly higher than the activity of the anterior deltoid. During the BP movement, muscle activity changes with exercise intensity, velocity of movement, fatigue, mental focus, movement phase and stability conditions, such as bar vibration or unstable surfaces. Under these circumstances, TB is the most common object of activity change. PM and TB EMG activity is more dominant and shows greater EMG amplitude than anterior deltoid during the BP. There are six factors that can influence muscle activity during the BP; however, the most important factor is exercise intensity, which interacts with all other factors. The research on muscle activity in the BP has several unresolved areas, such as clearly and strongly defined guidelines to perform EMG measurements (e.g., how to elaborate with surface EMG limits) or guidelines for the use of exact muscle models.

A computerized MRI biomarker quantification scheme for a canine model of Duchenne muscular dystrophy

PubMed Central

Wang, Jiahui; Fan, Zheng; Vandenborne, Krista; Walter, Glenn; Shiloh-Malawsky, Yael; An, Hongyu; Kornegay, Joe N.; Styner, Martin A.

2015-01-01

Purpose Golden retriever muscular dystrophy (GRMD) is a widely used canine model of Duchenne muscular dystrophy (DMD). Recent studies have shown that magnetic resonance imaging (MRI) can be used to non-invasively detect consistent changes in both DMD and GRMD. In this paper, we propose a semi-automated system to quantify MRI biomarkers of GRMD. Methods Our system was applied to a database of 45 MRI scans from 8 normal and 10 GRMD dogs in a longitudinal natural history study. We first segmented six proximal pelvic limb muscles using two competing schemes: 1) standard, limited muscle range segmentation and 2) semi-automatic full muscle segmentation. We then performed pre-processing, including: intensity inhomogeneity correction, spatial registration of different image sequences, intensity calibration of T2-weighted (T2w) and T2-weighted fat suppressed (T2fs) images, and calculation of MRI biomarker maps. Finally, for each of the segmented muscles, we automatically measured MRI biomarkers of muscle volume and intensity statistics over MRI biomarker maps, and statistical image texture features. Results The muscle volume and the mean intensities in T2 value, fat, and water maps showed group differences between normal and GRMD dogs. For the statistical texture biomarkers, both the histogram and run-length matrix features showed obvious group differences between normal and GRMD dogs. The full muscle segmentation shows significantly less error and variability in the proposed biomarkers when compared to the standard, limited muscle range segmentation. Conclusion The experimental results demonstrated that this quantification tool can reliably quantify MRI biomarkers in GRMD dogs, suggesting that it would also be useful for quantifying disease progression and measuring therapeutic effect in DMD patients. PMID:23299128

Development of Chewing in Children From 12 to 48 Months: Longitudinal Study of EMG Patterns

PubMed Central

GREEN, JORDAN R.; MOORE, CHRISTOPHER A.; RUARK, JACKI L.; RODDA, PAULA R.; MORVÉE, WENDY T.; VanWITZENBURG, MARCUS J.

2014-01-01

Developmental changes in the coordinative organization of masticatory muscles were examined longitudinally in four children over 49 experimental sessions spanning the age range of 12–48 mo. Electromyographic (EMG) records were obtained for right and left masseter muscles, right and left temporalis muscles, and the anterior belly of the digastric. Two independent analytic processes were employed, one that relied on identification of onset and offset of muscle activation and a second that used pairwise cross-correlational techniques. The results of these two analyses, which were found to be consistent with each other, demonstrated that the basic chewing pattern of reciprocally activated antagonistic muscle groups is established by 12 mo of age. Nevertheless, chewing efficiency appears to be improved through a variety of changes in the chewing pattern throughout early development. Coupling of activity among the jaw elevator muscles was shown to strengthen with maturation, and the synchrony of onset and offset of these muscles also increased. Coactivation of antagonistic muscles decreased significantly with development. This decrease in antagonistic coactivation and increase in synchrony among jaw elevators, and a parallel decrease in EMG burst duration, were taken as evidence of increased chewing efficiency. No significant differences in the frequency of chewing were found across the ages studied. Additional considerations include the appropriateness of this coordinative infrastructure for other developing oromotor skills, such as speech production. It is suggested that the relatively fixed coordinative framework for chewing exhibited by these children would not be suitable for adaptation to speech movements, which have been shown to rely on a much more variable and adjustable coordinative organization. PMID:9163386

Genome-wide patterns of promoter sharing and co-expression in bovine skeletal muscle.

PubMed

Gu, Quan; Nagaraj, Shivashankar H; Hudson, Nicholas J; Dalrymple, Brian P; Reverter, Antonio

2011-01-12

Gene regulation by transcription factors (TF) is species, tissue and time specific. To better understand how the genetic code controls gene expression in bovine muscle we associated gene expression data from developing Longissimus thoracis et lumborum skeletal muscle with bovine promoter sequence information. We created a highly conserved genome-wide promoter landscape comprising 87,408 interactions relating 333 TFs with their 9,242 predicted target genes (TGs). We discovered that the complete set of predicted TGs share an average of 2.75 predicted TF binding sites (TFBSs) and that the average co-expression between a TF and its predicted TGs is higher than the average co-expression between the same TF and all genes. Conversely, pairs of TFs sharing predicted TGs showed a co-expression correlation higher that pairs of TFs not sharing TGs. Finally, we exploited the co-occurrence of predicted TFBS in the context of muscle-derived functionally-coherent modules including cell cycle, mitochondria, immune system, fat metabolism, muscle/glycolysis, and ribosome. Our findings enabled us to reverse engineer a regulatory network of core processes, and correctly identified the involvement of E2F1, GATA2 and NFKB1 in the regulation of cell cycle, fat, and muscle/glycolysis, respectively. The pivotal implication of our research is two-fold: (1) there exists a robust genome-wide expression signal between TFs and their predicted TGs in cattle muscle consistent with the extent of promoter sharing; and (2) this signal can be exploited to recover the cellular mechanisms underpinning transcription regulation of muscle structure and development in bovine. Our study represents the first genome-wide report linking tissue specific co-expression to co-regulation in a non-model vertebrate.

Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.

PubMed

Oishi, Teruyo; Uezumi, Akiyoshi; Kanaji, Arihiko; Yamamoto, Naoki; Yamaguchi, Asami; Yamada, Harumoto; Tsuchida, Kunihiro

2013-01-01

Heterotopic ossification (HO) is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+) and PDGFRα(+) cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+) cells and PDGFRα(+) cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+) cells formed bone-like tissue and showed successful engraftment, while CD56(+) cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+) cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs) are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+) cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+) cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+) cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+) cells. Our results suggest that PDGFRα(+) cells may be the major source of HO and that the newly identified miRNAs may regulate osteogenic differentiation process of PDGFRα(+) cells.

The prevention and treatment of exercise-induced muscle damage.

PubMed

Howatson, Glyn; van Someren, Ken A

2008-01-01

Exercise-induced muscle damage (EIMD) can be caused by novel or unaccustomed exercise and results in a temporary decrease in muscle force production, a rise in passive tension, increased muscle soreness and swelling, and an increase in intramuscular proteins in blood. Consequently, EIMD can have a profound effect on the ability to perform subsequent bouts of exercise and therefore adhere to an exercise training programme. A variety of interventions have been used prophylactically and/or therapeutically in an attempt to reduce the negative effects associated with EIMD. This article focuses on some of the most commonly used strategies, including nutritional and pharmacological strategies, electrical and manual therapies and exercise. Long-term supplementation with antioxidants or beta-hydroxy-beta-methylbutyrate appears to provide a prophylactic effect in reducing EIMD, as does the ingestion of protein before and following exercise. Although the administration of high-dose NSAIDs may reduce EIMD and muscle soreness, it also attenuates the adaptive processes and should therefore not be prescribed for long-term treatment of EIMD. Whilst there is some evidence that stretching and massage may reduce muscle soreness, there is little evidence indicating any performance benefits. Electrical therapies and cryotherapy offer limited effect in the treatment of EIMD; however, inconsistencies in the dose and frequency of these and other interventions may account for the lack of consensus regarding their efficacy. Both as a cause and a consequence of this, there are very few evidence-based guidelines for the application of many of these interventions. Conversely, there is unequivocal evidence that prior bouts of eccentric exercise provide a protective effect against subsequent bouts of potentially damaging exercise. Further research is warranted to elucidate the most appropriate dose and frequency of interventions to attenuate EIMD and if these interventions attenuate the adaptation process. This will both clarify the efficacy of such strategies and provide guidelines for evidence-based practice.

Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation

PubMed Central

2013-01-01

Background Betaine (BET) is a component of many foods, including spinach and wheat. It is an essential osmolyte and a source of methyl groups. Recent studies have hypothesized that BET might play a role in athletic performance. However, BET effects on skeletal muscle differentiation and hypertrophy are still poorly understood. Methods We examined BET action on neo myotubes maturation and on differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR array, Western blot and immunofluorescence analysis to study the BET effects on morphological features of C2C12 and on signaling pathways involved in muscle differentiation and hypertrophy. Results We performed a dose–response study, establishing that 10 mM BET was the dose able to stimulate morphological changes and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to identify the expression profile of genes encoding proteins involved in IGF-1 pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R) expression. Western blot and immunofluorescence analysis, performed in neo myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of Myosin Heavy Chain (MyHC) and neo myotubes length. In addition, we investigated BET role on myoblasts proliferation and differentiation. During proliferation, BET did not modify C2C12 proliferative rate, but promoted myogenic induction, enhancing MyoD protein content and cellular elongation. During differentiation, BET caused an increase of muscle-specific markers and IGF-1 R protein levels. Conclusions Our findings provide the first evidence that BET could promote muscle fibers differentiation and increase myotubes size by IGF-1 pathway activation, suggesting that BET might represent a possible new drug/integrator strategy, not only in sport performance but also in clinical conditions characterized by muscle function impairment. PMID:23870626

Pulmonary Function, Muscle Strength and Mortality in Old Age

PubMed Central

Buchman, A. S.; Boyle, P. A.; Wilson, R.S.; Gu, Liping; Bienias, Julia L.; Bennett, D. A.

2009-01-01

Numerous reports have linked extremity muscle strength with mortality but the mechanism underlying this association is not known. We used data from 960 older persons without dementia participating in the Rush Memory and Aging Project to test two sequential hypotheses: first, that extremity muscle strength is a surrogate for respiratory muscle strength, and second, that the association of respiratory muscle strength with mortality is mediated by pulmonary function. In a series of proportional hazards models, we first demonstrated that the association of extremity muscle strength with mortality was no longer significant after including a term for respiratory muscle strength, controlling for age, sex, education, and body mass index. Next, the association of respiratory muscle strength with mortality was attenuated by more than 50% and no longer significant after including a term for pulmonary function. The findings were unchanged after controlling for cognitive function, parkinsonian signs, physical frailty, balance, physical activity, possible COPD, use of pulmonary medications, vascular risk factors including smoking, chronic vascular diseases, musculoskeletal joint pain, and history of falls. Overall, these findings suggest that pulmonary function may partially account for the association of muscle strength and mortality. PMID:18755207

Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle.

PubMed

Chao, Lily C; Zhang, Zidong; Pei, Liming; Saito, Tsugumichi; Tontonoz, Peter; Pilch, Paul F

2007-09-01

Innervation is important for normal metabolism in skeletal muscle, including insulin-sensitive glucose uptake. However, the transcription factors that transduce signals from the neuromuscular junction to the nucleus and affect changes in metabolic gene expression are not well defined. We demonstrate here that the orphan nuclear receptor Nur77 is a regulator of gene expression linked to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in glycolytic compared with oxidative muscle and is responsive to beta-adrenergic stimulation. Denervation of rat muscle compromises expression of Nur77 in parallel with that of numerous genes linked to glucose metabolism, including glucose transporter 4 and genes involved in glycolysis, glycogenolysis, and the glycerophosphate shuttle. Ectopic expression of Nur77, either in rat muscle or in C2C12 muscle cells, induces expression of a highly overlapping set of genes, including glucose transporter 4, muscle phosphofructokinase, and glycogen phosphorylase. Furthermore, selective knockdown of Nur77 in rat muscle by small hairpin RNA or genetic deletion of Nur77 in mice reduces the expression of a battery of genes involved in skeletal muscle glucose utilization in vivo. Finally, we show that Nur77 binds the promoter regions of multiple genes involved in glucose metabolism in muscle. These results identify Nur77 as a potential mediator of neuromuscular signaling in the control of metabolic gene expression.

Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle

PubMed Central

Chao, Lily C.; Zhang, Zidong; Pei, Liming; Saito, Tsugumichi; Tontonoz, Peter; Pilch, Paul F.

2008-01-01

Innervation is important for normal metabolism in skeletal muscle, including insulin-sensitive glucose uptake. However, the transcription factors that transduce signals from the neuromuscular junction to the nucleus and affect changes in metabolic gene expression are not well defined. We demonstrate here that the orphan nuclear receptor Nur77 is a regulator of gene expression linked to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in glycolytic compared to oxidative muscle and is responsive to β-adrenergic stimulation. Denervation of rat muscle compromises expression of Nur77 in parallel with that of numerous genes linked to glucose metabolism, including GLUT4 and genes involved in glycolysis, glycogenolysis, and the glycerophosphate shuttle. Ectopic expression of Nur77, either in rat muscle or in C2C12 muscle cells, induces expression of a highly overlapping set of genes, including GLUT4, muscle phosphofructokinase, and glycogen phosphorylase. Furthermore, selective knockdown of Nur77 in rat muscle by shRNA or genetic deletion of Nur77 in mice reduces the expression of a battery of genes involved in skeletal muscle glucose utilization in vivo. Finally, we show that Nur77 binds the promoter regions of multiple innervation-dependent genes in muscle. These results identify Nur77 as a potential mediator of neuromuscular signaling in the control of metabolic gene expression. PMID:17550977

Imaging of respiratory muscles in neuromuscular disease: A review.

PubMed

Harlaar, L; Ciet, P; van der Ploeg, A T; Brusse, E; van der Beek, N A M E; Wielopolski, P A; de Bruijne, M; Tiddens, H A W M; van Doorn, P A

2018-03-01

Respiratory muscle weakness frequently occurs in patients with neuromuscular disease. Measuring respiratory function with standard pulmonary function tests provides information about the contribution of all respiratory muscles, the lungs and airways. Imaging potentially enables the study of different respiratory muscles, including the diaphragm, separately. In this review, we provide an overview of imaging techniques used to study respiratory muscles in neuromuscular disease. We identified 26 studies which included a total of 573 patients with neuromuscular disease. Imaging of respiratory muscles was divided into static and dynamic techniques. Static techniques comprise chest radiography, B-mode (brightness mode) ultrasound, CT and MRI, and are used to assess the position and thickness of the diaphragm and the other respiratory muscles. Dynamic techniques include fluoroscopy, M-mode (motion mode) ultrasound and MRI, used to assess diaphragm motion in one or more directions. We discuss how these imaging techniques relate with spirometric values and whether these can be used to study the contribution of the different respiratory muscles in patients with neuromuscular disease. Copyright © 2017. Published by Elsevier B.V.

Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle

PubMed Central

Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

2016-01-01

The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling. PMID:26725948

Cadaveric validation of dry needle placement in the lateral pterygoid muscle.

PubMed

Mesa-Jiménez, Juan A; Sánchez-Gutiérrez, Jesús; de-la-Hoz-Aizpurua, José L; Fernández-de-las-Peñas, César

2015-02-01

The aim of this anatomical study was to determine if a needle is able to reach the lateral pterygoid muscle during the application of dry needling technique. A dry needling approach using 2 needles of 50 to 60 mm in length, one inserted over the zygomatic process posterior at the obituary arch (for the superior head) and other inserted below the zygomatic process between the mandibular condyle and the coronoid process (for the inferior head), was proposed. A progressive dissection into 3 stages was conducted into 2 heads of fresh male cadavers. First, dry needling of the lateral pterygoid muscle was applied on the cadaver. Second, a block dissection containing the lateral pterygoid was harvested. Finally, the ramus of the mandible was sectioned by osteotomy to visualize the lateral pterygoid muscle with the needle placements. With the needles inserted into the cadaver, the block dissection revealed that the superior needle reached the superior (sphenoid) head of the lateral pterygoid muscle and the inferior needle reached the inferior (pterygoid) head of the muscle. At the final stage of the dissection, when the ramus of the mandible was sectioned by osteotomy, it was revealed that the superior needle entered into the belly of the superior head of the lateral pterygoid muscle. This anatomical study supports that dry needling technique for the lateral pterygoid muscle can be properly conducted with the proposed approach. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Effects of Fiber Type and Size on the Heterogeneity of Oxygen Distribution in Exercising Skeletal Muscle

PubMed Central

Liu, Gang; Mac Gabhann, Feilim; Popel, Aleksander S.

2012-01-01

The process of oxygen delivery from capillary to muscle fiber is essential for a tissue with variable oxygen demand, such as skeletal muscle. Oxygen distribution in exercising skeletal muscle is regulated by convective oxygen transport in the blood vessels, oxygen diffusion and consumption in the tissue. Spatial heterogeneities in oxygen supply, such as microvascular architecture and hemodynamic variables, had been observed experimentally and their marked effects on oxygen exchange had been confirmed using mathematical models. In this study, we investigate the effects of heterogeneities in oxygen demand on tissue oxygenation distribution using a multiscale oxygen transport model. Muscles are composed of different ratios of the various fiber types. Each fiber type has characteristic values of several parameters, including fiber size, oxygen consumption, myoglobin concentration, and oxygen diffusivity. Using experimentally measured parameters for different fiber types and applying them to the rat extensor digitorum longus muscle, we evaluated the effects of heterogeneous fiber size and fiber type properties on the oxygen distribution profile. Our simulation results suggest a marked increase in spatial heterogeneity of oxygen due to fiber size distribution in a mixed muscle. Our simulations also suggest that the combined effects of fiber type properties, except size, do not contribute significantly to the tissue oxygen spatial heterogeneity. However, the incorporation of the difference in oxygen consumption rates of different fiber types alone causes higher oxygen heterogeneity compared to control cases with uniform fiber properties. In contrast, incorporating variation in other fiber type-specific properties, such as myoglobin concentration, causes little change in spatial tissue oxygenation profiles. PMID:23028531

Objective models of EMG signals for cyclic processes such as a human gait

NASA Astrophysics Data System (ADS)

Babska, Luiza; Selegrat, Monika; Dusza, Jacek J.

2016-09-01

EMG signals are small potentials appearing at the surface of human skin during muscle work. They arise due to changes in the physiological state of cell membranes in the muscle fibers. They are characterized by a relatively low frequency range (500 Hz) and a low amplitude signal (of the order of μV), making it difficult to record. Raw EMG signal is inherently random shape. However we can distinguish certain features related to the activation of the muscles of a deterministic or quasi-deterministic associated with the movement and its parametric description. Objective models of EMG signals were created on the base of actual data obtained from the VICON system installed at the University of Physical Education in Warsaw. The object of research (healthy woman) moved repeatedly after a fixed track. On her body 35 reflective markers to record the gait kinematics and 8 electrodes to record EMG signals were placed. We obtained research data included more than 1,000 EMG signals synchronized with the phases of gait. Test result of the work is an algorithm for obtaining the average EMG signal received from the multiple registration gait cycles carried out in the same reproducible conditions. The method described in the article is essentially a pre-finding measurement data from the two quasi-synchronous signals at different sampling frequencies for further processing. This signal is characterized by a significant reduction of high frequency noise and emphasis on the specific characteristics of individual records found in muscle activity.

Use of the Rigor Mortis Process as a Tool for Better Understanding of Skeletal Muscle Physiology: Effect of the Ante-Mortem Stress on the Progression of Rigor Mortis in Brook Charr (Salvelinus fontinalis).

ERIC Educational Resources Information Center

Diouf, Boucar; Rioux, Pierre

1999-01-01

Presents the rigor mortis process in brook charr (Salvelinus fontinalis) as a tool for better understanding skeletal muscle metabolism. Describes an activity that demonstrates how rigor mortis is related to the post-mortem decrease of muscular glycogen and ATP, how glycogen degradation produces lactic acid that lowers muscle pH, and how…

Localization of acetylcholine receptors and synaptic ultrastructure at nerve-muscle contacts in culture: dependence on nerve type

PubMed Central

Cohen, MW; Weldon, PR

1980-01-01

In cultures of xenopus myotomal muscle cells and spinal cord (SC) some of the nerve-muscle contacts exhibit a high density of acetylcholine receptors (AchRs [Anderson et al., 1977, J. Physiol. (Lond.). 268:731- 756,757-773]) and synaptic ultrastructure (Weldon and Cohen, 1979, J. Neurocytol. 8:239-259). We have examined whether similarly specialized contacts are established when the muscle cells are cultured with explants of xenopus dorsal root ganglia (DRG) or sympathetic ganglia (SG). The outgrowth from the ganglionic explants contained neuronal and non- neuronal cell processes. Although both types of processes approached within 100 A of muscle cells, synaptic ultrastructure was rarely observed at these contacts. Because patches of postsynaptic ultrastructure also develop on noncontacted muscle cells, the very few examples of contacts with such specializations probably occurred by chance. AChRs were stained with fluroscent α-bungarotoxin. More than 70 percent of the SC-contacted muscle cells exhibited a high receptor density along the path of contact. The corresponding values for DRG- and SG- contacted muscle cells were 10 and 6 percent. Similar values were obtained when the ganlionic and SC explants were cultured together in the same chamber. The few examples of high receptor density at ganglionic-muscle contacts resembled the characteristic receptor patches of noncontacted muscle cells rather than the narrow bands of high receptor density seen at SC-muscle contacts. In addition, more than 90 percent of these ganglionic- contacted muscle cells had receptor patches elsewhere, compared to less than 40 percent for the SC-contacted muscle cells. These findings indicate that the SC neurites possess a specific property which is important for the establishment of synaptically specialized contacts with muscle and that this property is lacking in the DRG and SG neurites. PMID:7400212

New Types of Artificial Muscles for Large Stroke and High Force Applications

DTIC Science & Technology

2012-10-10

University of Texas at Dallas and include Aerogel Muscles, Torsional and Tensile Yarn Muscles, Artificial Muscles Based on Polypyrrole Laminates and...Stroke, Superelastic Carbon Nanotube Aerogel Muscles 3. Torsional and Tensile Carbon Nanotube Yarn Muscles 4. Artificial Muscles Based on...in numerous press releases and TV programs. As we reported in Science 2009, carbon nanotube aerogel sheets are the sole component of new artificial

Role of ATF4 in skeletal muscle atrophy.

PubMed

Adams, Christopher M; Ebert, Scott M; Dyle, Michael C

2017-05-01

Here, we discuss recent work focused on the role of activating transcription factor 4 (ATF4) in skeletal muscle atrophy. Muscle atrophy involves and requires widespread changes in skeletal muscle gene expression; however, the transcriptional regulatory proteins responsible for those changes are not yet well defined. Recent work indicates that some forms of muscle atrophy require ATF4, a stress-inducible bZIP transcription factor subunit that helps to mediate a broad range of stress responses in mammalian cells. ATF4 expression in skeletal muscle fibers is sufficient to induce muscle fiber atrophy and required for muscle atrophy during several stress conditions, including aging, fasting, and limb immobilization. By helping to activate specific genes in muscle fibers, ATF4 contributes to the expression of numerous mRNAs, including at least two mRNAs (Gadd45a and p21) that encode mediators of muscle fiber atrophy. Gadd45a promotes muscle fiber atrophy by activating the protein kinase MEKK4. p21 promotes atrophy by reducing expression of spermine oxidase, a metabolic enzyme that helps to maintain muscle fiber size under nonstressed conditions. In skeletal muscle fibers, ATF4 is critical component of a complex and incompletely understood molecular signaling network that causes muscle atrophy during aging, fasting, and immobilization.

Surgical anatomy of the styloid muscles and the extracranial glossopharyngeal nerve.

PubMed

Prades, J M; Gavid, M; Asanau, A; Timoshenko, A P; Richard, C; Martin, C H

2014-03-01

The purpose of the study was to determine the relationships between the extracranial glossopharyngeal (IX) nerve and the muscles of the styloid diaphragm. In humans, the IX nerve is a hidden retrostyloid nerve which plays a critical role notably in swallowing and has to be preserved during infratemporal fossa and parapharyngeal spaces surgical procedures. In ten adult heads from cadavers (20 sides) fixed in formalin, dissection of the extracranial IX nerve was performed under operating microscope with special attention given to the relationships between this nerve and the styloid muscles of the styloid diaphragm. The three styloid muscles delimit three triangular intermuscular intervals which were each thoroughly explored. Different osseous landmarks were investigated for easy nerve location. The styloid process (SP) is the main superior osseous landmark for the three muscles of the styloid diaphragm. The stylohyoid muscle (SHM) is anteromedially located to the posterior belly of the digastric muscle. The styloglossus muscle (SGM) is medial and anterior to the SHM. The stylopharyngeal muscle (SPM) is the most vertical and medial of the three styloid muscles. It courses from the medial surface of the SP in a deep plane hidden between the SHM and the SGM. The extracranial IX nerve turns around the SPM superiorly with a vertical segment posterior to the SPM and inferiorly with a horizontal segment lateral to the SPM. The meeting point of the two segments of the IX nerve is about 10 mm anteriorly located from the transverse process of the atlas. The external carotid artery and some of its branches lie in contact with the lateral side of the IX nerve. Such relationships between the extracranial IX nerve, the styloid muscles and the transverse process of the atlas should be appreciated by clinician who treats patients with stylohyoid complex syndromes and by the surgeon for the parapharyngeal spaces approach.

Lactate: link between glycolytic and oxidative metabolism.

PubMed

Brooks, George A

2007-01-01

Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilised continuously under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of cell-cell shuttles include lactate exchanges (i) between white-glycolytic and red-oxidative fibres within a working muscle bed; (ii) between working skeletal muscle and heart; and (iii) between tissues of net lactate release and gluconeogenesis. Lactate shuttles exist in diverse tissues including in the brain, where a shuttle between astrocytes and neurons is linked to glutamatergic signalling. Because lactate, the product of glycogenolysis and glycolysis, is disposed of by oxidative metabolism, lactate shuttling unites the two major processes of cellular energy transduction. Lactate disposal is mainly through oxidation, especially during exercise when oxidation accounts for 70-75% of removal and gluconeogenesis the remainder. Lactate flux occurs down proton and concentration gradients that are established by the mitochondrial lactate oxidation complex. Marathon running is a power activity requiring high glycolytic and oxidative fluxes; such activities require lactate shuttling. Knowledge of the lactate shuttle is yet to be imparted to the sport.

Independent Aftereffects of Fat and Muscle: Implications for neural encoding, body space representation, and body image disturbance

PubMed Central

Sturman, Daniel; Stephen, Ian D.; Mond, Jonathan; Stevenson, Richard J; Brooks, Kevin R.

2017-01-01

Although research addressing body size misperception has focused on socio-cognitive processes, such as internalization of the “ideal” images of bodies in the media, the perceptual basis of this phenomenon remains largely unknown. Further, most studies focus on body size per se even though this depends on both fat and muscle mass – variables that have very different relationships with health. We tested visual adaptation as a mechanism for inducing body fat and muscle mass misperception, and assessed whether these two dimensions of body space are processed independently. Observers manipulated the apparent fat and muscle mass of bodies to make them appear “normal” before and after inspecting images from one of four adaptation conditions (increased fat/decreased fat/increased muscle/decreased muscle). Exposure resulted in a shift in the point of subjective normality in the direction of the adapting images along the relevant (fat or muscle) axis, suggesting that the neural mechanisms involved in body fat and muscle perception are independent. This supports the viability of adaptation as a model of real-world body size misperception, and extends its applicability to clinical manifestations of body image disturbance that entail not only preoccupation with thinness (e.g., anorexia nervosa) but also with muscularity (e.g., muscle dysmorphia). PMID:28071712

Independent Aftereffects of Fat and Muscle: Implications for neural encoding, body space representation, and body image disturbance.

PubMed

Sturman, Daniel; Stephen, Ian D; Mond, Jonathan; Stevenson, Richard J; Brooks, Kevin R

2017-01-10

Although research addressing body size misperception has focused on socio-cognitive processes, such as internalization of the "ideal" images of bodies in the media, the perceptual basis of this phenomenon remains largely unknown. Further, most studies focus on body size per se even though this depends on both fat and muscle mass - variables that have very different relationships with health. We tested visual adaptation as a mechanism for inducing body fat and muscle mass misperception, and assessed whether these two dimensions of body space are processed independently. Observers manipulated the apparent fat and muscle mass of bodies to make them appear "normal" before and after inspecting images from one of four adaptation conditions (increased fat/decreased fat/increased muscle/decreased muscle). Exposure resulted in a shift in the point of subjective normality in the direction of the adapting images along the relevant (fat or muscle) axis, suggesting that the neural mechanisms involved in body fat and muscle perception are independent. This supports the viability of adaptation as a model of real-world body size misperception, and extends its applicability to clinical manifestations of body image disturbance that entail not only preoccupation with thinness (e.g., anorexia nervosa) but also with muscularity (e.g., muscle dysmorphia).

Reflection of the State of Hunger in Impulse Activity of Nose Wing Muscles and Upper Esophageal Sphincter during Search behavior in Rabbits.

PubMed

Kromin, A A; Dvoenko, E E; Zenina, O Yu

2016-07-01

Reflection of the state of hunger in impulse activity of nose wing muscles and upper esophageal sphincter muscles was studied in chronic experiments on rabbits subjected to 24-h food deprivation in the absence of locomotion and during search behavior. In the absence of apparent behavioral activity, including sniffing, alai nasi muscles of hungry rabbits constantly generated bursts of action potentials synchronous with breathing, while upper esophageal sphincter muscles exhibited regular aperiodic low-amplitude impulse activity of tonic type. Latent form of food motivation was reflected in the structure of temporal organization of impulse activity of alai nasi muscles in the form of bimodal distribution of interpulse intervals and in temporal structure of impulse activity of upper esophageal sphincter muscles in the form of monomodal distribution. The latent form of food motivation was manifested in the structure of temporal organization of periods of the action potentials burst-like rhythm, generated by alai nasi muscles, in the form of monomodal distribution, characterized by a high degree of dispersion of respiratory cycle periods. In the absence of physical activity hungry animals sporadically exhibited sniffing activity, manifested in the change from the burst-like impulse activity of alai nasi muscles to the single-burst activity type with bimodal distribution of interpulse intervals and monomodal distribution of the burst-like action potentials rhythm periods, the maximum of which was shifted towards lower values, which was the cause of increased respiratory rate. At the same time, the monomodal temporal structure of impulse activity of the upper esophageal sphincter muscles was not changed. With increasing food motivation in the process of search behavior temporal structure of periods of the burst-like action potentials rhythm, generated by alai nasi muscles, became similar to that observed during sniffing, not accompanied by animal's locomotion, which is typical for the increased respiratory rhythm frequency. Increased hunger motivation was reflected in the temporal structure of impulse activity of upper esophageal sphincter muscles in the form of a shift to lower values of the maximum of monomodal distribution of interpulse intervals on the histogram, resulting in higher impulse activity frequency. The simultaneous increase in the frequency of action potentials bursts generation by alai nasi muscles and regular impulse activity of upper esophageal sphincter muscles is a reliable criterion for enhanced food motivation during search behavior in rabbits.

The emotional regulatory features of bulimic episodes and compulsive exercise in muscle dysmorphia: a case report.

PubMed

Murray, Stuart B; Maguire, Sarah; Russell, Janice; Touyz, Stephen W

2012-01-01

Muscle dysmorphia is a recently identified psychiatric condition, whose relationship to the eating disorders remains unclear. This case describes an adolescent male who met diagnostic criteria for both an eating disorder not otherwise specified and muscle dysmorphia, allowing the first examination of read muscle dysmorphia presentations. This case suggests that muscle dysmorphia may present inclusive of episodes of binge eating and purging in addition to compulsive exercise, which may serve an emotional regulation function. We suggest that the assessment of muscle dysmorphia include a comprehensive assessment of all eating disorder features including bulimic symptoms, and that treatment address these features. Clinical implications for the conceptualization of muscle dysmorphia are discussed. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.

Effect of spaceflight on the extracellular matrix of skeletal muscle after a crush injury

NASA Technical Reports Server (NTRS)

Stauber, W. T.; Fritz, V. K.; Burkovskaia, T. E.; Il'ina-Kakueva, E. I.

1992-01-01

The organization and composition of the extracellular matrix were studied in the crush-injured gastrocnemius muscle of rats subjected to 0 G. After 14 days of flight on Cosmos 2044, the gastrocnemius muscle was removed and evaluated by histochemical and immunohistochemical techniques from the five injured flight rodents and various earth-based treatment groups. In general, the repair process was similar in all injured muscle samples with regard to the organization of the extracellular matrix and myofibers. Small and large myofibers were present within an expanded extracellular matrix, indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with nonenlarged area of nonmuscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well organized and contained more macrophages and blood vessels in the repair region, indicative of a delayed repair process, but did not demonstrate any chronic inflammation. Myofiber repair did vary in muscles from the different groups, being slowest in the flight animals and most complete in the tail-suspended ones.

Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy.

PubMed

Kuraoka, Mutsuki; Kimura, En; Nagata, Tetsuya; Okada, Takashi; Aoki, Yoshitsugu; Tachimori, Hisateru; Yonemoto, Naohiro; Imamura, Michihiro; Takeda, Shin'ichi

2016-05-01

Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Enhancement of Muscle T Regulatory Cells and Improvement of Muscular Dystrophic Process in mdx Mice by Blockade of Extracellular ATP/P2X Axis.

