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The polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) affect vascular relaxation and involve factors (e.g., nitric oxide) that contribute to exercise-induced increases in skeletal-muscle blood flow (Q). The authors investigated whether DHA and EPA supplementation augments skeletal-muscle Q and vascular conductance (VC) and attenuates renal and splanchnic Q and VC in exercising rats. Rats were fed a diet of 5% lipids by weight, of which 20% was DHA and 30% EPA (PUFA group, n = 9), or 5% safflower oil (SO group, n = 8) for 6 wk. Heart rate (HR), blood pressure (MAP), and hind-limb, renal, and splanchnic Q were measured at rest and during moderate treadmill running. MAP, HR, and renal and splanchnic Q and VC were similar between the 2 groups at rest and during exercise. In the PUFA group, Q (158 ± 27 vs. 128 ± 28 ml · min-1 · 100 g-1) and VC (1.16 ± 0.21 vs. 0.92 ± 0.23 ml · min-1 · 100 g-1 · mm Hg-1) were greater in the exercising hind-limb muscle. Q and VC were also higher in 8 of 28 and 11 of 28 muscles and muscle parts, respectively. These increases were positively correlated to the percent sum of Types I and IIa fibers. Results suggest that DHA+EPA (a) enhances Q and VC in active skeletal muscle (especially Type I and IIa fibers) and that the increase in Q is due to an increase in cardiac output secondary to increases in VC and (b) has no apparent influence on vasoconstriction in renal and splanchnic tissue. [ABSTRACT FROM AUTHOR]

Consuming carbohydrate-rich meals before continuous endurance exercise improves performance, yet few studies have evaluated the ideal preexercise meal for high-intensity intermittent exercise, which is characteristic of many team sports. The authors' purpose was to investigate the effects of low- and high-glycemic-index (GI) meals on metabolism and performance during high-intensity, intermittent exercise. Sixteen male participants completed three 90-min high-intensity intermittent running trials in a single-blinded random order, separated by ~7 d, while fasted (control) and 2 hr after ingesting an isoenergetic low-GI (lentil), or high-GI (potato and egg white) preexercise meal. Serum free fatty acids were higher and insulin lower throughout exercise in the fasted condition (p < .05), but there were no differences in blood glucose during exercise between conditions. Distance covered on a repeated-sprint test at the end of exercise was significantly greater in the low-GI and high-GI conditions than in the control (p < .05). Rating of perceived exertion was lower in the low-GI condition than in the control (p = .01). In a subsample of 5 participants, muscle glycogen availability was greater in the low- and high-GI conditions versus fasted control before the repeated-sprint test (p < .05), with no differences between low and high GI. When exogenous carbohydrates are not provided during exercise both low- and high-GI preexercise meals improve high-intensity, intermittent exercise performance, probably by increasing the availability of muscle glycogen. However, the GI does not influence markers of substrate oxidation during high-intensity, intermittent exercise. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the effect of plyometric training (PT) on central and peripheral (muscle) fatigue in prepubertal girls and boys. The boys (n = 13, age 10.3 ± 0.3 years) and girls (n = 13, age, 10.2 ± 0.3 years) performed continuous 2-min maximal voluntary contractions (MVCs) before and after 16 high-intensity PT sessions. PT comprised two training sessions per week of 30 jumps in each session with 20 s between jumps. The greatest effect of PT was on excitation-contraction coupling, (twitch force increased by 323% in boys and 21% in girls) and height of a counter-movement jump (increased by 37% in boys and 38% in girls). In contrast, the quadriceps voluntary activation index, central activation ratio, and MVC did not change significantly after PT. The thickness of the quadriceps muscle increased by 9% in boys and 14% in girls after PT. In conclusion, boys and girls demonstrated similar changes in indicators of central fatigue (50-60% decrease) and peripheral fatigue (45-55% decrease) after MVC before and after PT. [ABSTRACT FROM AUTHOR]

Manipulating seat configuration (i.e., seat tube angle, seat height and pelvic orientation) alters the bicycle-rider geometry, which influences lower extremity muscle kinematics and ultimately muscle force and power generation during pedaling. Previous studies have sought to identify the optimal configuration, but isolating the effects of specific variables on rider performance from the confounding effect of rider adaptation makes such studies challenging. Of particular interest is the influence of seat tube angle on rider performance, as seat tube angle varies across riding disciplines (e.g., road racers vs. triathletes). The goals of the current study were to use muscle-actuated forward dynamics simulations of pedaling to 1) identify the overall optimal seat configuration that produces maximum crank power and 2) systematically vary seat tube angle to assess how it influences maximum crank power. The simulations showed that a seat height of 0.76 m (or 102% greater than trochanter height), seat tube angle of 85.1 deg, and pelvic orientation of 20.5 deg placed the major power- producing muscles on more favorable regions of the intrinsic force-length-velocity relationships to generate a maximum average crank power of 981 W. However, seat tube angle had little influence on crank power, with maximal values varying at most by 1% across a wide range of seat tube angles (65 to 110 deg). The similar power values across the wide range of seat tube angles were the result of nearly identical joint kinematics, which occurred using a similar optimal seat height and pelvic orientation while systematically shifting the pedal angle with increasing seat tube angles. [ABSTRACT FROM AUTHOR]

Soft-tissue vibrations can be used to quantify selected properties of human tissue and their response to impact. Vibrations are typically quantified using high-speed motion capture or accelerometry. The aim of this study was to compare the amplitude and frequency of soft-tissue vibrations during running when quantified by highspeed motion capture and accelerometry simultaneously. This study showed: (a) The estimated measurement errors for amplitude and frequency were of the same order of magnitude for both techniques. (b) There were no significant differences in the mean peak frequencies and peak amplitudes measured by the two methods. (c) The video method showed an inability to capture high frequency information. This study has shown that a tradeoff has to be made between the accuracy in amplitude and frequency when these methods are employed to quantify soft tissue vibrations in running. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the effects of resistance training on muscle and tendon properties between knee extensors and plantar flexors in vivo. Twenty healthy young men voluntarily participated in this study. The subjects were randomly divided into two training groups: knee extension group (n = 10) and plantar flexion group (n = 10). They performed five sets of exercises with a 1-min rest between sets, which consisted of unilateral knee extension for the knee extension group and plantar flexion for the plantar flexion group at 80% of 1 repetition maximum with 10 repetitions per set (4 days/wk, 12 wk). Before and after training, muscle strength, neural activation level (by interpolated twitch), muscle volume (by magnetic resonance imaging), and tendon stiffness (by ultrasonography) were measured. There were no differences in the training-induced increases in muscle strength, activation level, muscle volume, and tendon stiffness between knee extensors and plantar flexors. These results suggested that if the used protocol of training (i.e., intensity, repetition, etc.) were the same, there were no differences in the training-induced changes in muscle and tendon properties between knee extensors and plantar flexors. [ABSTRACT FROM AUTHOR]

Abstract The Myosin Binding Protein-C (MyBP-C) family is a group of sarcomeric proteins important for striated muscle structure and function. Comprising approximately 2% of the myofilament mass, MyBP-C has important roles in both contraction and relaxation. Three paralogs of MyBP-C are encoded by separate genes with distinct expression profiles in striated muscle. In mammals, cardiac MyBP-C is limited to the heart, and it is the most extensively studied owing to its involvement in cardiomyopathies. However, the roles of two skeletal paralogs, slow and fast, in muscle biology remain poorly characterized. Nonetheless, both have been recently implicated in the development of skeletal myopathies. This calls for a better understanding of their function in the pathophysiology of distal arthrogryposis. This review characterizes MyBP-C as a whole and points out knowledge gaps that still remain with respect to skeletal MyBP-C. [ABSTRACT FROM AUTHOR]

