Neuromuscular Research Articles

Systemic Effects of Molar and Incisor Biting on Walking Direction With and Without Visual Feedback

Gait stability and walking direction control are conventionally attributed to coordination among somatosensory, visual, and vestibular systems. Recent evidence of functional interdependence between masticatory and neuromuscular systems indicates that the stomatognathic system is neurologically integrated with various body systems relevant to movement planning and execution. This study investigated the effects of unilateral molar biting and incisor biting on walking with and without visual feedback. A cohort of 31 healthy young adults aged 21 to 30 years (average age of 23.93 ± 1.89) participated in this study. Three types of errors in walking direction (angle error, position error, and curve error) were computed. Our findings indicate that, in right-handed individuals, irrespective of visual feedback, unilateral biting caused systematic deviations toward the biting side from initiation to termination of walking. The consistent deviation in walking, particularly during unilateral right biting conditions in right-handed individuals, may indicate a complex interplay between masticatory function and gait control mechanism, potentially influenced by handedness and motor lateralization within the cortex. This study establishes a foundation for future research exploring the interrelation between bite location, visual feedback, and motor control in diverse populations. This research may provide insight for more efficient interventions for gait-related disorders.

Immune Checkpoint Inhibitor Myopathy: The Double-Edged Sword of Cancer Immunotherapy.

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of several malignancies, with improved survival. These monoclonal antibodies target immune checkpoints, including cytotoxic T-lymphocyte-associated protein 4 (ipilimumab and tremelimumab), programmed death 1 (nivolumab, pembrolizumab, cemiplimab, and dostarlimab), programmed death ligand 1 (atezolizumab, avelumab, and durvalumab), and lymphocyte activation gene 3 (relatlimab), and effectively augment the immune response against tumor cells. Releasing the brakes on the immune system has consequences, however, in the form of immune-related adverse events (irAEs), which may affect any organ. Neurologic irAEs represent 1%-3% of all irAEs, with immune-mediated myopathy (ICI myopathy) being the most common manifestation. Recent large patient series and systematic reviews have established the key features and highlighted new insights into ICI myopathy. ICI myopathy is characterized by an acute or subacute onset of oculobulbar and/or proximal limb weakness, with or without associated respiratory insufficiency and myocarditis. Creatine kinase elevation is common. Oculobulbar presentations with or without respiratory failure may be misattributed to neuromuscular junction disorders, particularly because acetylcholine receptor antibodies are present in up to 40% of patients; however, an electrodiagnostic evidence of a defect of neuromuscular transmission is often absent even in patients with severe weakness, highlighting that the myopathic process is the driving force behind these presentations. Muscle histopathology commonly demonstrates a unique signature of multifocal clusters of necrotic and regenerating fibers, differentiating ICI myopathy from other autoimmune myopathies. Transcriptomic analysis has uncovered distinct subgroups within ICI myopathy, revealing varying degrees of type 1 and type 2 interferon pathway activation alongside notable upregulation of the interleukin (IL)-6 pathway in affected muscle tissue. This discovery presents a promising avenue for intervention through the use of therapies that suppress the interferon pathway and target IL-6 or its receptor. Despite clinical improvements with immunomodulatory therapy, with corticosteroids the mainstay of treatment, mortality remains high, particularly in those with associated myocarditis or respiratory failure requiring intubation, where mortality occurs in up to 50%. ICI withdrawal can lead to cancer progression and death, highlighting a need for improved approaches to ICI rechallenge, performed in limited patients with variable success to date.

Impact of ageing and disuse on neuromuscular junction and mitochondrial function and morphology: Current evidence and controversies.