PubMed

Gazzerro, Elisabetta; Baldassari, Simona; Assereto, Stefania; Fruscione, Floriana; Pistorio, Angela; Panicucci, Chiara; Volpi, Stefano; Perruzza, Lisa; Fiorillo, Chiara; Minetti, Carlo; Traggiai, Elisabetta; Grassi, Fabio; Bruno, Claudio

2015-12-01

Infiltration of immune cells and chronic inflammation substantially affect skeletal and cardiac muscle degeneration in Duchenne muscular dystrophy. In the immune system, extracellular adenosine triphosphate (ATP) released by dying cells is sensed as a danger associated molecular pattern through P2 purinergic receptors. Specifically, the P2X7 subtype has a prominent role in regulating immune system physiology and contributes to inflammasome activation also in muscle cells. Here, we show that in vivo blockade of the extracellular ATP/P2X purinergic signaling pathway by periodate-oxidized ATP delayed the progression of the dystrophic phenotype and dampened the local inflammatory response in mdx mice, a spontaneous mouse model of dystrophin deficiency. Reduced infiltration of leukocytes and macrophages and decreased expression of IL-6 were revealed in the muscles of periodate-oxidized ATP-treated mdx mice. Concomitantly, an increase in Foxp3(+) immunosuppressive regulatory T cells was observed and correlated with enhanced myofiber regeneration. Moreover, we detected reduced concentrations of profibrotic cytokines, including transforming growth factor-β and connective tissue growth factor, in muscles of periodate-oxidized ATP-treated mdx mice. The improvement of inflammatory features was associated with increased strength and reduced necrosis, thus suggesting that pharmacologic purinergic antagonism altering the adaptive immune component in the muscle infiltrates might represent a promising therapeutic approach in Duchenne muscular dystrophy. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Transcriptome Profile Analysis of Breast Muscle Tissues from High or Low Levels of Atmospheric Ammonia Exposed Broilers (Gallus gallus)

PubMed Central

Sa, Renna; Zhong, Ruqing; Xing, Huan; Zhang, Hongfu

2016-01-01

Atmospheric ammonia is a common problem in poultry industry. High concentrations of aerial ammonia cause great harm to broilers' health and production. For the consideration of human health, the limit exposure concentration of ammonia in houses is set at 25 ppm. Previous reports have shown that 25 ppm is still detrimental to livestock, especially the gastrointestinal tract and respiratory tract, but the negative relationship between ammonia exposure and the tissue of breast muscle of broilers is still unknown. In the present study, 25 ppm ammonia in poultry houses was found to lower slaughter performance and breast yield. Then, high-throughput RNA sequencing was utilized to identify differentially expressed genes in breast muscle of broiler chickens exposed to high (25 ppm) or low (3 ppm) levels of atmospheric ammonia. The transcriptome analysis showed that 163 genes (fold change ≥ 2 or ≤ 0.5; P-value < 0.05) were differentially expressed between Ammonia25 (treatment group) and Ammonia3 (control group), including 96 down-regulated and 67 up-regulated genes. qRT-PCR analysis validated the transcriptomic results of RNA sequencing. Gene Ontology (GO) functional annotation analysis revealed potential genes, processes and pathways with putative involvement in growth and development inhibition of breast muscle in broilers caused by aerial ammonia exposure. This study facilitates understanding of the genetic architecture of the chicken breast muscle transcriptome, and has identified candidate genes for breast muscle response to atmospheric ammonia exposure. PMID:27611572

Telocytes in skeletal, cardiac and smooth muscle interstitium: morphological and functional aspects.

PubMed

Marini, Mirca; Rosa, Irene; Ibba-Manneschi, Lidia; Manetti, Mirko

2018-04-25

Telocytes (TCs) represent a new distinct type of cells found in the stromal compartment of many organs, including the skeletal, cardiac and smooth muscles. TCs are morphologically defined as interstitial cells with a small cellular body from which arise very long (up to hundreds of micrometers) and thin moniliform processes (named telopodes) featuring the alternation of slender segments (called podomers) and small dilated portions (called podoms) accommodating some organelles. Although these stromal cells are mainly characterized by their ultrastructural traits, in the last few years TCs have been increasingly studied for their immunophenotypes, microRNA profiles, and gene expression and proteomic signatures. By their long-distance spreading telopodes, TCs build a three-dimensional network throughout the whole stromal space and communicate with each other and neighboring cells through homocellular and heterocellular junctions, respectively. Moreover, increasing evidence suggests that TCs may exert paracrine functions being able to transfer genetic information and signaling molecules to other cells via the release of different types of extracellular vesicles. A close relationship between TCs and stem/progenitor cell niches has also been described in several organs. However, the specific functions of TCs located in the muscle interstitium remain to be unraveled. Here, we review the morphological and possible functional aspects of TCs in skeletal, cardiac and smooth muscle tissues. The potential involvement of TCs in muscle tissue pathological changes and future possibilities for targeting TCs as a novel promising therapeutic strategy to foster muscle tissue regeneration and repair are also discussed.

Muscle atrophy

MedlinePlus

... muscle atrophy may include: Burns Long-term corticosteroid therapy Malnutrition Muscular dystrophy and other diseases of the muscle Osteoarthritis Rheumatoid arthritis Home Care An exercise program ...

Muscle Strength and Muscle Mass in Older Patients during Hospitalization: The EMPOWER Study

PubMed Central

Van Ancum, Jeanine M.; Scheerman, Kira; Pierik, Vincent D.; Numans, Siger T.; Verlaan, Sjors; Smeenk, Hanne E.; Slee-Valentijn, Monique; Kruizinga, Roeliene C.; Meskers, Carel G.M.; Maier, Andrea B.

2017-01-01

Background Low muscle strength and muscle mass are associated with an increased length of hospital stay and higher mortality rate in inpatients. To what extent hospitalization affects muscle strength and muscle mass is unclear. Objective We aimed to assess muscle strength and muscle mass at admission and during hospitalization in older patients and its relation with being at risk of geriatric conditions. Methods The EMPOWER study included patients aged 70 years and older, admitted to 4 wards of the VU University Medical Center in the Netherlands between April and December 2015. At admission, patients were screened for being at risk of 4 geriatric conditions: delirium, falls, malnutrition, and functional disability. At admission and at discharge, muscle strength and muscle mass were assessed. Results A total of 373 patients (mean age, standard deviation [SD]: 79.6, 6.38 years) were included at admission, and 224 patients (mean age, SD: 80.1, 6.32 years) at discharge. At admission, lower muscle strength in both female and male patients and low muscle mass in male patients were associated with being at risk of a higher cumulative number of geriatric conditions. Muscle strength increased during hospitalization, but no change in muscle mass was observed. Changes in muscle measures were not associated with being at risk of geriatric conditions. Discussion Older patients with lower muscle strength and muscle mass at admission were at risk of a higher cumulative number of geriatric conditions. However, being at risk of geriatric conditions did not forecast further decrease in muscle strength and muscle mass during hospitalization PMID:28817825

Muscle Strength and Muscle Mass in Older Patients during Hospitalization: The EMPOWER Study.

PubMed

Van Ancum, Jeanine M; Scheerman, Kira; Pierik, Vincent D; Numans, Siger T; Verlaan, Sjors; Smeenk, Hanne E; Slee-Valentijn, Monique; Kruizinga, Roeliene C; Meskers, Carel G M; Maier, Andrea B

2017-01-01

Low muscle strength and muscle mass are associated with an increased length of hospital stay and higher mortality rate in inpatients. To what extent hospitalization affects muscle strength and muscle mass is unclear. We aimed to assess muscle strength and muscle mass at admission and during hospitalization in older patients and its relation with being at risk of geriatric conditions. The EMPOWER study included patients aged 70 years and older, admitted to 4 wards of the VU University Medical Center in the Netherlands between April and December 2015. At admission, patients were screened for being at risk of 4 geriatric conditions: delirium, falls, malnutrition, and functional disability. At admission and at discharge, muscle strength and muscle mass were assessed. A total of 373 patients (mean age, standard deviation [SD]: 79.6, 6.38 years) were included at admission, and 224 patients (mean age, SD: 80.1, 6.32 years) at discharge. At admission, lower muscle strength in both female and male patients and low muscle mass in male patients were associated with being at risk of a higher cumulative number of geriatric conditions. Muscle strength increased during hospitalization, but no change in muscle mass was observed. Changes in muscle measures were not associated with being at risk of geriatric conditions. Older patients with lower muscle strength and muscle mass at admission were at risk of a higher cumulative number of geriatric conditions. However, being at risk of geriatric conditions did not forecast further decrease in muscle strength and muscle mass during hospitalization. © 2017 The Author(s) Published by S. Karger AG, Basel.

Exercise Promotes Healthy Aging of Skeletal Muscle

PubMed Central

Cartee, Gregory D.; Hepple, Russell T.; Bamman, Marcas M.; Zierath, Juleen R.

2016-01-01

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics, and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes “healthy aging” by inducing modifications in skeletal muscle. PMID:27304505

Ultra-structural time-course study in the C. elegans model for Duchenne muscular dystrophy highlights a crucial role for sarcomere-anchoring structures and sarcolemma integrity in the earliest steps of the muscle degeneration process.

PubMed

Brouilly, Nicolas; Lecroisey, Claire; Martin, Edwige; Pierson, Laura; Mariol, Marie-Christine; Qadota, Hiroshi; Labouesse, Michel; Streichenberger, Nathalie; Mounier, Nicole; Gieseler, Kathrin

2015-11-15

Duchenne muscular dystrophy (DMD) is a genetic disease characterized by progressive muscle degeneration due to mutations in the dystrophin gene. In spite of great advances in the design of curative treatments, most patients currently receive palliative therapies with steroid molecules such as prednisone or deflazacort thought to act through their immunosuppressive properties. These molecules only slightly slow down the progression of the disease and lead to severe side effects. Fundamental research is still needed to reveal the mechanisms involved in the disease that could be exploited as therapeutic targets. By studying a Caenorhabditis elegans model for DMD, we show here that dystrophin-dependent muscle degeneration is likely to be cell autonomous and affects the muscle cells the most involved in locomotion. We demonstrate that muscle degeneration is dependent on exercise and force production. Exhaustive studies by electron microscopy allowed establishing for the first time the chronology of subcellular events occurring during the entire process of muscle degeneration. This chronology highlighted the crucial role for dystrophin in stabilizing sarcomeric anchoring structures and the sarcolemma. Our results suggest that the disruption of sarcomeric anchoring structures and sarcolemma integrity, observed at the onset of the muscle degeneration process, triggers subcellular consequences that lead to muscle cell death. An ultra-structural analysis of muscle biopsies from DMD patients suggested that the chronology of subcellular events established in C. elegans models the pathogenesis in human. Finally, we found that the loss of sarcolemma integrity was greatly reduced after prednisone treatment suggesting a role for this molecule in plasma membrane stabilization. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Inflammatory process in atherogenesis: new facts about old flame].

PubMed

Vucević, Danijela; Radak, Dorde; Radosavljević, Tatjana; Mladenović, Dusan; Milovanović, Ivan

2012-01-01

INTRODUCTION. Atherosclerosis is a progressive, multifactorial, diffuse, multisystemic, chronic, inflammatory disease, which is manifested by disorders of vascular, immune and metabolic system. Pathogenesis of this disease is not fully understood. Endothelial Dysfunction and Inflammatory Process. Endothelial dysfunction is recognized as the crucial step in atherogenesis. A lot of studies have confirmed the involvement of various mediators of inflammation in initial proatherogenic processes, such as the upregulation of adhesion molecules on endothelial cells, binding of low density lipoproteins to endothelium, activation of macrophages and proliferation of vascular smooth muscle cells. Fatty stain and Inflammatory Process. Fatty stain consists of foam cell accumulation. After foam cell formation, mediators of inflammation initiate a series ofintracellular events that include the induction of inflammatory cytokines. Thus, a vicious circle of inflammation, modification of lipoproteins and further inflammation can be maintained in the artery. Transitory Lesion and Inflammatory Process. In transitory lesion intensive phagocytosis of oxidized low density lipoproteins additionally activates monocytes and macrophages and consequently facilitates and exacerbates the inflammatory response. Fibrotic Plaque and Inflammatory Process. Inflammatory process, matrix-degrading metalloproteinases activity, platelets aggregation and smooth muscle cells proliferation play a central role in development of fibrotic plaque. Complex Lesion and Inflammatory Process. It has been shown that inflammation is closely related to the development of atherosclerotic plaque rupture. The contribution of inflammatory process has become increasingly meaningful in understanding the initiation, progression and clinical manifestations ofatherosclerosis.

Effect of limb immobilization on skeletal muscle

NASA Technical Reports Server (NTRS)

Booth, F. W.

1982-01-01

Current knowledge and questions remaining concerning the effects of limb immobilization on skeletal muscle is reviewed. The most dramatic of these effects is muscle atrophy, which has been noted in cases of muscles fixed at or below their resting length. Immobilization is also accompanied by a substantial decrease in motoneuronal discharges, which results in the conversion of slow-twitch muscle to muscle with fast-twitch characteristics. Sarcolemma effects include no change or a decrease in resting membrane potential, the appearance of extrajunctional acetylcholine receptors, and no change in acetylcholinesterase activity. Evidence of changes in motoneuron after hyperpolarization characteristics suggests that the muscle inactivity is responsible for neuronal changes, rather than vice versa. The rate of protein loss from atrophying muscles is determined solely by the first-order rate constant for degradation. Various other biochemical and functional changes have been noted, including decreased insulin responsiveness and protein synthesis. The model of limb immobilization may also be useful for related studies of muscle adaptation.

Grafting of a Single Donor Myofibre Promotes Hypertrophy in Dystrophic Mouse Muscle

PubMed Central

Boldrin, Luisa; Morgan, Jennifer E.

2013-01-01

Skeletal muscle has a remarkable capability of regeneration following injury. Satellite cells, the principal muscle stem cells, are responsible for this process. However, this regenerative capacity is reduced in muscular dystrophies or in old age: in both these situations, there is a net loss of muscle fibres. Promoting skeletal muscle muscle hypertrophy could therefore have potential applications for treating muscular dystrophies or sarcopenia. Here, we observed that muscles of dystrophic mdx nude host mice that had been acutely injured by myotoxin and grafted with a single myofibre derived from a normal donor mouse exhibited increased muscle area. Transplantation experiments revealed that the hypertrophic effect is mediated by the grafted fibre and does not require either an imposed injury to the host muscle, or the contribution of donor cells to the host muscle. These results suggest the presence of a crucial cross-talk between the donor fibre and the host muscle environment. PMID:23349935

Monitoring muscle optical scattering properties during rigor mortis

NASA Astrophysics Data System (ADS)

Xia, J.; Ranasinghesagara, J.; Ku, C. W.; Yao, G.

2007-09-01

Sarcomere is the fundamental functional unit in skeletal muscle for force generation. In addition, sarcomere structure is also an important factor that affects the eating quality of muscle food, the meat. The sarcomere structure is altered significantly during rigor mortis, which is the critical stage involved in transforming muscle to meat. In this paper, we investigated optical scattering changes during the rigor process in Sternomandibularis muscles. The measured optical scattering parameters were analyzed along with the simultaneously measured passive tension, pH value, and histology analysis. We found that the temporal changes of optical scattering, passive tension, pH value and fiber microstructures were closely correlated during the rigor process. These results suggested that sarcomere structure changes during rigor mortis can be monitored and characterized by optical scattering, which may find practical applications in predicting meat quality.

Spatially localized phosphorous metabolism of skeletal muscle in Duchenne muscular dystrophy patients: 24-month follow-up.

PubMed

Hooijmans, M T; Doorenweerd, N; Baligand, C; Verschuuren, J J G M; Ronen, I; Niks, E H; Webb, A G; Kan, H E

2017-01-01

To assess the changes in phosphodiester (PDE)-levels, detected by 31P magnetic resonance spectroscopy (MRS), over 24-months to determine the potential of PDE as marker for muscle tissue changes in Duchenne Muscular Dystrophy (DMD) patients. Spatially resolved phosphorous datasets were acquired in the right lower leg of 18 DMD patients (range: 5-15.4 years) and 12 age-matched healthy controls (range: 5-14 years) at three time-points (baseline, 12-months, and 24-months) using a 7T MR-System (Philips Achieva). 3-point Dixon images were acquired at 3T (Philips Ingenia) to determine muscle fat fraction. Analyses were done for six muscles that represent different stages of muscle wasting. Differences between groups and time-points were assessed with non-parametric tests with correction for multiple comparisons. Coefficient of variance (CV) were determined for PDE in four healthy adult volunteers in high and low signal-to-noise ratio (SNR) datasets. PDE-levels were significantly higher (two-fold) in DMD patients compared to controls in all analyzed muscles at almost every time point and did not change over the study period. Fat fraction was significantly elevated in all muscles at all time points compared to healthy controls, and increased significantly over time, except in the tibialis posterior muscle. The mean within subject CV for PDE-levels was 4.3% in datasets with high SNR (>10:1) and 5.7% in datasets with low SNR. The stable two-fold increase in PDE-levels found in DMD patients in muscles with different levels of muscle wasting over 2-year time, including DMD patients as young as 5.5 years-old, suggests that PDE-levels may increase very rapidly early in the disease process and remain elevated thereafter. The low CV values in high and low SNR datasets show that PDE-levels can be accurately and reproducibly quantified in all conditions. Our data confirms the great potential of PDE as a marker for muscle tissue changes in DMD patients.

Spatially localized phosphorous metabolism of skeletal muscle in Duchenne muscular dystrophy patients: 24–month follow-up

PubMed Central

Doorenweerd, N.; Baligand, C.; Verschuuren, J. J. G. M.; Ronen, I.; Niks, E. H.; Webb, A. G.; Kan, H. E.

2017-01-01

Objectives To assess the changes in phosphodiester (PDE)-levels, detected by 31P magnetic resonance spectroscopy (MRS), over 24-months to determine the potential of PDE as marker for muscle tissue changes in Duchenne Muscular Dystrophy (DMD) patients. Methods Spatially resolved phosphorous datasets were acquired in the right lower leg of 18 DMD patients (range: 5–15.4 years) and 12 age-matched healthy controls (range: 5–14 years) at three time-points (baseline, 12-months, and 24-months) using a 7T MR-System (Philips Achieva). 3-point Dixon images were acquired at 3T (Philips Ingenia) to determine muscle fat fraction. Analyses were done for six muscles that represent different stages of muscle wasting. Differences between groups and time-points were assessed with non-parametric tests with correction for multiple comparisons. Coefficient of variance (CV) were determined for PDE in four healthy adult volunteers in high and low signal-to-noise ratio (SNR) datasets. Results PDE-levels were significantly higher (two-fold) in DMD patients compared to controls in all analyzed muscles at almost every time point and did not change over the study period. Fat fraction was significantly elevated in all muscles at all time points compared to healthy controls, and increased significantly over time, except in the tibialis posterior muscle. The mean within subject CV for PDE-levels was 4.3% in datasets with high SNR (>10:1) and 5.7% in datasets with low SNR. Discussion and conclusion The stable two-fold increase in PDE-levels found in DMD patients in muscles with different levels of muscle wasting over 2-year time, including DMD patients as young as 5.5 years-old, suggests that PDE-levels may increase very rapidly early in the disease process and remain elevated thereafter. The low CV values in high and low SNR datasets show that PDE-levels can be accurately and reproducibly quantified in all conditions. Our data confirms the great potential of PDE as a marker for muscle tissue changes in DMD patients. PMID:28763477

Petri net-based prediction of therapeutic targets that recover abnormally phosphorylated proteins in muscle atrophy.

PubMed

Jung, Jinmyung; Kwon, Mijin; Bae, Sunghwa; Yim, Soorin; Lee, Doheon

2018-03-05

Muscle atrophy, an involuntary loss of muscle mass, is involved in various diseases and sometimes leads to mortality. However, therapeutics for muscle atrophy thus far have had limited effects. Here, we present a new approach for therapeutic target prediction using Petri net simulation of the status of phosphorylation, with a reasonable assumption that the recovery of abnormally phosphorylated proteins can be a treatment for muscle atrophy. The Petri net model was employed to simulate phosphorylation status in three states, i.e. reference, atrophic and each gene-inhibited state based on the myocyte-specific phosphorylation network. Here, we newly devised a phosphorylation specific Petri net that involves two types of transitions (phosphorylation or de-phosphorylation) and two types of places (activation with or without phosphorylation). Before predicting therapeutic targets, the simulation results in reference and atrophic states were validated by Western blotting experiments detecting five marker proteins, i.e. RELA, SMAD2, SMAD3, FOXO1 and FOXO3. Finally, we determined 37 potential therapeutic targets whose inhibition recovers the phosphorylation status from an atrophic state as indicated by the five validated marker proteins. In the evaluation, we confirmed that the 37 potential targets were enriched for muscle atrophy-related terms such as actin and muscle contraction processes, and they were also significantly overlapping with the genes associated with muscle atrophy reported in the Comparative Toxicogenomics Database (p-value < 0.05). Furthermore, we noticed that they included several proteins that could not be characterized by the shortest path analysis. The three potential targets, i.e. BMPR1B, ROCK, and LEPR, were manually validated with the literature. In this study, we suggest a new approach to predict potential therapeutic targets of muscle atrophy with an analysis of phosphorylation status simulated by Petri net. We generated a list of the potential therapeutic targets whose inhibition recovers abnormally phosphorylated proteins in an atrophic state. They were evaluated by various approaches, such as Western blotting, GO terms, literature, known muscle atrophy-related genes and shortest path analysis. We expect the new proposed strategy to provide an understanding of phosphorylation status in muscle atrophy and to provide assistance towards identifying new therapies.

Regulation of phosphorylase kinase by low concentrations of Ca ions upon muscle contraction: the connection between metabolism and muscle contraction and the connection between muscle physiology and Ca-dependent signal transduction

PubMed Central

OZAWA, Eijiro

2011-01-01

It had long been one of the crucial questions in muscle physiology how glycogenolysis is regulated in connection with muscle contraction, when we found the answer to this question in the last half of the 1960s. By that time, the two principal currents of muscle physiology, namely, the metabolic flow starting from glycogen and the mechanisms of muscle contraction, had already been clarified at the molecular level thanks to our senior researchers. Thus, the final question we had to answer was how to connect these two currents. We found that low concentrations of Ca ions (10−7–10−4 M) released from the sarcoplasmic reticulum for the regulation of muscle contraction simultaneously reversibly activate phosphorylase kinase, the enzyme regulating glycogenolysis. Moreover, we found that adenosine 3′,5′-monophosphate (cyclic AMP), which is already known to activate muscle phosphorylase kinase, is not effective in the absence of such concentrations of Ca ions. Thus, cyclic AMP is not effective by itself alone and only modifies the activation process in the presence of Ca ions (at that time, cyclic AMP-dependent protein kinase had not yet been identified). After a while, it turned out that our works have not only provided the solution to the above problem on muscle physiology, but have also been considered as the first report of Ca-dependent protein phosphorylation, which is one of the central problems in current cell biology. Phosphorylase kinase is the first protein kinase to phosphorylate a protein resulting in the change in the function of the phosphorylated protein, as shown by Krebs and Fischer. Our works further showed that this protein kinase is regulated in a Ca-dependent manner. Accordingly, our works introduced the concept of low concentrations of Ca ions, which were first identified as the regulatory substance of muscle contraction, to the vast field of Ca biology including signal transduction. PMID:21986313

Quantitative phosphoproteomic analysis of porcine muscle within 24 h postmortem.

PubMed

Huang, Honggang; Larsen, Martin R; Palmisano, Giuseppe; Dai, Jie; Lametsch, René

2014-06-25

Protein phosphorylation can regulate most of the important processes in muscle, such as metabolism and contraction. The postmortem (PM) metabolism and rigor mortis have essential effects on meat quality. In order to identify and characterize the protein phosphorylation events involved in meat quality development, a quantitative mass spectrometry-based phosphoproteomic study was performed to analyze the porcine muscle within 24h PM using dimethyl labeling combined with the TiSH phosphopeptide enrichment strategy. In total 305 unique proteins were identified, including 160 phosphoproteins with 784 phosphorylation sites. Among these, 184 phosphorylation sites on 93 proteins had their phosphorylation levels significantly changed. The proteins involved in glucose metabolism and muscle contraction were the two largest clusters of phosphoproteins with significantly changed phosphorylation levels in muscle within 24 h PM. The high phosphorylation level of heat shock proteins (HSPs) in early PM may be an adaptive response to slaughter stress and protect muscle cell from apoptosis, as observed in the serine 84 of HSP27. This work indicated that PM muscle proteins underwent significant changes at the phosphorylation level but were relatively stable at the total protein level, suggesting that protein phosphorylation may have important roles in meat quality development through the regulation of proteins involved in glucose metabolism and muscle contraction, thereby affecting glycolysis and rigor mortis development in PM muscle. The manuscript describes the characterization of postmortem (PM) porcine muscle within 24 h postmortem from the perspective of protein phosphorylation using advanced phosphoproteomic techniques. In the study, the authors employed the dimethyl labeling combined with the TiSH phosphopeptide enrichment and LC-MS/MS strategy. This was the first high-throughput quantitative phosphoproteomic study in PM muscle of farm animals. In the work, both the proteome and phosphoproteome were analyzed, and the large number of identified peptides, phosphopeptides and phosphorylation sites can greatly enrich the current farm animal protein database. The proteins involved in glycometabolism, muscle contraction and heat shock proteins (HSPs) showed significantly changed phosphorylation levels during PM meat development. This work indicated that PM muscle proteins underwent significant changes at phosphorylation level but were relatively stable at the total protein level, suggesting that protein phosphorylation may have important roles in meat development through the regulation of proteins involved in metabolism and muscle contraction, thereby affecting glycolysis and rigor mortis development in PM muscle. The work can promote the understanding of PM muscle metabolism and meat quality development, and be helpful for future meat quality control. Copyright © 2014 Elsevier B.V. All rights reserved.

Home-Based Functional Electrical Stimulation for Long-Term Denervated Human Muscle: History, Basics, Results and Perspectives of the Vienna Rehabilitation Strategy

PubMed Central

Kern, Helmut

2014-01-01

We will here discuss the following points related to Home-based Functional Electrical Stimulation (h-b FES) as treatment for patients with permanently denervated muscles in their legs: 1. Upper (UMN) and lower motor neuron (LMN) damage to the lower spinal cord; 2. Muscle atrophy/hypertrophy versus processes of degeneration, regeneration, and recovery; 3. Recovery of twitch- and tetanic-contractility by h-b FES; 4. Clinical effects of h-b FES using the protocol of the “Vienna School”; 5. Limitations and perspectives. Arguments in favor of using the Vienna protocol include: 1. Increased muscle size in both legs; 2. Improved tetanic force production after 3-5 months of percutaneous stimulation using long stimulus pulses (> 100 msec) of high amplitude (> 80 mAmp), tolerated only in patients with no pain sensibility; 3. Histological and electron microscopic evidence that two years of h-b FES return muscle fibers to a state typical of two weeks denervated muscles with respect to atrophy, disrupted myofibrillar structure, and disorganized Excitation-Contraction Coupling (E-CC) structures; 4. The excitability never recovers to that typical of normal or reinnervated muscles where pulses less than 1 msec in duration and 25 mAmp in intensity excite axons and thereby muscle fibres. It is important to motivate these patients for chronic stimulation throughout life, preferably standing up against the load of the body weight rather than sitting. Only younger and low weight patients can expect to be able to stand-up and do some steps more or less independently. Some patients like to maintain the h-b FES training for decades. Limitations of the procedure are obvious, in part related to the use of multiple, large surface electrodes and the amount of time patients are willing to use for such muscle training. PMID:26913127

Skeletal muscle as an endogenous nitrate reservoir

PubMed Central

Piknova, Barbora; Park, Ji Won; Swanson, Kathryn M.; Dey, Soumyadeep; Noguchi, Constance Tom; Schechter, Alan N

2015-01-01

The nitric oxide synthase (NOS) family of enzymes form nitric oxide (NO) from arginine in the presence of oxygen. At reduced oxygen availability NO is also generated from nitrate in a two step process by bacterial and mammalian molybdopterin proteins, and also directly from nitrite by a variety of five-coordinated ferrous hemoproteins. The mammalian NO cycle also involves direct oxidation of NO to nitrite, and both NO and nitrite to nitrate by oxy-ferrous hemoproteins. The liver and blood are considered the sites of active mammalian NO metabolism and nitrite and nitrate concentrations in the liver and blood of several mammalian species, including human, have been determined. However, the large tissue mass of skeletal muscle had not been generally considered in the analysis of the NO cycle, in spite of its long-known presence of significant levels of active neuronal NOS (nNOS or NOS1). We hypothesized that skeletal muscle participates in the NO cycle and, due to its NO oxidizing heme protein, oxymyoglobin, has high concentrations of nitrate ions. We measured nitrite and nitrate concentrations in rat and mouse leg skeletal muscle and found unusually high concentrations of nitrate but similar levels of nitrite, when compared to the liver. The nitrate reservoir in muscle is easily accessible via the bloodstream and therefore nitrate is available for transport to internal organs where it can be reduced to nitrite and NO. Nitrate levels in skeletal muscle and blood in nNOS−/− mice were dramatically lower when compared with controls, which support further our hypothesis. Although the nitrate reductase activity of xanthine oxidoreductase in muscle is less than that of liver, the residual activity in muscle could be very important in view of its total mass and the high basal level of nitrate. We suggest that skeletal muscle participates in overall NO metabolism, serving as a nitrate reservoir, for direct formation of nitrite and NO, and for determining levels of nitrate in other organs. PMID:25727730

Muscle wasting in myotonic dystrophies: a model of premature aging.

PubMed

Mateos-Aierdi, Alba Judith; Goicoechea, Maria; Aiastui, Ana; Fernández-Torrón, Roberto; Garcia-Puga, Mikel; Matheu, Ander; López de Munain, Adolfo

2015-01-01

Myotonic dystrophy type 1 (DM1 or Steinert's disease) and type 2 (DM2) are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, while other clinical manifestations such as cardiomyopathy, insulin resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTG) triplet expansion in the 3' untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9 (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and (CCUG)n-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular degeneration seen in DM patients, highlighting the similarities found with muscle aging.

The Relationship between Muscle Fiber Type-Specific PGC-1α Content and Mitochondrial Content Varies between Rodent Models and Humans

PubMed Central

Gouspillou, Gilles; Sgarioto, Nicolas; Norris, Brandon; Barbat-Artigas, Sébastien; Aubertin-Leheudre, Mylène; Morais, Jose A.; Burelle, Yan; Taivassalo, Tanja; Hepple, Russell T.

2014-01-01

PGC-1α regulates critical processes in muscle physiology, including mitochondrial biogenesis, lipid metabolism and angiogenesis. Furthermore, PGC-1α was suggested as an important regulator of fiber type determination. However, whether a muscle fiber type-specific PGC-1α content exists, whether PGC-1α content relates to basal levels of mitochondrial content, and whether such relationships are preserved between humans and classically used rodent models are all questions that have been either poorly addressed or never investigated. To address these issues, we investigated the fiber type-specific content of PGC-1α and its relationship to basal mitochondrial content in mouse, rat and human muscles using in situ immunolabeling and histochemical methods on muscle serial cross-sections. Whereas type IIa fibers exhibited the highest PGC-1α in all three species, other fiber types displayed a hierarchy of type IIx>I>IIb in mouse, type I = IIx> IIb in rat, and type IIx>I in human. In terms of mitochondrial content, we observed a hierarchy of IIa>IIx>I>IIb in mouse, IIa >I>IIx> IIb in rat, and I>IIa> IIx in human skeletal muscle. We also found in rat skeletal muscle that type I fibers displayed the highest capillarization followed by type IIa >IIx>IIb. Finally, we found in human skeletal muscle that type I fibers display the highest lipid content, followed by type IIa>IIx. Altogether, our results reveal that (i) the fiber type-specific PGC-1α and mitochondrial contents were only matched in mouse, (ii) the patterns of PGC-1α and mitochondrial contents observed in mice and rats do not correspond to that seen in humans in several respects, and (iii) the classical phenotypes thought to be regulated by PGC-1α do not vary exclusively as a function of PGC-1α content in rat and human muscles. PMID:25121500

Importance and challenges of measuring intrinsic foot muscle strength

PubMed Central

2012-01-01

Background Intrinsic foot muscle weakness has been implicated in a range of foot deformities and disorders. However, to establish a relationship between intrinsic muscle weakness and foot pathology, an objective measure of intrinsic muscle strength is needed. The aim of this review was to provide an overview of the anatomy and role of intrinsic foot muscles, implications of intrinsic weakness and evaluate the different methods used to measure intrinsic foot muscle strength. Method Literature was sourced from database searches of MEDLINE, PubMed, SCOPUS, Cochrane Library, PEDro and CINAHL up to June 2012. Results There is no widely accepted method of measuring intrinsic foot muscle strength. Methods to estimate toe flexor muscle strength include the paper grip test, plantar pressure, toe dynamometry, and the intrinsic positive test. Hand-held dynamometry has excellent interrater and intrarater reliability and limits toe curling, which is an action hypothesised to activate extrinsic toe flexor muscles. However, it is unclear whether any method can actually isolate intrinsic muscle strength. Also most methods measure only toe flexor strength and other actions such as toe extension and abduction have not been adequately assessed. Indirect methods to investigate intrinsic muscle structure and performance include CT, ultrasonography, MRI, EMG, and muscle biopsy. Indirect methods often discriminate between intrinsic and extrinsic muscles, but lack the ability to measure muscle force. Conclusions There are many challenges to accurately measure intrinsic muscle strength in isolation. Most studies have measured toe flexor strength as a surrogate measure of intrinsic muscle strength. Hand-held dynamometry appears to be a promising method of estimating intrinsic muscle strength. However, the contribution of extrinsic muscles cannot be excluded from toe flexor strength measurement. Future research should clarify the relative contribution of intrinsic and extrinsic muscles during intrinsic foot muscle strength testing. PMID:23181771

Finite Element Modeling Used to Study Stress Distribution on the Foot

NASA Technical Reports Server (NTRS)

Morales, Nelson; Davis, Brian; Tajaddini, Azita

2004-01-01

A method to study the stress distribution inside the forefoot during walking was developed at the Cleveland Clinic Foundation by a researcher from the NASA Glenn Research Center. In this method, a semiautomated process was outlined to create a three-dimensional, patient-specific, finite element model (FEM) of the forefoot using magnetic resonance images (MRI). The images were processed in Matlab using the k-nearest neighbor (k-NN) classification algorithm and Sobel edge detection to separate the different tissue types: bone, skin, fat, and muscle. This information was used to create curves and surfaces that were exported to an FEM preprocessor known as Truegrid. In Truegrid, eight-noded or brick elements were created by using surface mapping. The FEM was processed and postprocessed in Abaqus. Material properties of the models were obtained from past experiments such as fat pad confined compression, skin axial and biaxial tests, muscle in vivo compressive tests, and reference literature (bone properties). Nonlinear (hyperelastic) material models were used for the skin (epidermis and dermis), fat, and muscles; and a linear elastic model was used for the bones. Muscle activation during walking yielded uncertainties in the muscle material model since contracted muscles are stiffer than relaxed muscles. These uncertainties were resolved by performing a sensitivity analysis of the muscle material properties. The original properties were multiplied by arbitrary factors of 2, 3, 0.5, and 0.33. The strain and stress distributions, as well as the locations of peak values, were similar in all cases. The peak contact pressure P obtained for each case varied with respect to the applied factor f as follows:

Development of a bedrest muscle stress apparatus

NASA Technical Reports Server (NTRS)

Booher, C. R.; Hooper, S. L.; Setzer, D. N.