The recent high-resolution structure of the thick filament from Lethocerus asynchronous flight muscle shows aspects of thick filament structure never before revealed that may shed some light on how striated muscles function. The phenomenon of stretch activation underlies the function of asynchronous flight muscle. It is most highly developed in flight muscle, but is also observed in other striated muscles such as cardiac muscle. Although stretch activation is likely to be complex, involving more than a single structural aspect of striated muscle, the thick filament itself, would be a prime site for regulatory function because it must bear all of the tension produced by both its associated myosin motors and any externally applied force. Here we show the first structural evidence that the arrangement of myosin heads within the interacting heads motif is coupled to the structure of the thick filament backbone. We find that a change in helical angle of 0.16° disorders the blocked head preferentially within the Lethocerus interacting heads motif. This observation suggests a mechanism for how tension affects the dynamics of the myosin heads leading to a detailed hypothesis for stretch activation and shortening deactivation, in which the blocked head preferentially binds the thin filament followed by the free head when force production occurs. [ABSTRACT FROM AUTHOR]

In the comparative aspect the regeneration processes of striated muscles of hind left leg were researched in rats with posttraumatic reflex contractures against the background of physiotherapeutic treatment. Macroscopic and microscopic evaluation of pathomorphological changes has been conducted in this work. A relative area of myogenic elements (striated muscle elements), connective-tissue elements and neovasculature in the muscular-connective tissue in the scar in percentage has been determined using the method of point counting (field method). Depending on the signs of pain behavior (behavioral changes, additional signs), the intensity of myogenic pain syndrome (low, moderate, high, very high) has been studied. It has been established that the use of magnetic-laser therapy led to the formation of muscular-connective tissue scar up to the 28th day with a predominance of a portion of striated muscle tissue of 90.74±0.17%. Behavioral and motor responses became normalized; no pain was observed in 56% of rats, pain intensity was low in 44%. In animals with the same trauma that were not treated, the portion of striated muscle tissue was 37.08±0.34%, and signs of pain of high and moderate intensity were observed. By the 28th day, the animals could brace against their hind limbs while moving, but due to a sharp restriction of the function of the left hind limb, they could not move freely. The obtained results are the basis for developing new approaches to improving the methods of remedial treatment of contractures using magnetic-laser therapy. [ABSTRACT FROM AUTHOR]

Aim The study was undertaken to explore whether shortening of striated muscle during activity is associated with release of bound Ca2+ into the myofibrillar space as has previously been proposed in order to explain the depressant effect of active shortening. Methods The experiments were carried out on single muscle fibres isolated from the anterior tibialis muscle of Rana temporaria. The fibres were loaded with the calcium sensitive indicator Fluo-3. The fibres, stimulated to produce a partially fused isometric tetanus, were subjected to a shortening ramp or, alternatively, to a stretch ramp during activity while force, fibre length, sarcomere length and the Fluo-3 signal were recorded. Results A shortening ramp performed during a partially fused tetanus caused an increase in the myofibrillar free calcium concentration and produced, simultaneously, a decrease in active force. The isometric force recovered gradually after the shortening ramp, while the intracellular Ca2+ concentration stayed above the control level during the remainder of the stimulation period. A stretch ramp applied during a partially fused tetanus caused a considerably smaller change in the myofibrillar Ca2+ concentration. Conclusion The results provide evidence that the myosin cross-bridges interact with the calcium binding sites on the thin filaments during active shortening, causing sustained release of calcium and reduced contractile strength. [ABSTRACT FROM AUTHOR]

To explain disparate decay rates of cytosolic Ca2+ and structural changes in the thin filaments during a twitch, we model the time course of Ca2+ bound troponin (Tn) resulting from the free Ca2+ transient of fast skeletal muscle. In fibers stretched beyond overlap, the decay of Ca2+ as measured by a change in fluo 3 fluorescence is significantly slower than the intensity decay of the meridional 1/38.5 nm-1 reflection of Tn; this is not simply explained by considering only the Ca2+ binding properties of Tn alone (Matsuo, T., Iwamoto, H., and Yagi, N. (2010). Biophys. J. 99, 193-200). We apply a comprehensive model that includes the known Ca2+ binding properties of Tn in the context of the thin filament with and without cycling crossbridges. Calculations based on the model predict that the transient of Ca2+ bound Tn correlates with either the fluo 3 time course in muscle with overlapping thin and thick filaments or the intensity of the meridional 1/38.5 nm-1 reflection in overstretched muscle. Hence, cycling crossbridges delay the dissociation of Ca2+ from Tn. Correlation with the fluo 3 fluorescence change is not causal given that the transient of Ca2+ bound Tn depends on sarcomere length, whereas the fluo-3 fluorescence change does not. Transient positions of tropomyosin calculated from the time course of Ca2+ bound Tn are in reasonable agreement with the transient of measured perturbations of the Tn repeat in overlap and non-overlap muscle preparations.

Seasonal changes in proteolytic activity and content of calpains in striated muscles of the longtailed ground squirrel Spermophilus undulatus were studied by casein zymography and Western blotting analysis. The results testify to hyperactivation of calpain proteases in the skeletal muscles of awakened animals during the 'winter' activity. The observed changes are discussed in the context of adaptation of skeletal muscles of long-tailed ground squirrels to hibernation. [ABSTRACT FROM AUTHOR]

The dichotomy between smooth and striated myocytes is fundamental for bilaterian musculature, but its evolutionary origin is unsolved. In particular, interrelationships of visceral smooth muscles remain unclear. Absent in fly and nematode, they have not yet been characterized molecularly outside vertebrates. Here, we characterize expression profile, ultrastructure, contractility and innervation of the musculature in the marine annelid Platynereis dumerilii and identify smooth muscles around the midgut, hindgut and heart that resemble their vertebrate counterparts in molecular fingerprint, contraction speed and nervous control. Our data suggest that both visceral smooth and somatic striated myocytes were present in the protostome-deuterostome ancestor and that smooth myocytes later co-opted the striated contractile module repeatedly - for example, in vertebrate heart evolution. During these smooth-to-striated myocyte conversions, the core regulatory complex of transcription factors conveying myocyte identity remained unchanged, reflecting a general principle in cell type evolution. [ABSTRACT FROM AUTHOR]

Cellular and physiological adaptations to an atmosphere which became enriched in molecular oxygen spurred the development of a layered system of stress protection, including antioxidant and stress response proteins. At physiological levels reactive oxygen and nitrogen species regulate cell signalling as well as intracellular and intercellular communication. Exercise and physical activity confer a variety of stressors on skeletal muscle and the cardiovascular system: mechanical, metabolic, oxidative. Transient increases of stressors during acute bouts of exercise or exercise training stimulate enhancement of cellular stress protection against future insults of oxidative, metabolic and mechanical stressors that could induce injury or disease. This phenomenon has been termed both hormesis and exercise preconditioning (EPC). EPC stimulates transcription factors such as Nrf-1 and heat shock factor-1 and up-regulates gene expression of a cadre of cytosolic (e.g. glutathione peroxidase and heat shock proteins) and mitochondrial adaptive or stress proteins (e.g. manganese superoxide dismutase, mitochondrial KATP channels and peroxisome proliferator activated receptor γ coactivator-1 (PGC-1)). Stress response and antioxidant enzyme inducibility with exercise lead to protection against striated muscle damage, oxidative stress and injury. EPC may indeed provide significant clinical protection against ischaemia-reperfusion injury, Type II diabetes and ageing. New molecular mechanisms of protection, such as δ-opioid receptor regulation and mitophagy, reinforce the notion that mitochondrial adaptations (e.g. heat shock proteins, antioxidant enzymes and sirtuin-1/PGC-1 signalling) are central to the protective effects of exercise preconditioning. [ABSTRACT FROM AUTHOR]

