Neuromuscular Research Articles

Neuromuscular mechanisms for the fast decline in rate of force development with muscle disuse - a narrative review.

The removal of skeletal muscle tension (unloading or disuse) is followed by many changes in the neuromuscular system, including muscle atrophy and loss of isometric maximal strength (measured by maximal force, Fmax). Explosive strength, i.e. the ability to develop the highest force in the shortest possible time, to maximise rate of force development (RFD), is a fundamental neuromuscular capability, often more functionally relevant than maximal muscle strength. In the present review, we discuss data from studies that looked at the effect of muscle unloading on isometric maximal versus explosive strength. We present evidence that muscle unloading yields a greater decline in explosive relative to maximal strength. The longer the unloading duration, the smaller the difference between the decline in the two measures. Potential mechanisms that may explain the greater decline in measures of RFD relative to Fmax after unloading are higher recruitment thresholds and lower firing rates of motor units, slower twitch kinetics, impaired excitation-contraction coupling, and decreased tendon stiffness. Using a Hill-type force model, we showed that this ensemble of adaptations minimises the loss of force production at submaximal contraction intensities, at the expense of a disproportionately lower RFD. With regard to the high functional relevance of RFD on one hand, and the boosted detrimental effects of inactivity on RFD on the other hand, it seems crucial to implement specific exercises targeting explosive strength in populations that experience muscle disuse over a longer time.

MANEJO DO SORRISO GENGIVAL ATRAVÉS DO USO DA TOXINA BOTULÍNICA TIPO A

An aesthetically pleasing smile results from the combination of several factors, such as the position, size, shape, and color of the teeth, as well as the exposure and characteristics of the gingival tissue. When evaluating the gingival tissue in a smile, several important factors must be considered: excessive vertical growth of the maxilla, reduced length of the upper lip, excessive contraction of the upper lip, and disproportion between the length and width of the clinical crown of the anterior teeth. A minimally invasive approach that can be used as a complement to dental treatment is the application of botulinum toxin, a neurotoxin produced by the anaerobic bacterium Clostridium botulinum. This toxin blocks the release of acetylcholine in the presynaptic vesicles of neuromuscular junctions, inhibiting muscle contraction. The aim of this literature review was to analyze the use of botulinum toxin type A (BTX-A) in the management of gummy smile. The search was conducted in the databases Google Scholar, PubMed, Latin American and Caribbean Health Sciences Literature (LILACS), and Scientific Electronic Library Online (SciELO). The descriptors used for the search were "botulinum toxin," "gingiva," "periodontology," and "dental aesthetics," combined using the boolean operators AND and OR. Although the evidence demonstrates favorable results, the use of botulinum toxin to correct gummy smile has limitations. It is a temporary solution, and patients should be informed about the need for periodic reapplications and the potential side effects, such as facial asymmetries. The reviewed studies indicate that this technique is particularly effective in cases of gummy smile resulting from hyperactivity of the upper lip elevator muscle, providing a significant reduction in gingival exposure, with results lasting up to 12 weeks. The combination of different therapeutic approaches, along with a careful evaluation of the causes of gummy smile, allows dental professionals to offer more integrated and personalized solutions for each patient.

MBNL deficiency in motor neurons disrupts neuromuscular junction maintenance and gait coordination.

Muscleblind-like proteins (MBNLs) are a family of RNA-binding proteins that play essential roles in the regulation of RNA metabolism. Beyond their canonical role in RNA regulation, MBNL proteins have emerged as key players in the pathogenesis of Myotonic Dystrophy type 1 (DM1). In DM1, sequestration of MBNL proteins by expansion of the CUG repeat RNA leads to functional depletion of MBNL, resulting in deregulated alternative splicing and aberrant RNA processing, which underlie the clinical features of the disease. While attention to MBNL proteins has focused on their functions in skeletal muscle, new evidence suggests that their importance extends to motor neurons (MNs), pivotal cellular components in the control of motor skills and movement. To address this question, we generated conditional double knockout mice in which Mbnl1 and Mbnl2 were specifically deleted in motor neurons (MN-dKO). Adult MN-dKO mice develop gait coordination deficits associated with structural and ultrastructural defects in the neuromuscular junction, indicating that MBNL activity in MNs is crucial for the maintenance of the neuromuscular junction. In addition, transcriptome analysis performed on the spinal cord of MN-dKO mice identified mis-splicing events in genes associated with synaptic transmission and neuromuscular junction homeostasis. In summary, our results highlight the complex roles and regulatory mechanisms of MBNL proteins in MNs for muscle function and locomotion. This work provides valuable insights into fundamental aspects of RNA biology and offers promising avenues for therapeutic intervention in DM1 as well as a range of diseases associated with RNA dysregulation.