1979-01-01

In attempting further to define the deleterious effects of spaceflight on the human body, measurement systems and techniques were devised to determine the loss of skeletal muscle strength and tone as a result of spaceflight exposure. In order to determine how the muscle degradation process progresses with time during nonuse, a system for measuring muscle stress during bedrest was developed. The Bedrest Muscle Stress Apparatus is configured to slip snugly over the foot board of a standard hospital bed. Data collected with this device correlated well with pre- and post-bedrest data collected with the original skeletal muscle stress apparatus.

Loss of miR-29 in Myoblasts Contributes to Dystrophic Muscle Pathogenesis

PubMed Central

Wang, Lijun; Zhou, Liang; Jiang, Peiyong; Lu, Leina; Chen, Xiaona; Lan, Huiyao; Guttridge, Denis C; Sun, Hao; Wang, Huating

2012-01-01

microRNAs (miRNAs) are noncoding RNAs that regulate gene expression in post-transcriptional fashion, and emerging studies support their importance in a multitude of physiological and pathological processes. Here, we describe the regulation and function of miR-29 in Duchenne muscular dystrophy (DMD) and its potential use as therapeutic target. Our results demonstrate that miR-29 expression is downregulated in dystrophic muscles of mdx mice, a model of DMD. Restoration of its expression by intramuscular and intravenous injection improved dystrophy pathology by both promoting regeneration and inhibiting fibrogenesis. Mechanistic studies revealed that loss of miR-29 in muscle precursor cells (myoblasts) promotes their transdifferentiation into myofibroblasts through targeting extracellular molecules including collagens and microfibrillar-associated protein 5 (Mfap5). We further demonstrated that miR-29 is under negative regulation by transforming growth factor-β (TGF-β) signaling. Together, these results not only identify TGF-β–miR-29 as a novel regulatory axis during myoblasts conversion into myofibroblasts which constitutes a novel contributing route to muscle fibrogenesis of DMD but also implicate miR-29 replacement therapy as a promising treatment approach for DMD. PMID:22434133

Modulation of mTOR signaling as a strategy for the treatment of Pompe disease.

PubMed

Lim, Jeong-A; Li, Lishu; Shirihai, Orian S; Trudeau, Kyle M; Puertollano, Rosa; Raben, Nina

2017-03-01

Mechanistic target of rapamycin (mTOR) coordinates biosynthetic and catabolic processes in response to multiple extracellular and intracellular signals including growth factors and nutrients. This serine/threonine kinase has long been known as a critical regulator of muscle mass. The recent finding that the decision regarding its activation/inactivation takes place at the lysosome undeniably brings mTOR into the field of lysosomal storage diseases. In this study, we have examined the involvement of the mTOR pathway in the pathophysiology of a severe muscle wasting condition, Pompe disease, caused by excessive accumulation of lysosomal glycogen. Here, we report the dysregulation of mTOR signaling in the diseased muscle cells, and we focus on potential sites for therapeutic intervention. Reactivation of mTOR in the whole muscle of Pompe mice by TSC knockdown resulted in the reversal of atrophy and a striking removal of autophagic buildup. Of particular interest, we found that the aberrant mTOR signaling can be reversed by arginine. This finding can be translated into the clinic and may become a paradigm for targeted therapy in lysosomal, metabolic, and neuromuscular diseases. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Systemic bioinformatics analysis of skeletal muscle gene expression profiles of sepsis

PubMed Central

Yang, Fang; Wang, Yumei

2018-01-01

Sepsis is a type of systemic inflammatory response syndrome with high morbidity and mortality. Skeletal muscle dysfunction is one of the major complications of sepsis that may also influence the outcome of sepsis. The aim of the present study was to explore and identify potential mechanisms and therapeutic targets of sepsis. Systemic bioinformatics analysis of skeletal muscle gene expression profiles from the Gene Expression Omnibus was performed. Differentially expressed genes (DEGs) in samples from patients with sepsis and control samples were screened out using the limma package. Differential co-expression and coregulation (DCE and DCR, respectively) analysis was performed based on the Differential Co-expression Analysis package to identify differences in gene co-expression and coregulation patterns between the control and sepsis groups. Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways of DEGs were identified using the Database for Annotation, Visualization and Integrated Discovery, and inflammatory, cancer and skeletal muscle development-associated biological processes and pathways were identified. DCE and DCR analysis revealed several potential therapeutic targets for sepsis, including genes and transcription factors. The results of the present study may provide a basis for the development of novel therapeutic targets and treatment methods for sepsis. PMID:29805480

Long-Term Therapy With Omega-3 Ameliorates Myonecrosis and Benefits Skeletal Muscle Regeneration in Mdx Mice.

PubMed

Apolinário, Leticia Montanholi; De Carvalho, Samara Camaçari; Santo Neto, Humberto; Marques, Maria Julia

2015-09-01

In Duchenne muscle dystrophy (DMD) and in the mdx mouse model of DMD, a lack of dystrophin leads to myonecrosis and cardiorespiratory failure. Several lines of evidence suggest a detrimental role of the inflammatory process in the dystrophic process. Previously, we demonstrated that short-term therapy with eicosapentaenoic acid (EPA), at early stages of disease, ameliorated dystrophy progression in the mdx mouse. In the present study, we evaluated the effects of a long-term therapy with omega-3 later in dystrophy progression. Three-month-old mdx mice received omega-3 (300 mg/kg) or vehicle by gavage for 5 months. The quadriceps and diaphragm muscles were removed and processed for histopathology and Western blot. Long-term therapy with omega-3 increased the regulatory protein MyoD and muscle regeneration and reduced markers of inflammation (TNF-α and NF-kB) in both muscles studied. The present study supports the long-term use of omega-3 at later stages of dystrophy as a promising option to be investigated in DMD clinical trials. © 2015 Wiley Periodicals, Inc.

Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model.

PubMed

Isaacs, Jonathan; Feher, Joseph; Shall, Mary; Vota, Scott; Fox, Michael A; Mallu, Satya; Razavi, Ashkon; Friebe, Ilvy; Shah, Sagar; Spita, Nathalie

2013-10-01

Suboptimal recovery following repair of major peripheral nerves has been partially attributed to denervation atrophy. Administration of anabolic steroids in conjunction with neurotization may improve functional recovery of chronically denervated muscle. The purpose of this study was to evaluate the effect of the administration of nandrolone on muscle recovery following prolonged denervation in a rat model. Eight groups of female Sprague-Dawley rats (15 rats per group, 120 in all) were divided into 3- or 6-month denervated hind limb and sham surgery groups and, then, nandrolone treatment groups and sham treatment groups. Evaluation of treatment effects included nerve conduction, force of contraction, comparative morphology, histology (of muscle fibers), protein electrophoresis (for muscle fiber grouping), and immunohistochemical evaluation. Although a positive trend was noted, neither reinnervated nor normal muscle showed a statistically significant increase in peak muscle force following nandrolone treatment. Indirect measures, including muscle mass (weight and diameter), muscle cell size, muscle fiber type, and satellite cell counts, all failed to support significant anabolic effect. There does not seem to be a functional benefit from nandrolone treatment following reinnervation of either mild or moderately atrophic muscle (related to prolonged denervation) in a rodent model.

Modulatory effect of gastric pentadecapeptide BPC 157 on angiogenesis in muscle and tendon healing.

PubMed

Brcic, L; Brcic, I; Staresinic, M; Novinscak, T; Sikiric, P; Seiwerth, S

2009-12-01

Angiogenesis is a natural and complex process controlled by angiogenic and angiostatic molecules, with a central role in healing process. One of the most important modulating factors in angiogenesis is the vascular endothelial growth factor (VEGF). Pentadecapeptide BPC 157 promotes healing demonstrating particular angiogenic/angiomodulatory potential. We correlated the angiogenic effect of BPC 157 with VEGF expression using in vitro (cell culture) and in vivo (crushed muscle and transected muscle and tendon) models. Results revealed that there is no direct angiogenic effect of BPC 157 on cell cultures. On the other hand, immunohistochemical analysis of muscle and tendon healing using VEGF, CD34 and FVIII antibodies showed adequately modulated angiogenesis in BPC 157 treated animals, resulting in a more adequate healing. Therefore the angiogenic potential of BPC 157 seems to be closely related to the healing process in vivo with BPC 157 stimulating angiogenesis by up-regulating VEGF expression.

Microbiological aspects of polyphosphate injection in the processing and chill storage of poultry.

PubMed Central

Mead, G. C.; Adams, B. W.

1979-01-01

During commercial processing of broiler chickens, injection of polyphosphate (Puron 604 or 6040) resulted in microorganisms being added to the deep breast muscle. The level of contamination was related to the microbiological condition of the injection solution. Injection of polyphosphate had no effect on the shelf-life of fresh chilled carcasses held at 1 degree of 10 degrees C but changes were observed in the growth rate of microorganisms in the deep muscle and in the composition of the muscle microflora following storage. Cross-contamination of carcasses and the transfer of organisms from the skin to the deep muscle during injection was demonstrated with a marker strain of Clostridium perfringens. However, both processes were influenced by the number of marker organisms applied initially to the skin. The above findings are discussed in relation to the possible behaviour of any food poisoning bacteria present. PMID:216743

Skeletal muscle mechanics, energetics and plasticity.

PubMed

Lieber, Richard L; Roberts, Thomas J; Blemker, Silvia S; Lee, Sabrina S M; Herzog, Walter

2017-10-23

The following papers by Richard Lieber (Skeletal Muscle as an Actuator), Thomas Roberts (Elastic Mechanisms and Muscle Function), Silvia Blemker (Skeletal Muscle has a Mind of its Own: a Computational Framework to Model the Complex Process of Muscle Adaptation) and Sabrina Lee (Muscle Properties of Spastic Muscle (Stroke and CP) are summaries of their representative contributions for the session on skeletal muscle mechanics, energetics and plasticity at the 2016 Biomechanics and Neural Control of Movement Conference (BANCOM 2016). Dr. Lieber revisits the topic of sarcomere length as a fundamental property of skeletal muscle contraction. Specifically, problems associated with sarcomere length non-uniformity and the role of sarcomerogenesis in diseases such as cerebral palsy are critically discussed. Dr. Roberts then makes us aware of the (often neglected) role of the passive tissues in muscles and discusses the properties of parallel elasticity and series elasticity, and their role in muscle function. Specifically, he identifies the merits of analyzing muscle deformations in three dimensions (rather than just two), because of the potential decoupling of the parallel elastic element length from the contractile element length, and reviews the associated implications for the architectural gear ratio of skeletal muscle contraction. Dr. Blemker then tackles muscle adaptation using a novel way of looking at adaptive processes and what might drive adaptation. She argues that cells do not have pre-programmed behaviors that are controlled by the nervous system. Rather, the adaptive responses of muscle fibers are determined by sub-cellular signaling pathways that are affected by mechanical and biochemical stimuli; an exciting framework with lots of potential. Finally, Dr. Lee takes on the challenging task of determining human muscle properties in vivo. She identifies the dilemma of how we can demonstrate the effectiveness of a treatment, specifically in cases of muscle spasticity following stroke or in children with cerebral palsy. She then discusses the merits of ultrasound based elastography, and the clinical possibilities this technique might hold. Overall, we are treated to a vast array of basic and clinical problems in skeletal muscle mechanics and physiology, with some solutions, and many suggestions for future research.

Musculoskeletal Modeling Component of the NASA Digital Astronaut Project

NASA Technical Reports Server (NTRS)

Lewandowski, B. E.; Pennline, J. A.; Stalker, A. R.; Mulugeta, L.; Myers, J. G.

2011-01-01

The NASA Digital Astronaut Project s (DAP) objective is to provide computational tools that support research of the physiological response to low gravity environments and analyses of how changes cause health and safety risks to the astronauts and to the success of the mission. The spaceflight risk associated with muscle atrophy is impaired performance due to reduced muscle mass, strength and endurance. Risks of early onset of osteoporosis and bone fracture are among the spaceflight risks associated with loss of bone mineral density. METHODS: Tools under development include a neuromuscular model, a biomechanical model and a bone remodeling model. The neuromuscular model will include models of neuromuscular drive, muscle atrophy, fiber morphology and metabolic processes as a function of time in space. Human movement will be modeled with the biomechanical model, using muscle and bone model parameters at various states. The bone remodeling model will allow analysis of bone turnover, loss and adaptation. A comprehensive trade study was completed to identify the current state of the art in musculoskeletal modeling. The DAP musculoskeletal models will be developed using a combination of existing commercial software and academic research codes identified in the study, which will be modified for use in human spaceflight research. These individual models are highly dependent upon each other and will be integrated together once they reach sufficient levels of maturity. ANALYSES: The analyses performed with these models will include comparison of different countermeasure exercises for optimizing effectiveness and comparison of task requirements and the state of strength and endurance of a crew member at a particular time in a mission. DISCUSSION: The DAP musculoskeletal model has the potential to complement research conducted on spaceflight induced changes to the musculoskeletal system. It can help with hypothesis formation, identification of causative mechanisms and supplementing small data samples.

Adaptive Skeletal Muscle Action Requires Anticipation and “Conscious Broadcasting”

PubMed Central

Poehlman, T. Andrew; Jantz, Tiffany K.; Morsella, Ezequiel

2012-01-01

Historically, the conscious and anticipatory processes involved in voluntary action have been associated with the loftiest heights of nervous function. Concepts like mental time travel, “theory of mind,” and the formation of “the self” have been at the center of many attempts to determine the purpose of consciousness. Eventually, more reductionistic accounts of consciousness emerged, proposing rather that conscious states play a much more basic role in nervous function. Though the widely held integration consensus proposes that conscious states integrate information-processing structures and events that would otherwise be independent, Supramodular Interaction Theory (SIT) argues that conscious states are necessary for the integration of only certain kinds of information. As revealed in this selective review, this integration is related to what is casually referred to as “voluntary” action, which is intimately related to the skeletal muscle output system. Through a peculiar form of broadcasting, conscious integration often controls and guides action via “ideomotor” mechanisms, where anticipatory processes play a central role. Our selective review covers evidence (including findings from anesthesia research) for the integration consensus, SIT, and ideomotor theory. PMID:23264766

Clonal analysis reveals a common origin between nonsomite-derived neck muscles and heart myocardium

PubMed Central

Lescroart, Fabienne; Hamou, Wissam; Francou, Alexandre; Théveniau-Ruissy, Magali; Kelly, Robert G.; Buckingham, Margaret

2015-01-01

Neck muscles constitute a transition zone between somite-derived skeletal muscles of the trunk and limbs, and muscles of the head, which derive from cranial mesoderm. The trapezius and sternocleidomastoid neck muscles are formed from progenitor cells that have expressed markers of cranial pharyngeal mesoderm, whereas other muscles in the neck arise from Pax3-expressing cells in the somites. Mef2c-AHF-Cre genetic tracing experiments and Tbx1 mutant analysis show that nonsomitic neck muscles share a gene regulatory network with cardiac progenitor cells in pharyngeal mesoderm of the second heart field (SHF) and branchial arch-derived head muscles. Retrospective clonal analysis shows that this group of neck muscles includes laryngeal muscles and a component of the splenius muscle, of mixed somitic and nonsomitic origin. We demonstrate that the trapezius muscle group is clonally related to myocardium at the venous pole of the heart, which derives from the posterior SHF. The left clonal sublineage includes myocardium of the pulmonary trunk at the arterial pole of the heart. Although muscles derived from the first and second branchial arches also share a clonal relationship with different SHF-derived parts of the heart, neck muscles are clonally distinct from these muscles and define a third clonal population of common skeletal and cardiac muscle progenitor cells within cardiopharyngeal mesoderm. By linking neck muscle and heart development, our findings highlight the importance of cardiopharyngeal mesoderm in the evolution of the vertebrate heart and neck and in the pathophysiology of human congenital disease. PMID:25605943

Clonal analysis reveals a common origin between nonsomite-derived neck muscles and heart myocardium.

PubMed

Lescroart, Fabienne; Hamou, Wissam; Francou, Alexandre; Théveniau-Ruissy, Magali; Kelly, Robert G; Buckingham, Margaret

2015-02-03

Neck muscles constitute a transition zone between somite-derived skeletal muscles of the trunk and limbs, and muscles of the head, which derive from cranial mesoderm. The trapezius and sternocleidomastoid neck muscles are formed from progenitor cells that have expressed markers of cranial pharyngeal mesoderm, whereas other muscles in the neck arise from Pax3-expressing cells in the somites. Mef2c-AHF-Cre genetic tracing experiments and Tbx1 mutant analysis show that nonsomitic neck muscles share a gene regulatory network with cardiac progenitor cells in pharyngeal mesoderm of the second heart field (SHF) and branchial arch-derived head muscles. Retrospective clonal analysis shows that this group of neck muscles includes laryngeal muscles and a component of the splenius muscle, of mixed somitic and nonsomitic origin. We demonstrate that the trapezius muscle group is clonally related to myocardium at the venous pole of the heart, which derives from the posterior SHF. The left clonal sublineage includes myocardium of the pulmonary trunk at the arterial pole of the heart. Although muscles derived from the first and second branchial arches also share a clonal relationship with different SHF-derived parts of the heart, neck muscles are clonally distinct from these muscles and define a third clonal population of common skeletal and cardiac muscle progenitor cells within cardiopharyngeal mesoderm. By linking neck muscle and heart development, our findings highlight the importance of cardiopharyngeal mesoderm in the evolution of the vertebrate heart and neck and in the pathophysiology of human congenital disease.

DJ-1 links muscle ROS production with metabolic reprogramming and systemic energy homeostasis in mice.

PubMed

Shi, Sally Yu; Lu, Shun-Yan; Sivasubramaniyam, Tharini; Revelo, Xavier S; Cai, Erica P; Luk, Cynthia T; Schroer, Stephanie A; Patel, Prital; Kim, Raymond H; Bombardier, Eric; Quadrilatero, Joe; Tupling, A Russell; Mak, Tak W; Winer, Daniel A; Woo, Minna

2015-06-16

Reactive oxygen species (ROS) have been linked to a wide variety of pathologies, including obesity and diabetes, but ROS also act as endogenous signalling molecules, regulating numerous biological processes. DJ-1 is one of the most evolutionarily conserved proteins across species, and mutations in DJ-1 have been linked to some cases of Parkinson's disease. Here we show that DJ-1 maintains cellular metabolic homeostasis via modulating ROS levels in murine skeletal muscles, revealing a role of DJ-1 in maintaining efficient fuel utilization. We demonstrate that, in the absence of DJ-1, ROS uncouple mitochondrial respiration and activate AMP-activated protein kinase, which triggers Warburg-like metabolic reprogramming in muscle cells. Accordingly, DJ-1 knockout mice exhibit higher energy expenditure and are protected from obesity, insulin resistance and diabetes in the setting of fuel surplus. Our data suggest that promoting mitochondrial uncoupling may be a potential strategy for the treatment of obesity-associated metabolic disorders.

The importance of ATP-related compounds for the freshness and flavor of post-mortem fish and shellfish muscle: A review.

PubMed

Hong, Hui; Regenstein, Joe M; Luo, Yongkang

2017-06-13

ATP degradation is one of the most important biochemical changes in the post-mortem muscle of fish and shellfish. This process has long been recognized as an accurate way to evaluate freshness of fish and shellfish product. This review updates and condenses the overall history and recent advances in understanding the role of ATP-related compounds in post-mortem fish and shellfish muscle including a discussion of key analytical methods, their use as a freshness indicator, their roles in flavor enhancement, the factors affecting their transitions, and the possible mechanisms responsible for their impact on flavor and freshness. Moreover, some challenges and future directions for research regarding ATP-related compounds in fish and shellfish flavor and freshness are presented. With increasing consumer demands for fresh products with extended shelf life, understanding the relationships between ATP-related compounds and their involvement in the freshness and umami taste is a prerequisite for assuring the high quality of fish and shellfish.

Clinical management of chronic obstructive pulmonary disease patients with muscle dysfunction

PubMed Central

Casadevall, Carme; Pascual, Sergi; Orozco-Levi, Mauricio; Barreiro, Esther

2016-01-01

Muscle dysfunction is frequently observed in chronic obstructive pulmonary disease (COPD) patients, contributing to their exercise limitation and a worsening prognosis. The main factor leading to limb muscle dysfunction is deconditioning, whereas respiratory muscle dysfunction is mostly the result of pulmonary hyperinflation. However, both limb and respiratory muscles are also influenced by other negative factors, including smoking, systemic inflammation, nutritional abnormalities, exacerbations and some drugs. Limb muscle weakness is generally diagnosed through voluntary isometric maneuvers such as handgrip or quadriceps muscle contraction (dynamometry); while respiratory muscle loss of strength is usually recognized through a decrease in maximal static pressures measured at the mouth. Both types of measurements have validated reference values. Respiratory muscle strength can also be evaluated determining esophageal, gastric and transdiaphragmatic maximal pressures although there is a lack of widely accepted reference equations. Non-volitional maneuvers, obtained through electrical or magnetic stimulation, can be employed in patients unable to cooperate. Muscle endurance can also be assessed, generally using repeated submaximal maneuvers until exhaustion, but no validated reference values are available yet. The treatment of muscle dysfunction is multidimensional and includes improvement in lifestyle habits (smoking abstinence, healthy diet and a good level of physical activity, preferably outside), nutritional measures (diet supplements and occasionally, anabolic drugs), and different modalities of general and muscle training. PMID:28066619

Associations between muscle structure and contractile performance in seniors.

PubMed

Randhawa, Avleen; Wakeling, James M

2013-07-01

Changes in muscle structure due to aging occur in a process known as sarcopenia. These changes can alter muscle mechanics during contraction that may limit mobility in seniors. The purpose of this study was to investigate the effect of sarcopenia on muscle fascicle length, pennation and belly thickness in a contracting muscle during isokinetic movements. Fascicles within a pennate muscle shorten at a slower velocity than that of the muscle belly, in a process called belly gearing. Belly gearing may be affected by atrophy and so was also tested in these seniors. The gastrocnemii were tested using ultrasound from 10 young adults (20-40 years) and 9 seniors (70-85 years). The muscle structure was imaged during standing and maximal plantarflexion at four constant velocities on a dynamometer and torque, position and time were recorded during contractions. The muscle belly thickness and pennation in seniors were significantly lower than young adults during standing. Belly thickness, changes in pennation, the belly gearing, ankle torque and power output were all significantly lower in seniors during plantarflexion contractions of the medial gastrocnemius (MG) and lateral gastrocnemius (LG). The higher pennation observed in young adults is commonly associated with increased fascicle rotations during contraction causing an increased belly gearing. The decreased fascicle rotations in seniors resulted in reduced belly gearing but the size of this effect did not match the loss in strength or power from the muscles. Copyright © 2013 Elsevier Ltd. All rights reserved.

Coordinated Development of Muscles and Tendon-Like Structures: Early Interactions in the Drosophila Leg.

PubMed

Soler, Cedric; Laddada, Lilia; Jagla, Krzysztof

2016-01-01

The formation of the musculoskeletal system is a remarkable example of tissue assembly. In both vertebrates and invertebrates, precise connectivity between muscles and skeleton (or exoskeleton) via tendons or equivalent structures is fundamental for movement and stability of the body. The molecular and cellular processes underpinning muscle formation are well-established and significant advances have been made in understanding tendon development. However, the mechanisms contributing to proper connection between these two tissues have received less attention. Observations of coordinated development of tendons and muscles suggest these tissues may interact during the different steps in their development. There is growing evidence that, depending on animal model and muscle type, these interactions can take place from progenitor induction to the final step of the formation of the musculoskeletal system. Here, we briefly review and compare the mechanisms behind muscle and tendon interaction throughout the development of vertebrates and Drosophila before going on to discuss our recent findings on the coordinated development of muscles and tendon-like structures in Drosophila leg. By altering apodeme formation (the functional Drosophila equivalent of tendons in vertebrates) during the early steps of leg development, we affect the spatial localization of subsequent myoblasts. These findings provide the first evidence of the developmental impact of early interactions between muscle and tendon-like precursors, and confirm the appendicular Drosophila muscle system as a valuable model for studying these processes.

Coordinated Development of Muscles and Tendon-Like Structures: Early Interactions in the Drosophila Leg

PubMed Central

Soler, Cedric; Laddada, Lilia; Jagla, Krzysztof

2016-01-01

The formation of the musculoskeletal system is a remarkable example of tissue assembly. In both vertebrates and invertebrates, precise connectivity between muscles and skeleton (or exoskeleton) via tendons or equivalent structures is fundamental for movement and stability of the body. The molecular and cellular processes underpinning muscle formation are well-established and significant advances have been made in understanding tendon development. However, the mechanisms contributing to proper connection between these two tissues have received less attention. Observations of coordinated development of tendons and muscles suggest these tissues may interact during the different steps in their development. There is growing evidence that, depending on animal model and muscle type, these interactions can take place from progenitor induction to the final step of the formation of the musculoskeletal system. Here, we briefly review and compare the mechanisms behind muscle and tendon interaction throughout the development of vertebrates and Drosophila before going on to discuss our recent findings on the coordinated development of muscles and tendon-like structures in Drosophila leg. By altering apodeme formation (the functional Drosophila equivalent of tendons in vertebrates) during the early steps of leg development, we affect the spatial localization of subsequent myoblasts. These findings provide the first evidence of the developmental impact of early interactions between muscle and tendon-like precursors, and confirm the appendicular Drosophila muscle system as a valuable model for studying these processes. PMID:26869938

Reference values for muscle strength: a systematic review with a descriptive meta-analysis.

PubMed

Benfica, Poliana do Amaral; Aguiar, Larissa Tavares; Brito, Sherindan Ayessa Ferreira de; Bernardino, Luane Helena Nunes; Teixeira-Salmela, Luci Fuscaldi; Faria, Christina Danielli Coelho de Morais

2018-05-03

Muscle strength is an important component of health. To describe and evaluate the studies which have established the reference values for muscle strength on healthy individuals and to synthesize these values with a descriptive meta-analysis approach. A systematic review was performed in MEDLINE, LILACS, and SciELO databases. Studies that investigated the reference values for muscle strength of two or more appendicular/axial muscle groups of health individuals were included. Methodological quality, including risk of bias was assessed by the QUADAS-2. Data extracted included: country of the study, sample size, population characteristics, equipment/method used, and muscle groups evaluated. Of the 414 studies identified, 46 were included. Most of the studies had adequate methodological quality. Included studies evaluated: appendicular (80.4%) and axial (36.9%) muscles; adults (78.3%), elderly (58.7%), adolescents (43.5%), children (23.9%); isometric (91.3%) and isokinetic (17.4%) strength. Six studies (13%) with similar procedures were synthesized with meta-analysis. Generally, the coefficient of variation values that resulted from the meta-analysis ranged from 20.1% to 30% and were similar to those reported by the original studies. The meta-analysis synthesized the reference values of isometric strength of 14 muscle groups of the dominant/non-dominant sides of the upper/lower limbs of adults/elderly from developed countries, using dynamometers/myometer. Most of the included studies had adequate methodological quality. The meta-analysis provided reference values for the isometric strength of 14 appendicular muscle groups of the dominant/non-dominant sides, measured with dynamometers/myometers, of men/women, of adults/elderly. These data may be used to interpret the results of the evaluations and establish appropriate treatment goals. Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Exercise Promotes Healthy Aging of Skeletal Muscle.

PubMed

Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

2016-06-14

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. Copyright © 2016 Elsevier Inc. All rights reserved.

Ultrasound monitoring of shortwave diathermic treatment of gastrocnemius strain in a dog.

PubMed

Lideo, Luca; Milan, Roberto

2013-10-24

Rupture of the medial head of the gastrocnemius muscle occurs when the muscle is overstretched by dorsiflexion of the ankle with the knee in full extension. Muscle ultrasound (US) is a convenient diagnostic imaging technique for visualizing normal and pathological muscle tissue as it is a non-invasive real-time examination. Muscle US can also be used in the follow-up of patients with neuromuscular disorders. The aim of this paper is to describe US monitoring of the rehabilitation process in a dog undergoing diathermy treatment (TECAR) due to rupture of the proximal medial head of the gastrocnemius muscle and to show the changes in US appearance of the muscle before, during and after rehabilitation.

Orofacial Muscle Activity of Children Who Stutter: A Preliminary Study.

ERIC Educational Resources Information Center

Kelly, Ellen M.; And Others

1995-01-01

This preliminary investigation of stuttering development and maturation of speech motor processes recorded the electromyographic activity of the orofacial muscles of nine children who stuttered. Results suggest that the emergence of tremor-like instabilities in the speech motor processes of stuttering children may coincide with aspects of general…

Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

PubMed

Huard, J; Mu, X; Lu, A

2016-08-01

Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Sublethal effect of copper toxicity against histopathological changes in the spiny lobster, Panulirus homarus (Linnaeus, 1758).

PubMed

Maharajan, A; Rajalakshmi, S; Vijayakumaran, M; Kumarasamy, P

2012-02-01

The tissue damage induced by various organic pollutants in aquatic animals is well documented, but there is a dearth of information relating to the histological alterations induced by copper in the spiny lobster. In the present study, intermoult juveniles of the spiny lobster Panulirus homarus (average weight 150-200 g) were exposed to two sublethal concentrations of the copper (9.55 and 19.1 μg/l) for a period of 28 days. The muscle, hepatopancreas, midgut, gills, thoracic ganglion and heart of the lobsters were then dissected out and processed for light microscopic studies. Exposure to copper was found to result in several alterations in the histoarchitecture of the muscle, hepatopancreas, midgut, gills, thoracic ganglion and heart of P. homarus. The alterations included disruption and congestion of muscle bundle in muscle tissue; blackened haemocytes; distended lumen and F cell; necrosis of the tubules of the hepatopancreas; disarrangement of circular muscle of the midgut; accumulation of haemocytes in the haemocoelic space; swelling and fusion of lamellae; abnormal gill tips; hyperplastic, necrotic, and blackened secondary gill lamellae of the gills; damaged neurosecretory cell and sensory and motor fibre; necrotic of the thoracic ganglion; dispersedly arranged muscle bands; clumped satellite cells and nucleus of the heart. The results obtained suggest that the muscle, hepatopancreas, midgut, gills, thoracic ganglion and heart of lobsters exposed to copper were structurally altered. Such alterations could affect vital physiological functions, such as absorption, storage and secretion of the hepatopancreas, digestion of gut and respiration, osmotic and ionic regulations of the gills, which in turn could ultimately affect the survival and growth of P. homarus. Thus, all possible remedial measures should be adopted to prevent the occurrence of copper contamination in the aquatic environment.

Skeletal muscle morphology and contractile function in relation to muscle denervation in diabetic neuropathy

PubMed Central

Major, Brendan; Kimpinski, Kurt; Doherty, Timothy J.; Rice, Charles L.

2013-01-01

The objective of the study was to assess the effects of diabetic polyneuropathy (DPN) on muscle contractile properties in humans, and how these changes are related to alterations in muscle morphology and denervation. Patients with DPN (n = 12) were compared with age- and sex-matched controls (n = 12). Evoked and voluntary contractile properties, including stimulated twitch responses and maximal voluntary contractions, of the dorsiflexor muscles were assessed using an isometric ankle dynamometer. Motor unit number estimates (MUNE) of the tibialis anterior (TA) were performed via quantitative electromyography and decomposition-enhanced spike-triggered averaging. Peak tibialis anterior (TA) cross-sectional area (CSA; cm2), and relative proportion of contractile to noncontractile tissue (%) was determined from magnetic resonance images. Patients with DPN demonstrated decreased strength (−35%) and slower (−45%) dorsiflexion contractile properties for both evoked and voluntary contractions (P < 0.05). These findings were not accounted for by differences in voluntary activation (P > 0.05) or antagonist coactivation (P > 0.05). Additionally, patients with DPN were weaker when strength was normalized to TA total CSA (−30%; P < 0.05) or contractile tissue CSA (−26%; P < 0.05). In the DPN patient group, TA MUNEs were negatively related to both % noncontractile tissue (P < 0.05; r = 0.72) and twitch half-relaxation time (P < 0.05; r = 0.60), whereas no relationships were found between these variables in controls (P > 0.05). We conclude that patients with DPN demonstrated reduced strength and muscle quality as well as contractile slowing. This process may contribute to muscle power loss and functional impairments reported in patients with DPN, beyond the loss of strength commonly observed. PMID:24356519

Establishing the biomechanical properties of the pelvic soft tissues through an inverse finite element analysis using magnetic resonance imaging.