The ribosome has historically been considered to have no cell-specific function but rather serve in a 'housekeeping' capacity. This view is being challenged by evidence showing that heterogeneity in the protein composition of the ribosome can lead to the functional specialization of the ribosome. Expression profiling of different tissues revealed that ribosomal protein large 3-like ( Rpl3l) is exclusively expressed in striated muscle. In response to a hypertrophic stimulus, Rpl3l expression in skeletal muscle was significantly decreased by 82% whereas expression of the ubiquitous paralog Rpl3 was significantly increased by ∼fivefold. Based on these findings, we developed the hypothesis that Rpl3l functions as a negative regulator of muscle growth. To test this hypothesis, we used the Tet-On system to express Rpl3l in myoblasts during myotube formation. In support of our hypothesis, RPL3L expression significantly impaired myotube growth as assessed by myotube diameter (-23%) and protein content (-14%). Further analysis showed that the basis of this impairment was caused by a significant decrease in myoblast fusion as the fusion index was significantly lower (-17%) with RPL3L expression. These findings are the first evidence to support the novel concept of ribosome specialization in skeletal muscle and its role in the regulation of skeletal muscle growth. J. Cell. Physiol. 231: 1894-1902, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Striated muscle shows an amazing ability to adapt its structural apparatus based on contractile activity, loading conditions, fuel supply, or environmental factors. Studies with mammalian hibernators have identified a variety of molecular pathways which are strategically regulated and allow animals to endure multiple stresses associated with the hibernating season. Of particular interest is the observation that hibernators show little skeletal muscle atrophy despite the profound metabolic rate depression and mechanical unloading that they experience during long weeks of torpor. Additionally, the cardiac muscle of hibernators must adjust to low temperature and reduced perfusion, while the strength of contraction increases in order to pump cold, viscous blood. Consequently, hibernators hold a wealth of knowledge as it pertains to understanding the natural capacity of myocytes to alter structural, contractile and metabolic properties in response to environmental stimuli. The present review outlines the molecular and biochemical mechanisms which play a role in muscular atrophy, hypertrophy, and remodeling. In this capacity, four main networks are highlighted: (1) antioxidant defenses, (2) the regulation of structural, contractile and metabolic proteins, (3) ubiquitin proteosomal machinery, and (4) macroautophagy pathways. Subsequently, we discuss the role of transcription factors nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Myocyte enhancer factor 2 (MEF2), and Forkhead box (FOXO) and their associated posttranslational modifications as it pertains to regulating each of these networks. Finally, we propose that comparing and contrasting these concepts to data collected from model organisms able to withstand dramatic changes in muscular function without injury will allow researchers to delineate physiological versus pathological responses. [ABSTRACT FROM AUTHOR]

Enteric co-innervation is a peculiar innervation pattern of striated esophageal musculature. Both anatomical and functional data on enteric co-innervation related to various transmitters have been collected in different species, although its function remains enigmatic. However, it is unclear whether catecholaminergic components are involved in such a co-innervation. Thus, we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus, using immunohistochemistry with antibodies against tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT) and protein gene product 9.5 (PGP 9.5), α-bungarotoxin (α-BT) and PCR with primers for amplification of cDNA encoding TH and dopamine-β-hydroxylase (DBH). TH-positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14 % of α-BT-labelled motor endplates differing from VAChT-positive vagal nerve terminals. TH-positive perikarya represented a subpopulation of only about 2.8 % of all PGP 9.5-positive myenteric neurons. Analysis of mRNA showed both TH and DBH transcripts in the mouse esophagus. As ChAT-positive neurons in the compact formation of the nucleus ambiguus were negative for TH, the TH-positive nerve varicosities on motor endplates are presumably of enteric origin, although a sympathetic origin cannot be excluded. In the medulla oblongata, the cholinergic ambiguus neurons were densely supplied with TH-positive varicosities. Thus, catecholamines may modulate vagal motor innervation of esophageal-striated muscles not only at the peripheral level via enteric co-innervation but also at the central level via projections to the nucleus ambiguus. As Parkinson's disease, with a loss of central dopaminergic neurons, also affects the enteric nervous system and dysphagia is prevalent in patients with this disease, investigation of intrinsic catecholamines in the esophagus may be worthwhile to understand such a symptom. [ABSTRACT FROM AUTHOR]

Most physiological functions originate with the communication between organs. Mouse genetics has revived this holistic view of physiology through the identification of inter-organ communications that are unanticipated, functionally important, and would have been difficult to uncover otherwise. This Review highlights this point by showing how two tissues usually not seen as endocrine ones, bone and striated muscles, influence several physiological processes in a significant manner. [ABSTRACT FROM AUTHOR]

Understanding the interplay between the neurotransmitters dopamine and glutamate in the striatum has become the highlight of several theories of neuropsychiatric illnesses, such as schizophrenia. Using in vivo brain imaging in humans, alterations in dopamine and glutamate concentrations have been observed in several neuropsychiatric disorders. However, it is unclear a priori how alterations in striatal dopamine should modulate glutamate concentrations in the basal ganglia. In this selective mini-review, we examine the consequence of reducing striatal dopamine functioning on glutamate concentrations in the striatum and cortex; regions of interest heavily examined in the human brain imaging studies. We examine the predictions of the classical model of the basal ganglia, and contrast it with findings in humans and animals. The review concludes that chronic dopamine depletion (> 4 months) produces decreases in striatal glutamate levels which are consistent with the classical model of the basal ganglia. However, acute alterations in striatal dopamine functioning, specifically at the D 2 receptors, may produce opposite affects. This has important implications for models of the basal ganglia and theorizing about neurochemical alterations in neuropsychiatric diseases. Moreover, these findings may help guide a priori hypotheses for 1 H-MRS studies measuring glutamate changes given alterations in dopaminergic functioning in humans. [ABSTRACT FROM AUTHOR]

Dopamine (DA) is one of the key neurotransmitters in the striatum, which is functionally important for a variety of cognitive and motor behaviours. It is known that the striatum is vulnerable to damage from traumatic brain injury (TBI). However, a therapeutic approach has not yet been established to treat TBI. Hence, the present work aimed to evaluate the ability of Normobaric hyperoxia treatment (NBOT) to recover dopaminergic neurons following a fluid percussion injury (FPI) as a TBI experimental animal model. To examine this, mice were divided into four groups: (i) Control, (ii) Sham, (iii) FPI and (iv) FPI+NBOT. Mice were anesthetized and surgically prepared for FPI in the striatum and immediate exposure to NBOT at various time points (3, 6, 12 and 24 h). Dopamine levels were then estimated post injury by utilizing a commercially available ELISA method specific to DA. We found that DA levels were significantly reduced at 3 h, but there was no reduction at 6, 12 and 24 h in FPI groups when compared to the control and sham groups. Subjects receiving NBOT showed consistent increased DA levels at each time point when compared with Sham and FPI groups. These results suggest that FPI may alter DA levels at the early post-TBI stages but not in later stages. While DA levels increased in 6, 12 and 24 h in the FPI groups, NBOT could be used to accelerate the prevention of early dopaminergic neuronal damage following FPI injury and improve DA levels consistently. [ABSTRACT FROM PUBLISHER]