Skeletal muscle reprogramming enhances reinnervation after peripheral nerve injury

Peripheral Nerve Injuries (PNI) affect more than 20 million Americans and severely impact quality of life by causing long-term disability. PNI is characterized by nerve degeneration distal to the site of nerve injury resulting in long periods of skeletal muscle denervation. During this period, muscle fibers atrophy and frequently become incapable of “accepting” innervation because of the slow speed of axon regeneration post injury. We hypothesize that reprogramming the skeletal muscle to an embryonic-like state may preserve its reinnervation capability following PNI. To this end, we generate a mouse model in which NANOG, a pluripotency-associated transcription factor is expressed locally upon delivery of doxycycline (Dox) in a polymeric vehicle. NANOG expression in the muscle upregulates the percentage of Pax7+ nuclei and expression of eMYHC along with other genes that are involved in muscle development. In a sciatic nerve transection model, NANOG expression leads to upregulation of key genes associated with myogenesis, neurogenesis and neuromuscular junction (NMJ) formation. Further, NANOG mice demonstrate extensive overlap between synaptic vesicles and NMJ acetylcholine receptors (AChRs) indicating restored innervation. Indeed, NANOG mice show greater improvement in motor function as compared to wild-type (WT) animals, as evidenced by improved toe-spread reflex, EMG responses and isometric force production. In conclusion, we demonstrate that reprogramming muscle can be an effective strategy to improve reinnervation and functional outcomes after PNI.

Skeletal myotubes expressing ALS mutant SOD1 induce pathogenic changes, impair mitochondrial axonal transport, and trigger motoneuron death

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motoneurons (MNs), and despite progress, there is no effective treatment. A large body of evidence shows that astrocytes expressing ALS-linked mutant proteins cause non-cell autonomous toxicity of MNs. Although MNs innervate muscle fibers and ALS is characterized by the early disruption of the neuromuscular junction (NMJ) and axon degeneration, there are controversies about whether muscle contributes to non-cell-autonomous toxicity to MNs. In this study, we generated primary skeletal myotubes from myoblasts derived from ALS mice expressing human mutant SOD1G93A (termed hereafter mutSOD1). Characterization revealed that mutSOD1 skeletal myotubes display intrinsic phenotypic and functional differences compared to control myotubes generated from non-transgenic (NTg) littermates. Next, we analyzed whether ALS myotubes exert non-cell-autonomous toxicity to MNs. We report that conditioned media from mutSOD1 myotubes (mutSOD1-MCM), but not from control myotubes (NTg-MCM), induced robust death of primary MNs in mixed spinal cord cultures and compartmentalized microfluidic chambers. Our study further revealed that applying mutSOD1-MCM to the MN axonal side in microfluidic devices rapidly reduces mitochondrial axonal transport while increasing Ca2 + transients and reactive oxygen species (i.e., H2O2). These results indicate that soluble factor(s) released by mutSOD1 myotubes cause MN axonopathy that leads to lethal pathogenic changes.

Outcomes for standalone anterolateral corpectomy for thoracolumbar burst fractures.

There is a paucity of data available on the context preceding anterior fusion failure or the need for a posterior fusion, the timing of the second operation, or any correlation between the different instrumentation and failure rates. A retrospective chart review was performed of 131 identified patients who underwent anterolateral corpectomy and fusion for a thoracolumbar burst fracture from 2000 to 2012 in a single institution. 96 patients had clinical and radiographic follow up of greater than two months. Mean kyphosis correction from preoperative (14.1°) to postoperative kyphosis (6.3°) was 7.7° and 37% had loss of kyphotic correction at follow-up. In a univariate analysis, use of a bone strut graft (OR 3.2, p = 0.01), point-loaded graft position (OR4.9, p = 0.005), end plate damage/subsidence (OR 6.7, p < 0.0001), and graft to endplate width ratio of ≤ 45% on AP x-ray (OR 3.0, p = 0.02) were associated with loss of kyphotic correction. 41% demonstrated scoliosis of ≥ 5° at follow-up. Graft location towards the left of midline (OR 8.6, p < 0.0001), point-loaded graft position (OR 3.8, p = 0.01), and end plate damage/subsidence (OR 5.5, p = 0.0001) were also associated with scoliosis at the time of final follow-up. Five patients required posterior fusion and fifteen patients continued to have daily pain, only one of which was determined to be related to kyphosis. Use of a bone strut graft versus expandable cage, graft location, graft position, presence of early or late subsidence and width of the graft may be associated with loss of kyphotic correction and scoliosis.