PubMed

Silva, M E T; Brandão, S; Parente, M P L; Mascarenhas, T; Natal Jorge, R M

2016-04-01

The mechanical characteristics of the female pelvic floor are relevant when explaining pelvic dysfunction. The decreased elasticity of the tissue often causes inability to maintain urethral position, also leading to vaginal and rectal descend when coughing or defecating as a response to an increase in the internal abdominal pressure. These conditions can be associated with changes in the mechanical properties of the supportive structures-namely, the pelvic floor muscles-including impairment. In this work, we used an inverse finite element analysis to calculate the material constants for the passive mechanical behavior of the pelvic floor muscles. The numerical model of the pelvic floor muscles and bones was built from magnetic resonance axial images acquired at rest. Muscle deformation, simulating the Valsalva maneuver with a pressure of 4 KPa, was compared with the muscle displacement obtained through additional dynamic magnetic resonance imaging. The difference in displacement was of 0.15 mm in the antero-posterior direction and 3.69 mm in the supero-inferior direction, equating to a percentage error of 7.0% and 16.9%, respectively. We obtained the shortest difference in the displacements using an iterative process that reached the material constants for the Mooney-Rivlin constitutive model (c10=11.8 KPa and c20=5.53 E-02 KPa). For each iteration, the orthogonal distance between each node from the group of nodes which defined the puborectal muscle in the numerical model versus dynamic magnetic resonance imaging was computed. With the methodology used in this work, it was possible to obtain in vivo biomechanical properties of the pelvic floor muscles for a specific subject using input information acquired non-invasively. © IMechE 2016.

Skeletal muscle homeostasis and plasticity in youth and ageing: impact of nutrition and exercise.

PubMed

Brook, M S; Wilkinson, D J; Phillips, B E; Perez-Schindler, J; Philp, A; Smith, K; Atherton, P J

2016-01-01

Skeletal muscles comprise a substantial portion of whole body mass and are integral for locomotion and metabolic health. Increasing age is associated with declines in both muscle mass and function (e.g. strength-related performance, power) with declines in muscle function quantitatively outweighing those in muscle volume. The mechanisms behind these declines are multi-faceted involving both intrinsic age-related metabolic dysregulation and environmental influences such as nutritional and physical activity. Ageing is associated with a degree of 'anabolic resistance' to these key environmental inputs, which likely accelerates the intrinsic processes driving ageing. On this basis, strategies to sensitize and/or promote anabolic responses to nutrition and physical activity are likely to be imperative in alleviating the progression and trajectory of sarcopenia. Both resistance- and aerobic-type exercises are likely to confer functional and health benefits in older age, and a clutch of research suggests that enhancement of anabolic responsiveness to exercise and/or nutrition may be achieved by optimizing modifications of muscle-loading paradigms (workload, volume, blood flow restriction) or nutritional support (e.g. essential amino acid/leucine) patterns. Nonetheless, more work is needed in which a more holistic view in ageing studies is taken into account. This should include improved characterization of older study recruits, that is physical activity/nutritional behaviours, to limit confounding variables influencing whether findings are attributable to age, or other environmental influences. Nonetheless, on balance, ageing is associated with declines in muscle mass and function and a partially related decline in aerobic capacity. There is also good evidence that metabolic flexibility is impaired in older age. © 2015 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.

SURFACE ELECTROMYOGRAPHY OF MASSETER AND TEMPORAL MUSCLES WITH USE PERCENTAGE WHILE CHEWING ON CANDIDATES FOR GASTROPLASTY

PubMed Central

dos SANTOS, Andréa Cavalcante; da SILVA, Carlos Antonio Bruno

2016-01-01

ABSTRACT Background: Surface electromyography identifies changes in the electrical potential of the muscles during each contraction. The percentage of use is a way to treat values enabling comparison between groups. Aim: To analyze the electrical activity and the percentage of use of masseter and temporal muscles during chewing in candidates for gastric bypass. Methods: It was used Surface Electromyography Miotool 200,400 (Miotec (r), Porto Alegre/RS, Brazil) integrated with Miograph 2.0 software, involving patients between 20-40 years old. Were included data on electrical activity simultaneously and in pairs of temporal muscle groups and masseter at rest, maximum intercuspation and during the chewing of food previously classified. Results: Were enrolled 39 patients (59 women), mean age 27.1+/-5.7. The percentage of use focused on temporal muscle, in a range of 11-20, female literacy (n=11; 47.82) on the left side and 15 (65.21) on the right-hand side. In the male, nine (56.25) at left and 12 (75.00) on the right-hand side. In masseter, also in the range of 11 to 20, female literacy (n=10; 43.48) on the left side and 11 (47.83) on the right-hand side. In the male, nine (56.25) at left and eight (50.00) on the right-hand side. Conclusion: 40-50% of the sample showed electrical activity in muscles (masseter and temporal) with variable values, and after processing into percentage value, facilitating the comparison of load of used electrical activity between the group, as well as usage percentage was obtained of muscle fibers 11-20% values involving, representing a range that is considered as a reference to the group studied. The gender was not a variable. PMID:27683776

Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training

PubMed Central

Bowen, T Scott; Schuler, Gerhard; Adams, Volker

2015-01-01

Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Transmission of external stimuli to intracellular effector proteins via signalling pathways is a highly regulated and controlled process that determines muscle mass by balancing protein synthesis and protein degradation. An impaired balance between protein synthesis and breakdown leads to the development of specific myopathies. Sarcopenia and cachexia represent two distinct muscle wasting diseases characterized by inflammation and oxidative stress, where specific regulating molecules associated with wasting are either activated (e.g. members of the ubiquitin-proteasome system and myostatin) or repressed (e.g. insulin-like growth factor 1 and PGC-1α). At present, no therapeutic interventions are established to successfully treat muscle wasting in sarcopenia and cachexia. Exercise training, however, represents an intervention that can attenuate or even reverse the process of muscle wasting, by exerting anti-inflammatory and anti-oxidative effects that are able to attenuate signalling pathways associated with protein degradation and activate molecules associated with protein synthesis. This review will therefore discuss the molecular mechanisms associated with the pathology of muscle wasting in both sarcopenia and cachexia, as well as highlighting the intracellular effects of exercise training in attenuating the debilitating loss of muscle mass in these specific conditions. PMID:26401465

Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training.

PubMed

Bowen, T Scott; Schuler, Gerhard; Adams, Volker

2015-09-01

Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Transmission of external stimuli to intracellular effector proteins via signalling pathways is a highly regulated and controlled process that determines muscle mass by balancing protein synthesis and protein degradation. An impaired balance between protein synthesis and breakdown leads to the development of specific myopathies. Sarcopenia and cachexia represent two distinct muscle wasting diseases characterized by inflammation and oxidative stress, where specific regulating molecules associated with wasting are either activated (e.g. members of the ubiquitin-proteasome system and myostatin) or repressed (e.g. insulin-like growth factor 1 and PGC-1α). At present, no therapeutic interventions are established to successfully treat muscle wasting in sarcopenia and cachexia. Exercise training, however, represents an intervention that can attenuate or even reverse the process of muscle wasting, by exerting anti-inflammatory and anti-oxidative effects that are able to attenuate signalling pathways associated with protein degradation and activate molecules associated with protein synthesis. This review will therefore discuss the molecular mechanisms associated with the pathology of muscle wasting in both sarcopenia and cachexia, as well as highlighting the intracellular effects of exercise training in attenuating the debilitating loss of muscle mass in these specific conditions.

Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration.

PubMed

Gregorevic, Paul; Plant, David R; Stupka, Nicole; Lynch, Gordon S

2004-07-15

Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca(2+)- and Sr(2+)-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had approximately 10% of the maximal force producing capacity (P(o)) of control (uninjured) fibres, and an altered sensitivity to Ca(2+) and Sr(2+) at 7 days post-injury. Increased force production and a shift in Ca(2+) sensitivity consistent with fibre maturation were observed during regeneration such that P(o) was restored to 36-45% of that in control fibres by 21 days, and sensitivity to Ca(2+) and Sr(2+) was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed.

Effects of low level laser in the morphology of the skeletal muscle fiber during compensatory hypertrophy in plantar muscle of rats

NASA Astrophysics Data System (ADS)

Terena, Stella Maris Lins; Fernandes, Kristianne Porta Santos; Kalil, Sandra; Alves, Agnelo Neves; Mesquita Ferrari, Raquel Agnelli

2015-06-01

The hypertrophy is known as an increase the cross-sectional area of the muscle as a result of a muscular work against an overload, and it is compensatory because the overload is induced by functional elimination of synergistic muscles. The importance of study the compensatory hypertrophy is understand how this process can be influenced by the irradiation with regard to the weight and muscle cross-sectional area, to assist in the rehabilitation process and the effectiveness functional return. The aim was evaluate the effects of low-level laser irradiation on morphological aspects of muscle tissue, comparing the weight and cross-sectional area in rat skeletal muscle. Wistar rats were divided into three groups: control, hypertrophy group without irradiation (right plantar muscle) and hypertrophy group and irradiation (left plantar muscle), both analyzed after 7 and 14 days. The irradiation was performed daily immediately after the surgery. The parameters were: λ = 780nm, beam spot of 0.04 cm2, output power of 40mW, power density of 1W/cm2, energy density of 10J / cm2 and 10s exposure time with a total energy of 3.2 J. The results revealed that low level laser irradiation an increase the weight of the plantaris muscle after 7 and 14 days with a difference of 7.06% and 11.51% respectively. In conclusion, low level laser irradiation has an effect on compensatory hypertrophy to produce increased muscle weight and promoted an increase in cross-sectional area of muscle fibers in the compensatory hypertrophy model after 14 days with parameters cited above.

Low-level laser therapy (LLLT) accelerates the sternomastoid muscle regeneration process after myonecrosis due to bupivacaine.

PubMed

Alessi Pissulin, Cristiane Neves; Henrique Fernandes, Ana Angélica; Sanchez Orellana, Alejandro Manuel; Rossi E Silva, Renata Calciolari; Michelin Matheus, Selma Maria

2017-03-01

Because of its long-lasting analgesic action, bupivacaine is an anesthetic used for peripheral nerve block and relief of postoperative pain. Muscle degeneration and neurotoxicity are its main limitations. There is strong evidence that low-level laser therapy (LLLT) assists in muscle and nerve repair. The authors evaluated the effects of a Gallium Arsenide laser (GaAs), on the regeneration of muscle fibers of the sternomastoid muscle and accessory nerve after injection of bupivacaine. In total, 30 Wistar adult rats were divided into 2 groups: control group (C: n=15) and laser group (L: n=15). The groups were subdivided by antimere, with 0.5% bupivacaine injected on the right and 0.9% sodium chloride on the left. LLLT (GaAs 904nm, 0,05W, 2.8J per point) was administered for 5 consecutive days, starting 24h after injection of the solutions. Seven days after the trial period, blood samples were collected for determination of creatine kinase (CK). The sternomastoid nerve was removed for morphological and morphometric analyses; the surface portion of the sternomastoid muscle was used for histopathological and ultrastructural analyses. Muscle CK and TNFα protein levels were measured. The anesthetic promoted myonecrosis and increased muscle CK without neurotoxic effects. The LLLT reduced myonecrosis, characterized by a decrease in muscle CK levels, inflammation, necrosis, and atrophy, as well as the number of central nuclei in the muscle fibers and the percentage of collagen. TNFα values remained constant. LLLT, at the dose used, reduced fibrosis and myonecrosis in the sternomastoid muscle triggered by bupivacaine, accelerating the muscle regeneration process. Copyright © 2017 Elsevier B.V. All rights reserved.

Real-Time Classification of Hand Motions Using Ultrasound Imaging of Forearm Muscles.

PubMed

Akhlaghi, Nima; Baker, Clayton A; Lahlou, Mohamed; Zafar, Hozaifah; Murthy, Karthik G; Rangwala, Huzefa S; Kosecka, Jana; Joiner, Wilsaan M; Pancrazio, Joseph J; Sikdar, Siddhartha

2016-08-01

Surface electromyography (sEMG) has been the predominant method for sensing electrical activity for a number of applications involving muscle-computer interfaces, including myoelectric control of prostheses and rehabilitation robots. Ultrasound imaging for sensing mechanical deformation of functional muscle compartments can overcome several limitations of sEMG, including the inability to differentiate between deep contiguous muscle compartments, low signal-to-noise ratio, and lack of a robust graded signal. The objective of this study was to evaluate the feasibility of real-time graded control using a computationally efficient method to differentiate between complex hand motions based on ultrasound imaging of forearm muscles. Dynamic ultrasound images of the forearm muscles were obtained from six able-bodied volunteers and analyzed to map muscle activity based on the deformation of the contracting muscles during different hand motions. Each participant performed 15 different hand motions, including digit flexion, different grips (i.e., power grasp and pinch grip), and grips in combination with wrist pronation. During the training phase, we generated a database of activity patterns corresponding to different hand motions for each participant. During the testing phase, novel activity patterns were classified using a nearest neighbor classification algorithm based on that database. The average classification accuracy was 91%. Real-time image-based control of a virtual hand showed an average classification accuracy of 92%. Our results demonstrate the feasibility of using ultrasound imaging as a robust muscle-computer interface. Potential clinical applications include control of multiarticulated prosthetic hands, stroke rehabilitation, and fundamental investigations of motor control and biomechanics.

Knitting and weaving artificial muscles

PubMed Central

Maziz, Ali; Concas, Alessandro; Khaldi, Alexandre; Stålhand, Jonas; Persson, Nils-Krister; Jager, Edwin W. H.

2017-01-01

A need exists for artificial muscles that are silent, soft, and compliant, with performance characteristics similar to those of skeletal muscle, enabling natural interaction of assistive devices with humans. By combining one of humankind’s oldest technologies, textile processing, with electroactive polymers, we demonstrate here the feasibility of wearable, soft artificial muscles made by weaving and knitting, with tunable force and strain. These textile actuators were produced from cellulose yarns assembled into fabrics and coated with conducting polymers using a metal-free deposition. To increase the output force, we assembled yarns in parallel by weaving. The force scaled linearly with the number of yarns in the woven fabric. To amplify the strain, we knitted a stretchable fabric, exhibiting a 53-fold increase in strain. In addition, the textile construction added mechanical stability to the actuators. Textile processing permits scalable and rational production of wearable artificial muscles, and enables novel ways to design assistive devices. PMID:28138542

Insights into skeletal muscle development and applications in regenerative medicine.

PubMed

Tran, T; Andersen, R; Sherman, S P; Pyle, A D

2013-01-01

Embryonic and postnatal development of skeletal muscle entails highly regulated processes whose complexity continues to be deconstructed. One key stage of development is the satellite cell, whose niche is composed of multiple cell types that eventually contribute to terminally differentiated myotubes. Understanding these developmental processes will ultimately facilitate treatments of myopathies such as Duchenne muscular dystrophy (DMD), a disease characterized by compromised cell membrane structure, resulting in severe muscle wasting. One theoretical approach is to use pluripotent stem cells in a therapeutic setting to help replace degenerated muscle tissue. This chapter discusses key myogenic developmental stages and their regulatory pathways; artificial myogenic induction in pluripotent stem cells; advantages and disadvantages of DMD animal models; and therapeutic approaches targeting DMD. Furthermore, skeletal muscle serves as an excellent paradigm for understanding general cell fate decisions throughout development. Copyright © 2013 Elsevier Inc. All rights reserved.

Eccentric contraction-induced injury to type I, IIa, and IIa/IIx muscle fibers of elderly adults

USDA-ARS?s Scientific Manuscript database

Muscles of old laboratory rodents experience exaggerated force losses after eccentric contractile activity. We extended this line of inquiry to humans and investigated the influence of fiber myosin heavy chain (MHC) isoform content on the injury process. Skinned muscle fiber segments, prepared from ...

Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing.

PubMed

Banerjee, Ayan; Vest, Katherine E; Pavlath, Grace K; Corbett, Anita H

2017-10-13

The polyadenylate binding protein 1 (PABPN1) is a ubiquitously expressed RNA binding protein vital for multiple steps in RNA metabolism. Although PABPN1 plays a critical role in the regulation of RNA processing, mutation of the gene encoding this ubiquitously expressed RNA binding protein causes a specific form of muscular dystrophy termed oculopharyngeal muscular dystrophy (OPMD). Despite the tissue-specific pathology that occurs in this disease, only recently have studies of PABPN1 begun to explore the role of this protein in skeletal muscle. We have used co-immunoprecipitation and mass spectrometry to identify proteins that interact with PABPN1 in mouse skeletal muscles. Among the interacting proteins we identified Matrin 3 (MATR3) as a novel protein interactor of PABPN1. The MATR3 gene is mutated in a form of distal myopathy and amyotrophic lateral sclerosis (ALS). We demonstrate, that like PABPN1, MATR3 is critical for myogenesis. Furthermore, MATR3 controls critical aspects of RNA processing including alternative polyadenylation and intron retention. We provide evidence that MATR3 also binds and regulates the levels of long non-coding RNA (lncRNA) Neat1 and together with PABPN1 is required for normal paraspeckle function. We demonstrate that PABPN1 and MATR3 are required for paraspeckles, as well as for adenosine to inosine (A to I) RNA editing of Ctn RNA in muscle cells. We provide a functional link between PABPN1 and MATR3 through regulation of a common lncRNA target with downstream impact on paraspeckle morphology and function. We extend our analysis to a mouse model of OPMD and demonstrate altered paraspeckle morphology in the presence of endogenous levels of alanine-expanded PABPN1. In this study, we report protein-binding partners of PABPN1, which could provide insight into novel functions of PABPN1 in skeletal muscle and identify proteins that could be sequestered with alanine-expanded PABPN1 in the nuclear aggregates found in OPMD. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing

PubMed Central

Banerjee, Ayan; Vest, Katherine E.

2017-01-01

Abstract The polyadenylate binding protein 1 (PABPN1) is a ubiquitously expressed RNA binding protein vital for multiple steps in RNA metabolism. Although PABPN1 plays a critical role in the regulation of RNA processing, mutation of the gene encoding this ubiquitously expressed RNA binding protein causes a specific form of muscular dystrophy termed oculopharyngeal muscular dystrophy (OPMD). Despite the tissue-specific pathology that occurs in this disease, only recently have studies of PABPN1 begun to explore the role of this protein in skeletal muscle. We have used co-immunoprecipitation and mass spectrometry to identify proteins that interact with PABPN1 in mouse skeletal muscles. Among the interacting proteins we identified Matrin 3 (MATR3) as a novel protein interactor of PABPN1. The MATR3 gene is mutated in a form of distal myopathy and amyotrophic lateral sclerosis (ALS). We demonstrate, that like PABPN1, MATR3 is critical for myogenesis. Furthermore, MATR3 controls critical aspects of RNA processing including alternative polyadenylation and intron retention. We provide evidence that MATR3 also binds and regulates the levels of long non-coding RNA (lncRNA) Neat1 and together with PABPN1 is required for normal paraspeckle function. We demonstrate that PABPN1 and MATR3 are required for paraspeckles, as well as for adenosine to inosine (A to I) RNA editing of Ctn RNA in muscle cells. We provide a functional link between PABPN1 and MATR3 through regulation of a common lncRNA target with downstream impact on paraspeckle morphology and function. We extend our analysis to a mouse model of OPMD and demonstrate altered paraspeckle morphology in the presence of endogenous levels of alanine-expanded PABPN1. In this study, we report protein-binding partners of PABPN1, which could provide insight into novel functions of PABPN1 in skeletal muscle and identify proteins that could be sequestered with alanine-expanded PABPN1 in the nuclear aggregates found in OPMD. PMID:28977530

Mathematical Model Of Nerve/Muscle Interaction

NASA Technical Reports Server (NTRS)

Hannaford, Blake

1990-01-01

Phasic Excitation/Activation (PEA) mathematical model simulates short-term nonlinear dynamics of activation and control of muscle by nerve. Includes electronic and mechanical elements. Is homeomorphic at level of its three major building blocks, which represent motoneuron, dynamics of activation of muscle, and mechanics of muscle.

[The sodium-potassium-chloride cotransport of the cell membrane].

PubMed

Urazaev, A Kh

1998-01-01

Discovery and active exploration of the furosemid-sensitive derived-active co-transport of sodium-potassium-chlorine ions took place in the end of 1970-es-1980-es. This transportation mechanism was discovered in various types of cells, both of plant and of animal origin. This review describes properties of the transportation process, which was most comprehensive explored in experiments with erythrocytes, epithelium cells and muscles. The review covers the following properties: anion and cation selectivity of the chlorine transportation, its sensitivity to the specific blocking agents (furocemid, bumetanid, etc.), stoichiometry of the transportation process, etc. For energy source, the chlorine transportation is based on transmembrane electrochemical gradient for sodium ions. The article provides the most recent results of investigation of the chemical nature of the molecule of the chlorine membrane transport. Based on various studies, the molecule of this protein weighs from 120 to 200 kD, includes about 1200 amino acid residua, and forms long cytoplasmatic NH2 and COOH-termini. The gene encoding the amino acid sequence has been cloned. The article discusses the issues of regulation of the chlorine transportation. Humoral control of intensity of the chlorine transportation has been mostly studied in experiments with plain muscles, the issues related to nervous regulation--with only skeleton muscle fibers. The article provides specific data on the mechanisms of the above types of the physiological regulation of active chlorine transportation. In general, the humoral factors, which increase the intracellular concentration of cAMF stimulate chlorine transportation. On the contrary, the hormones, which increase concentration of cGMF in cytoplasm reduce its activity in plain muscles. The discussion of the mechanisms of the nervous controls of the chlorine transportation in the skeleton muscles includes the original results of the author. These results indicate that the suppressive influence of the motor innervation on intensity of the chlorine transportation involves the non-quantum acetilcholine and glutamate secreted from the motor nerves. These agents produce Ca(2+)-dependent molecules of nitrogen oxide in sarcoplasm, which act in the retrograde mode on the nervous terminal and activate there the synthesis of cGMF. Disruption of this bilateral transsynaptic signalization resulting from cutting a nerve of blocking of its axoflow creates more active chlorine transportation and subsequent de-innervation changes in properties of the muscle fibers. The functions of chlorine transportation, which are best studies as of today and therefore, discussed in more detail in the review, include participation of this process in the regulatory rehabilitation of the volume of various cells in non-isotonic medium, and the role of chlorine transportation in development of a negative charge at the interior side of membrane of the skeleton muscle fibers. The former function essentially means that dehydration of a cell in the hypertonic medium increases activity of the sodium, potassium and chlorine co-transport directed to the cell, resulting in increase of the amount of the osmosis-active cytoplasm material, and inflow of water, which fully restores the cell volume in these conditions. Starting from the pioneer studies by Hodgkin and Horowicz [correction of Hojkin and Gorovits], the role of chlorine ions in forming a charge on the membrane of excited cells has been generally interpreted as exclusively passive. I.e., distribution of these ions over both sides of membrane was assumed as equilibrium with the existing values of the membrane potential in the non-excited state. The review provides data obtained in the recent decade, which have proved that the non-excited membrane potential in muscle fibers is co-created by the diffusional potassium and chlorine potential. (ABSTRACT TRUNCATED)

Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases

PubMed Central

Kalyani, Rita Rastogi; Corriere, Mark; Ferrucci, Luigi

2014-01-01

The term sarcopenia refers to the loss of muscle mass that occurs with ageing. On the basis of study results showing that muscle mass is only moderately related to functional outcomes, international working groups have proposed that loss of muscle strength or physical function should also be included in the definition. Irrespective of how sarcopenia is defined, both low muscle mass and poor muscle strength are clearly highly prevalent and important risk factors for disability and potentially mortality in individuals as they age. Many chronic diseases, in addition to ageing, could also accelerate decrease of muscle mass and strength, and this effect could be a main underlying mechanism by which chronic diseases cause physical disability. In this Review, we address both age-related and disease-related muscle loss, with a focus on diabetes and obesity but including other disease states, and potential common mechanisms and treatments. Development of treatments for age-related and disease-related muscle loss might improve active life expectancy in older people, and lead to substantial health-care savings and improved quality of life. PMID:24731660

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering.

PubMed

Maffioletti, Sara Martina; Sarcar, Shilpita; Henderson, Alexander B H; Mannhardt, Ingra; Pinton, Luca; Moyle, Louise Anne; Steele-Stallard, Heather; Cappellari, Ornella; Wells, Kim E; Ferrari, Giulia; Mitchell, Jamie S; Tyzack, Giulia E; Kotiadis, Vassilios N; Khedr, Moustafa; Ragazzi, Martina; Wang, Weixin; Duchen, Michael R; Patani, Rickie; Zammit, Peter S; Wells, Dominic J; Eschenhagen, Thomas; Tedesco, Francesco Saverio

2018-04-17

Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Origin of the styloglossus muscle in the human fetus

PubMed Central

Mérida-Velasco, J R; Rodríguez-Vazquez, J F; de la Cuadra Blanco, C; Sánchez-Montesinos, I; Mérida-Velasco, J A

2006-01-01

The origin of the styloglossus muscle was histologically studied bilaterally in nine human fetuses (18 sides). In all cases, the muscle originated in Reichert's cartilage, which gives rise to the temporal styloid process. We identified three types of variation: type A, an accessory muscle fascicle originating from the mandibular angle, found in 7 cases (12 sides); type B, where the styloglossus muscle was attached to the mandibular angle by fibrous tracts, found in three cases (4 sides); and type C, where an accessory muscle fascicle arose from the fibrous tract connecting Reichert's cartilage to the mandibular angle; found in one case. In all cases (2 sides), the styloglossus muscle was innervated by the hypoglossal nerve. Relationships between the styloglossus muscle and vasculonervous elements of the prestyloid and retrostyloid spaces were analysed. PMID:16637887

On the anatomy of the temporomandibular joint and the muscles that act upon it: observations on the gray whale, Eschrichtius robustus.

PubMed

El Adli, Joseph J; Deméré, Thomas A

2015-04-01

The temporomandibular joint and its associated musculature are described in a neonate gray whale (Eschrichtius robustus) and serve as the basis for direct anatomical comparisons with the temporomandibular region in other clades of baleen whales (Mysticeti). Members of the right whale/bowhead whale clade (Balaenidae) are known to possess a synovial lower jaw joint, while members of the rorqual clade (Balaenopteridae) have a nonsynovial temporomandibular joint characterized by a highly flexible fibrocartilaginous pad and no joint capsule. In contrast, the gray whale possesses a modified temporomandibular joint (intermediate condition), with a vestigial joint cavity lacking a fibrous capsule, synovial membrane, and articular disk. In addition, the presence of a rudimentary fibrocartilaginous pad appears to be homologous to that seen in balaenopterid mysticetes. The intrinsic temporomandibular musculature in the gray whale was found to include a multibellied superficial masseter and a single-bellied deep masseter. The digastric and internal pterygoid muscles in E. robustus are enlarged relative to the condition documented in species of Balaenoptera. A relatively complex insertion of the temporalis muscle on the dentary is documented in the gray whale and the low, knob-like process on the gray whale dentary is determined to be homologous with the prominent coronoid process of rorquals. Comparison with the anatomy of the temporomandibular musculature in rorquals reveals an increased importance of alpha rotation of the dentary in the gray whale. This difference in muscular morphology and lines of muscle action is interpreted as representing adaptations for suction feeding. © 2015 Wiley Periodicals, Inc.

Spasticity

MedlinePlus

Exercise, including muscle stretching, can help make symptoms less severe. Physical therapy is also helpful. ... therapist. Physical therapy involves different exercises, including muscle stretching and strengthening exercises. Physical therapy exercises can be ...

Measurement of Contractile Stress Generated by Cultured Rat Muscle on Silicon Cantilevers for Toxin Detection and Muscle Performance Enhancement

DTIC Science & Technology

2010-06-01

muscle . J Clin Invest 117: 2388–2391. 13. Close R (1964) Dynamic properties of fast and slow skeletal muscles of the rat during development. J Physiol...cultured skeletal muscle [30], which reported average peak twitch stress values of 2.9 kPa (reported as specific peak twitch force in units of kN/m2), but...demonstrates that the myotubes were driven down a path towards a more mature phenotype, in the process developing fast - twitch isoforms of myosin, while

Muscle torque of healthy individuals and individuals with spastic hemiparesis after passive static streching.

PubMed

Tatsukawa DE Freitas, Sérgio Takeshi; DE Carvalho Abreu, Elizângela Márcia; Dos Reis, Mariane Cecilia; DE Souza Cunha, Bruna; Souza Moreira Prianti, Tamires; Pupio Silva Lima, Fernanda; Oliveira Lima, Mário

2016-01-01

Spasticity is one of the main causes of contracture, muscle weakness and subsequent functional incapacity. The passive static stretching can be included as having the purpose of increasing musculoskeletal flexibility, however, it also can influence the muscle torque. The objective is to verify the immediate effect of passive static stretching in the muscle strength of healthy and those who present spastic hemiparesis. There were assessed 20 subjects, 10 spastic hemiparetic (EG) and 10 healthy individuals (CG), including both sexes, aged between 22 and 78 years. The torque of extensor muscles of the knee was analyzed using isokinetic dynamometer. Results have shown that EG has less muscle torque compared to CG ( p < 0.01). In addition, EG presented a decrease in significance of muscle torque after stretching ( p < 0.05), however, it has not shown significant alteration in muscle torque of CG after performing the program that was prescribed. Immediately after the passive stretch, a significant torque decrease can be seen in hypertonic muscle; it is believed that this reduction may be associated with the physiological overlap between actin and myosin filaments and so preventing the muscle to develop a maximum contraction.

An eye on the head: the development and evolution of craniofacial muscles.

PubMed

Sambasivan, Ramkumar; Kuratani, Shigeru; Tajbakhsh, Shahragim

2011-06-01

Skeletal muscles exert diverse functions, enabling both crushing with great force and movement with exquisite precision. A remarkably distinct repertoire of genes and ontological features characterise this tissue, and recent evidence has shown that skeletal muscles of the head, the craniofacial muscles, are evolutionarily, morphologically and molecularly distinct from those of the trunk. Here, we review the molecular basis of craniofacial muscle development and discuss how this process is different to trunk and limb muscle development. Through evolutionary comparisons of primitive chordates (such as amphioxus) and jawless vertebrates (such as lampreys) with jawed vertebrates, we also provide some clues as to how this dichotomy arose.

Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy.

PubMed

Goh, Qingnian; Millay, Douglas P

2017-02-10

Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance of this process during adult muscle hypertrophy has not been explored. In response to muscle overload after synergist ablation in mice, we show that myomaker, a muscle specific membrane protein essential for myoblast fusion, is activated mainly in muscle progenitors and not myofibers. We rendered muscle progenitors fusion-incompetent through genetic deletion of myomaker in muscle stem cells and observed a complete reduction of overload-induced hypertrophy. This blunted hypertrophic response was associated with a reduction in Akt and p70s6k signaling and protein synthesis, suggesting a link between myonuclear accretion and activation of pro-hypertrophic pathways. Furthermore, fusion-incompetent muscle exhibited increased fibrosis after muscle overload, indicating a protective role for normal stem cell activity in reducing myofiber strain associated with hypertrophy. These findings reveal an essential contribution of myomaker-mediated stem cell fusion during physiological adult muscle hypertrophy.

Overexpression of IGF-1 attenuates skeletal muscle damage and accelerates muscle regeneration and functional recovery after disuse

PubMed Central

Ye, Fan; Mathur, Sunita; Liu, Min; Borst, Stephen E.; Walter, Glenn A.; Sweeney, H. Lee; Vandenborne, Krista

2014-01-01

Skeletal muscle is a highly dynamic tissue that responds to endogenous and external stimuli, including alterations in mechanical loading and growth factors. In particular, the antigravity soleus muscle experiences significant muscle atrophy during disuse and extensive muscle damage upon reloading. Since insulin-like growth factor-1 (IGF-1) has been implicated as a central regulator of muscle repair and modulation of muscle size, we examined the effect of viral mediated overexpression of IGF-1 on the soleus muscle following hindlimb cast immobilization and upon reloading. Recombinant IGF-1 cDNA virus was injected into one of the posterior hindlimbs of the mice, while the contralateral limb was injected with saline (control). At 20 weeks of age, both hindlimbs were immobilized for two weeks to induce muscle atrophy in the soleus and ankle plantar flexor muscle group. Subsequently, the mice were allowed to reambulate and muscle damage and recovery was monitored over a period of 2 to 21 days. The primary finding of this study was that IGF-1 overexpression attenuated reloading-induced muscle damage in the soleus muscle, and accelerated muscle regeneration and force recovery. Muscle T2 assessed by MRI, a nonspecific marker of muscle damage, was significantly lower in IGF-1 injected, compared to contralateral soleus muscles at 2 and 5 days reambulation (P<0.05). The reduced prevalence of muscle damage in IGF-1 injected soleus muscles was confirmed on histology, with a lower fraction area of abnormal muscle tissue in IGF-I injected muscles at 2 days reambulation (33.2±3.3%vs 54.1±3.6%, P<0.05). Evidence of the effect of IGF-1 on muscle regeneration included timely increases in the number of central nuclei (21% at 5 days reambulation), paired-box transcription factor 7 (36% at 5 days), embryonic myosin (37% at 10 days), and elevated MyoD mRNA (7-fold at 2 days) in IGF-1 injected limbs (P<0.05). These findings demonstrate a potential role of IGF-1 in protecting unloaded skeletal muscles from damage and accelerating muscle repair and regeneration. PMID:23291913

Overexpression of insulin-like growth factor-1 attenuates skeletal muscle damage and accelerates muscle regeneration and functional recovery after disuse.

