Autophagy is a critical process in the regulation of muscle mass, function and integrity. The molecular mechanisms regulating autophagy are complex and still partly understood. Here, we identify and characterize a novel FoxO-dependent gene, d230025d16rik which we named Mytho (Macroautophagy and YouTH Optimizer), as a regulator of autophagy and skeletal muscle integrity in vivo. Mytho is significantly up-regulated in various mouse models of skeletal muscle atrophy. Short term depletion of MYTHO in mice attenuates muscle atrophy caused by fasting, denervation, cancer cachexia and sepsis. While MYTHO overexpression is sufficient to trigger muscle atrophy, MYTHO knockdown results in a progressive increase in muscle mass associated with a sustained activation of the mTORC1 signaling pathway. Prolonged MYTHO knockdown is associated with severe myopathic features, including impaired autophagy, muscle weakness, myofiber degeneration, and extensive ultrastructural defects, such as accumulation of autophagic vacuoles and tubular aggregates. Inhibition of the mTORC1 signaling pathway in mice using rapamycin treatment attenuates the myopathic phenotype triggered by MYTHO knockdown. Skeletal muscles from human patients diagnosed with myotonic dystrophy type 1 (DM1) display reduced Mytho expression, activation of the mTORC1 signaling pathway and impaired autophagy, raising the possibility that low Mytho expression might contribute to the progression of the disease. We conclude that MYTHO is a key regulator of muscle autophagy and integrity.
Seven members of a 15-man U.S. military team that had operated in rural Malaysia developed an acute illness consisting of fever, myalgias, bronchospasm, fleeting pruritic rashes, transient lymphadenopathy, and subcutaneous nodules associated with eosinophilia, elevated erythrocyte sedimentation rate, and elevated levels of muscle creatinine kinase. Sarcocysts of an unidentified Sarcocystis species were found in skeletal muscle biopsies of the index case. Albendazole ameliorated symptoms in the index case; however, his symptoms persisted for more than 5 years. Symptoms in 5 other men were mild to moderate and self-limited, and 1 team member with laboratory abnormalities was asymptomatic. Of 8 team members tested for antibody to Sarcocystis, 6 were positive; of 4 with the eosinophilic myositis syndrome who were tested, all were positive. We attribute this outbreak of eosinophilic myositis to accidental tissue parasitism by Sarcocystis.
The aims of the current study, therefore, were to compare (1) free-living MPS and (2) muscle and metabolic adaptations to resistance exercise in South Asian and white European adults. Eighteen South Asian and 16 White European men were enrolled in the study. Free-living muscle protein synthesis was measured at baseline. Muscle strength, body composition, resting metabolic rate, VO2max and metabolic responses (insulin sensitivity) to a mixed meal were measured at baseline and following 12 weeks of resistance exercise training. Free-living muscle protein synthesis was not different between South Asians (1.48 ± 0.09%/day) and White Europeans (1.59 ± 0.15%/day) (p = 0.522). In response to resistance exercise training there were no differences, between South Asians and White Europeans, muscle mass, lower body strength or insulin sensitivity. However, there were differences between the ethnicities in response to resistance exercise training in body fat, resting carbohydrate and fat metabolism, blood pressure, VO2max and upper body strength with responses less favourable in South Asians. In this exploratory study there were no differences in muscle protein synthesis or anabolic and metabolic responses to resistance exercise, yet there were less favourable responses in several outcomes. These findings require further investigation.
This study examined the effects of bovine colostrum on exercise -induced modulation of antioxidant parameters in skeletal muscle in mice. Adult male BALB/c mice were randomly divided into four groups (control, colostrum alone, exercise and exercise with colostrum) and each group had three subgroups (day 0, 21 and 42). Colostrum groups of mice were given a daily oral supplement of 50 mg/kg body weight of bovine colostrum and the exercise group of mice were made to exercise on the treadmill for 30 minutes per day. Total antioxidants, lipid hydroperoxides, xanthine oxidase and super oxide dismutase level was assayed from the homogenate of hind limb skeletal muscle.