Inactivity and ageing can have a detrimental impact on skeletal muscle and the neuromuscular junction (NMJ). Decreased physical activity results in muscle atrophy, impaired mitochondrial function, and NMJ instability. Ageing is associated with a progressive decrease in muscle mass, deterioration of mitochondrial function in the motor axon terminals and in myofibres, NMJ instability and loss of motor units. Focusing on the impact of inactivity and ageing, this review examines the consequences on NMJ stability and the role of mitochondrial dysfunction, delving into their complex relationship with ageing and disuse. Evidence suggests that mitochondrial dysfunction can be a pathogenic driver for NMJ alterations, with studies revealing the role of mitochondrial defects in motor neuron degeneration and NMJ instability. Two perspectives behind NMJ instability are discussed: one is that mitochondrial dysfunction in skeletal muscle triggers NMJ deterioration, the other envisages dysfunction of motor terminal mitochondria as a primary contributor to NMJ instability. While evidence from these studies supports both perspectives on the relationship between NMJ dysfunction and mitochondrial impairment, gaps persist in the understanding of how mitochondrial dysfunction can cause NMJ deterioration. Further research, both in humans and in animal models, is essential for unravelling the mechanisms and potential interventions for age- and inactivity-related neuromuscular and mitochondrial alterations.

Exposure to an environmentally representative mixture of polybrominated diphenyl ethers (PBDEs) alters zebrafish neuromuscular development

Polybrominated diphenyl ethers (PBDEs) are a prevalent group of brominated flame retardants (BFRs) added to several products such as electronics, plastics, and textiles to reduce their flammability. They are reported as endocrine disruptors and neurodevelopmental toxicants that can accumulate in human and wildlife tissues, thus making their ability to leach out of products into the environment a great cause for concern. In this study, zebrafish (Danio rerio) embryos and larvae were exposed to a wide concentration range (1.5, 15, 150 and 300 pM) of a PBDE mixture from one to six days post-fertilization (dpf). Hatching rates, mortality and general morphology were assessed during the exposure period. A delay in hatching was observed at the two highest PBDEs concentrations and mortality rate increased at 6 dpf. By 4 dpf, larvae exposed to 150 pM and 300 pM PBDEs developed an upcurved phenotype. Analysis of motor behavior at 6 dpf revealed that PBDE exposure acutely reduced locomotion. To further analyze these motor deficits, we assessed the neural network density and motor neuron and neuromuscular junctions (NMJ) development by immunostaining and imaging. Acetylated α-tubulin staining revealed a significant loss of neurons in a dose-dependent manner. Synaptic vesicle protein 2 (SV2) and ⍺-bungarotoxin (⍺-BTX) staining revealed a similar pattern, with a significant loss of SV2 and nicotinic acetylcholine receptors, thus preventing the colocalization of presynaptic neurons with postsynaptic neurons. Consistent with these results, the presence of cleaved caspase-3 and acridine orange positive cells showed increased cell death in zebrafish larvae exposed to PBDEs. Our results suggest that exposure to PBDEs leads to deficits in the zebrafish neuromuscular system through neuron death, inducing morphological and motor deficiencies throughout their development. They provide valuable insight into the neurotoxic effects of PBDEs, further highlighting the relevance of the zebrafish model in toxicological studies.

Optimizing transport methods to preserve function of self-innervating muscle cells for laryngeal injection.

Recently, our laboratory has discovered a self-innervating population of muscle cells, called motor endplate-expressing cells (MEEs). The cells innately release a wide variety of neurotrophic factors into the microenvironment promoting innervation when used as an injectable treatment. Unlike other stem cells, the therapeutic potential of MEEs is dependent on the cells' ability to maintain phenotypical cell surface proteins in particular motor endplates (MEPs). The goal of this study is to identify transport conditions that preserve MEE viability and self-innervating function. Muscle progenitor cells (MPCs) of adult Yucatan pigs were cultured and induced to generate MEEs. Effects of short-term cryopreservation methods were studied on MPC and MEE stages. A minimally supplemented medium was investigated for suspension-mediated transport, and MEEs were loaded at a constant concentration (1 × 107 cells/mL) into plastic syringes. Samples were subjected to varying temperatures (4, 22, and 37°C) and durations (6, 18, 24, and 48 h), which was followed by statistical analysis of viability. Transport conditions maintaining viability acceptable for cellular therapy were examined for apoptosis rates and expression of desired myogenic, neurotrophic, neuromuscular junction, and angiogenic genes. Cryopreservation proved detrimental to our cell population. However, a minimally supplemented medium, theoretically safe for injection, was identified. Transport temperature and duration impacted cell viability, with warmer temperatures leading to faster death rates prior to the end of the study. Transport conditions did not appear to affect apoptotic rate. Any expression change of desirable genes fell within the acceptable range. Transport state, medium, duration, and temperature must be considered during the transport of injectable muscle cells as they can affect cell viability and expression of integral genes. These described factors are integral in the planning of general cell transport and may prove equally important when the cell population utilized for laryngeal injection is derived from a patient's own initial muscle biopsy.