Enhanced Age-Dependent Motor Impairment in Males of Drosophila melanogaster Modeling Spinocerebellar Ataxia Type 1 Is Linked to Dysregulation of a Matrix Metalloproteinase

Over the past two decades, Drosophila melanogaster has proven to be successful in modeling the polyglutamine (polyQ) (caused by CAG repeats) family of neurodegenerative disorders, including the faithful recapitulation of pathological features such as polyQ length-dependent formation of protein aggregates and progressive neuronal degeneration. In this study, pan-neuronal expression of human Ataxin-1 with long polyQ repeat of 82 amino acids was driven using an elav-GAL4 driver line. This would essentially model the polyQ disease spinocerebellar ataxia type 1 (SCA1). Longevity and behavioral analysis of male flies expressing human Ataxin-1 revealed compromised lifespan and accelerated locomotor activity deficits both in diurnal activity and negative geotaxis response compared to control flies. Interestingly, this decline in motor response was coupled to an enhancement of matrix metalloproteinase 1 (dMMP1) expression together with declining expression of extracellular matrix (ECM) fibroblast growth factor (FGF) signaling by hedgehog (Hh) and branchless (bnl) and a significant decrease in expression of survival motor neuron gene (dsmn) in old (30 d) flies. Taken together, our results indicate a role for dysregulation of matrix metalloproteinase in polyQ disease with consequent impact on ECM signaling factors, as well as SMN at the neuromuscular junction causing overt physiological and behavioral deficits.

DYRK1A interacts with the tuberous sclerosis complex and promotes mTORC1 activity.

DYRK1A, a ubiquitously expressed kinase, is linked to the dominant intellectual developmental disorder, microcephaly, and Down syndrome in humans. It regulates numerous cellular processes such as cell cycle, vesicle trafficking, and microtubule assembly. DYRK1A is a critical regulator of organ growth; however, how it regulates organ growth is not fully understood. Here, we show that the knockdown of DYRK1A in mammalian cells results in reduced cell size, which depends on mTORC1. Using proteomic approaches, we found that DYRK1A interacts with the tuberous sclerosis complex (TSC) proteins, namely TSC1 and TSC2, which negatively regulate mTORC1 activation. Furthermore, we show that DYRK1A phosphorylates TSC2 at T1462, a modification known to inhibit TSC activity and promote mTORC1 activity. We also found that the reduced cell growth upon knockdown of DYRK1A can be rescued by overexpression of RHEB, an activator of mTORC1. Our findings suggest that DYRK1A inhibits TSC complex activity through inhibitory phosphorylation on TSC2, thereby promoting mTORC1 activity. Furthermore, using the Drosophila neuromuscular junction as a model, we show that the mnb, the fly homologs of DYRK1A, is rescued by RHEB overexpression, suggesting a conserved role of DYRK1A in TORC1 regulation.

Grilled nux vomica alleviates myasthenia gravis by inhibiting the JAK2/STAT3 signaling pathway: a study in a mice model