A mechanomyography muscle contraction (MC) sensor, affixed to the skin surface, was used to quantify muscle tension during repetitive functional electrical stimulation (FES)-evoked isometric rectus femoris contractions to fatigue in individuals with spinal cord injury (SCI). Nine persons with motor complete SCI were seated on a commercial muscle dynamometer that quantified peak torque and average torque outputs, while measurements from the MC sensor were simultaneously recorded. MC-sensor-predicted measures of dynamometer torques, including the signal peak (SP) and signal average (SA), were highly associated with isometric knee extension peak torque (SP: r = 0.91, p < 0.0001), and average torque (SA: r = 0.89, p < 0.0001), respectively. Bland-Altman (BA) analyses with Lin's concordance (ρC) revealed good association between MC-sensor-predicted peak muscle torques (SP; ρC = 0.91) and average muscle torques (SA; ρC = 0.89) with the equivalent dynamometer measures, over a range of FES current amplitudes. The relationship of dynamometer torques and predicted MC torques during repetitive FES-evoked muscle contraction to fatigue were moderately associated (SP: r = 0.80, p < 0.0001; SA: r = 0.77; p < 0.0001), with BA associations between the two devices fair-moderate (SP; ρC = 0.70: SA; ρC = 0.30). These findings demonstrated that a skin-surface muscle mechanomyography sensor was an accurate proxy for electrically-evoked muscle contraction torques when directly measured during isometric dynamometry in individuals with SCI. The novel application of the MC sensor during FES-evoked muscle contractions suggested its possible application for real-world tasks (e.g., prolonged sit-to-stand, stepping,) where muscle forces during fatiguing activities cannot be directly measured.
We determined the effects of "periodized nutrition" on skeletal muscle and whole body responses to a bout of prolonged exercise the following morning. Seven cyclists completed two trials receiving isoenergetic diets differing in the timing of ingestion: they consumed either 8 g/kg body mass (BM) of carbohydrate (CHO) before undertaking an evening session of high-intensity training (HIT) and slept without eating (FASTED), or consumed 4 g/kg BM of CHO before HIT, then 4 g/kg BM of CHO before sleeping (FED). The next morning subjects completed 2 h of cycling (120SS) while overnight fasted. Muscle biopsies were taken on day 1 (D1) before and 2 h after HIT and on day 2 (D2) pre-, post-, and 4 h after 120SS. Muscle [glycogen] was higher in FED at all times post-HIT (P < 0.001). The cycling bouts increased PGC1α mRNA and PDK4 mRNA (P < 0.01) in both trials, with PDK4 mRNA being elevated to a greater extent in FASTED (P < 0.05). Resting phosphorylation of AMPK(Thr172), p38MAPK(Thr180/Tyr182), and p-ACC(Ser79) (D2) was greater in FASTED (P < 0.05). Fat oxidation during 120SS was higher in FASTED (P = 0.01), coinciding with increases in ACC(Ser79) and CPT1 as well as mRNA expression of CD36 and FABP3 (P < 0.05). Methylation on the gene promoter for COX4I1 and FABP3 increased 4 h after 120SS in both trials, whereas methylation of the PPARδ promoter increased only in FASTED. We provide evidence for shifts in DNA methylation that correspond with inverse changes in transcription for metabolically adaptive genes, although delaying postexercise feeding failed to augment markers of mitochondrial biogenesis.
Bungarus candidus and Bungarus fasciatus are two species of krait found in Southeast Asia. Envenoming by these snakes is often characterized by neurotoxicity and, without treatment, causes considerable morbidity and mortality. In this study, the in vitro neurotoxicity of each species, and the effectiveness of two monovalent antivenoms and a polyvalent antivenom, against the neurotoxic effects of the venoms, were examined in a skeletal muscle preparation. Both venoms caused concentration-dependent inhibition of indirect twitches, and attenuated responses to exogenous nicotinic receptor agonists, in the chick biventer preparation, with B. candidus venom being more potent than B. fasciatus venom. SDS-PAGE and western blot analysis indicated different profiles between the venoms. Despite these differences, most proteins bands were recognized by all three antivenoms. Antivenom, added prior to the venoms, attenuated the neurotoxic effect of the venoms. Interestingly, the respective monovalent antivenoms did not neutralize the effects of the venom from the other Bungarus species indicating a relative absence of cross-neutralization. Addition of a high concentration of polyvalent antivenom, at the t90 time point after addition of venom, partially reversed the neurotoxicity of B. fasciatus venom but not B. candidus venom. The monovalent antivenoms had no significant effect when added at the t90 time point. This study showed that B. candidus and B. fasciatus venoms display marked in vitro neurotoxicity in the chick biventer preparation and administration of antivenoms at high dose is necessary to prevent or reverse neurotoxicity.