PubMed

Ye, Fan; Mathur, Sunita; Liu, Min; Borst, Stephen E; Walter, Glenn A; Sweeney, H Lee; Vandenborne, Krista

2013-05-01

Skeletal muscle is a highly dynamic tissue that responds to endogenous and external stimuli, including alterations in mechanical loading and growth factors. In particular, the antigravity soleus muscle experiences significant muscle atrophy during disuse and extensive muscle damage upon reloading. Given that insulin-like growth factor-1 (IGF-1) has been implicated as a central regulator of muscle repair and modulation of muscle size, we examined the effect of virally mediated overexpression of IGF-1 on the soleus muscle following hindlimb cast immobilization and upon reloading. Recombinant IGF-1 cDNA virus was injected into one of the posterior hindlimbs of the mice, while the contralateral limb was injected with saline (control). At 20 weeks of age, both hindlimbs were immobilized for 2 weeks to induce muscle atrophy in the soleus and ankle plantarflexor muscle group. Subsequently, the mice were allowed to reambulate, and muscle damage and recovery were monitored over a period of 2-21 days. The primary finding of this study was that IGF-1 overexpression attenuated reloading-induced muscle damage in the soleus muscle, and accelerated muscle regeneration and force recovery. Muscle T2 assessed by magnetic resonance imaging, a non-specific marker of muscle damage, was significantly lower in IGF-1-injected compared with contralateral soleus muscles at 2 and 5 days reambulation (P<0.05). The reduced prevalence of muscle damage in IGF-1-injected soleus muscles was confirmed on histology, with a lower fractional area of abnormal muscle tissue in IGF-1-injected muscles at 2 days reambulation (33.2±3.3 versus 54.1±3.6%, P<0.05). Evidence of the effect of IGF-1 on muscle regeneration included timely increases in the number of central nuclei (21% at 5 days reambulation), paired-box transcription factor 7 (36% at 5 days), embryonic myosin (37% at 10 days) and elevated MyoD mRNA (7-fold at 2 days) in IGF-1-injected limbs (P<0.05). These findings demonstrate a potential role of IGF-1 in protecting unloaded skeletal muscles from damage and accelerating muscle repair and regeneration.

MCAT elements and the TEF-1 family of transcription factors in muscle development and disease.

PubMed

Yoshida, Tadashi

2008-01-01

MCAT elements are located in the promoter-enhancer regions of cardiac, smooth, and skeletal muscle-specific genes including cardiac troponin T, beta-myosin heavy chain, smooth muscle alpha-actin, and skeletal alpha-actin, and play a key role in the regulation of these genes during muscle development and disease. The binding factors of MCAT elements are members of the transcriptional enhancer factor-1 (TEF-1) family. However, it has not been fully understood how these transcription factors confer cell-specific expression in muscle, because their expression patterns are relatively broad. Results of recent studies revealed multiple mechanisms whereby TEF-1 family members control MCAT element-dependent muscle-specific gene expression, including posttranslational modifications of TEF-1 family members, the presence of muscle-selective TEF-1 cofactors, and cell-selective control of TEF-1 accessibility to MCAT elements. In addition, of particular interest, recent studies regarding MCAT element-dependent transcription of the myocardin gene and the smooth muscle alpha-actin gene in muscle provide evidence for the transcriptional diversity among distinct cell types and subtypes. This article summarizes the role of MCAT elements and the TEF-1 family of transcription factors in muscle development and disease, and reviews recent progress in our understanding of the transcriptional regulatory mechanisms involved in MCAT element-dependent muscle-specific gene expression.

Deletion of Pofut1 in Mouse Skeletal Myofibers Induces Muscle Aging-Related Phenotypes in cis and in trans

PubMed Central

Zygmunt, Deborah A.; Singhal, Neha; Kim, Mi-Lyang; Cramer, Megan L.; Crowe, Kelly E.; Xu, Rui; Jia, Ying; Adair, Jessica; Martinez-Pena y Valenzuela, Isabel; Akaaboune, Mohammed; White, Peter; Janssen, Paulus M.

2017-01-01

ABSTRACT Sarcopenia, the loss of muscle mass and strength during normal aging, involves coordinate changes in skeletal myofibers and the cells that contact them, including satellite cells and motor neurons. Here we show that the protein O-fucosyltransferase 1 gene (Pofut1), which encodes a glycosyltransferase required for NotchR-mediated cell-cell signaling, has reduced expression in aging skeletal muscle. Moreover, premature postnatal deletion of Pofut1 in skeletal myofibers can induce aging-related phenotypes in cis within skeletal myofibers and in trans within satellite cells and within motor neurons via the neuromuscular junction. Changed phenotypes include reduced skeletal muscle size and strength, decreased myofiber size, increased slow fiber (type 1) density, increased muscle degeneration and regeneration in aged muscles, decreased satellite cell self-renewal and regenerative potential, and increased neuromuscular fragmentation and occasional denervation. Pofut1 deletion in skeletal myofibers reduced NotchR signaling in young adult muscles, but this effect was lost with age. Increasing muscle NotchR signaling also reduced muscle size. Gene expression studies point to regulation of cell cycle genes, muscle myosins, NotchR and Wnt pathway genes, and connective tissue growth factor by Pofut1 in skeletal muscle, with additional effects on α dystroglycan glycosylation. PMID:28265002

Innervation of the anterior byssal retractor muscle in Mytilus edulis L. II. Ultrastructure of the glio-interstitial cells.

PubMed

Gilloteaux, J

1975-08-27

Studies on the intrinsic innervation of the anterior byssal retractor muscle (ABRM) in Mytilus edulis L. were continued at the ultrastructural level. Electron micrographs show nerve processes ensheathed by glio-interstitial cells running between muscle fibers. The glio-interstitial cells may represent all the types of osmiophilic cells previously described by the light microscopic ZIO technique in the anterior byssal retractor muscle.

New therapeutic approaches for management of sport-induced muscle strains.

PubMed

De Carli, Angelo; Volpi, Piero; Pelosini, Iva; Ferretti, Andrea; Melegati, Gianluca; Mossa, Luigi; Tornese, Davide; de Girolamo, Laura; Scarpignato, Carmelo

2009-12-01

Muscle strains are one of the most common sports-induced injuries. Depending on the severity and location of the muscle strain, different treatment approaches can be taken. This review highlights recent trends in conservative, pharmacologic, and surgical approaches to the management of sports-induced muscle injuries as presented at a symposium held during the 93rd Annual Congress of the Italian Society of Orthopedics and Traumatology (SIOT) in Rome, Italy in November 2008. Conservative approaches now include growth factor therapy and administration of autologous platelet-rich plasma during the early postinjury period; however, its use is currently considered a doping violation under the World Anti-Doping Agency code, therefore restricting its use to nonelite sports people only. Topical anti-inflammatory therapy is a promising therapeutic strategy, since it allows local analgesic and anti-inflammatory effects while minimizing systemic adverse events. As the drug delivery system is critical to clinical effectiveness, the advent of a new delivery system for ketoprofen via a new-generation plaster with a marked increase in tissue penetration and a clinical efficacy comparable with that of oral administration, provides a viable option in the treatment of single sport lesions. Surgical treatment of muscle lesions is less common than conservative and topical therapies and indications are limited to more serious injuries. Presentations from SIOT 2008 show that advances in our understanding of the healing process and in conservative, pharmacologic, and surgical treatment approaches to the management of sports-induced muscle strains contribute to better clinical outcomes, faster healing, and a swifter return to normal training and activity levels.

Evidence that a maternal "junk food" diet during pregnancy and lactation can reduce muscle force in offspring.

PubMed

Bayol, Stéphanie A; Macharia, Raymond; Farrington, Samantha J; Simbi, Bigboy H; Stickland, Neil C

2009-02-01

Obesity is a multi-factorial condition generally attributed to an unbalanced diet and lack of exercise. Recent evidence suggests that maternal malnutrition during pregnancy and lactation can also contribute to the development of obesity in offspring. We have developed an animal model in rats to examine the effects of maternal overeating on a westernized "junk food" diet using palatable processed foods rich in fat, sugar and salt designed for human consumption. Using this model, we have shown that such a maternal diet can promote overeating and a greater preference for junk food in offspring at the end of adolescence. The maternal junk food diet also promoted adiposity and muscle atrophy at weaning. Impaired muscle development may permanently affect the function of this tissue including its ability to generate force. The aim of this study is to determine whether a maternal junk food diet can impair muscle force generation in offspring. Twitch and tetanic tensions were measured in offspring fed either chow alone (C) or with a junk food diet (J) during gestation, lactation and/or post-weaning up to the end of adolescence such that three groups of offspring were used, namely the CCC, JJC and JJJ groups. We show that adult offspring from mothers fed the junk food diet in pregnancy and lactation display reduced muscle force (both specific twitch and tetanic tensions) regardless of the post-weaning diet compared with offspring from mothers fed a balanced diet. Maternal malnutrition can influence muscle force production in offspring which may affect an individual's ability to exercise and thereby combat obesity.

Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen

PubMed Central

Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

2016-01-01

Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active, i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. Trial Registration: ClinicalTrials.gov: NCT01679977 PMID:28078066

Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen.

PubMed

Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

2016-09-15

Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active, i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. ClinicalTrials.gov: NCT01679977.

Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles

PubMed Central

Park, Ki Ho; Brotto, Leticia; Lehoang, Oanh; Brotto, Marco; Ma, Jianjie; Zhao, Xiaoli

2012-01-01

Described here is a method to measure contractility of isolated skeletal muscles. Parameters such as muscle force, muscle power, contractile kinetics, fatigability, and recovery after fatigue can be obtained to assess specific aspects of the excitation-contraction coupling (ECC) process such as excitability, contractile machinery and Ca2+ handling ability. This method removes the nerve and blood supply and focuses on the isolated skeletal muscle itself. We routinely use this method to identify genetic components that alter the contractile property of skeletal muscle though modulating Ca2+ signaling pathways. Here, we describe a newly identified skeletal muscle phenotype, i.e., mechanic alternans, as an example of the various and rich information that can be obtained using the in vitro muscle contractility assay. Combination of this assay with single cell assays, genetic approaches and biochemistry assays can provide important insights into the mechanisms of ECC in skeletal muscle. PMID:23149471

Variability of manual ciliary muscle segmentation in optical coherence tomography images.

PubMed

Chang, Yu-Cherng; Liu, Keke; Cabot, Florence; Yoo, Sonia H; Ruggeri, Marco; Ho, Arthur; Parel, Jean-Marie; Manns, Fabrice

2018-02-01

Optical coherence tomography (OCT) offers new options for imaging the ciliary muscle allowing direct in vivo visualization. However, variation in image quality along the length of the muscle prevents accurate delineation and quantification of the muscle. Quantitative analyses of the muscle are accompanied by variability in segmentation between examiners and between sessions for the same examiner. In processes such as accommodation where changes in muscle thickness may be tens of microns- the equivalent of a small number of image pixels, differences in segmentation can influence the magnitude and potentially the direction of thickness change. A detailed analysis of variability in ciliary muscle thickness measurements was performed to serve as a benchmark for the extent of this variability in studies on the ciliary muscle. Variation between sessions and examiners were found to be insignificant but the magnitude of variation should be considered when interpreting ciliary muscle results.

Nutrition, somatomedins, and the brain.

PubMed

Phillips, L S

1986-01-01

Conditions of decreased nutrient supply (malnutrition) and/or decreased nutrient utilization (diabetes) are attended by impairment of growth despite an increase in circulating levels of growth hormone (GH). Growth involves the actions of somatomedins, circulating insulinlike polypeptides with anabolic effects on cartilage, fat, and muscle. In malnutrition and diabetes, mechanisms of growth impairment appear to include a decrease in GH-induced generation of somatomedins, together with an increase in somatomedin inhibitors, factors which antagonize somatomedin action. Brain mediation of these alterations involves a rise in GH secretion due to decreased negative feedback from somatomedins, perhaps accentuated by blunting of feedback via actions of somatomedin inhibitors. In combination these processes lead to shunting of metabolic fuels toward vital processes and away from growth (via decreased somatomedin action) and to protein-sparing and increase in alternate metabolic fuels (via direct GH actions on muscle and fat). Further study of involved hypothalamic and pituitary mechanisms should yield additional insights into the role of the brain in metabolic homeostasis.

Prevalence of adult Pompe disease in patients with proximal myopathic syndrome and undiagnosed muscle biopsy.

PubMed

Golsari, Amir; Nasimzadah, Arzoo; Thomalla, Götz; Keller, Sarah; Gerloff, Christian; Magnus, Tim

2018-03-01

We examined patients with limb-girdle muscle weakness and/or hyper-CKaemia and undiagnosed muscle biopsy for late onset Pompe disease (LOPD). Patients with an inconclusive limb-girdle muscle weakness who presented at our neuromuscular centre between 2005 and 2015 with undiagnosed muscle biopsies were examined by dry blood spot testing (DBS) including determination of the enzyme activity of acid alpha-glucosidase (GAA). In the case of depressed enzyme activity, additional gene testing of the GAA gene was carried out. Of the 340 evaluated muscle biopsies, 69 patients fulfilled the inclusion criteria and were examined with DBS. Among those patients, 76% showed a limb-girdle muscle weakness and 14% showed a hyper-CKaemia. A diagnosis of LOPD could be established in the case of two patients (2.9%) with reduced GAA enzyme activity and proof of mutations in the GAA gene. One of the two patients presents in the muscle biopsy suggestive features of Pompe disease including vacuoles with positive acid phosphatase reaction. In summary, our results show that a muscle biopsy can be helpful in identifying LOPD patients, but vacuolation with glycogen storage can also be absent. An inconspicuous muscle biopsy does not rule out Pompe disease. Consequently, all patients with limb-girdle muscle weakness should be examined by DBS before conducting a muscle biopsy. Copyright © 2017 Elsevier B.V. All rights reserved.

Computational Failure Modeling of Lower Extremities

DTIC Science & Technology

2012-01-01

bone fracture, ligament tear, and muscle rupture . While these injuries may seem well-defined through medical imaging, the process of injury and the...to vehicles from improvised explosives cause severe injuries to the lower extremities, in- cluding bone fracture, ligament tear, and muscle rupture ...modeling offers a powerful tool to explore the insult-to-injury process with high-resolution. When studying a complex dynamic process such as this, it is

Muscle-Strengthening Activities and Participation among Adults in the United States

ERIC Educational Resources Information Center

Loustalot, Fleetwood; Carlson, Susan A.; Kruger, Judy; Buchner, David M.; Fulton, Janet E.

2013-01-01

Purpose: To describe those who reported meeting the "2008 Physical Activity Guidelines for Americans" ("2008 Guidelines") muscle-strengthening standard of 2 or more days per week, including all seven muscle groups, and to assess the type and location of muscle-strengthening activities performed. Method: Data from HealthStyles…

Syringomyelia

MedlinePlus

... are symptoms, they may include: Headache Loss of muscle mass ( wasting , atrophy), often in the arms and hands Spasms or tightness in the leg or hand and arm muscles Muscle function loss , loss of ability to use ...

The Molecular Basis for Load-Induced Skeletal Muscle Hypertrophy

PubMed Central

Marcotte, George R.; West, Daniel W.D.; Baar, Keith

2016-01-01

In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance. A tight relationship between muscle hypertrophy, acute increases in protein balance, and the activity of the mechanistic target of rapamycin complex 1 (mTORC1) was demonstrated 15 years ago. Since then, our understanding of the signals that regulate load-induced hypertrophy has evolved considerably. For example, we now know that mechanical load activates mTORC1 in the same way as growth factors, by moving TSC2 (a primary inhibitor of mTORC1) away from its target (the mTORC activator) Rheb. However, the kinase that phosphorylates and moves TSC2 is different in the two processes. Similarly, we have learned that a distinct pathway exists whereby amino acids activate mTORC1 by moving it to Rheb. While mTORC1 remains at the forefront of load-induced hypertrophy, the importance of other pathways that regulate muscle mass are becoming clearer. Myostatin, is best known for its control of developmental muscle size. However, new mechanisms to explain how loading regulates this process are suggesting that it could play an important role in hypertrophic muscle growth as well. Lastly, new mechanisms are highlighted for how β2 receptor agonists could be involved in load-induced muscle growth and why these agents are being developed as non-exercise-based therapies for muscle atrophy. Overall, the results highlight how studying the mechanism of load-induced skeletal muscle mass is leading the development of pharmaceutical interventions to promote muscle growth in those unwilling or unable to perform resistance exercise. PMID:25359125

An anatomical study of the transversus nuchae muscle: Application to better understanding occipital neuralgia.

PubMed

Watanabe, Koichi; Saga, Tsuyoshi; Iwanaga, Joe; Tabira, Yoko; Yamaki, Koh-Ichi

2017-01-01

The transversus nuchae muscle appears inconsistently in the occipital region. It has gained attention as one of the muscles composing the superficial musculoaponeurotic system (SMAS). The purpose of this study was to clarify its detailed anatomical features. We examined 124 sides of 62 cadavers. The transversus nuchae muscle was identified when present and examined after it had been completely exposed. We also examined its relationship to the occipital cutaneous nerves.The transversus nuchae muscle was detected in 40 sides (40/124, 32.2%) of 26 cadavers; it was present bilaterally in 14 and unilaterally in 12. It originated from the external occipital protuberance; 43% of the observed muscles inserted around the mastoid process, and 58% curved upward around the mastoid process and became the uppermost bundle of the platysma. In one case, an additional bundle originated from the lower posterior border of the sternocleidomastoid muscle and coursed obliquely upward along with platysma. Ninety percent of the muscles ran below the sling through which the greater occipital nerve passed; 65% of the lesser occipital nerves ran deep to the muscle, and 55% of the great auricular nerves ran superficial to it. Our observations clarify the unique anatomical features of the transversus nuchae muscle. We found that it occurs at a rate similar to that described in previous reports, but its arrangement is variable. Further investigations will be performed to clarify its innervation and other anatomical features. Clin. Anat. 30:32-38, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Skeletal Muscle Function during Exercise—Fine-Tuning of Diverse Subsystems by Nitric Oxide

PubMed Central

Suhr, Frank; Gehlert, Sebastian; Grau, Marijke; Bloch, Wilhelm

2013-01-01

Skeletal muscle is responsible for altered acute and chronic workload as induced by exercise. Skeletal muscle adaptations range from immediate change of contractility to structural adaptation to adjust the demanded performance capacities. These processes are regulated by mechanically and metabolically induced signaling pathways, which are more or less involved in all of these regulations. Nitric oxide is one of the central signaling molecules involved in functional and structural adaption in different cell types. It is mainly produced by nitric oxide synthases (NOS) and by non-enzymatic pathways also in skeletal muscle. The relevance of a NOS-dependent NO signaling in skeletal muscle is underlined by the differential subcellular expression of NOS1, NOS2, and NOS3, and the alteration of NO production provoked by changes of workload. In skeletal muscle, a variety of highly relevant tasks to maintain skeletal muscle integrity and proper signaling mechanisms during adaptation processes towards mechanical and metabolic stimulations are taken over by NO signaling. The NO signaling can be mediated by cGMP-dependent and -independent signaling, such as S-nitrosylation-dependent modulation of effector molecules involved in contractile and metabolic adaptation to exercise. In this review, we describe the most recent findings of NO signaling in skeletal muscle with a special emphasis on exercise conditions. However, to gain a more detailed understanding of the complex role of NO signaling for functional adaptation of skeletal muscle (during exercise), additional sophisticated studies are needed to provide deeper insights into NO-mediated signaling and the role of non-enzymatic-derived NO in skeletal muscle physiology. PMID:23538841

[The significance of Ulex europaeus agglutinin I lectin binding fibers in various muscular diseases].

PubMed

Yatabe, K; Hiraguri, M; Sueishi, M; Takeuchi, M; Nonaka, I; Kawai, M

1998-05-01

In the present study, we have reported that Ulex europaeus agglutinin I (UEA I) lectin labeled muscle fibers in distal myopathy with rimmed vacuole formation (DMRV). UEA I binding to muscle fibers was also observed in a small number of biopsies with inflammatory myopathy, but not in other diseases, including neurogenic muscular atrophies and muscular dystrophies. In order to elucidate the relationship between this UEA I binding, rimmed vacuole formation and active autophagocytosis, we examined the UEA I binding fibers in other myopathies which frequently showed rimmed vacuoles, including adult onset acid maltase deficiency, oculo-pharyngo-distal type myopathy and oculopharyngeal muscular dystrophy. No UEA I lectin labeling fiber was observed in the diseases examined. We then studied UEA I binding behavior on 70 biopsies of inflammatory myopathy to characterize the clinical features of UEA I binding positive patients. UEA I binding fibers were observed in 3 of 28 patients (11%) with other collagen diseases, 11 of 36 (31%) without these disorders, and 2 of 6 (33%) with inclusion body myositis. There were no common clinical histories, complications or laboratory findings among the UEA I binding positive patients. In conclusion, a common process may exist between the muscle fiber degeneration in DMRV and subgroups of inflammatory myopathy patients, but the basic mechanism remains to be elucidated.

A systematic review of surface electromyography analyses of the bench press movement task

PubMed Central

Gołaś, Artur; Blazek, Dusan; Maszczyk, Adam; Wilk, Michał; Pietraszewski, Przemysław; Petr, Miroslav; Uhlir, Petr; Zając, Adam

2017-01-01

Background The bench press exercise (BP) plays an important role in recreational and professional training, in which muscle activity is an important multifactorial phenomenon. The objective of this paper is to systematically review electromyography (EMG) studies performed on the barbell BP exercise to answer the following research questions: Which muscles show the greatest activity during the flat BP? Which changes in muscle activity are related to specific conditions under which the BP movement is performed? Strategy PubMed, Scopus, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library were searched through June 10, 2016. A combination of the following search terms was used: bench press, chest press, board press, test, measure, assessment, dynamometer, kinematics and biomechanics. Only original, full-text articles were considered. Results The search process resulted in 14 relevant studies that were included in the discussion. The triceps brachii (TB) and pectoralis major (PM) muscles were found to have similar activity during the BP, which was significantly higher than the activity of the anterior deltoid. During the BP movement, muscle activity changes with exercise intensity, velocity of movement, fatigue, mental focus, movement phase and stability conditions, such as bar vibration or unstable surfaces. Under these circumstances, TB is the most common object of activity change. Conclusions PM and TB EMG activity is more dominant and shows greater EMG amplitude than anterior deltoid during the BP. There are six factors that can influence muscle activity during the BP; however, the most important factor is exercise intensity, which interacts with all other factors. The research on muscle activity in the BP has several unresolved areas, such as clearly and strongly defined guidelines to perform EMG measurements (e.g., how to elaborate with surface EMG limits) or guidelines for the use of exact muscle models. PMID:28170449

A peripheral governor regulates muscle contraction.

PubMed

MacIntosh, Brian R; Shahi, M Reza S

2011-02-01

Active skeletal muscles are capable of keeping the global [adenosine triphosphate (ATP)] reasonably constant during exercise, whether it is mild exercise, activating a few motor units, or all-out exercise using a substantial mass of muscle. This could only be accomplished if there were regulatory processes in place not only to replenish ATP as quickly as possible, but also to modulate the rate of ATP use when that rate threatens to exceed the rate of ATP replenishment, a situation that could lead to metabolic catastrophe. This paper proposes that there is a regulatory process or "peripheral governor" that can modulate activation of muscle to avoid metabolic catastrophe. A peripheral governor, working at the cellular level, should be able to reduce the cellular rate of ATP hydrolysis associated with muscle contraction by attenuating activation. This would necessarily cause something we call peripheral fatigue (i.e., reduced contractile response to a given stimulation). There is no doubt that peripheral fatigue occurs. It has been demonstrated in isolated muscles, in muscles in situ with no central nervous system input, and in intact human subjects performing voluntary exercise with small muscle groups or doing whole-body exercise. The regulation of muscle activation is achieved in at least 3 ways (decreasing membrane excitability, inhibiting Ca2+ release through ryanodine receptors, and decreasing the availability of Ca2+ in the sarcoplasmic reticulum), making this a highly redundant control system. The peripheral governor attenuates cellular activation to reduce the metabolic demand, thereby preserving ATP and the integrity of the cell.

Differentiation of original and regenerated skeletal muscle fibres in mdx dystrophic muscles.

PubMed

Earnshaw, John C; Kyprianou, Phillip; Krishan, Kewal; Dhoot, Gurtej K

2002-07-01

The differentiation of both original muscle fibres and the regenerated muscle fibres following necrosis in mdx muscles was investigated using immunoblotting and immunocytochemical procedures. Before the onset of necrosis, postnatal skeletal muscles in mdx mouse differentiated well with only a slight delay in differentiation indicated by the level of developmental isoforms of troponin T. Prior to the onset of apparent myopathic change, both fast and slow skeletal muscle fibre types in mdx leg muscles also differentiated well when investigated by analysis of specific myosin heavy chain expression pattern. While the original muscle fibres in mdx leg muscles developed well, the differentiation of regenerated myotubes into both slow and distinct fast muscle fibre types, however, was markedly delayed or inhibited as indicated by several clusters of homogeneously staining fibres even at 14 weeks of age. The number of slow myosin heavy chain-positive myotubes amongst the regenerated muscle clusters was quite small even in soleus. This study thus established that while muscle fibres initially develop normally with only a slight delay in the differentiation process, the differentiation of regenerated myotubes in mdx muscles is markedly compromised and consequently delayed.

Composition of Muscle Fiber Types in Rat Rotator Cuff Muscles.

PubMed

Rui, Yongjun; Pan, Feng; Mi, Jingyi

2016-10-01

The rat is a suitable model to study human rotator cuff pathology owing to the similarities in morphological anatomy structure. However, few studies have reported the composition muscle fiber types of rotator cuff muscles in the rat. In this study, the myosin heavy chain (MyHC) isoforms were stained by immunofluorescence to show the muscle fiber types composition and distribution in rotator cuff muscles of the rat. It was found that rotator cuff muscles in the rat were of mixed fiber type composition. The majority of rotator cuff fibers labeled positively for MyHCII. Moreover, the rat rotator cuff muscles contained hybrid fibers. So, compared with human rotator cuff muscles composed partly of slow-twitch fibers, the majority of fast-twitch fibers in rat rotator cuff muscles should be considered when the rat model study focus on the pathological process of rotator cuff muscles after injury. Gaining greater insight into muscle fiber types in rotator cuff muscles of the rat may contribute to elucidate the mechanism of pathological change in rotator cuff muscles-related diseases. Anat Rec, 299:1397-1401, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fate of 3H-thymidine labelled myogenic cells in regeneration of muscle isografts.

PubMed

Gutmann, E; Mares, V; Stichová, J

1976-03-05

Intact and denervated extensor digitorum longus (EDL) muscles of 20-day-old inbred Lewis-Wistar rats were labelled with 3H-thymidine. Ninety minutes after the injection of the isotope 4.0% of the nuclei were labelled in the intact (i.e. innervated) and 9.6% in the muscles, denervated 3 days before administration of the isotope. The labelled EDL muscles were grafted into the bed of the previously removed EDL muscles of inbred animals and these isografts were studied 30 days later. In the EDL muscles, regenerated from innervated isografts only occasionally labelled endothelial cells were found whereas in the muscles regenerated from denervated isografts also parenchymal muscle nuclei were regularly labelled. The incidence of labelled nuclei in the regenerated EDL muscles was, however, about 20 times lower than in the donor EDL muscles. The presen experiments provide a direct proof of utilization of donor satelite cell nuclei for regeneration in grafted muscle tissue. With respect to the low incidence of labelled nuclei in regenerated EDL muscles, other sources of cells apparently also contribute to the regeneration process.

Kinesthetic illusions attenuate experimental muscle pain, as do muscle and cutaneous stimulation.

PubMed

Gay, André; Aimonetti, Jean-Marc; Roll, Jean-Pierre; Ribot-Ciscar, Edith

2015-07-30

In the present study, muscle pain was induced experimentally in healthy subjects by administrating hypertonic saline injections into the tibialis anterior (TA) muscle. We first aimed at comparing the analgesic effects of mechanical vibration applied to either cutaneous or muscle receptors of the TA or to both types simultaneously. Secondly, pain alleviation was compared in subjects in whom muscle tendon vibration evoked kinesthetic illusions of the ankle joint. Muscle tendon vibration, which primarily activated muscle receptors, reduced pain intensity by 30% (p<0.01). In addition, tangential skin vibration reduced pain intensity by 33% (p<0.01), primarily by activating cutaneous receptors. Concurrently stimulating both sensory channels induced stronger analgesic effects (-51%, p<0.01), as shown by the lower levels of electrodermal activity. The strongest analgesic effects of the vibration-induced muscle inputs occurred when illusory movements were perceived (-38%, p=0.01). The results suggest that both cutaneous and muscle sensory feedback reduce muscle pain, most likely via segmental and supraspinal processes. Further clinical trials are needed to investigate these new methods of muscle pain relief. Copyright © 2015 Elsevier B.V. All rights reserved.

The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

PubMed Central

Chen, Justin L.; Qian, Hongwei; Liu, Yingying; Bernardo, Bianca C.; Beyer, Claudia; Watt, Kevin I.; Thomson, Rachel E.; Connor, Timothy; Turner, Bradley J.; McMullen, Julie R.; Larsson, Lars; McGee, Sean L.; Harrison, Craig A.

2013-01-01

Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders. PMID:24145169

Optical Cross-Sectional Muscle Area Determination of Drosophila Melanogaster Adult Indirect Flight Muscles.

PubMed

Selma-Soriano, Estela; Artero, Rubén; Llamusi, Beatriz

2018-03-31

Muscle mass wasting, known as muscle atrophy, is a common phenotype in Drosophila models of neuromuscular diseases. We have used the indirect flight muscles (IFMs) of flies, specifically the dorso-longitudinal muscles (DLM), as the experimental subject to measure the atrophic phenotype brought about by different genetic causes. In this protocol, we describe how to embed fly thorax muscles for semi thin sectioning, how to obtain a good contrast between muscle and the surrounding tissue, and how to process optical microscope images for semiautomatic acquisition of quantifiable data and analysis. We describe three specific applications of the methodological pipeline. First, we show how the method can be applied to quantify muscle degeneration in a myotonic dystrophy fly model; second, measurement of muscle cross-sectional area can help to identify genes that either promote or prevent muscle atrophy and/or muscle degeneration; third, this protocol can be applied to determine whether a candidate compound is able to significantly modify a given atrophic phenotype induced by a disease-causing mutation or by an environmental trigger.

Constitutive activation of CaMKKα signaling is sufficient but not necessary for mTORC1 activation and growth in mouse skeletal muscle.

PubMed

Ferey, Jeremie L A; Brault, Jeffrey J; Smith, Cheryl A S; Witczak, Carol A

2014-10-15

Skeletal muscle loading/overload stimulates the Ca²⁺-activated, serine/threonine kinase Ca²⁺/calmodulin-dependent protein kinase kinase-α (CaMKKα); yet to date, no studies have examined whether CaMKKα regulates muscle growth. The purpose of this study was to determine if constitutive activation of CaMKKα signaling could stimulate muscle growth and if so whether CaMKKα is essential for this process. CaMKKα signaling was selectively activated in mouse muscle via expression of a constitutively active form of CaMKKα using in vivo electroporation. After 2 wk, constitutively active CaMKKα expression increased muscle weight (~10%) and protein content (~10%), demonstrating that activation of CaMKKα signaling can stimulate muscle growth. To determine if active CaMKKα expression stimulated muscle growth via increased mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis, [³H]phenylalanine incorporation into proteins was assessed with or without the mTORC1 inhibitor rapamycin. Constitutively active CaMKKα increased protein synthesis ~60%, and this increase was prevented by rapamycin, demonstrating a critical role for mTORC1 in this process. To determine if CaMKKα is essential for growth, muscles from CaMKKα knockout mice were stimulated to hypertrophy via unilateral ablation of synergist muscles (overload). Surprisingly, compared with wild-type mice, muscles from CaMKKα knockout mice exhibited greater growth (~15%) and phosphorylation of the mTORC1 substrate 70-kDa ribosomal protein S6 kinase (Thr³⁸⁹; ~50%), demonstrating that CaMKKα is not essential for overload-induced mTORC1 activation or muscle growth. Collectively, these results demonstrate that activation of CaMKKα signaling is sufficient but not necessary for activation of mTORC1 signaling and growth in mouse skeletal muscle. Copyright © 2014 the American Physiological Society.

Constitutive activation of CaMKKα signaling is sufficient but not necessary for mTORC1 activation and growth in mouse skeletal muscle

PubMed Central

Ferey, Jeremie L. A.; Brault, Jeffrey J.; Smith, Cheryl A. S.

2014-01-01

Skeletal muscle loading/overload stimulates the Ca2+-activated, serine/threonine kinase Ca2+/calmodulin-dependent protein kinase kinase-α (CaMKKα); yet to date, no studies have examined whether CaMKKα regulates muscle growth. The purpose of this study was to determine if constitutive activation of CaMKKα signaling could stimulate muscle growth and if so whether CaMKKα is essential for this process. CaMKKα signaling was selectively activated in mouse muscle via expression of a constitutively active form of CaMKKα using in vivo electroporation. After 2 wk, constitutively active CaMKKα expression increased muscle weight (∼10%) and protein content (∼10%), demonstrating that activation of CaMKKα signaling can stimulate muscle growth. To determine if active CaMKKα expression stimulated muscle growth via increased mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis, [3H]phenylalanine incorporation into proteins was assessed with or without the mTORC1 inhibitor rapamycin. Constitutively active CaMKKα increased protein synthesis ∼60%, and this increase was prevented by rapamycin, demonstrating a critical role for mTORC1 in this process. To determine if CaMKKα is essential for growth, muscles from CaMKKα knockout mice were stimulated to hypertrophy via unilateral ablation of synergist muscles (overload). Surprisingly, compared with wild-type mice, muscles from CaMKKα knockout mice exhibited greater growth (∼15%) and phosphorylation of the mTORC1 substrate 70-kDa ribosomal protein S6 kinase (Thr389; ∼50%), demonstrating that CaMKKα is not essential for overload-induced mTORC1 activation or muscle growth. Collectively, these results demonstrate that activation of CaMKKα signaling is sufficient but not necessary for activation of mTORC1 signaling and growth in mouse skeletal muscle. PMID:25159322

Functional β-Adrenoceptors Are Important for Early Muscle Regeneration in Mice through Effects on Myoblast Proliferation and Differentiation

PubMed Central

Church, Jarrod E.; Trieu, Jennifer; Sheorey, Radhika; Chee, Annabel Y. -M.; Naim, Timur; Baum, Dale M.; Ryall, James G.; Gregorevic, Paul; Lynch, Gordon S.

