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4 Transmission electron micrograph (TEM) of a longitudinal section through the skeletal muscle. The striations are due to the presence of sarcomeres consisting of the darker bands-A bands (includes a lighter central zone, called the H band)-and the lighter bands, I bands. Each I band is bisected by a dark transverse line called the Z line flanked by mitochondria. Paired mitochondria are on either side of the electron opaque Z line. The Z Line marks the longitudinal extent of a sarcomere unit
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Muscle tissue is a highly specialized type of tissue, made up of cells that have as their fundamental properties excitability and contractility. The cellular elements that make up this type of tissue are called muscle fibers, or myofibers, because of the elongated shape they have. Contractility is due to the presence of myofibrils in the muscle fib...
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In vertebrate skeletal muscles, the architecture of myofibrils is particularly well conserved throughout the taxa. It is composed of suites of repeating functional units called sarcomeres which give the muscle its striated structure. Here, we show that the skeletal sound producing muscles of the cusk eel Parophidion vassali have a different organis...
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... Myofibers can be subdivided into two major subtypes, termed slow (type 1) or fast (type 2), which is dependent on their functional properties and the expression of ATPase or myosin heavy chain isoforms (Cretoiu et al. 2018). Type 1 myofibers are slow twitch, utilize oxidative metabolism and possess relatively greater endurance than type 2 myofibers, whereas type 2 myofibers are fast twitch and designed for strength. ...
Skeletal muscle comprises the major organ system in our bodies and is the effector tissue for fundamental processes, such as movement, breathing and glucose homeostasis. However, muscle regeneration can be insufficient to repair major injuries or become exhausted by the ongoing fiber damage that occurs in muscular dystrophy. Cell therapy to provide a source of myogenic stem cells that repopulate the lost muscle fibers is an attractive option to treat skeletal muscle injury or dystrophy. Induced pluripotent stem cells (iPSCs) have the potential to be an ideal source of donor muscle cells. This review will discuss major research applications of iPSCs to facilitate skeletal muscle repair, which involve myogenic cell transplantation, in vitro modeling of normal and dystrophic muscle tissue, and drug screening protocols. Recent advances in these fields will be discussed in this review, such as the production of neuromuscular junctions between muscle fibers and motor neurons, along with an overview of the problems that currently prevent iPSCs from being a clinically valid source of transplantable skeletal muscle stem cells. Potential future applications of iPSCs to enhance skeletal muscle regeneration will also be discussed.
... Skeletal muscle can be roughly classified into the type I myofibers, which have a slow contraction rate, and the type II myofibers, which have a fast contraction rate and a strong contractile force (47). Type II myofibers can be further divided into the type IIA myofibers with high aerobic glycolytic capacity and the type IIB myofibers with low aerobic glycolytic capacity (47). ...
... Skeletal muscle can be roughly classified into the type I myofibers, which have a slow contraction rate, and the type II myofibers, which have a fast contraction rate and a strong contractile force (47). Type II myofibers can be further divided into the type IIA myofibers with high aerobic glycolytic capacity and the type IIB myofibers with low aerobic glycolytic capacity (47). Type I and IIA myofibers with high aerobic glycolytic capacity have higher mitochondrial density and activity, actively metabolize glucose and lipids, and are less fatigued during endurance exercise (48). ...
Skeletal muscle is the largest and most energy‑consuming organ in the human body, which plays an important role in energy metabolism and glucose uptake. There is a notable decrease in glucose uptake in the skeletal muscle of patients with type 2 diabetes mellitus (DM). Endurance exercise can reduce hyperglycemia and improve insulin resistance in patients with type 2 DM. Insulin exerts a variety of effects, many of which are mediated by Akt, including increasing glucose uptake, promoting glycogen synthesis and inhibiting glycogen degradation, increasing free fatty acid uptake, increasing protein synthesis, promoting muscle hypertrophy and inhibiting protein degradation. Skeletal muscle mass progressively declines with aging, resulting in loss of muscle strength and physical function. Sarcopenia is a syndrome characterized by loss of skeletal muscle mass and muscle weakness or loss of physical function, and frailty is another syndrome that has received great interest in recent years. Decreased organ function results in vulnerability to external stress. Frailty is associated with falls, fractures and hospitalization; however, there is the reversibility of returning to a healthy state with appropriate interventions. Frailty is classified into three subgroups: Physical frailty, social frailty and cognitive frailty, whereby sarcopenia is the main component of physical frailty. The present review discusses the associations between sarcopenia, frailty and type 2 DM based on current evidence.