BackgroundGrilled Nux Vomica (GNV) is a promising traditional Chinese medicine to treat myasthenia gravis (MG), but its effects and mechanisms need further exploration.MethodsExperimental autoimmune MG (EAMG) model was established by muscle-specific kinase (MuSK) induction on C57BL/6 J mice. Mice were treated with GNV and/or ruxolitinib (JAK2 inhibitor) or AG490 (STAT3 inhibitor) for 30 days via gavage after modeling and randomized into 7 groups: control, model, low-dose GNV, middle-dose GNV, high-dose GNV, GNV + ruxolitinib, GNV + AG490. Body weight, muscle strength, clinical score, MuSK level, neuromuscular junction integrity (agrin and acetylcholine receptor [AChR] levels), inflammatory factors (IL-2 and IL-6), and the activation of the JAK2/STAT3 pathway were measured and compared between groups.ResultsGNV significantly improved body weight and muscle strength, as well as reduced clinical scores, MuSK levels, and inflammatory markers (IL-2 and IL-6) levels compared with untreated EAMG mice. GNV also protected the neuromuscular junction and increased agrin and AChR co-expression in a dose-dependent manner. In addition, GNV attenuated the levels of p-JAK2 and p-STAT3, which are aberrantly upregulated in EAMG mice. After co-treatment with ruxolitinib or AG490, the effect of GNV on body weight, muscle strength, clinical score, MuSK level, neuromuscular junction integrity, levels of inflammatory factors, and JAK2/STAT3 pathway was further amplified in EAMG mice.ConclusionsGNV improves MG by inhibiting the JAK2/STAT3 pathway, which might be an effective therapeutic strategy for MG.

The effects of anaesthesia on the cardiovascular, respiratory and nervous systems during inhalational anaesthesia: A case report.

Our understanding of the effects of anaesthesia is incomplete. Anaesthesia works primarily by causing widespread depression of the central nervous system. This article will consider the anaesthesia provided for a patient undergoing a hysteroscopy, endometrial ablation and biopsy for abnormal uterine bleeding. The relationship between physiology and the effects of anaesthesia is discussed. Several effects of anaesthesia are observed during the case. Relating to the respiratory system, preoxygenation increased end tidal oxygen by 39%, delaying desaturation during apnoea. Propofol had a profound effect on the patient's respiratory rate by inhibiting the ventilatory drive, resulting in apnoea. The cardiovascular system was affected by tracheal intubation. Stimulation of the sympathetic nervous system caused a 96% increase in heart rate. Induction of anaesthesia resulted in hypotension, treated with the administration of ephedrine, causing vasoconstriction. Modified rapid sequence induction required an increased dose of rocuronium, resulting in an increased duration of action at the neuromuscular junction. The prolonging muscle paralysis required sugammadex as a reversal agent. This case demonstrated the effects of anaesthesia on the respiratory, cardiovascular and nervous systems.

Load transfer behavior of 3D printed concrete formwork for ribbed slabs under eccentric axial loads

3D printed concrete (3DPC) has primarily been used for non-structural applications, with limited exploration into its potential for structural load-bearing applications. This is mainly due to the layered structure of 3DPC and the lack of compatibility of conventional reinforcement strategies to be integrated within the 3D concrete printing process. The post-tensioning of 3DPC structures presents an effective solution to improve the load-carrying capacity and cracking behavior of 3DPC. However, understanding the load transfer behavior and failure modes of 3DPC structures under a particular post-tensioning configuration are crucial to determine the permissible post-tensioning load for a structure without premature failure and to understand the distribution of stresses within the concrete structure under post-tensioning loads. The current study aims to investigate the load transfer behavior and failure mode of a 30 mm thick 3DPC formwork designed for one-way ribbed slabs when subjected to end-anchorage post-tensioning. For this purpose, a series of mechanical characterization and load transfer experiments were conducted on ribbed 3DPC formwork. The mechanical characterization investigations involved examining the compressive and flexural strength, as well as the elastic modulus of 3DPC, under various loading orientations relative to the print path. In the load transfer experiments, the end anchorage post-tensioning system was simulated by applying the axial load to the specimen via end plates bonded to the specimen. The variable parameters of the load transfer experiments were the boundary conditions, the eccentricity of the axial load from the neutral axis, and the topology of the ribbed 3DPC formwork. A digital image correlation system was used to study the axial and transverse strain evolution during the load transfer experiments. The experimental results showed that, regardless of the eccentricity of the applied load, the ribbed 3DPC formwork specimens exhibited higher axial load capacity when the load was applied near the bottom flange rather than the top flange. This was because of the reduced effective cross-sectional area for compression when the load was positioned near the top flanges, a consequence of the selected formwork topology, where top flanges were discontinuous to allow for pouring of the cast concrete within the formwork.