2014-01-01

Muscles can be injured in different ways and the trauma and subsequent loss of function and physical capacity can impact significantly on the lives of patients through physical impairments and compromised quality of life. The relative success of muscle repair after injury will largely determine the extent of functional recovery. Unfortunately, regenerative processes are often slow and incomplete, and so developing novel strategies to enhance muscle regeneration is important. While the capacity to enhance muscle repair by stimulating β2-adrenoceptors (β-ARs) using β2-AR agonists (β2-agonists) has been demonstrated previously, the exact role β-ARs play in regulating the regenerative process remains unclear. To investigate β-AR-mediated signaling in muscle regeneration after myotoxic damage, we examined the regenerative capacity of tibialis anterior and extensor digitorum longus muscles from mice lacking either β1-AR (β1-KO) and/or β2-ARs (β2-KO), testing the hypothesis that muscles from mice lacking the β2-AR would exhibit impaired functional regeneration after damage compared with muscles from β1-KO or β1/β2-AR null (β1/β2-KO) KO mice. At 7 days post-injury, regenerating muscles from β1/β2-KO mice produced less force than those of controls but muscles from β1-KO or β2-KO mice did not exhibit any delay in functional restoration. Compared with controls, β1/β2-KO mice exhibited an enhanced inflammatory response to injury, which delayed early muscle regeneration, but an enhanced myoblast proliferation later during regeneration ensured a similar functional recovery (to controls) by 14 days post-injury. This apparent redundancy in the β-AR signaling pathway was unexpected and may have important implications for manipulating β-AR signaling to improve the rate, extent and efficacy of muscle regeneration to enhance functional recovery after injury. PMID:25000590

Desmin Is Essential for the Tensile Strength and Integrity of Myofibrils but Not for Myogenic Commitment, Differentiation, and Fusion of Skeletal Muscle

PubMed Central

Li, Zhenlin; Mericskay, Mathias; Agbulut, Onnik; Butler-Browne, Gillian; Carlsson, Lena; Thornell, Lars-Eric; Babinet, Charles; Paulin, Denise

1997-01-01

A null mutation was introduced into the mouse desmin gene by homologous recombination. The desmin knockout mice (Des −/−) develop normally and are fertile. However, defects were observed after birth in skeletal, smooth, and cardiac muscles (Li, Z., E. Colucci-Guyon, M. Pincon-Raymond, M. Mericskay, S. Pournin, D. Paulin, and C. Babinet. 1996. Dev. Biol. 175:362–366; Milner, D.J., G. Weitzer, D. Tran, A. Bradley, and Y. Capetanaki. 1996. J. Cell Biol. 134:1255– 1270). In the present study we have carried out a detailed analysis of somitogenesis, muscle formation, maturation, degeneration, and regeneration in Des −/− mice. Our results demonstrate that all early stages of muscle differentiation and cell fusion occur normally. However, after birth, modifications were observed essentially in weight-bearing muscles such as the soleus or continually used muscles such as the diaphragm and the heart. In the absence of desmin, mice were weaker and fatigued more easily. The lack of desmin renders these fibers more susceptible to damage during contraction. We observed a process of degeneration of myofibers, accompanied by macrophage infiltration, and followed by a process of regeneration. These cycles of degeneration and regeneration resulted in a relative increase in slow myosin heavy chain (MHC) and decrease in fast MHC. Interestingly, this second wave of myofibrillogenesis during regeneration was often aberrant and showed signs of disorganization. Subsarcolemmal accumulation of mitochondria were also observed in these muscles. The lack of desmin was not compensated by an upregulation of vimentin in these mice either during development or regeneration. Absence of desmin filaments within the sarcomere does not interfere with primary muscle formation or regeneration. However, myofibrillogenesis in regenerating fibers is often abortive, indicating that desmin may be implicated in this repair process. The results presented here show that desmin is essential to maintain the structural integrity of highly solicited skeletal muscle. PMID:9314534

Influence of Passive Muscle Tension on Electromechanical Delay in Humans

PubMed Central

Lacourpaille, Lilian; Hug, François; Nordez, Antoine

2013-01-01

Background Electromechanical delay is the time lag between onsets of muscle activation and muscle force production and reflects both electro-chemical processes and mechanical processes. The aims of the present study were two-fold: to experimentally determine the slack length of each head of the biceps brachii using elastography and to determine the influence of the length of biceps brachii on electromechanical delay and its electro-chemical/mechanical processes using very high frame rate ultrasound. Methods/Results First, 12 participants performed two passive stretches to evaluate the change in passive tension for each head of the biceps brachii. Then, they underwent two electrically evoked contractions from 120 to 20° of elbow flexion (0°: full extension), with the echographic probe maintained over the muscle belly and the myotendinous junction of biceps brachii. The slack length was found to occur at 95.5 ± 6.3° and 95.3 ± 8.2° of the elbow joint angle for the long and short heads of the biceps brachii, respectively. The electromechanical delay was significantly longer at 120° (16.9 ± 3.1 ms; p<0.001), 110° (15.0 ± 3.1 ms; p<0.001) and 100° (12.7 ± 2.5 ms; p = 0.01) of elbow joint angle compared to 90° (11.1 ± 1.7 ms). However, the delay between the onset of electrical stimulation and the onset of both muscle fascicles (3.9 ± 0.2 ms) and myotendinous junction (3.7 ± 0.3 ms) motion was not significantly affected by the joint angle (p>0.95). Conclusion In contrast to previous observations on gastrocnemius medialis, the onset of muscle motion and the onset of myotendinous junction motion occurred simultaneously regardless of the length of the biceps brachii. That suggests that the between-muscles differences reported in the literature cannot be explained by different muscle passive tension but instead may be attributable to muscle architectural differences. PMID:23308153

3D finite element models of shoulder muscles for computing lines of actions and moment arms.

PubMed

Webb, Joshua D; Blemker, Silvia S; Delp, Scott L

2014-01-01

Accurate representation of musculoskeletal geometry is needed to characterise the function of shoulder muscles. Previous models of shoulder muscles have represented muscle geometry as a collection of line segments, making it difficult to account for the large attachment areas, muscle-muscle interactions and complex muscle fibre trajectories typical of shoulder muscles. To better represent shoulder muscle geometry, we developed 3D finite element models of the deltoid and rotator cuff muscles and used the models to examine muscle function. Muscle fibre paths within the muscles were approximated, and moment arms were calculated for two motions: thoracohumeral abduction and internal/external rotation. We found that muscle fibre moment arms varied substantially across each muscle. For example, supraspinatus is considered a weak external rotator, but the 3D model of supraspinatus showed that the anterior fibres provide substantial internal rotation while the posterior fibres act as external rotators. Including the effects of large attachment regions and 3D mechanical interactions of muscle fibres constrains muscle motion, generates more realistic muscle paths and allows deeper analysis of shoulder muscle function.

3D Finite Element Models of Shoulder Muscles for Computing Lines of Actions and Moment Arms

PubMed Central

Webb, Joshua D.; Blemker, Silvia S.; Delp, Scott L.

2014-01-01

Accurate representation of musculoskeletal geometry is needed to characterize the function of shoulder muscles. Previous models of shoulder muscles have represented muscle geometry as a collection of line segments, making it difficult to account the large attachment areas, muscle-muscle interactions, and complex muscle fiber trajectories typical of shoulder muscles. To better represent shoulder muscle geometry we developed three-dimensional finite element models of the deltoid and rotator cuff muscles and used the models to examine muscle function. Muscle fiber paths within the muscles were approximated, and moment arms were calculated for two motions: thoracohumeral abduction and internal/external rotation. We found that muscle fiber moment arms varied substantially across each muscle. For example, supraspinatus is considered a weak external rotator, but the three-dimensional model of supraspinatus showed that the anterior fibers provide substantial internal rotation while the posterior fibers act as external rotators. Including the effects of large attachment regions and three-dimensional mechanical interactions of muscle fibers constrains muscle motion, generates more realistic muscle paths, and allows deeper analysis of shoulder muscle function. PMID:22994141

Correction to: Comparison of multiple transcriptomes exposes unified and divergent features of quiescent and activated skeletal muscle stem cells.

PubMed

Pietrosemoli, Natalia; Mella, Sébastien; Yennek, Siham; Baghdadi, Meryem B; Sakai, Hiroshi; Sambasivan, Ramkumar; Pala, Francesca; Di Girolamo, Daniela; Tajbakhsh, Shahragim

2018-06-06

After publication of this article [1], the authors noted that the legends for supplementary files Figures S3 and S4 were truncated in the production process, therefore lacking some information concerning these Figures. The complete legends are included in this Correction. The authors apologize for any inconvenience that this might have caused.

Morphology of the lumbar transversospinal muscles examined in a mouse bearing a muscle fiber-specific nuclear marker.

PubMed

Cornwall, Jon; Deries, Marianne; Duxson, Marilyn

2010-12-01

Although the morphology of human lumbar transversospinal (TSP) muscles has been studied, little is known about the structure of these muscles in the mouse (Mus musculus). Such information is relevant given mice are often used as a "normal" phenotype for studies modeling human development. This study describes the gross morphology, muscle fiber arrangement, and innervation pattern of the mouse lumbar TSP muscles. A unique feature of the study is the use of a transgenic mouse line bearing a muscle-specific nuclear marker that allows clear delineation of muscle fiber and connective tissue boundaries. The lumbar TSP muscles of five mice were examined bilaterally; at each spinal level muscles attached to the caudal edge of the spinous process and passed caudally as a single complex unit. Fibers progressively terminated over the four vertebral segments caudad, with multiple points of muscle fiber attachment on each vertebra. Motor endplates, defined with acetylcholinesterase histochemistry, were consistently located half way along each muscle fiber, regardless of length, with all muscle fibers arranged in-parallel rather than in-series. These results provide information relevant to interpretation of developmental and functional studies involving this muscle group in the mouse and show mouse lumbar TSP muscles are different in form to descriptions of equivalent muscles in humans and horses.

Multi-functional dielectric elastomer artificial muscles for soft and smart machines

NASA Astrophysics Data System (ADS)

Anderson, Iain A.; Gisby, Todd A.; McKay, Thomas G.; O'Brien, Benjamin M.; Calius, Emilio P.

2012-08-01

Dielectric elastomer (DE) actuators are popularly referred to as artificial muscles because their impressive actuation strain and speed, low density, compliant nature, and silent operation capture many of the desirable physical properties of muscle. Unlike conventional robots and machines, whose mechanisms and drive systems rapidly become very complex as the number of degrees of freedom increases, groups of DE artificial muscles have the potential to generate rich motions combining many translational and rotational degrees of freedom. These artificial muscle systems can mimic the agonist-antagonist approach found in nature, so that active expansion of one artificial muscle is taken up by passive contraction in the other. They can also vary their stiffness. In addition, they have the ability to produce electricity from movement. But departing from the high stiffness paradigm of electromagnetic motors and gearboxes leads to new control challenges, and for soft machines to be truly dexterous like their biological analogues, they need precise control. Humans control their limbs using sensory feedback from strain sensitive cells embedded in muscle. In DE actuators, deformation is inextricably linked to changes in electrical parameters that include capacitance and resistance, so the state of strain can be inferred by sensing these changes, enabling the closed loop control that is critical for a soft machine. But the increased information processing required for a soft machine can impose a substantial burden on a central controller. The natural solution is to distribute control within the mechanism itself. The octopus arm is an example of a soft actuator with a virtually infinite number of degrees of freedom (DOF). The arm utilizes neural ganglia to process sensory data at the local "arm" level and perform complex tasks. Recent advances in soft electronics such as the piezoresistive dielectric elastomer switch (DES) have the potential to be fully integrated with actuators and sensors. With the DE switch, we can produce logic gates, oscillators, and a memory element, the building blocks for a soft computer, thus bringing us closer to emulating smart living structures like the octopus arm. The goal of future research is to develop fully soft machines that exploit smart actuation networks to gain capabilities formerly reserved to nature, and open new vistas in mechanical engineering.

Follistatin: A Potential Anabolic Treatment for Re-Innervated Muscle

DTIC Science & Technology

2017-09-01

Observations: ELISA , muscle histology, nerve histology, etc.are pending and no final conclusions can be made. 1. 3-month Protein: a. Muscle Weight: No...and virus needed for the study and also helped in Pilot Study- ELISA . He presented the following abstract in VCU School of Medicine Student Research...denervation groups (1-6): ▪ Follistatin ELISA – Run the assay, collect data, and prepare to present data ▪ Muscle Histology – Process tissue, image the

Cooling improves the writing performance of patients with writer's cramp.

PubMed

Pohl, Christoph; Happe, Jörg; Klockgether, Thomas

2002-11-01

Cooling of hand and forearm muscles by immersion in 15 degrees C cold water for 5 minutes improved the writing performance of patients with writer's cramp. Since abnormal processing of muscle spindle afferent discharges contributes to the pathology of writer's cramp, this effect might result from a reduction in muscle spindle activity by lowering muscle temperature. Cooling is a simple, cheap, and safe procedure, providing temporary relief for patients with writer's cramp. Copyright 2002 Movement Disorder Society

Assignment and expression patterns of porcine muscle-specific isoform of phosphoglycerate mutase gene.

PubMed

Qiu, Haifang; Zhao, Shuhong; Xu, Xuewen; Yerle, Martine; Liu, Bang

2008-05-01

It has been reported that the muscle-specific isoform (type M, PGAM2) of phosphoglycerate mutase (PGAM) is a housekeeping enzyme; it catalyzes the conversion of 3-phosphoglycerate into 2-phosphoglycerate in the glycolysis process to release energy. It is encoded by the Pgam2 gene. In this study, the cDNA of the porcine Pgam2 was cloned. This gene contains an open reading frame of 765 bp encoding a protein of 253 residues, and the predicted protein sequences share high similarity with other mammalians, 96% identity with humans, and 94% identity with mouse and rats. Pgam2 was mapped to SSC18q13-q21 by the RH panel. In this region, there are several QTLs, such as fat ratio, lean percentage, and diameter of muscle fiber, which affect meat production and quality. The reverse transcriptase-polymerase chain reaction revealed that the porcine Pgam2 gene was mainly expressed in the muscle tissue (skeletal muscle and cardiac muscle), and was expressed highly at skeletal muscle development stages (embryonic periods: 33, 65, and 90 days post-conception (dpc); postnatal pigs: 4 days and adult). This indicates that the Pgam2 gene plays an important role in muscle growth and development. In addition, it was demonstrated that PGAM2 locates both in cytoplasm and nuclei, and takes part in the glycometabolism process of cytoplasm and nuclei.

Muscle activation described with a differential equation model for large ensembles of locally coupled molecular motors.

PubMed

Walcott, Sam

2014-10-01

Molecular motors, by turning chemical energy into mechanical work, are responsible for active cellular processes. Often groups of these motors work together to perform their biological role. Motors in an ensemble are coupled and exhibit complex emergent behavior. Although large motor ensembles can be modeled with partial differential equations (PDEs) by assuming that molecules function independently of their neighbors, this assumption is violated when motors are coupled locally. It is therefore unclear how to describe the ensemble behavior of the locally coupled motors responsible for biological processes such as calcium-dependent skeletal muscle activation. Here we develop a theory to describe locally coupled motor ensembles and apply the theory to skeletal muscle activation. The central idea is that a muscle filament can be divided into two phases: an active and an inactive phase. Dynamic changes in the relative size of these phases are described by a set of linear ordinary differential equations (ODEs). As the dynamics of the active phase are described by PDEs, muscle activation is governed by a set of coupled ODEs and PDEs, building on previous PDE models. With comparison to Monte Carlo simulations, we demonstrate that the theory captures the behavior of locally coupled ensembles. The theory also plausibly describes and predicts muscle experiments from molecular to whole muscle scales, suggesting that a micro- to macroscale muscle model is within reach.

Effects of hyperthyroidism and hypothyroidism on glutamine metabolism by skeletal muscle of the rat.

PubMed Central

Parry-Billings, M; Dimitriadis, G D; Leighton, B; Bond, J; Bevan, S J; Opara, E; Newsholme, E A

1990-01-01

1. The effects of hyperthyroidism and hypothyroidism on the concentrations of glutamine and other amino acids in the muscle and plasma and on the rates of glutamine and alanine release from incubated isolated stripped soleus muscle of the rat were investigated. 2. Hyperthyroidism decreased the concentration of glutamine in soleus muscle but was without effect on that in the gastrocnemius muscle or in the plasma. Hyperthyroidism also increased markedly the rate of release of glutamine from the incubated soleus muscle. 3. Hypothyroidism decreased the concentrations of glutamine in the gastrocnemius muscle and plasma but was without effect on that in soleus muscle. Hypothyroidism also decreased markedly the rate of glutamine release from the incubated soleus muscle. 4. Thyroid status was found to have marked effects on the rate of glutamine release by skeletal muscle per se, and may be important in the control of this process in both physiological and pathological conditions. PMID:2268261

PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity.

PubMed

Jans, Anneke; Konings, Ellen; Goossens, Gijs H; Bouwman, Freek G; Moors, Chantalle C; Boekschoten, Mark V; Afman, Lydia A; Müller, Michael; Mariman, Edwin C; Blaak, Ellen E

2012-04-01

Dietary fat quality may influence skeletal muscle lipid processing and fat accumulation, thereby modulating insulin sensitivity. The objective was to examine the acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA processing and postprandial insulin sensitivity in obese, insulin-resistant men. In a single-blind, randomized, crossover study, 10 insulin-resistant men consumed 3 high-fat mixed meals (2.6 MJ), which were high in SFAs, MUFAs, or PUFAs. Fasting and postprandial skeletal muscle FA processing was examined by measuring differences in arteriovenous concentrations across the forearm muscle. [²H₂]Palmitate was infused intravenously to label endogenous triacylglycerol and FFAs in the circulation, and [U-¹³C]palmitate was added to the meal to label chylomicron-triacylglycerol. Skeletal muscle biopsy samples were taken to assess intramuscular lipid metabolism and gene expression. Insulin and glucose responses (AUC) after the SFA meal were significantly higher than those after the PUFA meal (P = 0.006 and 0.033, respectively). Uptake of triacylglycerol-derived FAs was lower in the postprandial phase after the PUFA meal than after the other meals (AUC₆₀₋₂₄₀; P = 0.02). The fractional synthetic rate of the triacylglycerol, diacylglycerol, and phospholipid pool was higher after the MUFA meal than after the SFA meal. PUFA induced less transcriptional downregulation of oxidative pathways than did the other meals. PUFAs reduced triacylglycerol-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity, a more transcriptional oxidative phenotype, and altered intramyocellular lipid partitioning and may therefore be protective against the development of insulin resistance.

The multilevel antibiotic-induced perturbations to biological systems: Early-life exposure induces long-lasting damages to muscle structure and mitochondrial metabolism in flies.

PubMed

Renault, David; Yousef, Hesham; Mohamed, Amr A

2018-06-07

Antibiotics have been increasingly used over the past decades for human medicine, food-animal agriculture, aquaculture, and plant production. A significant part of the active molecules of antibiotics can be released into the environment, in turn affecting ecosystem functioning and biogeochemical processes. At lower organizational scales, these substances affect bacterial symbionts of insects, with negative consequences on growth and development of juveniles, and population dynamics. Yet, the multiple alterations of cellular physiology and metabolic processes have remained insufficiently explored in insects. We evaluated the effects of five antibiotics with different mode of action, i.e. ampicillin, cefradine, chloramphenicol, cycloheximide, and tetracycline, on the survival and ultrastructural organization of the flight muscles of newly emerged blow flies Chrysomya albiceps. Then, we examined the effects of different concentrations of antibiotics on mitochondrial protein content, efficiency of oxidative phosphorylation, and activity of transaminases (Glutamate oxaloacetate transaminase and glutamate pyruvate transaminase) and described the cellular metabolic perturbations of flies treated with antibiotics. All antibiotics affected the survival of the insects and decreased the total mitochondrial protein content in a dose-dependent manner. Ultrastructural organization of flight muscles in treated flies differs dramatically compared to the control groups and severe pathological damages/structures disorganization of mitochondria appeared. The activities of mitochondrial transaminases significantly increased with increased antibiotic concentrations. The oxidation rate of pyruvate + proline from isolated mitochondria of the flight muscles of 1-day-old flies was significantly reduced at high doses of antibiotics. In parallel, the level of several metabolites, including TCA cycle intermediates, was reduced in antibiotics-treated flies. Overall, antibiotics provoked a system-wide alteration of the structure and physiology of flight muscles of the blow fly Ch. albiceps, and may have fitness consequences at the organism level. Environmental antibiotic pollution is likely to have unwanted cascading ecological effects of insect population dynamics and community structure. Copyright © 2018 Elsevier Ltd. All rights reserved.

Influence of Unweighting on Insulin Signal Transduction in Muscle

NASA Technical Reports Server (NTRS)

Tischler, Marc E.

2002-01-01

Unweighting of the juvenile soleus muscle is characterized by an increased binding capacity for insulin relative to muscle mass due to sparing of the receptors during atrophy. Although carbohydrate metabolism and protein degradation in the unweighted muscle develop increased sensitivity to insulin in vivo, protein synthesis in vivo and system A amino acid transport in vitro do not appear to develop such an enhanced response. The long-term goal is to identify the precise nature of this apparent resistance in the insulin signal transduction pathway and to consider how reduced weight-bearing may elicit this effect, by evaluating specific components of the insulin signalling pathway. Because the insulin-signalling pathway has components in common with the signal transduction pathway for insulin-like growth factor (IGF-1) and potentially other growth factors, the study could have important implications in the role of weight-bearing function on muscle growth and development. Since the insulin signalling pathway diverges following activation of insulin receptor tyrosine kinase, the immediate specific aims will be to study the receptor tyrosine kinase (IRTK) and those branches, which lead to phosphorylation of insulin receptor substrate-1 (IRS-1) and of Shc protein. To achieve these broader objectives, we will test in situ, by intramuscular injection, the responses of glucose transport, system A amino acid transport and protein synthesis to insulin analogues for which the receptor has either a weaker or much stronger binding affinity compared to insulin. Studies will include: (1) estimation of the ED(sub 50) for each analogue for these three processes; (2) the effect of duration (one to four days) of unweighting on the response of each process to all analogues tested; (3) the effect of unweighting and the analogues on IRTK activity; and (4) the comparative effects of unweighting and analogue binding on the tyrosine phosphorylation of IRTK, IRS-1, and Shc protein.

Hierarchical signaling transduction of the immune and muscle cell crosstalk in muscle regeneration.

PubMed

Yang, Wenjun; Hu, Ping

2018-04-01

The muscle regeneration is a complicated bioprocess that involved in many cell types, including necrotic muscle cells, satellite cells, mesenchymal cells, pericytes, immune cells, and other cell types present at the injury site. Immune cells involved in both innate and adaptive immune responses regulate the progress of muscle regeneration. In this review, we discussed the roles of different immune cells in muscle regeneration. The immune cells regulate muscle regeneration through cytokine production, cell-cell contacts, and general immune environment regulation. We also describe the current known mechanism of how immune cells regulating muscle regeneration. Copyright © 2017. Published by Elsevier Inc.

The role of skeletal muscle in the pathophysiology and management of knee osteoarthritis.

PubMed

Krishnasamy, Priathashini; Hall, Michelle; Robbins, Sarah R

2018-05-01

The role of skeletal muscle in the pathophysiology of knee OA is poorly understood. To date, the majority of literature has focused on the association of muscle strength with OA symptoms, disease onset and progression. However, deficits or improvements in skeletal muscle strength do not fully explain the mechanisms behind outcome measures in knee OA, such as pain, function and structural disease. This review aims to summarize components of skeletal muscle, providing a holistic view of skeletal muscle mechanisms that includes muscle function, quality and composition and their interactions. Similarly, the role of skeletal muscle in the management of knee OA will be discussed.

Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

PubMed

Cornelison, Ddw; Perdiguero, Eusebio

2017-01-01

Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

Activated Eosinophils are Present in Esophageal Muscle in Patients with Achalasia of the Esophagus

PubMed Central

Jin, Hong; Wang, Bin; Zhang, Li-li

2018-01-01

Background The aim of this study was to undertake a histological evaluation of the presence of eosinophils in esophageal muscle in patients with achalasia before treatment with peroral endoscopic myotomy (POEM), with clinical follow-up at one year. Material/Methods Before treatment, esophageal biopsies including mucosa and esophageal muscle were obtained from 28 patients with achalasia. Nine patients who had undergone esophagectomy for esophageal carcinoma were included in the control group. The Eckardt Score was used to evaluate the clinical symptoms of achalasia. Histology of routinely processed tissue sections was used to perform eosinophil cell counts (0 to +++), and immunohistochemistry was used to detect expression of eosinophil major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and S100 protein in cases of achalasia (n=28) and controls (n=9). The findings in patients with achalasia were compared before and one year following POEM. Results Esophageal tissue from patients with achalasia showed eosinophils infiltrating into the muscularis externa in 85.7% (24/28), into the muscularis propria in 28.6% (8/28), and in 89% (25/28) there were few remaining myenteric ganglion cells, before POEM. The extent of inflammation was similar in all regions of the esophagus and between subtypes of achalasia. At one year following POEM, the Eckardt Scores between the former eosinophil (0) group and the eosinophil (+++) group were significantly different (Z=3.50, P=0.030). Conclusions Achalasia of the esophagus was associated with infiltration of the esophageal muscle by activated eosinophils and a decrease in the density of ganglion cells in the myenteric esophageal plexus. PMID:29672471

Disruption of Canonical TGFβ-signaling in Murine Coronary Progenitor Cells by Low Level Arsenic

PubMed Central

Allison, Patrick; Huang, Tianfang; Broka, Derrick; Parker, Patti; Barnett, Joey V.; Camenisch, Todd D.

2013-01-01

Exposure to arsenic results in several types of cancers as well as heart disease. A major contributor to ischemic heart pathologies is coronary artery disease, however the influences by environmental arsenic in this disease process are not known. Similarly, the impact of toxicants on blood vessel formation and function during development has not been studied. During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types including smooth muscle cells which contribute to the coronary vessels. The TGFβ family of ligands and receptors are essential for developmental cardiac epithelial to mesenchymal transition (EMT) and differentiation into coronary smooth muscle cells. In this in vitrostudy, 18 hour exposure to 1.34 μMarsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGFβ2, TGFβ receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGFβ2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34 μMarsenite. There is also loss of nuclear accumulation pSmad due to arsenite exposure. These observations coincide with a decrease invimentinpositive mesenchymal cells invading three-dimensional collagen gels. However, arsenite does not block TGFβ2 mediated smooth muscle cell differentiation by epicardial cells. Overall these results show that arsenic exposure blocks developmental EMT gene programming in murine coronary progenitor cells by disrupting TGFβ2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity. PMID:23732083

A review of concepts regarding the origin of respiratory muscle fatigue

NASA Astrophysics Data System (ADS)

Kuraszkiewicz, Bożena; Piotrkiewicz, Maria

2011-01-01

In this review, the classification of respiratory muscle fatigue from the perspective of its origin is presented. The fatigue is classified as central or peripheral, and the latter further subdivided into high- and low-frequency fatigue. However, muscle fatigue is a complex process and all three types of fatigue probably occur simultaneously in the overloaded respiratory muscles. The relative importance of each type depends on the duration of respiratory loading and other physiological variables. However, central and high-frequency fatigue resolve rapidly once muscle overload is removed, whereas low-frequency fatigue persists over long time.

Skeletal muscle and fetal alcohol spectrum disorder.

PubMed

Myrie, Semone B; Pinder, Mark A

2018-04-01

Skeletal muscle is critical for mobility and many metabolic functions integral to survival and long-term health. Alcohol can affect skeletal muscle physiology and metabolism, which will have immediate and long-term consequences on health. While skeletal muscle abnormalities, including morphological, biochemical, and functional impairments, are well-documented in adults that excessively consume alcohol, there is a scarcity of information about the skeletal muscle in the offspring prenatally exposed to alcohol ("prenatal alcohol exposure"; PAE). This minireview examines the available studies addressing skeletal muscle abnormalities due to PAE. Growth restriction, fetal alcohol myopathy, and abnormalities in the neuromuscular system, which contribute to deficits in locomotion, are some direct, immediate consequences of PAE on skeletal muscle morphology and function. Long-term health consequences of PAE-related skeletal abnormalities include impaired glucose metabolism in the skeletal muscle, resulting in glucose intolerance and insulin resistance, leading to an increased risk of type 2 diabetes. In general, there is limited information on the morphological, biochemical, and functional features of skeletal abnormalities in PAE offspring. There is a need to understand how PAE affects muscle growth and function at the cellular level during early development to improve the immediate and long-term health of offspring suffering from PAE.

Emerging therapies for the treatment of skeletal muscle wasting in chronic obstructive pulmonary disease.

PubMed

Passey, Samantha L; Hansen, Michelle J; Bozinovski, Steven; McDonald, Christine F; Holland, Anne E; Vlahos, Ross

2016-10-01

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that constitutes a major global health burden. A significant proportion of patients experience skeletal muscle wasting and loss of strength as a comorbidity of their COPD, a condition that severely impacts on their quality of life and survival. At present, the lung pathology is considered to be largely irreversible; however, the inherent adaptability of muscle tissue offers therapeutic opportunities to tackle muscle wasting and potentially reverse or delay the progression of this aspect of the disease, to improve patients' quality of life. Muscle wasting in COPD is complex, with contributions from a number of factors including inflammatory cytokines, oxidative stress, growth and anabolic hormones, nutritional status, and physical activity. In this review, we discuss current and emerging therapeutic approaches to treat muscle wasting in COPD, including a number of pharmacological therapies that are in development for muscle atrophy in other pathological states that could be of relevance for treating muscle wasting in COPD patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of Statins on Skeletal Muscle: Exercise, Myopathy, and Muscle Outcomes

PubMed Central

Parker, Beth A.; Thompson, Paul D.

2012-01-01

Statins are effective for reducing low-density lipoprotein cholesterol and cardiac events, but can produce muscle side effects. We have hypothesized that statin-related muscle complaints are exacerbated by exercise and influenced by factors including mitochondrial dysfunction, membrane disruption and/or calcium handling. The interaction between statins, exercise and muscle symptoms may be more effectively diagnosed and treated as rigorous scientific studies accumulate. PMID:23000957

Does Skeletal Muscle Mass Influence Breast Cancer? Evaluating Mammary Tumorigenesis and Progression Genetically Hyper-Muscular Mice

DTIC Science & Technology

2006-07-01

the skeletal muscle-specific muscle growth inhibitor myostatin and mice expressing a dominant negative form of the myostatin receptor, Activin...and rates of breast cancer initiation and progression. 15. SUBJECT TERMS Breast cancer, skeletal muscle, myostatin , MPA, DMBA, Activin receptor 16...including interleukins, Insulin-like Growth Factor (IGF) isoforms, IGF-binding proteins and myostatin . To determine the effect of skeletal muscle mass

Muscle fatigue: general understanding and treatment

PubMed Central

Wan, Jing-jing; Qin, Zhen; Wang, Peng-yuan; Sun, Yang; Liu, Xia

2017-01-01

Muscle fatigue is a common complaint in clinical practice. In humans, muscle fatigue can be defined as exercise-induced decrease in the ability to produce force. Here, to provide a general understanding and describe potential therapies for muscle fatigue, we summarize studies on muscle fatigue, including topics such as the sequence of events observed during force production, in vivo fatigue-site evaluation techniques, diagnostic markers and non-specific but effective treatments. PMID:28983090

[The respiratory muscles in emphysema. The effects of thoracic distension].

PubMed

Cassart, M; Estenne, M

2000-04-01

Besides increasing the work of ventilation, emphysema increases lung volume which in itself has a deleterious effect on the inspiratory muscles. We review here the effects of an acute change in lung volume on the configuration of the rib cage and muscle function. We also discuss the effects of the chronic distension associated with emphysema. The effects produced by changes in muscle length and configuration on the mechanical force and action of inspiratory muscles is detailed with particular focus on the diaphragm and its structural adaptations to experimental emphysema. We also analyze the activation pattern of inspiratory and expiratory muscles during the breathing process in patients with emphysema. Finally, we discuss the effects of single-lung transplantation and reduction surgery on chest distension and improved inspiratory muscle function.

Mechanically induced alterations in cultured skeletal muscle growth

NASA Technical Reports Server (NTRS)

Vandenburgh, H. H.; Hatfaludy, S.; Karlisch, P.; Shansky, J.

1991-01-01

Model systems are available for mechanically stimulating cultured skeletal muscle cells by passive tensile forces which simulate those found in vivo. When applied to embryonic muscle cells in vitro these forces induce tissue organogenesis, metabolic adaptations, and muscle cell growth. The mechanical stimulation of muscle cell growth correlates with stretch-induced increases in the efflux of prostaglandins PGE2 and PGF2(alpha) in a time and frequency dependent manner. These prostaglandins act as mechanical 'second messengers' regulating skeletal muscle protein turnover rates. Since they also effect bone remodelling in response to tissue loading and unloading, secreted prostaglandins may serve as paracrine growth factors, coordinating the growth rates of muscle and bone in response to external mechanical forces. Cell culture model systems will supplement other models in understanding mechanical transduction processes at the molecular level.