What Is in the Neuromuscular Junction Literature?

Abstract This update starts with an interesting series of children and adults with congenital myasthenic syndrome with a DOK7 variant. The next section is on autoimmune myasthenia gravis (MG) epidemiology, cost of care, and hospitalizations. A number of studies on the newer treatments are discussed including a phase 2 trial of nipocalimab and recommendations for using some of these drugs. A large trial emphasizing the negative effects of pyridostigmine in muscle-specific kinase MG is covered. A study on the incidence of taste disorders and alopecia in MG follows. The update ends with the topic of the burden of disease in MG and Lambert–Eaton myasthenic syndrome.

Nomogram for predicting pregnancy-related relapse of myasthenia gravis

BackgroundMyasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies primarily affecting the neuromuscular junction. This study aims to identify risk factors for pregnancy-related MG relapse and develop a predictive model to improve clinical outcomes.MethodsWe enrolled 113 MG female patients with a pregnancy history during follow-up at Huashan Hospital affiliated with Fudan University, between January 2015 and October 2021. The study analyzed relapse rates and risk factors during pregnancy and postpartum using multivariate logistic regression. A nomogram was constructed to predict relapse probability, with model performance evaluated by discrimination and calibration metrics.ResultsOf the 113 patients, 52 (46.02%) experienced 115 relapses, including 52 (45.22%) occurring during the first trimester of pregnancy, 11 (9.56%) during the second trimester of pregnancy, and 52 relapses (45.22%) during the three months after delivery/abortion. Significant factors associated with pregnancy-relate relapse, included age at delivery/abortion (OR 0.21, 95% CI 0.06–0.65), MG stable duration (OR 0.24, 95% CI 0.09–0.63), thymic hyperplasia (OR 3.45, 95% CI 1.35–9.3), pre-pregnancy thymectomy (OR 0.08, 95% CI 0.01–0.36), and inadequate treatment during pregnancy (OR 4.44, 95% CI 1.35–17.76). The Nomogram model demonstrated robust predictive performance.ConclusionThe first trimester of pregnancy and three months following delivery or abortion are high-risk periods for MG relapse. Younger ages, shorter MG stable duration before pregnancy, thymic hyperplasia, and inadequate treatments during pregnancy increase relapse risk.

Investigation of Pressure Pulsation and Vibration of the Internally Geared Screw Compressor

Abstract The Internally Geared Screw Machine (IGSM) is a relatively novel and promising type of positive displacement compressor concept that takes inspiration from classic gerotor pumps. The IGSM uses two rotors rotating in the same direction about parallel axes while maintaining continuous contact between both rotors which isolates several working chambers. By using ported end plate, the IGSM can determine the timing of the fluid entering and exiting the working chamber. There are several key advantages to the IGSM over traditional twin-screw compressors including reduction of the rotor to casting leakage, elimination of the blow hole area, reduction in sliding velocity at the point of contact, and a uniform circumferential rotor temperature profile. Although there is some research regarding the geometric profiling and chamber modeling of this type of machine, there is no research currently available on the pressure pulsation and vibration characteristics of the IGSM. The purpose of this paper is to provide an initial look into the pressure pulsation and vibration characteristics of the IGSM and how they differ from that of a traditional twin-screw machine. By explicating the key differences between the IGSM and the industry standard twin-screw compressor, this paper aims to better understand an important yet underdeveloped area of IGSM design.