Calcium signaling regulates synaptic plasticity and many other functions in striatal medium spiny neurons to modulate basal ganglia function. Ca 2 + /calmodulin-dependent protein kinase II (CaMKII) is a major calcium-dependent signaling protein that couples calcium entry to diverse cellular changes. CaMKII activation results in autophosphorylation at Thr286 and sustained calcium-independent CaMKII activity after calcium signals dissipate. However, little is known about the mechanisms regulating striatal CaMKII. To address this, mouse brain slices were treated with pharmacological modulators of calcium channels and punches of dorsal striatum were immunoblotted for CaMKII Thr286 autophosphorylation as an index of CaMKII activation. KCl depolarization increased levels of CaMKII autophosphorylation ~ 2-fold; this increase was blocked by an LTCC antagonist and was mimicked by treatment with pharmacological LTCC activators. The chelation of extracellular calcium robustly decreased basal CaMKII autophosphorylation within 5 min and increased levels of total CaMKII in cytosolic fractions, in addition to decreasing the phosphorylation of CaMKII sites in the GluN2B subunit of NMDA receptors and the GluA1 subunit of AMPA receptors. We also found that the maintenance of basal levels of CaMKII autophosphorylation requires low-voltage gated T-type calcium channels, but not LTCCs or R-type calcium channels. Our findings indicate that CaMKII activity is dynamically regulated by multiple calcium channels in the striatum thus coupling calcium entry to key downstream substrates. [ABSTRACT FROM AUTHOR]

We mathematically compared two models of mammalian striated muscle activation dynamics proposed by Hatze and Zajac. Both models are representative for a broad variety of biomechanical models formulated as ordinary differential equations (ODEs). These models incorporate parameters that directly represent known physiological properties. Other parameters have been introduced to reproduce empirical observations. We used sensitivity analysis to investigate the influence of model parameters on the ODE solutions. In addition, we expanded an existing approach to treating initial conditions as parameters and to calculating second-order sensitivities. Furthermore, we used a global sensitivity analysis approach to include finite ranges of parameter values. Hence, a theoretician striving for model reduction could use the method for identifying particularly low sensitivities to detect superfluous parameters. An experimenter could use it for identifying particularly high sensitivities to improve parameter estimation. Hatze’s nonlinear model incorporates some parameters to which activation dynamics is clearly more sensitive than to any parameter in Zajac’s linear model. Other than Zajac’s model, Hatze’s model can, however, reproduce measured shifts in optimal muscle length with varied muscle activity. Accordingly we extracted a specific parameter set for Hatze’s model that combines best with a particular muscle force-length relation. [ABSTRACT FROM AUTHOR]

Muscle LIM Protein (MLP) has emerged as a key regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 ( CSRP3 ), the gene encoding MLP, are causative of human cardiomyopathies, whereas altered expression patterns are observed in human failing heart and skeletal myopathies. In vitro and in vivo evidences reveal a complex and diverse functional role of MLP in striated muscle, which is determined by its multiple interacting partners and subcellular distribution. Experimental evidence suggests that MLP is implicated in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles still unfolds. [ABSTRACT FROM AUTHOR]

Background: Rosai-Dorfman disease is a form of histiocytosis affecting the systemic lymph nodes. Intracranial Rosai-Dorfman disease is rare and presents with extra-parenchymal or intraparenchymal proliferative mass lesions. Cranial neuropathy has not been reported in Rosai-Dorfman disease except when caused by mass effect by an adjacent lesion.Patient Description: We describe a girl with Rosai-Dorfman disease who presented with peripheral and multiple cranial neuropathies. Detailed clinical, immunologic, neurophysiology, imaging, and genetic studies were performed. She had a prolonged course but recovered fully after immune therapies. She had increased titers of striated muscle and smooth muscle antibodies. Imaging studies revealed contrast enhancement of cranial nerves and striated muscles. Demyelination was evident in the nerve twigs from muscle biopsy. Exome sequencing did not reveal a genetic mutation.Conclusions: Most patients with Rosai-Dorfman disease have a benign course, but severe neurological dysfunction due to bulbar involvement and cranial and peripheral neuropathies may occur. Treatment with immunoglobulin and steroids may be of benefit. [ABSTRACT FROM AUTHOR]

Immediate neurochemical alterations produced by 6-OHDA could explain the general toxic pattern in the central nervous system. However, no evidences describe the effects of 6-OHDA on early changes of neurotransmitters in rats' striatum, cortex and hippocampus. In our study, unilateral 6-OHDA injection into medial forebrain bundle (MFB) was used in rats, then five neurotransmitters were analyzed at 3, 6, 12, 24, 48 and 72 h, respectively. Results showed that 6-OHDA injection caused a sharp decline of striatal dopamine (DA) levels in the first 12 h followed by a further reduction between 12 and 48 h. However, striatal levels of homovanillic acid (HVA) were stable in the first 12 h and showed a marked reduction between 12 and 24 h. Striatal levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) decreased linearly for 72 h, whereas levels of norepinephrine (NE) showed a slight reduction in the first 48 h, and returned back to normal afterwards. Striatal HVA/DA ratio increased significantly in the first 12 h, but 5-HIAA/5-HT ratio showed a sharp increase between 12 and 72 h. Besides, neurochemical alterations were also found in hippocampus and cortex, and the correlations of neurotransmitters were analyzed. Our study indicated that NE system had little influence in the early phase of 6-OHDA injection, moreover, early neurochemical alterations were involved with striatum, hippocampus and cortex. [ABSTRACT FROM AUTHOR]

ZASP is a cytoskeletal PDZ-LIM protein predominantly expressed in striated muscle. It forms multiprotein complexes and plays a pivotal role in the structural integrity of sarcomeres. Mutations in the ZASP protein are associated with myofibrillar myopathy, left ventricular non-compaction and dilated cardiomyopathy. The ablation of its murine homologue Cypher results in neonatal lethality. ZASP has several alternatively spliced isoforms, in this paper we clarify the nomenclature of its human isoforms as well as their dynamics and expression pattern in striated muscle. Interaction is demonstrated between ZASP and two new binding partners both of which have roles in signalling, regulation of gene expression and muscle differentiation; the mechanosensing protein Ankrd2 and the tumour suppressor protein p53. These proteins and ZASP form a triple complex that appears to facilitate poly-SUMOylation of p53. We also show the importance of two of its functional domains, the ZM-motif and the PDZ domain. The PDZ domain can bind directly to both Ankrd2 and p53 indicating that there is no competition between it and p53 for the same binding site on Ankrd2. However there is competition for this binding site between p53 and a region of the ZASP protein lacking the PDZ domain, but containing the ZM-motif. ZASP is negative regulator of p53 in transactivation experiments with the p53-responsive promoters, MDM2 and BAX. Mutations in the ZASP ZM-motif induce modification in protein turnover. In fact, two mutants, A165V and A171T, were not able to bind Ankrd2 and bound only poorly to alpha-actinin2. This is important since the A165V mutation is responsible for zaspopathy, a well characterized autosomal dominant distal myopathy. Although the mechanism by which this mutant causes disease is still unknown, this is the first indication of how a ZASP disease associated mutant protein differs from that of the wild type ZASP protein. [ABSTRACT FROM AUTHOR]