Developmental Stage, Muscle and Genetic Type Modify Muscle Transcriptome in Pigs: Effects on Gene Expression and Regulatory Factors Involved in Growth and Metabolism.

PubMed

Ayuso, Miriam; Fernández, Almudena; Núñez, Yolanda; Benítez, Rita; Isabel, Beatriz; Fernández, Ana I; Rey, Ana I; González-Bulnes, Antonio; Medrano, Juan F; Cánovas, Ángela; López-Bote, Clemente J; Óvilo, Cristina

2016-01-01

Iberian pig production includes purebred (IB) and Duroc-crossbred (IBxDU) pigs, which show important differences in growth, fattening and tissue composition. This experiment was conducted to investigate the effects of genetic type and muscle (Longissimus dorsi (LD) vs Biceps femoris (BF)) on gene expression and transcriptional regulation at two developmental stages. Nine IB and 10 IBxDU piglets were slaughtered at birth, and seven IB and 10 IBxDU at four months of age (growing period). Carcass traits and LD intramuscular fat (IMF) content were measured. Muscle transcriptome was analyzed on LD samples with RNA-Seq technology. Carcasses were smaller in IB than in IBxDU neonates (p < 0.001), while growing IB pigs showed greater IMF content (p < 0.05). Gene expression was affected (p < 0.01 and Fold change > 1.5) by the developmental stage (5,812 genes), muscle type (135 genes), and genetic type (261 genes at birth and 113 at growth). Newborns transcriptome reflected a highly proliferative developmental stage, while older pigs showed upregulation of catabolic and muscle functioning processes. Regarding the genetic type effect, IBxDU newborns showed enrichment of gene pathways involved in muscle growth, in agreement with the higher prenatal growth observed in these pigs. However, IB growing pigs showed enrichment of pathways involved in protein deposition and cellular growth, supporting the compensatory gain experienced by IB pigs during this period. Moreover, newborn and growing IB pigs showed more active glucose and lipid metabolism than IBxDU pigs. Moreover, LD muscle seems to have more active muscular and cell growth, while BF points towards lipid metabolism and fat deposition. Several regulators controlling transcriptome changes in both genotypes were identified across muscles and ages (SIM1, PVALB, MEFs, TCF7L2 or FOXO1), being strong candidate genes to drive expression and thus, phenotypic differences between IB and IBxDU pigs. Many of the identified regulators were known to be involved in muscle and adipose tissues development, but others not previously associated with pig muscle growth were also identified, as PVALB, KLF1 or IRF2. The present study discloses potential molecular mechanisms underlying phenotypic differences observed between IB and IBxDU pigs and highlights candidate genes implicated in these molecular mechanisms.

Effect of spaceflight on the functional, biochemical, and metabolic properties of skeletal muscle

NASA Technical Reports Server (NTRS)

Baldwin, K. M.

1996-01-01

This paper summarizes the effects of spaceflight on the functional, morphological, and biochemical properties of human and rodent skeletal muscle. The findings suggest that following as little as 5-6 in space there are deficits in both human and rodent motor capacity, strength, and endurance properties of skeletal muscle. The reduced strength is associated, in part, with a reduction in muscle mass as reflected in smaller cross-sectional areas of both fast- and slow-twitch fibers. Available evidence in animal models suggests that slow-twitch fibers are more sensitive to the atrophying process. Accompanying the atrophy is a transformation of slow to fast protein phenotype involving myosin heavy chain and sarcoplasmic reticulum protein isoforms. These transformations appear to be regulated, in part, by pretranslational processes. Data on the oxidative capacity of rodent skeletal muscle suggest a bias toward preferential utilization of carbohydrate as the primary substrate. These collective findings suggest that skeletal muscles comprised chiefly of slow fibers are highly dependent on gravity for the normal expression of protein mass and slow phenotype. Future studies need to focus on elucidating the mechanisms associated with the atrophy response, as well as identifying suitable exercise and other countermeasures capable of preserving the structural and functional integrity of skeletal muscle.

Strain in shock-loaded skeletal muscle and the time scale of muscular wobbling mass dynamics.

PubMed

Christensen, Kasper B; Günther, Michael; Schmitt, Syn; Siebert, Tobias

2017-10-16

In terrestrial locomotion, muscles undergo damped oscillations in response to limb impacts with the ground. Muscles are also actuators that generate mechanical power to allow locomotion. The corresponding elementary contractile process is the work stroke of an actin-myosin cross-bridge, which may be forcibly detached by superposed oscillations. By experimentally emulating rat leg impacts, we found that full activity and non-fatigue must meet to possibly prevent forcible cross-bridge detachment. Because submaximal muscle force represents the ordinary locomotor condition, our results show that forcible, eccentric cross-bridge detachment is a common, physiological process even during isometric muscle contractions. We also calculated the stiffnesses of the whole muscle-tendon complex and the fibre material separately, as well as Young's modulus of the latter: 1.8 MPa and 0.75 MPa for fresh, fully active and passive fibres, respectively. Our inferred Young's modulus of the tendon-aponeurosis complex suggests that stiffness in series to the fibre material is determined by the elastic properties of the aponeurosis region, rather than the tendon material. Knowing these stiffnesses and the muscle mass, the complex' eigenfrequency for responses to impacts can be quantified, as well as the size-dependency of this time scale of muscular wobbling mass dynamics.

Jaw-muscle fiber architecture in tufted capuchins favors generating relatively large muscle forces without compromising jaw gape.

PubMed

Taylor, Andrea B; Vinyard, Christopher J

2009-12-01

Tufted capuchins (sensu lato) are renowned for their dietary flexibility and capacity to exploit hard and tough objects. Cebus apella differs from other capuchins in displaying a suite of craniodental features that have been functionally and adaptively linked to their feeding behavior, particularly the generation and dissipation of relatively large jaw forces. We compared fiber architecture of the masseter and temporalis muscles between C. apella (n=12) and two "untufted" capuchins (C. capucinus, n=3; C. albifrons, n=5). These three species share broadly similar diets, but tufted capuchins occasionally exploit mechanically challenging tissues. We tested the hypothesis that tufted capuchins exhibit architectural properties of their jaw muscles that facilitate relatively large forces including relatively greater physiologic cross-sectional areas (PCSA), more pinnate fibers, and lower ratios of mass to tetanic tension (Mass/P(0)). Results show some evidence supporting these predictions, as C. apella has relatively greater superficial masseter and temporalis PCSAs, significantly so only for the temporalis following Bonferroni adjustment. Capuchins did not differ in pinnation angle or Mass/P(0). As an architectural trade-off between maximizing muscle force and muscle excursion/contraction velocity, we also tested the hypothesis that C. apella exhibits relatively shorter muscle fibers. Contrary to our prediction, there are no significant differences in relative fiber lengths between tufted and untufted capuchins. Therefore, we attribute the relatively greater PCSAs in tufted capuchins primarily to their larger muscle masses. These findings suggest that relatively large jaw-muscle PCSAs can be added to the suite of masticatory features that have been functionally linked to the exploitation of a more resistant diet by C. apella. By enlarging jaw-muscle mass to increase PCSA, rather than reducing fiber lengths and increasing pinnation, tufted capuchins appear to have increased jaw-muscle and bite forces without markedly compromising muscle excursion and contraction velocity. One performance advantage of this morphology is that it promotes relatively large bite forces at wide jaw gapes, which may be useful for processing large food items along the posterior dentition. We further hypothesize that this morphological pattern may have the ecological benefit of facilitating the dietary diversity seen in tufted capuchins. Lastly, the observed feeding on large objects, coupled with a jaw-muscle architecture that facilitates this behavior, raises concerns about utilizing C. apella as an extant behavioral model for hominins that might have specialized on small objects in their diets.

Ultrasound Elastography: The New Frontier in Direct Measurement of Muscle Stiffness

PubMed Central

Brandenburg, Joline E.; Eby, Sarah F.; Song, Pengfei; Zhao, Heng; Brault, Jeffrey S.; Chen, Shigao; An, Kai-Nan

2014-01-01

The use of brightness-mode ultrasound and Doppler ultrasound in physical medicine and rehabilitation has increased dramatically. The continuing evolution of ultrasound technology has also produced ultrasound elastography, a cutting-edge technology that can directly measure the mechanical properties of tissue, including muscle stiffness. Its real-time and direct measurements of muscle stiffness can aid the diagnosis and rehabilitation of acute musculoskeletal injuries and chronic myofascial pain. It can also help monitor outcomes of interventions affecting muscle in neuromuscular and musculoskeletal diseases, and it can better inform the functional prognosis. This technology has implications for even broader use of ultrasound in physical medicine and rehabilitation practice, but more knowledge about its uses and limitations is essential to its appropriate clinical implementation. In this review, we describe different ultrasound elastography techniques for studying muscle stiffness, including strain elastography, acoustic radiation force impulse imaging, and shear-wave elastography. We discuss the basic principles of these techniques, including the strengths and limitations of their measurement capabilities. We review the current muscle research, discuss physiatric clinical applications of these techniques, and note directions for future research. PMID:25064780

The Association of Vitamin D Status in Lower Extremity Muscle Strains and Core Muscle Injuries at the National Football League Combine.

PubMed

Rebolledo, Brian J; Bernard, Johnathan A; Werner, Brian C; Finlay, Andrea K; Nwachukwu, Benedict U; Dare, David M; Warren, Russell F; Rodeo, Scott A

2018-04-01

To evaluate the association between serum vitamin D level and the prevalence of lower extremity muscle strains and core muscle injuries in elite level athletes at the National Football League (NFL) combine. During the 2015 NFL combine, all athletes with available serum vitamin D levels were included for study. Baseline data were collected, including age, race, body mass index, position, injury history specific to lower extremity muscle strain or core muscle injury, and Functional Movement Screen scores. Serum 25-hydroxyvitamin D was collected and defined as normal (≥32 ng/mL), insufficient (20-31 ng/mL), and deficient (<20 ng/mL). Univariate regression analysis was used to examine the association of vitamin D level and injury history. Subsequent multivariate regression analysis was used to examine this relation with adjustment for collected baseline data variables. The study population included 214 athletes, including 78% African American athletes and 51% skilled position players. Inadequate vitamin D was present in 59%, including 10% with deficient levels. Lower extremity muscle strain or core muscle injury was present in 50% of athletes, which was associated with lower vitamin D levels (P = .03). Athletes with a positive injury history also showed significantly lower vitamin D levels as compared with uninjured athletes (P = .03). African American/black race (P < .001) and injury history (P < .001) was associated with lower vitamin D. Vitamin D groups showed no differences in age (P = .9), body mass index (P = .9), or Functional Movement Screen testing (P = .2). Univariate analysis of inadequate vitamin D levels showed a 1.86 higher odds of lower extremity strain or core muscle injury (P = .03), and 3.61 higher odds of hamstring injury (P < .001). Multivariate analysis did not reach an independent association of low vitamin D with injury history (P = .07). Inadequate vitamin D levels are a widespread finding in athletes at the NFL combine. Players with a history of lower extremity muscle strain and core muscle injury had a higher prevalence of inadequate vitamin D. Level IV, retrospective study-case series. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Myomaker: A membrane activator of myoblast fusion and muscle formation

PubMed Central

Millay, Douglas P.; O’Rourke, Jason R.; Sutherland, Lillian B.; Bezprozvannaya, Svetlana; Shelton, John M.; Bassel-Duby, Rhonda; Olson, Eric N.

2013-01-01

Summary Fusion of myoblasts is essential for the formation of multi-nucleated muscle fibers. However, the identity of myogenic proteins that directly govern this fusion process has remained elusive. Here, we discovered a muscle-specific membrane protein, named Myomaker, that controls myoblast fusion. Myomaker is expressed on the cell surface of myoblasts during fusion and is down-regulated thereafter. Over-expression of Myomaker in myoblasts dramatically enhances fusion and genetic disruption of Myomaker in mice causes perinatal death due to an absence of multi-nucleated muscle fibers. Remarkably, forced expression of Myomaker in fibroblasts promotes fusion with myoblasts, demonstrating the direct participation of this protein in the fusion process. Pharmacologic perturbation of the actin cytoskeleton abolishes the activity of Myomaker, consistent with prior studies implicating actin dynamics in myoblast fusion. These findings reveal a long-sought myogenic fusion protein both necessary and sufficient for mammalian myoblast fusion and provide new insights into the molecular underpinnings of muscle formation. PMID:23868259

Development of active, nanoparticle, antimicrobial technologies for muscle-based packaging applications.

PubMed

Morris, Michael A; Padmanabhan, Sibu C; Cruz-Romero, Malco C; Cummins, Enda; Kerry, Joseph P

2017-10-01

Fresh and processed muscle-based foods are highly perishable food products and packaging plays a crucial role in providing containment so that the full effect of preservation can be achieved through the provision of shelf-life extension. Conventional packaging materials and systems have served the industry well, however, greater demands are being placed upon industrial packaging formats owing to the movement of muscle-based products to increasingly distant markets, as well as increased customer demands for longer product shelf-life and storage capability. Consequently, conventional packaging materials and systems will have to evolve to meet these challenges. This review presents some of the new strategies that have been developed by employing novel nanotechnological concepts which have demonstrated some promise in significantly extending the shelf-life of muscle-based foods by providing commercially-applicable, antimicrobially-active, smart packaging solutions. The primary focus of this paper is applied to subject aspects, such as; material chemistries employed, forming methods utilised, interactions of the packaging functionalities including nanomaterials employed with polymer substrates and how such materials ultimately affect microbes. In order that such materials become industrially feasible, it is important that safe, stable and commercially-viable packaging materials are shown to be producible and effective in order to gain public acceptance, legislative approval and industrial adoption. Copyright © 2017. Published by Elsevier Ltd.

Muscle aging is associated with compromised Ca2+ spark signaling and segregated intracellular Ca2+ release

PubMed Central

Weisleder, Noah; Brotto, Marco; Komazaki, Shinji; Pan, Zui; Zhao, Xiaoli; Nosek, Thomas; Parness, Jerome; Takeshima, Hiroshi; Ma, Jianjie

2006-01-01

Reduced homeostatic capacity for intracellular Ca2+ ([Ca2+]i) movement may underlie the progression of sarcopenia and contractile dysfunction during muscle aging. We report two alterations to Ca2+ homeostasis in skeletal muscle that are associated with aging. Ca2+ sparks, which are the elemental units of Ca2+ release from sarcoplasmic reticulum, are silent under resting conditions in young muscle, yet activate in a dynamic manner upon deformation of membrane structures. The dynamic nature of Ca2+ sparks appears to be lost in aged skeletal muscle. Using repetitive voltage stimulation on isolated muscle preparations, we identify a segregated [Ca2+]i reserve that uncouples from the normal excitation–contraction process in aged skeletal muscle. Similar phenotypes are observed in adolescent muscle null for a synaptophysin-family protein named mitsugumin-29 (MG29) that is involved in maintenance of muscle membrane ultrastructure and Ca2+ signaling. This finding, coupled with decreased expression of MG29 in aged skeletal muscle, suggests that MG29 expression is important in maintaining skeletal muscle Ca2+ homeostasis during aging. PMID:16943181

Muscle activity characterization by laser Doppler Myography

NASA Astrophysics Data System (ADS)

Scalise, Lorenzo; Casaccia, Sara; Marchionni, Paolo; Ercoli, Ilaria; Primo Tomasini, Enrico

2013-09-01

Electromiography (EMG) is the gold-standard technique used for the evaluation of muscle activity. This technique is used in biomechanics, sport medicine, neurology and rehabilitation therapy and it provides the electrical activity produced by skeletal muscles. Among the parameters measured with EMG, two very important quantities are: signal amplitude and duration of muscle contraction, muscle fatigue and maximum muscle power. Recently, a new measurement procedure, named Laser Doppler Myography (LDMi), for the non contact assessment of muscle activity has been proposed to measure the vibro-mechanical behaviour of the muscle. The aim of this study is to present the LDMi technique and to evaluate its capacity to measure some characteristic features proper of the muscle. In this paper LDMi is compared with standard superficial EMG (sEMG) requiring the application of sensors on the skin of each patient. sEMG and LDMi signals have been simultaneously acquired and processed to test correlations. Three parameters has been analyzed to compare these techniques: Muscle activation timing, signal amplitude and muscle fatigue. LDMi appears to be a reliable and promising measurement technique allowing the measurements without contact with the patient skin.

Effect of spinal manipulation on the development of history-dependent responsiveness of lumbar paraspinal muscle spindles in the cat

PubMed Central

Cao, Dong-Yuan; Pickar, Joel G.

2014-01-01

We determined whether spinal manipulation could prevent and/or reverse the decrease and increase in paraspinal muscle spindle responsiveness caused respectively by lengthening and shortening histories of the lumbar muscles. Single unit spindle activity from multifidus and longissimus muscles was recorded in the L6 dorsal root in anesthetized cats. Muscle history was created and spinal manipulation delivered (thrust amplitude: 1.0mm, duration: 100ms) using a feedback-controlled motor attached to the L6 spinous process. Muscle spindle discharge to a fixed vertebral position (static test) and to vertebral movement (dynamic test) was evaluated following the lengthening and shortening histories. For the static test, changes in muscle spindle responsiveness were significantly less when spinal manipulation followed muscle history (p<0.01), but not when spinal manipulation preceded it (p>0.05). For the dynamic test, spinal manipulation did not significantly affect the history-induced change in muscle spindle responsiveness. Spinal manipulation may partially reverse the effects of muscle history on muscle spindle signaling of vertebral position. PMID:24932019

Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy

PubMed Central

Goh, Qingnian; Millay, Douglas P

2017-01-01

Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance of this process during adult muscle hypertrophy has not been explored. In response to muscle overload after synergist ablation in mice, we show that myomaker, a muscle specific membrane protein essential for myoblast fusion, is activated mainly in muscle progenitors and not myofibers. We rendered muscle progenitors fusion-incompetent through genetic deletion of myomaker in muscle stem cells and observed a complete reduction of overload-induced hypertrophy. This blunted hypertrophic response was associated with a reduction in Akt and p70s6k signaling and protein synthesis, suggesting a link between myonuclear accretion and activation of pro-hypertrophic pathways. Furthermore, fusion-incompetent muscle exhibited increased fibrosis after muscle overload, indicating a protective role for normal stem cell activity in reducing myofiber strain associated with hypertrophy. These findings reveal an essential contribution of myomaker-mediated stem cell fusion during physiological adult muscle hypertrophy. DOI: http://dx.doi.org/10.7554/eLife.20007.001 PMID:28186492

Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles

PubMed Central

Valdez, Gregorio; Tapia, Juan C.; Lichtman, Jeff W.; Fox, Michael A.; Sanes, Joshua R.

2012-01-01

Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to change. A third set of muscles, including several muscles of facial expression and the external anal sphinter, succumb to aging but not until the third postnatal year. We asked whether susceptible and resistant muscles differed in rostrocaudal or proximodistal position, source of innervation, motor unit size, or fiber type composition. Of these factors, muscle innervation by brainstem motor neurons correlated best with resistance to age-related decline. Finally, we compared synaptic alterations in normally aging muscles to those in a mouse model of amyotrophic lateral sclerosis (ALS). Patterns of resistance and susceptibility were strikingly correlated in the two conditions. Moreover, damage to NMJs in aged muscles correlated with altered expression and distribution of CRMP4a and TDP-43, which are both altered in motor neurons affected by ALS. Together, these results reveal novel structural, regional and molecular parallels between aging and ALS. PMID:22485182

Transcriptional profile of a myotube starvation model of atrophy

NASA Technical Reports Server (NTRS)

Stevenson, Eric J.; Koncarevic, Alan; Giresi, Paul G.; Jackman, Robert W.; Kandarian, Susan C.

2005-01-01

Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

Attenuation of p38α MAPK stress response signaling delays the in vivo aging of skeletal muscle myofibers and progenitor cells.

PubMed

Papaconstantinou, John; Wang, Chen Z; Zhang, Min; Yang, San; Deford, James; Bulavin, Dmitry V; Ansari, Naseem H

2015-09-01

Functional competence and self-renewal of mammalian skeletal muscle myofibers and progenitor cells declines with age. Progression of the muscle aging phenotype involves the decline of juvenile protective factorsi.e., proteins whose beneficial functions translate directly to the quality of life, and self-renewal of progenitor cells. These characteristics occur simultaneously with the age-associated increase of p38α stress response signaling. This suggests that the maintenance of low levels of p38α activity of juvenile tissues may delay or attenuate aging. We used the dominant negative haploinsufficient p38α mouse (DN-p38α(AF/+)) to demonstrate that in vivo attenuation of p38α activity in the gastrocnemius of the aged mutant delays age-associated processes that include: a) the decline of the juvenile protective factors, BubR1, aldehyde dehydrogenase 1A (ALDH1A1), and aldehyde dehydrogenase 2 (ALDH2); b) attenuated expression of p16(Ink4a) and p19(Arf) tumor suppressor genes of the Cdkn2a locus; c) decreased levels of hydroxynonenal protein adducts, expression of COX2 and iNOS; d) decline of the senescent progenitor cell pool level and d) the loss of gastrocnemius muscle mass. We propose that elevated P-p38α activity promotes skeletal muscle aging and that the homeostasis of p38α impacts the maintenance of a beneficial healthspan.

Animal electricity, Ca2+ and muscle contraction. A brief history of muscle research.

PubMed

Martonosi, A N

2000-01-01

This brief review attempts to summarize some of the major phases of muscle research from Leeuwenhoek's description of sarcomeres in 1674, through Galvani's observation of "animal electricity" in 1791, to the discovery of Ca2+ as the key messenger in the coupling of nerve excitation to muscle contraction. The emerging molecular mechanism of the contraction process is one of the great achievements of biology, reflecting the intimate links between physics, chemistry and the life Sciences in the solution of biological problems.

Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men.

PubMed

Nedergaard, Anders; Sun, Shu; Karsdal, Morten A; Henriksen, Kim; Kjær, Michael; Lou, Yunyun; He, Yi; Zheng, Qinlong; Suetta, Charlotte

2013-12-01

Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain is reflected by peptide biomarkers derived from type VI collagen processing released in the circulation. In order to test this hypothesis, we set out to develop an ELISA assay against an type VI collagen N-terminal globular domain epitope (IC6) and measured the levels of IC6 and an MMP-generated degradation fragment of collagen 6, (C6M) in a human immobilization-remobilization study setup with young (n = 11) and old (n = 9) men. They were subjected to 2 weeks of unilateral lower limb immobilization followed by 4 weeks of remobilization including thrice weekly resistance training, using the contralateral leg as internal controls. Subjects were sampled for strength, quadriceps muscle volume and blood at baseline (PRE), post-immobilization (2W), and post-remobilization (4W). Blood were subsequently analyzed for levels of the C6M and IC6 biomarkers. We subsequently tested if there was any correlation between C6M, IC6, or the C6M/IC6 ratio and muscle mass or strength at baseline. We also tested whether there was any relation between these biomarkers and changes in muscle mass or strength with immobilization or remobilization. The model produced significant loss of muscle mass and strength in the immobilized leg. This loss was bigger in young subjects than in elderly, but whereas the young recovered almost fully, the elderly had limited regrowth of muscle. We found a significant correlation between IC6 and muscle mass at baseline in young subjects (R (2) = 0.6563, p = 0.0045), but none in the elderly. We also found a significant correlation between C6M measured at the 4W time point and the change in muscle mass during remobilization, again only manifesting in the young men(R (2) = 0.6523, p = 0.0085). This discrepancy between the young and the elderly may be caused in part by much smaller changes in muscle mass in the elderly and partly by the relative small sample size. While we cannot rule out the possibility that these biomarkers in part stem from other tissues, our results strongly indicate that these markers represent novel biomarkers of muscle mass or change in muscle mass in young men.

Age-related changes in rat intrinsic laryngeal muscles: analysis of muscle fibers, muscle fiber proteins, and subneural apparatuses.

PubMed

Nishida, Naoya; Taguchi, Aki; Motoyoshi, Kazumi; Hyodo, Masamitsu; Gyo, Kiyofumi; Desaki, Junzo

2013-03-01

We compared age-related changes in the intrinsic laryngeal muscles of aged and young adult rats by determining the number and diameter of muscle fibers, contractile muscle protein (myosin heavy chain isoforms, MHC) composition, and the morphology of the subneural apparatuses. In aged rats, both the numbers and the diameters of muscle fibers decreased in the cricothyroid (CT) muscle. The number of fibers, but not diameter, decreased in the thyroarytenoid (TA) muscle. In the posterior cricoarytenoid (PCA) muscle, neither the number nor the diameter of fibers changed significantly. Aging was associated with a decrease in type IIB and an increase in type IIA MHC isoform levels in CT muscle, but no such changes were observed in the TA or PCA muscles. Morphological examination of primary synaptic clefts of the subneural apparatus revealed that aging resulted in decreased labyrinthine and increased depression types in only the CT muscle. In the aged group, morphologically immature subneural apparatuses were found infrequently in the CT muscle, indicating continued tissue remodeling. We suggest, therefore, that age-related changes in the intrinsic laryngeal muscles primarily involve the CT muscle, whereas the structures of the TA and PCA muscles may better resist aging processes and therefore are less vulnerable to functional impairment. This may reflect differences in their roles; the CT muscle controls the tone of the vocal folds, while the TA and PCA muscles play an essential role in vital activities such as respiration and swallowing.

MOR23 promotes muscle regeneration and regulates cell adhesion and migration

PubMed Central

Griffin, Christine A.; Kafadar, Kimberly A.; Pavlath, Grace K.

2009-01-01

Summary Odorant receptors (ORs) in the olfactory epithelium bind to volatile small molecules leading to the perception of smell. ORs are expressed in many tissues but their functions are largely unknown. We show multiple ORs display distinct mRNA expression patterns during myogenesis in vitro and muscle regeneration in vivo. Mouse OR23 (MOR23) expression is induced during muscle regeneration when muscle cells are extensively fusing and plays a key role in regulating migration and adhesion of muscle cells in vitro, two processes common during tissue repair. A soluble ligand for MOR23 is secreted by muscle cells in vitro and muscle tissue in vivo. MOR23 is necessary for proper skeletal muscle regeneration as loss of MOR23 leads to increased myofiber branching, commonly associated with muscular dystrophy. Together these data identify a functional role for an OR outside of the nose and suggest a larger role for ORs during tissue repair. PMID:19922870

Morphological and biochemical changes in soleus and extensor digitorum longus muscles of rats orbited in Spacelab 3

NASA Technical Reports Server (NTRS)

Riley, D. A.; Slocum, T.; Bain, J. L. W.; Sedlak, F. R.; Elis, S.; Satyanarayana, T.

1985-01-01

Muscle atrophy in rats exposed to hypogravity for seven days aboard Spacelab 3 is examined. Hindlimb muscles were harvested 12-16 days postflight, and prepared for enzyme studies and electron microscopy. Simple cell shrinkage was found, with a mean fiber area decrease of 35.8 percent for soleus and 24.9 percent for extensor digitorum longus (EDL) flight muscle fibers, as compared with control muscle fibers. EDL and soleus muscles showed increases in alkaline myofibrillar ATPase, alpha glycerophosphate dehydrogenase, and glycogen, and a decrease in NADH dehydrogenase staining. The 26 percent increase in calcium activated protease suggests that the focal degradation of myofibrils is the key process of myofibril breakdown. The presence in the flight soleus muscles of one percent necrotic fibers is unexplained. The observed shift towards histochemical fast-muscle type properties is consistent with previous findings.

Should the Equilibrium Point Hypothesis (EPH) be Considered a Scientific Theory?

PubMed Central

Sainburg, Robert L.

2017-01-01

The purpose of this commentary is to discuss factors that limit consideration of the equilibrium point hypothesis as a scientific theory. The EPH describes control of motor neuron threshold through the variable lambda, which corresponds to a unique referent configuration for a muscle, joint, or combination of joints. One of the most compelling features of the equilibrium point hypothesis is the integration of posture and movement control into a single mechanism. While the essential core of the hypothesis is based upon spinal circuitry interacting with peripheral mechanics, the proponents have extended the theory to include the higher-level processes that generate lambda, and in doing so, imposed an injunction against the supraspinal nervous system modeling, computing, or predicting dynamics. This limitation contradicts evidence that humans take account of body and environmental dynamics in motor selection, motor control, and motor adaptation processes. A number of unresolved limitations to the EPH have been debated in the literature for many years, including whether muscle resistance to displacement, measured during movement, is adequate to support this form of control, violations in equifinality predictions, spinal circuits that alter the proposed invariant characteristic for muscles, and limitations in the description of how the complexity of spinal circuitry might be integrated to yield a unique and stable equilibrium position for a given motor neuron threshold. In addition, an important empirical limitation of EPH is the measurement of the invariant characteristic, which needs to be done under a constant central state. While there is no question that the EPH is an elegant and generative hypothesis for motor control research, the claim that this hypothesis has reached the status of a scientific theory is premature. PMID:25386681

Should the Equilibrium Point Hypothesis (EPH) be Considered a Scientific Theory?

PubMed

Sainburg, Robert L

2015-04-01

The purpose of this commentary is to discuss factors that limit consideration of the equilibrium point hypothesis as a scientific theory. The EPH describes control of motor neuron threshold through the variable lambda, which corresponds to a unique referent configuration for a muscle, joint, or combination of joints. One of the most compelling features of the equilibrium point hypothesis is the integration of posture and movement control into a single mechanism. While the essential core of the hypothesis is based upon spinal circuitry interacting with peripheral mechanics, the proponents have extended the theory to include the higher-level processes that generate lambda, and in doing so, imposed an injunction against the supraspinal nervous system modeling, computing, or predicting dynamics. This limitation contradicts evidence that humans take account of body and environmental dynamics in motor selection, motor control, and motor adaptation processes. A number of unresolved limitations to the EPH have been debated in the literature for many years, including whether muscle resistance to displacement, measured during movement, is adequate to support this form of control, violations in equifinality predictions, spinal circuits that alter the proposed invariant characteristic for muscles, and limitations in the description of how the complexity of spinal circuitry might be integrated to yield a unique and stable equilibrium position for a given motor neuron threshold. In addition, an important empirical limitation of EPH is the measurement of the invariant characteristic, which needs to be done under a constant central state. While there is no question that the EPH is an elegant and generative hypothesis for motor control research, the claim that this hypothesis has reached the status of a scientific theory is premature.

Genes in sport and doping.

PubMed

Pokrywka, A; Kaliszewski, P; Majorczyk, E; Zembroń-Łacny, A

2013-09-01

Genes control biological processes such as muscle production of energy, mitochondria biogenesis, bone formation, erythropoiesis, angiogenesis, vasodilation, neurogenesis, etc. DNA profiling for athletes reveals genetic variations that may be associated with endurance ability, muscle performance and power exercise, tendon susceptibility to injuries and psychological aptitude. Already, over 200 genes relating to physical performance have been identified by several research groups. Athletes' genotyping is developing as a tool for the formulation of personalized training and nutritional programmes to optimize sport training as well as for the prediction of exercise-related injuries. On the other hand, development of molecular technology and gene therapy creates a risk of non-therapeutic use of cells, genes and genetic elements to improve athletic performance. Therefore, the World Anti-Doping Agency decided to include prohibition of gene doping within their World Anti-Doping Code in 2003. In this review article, we will provide a current overview of genes for use in athletes' genotyping and gene doping possibilities, including their development and detection techniques.

GENES IN SPORT AND DOPING

PubMed Central

Kaliszewski, P.; Majorczyk, E.; Zembroń-Łacny, A.

2013-01-01

Genes control biological processes such as muscle production of energy, mitochondria biogenesis, bone formation, erythropoiesis, angiogenesis, vasodilation, neurogenesis, etc. DNA profiling for athletes reveals genetic variations that may be associated with endurance ability, muscle performance and power exercise, tendon susceptibility to injuries and psychological aptitude. Already, over 200 genes relating to physical performance have been identified by several research groups. Athletes’ genotyping is developing as a tool for the formulation of personalized training and nutritional programmes to optimize sport training as well as for the prediction of exercise-related injuries. On the other hand, development of molecular technology and gene therapy creates a risk of non-therapeutic use of cells, genes and genetic elements to improve athletic performance. Therefore, the World Anti-Doping Agency decided to include prohibition of gene doping within their World Anti-Doping Code in 2003. In this review article, we will provide a current overview of genes for use in athletes’ genotyping and gene doping possibilities, including their development and detection techniques. PMID:24744482

Decreased Respiratory Muscle Function Is Associated with Impaired Trunk Balance among Chronic Stroke Patients: A Cross-sectional Study.

PubMed

Lee, Kyeongbong; Cho, Ji-Eun; Hwang, Dal-Yeon; Lee, WanHee

2018-06-01

The abdominal muscles play a role in trunk balance. Abdominal muscle thickness is asymmetrical in stroke survivors, who also have decreased respiratory muscle function. We compared the thickness of the abdominal muscles between the affected and less affected sides in stroke survivors. In addition, the relationship between respiratory muscle function and trunk balance was evaluated. Chronic stroke patients (18 men, 15 women; mean age, 58.94 ± 12.30 years; Mini-Mental Status Examination score ≥ 24) who could sit without assist were enrolled. Abdominal muscle thickness during rest and contraction was measured with ultrasonography, and the thickening ratio was calculated. Respiratory muscle function assessment included maximum respiratory pressure, peak flow, and air volume. Trunk function was evaluated using the Trunk Impairment Scale, and trunk balance was estimated based on the center of pressure velocity and path length within the limit of stability in sitting posture. Abdominal muscles were significantly thinner on the affected side, and the thickening ratio was lower in the affected side (P < 0.05). In addition, the higher thickening ratio of the affected side showed significant relationship with higher trunk function. Moreover, higher respiratory muscle function was significantly correlated with higher level of trunk function and balance in stroke patients (P < 0.05). Thus, chronic stroke survivors have decreased abdominal muscle thickness on the affected side, and respiratory muscle function has positive correlation with trunk function and balance. We propose that respiratory muscle training should be included as part of trunk balance training in chronic stroke patients.