High-resolution simulations of gas-liquid Couette-type sealing gap flows

Abstract The two-phase flow in sealing gaps of twin-screw compressors is investigated using highly resolved coupled multiphase simulations. Oil-injected rotary-type positive displacement compressors (RPDC) such as twin-screw machines are used for the compression of refrigerants in HVAC (Heating, Ventilation, and Air Conditioning) systems. The efficiency of such machines is largely determined by the inevitable two-phase surge and gap flows. The simulation of flows in such compressors is still a challenge due to the complexity of the two-phase flow in the narrow gaps (<0.3mm) with organic working fluids and moving boundaries. Due to the rotation of the screws relative to the housing, gaps are present between the rotors and the end plates of the housing and between the tips of the rotors and the cylindrical housing walls. Oil injection can increase the efficiency of screw compressors or expanders by more than 10%, since oil enhances the sealing of the gaps where leakage occurs. On the other hand, additional momentum losses are caused by the two-phase gap flows. The oil injection, however, increases the hydraulic losses which depend on the geometry of the gap, the liquid, and the kinematics of the established multiphase flow in the gap. In this work, a highly efficient, high-resolution numerical method is used for the simulation of the gas-liquid multiphase flow in the screw compressor gap between the rotor tip and the stationary housing. The Lattice-Boltzmann method (LBM) defines the basis of the method used in this work, forming an in-house developed framework in which each fluid phase is solved by a separate solution algorithm. To capture the motion of the liquid-gas phase boundary, a level-set method is used. In the present work, a generic gap flow is considered. A Couette-type flow configuration, where the sealant flow in the gap is driven by the moving inner wall, is investigated. The Reynolds number based on the height of the channel is Re = 20000. Finally, we discuss the impact of bubble-laden sealing gaps on the momentum losses of the system.

Flexural strength of end-plate connection with several different bolt arrangements

Abstract An end-plate connection is one of the common connections implemented in beam-column joints. This connection used a combination of bolts and welds as the connectors, so it is also specified as a semi-rigid connection. In general, the end-plate connection is applied to withstand the bending moment and to enhance its bending capacity, the connection area of the end-plate is generally enlarged. So far, the studies carried out to obtain the contribution of bolt arrangements to flexural strength are very limited, so maximum flexural capacity has not yet been optimally achieved. This research aims to examine the flexural strength of end-plate connections varied by bolt arrangements and bolt connection areas. The study was first conducted by analytically modeling the end-plate connection in SAP 2000, where the internal forces, i.e., shear force and moment were obtained from this numerical study. The theoretical studies were also carried out by considering internal troops to discover the influence of the bolt configuration on the end-plate connection to the flexural strength. The height of the area connection was also assorted, i.e., 100 mm, 200 mm, and 300 mm. The study revealed that enlarging area connections and increasing the number of bolts, reduce the tensile and shear stress at the maximum rate of 97.6 and 50 %, respectively. However, it can increase the flexural strength up to the rate 15 times from the minimum flexural strength. This result revealed that enlarging the connection area and adding the number of bolts can be suggested to enhance the flexural capacity when the end plate connection deals with a strong bending moment.

Acute Neuromuscular Fatigue of a Random Vs Constant Session of Repeated Standing Long Jumps.

There is little evidence of the acute effect of random practice, performed by solely varying the intensity but not the task itself, as compared to block practice, i.e. when one task is repeated in a constant manner. This study aimed to examine the acute neuromuscular effects of physical exercise consisting of repeated jumps of randomized length. Fifteen healthy young participants completed 2 separate sessions of 90 minutes. They did 20 minutes of fatiguing exercise, consisting of 100 repeated standing long jumps (SLJ), in two different manners: one session with targeted jump length kept constant (CO), and one with targeted jump length being varied and unpredictable (RA). Pre- and post-tests were conducted before and immediately after, including measurements of Countermovement Jump (CMJ), SLJ, leg extension maximal voluntary isometric contractions (MViC), EMG activities of leg muscles and patellar tendon reflex amplitude (T-reflex: strike force and evoked force). Results showed that performances decreased after the repeated SLJs, independently of the condition (MViC decreased from 448 ± 118 N to 399 ± 122 N; CMJ decreased from 36.7 ± 7.2 cm to 34.6 ± 6.6 cm). EMG during MViC decreased by 21 ± 28 % from pre- to post-intervention. T-reflex decreased after both conditions ([Force/Strike] ratio decreased by 38 ± 69 % from pre to post). Subjective measures showed a greater sense of personal performance and enjoyment after the RA session. Results suggest that a randomly organized intensity of effort led to a similar decrease in physical performance compared to constant intensity when the session loads were matched. It also led to similar fatigue of the neuromuscular system as shown by T-reflexes and EMG measures. Nonetheless, random practice presents the benefit of being markedly more appreciated by participants.

