Signaling In Muscle Research Articles

CircUSP13 facilitates the fast-to-slow myofiber shift via the MAPK/ERK signaling pathway in goat skeletal muscles.

Understanding how skeletal muscle fiber proportions are regulated is essential for understanding muscle function and improving the quality of mutton. While circular RNA (circRNA) has a critical function in myofiber type transformation, the specific mechanisms are not yet fully understood. Prior evidence indicates that circular ubiquitin-specific peptidase 13 (circUSP13) can promote myoblast differentiation by acting as a ceRNA, but its potential role in myofiber switching is still unknown. Herein, we found that circUSP13 enhanced slow myosin heavy chain (MyHC-slow) and suppressed MyHC-fast expression in goat primary myoblasts (GPMs). Meanwhile, circUSP13 evidently enhanced the remodeling of the mitochondrial network while inhibiting the autophagy of GPMs. We obtained fast-dominated myofibers, via treatment with rotenone, and further demonstrated the positive role of circUSP13 in the fast-to-slow transition. Mechanistically, activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway significantly impaired the slow-to-fast shift in fully differentiated myotubes, which was restored by circUSP13 or IGF1 overexpression. In conclusion, circUSP13 promoted the fast-to-slow myofiber type transition through MAPK/ERK signaling in goat skeletal muscle. These findings provide novel insights into the role of circUSP13 in myofiber type transition and contribute to a better understanding of the genetic mechanisms underlying meat quality.

MultiSenseBadminton: Wearable Sensor–Based Biomechanical Dataset for Evaluation of Badminton Performance

The sports industry is witnessing an increasing trend of utilizing multiple synchronized sensors for player data collection, enabling personalized training systems with multi-perspective real-time feedback. Badminton could benefit from these various sensors, but there is a scarcity of comprehensive badminton action datasets for analysis and training feedback. Addressing this gap, this paper introduces a multi-sensor badminton dataset for forehand clear and backhand drive strokes, based on interviews with coaches for optimal usability. The dataset covers various skill levels, including beginners, intermediates, and experts, providing resources for understanding biomechanics across skill levels. It encompasses 7,763 badminton swing data from 25 players, featuring sensor data on eye tracking, body tracking, muscle signals, and foot pressure. The dataset also includes video recordings, detailed annotations on stroke type, skill level, sound, ball landing, and hitting location, as well as survey and interview data. We validated our dataset by applying a proof-of-concept machine learning model to all annotation data, demonstrating its comprehensive applicability in advanced badminton training and research.

Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training.

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross-sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three-point bending and microcomputer tomography were measured in the femur. Follow-up experiments in human primary muscle cells were used to explore supra-physiological effects of ACE. Data were analyzed using a two-way ANOVA for treatment (ACE or placebo) and condition (exercise or non-exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey's adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p > .05). There was a treatment-by-condition effect for Young's Modulus where placebo exercise was significantly lower than placebo control (p < .05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated-AMPK was significantly increased with exercise (p < .05) and this was attenuated with ACE treatment. Furthermore, phospho-4EBP1 was depressed in the exercise group compared to the control (p < .05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p < .05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post-exercise.

JAK/STAT mediated insulin resistance in muscles is essential for effective immune response

BackgroundThe metabolically demanding nature of immune response requires nutrients to be preferentially directed towards the immune system at the expense of peripheral tissues. We study the mechanisms by which this metabolic reprograming occurs using the parasitoid infection of Drosophila larvae. To overcome such an immune challenge hemocytes differentiate into lamellocytes, which encapsulate and melanize the parasitoid egg. Hemocytes acquire the energy for this process by expressing JAK/STAT ligands upd2 and upd3, which activates JAK/STAT signaling in muscles and redirects carbohydrates away from muscles in favor of immune cells.MethodsImmune response of Drosophila larvae was induced by parasitoid wasp infestation. Carbohydrate levels, larval locomotion and gene expression of key proteins were compared between control and infected animals. Efficacy of lamellocyte production and resistance to wasp infection was observed for RNAi and mutant animals.ResultsAbsence of upd/JAK/STAT signaling leads to an impaired immune response and increased mortality. We demonstrate how JAK/STAT signaling in muscles leads to suppression of insulin signaling through activation of ImpL2, the inhibitor of Drosophila insulin like peptides.ConclusionsOur findings reveal cross-talk between immune cells and muscles mediates a metabolic shift, redirecting carbohydrates towards immune cells. We emphasize the crucial function of muscles during immune response and show the benefits of insulin resistance as an adaptive mechanism that is necessary for survival.