Significance: Mechanical activation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) occurs in striated muscle and affects Ca2+ signaling and contractile function. ROS/RNS signaling is tightly controlled, spatially compartmentalized, and source specific. Recent Advances: Here, we review the evidence that within the contracting myocyte, the trans-membrane protein NADPH oxidase 2 (Nox2) is the primary source of ROS generated during contraction. We also review a newly characterized signaling cascade in cardiac and skeletal muscle in which the microtubule network acts as a mechanotransduction element that activates Nox2-dependent ROS generation during mechanical stretch, a pathway termed X-ROS signaling. Critical Issues: In the heart, X-ROS acts locally and affects the sarcoplasmic reticulum (SR) Ca2+ release channels (ryanodine receptors) and tunes Ca2+ signaling during physiological behavior, but excessive X-ROS can promote Ca2+-dependent arrhythmias in pathology. In skeletal muscle, X-ROS sensitizes Ca2+-permeable sarcolemmal 'transient receptor potential' channels, a pathway that is critical for sustaining SR load during repetitive contractions, but when in excess, it is maladaptive in diseases such as Duchenne Musclar dystrophy. Future Directions: New advances in ROS/RNS detection as well as molecular manipulation of signaling pathways will provide critical new mechanistic insights into the details of X-ROS signaling. These efforts will undoubtedly reveal new avenues for therapeutic intervention in the numerous diseases of striated muscle in which altered mechanoactivation of ROS/RNS production has been identified. Antioxid. Redox Signal. 20, 929-936. [ABSTRACT FROM AUTHOR]

Bcl-2 and Bax proteins are expressed in cells of the tails of Pelophylax ridibundus larvae. We investigated the levels of these proteins in tails undergoing apoptosis. Apoptotic cells were observed in the epidermis, muscle and notochord of tails of different lengths. The apoptotic cells in epidermis exhibited the typical features of apoptosis. Amorphous masses and irregularities in striated muscle tissue undergoing apoptosis and apoptotic remnants in the notochord also were observed. In general, Bax staining in the epidermis, subepidermal fibroblast layer, muscle and notochord cells increased, while Bcl-2 staining decreased as the tail regressed. Our results suggest that during tail regression due to metamorphosis, Bcl-2 and Bax proteins play key roles in the apoptosis of tail epidermis, subepidermal fibroblast layer, muscle and notochord cells. [ABSTRACT FROM AUTHOR]

Abstract: Little is known about the architecture of the vagal motor units that control esophageal striated muscle, in spite of the fact that these units are necessary, and responsible, for peristalsis. The present experiment was designed to characterize the motor neuron projection fields and terminal arbors forming esophageal motor units. Nucleus ambiguus compact formation neurons of the rat were labeled by bilateral intracranial injections of the anterograde tracer dextran biotin. After tracer transport, thoracic and abdominal esophagi were removed and prepared as whole mounts of muscle wall without mucosa or submucosa. Labeled terminal arbors of individual vagal motor neurons (n=78) in the esophageal wall were inventoried, digitized and analyzed morphometrically. The size of individual vagal motor units innervating striated muscle, throughout thoracic and abdominal esophagus, averaged 52 endplates per motor neuron, a value indicative of fine motor control. A majority (77%) of the motor terminal arbors also issued one or more collateral branches that contacted neurons, including nitric oxide synthase-positive neurons, of local myenteric ganglia. Individual motor neuron terminal arbors co-innervated, or supplied endplates in tandem to, both longitudinal and circular muscle fibers in roughly similar proportions (i.e., two endplates to longitudinal for every three endplates to circular fibers). Both the observation that vagal motor unit collaterals project to myenteric ganglia and the fact that individual motor units co-innervate longitudinal and circular muscle layers are consistent with the hypothesis that elements contributing to peristaltic programming inhere, or are “hardwired,” in the peripheral architecture of esophageal motor units. [Copyright &y& Elsevier]

Lymphatic muscle (LM) is widely considered to be a type of vascular smooth muscle, even though LM cells uniquely express contractile proteins from both smooth muscle and cardiac muscle. We tested the hypothesis that LM exhibits an unloaded maximum shortening velocity (Vmax) intermediate between that of smooth muscle and cardiac muscle. Single lymphatic vessels were dissected from the rat mesentery, mounted in a servo-controlled wire myograph, and subjected to isotonic quick release protocols during spontaneous or agonist-evoked contractions. After maximal activation, isotonic quick releases were performed at both the peak and plateau phases of contraction. Vmax was 0.48 ± 0.04 lengths (L)/s at the peak: 2.3 times higher than that of mesenteric arteries and 11.4 times higher than mesenteric veins. In cannulated, pressurized lymphatic vessels, shortening velocity was determined from the maximal rate of constriction [rate of change in internal diameter (-dD/dt)] during spontaneous contractions at optimal preload and minimal afterload; peak -dD/dt exceeded that obtained during any of the isotonic quick release protocols (2.14 ± 0.30 L/s). Peak -dD/dt declined with pressure elevation or activation using substance P. Thus, isotonic methods yielded Vmax values for LM in the mid to high end (0.48 L/s) of those the recorded for phasic smooth muscle (0.05- 0.5 L/s), whereas isobaric measurements yielded values (>2.0 L/s) that overlapped the midrange of values for cardiac muscle (0.6 -3.3 L/s). Our results challenge the dogma that LM is classical vascular smooth muscle, and its unusually high Vmax is consistent with the expression of cardiac muscle contractile proteins in the lymphatic vessel wall. [ABSTRACT FROM AUTHOR]

The striated muscle activator of Rho signaling (STARS) protein and members of its downstream signaling pathway, including myocardin-related transcription factor-A (MRTF-A) and SRF, are increased in response to prolonged resistance exercise training but also following a single bout of endurance cycling. The aim of the present study was to measure and compare the regulation of STARS, MRTF-A and SRF mRNA and protein following 10 weeks of endurance training (ET) versus resistance training (RT), as well as before and following a single bout of endurance (EE) versus resistance exercise (RE). Following prolonged training, STARS, MRTF-A and SRF mRNA levels were all increased by similar magnitude, irrespective of training type. In the training-habituated state, STARS mRNA increased following a single-bout RE when measured 2.5 and 5 h post-exercise and had returned to resting level by 22 h following exercise. MRTF-A and SRF mRNA levels were decreased by 2.5, 5, and 22 h following a single bout of RE and EE exercise when compared to their respective basal levels, with no significant difference seen between the groups at any of the time points. No changes in protein levels were observed following the two modes of exercise training or a single bout of exercise. This study demonstrates that the stress signals elicited by ET and RT result in a comparable regulation of members of the STARS pathway. In contrast, a single bout of EE and RE, performed in the trained state, elicit different responses. These observations suggest that in the trained state, the acute regulation of the STARS pathway following EE or RE may be responsible for exercise-specific muscle adaptations. [ABSTRACT FROM AUTHOR]

Abstract: Contrary to the classical view, according to which all proteins adopt a specific folded conformation necessary for their function, intrinsically unstructured proteins (IUPs) display random-coil-like conformation under physiological conditions. We compared the structured and unstructured domains from titin, a giant protein responsible for striated-muscle elasticity. A 171-residue-long fragment (polyE) of the disordered PEVK domain, and an Ig domain (I27) with ordered structure were investigated. FTIR (Fourier transform infrared) and fluorescence spectroscopy combined with a diamond anvil cell were used for investigation of the secondary structures under wide range of pressure and temperature. PolyE preserves its disordered characteristics across the entire range of investigated pressure (0–16kbar), temperature (0–100°C), pD (3–10.5) and different solvent conditions. The detailed temperature–pressure phase diagram of titin I27 was determined. At 30°C, increasing pressure unfolds titin I27 in one step at 10.5kbar. Increasing temperature at atmospheric pressure results in two transitions. At 50°C the secondary structure is loosened and the protein transforms into a molten-globule state. At 65°C the protein completely unfolds. Unfolding is followed by aggregation at ambient pressure. Moderate pressures (>2kbar), however, can prevent the protein from aggregation. Our experiments in wide range of physical parameters revealed four different structures for I27, while the unstructured character of the PEVK fragment is insensitive to these parameters. [Copyright &y& Elsevier]