The anillin knockdown in the Drosophila nervous system shows locomotor and learning defects

Anillin (Ani) is an evolutionarily conserved protein with a multi-domain structure that cross-links cytoskeletal proteins and plays an essential role in the formation of the contractile ring during cytokinesis. However, Ani is highly expressed in the human central nervous system (CNS), and it scaffolds myelin in the CNS of mice and modulates neuronal migration and growth in Caenorhabditis elegans. Although Ani is also highly expressed in the Drosophila CNS, its role remains unclear. In the present study, we showed that Ani is not only highly expressed in larval neuroblasts of the CNS, but also weakly expressed in the neuromuscular junction (NMJ) and axons. In addition, the ani knockdown in the nervous system led to pupal lethality, larval locomotor defects, and learning disability, along with abnormal morphology of the NMJ and distribution patterns of the mature neuropil in the CNS. These results show that Ani plays an important role also in the Drosophila nervous system.

CFD Modelling and Simulation of the Thermal Management in a Polymer Electrolyte Membrane (PEM) Fuel Cell Stack

Polymer Electrolyte Membrane fuel cells are a promising technology for clean energy conversion due to their high efficiency and low emissions. However, one of the critical challenges in the operation of fuel cells is the effective management of temperature and humidity within the fuel cell stack. Uneven temperature distribution can cause uneven water vapor condensation, leading to performance inconsistencies among individual cells in the stack. This necessitates a comprehensive understanding and control of the thermal and humidity dynamics within the fuel cell stack to ensure optimal performance and longevity. In this study, with the use of COMSOL Multiphysics, a mathematical polymer exchange membrane fuel cell stack model is designed and is applied to assess the thermal control of a stack of polymer exchange membrane fuel cell made up of two end plates, five membranes electrode assembly, and five cells. The boundary conditions are established and the mathematical equations are numerically solved. The obtained results indicate that that the thermal and electrochemical performance within the fuel cell stack is significantly influenced by the distribution of cooling flow and gas reactants. Higher temperatures near the outlet highlight the importance of optimizing cooling strategies to prevent overheating and ensure uniform temperature distribution. Moreover, the observed variations in relative humidity suggest that water management is crucial for avoiding flooding, particularly in the first and last cells. This study also reveals the intricate relationship between temperature, humidity, and gas flow, which must be carefully balanced to prevent performance degradation. These insights suggest that optimizing the thermal and humidity management strategies is crucial for improving the durability and reliability of polymer exchange membrane fuel cell stacks.

The Association Between Facet Joint Tropism and Lumbar Disc Herniation

Objective: Facet joint tropism is thought to be associated with lumbar disc herniation (LDH), but this relationship has not been fully established. The aim of this study was to investigate the relationship between facet joint tropism and LDH in patients (25-30 years old and body-mass index 28-30 kg/m²) using computed tomography (CT) and lumbar magnetic resonance imaging (MRI). Method: Facet joint angles were measured on lumbar MRI and CT images of 24 male patients with left-sided LDH; 16 patients with right-sided LDH. Facet joint angle was measured by calculating the angle of the facet joints with the vertebral sagittal line in axial sections parallel to the end plate plane. Patients with trauma, rheumatic and oncologic diseases, additional lumbar or spinal and systemic diseases, patients with far lateral, foraminal and central lumbar disc herniations were excluded. Results: The mean left facet joint angle was 44,56º+/-11,29° and the mean right facet joint angle was 41,2º+/-11,27° in 24 patients with left-sided LDH. In 16 patients with right-sided LDH, the mean right facet joint angle was 45,87º +/-16,41°and the mean left facet joint angle was 42,74º+/-12,54°. Conclusion: In the statistical evaluation, no significant correlation was found between LDH and facet joint angle, but in the numerical analysis, it was observed that the left facet joint angle was larger in patients with left-sided LDH and the right facet joint angle was larger in patients with right-sided LDH.