Unsupervised neural decoding for concurrent and continuous multi-finger force prediction

Reliable prediction of multi-finger forces is crucial for neural-machine interfaces. Various neural decoding methods have progressed substantially for accurate motor output predictions. However, most neural decoding methods are performed in a supervised manner, i.e., the finger forces are needed for model training, which may not be suitable in certain contexts, especially in scenarios involving individuals with an arm amputation. To address this issue, we developed an unsupervised neural decoding approach to predict multi-finger forces using spinal motoneuron firing information. We acquired high-density surface electromyogram (sEMG) signals of the finger extensor muscle when subjects performed single-finger and multi-finger tasks of isometric extensions. We first extracted motor units (MUs) from sEMG signals of the single-finger tasks. Because of inevitable finger muscle co-activation, MUs controlling the non-targeted fingers can also be recruited. To ensure an accurate finger force prediction, these MUs need to be teased out. To this end, we clustered the decomposed MUs based on inter-MU distances measured by the dynamic time warping technique, and we then labeled the MUs using the mean firing rate or the firing rate phase amplitude. We merged the clustered MUs related to the same target finger and assigned weights based on the consistency of the MUs being retained. As a result, compared with the supervised neural decoding approach and the conventional sEMG amplitude approach, our new approach can achieve a higher R2 (0.77 ± 0.036 vs. 0.71 ± 0.11 vs. 0.61 ± 0.09) and a lower root mean square error (5.16 ± 0.58 %MVC vs. 5.88 ± 1.34 %MVC vs. 7.56 ± 1.60 %MVC). Our findings can pave the way for the development of accurate and robust neural-machine interfaces, which can significantly enhance the experience during human-robotic hand interactions in diverse contexts.

CGRP sensory neurons promote tissue healing via neutrophils and macrophages

The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective1,2. This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury2,3. Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context4–12. However, how neuro–immune interactions affect tissue repair and regeneration following acute injury is unclear. Here we show that ablation of the NaV1.8 nociceptor impairs skin wound repair and muscle regeneration after acute tissue injury. Nociceptor endings grow into injured skin and muscle tissues and signal to immune cells through the neuropeptide calcitonin gene-related peptide (CGRP) during the healing process. CGRP acts via receptor activity-modifying protein 1 (RAMP1) on neutrophils, monocytes and macrophages to inhibit recruitment, accelerate death, enhance efferocytosis and polarize macrophages towards a pro-repair phenotype. The effects of CGRP on neutrophils and macrophages are mediated via thrombospondin-1 release and its subsequent autocrine and/or paracrine effects. In mice without nociceptors and diabetic mice with peripheral neuropathies, delivery of an engineered version of CGRP accelerated wound healing and promoted muscle regeneration. Harnessing neuro–immune interactions has potential to treat non-healing tissues in which dysregulated neuro–immune interactions impair tissue healing.

Prosthetics for Lower Limb Amputees: A Comprehensive Review of Technologies, Applications, and Future Directions

With improvements in active prosthetics, new possibilities have emerged for managing lower limb amputations, significantly enhancing both functional performance and quality of life for users. Recent technological developments, including electromyography (EMG) sensors, adaptive control systems, real-time feedback mechanisms, and remote-control functionality, have introduced advanced capabilities that mimic natural limb movements, greatly benefiting users of artificial limbs. This review paper provides a comprehensive overview of these advancements and assesses their potential clinical impact. EMG sensors have increased prosthetic control by up to 30% by detecting muscle signals with high precision. Adaptive control systems have enhanced the naturalness of gait by approximately 25%, closely approximating normal human locomotion. Real-time feedback systems, such as haptics and vibration alerts, have improved user confidence and mobility by 40% by providing immediate tactile sensory information about the prosthetic’s position. The addition of remote-control systems has improved efficiency by 20% through easier adjustments and real-time tuning of the prosthesis. Researchers have observed a 35% reduction in recovery time for patients using active prosthetics, which enable quicker walking and reduce the effort required from other limbs. In recreational and sporting contexts, these prosthetics have nearly matched non-amputees in peak speed, achieving up to 50% of human performance in power and non-power metrics. AI-enabled improvements are anticipated to further enhance adaptivity and responsiveness in the future. Overall, these high-tech developments represent a significant advancement in aiding lower limb amputees in their daily lives, with considerable potential for future growth and improvement.