Bungarus fasciatus is one of three species of krait found in Malaysia. Envenoming by B. fasciatus results in neurotoxicity due to the presence of presynaptic and postsynaptic neurotoxins. Antivenom, either monovalent or polyvalent, is the treatment of choice in systemically envenomed patients. In this study, we have isolated a postsynaptic neurotoxin which we named α-elapitoxin-Bf1b. This toxin has an approximate molecular weight of 6.9 kDa, with LCMS/MS data showing that it is highly homologous with Neurotoxin 3FTx-RI, a toxin identified in the Bungarus fasciatus venom gland transcriptome. α-Elapitoxin-Bf1b also shared similarity with short-chain neurotoxins from Laticauda colubrina and Pseudechis australis. α-Elapitoxin-Bf1b produced concentration- and time-dependent neurotoxicity in the indirectly-stimulated chick biventer cervicis muscle preparation, an effect partially reversible by repetitive washing of the preparation. The pA2 value for α-elapitoxin-Bf1b of 9.17 ± 0.64, determined by examining the effects of the toxin on cumulative carbacol concentration-response curves, indicated that the toxin is more potent than tubocurarine and α-bungarotoxin. Pre-incubation of Bungarus fasciatus monovalent and neuro polyvalent antivenom failed to prevent the neurotoxic effects of α-elapitoxin-Bf1b in the chick biventer cervicis muscle preparation. In conclusion, the isolation of a postsynaptic neurotoxin that cannot be neutralized by either monovalent and polyvalent antivenoms may indicate the presence of isoforms of postsynaptic neurotoxins in Malaysian B. fasciatus venom.
Many human behaviours and pathologies have been attributed to the putative mirror neuron system, a neural system that is active during both the observation and execution of actions. While there are now a very large number of papers on the mirror neuron system, variations in the methods and analyses employed by researchers mean that the basic characteristics of the mirror response are not clear. This review focuses on three important aspects of the mirror response, as measured by modulations in corticospinal excitability: (1) muscle specificity; (2) direction; and (3) timing of modulation. We focus mainly on electromyographic (EMG) data gathered following single-pulse transcranial magnetic stimulation (TMS), because this method provides precise information regarding these three aspects of the response. Data from paired-pulse TMS paradigms and peripheral nerve stimulation (PNS) are also considered when we discuss the possible mechanisms underlying the mirror response. In this systematic review of the literature, we examine the findings of 85 TMS and PNS studies of the human mirror response, and consider the limitations and advantages of the different methodological approaches these have adopted in relation to discrepancies between their findings. We conclude by proposing a testable model of how action observation modulates corticospinal excitability in humans. Specifically, we propose that action observation elicits an early, non-specific facilitation of corticospinal excitability (at around 90ms from action onset), followed by a later modulation of activity specific to the muscles involved in the observed action (from around 200ms). Testing this model will greatly advance our understanding of the mirror mechanism and provide a more stable grounding on which to base inferences about its role in human behaviour.
Volumetric Muscle Loss (VML) is associated with muscle loss function and often untreated and considered part of the natural sequelae of trauma. Various types of biomaterials with different physical and properties have been developed to treat VML. However, much work remains yet to be done before the scaffolds can pass from the bench to the bedside. The present review aims to provide a comprehensive summary of the latest developments in the construction and application of natural polymers-based tissue scaffolding for volumetric muscle injury. Here, the tissue engineering approaches for treating volumetric muscle loss injury are highlighted and recent advances in cell-based therapies using various sources of stem cells are elaborated in detail. An overview of different strategies of tissue scaffolding and their efficacy on skeletal muscle cells regeneration and migration are presented. Furthermore, the present paper discusses a wide range of natural polymers with a special focus on proteins and polysaccharides that are major components of the extracellular matrices. The natural polymers are biologically active and excellently promote cell adhesion and growth. These bio-characteristics justify natural polymers as one of the most attractive options for developing scaffolds for muscle cell regeneration.
Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.
The metabolic syndrome (MetS) is a cluster of metabolic abnormalities comprising visceral obesity, dyslipidaemia and insulin resistance (IR). With the onset of IR, the expression of lipoprotein lipase (LPL), a key regulator of lipoprotein metabolism, is reduced. Increased activation of glucocorticoid receptors results in MetS symptoms and is thus speculated to have a role in the pathophysiology of the MetS. Glycyrrhizic acid (GA), the bioactive constituent of licorice roots (Glycyrrhiza glabra) inhibits 11beta-hydroxysteroid dehydrogenase type 1 that catalyzes the activation of glucocorticoids. Thus, oral administration of GA is postulated to ameliorate the MetS.