Oropharyngeal Dysphagia as The Presenting Symptom of Myasthenia Gravis with Diabetes Mellitus

Background: Oropharyngeal dysphagia may caused by a variety of causes. Myasthenia gravis is a common autoimmune disease affecting the neuromuscular junction. While ocular symptoms are common in myasthenia gravis, bulbar symptoms such as dysarthria and dysphagia are less common. Aim: To present the importance of recognizing atypical presentations of myasthenia gravis and utilizing electromyography in diagnosis when AChR antibody testing is unavailable. Case Presentation: A 57-year-old woman was referred because of progressive dysphagia for both solid and liquid food. She also experienced weight loss, heaviness of the right eyelid, drooling, and chewing difficulty. Medical history revealed diabetes. Vital signs were stable. Physical examination revealed right ptosis without any other neurological deficits. Wartenberg test and dysarthria counting test were positive. Laboratory examination revealed a blood glucose level of 270 mg/dL and an HbA1c level of 9.4%. The barium swallow study revealedno abnormalities. Esophagogastroduodenoscopy revealed esophageal candidiasis. Electromyography showed more than 20% decremental response of the orbicularis oculi muscle. This result is suggestive of neuromuscular junction disorder. Improvement of the condition was achieved after the administration of intravenous steroids and oral pyridostigmine combined with therapeutic plasma exchange. Discussion: Oropharyngeal dysphagia accompanied by ptosis and positive Wartenberg & dysarthria counting test is suggestive of myasthenia gravis. Although an AChR antibody test cannot be performed, significant electromyography alongside relevant clinical presentation is sufficient to diagnose myasthenia gravis. Conclusion: It is crucial to recognize the accompanying signs and symptoms of oropharyngeal dysphagia. EMG may be used to diagnose MG in the appropriate clinical context.

Is the Force-Velocity Profile for Free Jumping a Sound Basis for Individualized Jump Training Prescriptions?

Formulating individualized optimized jump training prescriptions based on the force-velocity profile has become popular, but its effectiveness has been contested. Such training programs have opposite effects on 'maximal average force' and 'maximal average shortening velocity', and we set out to investigate which training-induced changes in the neuromuscular system could cause such effects. We used a musculoskeletal simulation model with four body segments and six muscle-tendon actuators to simulate vertical squat jumps with different loads. Independent input was muscle stimulation over time, which was optimized for maximal jump height. We determined the force-velocity profile for a reference model and investigated how it changed when we modified muscle properties and initial postures. We could not reproduce the reported training effects by realistically improving muscle properties (maximal force, shortening velocity and rate of force development) or modifying initial postures of the model. However, the profile was very sensitive to gains in jump height at low-loads but not high loads, or vice versa. Reaching maximal height in force-velocity profile jumps requires skill. We argued that submaximal performance in low-load or high-load jumps caused by lack of skill could be responsible for large imbalances in profiles before training. Differential skill training promoted by the individualized optimized approach could explain quick changes toward a balanced profile. If the success of individualized optimized training studies is explained by selective skill improvements, training effects are unlikely to transfer to other tasks, and individualized optimized training will not be superior to other types of training.

The gating properties of Drosophila NMJ glutamate receptors and their dependence on Neto.

The Drosophila neuromuscular junction (NMJ) is a powerful genetic system that has revealed numerous conserved mechanisms for synapse development and homeostasis. The fly NMJ uses glutamate as the excitatory neurotransmitter and relies on kainate-type glutamate receptors and their auxiliary protein Neto for synapse assembly and function. However, despite decades of study, the reconstitution of NMJ glutamate receptors using heterologous systems has been achieved only recently, and there are no reports on the gating properties for the recombinant receptors. Here, using outside-out, patch clamp recordings and fast ligand application, we examine for the first time the biophysical properties of native type-A and type-B NMJ receptors in complexes with either Neto-α or Neto-β and compare them with recombinant receptors expressed in HEK293T cells. We found that type-A and type-B receptors have strikingly different gating properties that are further modulated by Neto-α and Neto-β. We captured single-channel events and revealed major differences between type-A and type-B receptors and also between Neto splice variants. Surprisingly, we found that deactivation is extremely fast and that the decay of synaptic currents resembles the rate of ionotropic glutamate receptor (iGluR) desensitization. The functional analyses of recombinant iGluRs that we report here should greatly facilitate the interpretation of compound in vivo phenotypes of mutant animals. KEY POINTS: We report the reconstitution of Drosophila neuromuscular junction ionotropic glutamate receptors (iGluRs) with Neto splice forms. Using outside-out patches and fast ligand application, we examine the deactivation and desensitization of the four iGluR/Neto complexes found in vivo. Expression of functional channels is absolutely dependent on Neto. Single-channel recordings revealed different lifetimes for different receptor complexes. The decay of synaptic currents is controlled by desensitization.