A Theoretical and Experimental Investigation of the Effects of Inverted Wings Modifications on the Stability and Aerodynamic Performance of a Sedan Car at Cornering

ABSTRACTThis research examines the impact of cornering on the aerodynamic forces and stability of a Nissan Versa (Almera) passenger sedan car by introducing novel modifications. These modifications included single inverted wings with end plates as a front spoiler, double‐element inverted wings with end plates as a rear spoiler, and incorporating the ground as a diffuser under the car trunk. The goal is to enhance the performance and stability of conventional passenger cars. To ensure the accuracy of the numerical data, the study utilized multiple methodologies to model the turbulence model, ultimately selecting the most suitable option. This involved comparing numerical data with wind tunnel experimental data using force balance and pressure distribution. Once validated, the computational fluid dynamics (CFD) was employed to analyze the vehicle's aerodynamic performance relative to the straight‐line condition under cornering conditions. The car simulation in a cornering condition was conducted at a representative Reynolds number based on the vehicle length of about 1.3 × 107. The study discovered that asymmetry was a recurring theme regarding surface pressure distribution, with greater prominence under cornering conditions. All modified models exhibited a more favorable lift‐to‐drag ratio than the baseline, indicating improved aerodynamic efficiency. The underbody double‐element diffuser proved most effective for enhancing fuel efficiency and stability. Mesh refinement with a polyhedral algorithm consisting of 11.27 million elements and a computational domain with a frontal area of 91.8 m2 and a curved length of 31 m (˜7 times car length) was crucial for achieving accurate and repeatable results. The study employed multiple turbulence models within the CFD framework. The realizable k‐ε model was chosen due to its balance between accuracy and computational cost for all Nissan Versa models. These findings are limited to the selected parameters and wind tunnel conditions, and further investigations might be needed for extreme driving scenarios.

Glutamate signaling and neuroligin/neurexin adhesion play opposing roles that are mediated by major histocompatibility complex I molecules in cortical synapse formation.

Although neurons release neurotransmitter before contact, the role for this release in synapse formation remains unclear. Cortical synapses do not require synaptic vesicle release for formation (Verhage et al., 2000; Sando et al., 2017; Sigler et al., 2017; Held et al., 2020), yet glutamate clearly regulates glutamate receptor trafficking (Roche et al., 2001; Nong et al., 2004) and induces spine formation (Engert and Bonhoeffer, 1999; Maletic-Savatic et al., 1999; Toni et al., 1999; Kwon and Sabatini, 2011; Oh et al., 2016). Using rat and murine culture systems to dissect molecular mechanisms, we found that glutamate rapidly decreases synapse density specifically in young cortical neurons in a local and calcium-dependent manner through decreasing N-methyl-D-aspartate receptor (NMDAR) transport and surface expression as well as co-transport with neuroligin (NL1). Adhesion between NL1 and neurexin 1 protects against this glutamate-induced synapse loss. Major histocompatibility I (MHCI) molecules are required for the effects of glutamate in causing synapse loss through negatively regulating NL1 levels in both sexes. Thus, like acetylcholine at the neuromuscular junction (NMJ), glutamate acts as a dispersal signal for NMDARs and causes rapid synapse loss unless opposed by NL1-mediated trans-synaptic adhesion. Together, glutamate, MHCI and NL1 mediate a novel form of homeostatic plasticity in young neurons that induces rapid changes in NMDARs to regulate when and where nascent glutamatergic synapses are formed.Significance Statement The role for neurotransmitter release in synaptogenesis in the central nervous system (CNS) remains unclear. Here, we reconcile conflicting results in the field by showing that glutamate plays an important role in synapse formation by acting as a dispersal signal for NMDARs that is counteracted by trans-synaptic adhesion in intact tissue, similar to the role for neurotransmitter at the NMJ. We also describe a novel form of homeostatic plasticity in young neurons that allows them to respond to changes in activity through surprisingly rapid changes in synapse density. Finally, we show that this plasticity is modulated by immune proteins-MHCI molecules-through negative regulation of NL1 levels, connecting two important synaptic signaling pathways for the first time.