Background: During total hip arthroplasty (THA), medialisation of the cup decreases the lever arm of body weight and is considered to be beneficial. Theoretically it should be compensated by an equivalent increase of the femoral offset in order to maintain global offset. Goal of the study: We investigated via a numerical model the forces on each bundle of the abductor muscles and the loading forces at the head-cup interface. We compared THA with and without medialisation of the cup and with and without restoration of the global offset. Method: A digital finite element model of the hip joint with THA was constructed. Monopodal weight-bearing was simulated with the cup positioned so that the hip centre of rotation was left unchanged. Forces in the abductors and pressure on the prosthetic head were measured and then compared with three other configurations: 1. Medialisation of the cup by 5 to 15mm with reproduction of the native femoral offset or; 2. with an increased femoral offset compensating for the cup medialisation and; 3. no medialisation of the cup with a femoral offset increased. Results: Medialisation of the cup decreased stresses on the head-cup interface and on the abductor muscles, even when the global offset was not restored. Anatomical placement of the cup did not give the best results. The optimal outcome in terms of stress was observed when the cup was medialised but global offset restored. Any increase of global offset significantly increases the length and the tension in the anterior bundles of the abductor muscles. [ABSTRACT FROM AUTHOR]

We hypothesized that 12 weeks of downhill skiing mitigates the functional deficits of knee extensor muscles in elderly subjects due to the specific recruitment of fast motor units during forceful turns on the slope. Downhill skiing led to a 1.4-fold increase in the mean cross-sectional area of slow ( P=0.04)- and fast ( P=0.08)-type muscle fibers. Fold changes in the expression of the structural component of focal adhesions, gamma-vinculin, were correlated with alterations in concentric force ( r=0.64). Hypertrophy of fast fibers was more pronounced in women than in men (1.7 vs 1.1). Gender-specific structural-functional adjustments of knee extensor muscles and attached patellar tendon were reflected by altered expression of pro- vs de-adhesive proteins and a number of correlations. The de-adhesive protein tenascin-C was selectively increased in women compared with men (1.7 vs 1.1) while the content of the adhesive collagen XII was specifically reduced in women. The pro-adhesive focal adhesion kinase showed a specific increase in men compared with women (1.9 vs 1.1). Our findings indicate that quantitatively matched adaptations in slow and fast motor units of extensor muscle underlie the preventive effect of skiing against sarcopenia and support that hypertrophy and reinforcement of fiber adhesion operate in the improvement of muscle strength. [ABSTRACT FROM AUTHOR]

This study investigated whether regular alpine skiing could reverse sarcopenia and muscle weakness in older individuals. Twenty-two older men and women (67 ± 2 years) underwent 12 weeks of recreational skiing, two to three times a week, each session lasting∼3.5 h. An age-matched, inactive group ( n=20, 67 ± 4 years) served as a control (CTRL). Before and after the training period, knee extensors muscle thickness ( T), pennation angle (θ) and fascicle length ( L) of the vastus lateralis muscle were measured by ultrasound. Maximum isokinetic knee extensor torque (MIT) at an angular velocity of 60°/s was measured by dynamometry. After the training, T increased by 7.1% ( P<0.001), L by 5.4% ( P<0.02) and θ by 3.4% ( P<0.05). The increase in T was matched by a significant gain in MIT (13.3%, P<0.001). No significant changes, except for a decrease in θ (2.1%, P<0.02), were found in the CTRL group. The gain in T in the training group correlated significantly with an increase in the focal adhesion kinase content, pointing to a primary role of this mechano-sensitive protein in sarcomere remodeling with muscle hypertrophy. Overall, the results show that alpine skiing is an effective intervention for combating sarcopenia and weakness in old age. [ABSTRACT FROM AUTHOR]

Abstract: Background: Femoral osseointegrated implants represent a new development in amputee rehabilitation, eliminating socket pressure discomfort, improving hip range of movement and facilitating prosthetic limb attachment. A clinical aspect that has not previously been reported on is the function of muscles in the residuum with implications concerning energy expenditure, hip-hiking and viability of the electrogram as a myoprocessor. Typically, amputees fitted with osseointegrated fixation have shorter residuums and weaker attachment of cleaved muscles. Function of muscle can be assessed by surface electromyography through changes in amplitude and median frequency of the signal. Methods: Five male transfemoral amputees with osseointegrated fixations participated together with a control group comprised of ten adult males. Electrodes recorded surface electromyographic activity of five residual limb muscles or left lower limb muscles of control subjects. Isometric contractions were performed against resistance. The increase in mean rectified amplitude from resting to maximally contracting was calculated and median frequencies estimated. Findings: The amputees were unable to maintain a maximum voluntary contraction of constant amplitude. Amplitude increase was lowest for rectus femoris and adductor magnus. The median frequency of adductor magnus was significantly greater (P =0.02) for the amputees than intact subjects and there was a significant difference (P <0.01) between gluteus maximus and adductor magnus for amputee subjects. Interpretation: High electromyographic amplitude variability suggests that using residuum muscles singly as a myoprocessor might be challenging. Adductor magnus displayed a different sEMG profile compared to intact subjects indicating decreased function and neuromuscular changes. Further work into optimal muscle anchorage is required to ensure maximal mechanical performance. [Copyright &y& Elsevier]

Following the onset of maturation, female athletes have a significantly higher risk for anterior cruciate ligament (ACL) injury compared with male athletes. While multiple sex differences in lower-extremity neuromuscular control and biomechanics have been identified as potential risk factors for ACL injury in females, the majority of these studies have focused specifically on the knee joint. However, increasing evidence in the literature indicates that lumbo-pelvic (core) control may have a large effect on knee-joint control and injury risk. This review examines the published evidence on the contributions of the trunk and hip to knee-joint control. Specifically, the sex differences in potential proximal controllers of the knee as risk factors for ACL injury are identified and discussed. Sex differences in trunk and hip biomechanics have been identified in all planes of motion (sagittal, coronal and transverse). Essentially, female athletes show greater lateral trunk displacement, altered trunk and hip ulexion angles, greater ranges of trunk motion, and increased hip adduction and internal rotation during sport manoeuvres, compared with their male counterparts. These differences may increase the risk of ACL injury among female athletes. Prevention programmes targeted towards trunk and hip neuromuscular control may decrease the risk for ACL injuries. [ABSTRACT FROM AUTHOR]

Abstract: Background: Ageing is associated with geometrical changes in muscle fascicles that may lead to deteriorations in physical functions. The purpose of this study was to study the effects of ageing on fibre orientation and strength of the lumbar extensor muscles. Methods: Fifty two healthy, 26 younger (10 males and 16 females, aged from 20 to 35) and 26 older (10 males and 16 females, aged from 65 to 90) volunteers participated in this study. Ultrasound images of the lumbar extensor muscles were obtained with the participants in relaxed standing and half flexion (50% of the range of trunk flexion). The fibre angles at the mid-substance of the muscle were recorded. Lumbar extensor muscle strength was measured in the upright posture with a load cell. Findings: The mean lumbar extensor fibre angles were found to significantly decrease in the half flexion posture when compared to upright stance (P <0.01). Both the fibre angle and the moment generation capability of the muscles decreased with ageing (P <0.01). There was a moderate correlation between the fibre angles in the upright posture and the muscle strength measured in this posture (r=0.40, P <0.01). Interpretation: Age-related changes in muscle geometry and posture may partly account for the deterioration in muscle function in the elderly. [Copyright &y& Elsevier]