Compensatory hypertrophy of the teres minor muscle after large rotator cuff tear model in adult male rat.

PubMed

Ichinose, Tsuyoshi; Yamamoto, Atsushi; Kobayashi, Tsutomu; Shitara, Hitoshi; Shimoyama, Daisuke; Iizuka, Haku; Koibuchi, Noriyuki; Takagishi, Kenji

2016-02-01

Rotator cuff tear (RCT) is a common musculoskeletal disorder in the elderly. The large RCT is often irreparable due to the retraction and degeneration of the rotator cuff muscle. The integrity of the teres minor (TM) muscle is thought to affect postoperative functional recovery in some surgical treatments. Hypertrophy of the TM is found in some patients with large RCTs; however, the process underlying this hypertrophy is still unclear. The objective of this study was to determine if compensatory hypertrophy of the TM muscle occurs in a large RCT rat model. Twelve Wistar rats underwent transection of the suprascapular nerve and the supraspinatus and infraspinatus tendons in the left shoulder. The rats were euthanized 4 weeks after the surgery, and the cuff muscles were collected and weighed. The cross-sectional area and the involvement of Akt/mammalian target of rapamycin (mTOR) signaling were examined in the remaining TM muscle. The weight and cross-sectional area of the TM muscle was higher in the operated-on side than in the control side. The phosphorylated Akt/Akt protein ratio was not significantly different between these sides. The phosphorylated-mTOR/mTOR protein ratio was significantly higher on the operated-on side. Transection of the suprascapular nerve and the supraspinatus and infraspinatus tendons activates mTOR signaling in the TM muscle, which results in muscle hypertrophy. The Akt-signaling pathway may not be involved in this process. Nevertheless, activation of mTOR signaling in the TM muscle after RCT may be an effective therapeutic target of a large RCT. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Losartan Restores Skeletal Muscle Remodeling and Protects Against Disuse Atrophy in Sarcopenia

PubMed Central

Burks, Tyesha N.; Andres-Mateos, Eva; Marx, Ruth; Mejias, Rebeca; Van Erp, Christel; Simmers, Jessica L.; Walston, Jeremy D.; Ward, Christopher W.; Cohn, Ronald D.

2011-01-01

Sarcopenia, a critical loss of muscle mass and function because of the physiological process of aging, contributes to disability and mortality in older adults. It increases the incidence of pathologic fractures, causing prolonged periods of hospitalization and rehabilitation. The molecular mechanisms underlying sarcopenia are poorly understood, but recent evidence suggests that increased transforming growth factor–β (TGF-β) signaling contributes to impaired satellite cell function and muscle repair in aged skeletal muscle. We therefore evaluated whether antagonism of TGF-β signaling via losartan, an angiotensin II receptor antagonist commonly used to treat high blood pressure, had a beneficial impact on the muscle remodeling process of sarcopenic mice. We demonstrated that mice treated with losartan developed significantly less fibrosis and exhibited improved in vivo muscle function after cardiotoxin-induced injury. We found that losartan not only blunted the canonical TGF-β signaling cascade but also modulated the noncanonical TGF-β mitogen-activated protein kinase pathway. We next assessed whether losartan was able to combat disuse atrophy in aged mice that were subjected to hindlimb immobilization. We showed that immobilized mice treated with losartan were protected against loss of muscle mass. Unexpectedly, this protective mechanism was not mediated by TGF-β signaling but was due to an increased activation of the insulin-like growth factor 1 (IGF-1)/Akt/mammalian target of rapamycin (mTOR) pathway. Thus, blockade of the AT1 (angiotensin II type I) receptor improved muscle remodeling and protected against disuse atrophy by differentially regulating the TGF-β and IGF-1/Akt/mTOR signaling cascades, two pathways critical for skeletal muscle homeostasis. Thus, losartan, a Food and Drug Administration–approved drug, may prove to have clinical benefits to combat injury-related muscle remodeling and provide protection against disuse atrophy in humans with sarcopenia. PMID:21562229

Serial Changes of Quadriceps and Hamstring Muscle Strength Following Total Knee Arthroplasty: A Meta-Analysis

PubMed Central

Ahn, Hyeong-Sik; Lee, Dae-Hee

2016-01-01

This meta-analysis was performed to analyze serial changes in thigh muscles, including quadriceps and hamstring muscles, from before to one year after total knee arthroplasty (TKA). All studies sequentially comparing isokinetic quadriceps and hamstring muscle strengths between the TKA side and the contralateral uninjured limb were included in this meta-analysis. Five studies with 7 cohorts were included in this meta-analysis. The mean differences in the strengths of quadriceps and hamstring muscles between the TKA and uninjured sides were greatest three months after surgery (26.8 N∙m, 12.8 N∙m, P<0.001), but were similar to preoperative level at six months (18.4 N∙m, 7.4 N∙m P<0.001) and were maintained for up to one year (15.9 N∙m, 4.1 N∙m P<0.001). The pooled mean differences in changes in quadriceps and hamstring strengths relative to preoperative levels were 9.2 N∙m and 4.9 N∙m, respectively, three months postoperatively (P = 0.041), but were no longer significant after six months and one year. During the year after TKA, quadriceps and hamstring muscle strengths were lowest after 3 months, recovering to preoperative level after six months, but not reaching the muscle strength on the contralateral side. Relative to preoperative levels, the difference in muscle strength between the TKA and contralateral knees was only significant at three months. Because decrease of strength of the quadriceps was significantly greater than decrease in hamstring muscle strength at postoperative three months, early rehabilitation after TKA should focus on recovery of quadriceps muscle strength. PMID:26849808

Module-based multiscale simulation of angiogenesis in skeletal muscle

PubMed Central

2011-01-01

Background Mathematical modeling of angiogenesis has been gaining momentum as a means to shed new light on the biological complexity underlying blood vessel growth. A variety of computational models have been developed, each focusing on different aspects of the angiogenesis process and occurring at different biological scales, ranging from the molecular to the tissue levels. Integration of models at different scales is a challenging and currently unsolved problem. Results We present an object-oriented module-based computational integration strategy to build a multiscale model of angiogenesis that links currently available models. As an example case, we use this approach to integrate modules representing microvascular blood flow, oxygen transport, vascular endothelial growth factor transport and endothelial cell behavior (sensing, migration and proliferation). Modeling methodologies in these modules include algebraic equations, partial differential equations and agent-based models with complex logical rules. We apply this integrated model to simulate exercise-induced angiogenesis in skeletal muscle. The simulation results compare capillary growth patterns between different exercise conditions for a single bout of exercise. Results demonstrate how the computational infrastructure can effectively integrate multiple modules by coordinating their connectivity and data exchange. Model parameterization offers simulation flexibility and a platform for performing sensitivity analysis. Conclusions This systems biology strategy can be applied to larger scale integration of computational models of angiogenesis in skeletal muscle, or other complex processes in other tissues under physiological and pathological conditions. PMID:21463529

PDGFRA, HSD17B4 and HMGB2 are potential therapeutic targets in polycystic ovarian syndrome and breast cancer.

PubMed

Xu, Huiyu; Han, Yong; Lou, Jiaying; Zhang, Hongxian; Zhao, Yue; Győrffy, Balázs; Li, Rong

2017-09-19

To explore the key genes associated with both PCOS and breast cancer, we overlapped the synchronously differently expressed genes in two obese insulin-resistant GEO datasets in muscle tissue and genes exert essential roles in breast cancer prognosis together base on the following reasons: (1) Androgens excess is believed to contribute to the onset of both PCOS and breast cancer. (2) PCOS is usually complicated with metabolic symptoms, such as obesity and insulin-resistance. (3) Muscle is the main place where energy metabolism and material metabolism take place. Consequently, 53 genes were found, functionally enriched in pathways such as pyruvate metabolism, muscle system process and development of primary male sexual characteristics etc. We further lay our eyes on genes correlated with male sexual characteristics, which may be involved in the onset of both PCOS and breast cancer. Three genes were indicated to be associated with this process, including hydroxysteroid (17-beta) dehydrogenase 4/HSD17B4, platelet-derived growth factor receptor, alpha polypeptide/PDGFRA and high-mobility group box 2/HMGB2. Gene-drug interaction network about the three genes were then constructed. Drugs or chemicals that contribute to correcting the disorder of lipid metabolism were detected to restore the abnormal expression of the three genes in PCOS, such as simvastatin, bezafibrate, fenofibrate et al, which provide further choices for managing patients with PCOS.

Molecular Determinants of Cephalopod Muscles and Their Implication in Muscle Regeneration

PubMed Central

Zullo, Letizia; Fossati, Sara M.; Imperadore, Pamela; Nödl, Marie-Therese

2017-01-01

The ability to regenerate whole-body structures has been studied for many decades and is of particular interest for stem cell research due to its therapeutic potential. Several vertebrate and invertebrate species have been used as model systems to study pathways involved in regeneration in the past. Among invertebrates, cephalopods are considered as highly evolved organisms, which exhibit elaborate behavioral characteristics when compared to other mollusks including active predation, extraordinary manipulation, and learning abilities. These are enabled by a complex nervous system and a number of adaptations of their body plan, which were acquired over evolutionary time. Some of these novel features show similarities to structures present in vertebrates and seem to have evolved through a convergent evolutionary process. Octopus vulgaris (the common octopus) is a representative of modern cephalopods and is characterized by a sophisticated motor and sensory system as well as highly developed cognitive capabilities. Due to its phylogenetic position and its high regenerative power the octopus has become of increasing interest for studies on regenerative processes. In this paper we provide an overview over the current knowledge of cephalopod muscle types and structures and present a possible link between these characteristics and their high regenerative potential. This may help identify conserved molecular pathways underlying regeneration in invertebrate and vertebrate animal species as well as discover new leads for targeted tissue treatments in humans. PMID:28555185

Granulocyte colony-stimulating factor (G-CSF) positive effects on muscle fiber degeneration and gait recovery after nerve lesion in MDX mice

PubMed Central

Simões, Gustavo F; Benitez, Suzana U; Oliveira, Alexandre L R

2014-01-01

Background G-CSF has been shown to decrease inflammatory processes and to act positively on the process of peripheral nerve regeneration during the course of muscular dystrophy. Aims The aims of this study were to investigate the effects of treatment of G-CSF during sciatic nerve regeneration and histological analysis in the soleus muscle in MDX mice. Methods Six-week-old male MDX mice underwent left sciatic nerve crush and were G-CSF treated at 7 days prior to and 21 days after crush. Ten and twenty-one days after surgery, the mice were euthanized, and the sciatic nerves were processed for immunohistochemistry (anti-p75NTR and anti-neurofilament) and transmission electron microscopy. The soleus muscles were dissected out and processed for H&E staining and subsequent morphologic analysis. Motor function analyses were performed at 7 days prior to and 21 days after sciatic crush using the CatWalk system and the sciatic nerve index. Results Both groups treated with G-CSF showed increased p75NTR and neurofilament expression after sciatic crush. G-CSF treatment decreased the number of degenerated and regenerated muscle fibers, thereby increasing the number of normal muscle fibers. Conclusions The reduction in p75NTR and neurofilament indicates a decreased regenerative capacity in MDX mice following a lesion to a peripheral nerve. The reduction in motor function in the crushed group compared with the control groups may reflect the cycles of muscle degeneration/regeneration that occur postnatally. Thus, G-CSF treatment increases motor function in MDX mice. Nevertheless, the decrease in baseline motor function in these mice is not reversed completely by G-CSF. PMID:25328849

Time-Course of Muscle Mass Loss, Damage, and Proteolysis in Gastrocnemius following Unloading and Reloading: Implications in Chronic Diseases

PubMed Central

Chacon-Cabrera, Alba; Lund-Palau, Helena; Gea, Joaquim; Barreiro, Esther

2016-01-01

Background Disuse muscle atrophy is a major comorbidity in patients with chronic diseases including cancer. We sought to explore the kinetics of molecular mechanisms shown to be involved in muscle mass loss throughout time in a mouse model of disuse muscle atrophy and recovery following immobilization. Methods Body and muscle weights, grip strength, muscle phenotype (fiber type composition and morphometry and muscle structural alterations), proteolysis, contractile proteins, systemic troponin I, and mitochondrial content were assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15 and 30 days) of non-invasive hindlimb immobilization (plastic splint, I cohorts) and in those exposed to reloading for different time-points (1, 3, 7, 15, and 30 days, R cohorts) following a seven-day period of immobilization. Groups of control animals were also used. Results Compared to non-exposed controls, muscle weight, limb strength, slow- and fast-twitch cross-sectional areas, mtDNA/nDNA, and myosin content were decreased in mice of I cohorts, whereas tyrosine release, ubiquitin-proteasome activity, muscle injury and systemic troponin I levels were increased. Gastrocnemius reloading following splint removal improved muscle mass loss, strength, fiber atrophy, injury, myosin content, and mtDNA/nDNA, while reducing ubiquitin-proteasome activity and proteolysis. Conclusions A consistent program of molecular and cellular events leading to reduced gastrocnemius muscle mass and mitochondrial content and reduced strength, enhanced proteolysis, and injury, was seen in this non-invasive mouse model of disuse muscle atrophy. Unloading of the muscle following removal of the splint significantly improved the alterations seen during unloading, characterized by a specific kinetic profile of molecular events involved in muscle regeneration. These findings have implications in patients with chronic diseases including cancer in whom physical activity may be severely compromised. PMID:27792730

Pasture-feeding of Charolais steers influences skeletal muscle metabolism and gene expression.

PubMed

Cassar-Malek, I; Jurie, C; Bernard, C; Barnola, I; Micol, D; Hocquette, J-F

2009-10-01

Extensive beef production systems on pasture are promoted to improve animal welfare and beef quality. This study aimed to compare the influence on muscle characteristics of two management approaches representative of intensive and extensive production systems. One group of 6 Charolais steers was fed maize-silage indoors and another group of 6 Charolais steers grazed on pasture. Activities of enzymes representative of glycolytic and oxidative (Isocitrate dehydrogenase [ICDH], citrate synthase [CS], hydroxyacyl-CoA dehydrogenase [HAD]) muscle metabolism were assessed in Rectus abdominis (RA) and Semitendinosus (ST) muscles. Activities of oxidative enzymes ICDH, CS and HAD were higher in muscles from grazing animals demonstrating a plasticity of muscle metabolism according to the production and feeding system. Gene expression profiling in RA and ST muscles was performed on both production groups using a multi-tissue bovine cDNA repertoire. Variance analysis showed an effect of the muscle type and of the production system on gene expression (P<0.001). A list of the 212 most variable genes according to the production system was established, of which 149 genes corresponded to identified genes. They were classified according to their gene function annotation mainly in the "protein metabolism and modification", "signal transduction", "cell cycle", "developmental processes" and "muscle contraction" biological processes. Selenoprotein W was found to be underexpressed in pasture-fed animals and could be proposed as a putative gene marker of the grass-based system. In conclusion, enzyme-specific adaptations and gene expression modifications were observed in response to the production system and some of them could be candidates for grazing or grass-feeding traceability.

Evidence for an elastic projection mechanism in the chameleon tongue.

PubMed Central

de Groot, Jurriaan H.; van Leeuwen, Johan L.

2004-01-01

To capture prey, chameleons ballistically project their tongues as far as 1.5 body lengths with accelerations of up to 500 m s(-2). At the core of a chameleon's tongue is a cylindrical tongue skeleton surrounded by the accelerator muscle. Previously, the cylindrical accelerator muscle was assumed to power tongue projection directly during the actual fast projection of the tongue. However, high-speed recordings of Chamaeleo melleri and C. pardalis reveal that peak powers of 3000 W kg(-1) are necessary to generate the observed accelerations, which exceed the accelerator muscle's capacity by at least five- to 10-fold. Extrinsic structures might power projection via the tongue skeleton. High-speed fluoroscopy suggests that they contribute less than 10% of the required peak instantaneous power. Thus, the projection power must be generated predominantly within the tongue, and an energy-storage-and-release mechanism must be at work. The key structure in the projection mechanism is probably a cylindrical connective-tissue layer, which surrounds the entoglossal process and was previously suggested to act as lubricating tissue. This tissue layer comprises at least 10 sheaths that envelop the entoglossal process. The outer portion connects anteriorly to the accelerator muscle and the inner portion to the retractor structures. The sheaths contain helical arrays of collagen fibres. Prior to projection, the sheaths are longitudinally loaded by the combined radial contraction and hydrostatic lengthening of the accelerator muscle, at an estimated mean power of 144 W kg(-1) in C. melleri. Tongue projection is triggered as the accelerator muscle and the loaded portions of the sheaths start to slide over the tip of the entoglossal process. The springs relax radially while pushing off the rounded tip of the entoglossal process, making the elastic energy stored in the helical fibres available for a simultaneous forward acceleration of the tongue pad, accelerator muscle and retractor structures. The energy release continues as the multilayered spring slides over the tip of the smooth and lubricated entoglossal process. This sliding-spring theory predicts that the sheaths deliver most of the instantaneous power required for tongue projection. The release power of the sliding tubular springs exceeds the work rate of the accelerator muscle by at least a factor of 10 because the elastic-energy release occurs much faster than the loading process. Thus, we have identified a unique catapult mechanism that is very different from standard engineering designs. Our morphological and kinematic observations, as well as the available literature data, are consistent with the proposed mechanism of tongue projection, although experimental tests of the sheath strain and the lubrication of the entoglossal process are currently beyond our technical scope. PMID:15209111

Evidence for an elastic projection mechanism in the chameleon tongue.

PubMed

de Groot, Jurriaan H; van Leeuwen, Johan L

2004-04-07

To capture prey, chameleons ballistically project their tongues as far as 1.5 body lengths with accelerations of up to 500 m s(-2). At the core of a chameleon's tongue is a cylindrical tongue skeleton surrounded by the accelerator muscle. Previously, the cylindrical accelerator muscle was assumed to power tongue projection directly during the actual fast projection of the tongue. However, high-speed recordings of Chamaeleo melleri and C. pardalis reveal that peak powers of 3000 W kg(-1) are necessary to generate the observed accelerations, which exceed the accelerator muscle's capacity by at least five- to 10-fold. Extrinsic structures might power projection via the tongue skeleton. High-speed fluoroscopy suggests that they contribute less than 10% of the required peak instantaneous power. Thus, the projection power must be generated predominantly within the tongue, and an energy-storage-and-release mechanism must be at work. The key structure in the projection mechanism is probably a cylindrical connective-tissue layer, which surrounds the entoglossal process and was previously suggested to act as lubricating tissue. This tissue layer comprises at least 10 sheaths that envelop the entoglossal process. The outer portion connects anteriorly to the accelerator muscle and the inner portion to the retractor structures. The sheaths contain helical arrays of collagen fibres. Prior to projection, the sheaths are longitudinally loaded by the combined radial contraction and hydrostatic lengthening of the accelerator muscle, at an estimated mean power of 144 W kg(-1) in C. melleri. Tongue projection is triggered as the accelerator muscle and the loaded portions of the sheaths start to slide over the tip of the entoglossal process. The springs relax radially while pushing off the rounded tip of the entoglossal process, making the elastic energy stored in the helical fibres available for a simultaneous forward acceleration of the tongue pad, accelerator muscle and retractor structures. The energy release continues as the multilayered spring slides over the tip of the smooth and lubricated entoglossal process. This sliding-spring theory predicts that the sheaths deliver most of the instantaneous power required for tongue projection. The release power of the sliding tubular springs exceeds the work rate of the accelerator muscle by at least a factor of 10 because the elastic-energy release occurs much faster than the loading process. Thus, we have identified a unique catapult mechanism that is very different from standard engineering designs. Our morphological and kinematic observations, as well as the available literature data, are consistent with the proposed mechanism of tongue projection, although experimental tests of the sheath strain and the lubrication of the entoglossal process are currently beyond our technical scope.

A Systematic Review on the Effects of Botanicals on Skeletal Muscle Health in Order to Prevent Sarcopenia

PubMed Central

Rondanelli, M.; Miccono, A.; Peroni, G.; Guerriero, F.; Morazzoni, P.; Riva, A.; Guido, D.

2016-01-01

We performed a systematic review to evaluate the evidence-based medicine regarding the main botanical extracts and their nutraceutical compounds correlated to skeletal muscle health in order to identify novel strategies that effectively attenuate skeletal muscle loss and enhance muscle function and to improve the quality of life of older subjects. This review contains all eligible studies from 2010 to 2015 and included 57 publications. We focused our attention on effects of botanical extracts on growth and health of muscle and divided these effects into five categories: anti-inflammation, muscle damage prevention, antifatigue, muscle atrophy prevention, and muscle regeneration and differentiation. PMID:27051451

Morphological Changes of Myoepithelial Cells in the Rat Submandibular Gland Following the Application of Surgical Stimuli.

PubMed

Kawabe, Yoshihiro; Mizobe, Kenich; Bando, Yasuhiko; Sakiyama, Koji; Taira, Fuyoko; Tomomura, Akito; Araki, Hisao; Amano, Osamu

2016-12-28

Myoepithelial cells (MECs) exist on the basal surface of acini in major exocrine glands, include myofilaments and various constructive proteins, and share characteristics with smooth muscle and epithelial cells. MECs project several ramified processes to invest acini, and possibly contract to compress acini to support the secretion by the glandular cells. However, the functional roles of MECs in salivary secretion are still unclear. We investigated morphological changes in immunostained MECs using the anti-α-smooth muscle actin (αSMA) antibody in operated or non-operated contralateral (NC) submandibular glands after partial or total resection. Furthermore, we investigated and discuss other salivary glands of rats. MECs in the parotid, sublingual and submandibular gland of adult rats exhibited different shapes and localizations. After surgery, in both operated and NC glands, the number of MECs and αSMA-immunopositive areas increased significantly. Three-dimensional analysis using a confocal laser-scanning microscope revealed that substantial and significant enhancement became evident in the number, length, and thickness of MEC-processes covering acini of the operated and NC submandibular glands. The preset findings indicate that MECs alter the morphology of their processes in operated and NC glands after surgery of the partial or total resection. It is suggested that MECs promote salivary secretion using elongated, thickened, and more ramified processes.

Ubiquitin-protein ligases in muscle wasting: multiple parallel pathways?

NASA Technical Reports Server (NTRS)

Lecker, Stewart H.; Goldberg, A. L. (Principal Investigator)

2003-01-01

PURPOSE OF REVIEW: Studies in a wide variety of animal models of muscle wasting have led to the concept that increased protein breakdown via the ubiquitin-proteasome pathway is responsible for the loss of muscle mass seen as muscle atrophy. The complexity of the ubiquitination apparatus has hampered our understanding of how this pathway is activated in atrophying muscles and which ubiquitin-conjugating enzymes in muscle are responsible. RECENT FINDINGS: Recent experiments have shown that two newly identified ubiquitin-protein ligases (E3s), atrogin-1/MAFbx and MURF-1, are critical in the development of muscle atrophy. Other in-vitro studies also implicated E2(14k) and E3alpha, of the N-end rule pathway, as playing an important role in the process. SUMMARY: It seems likely that multiple pathways of ubiquitin conjugation are activated in parallel in atrophying muscle, perhaps to target for degradation specific classes of muscle proteins. The emerging challenge will be to define the protein targets for, as well as inhibitors of, these E3s.

Effect of Botulinum Toxin A on Muscle Healing and its Implications in Aesthetic and Reconstructive Surgery.

PubMed

Silberstein, Eldad; Maor, Ehud; Sukmanov, Oleg; Bogdanov Berezovsky, Alexander; Shoham, Yaron; Krieger, Yuval

2018-04-06

Muscle activity contributes to the enhancement of facial aging deformity, blepharospasm, cerebral palsy spasticity, trismus, torticollis, and other conditions. Myotomy of the involved muscles in order to reduce the deformity has variable success rates due to muscle healing and regeneration of activity. The goal of this study was to investigate whether blocking striated muscle activity with Botulinum toxin (BtxA) during the healing time after myotomy alters the healing process and reduces long-term muscle activity. Eighteen Sprague Dawley rats where divided into 3 groups: group A (n = 7) underwent myotomy of their Latisimus Dorsi muscle; group B (n = 7) underwent myotomy and injection of BtxA into their severed muscle; group C (n = 4) injection of BtxA only. Muscle strength was tested periodically using a grip test. Starting at week 16 and until the termination of study at week 22, group B (Myotomy + BtxA) showed significant reduction in muscle power compared to the two control groups. Addition of BtxA injection into a muscle immediately after myotomy may interfere with muscle healing and contribute to a more successful long-term result.

Identification of mechanosensitive genes during skeletal development: alteration of genes associated with cytoskeletal rearrangement and cell signalling pathways.

PubMed

Rolfe, Rebecca A; Nowlan, Niamh C; Kenny, Elaine M; Cormican, Paul; Morris, Derek W; Prendergast, Patrick J; Kelly, Daniel; Murphy, Paula

2014-01-20

Mechanical stimulation is necessary for regulating correct formation of the skeleton. Here we test the hypothesis that mechanical stimulation of the embryonic skeletal system impacts expression levels of genes implicated in developmentally important signalling pathways in a genome wide approach. We use a mutant mouse model with altered mechanical stimulation due to the absence of limb skeletal muscle (Splotch-delayed) where muscle-less embryos show specific defects in skeletal elements including delayed ossification, changes in the size and shape of cartilage rudiments and joint fusion. We used Microarray and RNA sequencing analysis tools to identify differentially expressed genes between muscle-less and control embryonic (TS23) humerus tissue. We found that 680 independent genes were down-regulated and 452 genes up-regulated in humeri from muscle-less Spd embryos compared to littermate controls (at least 2-fold; corrected p-value ≤0.05). We analysed the resulting differentially expressed gene sets using Gene Ontology annotations to identify significant enrichment of genes associated with particular biological processes, showing that removal of mechanical stimuli from muscle contractions affected genes associated with development and differentiation, cytoskeletal architecture and cell signalling. Among cell signalling pathways, the most strongly disturbed was Wnt signalling, with 34 genes including 19 pathway target genes affected. Spatial gene expression analysis showed that both a Wnt ligand encoding gene (Wnt4) and a pathway antagonist (Sfrp2) are up-regulated specifically in the developing joint line, while the expression of a Wnt target gene, Cd44, is no longer detectable in muscle-less embryos. The identification of 84 genes associated with the cytoskeleton that are down-regulated in the absence of muscle indicates a number of candidate genes that are both mechanoresponsive and potentially involved in mechanotransduction, converting a mechanical stimulus into a transcriptional response. This work identifies key developmental regulatory genes impacted by altered mechanical stimulation, sheds light on the molecular mechanisms that interpret mechanical stimulation during skeletal development and provides valuable resources for further investigation of the mechanistic basis of mechanoregulation. In particular it highlights the Wnt signalling pathway as a potential point of integration of mechanical and molecular signalling and cytoskeletal components as mediators of the response.

Identification of mechanosensitive genes during skeletal development: alteration of genes associated with cytoskeletal rearrangement and cell signalling pathways

PubMed Central

2014-01-01

Background Mechanical stimulation is necessary for regulating correct formation of the skeleton. Here we test the hypothesis that mechanical stimulation of the embryonic skeletal system impacts expression levels of genes implicated in developmentally important signalling pathways in a genome wide approach. We use a mutant mouse model with altered mechanical stimulation due to the absence of limb skeletal muscle (Splotch-delayed) where muscle-less embryos show specific defects in skeletal elements including delayed ossification, changes in the size and shape of cartilage rudiments and joint fusion. We used Microarray and RNA sequencing analysis tools to identify differentially expressed genes between muscle-less and control embryonic (TS23) humerus tissue. Results We found that 680 independent genes were down-regulated and 452 genes up-regulated in humeri from muscle-less Spd embryos compared to littermate controls (at least 2-fold; corrected p-value ≤0.05). We analysed the resulting differentially expressed gene sets using Gene Ontology annotations to identify significant enrichment of genes associated with particular biological processes, showing that removal of mechanical stimuli from muscle contractions affected genes associated with development and differentiation, cytoskeletal architecture and cell signalling. Among cell signalling pathways, the most strongly disturbed was Wnt signalling, with 34 genes including 19 pathway target genes affected. Spatial gene expression analysis showed that both a Wnt ligand encoding gene (Wnt4) and a pathway antagonist (Sfrp2) are up-regulated specifically in the developing joint line, while the expression of a Wnt target gene, Cd44, is no longer detectable in muscle-less embryos. The identification of 84 genes associated with the cytoskeleton that are down-regulated in the absence of muscle indicates a number of candidate genes that are both mechanoresponsive and potentially involved in mechanotransduction, converting a mechanical stimulus into a transcriptional response. Conclusions This work identifies key developmental regulatory genes impacted by altered mechanical stimulation, sheds light on the molecular mechanisms that interpret mechanical stimulation during skeletal development and provides valuable resources for further investigation of the mechanistic basis of mechanoregulation. In particular it highlights the Wnt signalling pathway as a potential point of integration of mechanical and molecular signalling and cytoskeletal components as mediators of the response. PMID:24443808

Onto-phylogenetic aspect of myotomal myogenesis in Chordata.

PubMed

Kiełbówna, Leokadia; Daczewska, Małgorzata

2004-01-01

This paper presents an onto- and phylogenetic aspect of myotoamal myogenesis in Chordata. A comparative analysis of early stages of myotomal myogenesis in Chordata indicates that the myogenic process in this phylum underwent evolutionary changes. The first stage of the process is myogenesis leading to development of mononucleate mature muscle cells, the most advanced stage is formation of multinucleate muscle fibres.

Effect of inspiratory muscle training with load compared with sham training on blood pressure in individuals with hypertension: study protocol of a double-blind randomized clinical trial.

PubMed

Posser, Simone Regina; Callegaro, Carine Cristina; Beltrami-Moreira, Marina; Moreira, Leila Beltrami

2016-08-02

Hypertension is a complex chronic condition characterized by elevated arterial blood pressure. Management of hypertension includes non-pharmacologic strategies, which may include techniques that effectively reduce autonomic sympathetic activity. Respiratory exercises improve autonomic control over cardiovascular system and attenuate muscle metaboreflex. Because of these effects, respiratory exercises may be useful to lower blood pressure in subjects with hypertension. This randomized, double-blind clinical trial will test the efficacy of inspiratory muscle training in reducing blood pressure in adults with essential hypertension. Subjects are randomly allocated to intervention or control groups. Intervention consists of inspiratory muscle training loaded with 40 % of maximum inspiratory pressure, readjusted weekly. Control sham intervention consists of unloaded exercises. Systolic and diastolic blood pressures are co-primary endpoint measures assessed with 24 h ambulatory blood pressure monitoring. Secondary outcome measures include cardiovascular autonomic control, inspiratory muscle metaboreflex, cardiopulmonary capacity, and inspiratory muscle strength and endurance. Previously published work suggests that inspiratory muscle training reduces blood pressure in persons with hypertension, but the effectiveness of this intervention is yet to be established. We propose an adequately sized randomized clinical trial to test this hypothesis rigorously. If an effect is found, this study will allow for the investigation of putative mechanisms to mediate this effect, including autonomic cardiovascular control and metaboreflex. ClinicalTrials.gov NCT02275377 . Registered on 30 September 2014.

Short‐term disuse promotes fatty acid infiltration into skeletal muscle

PubMed Central

Pagano, Allan F.; Brioche, Thomas; Arc‐Chagnaud, Coralie; Demangel, Rémi; Chopard, Angèle

2017-01-01

Abstract Background Many physiological and/or pathological conditions lead to muscle deconditioning, a well‐described phenomenon characterized by a loss of strength and muscle power mainly due to the loss of muscle mass. Fatty infiltrations, or intermuscular adipose tissue (IMAT), are currently well‐recognized components of muscle deconditioning. Despite the fact that IMAT is present in healthy human skeletal muscle, its increase and accumulation are linked to muscle dysfunction. Although IMAT development has been largely attributable to inactivity, the precise mechanisms of its establishment are still poorly understood. Because the sedentary lifestyle that accompanies age‐related sarcopenia may favour IMAT development, deciphering the early processes of muscle disuse is of great importance before implementing strategies to limit IMAT deposition. Methods In our study, we took advantage of the dry immersion (DI) model of severe muscle inactivity to induce rapid muscle deconditioning during a short period. During the DI, healthy adult men (n = 12; age: 32 ± 5) remained strictly immersed, in a supine position, in a controlled thermo‐neutral water bath. Skeletal muscle biopsies were obtained from the vastus lateralis before and after 3 days of DI. Results We showed that DI for only 3 days was able to decrease myofiber cross‐sectional areas (−10.6%). Moreover, protein expression levels of two key markers commonly used to assess IMAT, perilipin, and fatty acid binding protein 4, were upregulated. We also observed an increase in the C/EBPα and PPARγ protein expression levels, indicating an increase in late adipogenic processes leading to IMAT development. While many stem cells in the muscle environment can adopt the capacity to differentiate into adipocytes, fibro‐adipogenic progenitors (FAPs) represent the population that appears to play a major role in IMAT development. In our study, we showed an increase in the protein expression of PDGFRα, the specific cell surface marker of FAPs, in response to 3 days of DI. It is well recognized that an unfavourable muscle environment drives FAPs to ectopic adiposity and/or fibrosis. Conclusions This study is the first to emphasize that during a short period of severe inactivity, muscle deconditioning is associated with IMAT development. Our study also reveals that FAPs could be the main resident muscle stem cell population implicated in ectopic adiposity development in human skeletal muscle. PMID:29248005