... A subset of mRNAs are spread throughout the myofiber To determine whether the observed perinuclear enrichment of total mRNA is due to the accumulation of a particular subset of mRNAs, we performed smFISH to observe the spatial distribution of specific mRNA transcripts. We explored the distribution of mRNAs encoding proteins of sarcomeres, triads and costameres (Cretoiu et al., 2018) (characteristics of analyzed transcripts are summarized in Table S1). ...
... Besides being the largest cells in the body, myofibers are also structurally unique: triads and sarcomeres are packed in the cytoplasm in numerous repeats of the same structures (Cretoiu et al., 2018). Thus, skeletal muscle constitutes an interesting system to study long-range mRNA transport for local protein delivery. ...
Skeletal muscle myofibers are large and elongated cells with multiple and evenly distributed nuclei. Nuclear distribution suggests that each nucleus influences a specific compartment within the myofiber and implies a functional role for nuclear positioning. Compartmentalization of specific mRNAs and proteins has been reported at the neuromuscular and myotendinous junctions, but mRNA distribution in non-specialized regions of the myofibers remains largely unexplored. We report that the bulk of mRNAs is enriched around the nucleus of origin and that this perinuclear accumulation depends on recently transcribed mRNAs. Surprisingly, mRNAs encoding large proteins – giant mRNAs – are spread throughout the cell and do not exhibit perinuclear accumulation. Furthermore, by expressing exogenous transcripts with different sizes we found that size contributes to mRNA spreading independently of mRNA sequence. Both these mRNA distribution patterns depend on microtubules and are independent of nuclear dispersion, mRNA expression level and stability, and the characteristics of the encoded protein. Thus, we propose that mRNA distribution in non-specialized regions of skeletal muscle is size selective to ensure cellular compartmentalization and simultaneous long-range distribution of giant mRNAs.
... Myofibers are commonly classified based on myofibrillar ATPase activity, which is directly correlated to Myosin heavy chain (Myh) gene isoform expression, as type I (slow) or type II (fast). Type II fibers are further subdivided based on metabolic differences into type IIA (fast oxidative), type IIX and type IIB (fast glycolytic) [47,48]. Slower fibers in this simple classification produce lower forces and have largely oxidative metabolism, thus are fatigue resistant. ...
... Excellent reviews of fiber-type specification, morphology and contractility are available (e.g. [5,47,48,[50][51][52]), thus we refrain from a more detailed description here. ...
Animals possess a wide variety of muscle types that support different kinds of movements. Different muscles have distinct locations, morphologies and contractile properties, raising the question of how muscle diversity is generated during development. Normal aging processes and muscle disorders differentially affect particular muscle types, thus understanding how muscles normally develop and are maintained provides insight into alterations in disease and senescence. As muscle structure and basic developmental mechanisms are highly conserved, many important insights into disease mechanisms in humans as well as into basic principles of muscle development have come from model organisms such as Drosophila, zebrafish and mouse. While transcriptional regulation has been characterized to play an important role in myogenesis, there is a growing recognition of the contributions of alternative splicing to myogenesis and the refinement of muscle function. Here we review our current understanding of muscle type specific alternative splicing, using examples of isoforms with distinct functions from both vertebrates and Drosophila. Future exploration of the vast potential of alternative splicing to fine-tune muscle development and function will likely uncover novel mechanisms of isoform-specific regulation and a more holistic understanding of muscle development, disease and aging.
... As a result, muscle function is reduced until the muscle recovers from injury (Lu et al., 2011;Jarvinen et al., 2013;Souza and Gottfried, 2013;Wall et al., 2015;Hardy et al., 2016). After acute muscle injury, many cell types within the skeletal muscle microenvironment must respond sequentially to mitigate damage and regenerate myofibers, the cell type responsible for muscle contraction (Bentzinger et al., 2013;Juban and Chazaud, 2017;Tidball, 2017;Cretoiu et al., 2018). Myeloid immune cell infiltration peaks at 2-3 days post-injury in mice to remove cellular debris resulting from damaged myofibers (Bentzinger et al., 2013;Juban and Chazaud, 2017;Tidball, 2017). ...