Severe dynein dysfunction in cholinergic neurons exacerbates ALS-like phenotypes in a new mouse model

Cytoplasmic dynein 1, a motor protein essential for retrograde axonal transport, is increasingly implicated in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). In this study, we developed a novel mouse model that combines the Legs at odd angles (Loa, F580Y) point mutation in the dynein heavy chain with a cholinergic neuron-specific knockout of the dynein heavy chain. This model, for the first time, allows us to investigate the impact of Loa allele exclusivity in these neurons into adulthood. Our findings reveal that this selective increase in dynein dysfunction exacerbated the phenotypes observed in heterozygous Loa mice including pre-wean survival, reduced body weight and grip strength. Additionally, it induced ALS-like pathology in neuromuscular junctions (NMJs) not seen in heterozygous Loa mice. Notably, we also found a previously unobserved significant increase in neurons displaying TDP-43 puncta in both Loa mutants, suggesting early TDP-43 mislocalisation – a hallmark of ALS. The novel model also exhibited a concurrent rise in p62 puncta that did not co-localise with TDP-43, indicating broader impairments in autophagic clearance mechanisms. Overall, this new model underscores the fact that dynein impairment alone can induce ALS-like pathology and provides a valuable platform to further explore the role of dynein in ALS.

The ketone body β-hydroxybutyrate ameliorates neurodevelopmental deficits in the GABAergic system of daf-18/PTEN Caenorhabditis elegans mutants.

A finely tuned balance between excitation and inhibition (E/I) is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders, including autism spectrum disorders (ASDs). Mutations in Phosphatase and Tensin Homolog (PTEN), the main negative regulator of the phosphatidylinositol 3-phosphate kinase/Akt pathway, are strongly associated with ASD. However, it is unclear whether PTEN deficiencies can differentially affect inhibitory and excitatory signaling. Using the Caenorhabditis elegans neuromuscular system, where both excitatory (cholinergic) and inhibitory (GABAergic) inputs regulate muscle activity, we found that daf-18/PTEN mutations impact GABAergic (but not cholinergic) neurodevelopment and function. This selective impact results in a deficiency in inhibitory signaling. The defects observed in the GABAergic system in daf-18/PTEN mutants are due to reduced activity of DAF-16/FOXO during development. Ketogenic diets (KGDs) have proven effective for disorders associated with E/I imbalances. However, the mechanisms underlying their action remain largely elusive. We found that a diet enriched with the ketone body β-hydroxybutyrate during early development induces DAF-16/FOXO activity, therefore improving GABAergic neurodevelopment and function in daf-18/PTEN mutants. Our study provides valuable insights into the link between PTEN mutations and neurodevelopmental defects and delves into the mechanisms underlying the potential therapeutic effects of KGDs.

The ketone body β-hydroxybutyrate ameliorates neurodevelopmental deficits in the GABAergic system of daf-18/PTEN Caenorhabditis elegans mutants

A finely tuned balance between excitation and inhibition (E/I) is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders, including autism spectrum disorders (ASDs). Mutations in Phosphatase and Tensin Homolog (PTEN), the main negative regulator of the phosphatidylinositol 3-phosphate kinase/Akt pathway, are strongly associated with ASD. However, it is unclear whether PTEN deficiencies can differentially affect inhibitory and excitatory signaling. Using the Caenorhabditis elegans neuromuscular system, where both excitatory (cholinergic) and inhibitory (GABAergic) inputs regulate muscle activity, we found that daf-18/PTEN mutations impact GABAergic (but not cholinergic) neurodevelopment and function. This selective impact results in a deficiency in inhibitory signaling. The defects observed in the GABAergic system in daf-18/PTEN mutants are due to reduced activity of DAF-16/FOXO during development. Ketogenic diets (KGDs) have proven effective for disorders associated with E/I imbalances. However, the mechanisms underlying their action remain largely elusive. We found that a diet enriched with the ketone body β-hydroxybutyrate during early development induces DAF-16/FOXO activity, therefore improving GABAergic neurodevelopment and function in daf-18/PTEN mutants. Our study provides valuable insights into the link between PTEN mutations and neurodevelopmental defects and delves into the mechanisms underlying the potential therapeutic effects of KGDs.

From a solitary blood-derived biomarker to combined biomarkers of sarcopenia: Experiences from the Korean Frailty and Aging Cohort Study.