To make robotic hand devices controlled by surface electromyography (sEMG) signals feasible and practical tools for assisting patients with hand impairments, the problems that prevent these devices from being widely used have to be overcome. The most significant problem is the involuntary amplitude variation of the sEMG signals due to the movement of electrodes during forearm motion. Moreover, for patients who have had a stroke or another neurological disease, the muscle activity of the impaired hand is weak and has a low signal-to-noise ratio (SNR). Thus, muscle activity detection methods intended for controlling robotic hand devices should not depend mainly on the amplitude characteristics of the sEMG signal in the detection process, and they need to be more reliable for sEMG signals that have a low SNR. Since amplitude-independent muscle activity detection methods meet these requirements, this paper investigates the performance of such a method on people who have had a stroke in terms of the detection of weak muscle activity and resistance to false alarms caused by the involuntary amplitude variation of sEMG signals; these two parameters are very important for achieving the reliable control of robotic hand devices intended for people with disabilities. A comparison between the performance of an amplitude-independent muscle activity detection algorithm and three amplitude-dependent algorithms was conducted by using sEMG signals recorded from six hemiparesis stroke survivors and from six healthy subjects. The results showed that the amplitude-independent algorithm performed better in terms of detecting weak muscle activity and resisting false alarms.
This study aimed to determine effects of 6-day progressive increase in salinity from 1 per thousand to 15 per thousand on nitrogen metabolism and excretion in the soft-shelled turtle, Pelodiscus sinensis. For turtles exposed to 15 per thousand water on day 6, the plasma osmolality and concentrations of Na+, Cl- and urea increased significantly, which presumably decreased the osmotic loss of water. Simultaneously, there were significant increases in contents of urea, certain free amino acids (FAAs) and water-soluble proteins that were involved in cell volume regulation in various tissues. There was an apparent increase in proteolysis, releasing FAAs as osmolytes. In addition, there might be an increase in catabolism of certain amino acids, producing more ammonia. The excess ammonia was retained as indicated by a significant decrease in the rate of ammonia excretion on day 4 in 15 per thousand water, and a major portion of it was converted to urea. The rate of urea synthesis increased 1.4-fold during the 6-day period, although the capacity of the hepatic ornithine urea cycle remained unchanged. Urea was retained for osmoregulation because there was a significant decrease in urea excretion on day 4. Increased protein degradation and urea synthesis implies greater metabolic demands, and indeed turtles exposed to 15 per thousand water had significantly higher O2 consumption rate than the freshwater (FW) control. When turtles were returned from 15 per thousand water to FW on day 7, there were significant increases in ammonia (probably released through increased amino acid catabolism) and urea excretion, confirming that FAAs and urea were retained for osmoregulatory purposes in brackish water.
White rice (WR) is a major staple food for people in developing countries and it may be responsible for the growing incidence of type 2 diabetes. Nonpregnant Female Sprague Dawley rats fed with WR or brown rice (BR) for 8 weeks were mated with age-matched male rats maintained on normal pellet over the same period. Offsprings were fed normal pellet after weaning until 8 weeks postdelivery. Rats fed with WR and their offsprings showed worsened oral glucose tolerance test, lower serum adiponectin levels, and higher weights, homeostatic model assessment of insulin resistance, serum retinol binding protein-4 levels, and leptin levels, compared with the normal and BR groups, suggesting an increased risk of insulin resistance. Furthermore, transcriptional levels of genes involved in insulin signaling showed different expression patterns in the liver, muscle, and adipose tissues of mothers and offsprings in both WR and BR groups. The results propose that the cycle of WR-induced insulin resistance in offsprings due to prenatal exposure, followed by their consumption of WR later in life may contribute to diabetes incidents. These findings are worth studying further.