Reactive oxygen species in skeletal muscle injury, fatigue, regeneration and ageing: In memory of John Faulkner

One of the most critical factors impacting healthspan in the elderly is the loss of muscle mass and function, clinically referred to as sarcopenia. Muscle atrophy and weakness lead to loss of mobility, increased risk of injury, metabolic changes and loss of independence. Thus, defining the underlying mechanisms of sarcopenia is imperative to enable the development of effective interventions to preserve muscle function and quality in the elderly and improve healthspan. Over the past few decades, understanding the roles of mitochondrial dysfunction and oxidative stress has been a major focus of studies seeking to reveal critical molecular pathways impacted during aging. In this review, we will highlight how oxidative stress might contribute to sarcopenia by discussing the impact of oxidative stress on the loss of innervation and alteration in the neuromuscular junction (NMJ), on muscle mitochondrial function and atrophy pathways, and finally on muscle contractile function.

FMR1 genetically interacts with DISC1 to regulate glutamatergic synaptogenesis

Synaptic development and functions have been hypothesized as crucial mechanisms of diverse neuropsychiatric disorders. Studies in past years suggest that mutations in the fragile X mental retardation 1 (FMR1) are associated with diverse mental disorders including intellectual disability, autistic spectrum disorder, and schizophrenia. In this study, we have examined genetical interactions between a select set of risk factor genes using fruit flies to find that dfmr1, the Drosophila homolog of the human FMR1 gene, exhibits functional interactions with DISC1 in synaptic development. We show that DISC1 overexpression in the dfmr1null heterozygous background causes synaptic alterations at the larval neuromuscular junctions that are distinct from those in the wild-type background. Loss of dfmr1 modifies the DISC1 overexpression phenotype in synaptic formation, suppressing the formation of synapse boutons. Interaction between the two genes was further supported molecularly by the results that dfmr1 mutations suppress the DISC1-mediated upregulations of the postsynaptic expression of a glutamate receptor and the expression of ELKS/CAST protein, Bruchpilot, in presynaptic motoneurons. Moreover, DISC1 overexpression in the dfmr1null heterozygous background causes downregulation of a MAP1 family protein, Futsch. These results thus suggest an intriguing converging mechanism controlled by FMR1 and DISC1 in the developing glutamatergic synapses.

Study on Mechanical Properties of Prefabricated Lattice Beam Joint

The slope protection structure of the prefabricated lattice beam is one of the most widely used and studied systems in slope structure, with the connection between the lattice beam joint and the longitudinal and transverse beams being critical for structural performance and stability in engineering applications. Because the prefabricated structure is weak in its structural integrity, it is necessary to study the influence of prefabricated lattice beam joints and the longitudinal and transverse beams on the overall mechanical properties of the structure. In this paper, one ordinary cast-in-place concrete beam and six prefabricated beams with different joint-connection modes are designed, and the influence of different connection modes on the bending capacity of the beams is accordingly explored. Moreover, the flexural capacity, bending stiffness change, ductility, and energy absorption capacity of the beams are analyzed through three-point bending test. The test results show that the connection mode at the joints could significantly affect the overall mechanical properties of the structure. By embedding holes in steel sleeves, filling cement mortar in the middle, and using steel plates with a thickness of 16 mm for anchoring treatment joints of end plates, the specimen beams are thus obtained with the same flexural capacity, ductility, and energy absorption capacity as ordinary cast-in-place concrete beams. This study provides valuable insights into optimizing connection methods for prefabricated beams, which can lead to improved structural performance and wider adoption of prefabricated structures in the construction industry.