The aims of the present study were to examine quantitatively ground reaction forces, kinematics, and muscle activations during the windmill softball pitch, and to determine relationships between knee valgus and muscle activations, ball velocity and muscle activation as well as ball velocity and ground reaction forces. It was hypothesized that there would be an inverse relationship between degree of knee valgus and muscle activation, a direct relationship between ground reaction forces and ball velocity, and non-stride leg muscle activations and ball velocity. Ten female windmill softball pitchers (age 17.6 ± 3.47 years, stature 1.67 ± 0.07 m, weight 67.4 ± 12.2 kg) participated. Dependent variables were ball velocity, surface electromyographic (sEMG), kinematic, and kinetic data while the participant was the independent variable. Stride foot contact reported peak vertical forces of 179% body weight. There were positive relationships between ball velocity and ground reaction force (r = 0.758, n = 10, P = 0.029) as well as ball velocity and non-stride leg gluteus maximus (r = 0.851, n = 10, P = 0.007) and medius (r = 0.760, n = 10, P = 0.029) muscle activity, while there was no notable relationship between knee valgus and muscle activation. As the windmill softball pitcher increased ball velocity, her vertical ground reaction forces also increased. Proper conditioning of the lumbopelvic–hip complex, including the gluteals, is essential for injury prevention. From the data presented, it is evident that bilateral strength and conditioning of the gluteal muscle group is salient in the windmill softball pitch as an attempt to decrease incidence of injury. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: Depletion of glycogen stores is associated with fatigue during both sprint and endurance exercises and therefore it is considered important to maintain adequate tissue stores of glycogen during exercise. The aims of the present study in rats were therefore to investigate the effects of preexercise supplementation with carbohydrate and whey protein hydrolysates (WPH) on glycogen content, and phosphorylated signaling molecules of key enzymes that regulate glucose uptake and glycogen synthesis during exercise. Methods: Male SD rats were used in the study (n = 7/group). Prior to exercise, one group of rats was sacrificed, whereas the other groups were given either water, glucose, or glucose plus WPH solutions. After ingestion of the test solutions, glycogen-depleting exercise was carried out for 60 min. The rats were then sacrificed and the triceps muscles excised quickly. Results: Compared to water or glucose only, preexercise ingestion of glucose plus WPH caused a significant attenuation of muscle glycogen depletion during the postexercise period. Coingestion of glucose and WPH also significantly lowered phosphorylated glycogen synthase levels compared to ingestion of water only. In the glucose plus WPH group, the levels of phosphorylated Akt were increased significantly compared to the group ingesting water only, while the levels of phosphorylated PKC were significantly higher than in the groups ingesting only water or glucose. Conclusion: Taken together, these results indicate that, compared to ingestion of glucose or water only, preexercise ingestion of carbohydrate plus WPH activates skeletal muscle proteins of key enzymes that regulate glucose uptake and glycogen synthesis during exercise, thereby attenuating exercise-induced glycogen depletion. [Copyright &y& Elsevier]

Abstract: Objective: Weight loss, glucose intolerance, and insulin resistance are seen in patients with pancreatic ductal adenocarcinoma (PDAC). Peripheral insulin resistance is decreased after tumor resection in patients with PDAC, which is consistent with the hypothesis that factors from the tumor may induce skeletal muscle insulin resistance. Our aim was to investigate the possible mechanisms for their skeletal muscle insulin resistance. Accordingly, the action of insulin on glucose metabolism and content of energy metabolites in muscle of patients with PDAC were investigated. To explore whether PDAC cells could influence muscle glucose uptake, myotubes were exposed to media conditioned by PDAC cells. Methods: Muscle biopsies from patients with PDAC (n = 13), cancer of other sites (n = 8), chronic pancreatitis (n = 8), and controls with benign diseases (n = 8) were assessed for glycogen, adenosine triphosphate, and phosphocreatine content. Basal and insulin-stimulated glucose transport and incorporation into glycogen were also assessed. Myotubes were treated with media conditioned by PDAC (MiaPaca 2) cells and glucose transport was monitored. Results: Insulin-stimulated glucose transport, muscle glycogen, and adenosine triphosphate content were decreased in patients with PDAC compared with controls, and insulin stimulation did not significantly increase glucose incorporation into glycogen in vitro in patients with PDAC. Adenosine triphosphate content correlated with glycogen content but not with glucose transport in skeletal muscle. Media conditioned with human PDAC cells did not affect basal or insulin-stimulated glucose transport in L6 myotubes. Conclusion: In patients with PDAC, muscle insulin resistance is an early and specific finding unrelated to weight loss, plasma free fatty acid levels, and energy status of the cell. PDAC cell-derived factors did not directly induce insulin resistance in myotubes, suggesting a lack of direct tumor-related effects. [Copyright &y& Elsevier]

To examine the time course of alteration in neural process (spinal loop properties) during prolonged tennis playing, 12 competitive players performed a series of neuromuscular tests every 30 min during a 3-h match protocol. Muscle activation (twitch interpolation) and normalized EMG activity were assessed during maximal voluntary contraction (MVC) of plantar flexors. Spinal reflexes and M-waves were evoked at rest (i.e., H and M, respectively) and during MVC (i.e., H, V-wave, M, respectively). MVC torque declined significantly ( P<0.001) across the match protocol, due to decrease ( P<0.001) in muscle activation and in normalized EMG activity. The impairment in MVC was significantly correlated ( r=0.77; P<0.05) with the decline in muscle activation. H/ M ( P<0.001), H/ M ( P<0.01) and V/ M ( P<0.05) ratios were depressed with fatigue and decreased by ∼80%, 46% and 61% at the end of exercise, respectively. Simultaneously, peak twitch torque and M-wave amplitude were significantly ( P<0.01) altered with exercise, suggesting peripheral alterations. During prolonged tennis playing, the compromised voluntary strength capacity is linked to a reduced neural input to the working muscles. This central activation deficit partly results from a modulation in spinal loop properties. [ABSTRACT FROM AUTHOR]

To investigate the effect of supplementing high-volume endurance training with heavy strength training on muscle adaptations and physical performance in elite cross country skiers. Eleven male (18-26 years) and eight female (18-27 years) were assigned to either a strength group (STR) ( n=9) or a control group (CON) ( n=10). STR performed strength training twice a week for 12 weeks in addition to their normal endurance training. STR improved 1 repetition maximum (RM) for seated pull-down and half squat (19±2% and 12±2%, respectively), while no change was observed in CON. Cross-sectional area (CSA) increased in m. triceps brachii for both STR and CON, while there was no change in the m. quadriceps CSA. VO during skate-rollerskiing increased in STR (7±1%), while VO during running was unchanged. No change was observed in energy consumption during rollerskiing at submaximal intensities. Double-poling performance improved more for STR than for CON. Both groups showed a similar improvement in rollerski time-trial performance. In conclusion, 12 weeks of supplemental heavy strength training improved the strength in leg and upper body muscles, but had little effect on the muscle CSA in thigh muscles. The supplemental strength training improved both VO during skate-rollerskiing and double-poling performance. [ABSTRACT FROM AUTHOR]