An Association between OXPHOS-Related Gene Expression and Malignant Hyperthermia Susceptibility in Human Skeletal Muscle Biopsies.

Malignant hyperthermia (MH) is a pharmacogenetic condition of skeletal muscle that manifests in hypermetabolic responses upon exposure to volatile anaesthetics. This condition is caused primarily by pathogenic variants in the calcium-release channel RYR1, which disrupts calcium signalling in skeletal muscle. However, our understanding of MH genetics is incomplete, with no variant identified in a significant number of cases and considerable phenotype diversity. In this study, we applied a transcriptomic approach to investigate the genome-wide gene expression in MH-susceptible cases using muscle biopsies taken for diagnostic testing. Baseline comparisons between muscle from MH-susceptible individuals (MHS, n = 8) and non-susceptible controls (MHN, n = 4) identified 822 differentially expressed genes (203 upregulated and 619 downregulated) with significant enrichment in genes associated with oxidative phosphorylation (OXPHOS) and fatty acid metabolism. Investigations of 10 OXPHOS target genes in a larger cohort (MHN: n = 36; MHS: n = 36) validated the reduced expression of ATP5MD and COQ6 in MHS samples, but the remaining 8 selected were not statistically significant. Further analysis also identified evidence of a sex-linked effect in SDHB and UQCC3 expression, and a difference in ATP5MD expression across individuals with MH sub-phenotypes (trigger from in vitro halothane exposure only, MHSh (n = 4); trigger to both in vitro halothane and caffeine exposure, MHShc (n = 4)). Our data support a link between MH-susceptibility and dysregulated gene expression associated with mitochondrial bioenergetics, which we speculate plays a role in the phenotypic variability observed within MH.

Motion Picture Analysis: A Mechanical Study of Tennis Players during Forehand and Backhand Strokes

Objectives: The purpose of this article is to utilize video images for the examination of lower limb biomechanics in tennis players while executing forehand and backhand strokes, providing a reference for training. Methods: This article provides a brief introduction to forehand and backhand strokes in the sport of tennis. Subsequently, a biomechanical analysis of the lower limbs during forehand and backhand strokes was conducted on ten level 2 tennis players and ten specialized tennis students at XX Sports University. Findings: Level 2 athletes who have undergone a long training exhibited higher linear velocity and joint torque in the lower-limb joints during the preparatory and striking phases of forehand and backhand strokes. Additionally, they exhibited more pronounced surface electromyographic signals in the rectus femoris muscle of the lower limbs. Novelty:The novelty of this article lies in the use of video imagery, a non-contact and non-intrusive method that does not affect the athletes' movements, to study the biomechanics of their lower limbs. Doi: 10.28991/HIJ-2024-05-01-07 Full Text: PDF

IMU-Based Approach to Detect Spastic Cerebral Palsy in Infants at Early Stages

INTRODUCTION: Cerebral Palsy (CP) is a non-progressive neurological disorder affecting muscle control in early childhood, leading to permanent alterations in body posture and movement. Early identification is crucial for accurate diagnosis and therapy-based interventions. In recent years, an automated monitoring system has been developed to facilitate the health assessment of infants, enabling early recognition of neurological dysfunctions in high-risk infants. However, the interpretation of these assessments lacks standardization and is subject to examiner bias.&#x0D; OBJECTIVES: Many infants with CP exhibit increased tonic stretch reflexes due to Upper Motor Neuron Syndrome (UMNS), resulting from motor neuron damage that disrupts muscle signalling.&#x0D; METHOD: To detect abnormal muscle reactions, our team employed an Inertial Measurement Unit (IMU) sensor, comprising three tri-axial sensors (accelerometer, gyroscope, magnetometer) that capture movement data continuously and unobtrusively. IMU sensors are compact, cost-effective, and have low processing requirements, requiring attachment to the infant's body to measure inter-body part angles. Our team analyzed muscle activity and posture using IMU sensors, collecting tri-axial data from 43 infants in real-time. Additional factors like age, stride length, and leg length were incorporated into the dataset.&#x0D; RESULTS: Our team has applied various supervised machine learning approaches to predict CP in infants due to the limited dataset size, validating models through k-fold cross-validation. Among the models, Naive Bayes (NB) outperformed Logistic Regression (LR), Decision Tree (DT), Linear Discriminant Analysis (LDA), k-Nearest Neighbors (kNN), and Support Vector Machine (SVM), achieving an accuracy of 88%. CONCLUSION: This research contributes to the early detection and intervention of CP in infants, potentially improving their long-term outcomes.