Sarcopenia is recognized as a complex and multifactorial disorder that includes nutritional deficiency, inactivity, proinflammatory status, hormonal changes, neurological degeneration, and metabolic disturbances. Its' pathogenesis is not fully understood. Therefore, identifying specific biomarkers of sarcopenia will help us understand its pathophysiology. The most frequently reported blood-derived biomarkers of sarcopenia are growth factors, neuromuscular junctions, endocrine systems, mitochondrial dysfunction, inflammation-mediated and redox processes, muscle protein turnover, blood metabolomics, and behavior-mediated biomarkers. Here, we address the implications of sarcopenia biomarkers based on our research experience with KFACS cohort data. It includes free testosterone, myostatin, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF-15), procollagen type III N-terminal peptide (P3NP), creatinine-based biomarkers, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), brain-derived neurotrophic factor (BDNF), metabolites (proline, alanine, tryptophan), and multi-biomarker risk score. We attempted to explain the paradoxical findings of myostatin and FGF-21 levels in relation to sarcopenia. GDF-15 levels were associated with sarcopenia prevalence but not its incidence. Plasma P3NP and BDNF levels may be biomarkers of muscle quality rather than quantity. Lower erythrocyte EPA and DHA levels were associated with slow gait speed, and erythrocyte EPA levels were associated with low handgrip strength. We developed a multi-biomarker risk score for sarcopenia and found that its accuracy in diagnosing sarcopenia was higher than that of any single biomarker.

Perspective on the Development and Integration of Hydrogen Sensors for Fuel Cell Control

The measurement of hydrogen concentration in fuel cell systems is an important prerequisite for the development of a control strategy to enhance system performance, reduce purge losses and minimize fuel cell aging effects. In this perspective paper, the working principles of hydrogen sensors are analyzed and their requirements for hydrogen control in fuel cell systems are critically discussed. The wide measurement range, absence of oxygen, high humidity and limited space turn out to be most limiting. A perspective on the development of hydrogen sensors based on palladium as a gas-sensitive metal and based on the organic magnetic field effect in organic light-emitting devices is presented. The design of a test chamber, where the sensor response can easily be analyzed under fuel cell-like conditions is proposed. This allows the generation of practical knowledge for further sensor development. The presented sensors could be integrated into the end plate to measure the hydrogen concentration at the anode in- and outlet. Further miniaturization is necessary to integrate them into the flow field of the fuel cell to avoid fuel starvation in each single cell. Compressed sensing methods are used for more efficient data analysis. By using a dynamical sensor model, control algorithms are applied with high frequency to control the hydrogen concentration, the purge process, and the recirculation pump.

The Presence of Septin Proteins in the Neuromuscular Junction of Somatic Muscle in the Earthworm Lumbricus terrestris

Using fluorescent confocal microscopy it has been shown that proteins belonging to the septin family such as Septin 2, 3, 5, 7, and 9 are present in the somatic muscle of the earthworm Lumbricus terrestris. Septins 2 and 9 are associated with the lack of their specific concentrations in a cholinergic synapse, while septins 3, 5, and especially 7 levels correlate with quantitatively expressed binding in their localization to the motor end plate. It is assumed that Septins 3, 5 and, mostly, 7 can be involved in the mechanisms of modulation of quantal release of neurotransmitters.

Electrochemical Behavior of Tantalum Nitride Protective Layers for PEMFC Application

Proton Exchange Membrane Fuel Cells (PEMFCs) are promising technology to convert chemical energy from dihydrogen in electrical energy. HT-PEMFCs are working at high temperatures (above 120 °C) and with doped orthophosphoric acid H3PO4 PBI membranes. In such devices, bipolar metallic plates are used to provide reactive gas inside the fuel cell and collect the electrical current. The metallic elements used as bipolar plates, end plates, and interconnectors in acid electrolyte and gaseous fuel cells are severely damaged by a combination of oxidation (due in particular to the use of oxygen, whether pure or contained in the air) and corrosion (due in particular to acid effluents from the electrolyte). This degradation rapidly leads to the loss of the electrical conductivity of the metallic elements and today requires the use of very specific alloys, possibly coated with pure gold. The solution investigated in the present study is the use of a protective coating based on single-phase nitrides obtained by reactive magnetron sputtering or reactive HiPIMS (High-Power Impulse Magnetron Sputtering). The influence of the microstructure on the physical–chemical properties was studied. The electrochemical properties were quantified following two approaches. First, the corrosion current of the developed coatings was measured at room temperature and at higher temperatures using the Linear Sweep Voltammetry (LSV) technique. Then, Electrochemical Impedance Spectroscopy (EIS) measurements were performed to better identify and evaluate their corrosion-resistance performances.