Theoretical studies of mammalian cortex argue that efficient neural codes should be sparse. However, theoretical and experimental studies have used different definitions of the term "sparse" leading to three assumptions about the nature of sparse codes. First, codes that have high lifetime sparseness require few action potentials. Second, lifetime-sparse codes are also population-sparse. Third, neural codes are optimized to maximize lifetime sparseness. Here, we examine these assumptions in detail and test their validity in primate visual cortex. We show that lifetime and population sparseness are not necessarily correlated and that a code may have high lifetime sparseness regardless of how many action potentials it uses. We measure lifetime sparseness during presentation of natural images in three areas of macaque visual cortex, V1, V2, and V4. We find that lifetime sparseness does not increase across the visual hierarchy. This suggests that the neural code is not simply optimized to maximize lifetime sparseness. We also find that firing rates during a challenging visual task are higher than theoretical values based on metabolic limits and that responses in V1, V2, and V4 are well-described by exponential distributions. These findings are consistent with the hypothesis that neurons are optimized to maximize information transmission subject to metabolic constraints on mean firing rate. [ABSTRACT FROM AUTHOR]

Some 12 years ago, a polymorphism of the angiotensin I-converting enzyme (ACE) gene became the first genetic element shown to impact substantially on human physical performance. The renin-angiotensin system (RAS) exists not just as an endocrine regulator, but also within local tissue and cells, where it serves a variety of functions. Functional genetic polymorphic variants have been identified for most components of RAS, of which the best known and studied is a polymorphism of the ACE gene. The ACE insertion/deletion (I/D) polymorphism has been associated with improvements in performance and exercise duration in a variety of populations. The I allele has been consistently demonstrated to be associated with endurance- orientated events, notably, in triathlons. Meanwhile, the D allele is associated with strength- and power-orientated performance, and has been found in significant excess among elite swimmers. Exceptions to these associations do exist, and are discussed. In theory, associations with ACE genotype may be due to functional variants in nearby loci, and/or related genetic polymorphism such as the angiotensin receptor, growth hormone and bradykinin genes. Studies of growth hormone gene variants have not shown significant associations with performance in studies involving both triathletes and military recruits. The angiotensin type-1 receptor has two functional polymorphisms that have not been shown to be associated with performance, although studies of hypoxic ascent have yielded conflicting results. ACE genotype influences bradykinin levels, and a common gene variant in the bradykinin 2 receptor exists. The high kinin activity haplotye has been associated with increased endurance performance at an Olympic level, and similar results of metabolic efficiency have been demonstrated in triathletes. Whilst the ACE genotype is associated with overall performance ability, at a single organ level, the ACE genotype and related polymorphism have significant associations. In cardiac muscle, ACE genotype has associations with left ventricular mass changes in response to stimulus, in both the health and diseased states. The D allele is associated with an exaggerated response to training, and the I allele with the lowest cardiac growth response. In light of the I-allele association with endurance performance, it seems likely that other regulatory mechanisms exist. Similarly in skeletal muscle, the D allele is associated with greater strength gains in response to training, in both healthy individuals and chronic disease states. As in overall performance, those genetic polymorphisms related to the ACE genotype, such as the bradykinin 2 gene, also influence skeletal muscle strength. Finally, the ACE genotype may influence metabolic efficiency, and elite mountaineers have demonstrated an excess of I alleles and I/I genotype frequency in comparison to controls. Interestingly, this was not seen in amateur climbers. Corroboratory evidence exists among high-altitude settlements in both South America and India, where the I allele exists in greater frequency in those who migrated from the lowlands. Unfortunately, if the ACE genotype does influence metabolic efficiency, associations with peak maximal oxygen consumption have yet to be rigorously demonstrated. The ACE genotype is an important but single factor in the determinant of sporting phenotype. Much of the mechanisms underlying this remain unexplored despite 12 years of research. [ABSTRACT FROM AUTHOR]

While the industrialized world adopts a largely sedentary lifestyle, ultra- marathon running races have become increasingly popular in the last few years in many countries. The ability to run long distances is also considered to have played a role in human evolution. This makes the issue of ultra-long distance physiology important. In the ability to run multiples of 10km (up to 1000km in one stage), fatigue resistance is critical. Fatigue is generally defined as strength loss (i.e. a decrease in maximal voluntary contraction [MVC]), which is known to be dependent on the type of exercise. Critical task variables include the intensity and duration of the activity, both of which are very specific to ultra-endurance sports. They also include the muscle groups involved and the type of muscle contraction, two variables that depend on the sport under consideration. The first part of this article focuses on the central and peripheral causes of the alterations to neuromuscular function that occur in ultra-marathon running. Neuromuscular function evaluation requires measurements of MVCs and maximal electrical/magnetic stimulations; these provide an insight into the factors in the CNS and the muscles implicated in fatigue. However, such measurements do not necessarily predict how muscle function may influence ultra-endurance running and whether this has an effect on speed regulation during a real competition (i.e. when pacing strategies are involved). In other words, the nature of the relationship between fatigue as measured using maximal contractions/stimulation and submaximal performance limitation/regulation is questionable. To investigate this issue, we are suggesting a holistic model in the second part of this article. This model can be applied to all endurance activities, but is specifically adapted to ultra-endurance running: the flush model. This model has the following four components: (i) the ball-cock (or buoy), which can be compared with the rate of perceived exertion, and can increase or decrease based on (ii) the filling rate and (iii) the water evacuated through the waste pipe, and (iv) a security reserve that allows the subject to prevent physiological damage. We are suggesting that central regulation is not only based on afferent signals arising from the muscles and penpheral organs, but is also dependent on peripheral fatigue and spinal/supraspinal inhibition (or disfacilitation) since these alterations imply a higher central drive for a given power output. This holistic model also explains how environmental conditions, sleep deprivation/mental fatigue, pain-killers or psychostimulants, cognitive or nutritional strategies may affect ultra-running performance. [ABSTRACT FROM AUTHOR]

im: To investigate the effects of a neonatal low-protein diet on the morphology of myotubes in culture and the expression of key proteins that regulate myogenesis in young and adult rats. Methods: Male Wistar rats ( n = 18) were suckled by mothers fed diets containing 17% protein (controls, C) or 8% protein (undernourished, UN). All rats were fed a normal protein diet after weaning. Muscles were removed from the legs of 42-, 60- and 90-day-old rats. Muscle cells were cultured to assess cell number, morphology and the expression of major proteins involved in myogenesis (Pax7, cadherins, β1 integrin, IL-4Rα and myogenin) by western blotting. IL-4 levels in culture supernatants were measured by ELISA. Results: Offspring from mothers fed a low-protein diet showed a lower body weight gain. Cell number and myotube expansion were reduced in cultured muscle cells from UN, but the expression of myogenic marker proteins was unaltered. Conclusions: Dietary restriction during lactation had no impact on the synthesis of myogenic marker proteins, and myocyte differentiation occurred normally in the muscles of offspring aged 42, 60 or 90 days. Nevertheless, the number and morphology of the myotubes are altered. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the benefits and limitations of using three dimensional (3D) musculoskeletal modelling (LifeModeler™) in assessing the safety and efficacy of exercising on a seated biceps curl resistance training machine. Three anthropometric cases were studied, representing a 5th percentile female, 50th percentile and 95th percentile male. Results indicated that the LifeModeler™ default model was not adequate to solve the forward dynamics simulations. Therefore adjustments had to be made to the default model to successfully complete the forward dynamics simulations. The software was able to sufficiently highlight the shortcomings of the biceps curl machine's engineered adjustability in relation to the anthropometric dimensions of the studied cases, as the 5th percentile female could not be accommodated suitably on the machine. High lumbar spine anterior/posterior shear forces for all anthropometric cases and maximum muscle tensions for the female and 50th percentile male indicate that the seated biceps curl exercise may pose risks for injuries. To conclude, it appears that 3D musculoskeletal modelling can be used to evaluate resistance training equipment such as the seated biceps curl machine. However the limitations as indicated by this study must be taken into consideration, especially when using the default LifeModeler™ model. [ABSTRACT FROM AUTHOR]