Gd-EOB-DTPA-enhanced MRI Image Characteristics and Radiomics Characteristics Combined with Machine Learning for Assessment of Functional Liver Reserve.

To investigate the feasibility of image characteristics and radiomics combined with machine learning based on Gd-EOB-DTPA-enhanced MRI for functional liver reserve assessment in cirrhotic patients. 123 patients with cirrhosis were retrospectively analyzed; all our patients underwent pre-contrast MRI, triphasic (arterial phase, venous phase, equilibrium phase) Gd-EOB-DTPA dynamic enhancement and hepatobiliary phase (20 minutes delayed). The relative enhancement (RE) of the patient's liver, the liver-spleen signal ratio in the hepatobiliary phase (SI liver/ spleen), the liver-vertical muscle signal ratio in the hepatobiliary phase (SI liver/ muscle), the bile duct signal intensity contrast ratio (SIR), and the radiomics features were evaluated. The support vector machine (SVM) was used as the core of machine learning to construct the liver function classification model using image and radiomics characteristics, respectively. The area under the curve was the largest in SIR to identify Child-Pugh group A versus Child-Pugh group B+C in the image characteristics, AUC = 0.740, and Perc. 10% to identify Child-Pugh group A versus Child-Pugh group B+C in the radiomics characteristics, AUC = 0.9337. The efficacy of the SVM model constructed using radiomics characteristics was better, with an area under the curve of 0.918, a sensitivity of 95.45%, a specificity of 80.00%, and an accuracy of 89.19%. The image and radiomics characteristics based on Gd-EOB-DTPA-enhanced MRI can reflect liver function, and the model constructed based on radiomics characteristics combined with machine learning methods can better assess functional liver reserve.

Detecting Psychological Interventions Using Bilateral Electromyographic Wearable Sensors.

This study investigated the impact of auditory stimuli on muscular activation patterns using wearable surface electromyography (EMG) sensors. Employing four key muscles (Sternocleidomastoid Muscle (SCM), Cervical Erector Muscle (CEM), Quadricep Muscles (QMs), and Tibialis Muscle (TM)) and time domain features, we differentiated the effects of four interventions: silence, music, positive reinforcement, and negative reinforcement. The results demonstrated distinct muscle responses to the interventions, with the SCM and CEM being the most sensitive to changes and the TM being the most active and stimulus dependent. Post hoc analyses revealed significant intervention-specific activations in the CEM and TM for specific time points and intervention pairs, suggesting dynamic modulation and time-dependent integration. Multi-feature analysis identified both statistical and Hjorth features as potent discriminators, reflecting diverse adaptations in muscle recruitment, activation intensity, control, and signal dynamics. These features hold promise as potential biomarkers for monitoring muscle function in various clinical and research applications. Finally, muscle-specific Random Forest classification achieved the highest accuracy and Area Under the ROC Curve for the TM, indicating its potential for differentiating interventions with high precision. This study paves the way for personalized neuroadaptive interventions in rehabilitation, sports science, ergonomics, and healthcare by exploiting the diverse and dynamic landscape of muscle responses to auditory stimuli.

A Wearable Upper Limb Exoskeleton System and Intelligent Control Strategy.