Acute skeletal muscle injury is followed by a temporal response of immune cells, fibroblasts, and muscle progenitor cells within the muscle microenvironment to restore function. These same cell types are repeatedly activated in muscular dystrophy from chronic muscle injury, but eventually, the regenerative portion of the cycle is disrupted and fibrosis replaces degenerated muscle fibers. Mineralocorticoid receptor (MR) antagonist drugs have been demonstrated to increase skeletal muscle function, decrease fibrosis, and directly improve membrane integrity in muscular dystrophy mice, and therefore are being tested clinically. Conditional knockout of MR from muscle fibers in muscular dystrophy mice also improves skeletal muscle function and decreases fibrosis. The mechanism of efficacy likely results from blocking MR signaling by its endogenous agonist aldosterone, being produced at high local levels in regions of muscle damage by infiltrating myeloid cells. Since chronic and acute injuries share the same cellular processes to regenerate muscle, and MR antagonists are clinically used for a wide variety of conditions, it is crucial to define the role of MR signaling in normal muscle repair after injury. In this study, we performed acute injuries using barium chloride injections into tibialis anterior muscles both in myofiber MR conditional knockout mice on a wild-type background (MRcko) and in MR antagonist-treated wild-type mice. Steps of the muscle regeneration response were analyzed at 1, 4, 7, or 14 days after injury. Presence of the aldosterone synthase enzyme was also assessed during the injury repair process. We show for the first time aldosterone synthase localization in infiltrating immune cells of normal skeletal muscle after acute injury. MRcko mice had an increased muscle area infiltrated by aldosterone synthase positive myeloid cells compared to control injured animals. Both MRcko and MR antagonist treatment stabilized damaged myofibers and increased collagen infiltration or compaction at 4 days post-injury. MR antagonist treatment also led to reduced myofiber size at 7 and 14 days post-injury. These data support that MR signaling contributes to the normal muscle repair process following acute injury. MR antagonist treatment delays muscle fiber growth, so temporary discontinuation of these drugs after a severe muscle injury could be considered.
The performance of robotic systems could benefit from low‐density material actuators that emulate muscle typology (e.g., fast and slow twitch) of natural systems. Recent reports detail the thermomechanical, chemical, electrical, and pneumatic response of twisted and coiled fibers. The geometrical constraints imparted on typically commodity materials realize distinguished stimuli‐induced actuation including low density, high force, and moderate stroke. Here, we prepare actuators by twisting fibers composed of liquid crystal elastomers (LCEs). The actuators combine the inherent stimuli‐response of LCEs with the geometrical constraints of twisted fiber actuators to dramatically increase the deformation rate, specific work, and achievable force output. In some geometries, the thermomechanical response of the LCE exhibits a pseudo‐first‐order transition.
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Coordinated cardiomyocyte contraction drives the mammalian heart to beat and circulate blood. No consensus model of cardiomyocyte geometrical arrangement exists, due to the limited spatial resolution of whole heart imaging methods and the piecemeal nature of studies based on histological sections. By combining microscopy and computer vision, we produced the first-ever three-dimensional cardiomyocyte orientation reconstruction across mouse ventricular walls at the micrometer scale, representing a gain of three orders of magnitude in spatial resolution. We recovered a cardiomyocyte arrangement aligned to the long-axis direction of the outer ventricular walls. This cellular network lies in a thin shell and forms a continuum with longitudinally arranged cardiomyocytes in the inner walls, with a complex geometry at the apex. Our reconstruction methods can be applied at fine spatial scales to further understanding of heart wall electrical function and mechanics, and set the stage for the study of micron-scale fiber remodeling in heart disease.
Androgens are a class of steroid hormones primarily associated with male sexual development and physiology, but exert pleiotropic effects in either sex. They have a crucial role in various physiological processes, including the regulation of skeletal muscle and adipose tissue homeostasis. The effects of androgens are mainly mediated through the androgen receptor (AR), a ligand-activated nuclear receptor expressed in both tissues. In skeletal muscle, androgens via AR exert a multitude of effects, ranging from increased muscle mass and strength, to the regulation of muscle fiber type composition, contraction and metabolic functions. In adipose tissue, androgens influence several processes including proliferation, fat distribution, and metabolism but they display depot-specific and organism-specific effects which differ in certain context. This review further explores the potential mechanisms underlying androgen-AR signaling in skeletal muscle and adipose tissue. Understanding the roles of androgens and their receptor in skeletal muscle and adipose tissue is essential for elucidating their contributions to physiological processes, disease conditions, and potential therapeutic interventions.