Cricket bowling generates forces with torques on the upper limb muscles and makes the biceps brachii (BB) muscle vulnerable to overuse injury. The aim of this study was to investigate whether there are differences in the amplitude of the EMG signal of the BB muscle during fast and spin delivery, during the seven phases of both types of bowling and the kinesiological interpretation of the bowling arm for muscle contraction mechanisms during bowling. A group of 16 male amateur bowlers participated in this study, among them 8 fast bowlers (FB) and 8 spin bowlers (SB). The root mean square (EMGRMS), the average sEMG (EMGAVG), the maximum peak amplitude (EMGpeak), and the variability of the signal were calculated using the coefficient of variance (EMGCV) from the BB muscle of each bowler (FB and SB) during each bowling phase. The results demonstrate that, (i) the BB muscle is more active during FB than during SB, (ii) the point of ball release and follow-through generated higher signals than the other five movements during both bowling categories, (iii) the BB muscle variability is higher during SB compared with FB, (iv) four statistically significant differences (p<0.05) found between the bowling phases in fast bowling and three in spin bowling, and (v) several arm mechanics occurred for muscle contraction. There are possible clinical significances from the outcomes; like, recurring dynamic contractions on BB muscle can facilitate to clarify the maximum occurrence of shoulder pain as well as biceps tendonitis those are medically observed in professional cricket bowlers, and treatment methods with specific injury prevention programmes should focus on the different bowling phases with the maximum muscle effect. Finally, these considerations will be of particular importance in assessing different physical therapy on bowler's muscle which can improve the ball delivery performance and stability of cricket bowlers.
Sarcosporidiosis is a disease caused by intracellular protozoan parasites, namely, Sarcocystis spp. In pigs, three species of Sarcocystis spp. have been recognised, including Sarcocystis meischeriana, Sarcocystis porcifelis and Sarcocystis suihominis. The aim of this study is to determine the prevalence of muscular sarcosporidiosis in pigs using the pepsin digestion technique. A total of 150 fresh heart, oesophagus and thigh muscle samples from 50 Yorkshire and Landrace pigs were collected from two local abattoirs in Perak from May to August 2014. All the fresh muscle samples were thoroughly examined for macrocyst-forming Sarcocystis spp. and processed using the peptic digestion technique to detect bradyzoites. The results from the muscle samples showed that 58% (29 out of 50) of the pigs were positive for Sarcocystis spp. These findings highlight the importance of implementing stringent measures for screening pigs in abattoirs for Sarcocystis spp. infection because this infection in pigs is a public health concern.
The present study aims to evaluate the effects of feeding palm oil by-products based diets on different muscle fatty acid profiles in goats. Thirty-two Cacang × Boer goats were randomly assigned to four dietary treatments: (1) control diet (CD), (2) 80% decanter cake diet (DCD), (3) 80% palm kernel cake diet (PKCD) and (4) CD plus 5% palm oil (PO) supplemented diet (CPOD). After 100 days of feeding, four goats from each group were slaughtered and longissimus dorsi (LD), infraspinatus (IS) and biceps femoris (BF) were sampled for analysis of fatty acids. Goats fed the PKCD had higher (P<0.05) concentration of lauric acid (C12:0) than those fed the other diets in all the muscles tested. Compared to the other diets, the concentrations of palmitic acid (C16:0) and stearic acid (C18:0) were lower (P<0.05) and that of linoleic acid (C18:2 n-6) was higher (P<0.05) in the muscles from goats fed the CD. It was concluded that palm kernel cake and decanter cake can be included in the diet of goats up to 80% with more beneficial than detrimental effects on the fatty acid profile of their meat.
Thirty-two male goats were randomly assigned to four dietary treatments namely, basal diet 70% concentrate and 30% oil palm fronds (control, CN), CN + 400 mg/kg vitamin E (VE), 0.5% turmeric (TU) or 0.5% Anderographis paniculata (AP). After 100 days of feeding, the goats were slaughtered and longissimus dorsi (LD) muscle was sampled. The muscle was vacuum-packaged and conditioned for 0, 7 and 14 days in a chiller (4 °C). The drip loss of the LD muscle increased (P < 0.05) with aging time. Meat tenderness was improved (p < 0.05) at 14 days aging. All antioxidant supplements improved (P < 0.05) colour of the meat. The TBARS value increased (P < 0.05) at 7 days of aging while the fatty acid composition was not affected by the dietary supplements. It is concluded that TU and AP are potential dietary antioxidant supplements, for the purpose of improving the quality of chevon.
Disorders of rotator cuff tendons results in acute pain limiting the normal range of motion for shoulder. Of all the tendons in rotator cuff, supraspinatus (SSP) tendon is affected first of any pathological changes. Diagnosis of SSP tendon using ultrasound is considered to be operator dependent with its accuracy being related to operator's level of experience.