Heavy lifting operations frequently lead to upper limb muscle fatigue and injury. In order to reduce muscle fatigue, auxiliary force for upper limbs can be provided. This paper presents the development and evaluation of a wearable upper limb exoskeleton (ULE) robot system. A flexible cable transmits auxiliary torque and is connected to the upper limb by bypassing the shoulder. Based on the K-nearest neighbors (KNN) algorithm and integrated fuzzy PID control strategy, the ULE identifies the handling posture and provides accurate active auxiliary force automatically. Overall, it has the quality of being light and easy to wear. In unassisted mode, the wearer's upper limbs minimally affect the range of movement. The KNN algorithm uses multi-dimensional motion information collected by the sensor, and the test accuracy is 94.59%. Brachioradialis muscle (BM), triceps brachii (TB), and biceps brachii (BB) electromyogram (EMG) signals were evaluated by 5 kg, 10 kg, and 15 kg weight conditions for five subjects, respectively, during lifting, holding, and squatting. Compared with the ULE without assistance and with assistance, the average peak values of EMG signals of BM, TB, and BB were reduced by 19-30% during the whole handling process, which verified that the developed ULE could provide practical assistance under different load conditions.

The central pattern of weakness of ALS: Morphological correlates in whole-body muscle MRI.

Monosynaptically cortically innervated α-motoneurons are early and strongly involved in amyotrophic lateral sclerosis (ALS). Consequently, the muscles that receive the strongest direct corticomotoneuronal input are the clinically most affected. To objectify this concept in vivo through morphological image correlates, whole-body magnetic resonance imaging (MRI) with muscle signal analysis was performed in patients with ALS compared to healthy controls. Modified Dixon-based whole-body MRI was acquired in patients with ALS (n = 33) and matched healthy controls (n = 30). Manual labeling of limb muscle MRI was performed, and a specific subset of nine muscles, selected as pairs of muscle groups with different corticomotoneuronal input, was analyzed per subject based on their volume, fat fraction, and functional remaining muscle area (fRMA). Statistical analysis of 978 muscles in total revealed significantly decreased volumes, decreased fRMA, and increased fat fraction in the muscles of patients with ALS compared to controls. The clinical degree of pareses of directly innervated muscles was significantly worse than that of less directly innervated muscles in each comparison. The muscles receiving stronger direct corticomotoneuronal input showed more pronounced morphological involvement compared to those with less monosynaptic corticomotoneuronal input (fRMA, significant in three pairwise comparisons). In conclusion, whole-body MRI-based muscle analysis provided additional evidence for a characteristic pattern of pareses in ALS. This technical approach (parameterization and quantification of muscle alterations from MRI) to patients with ALS could pave the way for the future establishment of a diagnostic algorithm of muscle MRI for ALS and may serve as a biomarker.

Effect of CB1 Receptor Deficiency on Mitochondrial Quality Control Pathways in Gastrocnemius Muscle.

This study aims to explore the complex role of cannabinoid type 1 receptor (CB1) signaling in the gastrocnemius muscle, assessing physiological processes in both CB1+/+ and CB1-/- mice. The primary focus is to enhance our understanding of how CB1 contributes to mitochondrial homeostasis. At the tissue level, CB1-/- mice exhibit a substantial miRNA-related alteration in muscle fiber composition, characterized by an enrichment of oxidative fibers. CB1 absence induces a significant increase in the oxidative capacity of muscle, supported by elevated in-gel activity of Complex I and Complex IV of the mitochondrial respiratory chain. The increased oxidative capacity is associated with elevated oxidative stress and impaired antioxidant defense systems. Analysis of mitochondrial biogenesis markers indicates an enhanced capacity for new mitochondria production in CB1-/- mice, possibly adapting to altered muscle fiber composition. Changes in mitochondrial dynamics, mitophagy response, and unfolded protein response (UPR) pathways reveal a dynamic interplay in response to CB1 absence. The interconnected mitochondrial network, influenced by increased fusion and mitochondrial UPR components, underlines the dual role of CB1 in regulating both protein quality control and the generation of new mitochondria. These findings deepen our comprehension of the CB1 impact on muscle physiology, oxidative stress, and MQC processes, highlighting cellular adaptability to CB1-/-. This study paves the way for further exploration of intricate signaling cascades and cross-talk between cellular compartments in the context of CB1 and mitochondrial homeostasis.

Concept Design of a Smart Haptic Suit for a Biological Signal Recognition and Feedback to Human Body Movements

The ultimate purpose of monitoring bio-signals in the form of individually tailored clothing is to monitor an unconstrained bio-signals during the wearer's physiological activities and provide freedom of movement, thereby eliminating inconvenience in workspace of HMI (Human-Machine Interaction) or HRI (Human-Robot Interaction), and healthcare life. In the form of smart clothing for human collaboration industries or everyday life, there is a need to provide new sensitive and high accurate functions to the wearer while also faithfully performing the functions of existing clothing. In this respect, auxetic pattern-based sensors and actuators can be said to be one of the most promising candidates to be combined with smart wearable technology. There is an emerging need to research the concepts of these new sensors and actuators and present a paradigm for clothing research on innovative smart haptic suits. Accordingly, there is a need for a concept of smart haptic system suitable to meet the conditions of sensors and actuators with improved sensitivity, conductivity, and receptivity that can have characteristics such as microporosity, flexibility, and large surface area of nano and micro web structures. When measuring a bio-signal sensing and motion feedback using an electro-active structural pattern, the signal waveform can be confirmed to have a similar signal waveform to the measured signal through direct visual evaluation, and muscle signals for each body part can be measured using a commercialized sensor. The same signal can be confirmed. Through Pearson's correlation analysis using statistical analysis techniques, signal data between nano and micro web structure-based respiration sensors and existing respiration sensors showed significant correlation with each other, indicating respiration obtained from nano and micro web-based sensors. A theoretical model which predicts the actuation stroke of the system based on the material properties of the auxetic SMM (Shape Memory Material) and bias components as well as the geometry of the metamaterial system was developed.

Gpcpd1-GPC metabolic pathway is dysfunctional in aging and its deficiency severely perturbs glucose metabolism.

Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, this function is perturbed, initiating multiple chronic diseases. Our knowledge of mechanisms responsible for this decline is limited. Glycerophosphocholine phosphodiesterase 1 (Gpcpd1) is a highly abundant muscle enzyme that hydrolyzes glycerophosphocholine (GPC). The physiological functions of Gpcpd1 remain largely unknown. Here we show, in mice, that the Gpcpd1-GPC metabolic pathway is perturbed in aged muscles. Further, muscle-specific, but not liver- or fat-specific, inactivation of Gpcpd1 resulted in severely impaired glucose metabolism. Western-type diets markedly worsened this condition. Mechanistically, Gpcpd1 muscle deficiency resulted in accumulation of GPC, causing an 'aged-like' transcriptomic signature and impaired insulin signaling in young Gpcpd1-deficient muscles. Finally, we report that the muscle GPC levels are markedly altered in both aged humans and patients with type 2 diabetes, displaying a high positive correlation between GPC levels and chronological age. Our findings reveal that the muscle GPCPD1-GPC metabolic pathway has an important role in the regulation of glucose homeostasis and that it is impaired during aging, which may contribute to glucose intolerance in aging.

Combined transcriptome and metabolome analysis reveals breed-specific regulatory mechanisms in Dorper and Tan sheep

BackgroundDorper and Tan sheep are renowned for their rapid growth and exceptional meat quality, respectively. Previous research has provided evidence of the impact of gut microbiota on breed characteristics. The precise correlation between the gastrointestinal tract and peripheral organs in each breed is still unclear. Investigating the metabolic network of the intestinal organ has the potential to improve animal growth performance and enhance economic benefits through the regulation of intestinal metabolites.ResultsIn this study, we identified the growth advantage of Dorper sheep and the high fat content of Tan sheep. A transcriptome study of the brain, liver, skeletal muscle, and intestinal tissues of both breeds revealed 3,750 differentially expressed genes (DEGs). The genes PPARGC1A, LPL, and PHGDH were found to be highly expressed in Doper, resulting in the up-regulation of pathways related to lipid oxidation, glycerophospholipid metabolism, and amino acid anabolism. Tan sheep highly express the BSEP, LDLR, and ACHE genes, which up-regulate the pathways involved in bile transport and cholesterol homeostasis. Hindgut content analysis identified 200 differentially accumulated metabolites (DAMs). Purines, pyrimidines, bile acids, and fatty acid substances were more abundant in Dorper sheep. Based on combined gene and metabolite analyses, we have identified glycine, serine, and threonine metabolism, tryptophan metabolism, bile secretion, cholesterol metabolism, and neuroactive ligand-receptor interaction as key factors contributing to the differences among the breeds.ConclusionsThis study indicates that different breeds of sheep exhibit unique breed characteristics through various physiological regulatory methods. Dorper sheep upregulate metabolic signals related to glycine, serine, and threonine, resulting in an increase in purine and pyrimidine substances. This, in turn, promotes the synthesis of amino acids and facilitates body development, resulting in a faster rate of weight gain. Tan sheep accelerate bile transport, reduce bile accumulation in the intestine, and upregulate cholesterol homeostasis signals in skeletal muscles. This promotes the accumulation of peripheral and intramuscular fat, resulting in improved meat quality. This work adopts a joint analysis method of multi-tissue transcriptome and gut metabolome, providing a successful case for analyzing the mechanisms underlying the formation of various traits.

Modified motor unit properties in residual muscle following transtibial amputation

Objective. Neural signals in residual muscles of amputated limbs are frequently decoded to control powered prostheses. Yet myoelectric controllers assume muscle activities of residual muscles are similar to that of intact muscles. This study sought to understand potential changes to motor unit (MU) properties after limb amputation. Approach. Six people with unilateral transtibial amputation were recruited. Surface electromyogram (EMG) of residual and intact tibialis anterior (TA) and gastrocnemius (GA) muscles were recorded while subjects traced profiles targeting up to 20% and 35% of maximum activation for each muscle (isometric for intact limbs). EMG was decomposed into groups of MU spike trains. MU recruitment thresholds, action potential amplitudes (MU size), and firing rates were correlated to model Henneman’s size principle, the onion-skin phenomenon, and rate-size associations. Organization (correlation) and modulation (rates of change) of relations were compared between intact and residual muscles. Main results. The residual TA exhibited significantly lower correlation and flatter slopes in the size principle and onion-skin, and each outcome covaried between the MU relations. The residual GA was unaffected for most subjects. Subjects trained prior with myoelectric prostheses had minimally affected slopes in the TA. Rate-size association correlations were preserved, but both residual muscles exhibited flatter decay rates. Significance. We showed peripheral neuromuscular damage also leads to spinal-level functional reorganizations. Our findings suggest models of MU recruitment and discharge patterns for residual muscle EMG generation need reparameterization to account for disturbances observed. In the future, tracking MU pool adaptations may also provide a biomarker of neuromuscular control to aid training with myoelectric prostheses.

Ultrasound Pressure-Dependent Cytokine and Immune Cell Response Lost in Aged Muscle

ObjectiveTherapeutic ultrasound remains a highly discussed topic in physical therapy due to uncertainty between treatment regimens and biological benefits. Its impact on aged populations, who are vulnerable to insufficient healing after muscle injury due to sarcopenia, is understudied. Despite the coupling between muscle inflammation and regeneration, research on the immune response after therapeutic ultrasound is limited. The objective of this study was to evaluate structure, inflammatory cytokine signaling and immune cell infiltration after therapeutic ultrasound in young and aging murine muscle. MethodsYoung (6-weeks-old) and Adult (52-weeks-old) male and female mice non-injured gastrocnemii were treated with either low intensity pulsed ultrasound at 2 W/cm2 (∼0.243 MPa) or high intensity pulsed focused ultrasound at 554 W/cm2 (∼5.96 MPa). Cytokine expression was evaluated at 1-, 8-, and 24-hours, cell infiltration was measured via flow cytometry at 1- and 24-hours, and immunofluorescence assessed muscle fiber area, fibrosis and satellite cells at 24-hours after sonication. ResultsLow intensity pulsed ultrasound induced an early, transient inflammatory response where IL-15 and macrophages (M2 > M1) were increased 1-hour post-sonication. High intensity pulsed focused ultrasound caused a late, extended immune response where MCP-1, neutrophils, monocytes, and macrophages (M1 > M2) were increased 24-hours post-sonication. Notably, these changes manifested solely in Young gastrocnemius. The Adult gastrocnemius exhibited decreased cytokine expression (IL-1α, IL-6, IL-15, M-CSF) and no alteration in immune cell recruitment post-sonication. There was no damage to muscle structure. ConclusionsTherapeutic ultrasound induced a pressure dependent inflammatory response that can augment or mitigate intrinsic muscle cytokine signaling and cell recruitment in adolescent or aged muscle, respectively.