Tibialis Anterior Research Articles

Motor evoked potentials in the human upper and lower limb do not increase after single 30-minute sessions of acute intermittent hypoxia.

Acute Intermittent Hypoxia (AIH) can induce sustained facilitation of motor output in people with spinal cord injury (SCI). Most studies of corticospinal tract excitability in humans have used 9% FiO2 AIH (AIH-9%), with inconsistent outcomes. We investigated the effect of single sessions of 9% FiO2 and 12% FiO2 AIH (AIH-12%) on corticospinal excitability of a hand and leg muscle in able-bodied adults. Ten naïve participants without SCI completed three sessions comprising 15 cycles of one minute of AIH-9%, AIH-12% or sham (SHAM-21%) followed by one minute of room air (21% FiO2) in a randomised crossover design. Motor evoked potentials (MEPs, n=30, ~1mV) elicited at rest by transcranial magnetic stimulation and maximal M-waves (Mmax) evoked by peripheral nerve stimulation were measured from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles at baseline and at ~0, 20, 40, and 60 minutes post-intervention. AIH-9% induced the greatest reduction in SpO2 (to 85% vs 93% and 100% in AIH-12% and SHAM-21%, respectively; p < 0.001) and the greatest increase in ventilation (by 22% vs 12% and -3% in AIH-12% and SHAM-21%, respectively (p<0.001)). There was no difference in MEP amplitudes (%Mmax) after any of the three conditions (AIH-9%, AIH-12%, SHAM-21%) for both FDI (p=0.399) and TA (p=0.582). Despite greater cardiorespiratory changes during AIH-9%, there was no evidence of corticospinal facilitation (tested with MEPs) in this study. Further studies could explore variability in response to AIH between individuals and other methods to measure motor facilitation in people with and without spinal cord injuries.

Muscle contractile properties directly influence shared synaptic inputs to spinal motor neurons.

Alpha band oscillations in shared synaptic inputs to the alpha motor neuron pool can be considered an involuntary source of noise that hinders precise voluntary force production. This study investigated the impact of changing muscle length on the shared synaptic oscillations to spinal motor neurons, particularly in the physiological tremor band. Fourteen healthy individuals performed low-level dorsiflexion contractions at ankle joint angles of 90° and 130°, while high-density surface electromyography (HDsEMG) was recorded from the tibialis anterior (TA). We decomposed the HDsEMG into motor units spike trains and calculated the motor units' coherence within the delta (1-5Hz), alpha (5-15Hz), and beta (15-35Hz) bands. Additionally, force steadiness and force spectral power within the tremor band were quantified. Results showed no significant differences in force steadiness between 90° and 130°. In contrast, alpha band oscillations in both synaptic inputs and force output decreased as the length of the TA was moved from shorter (90°) to longer (130°), with no changes in delta and beta bands. In a second set of experiments (10 participants), evoked twitches were recorded with the ankle joint at 90° and 130°, revealing longer twitch durations in the longer TA muscle length condition compared to the shorter. These experimental results, supported by a simple computational simulation, suggest that increasing muscle length enhances the muscle's low-pass filtering properties, influencing the oscillations generated by the Ia afferent feedback loop. Therefore, this study provides valuable insights into the interplay between muscle biomechanics and neural oscillations. KEY POINTS: We investigated whether changes in muscle length, achieved by changing joint position, could influence common synaptic oscillations to spinal motor neurons, particularly in the tremor band (5-15Hz). Our results demonstrate that changing muscle length from shorter to longer induces reductions in the magnitude of alpha band oscillations in common synaptic inputs. Importantly, these reductions were reflected in the oscillations of muscle force output within the alpha band. Longer twitch durations were observed in the longer muscle length condition compared to the shorter, suggesting that increasing muscle length enhances the muscle's low-pass filtering properties. Changes in the peripheral contractile properties of motor units due to changes in muscle length significantly influence the transmission of shared synaptic inputs into muscle force output. These findings prove the interplay between muscle mechanics and neural adaptations.

Metabolome in Tibialis and Soleus Muscles in Wild-Type and Pin1 Knockout Mice through High-Resolution Magic Angle Spinning 1H Nuclear Magnetic Resonance Spectroscopy

Skeletal muscles are heterogenous tissues composed of different myofiber types that can be classified as slow oxidative, fast oxidative, and fast glycolytic which are distinguished on the basis of their contractile and metabolic properties. Improving oxidative metabolism in skeletal muscles can prevent metabolic diseases and plays a protective role against muscle wasting in a number of neuromuscular diseases. Therefore, achieving a detailed understanding of the factors that regulate myofiber metabolic properties might provide new therapeutic opportunities for these diseases. Here, we investigated whether peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) is involved in the control of myofiber metabolic behaviors. Indeed, PIN1 controls glucose and lipid metabolism in a number of tissues, and it is also abundant in adult skeletal muscles; however, its role in the control of energy homeostasis in this tissue is still to be defined. To start clarifying this topic, we compared the metabolome of the tibialis anterior muscle (mainly glycolytic) and soleus muscle (oxidative) in wild-type and Pin1 knockout mice with High-Resolution Magic Angle Spinning (HR-MAS) NMR on intact tissues. Our analysis reveals a clear demarcation between the metabolomes in the two types of muscles and allows us to decode a signature able to discriminate the glycolytic versus oxidative muscle phenotype. We also detected some changes in Pin1-depleted muscles that suggest a role for PIN1 in regulating the metabolic phenotype of skeletal muscles.

Muscle ultrasound to identify prednisone-induced muscle damage in adults with nephrotic syndrome

Steroid myopathy is a non-inflammatory toxic myopathy that primarily affects the proximal muscles of the lower limbs. Due to its non-specific symptoms, it is often overshadowed by patients’ underlying conditions. Prolonged or high-dosage use of glucocorticoids leads to a gradual decline in muscle mass. There are no tools available to identify the course of steroid myopathy before the patient displays substantial clinical symptoms. In this study, we investigated individuals with nephrotic syndrome receiving prednisone who underwent muscle ultrasound to obtain cross-sectional and longitudinal pictures of three major proximal muscles in the lower limbs: the vastus lateralis, tibialis anterior, and medial gastrocnemius muscles. Our findings revealed that grip strength was impaired in the prednisolone group, creatine kinase levels were reduced within the normal range; echo intensity of the vastus lateralis and medial gastrocnemius muscles was enhanced, the pennation angle was reduced, and the tibialis anterior muscle exhibited increased echo intensity and decreased thickness. The total dose of prednisone and the total duration of treatment impacted the degree of muscle damage. Our findings indicate that muscle ultrasound effectively monitors muscle structure changes in steroid myopathy. Combining clinical symptoms, serum creatine kinase levels, and grip strength improves the accuracy of muscle injury evaluation.

A comparison of two versus five epineural sutures to achieve successful polyethylene glycol (PEG) nerve fusion in a rat sciatic nerve repair model.

We compared rates of successful polyethylene glycol (PEG) nerve fusion between two epineural suture repairs (2SR) and five epineural suture repairs (5SR) in a rat sciatic nerve transection neurorrhaphy model. We hypothesise that the two and five epineural neural suture repair groups will achieve a similar rate of PEG fusion. Twenty-five Lewis rats underwent bilateral sciatic nerve transection. Primary neurorrhaphy (PN) consisting of 2SR in one hind limb and 5SR in the contralateral hind limb was performed utilizing PEG fusion. Successful PEG fusion was confirmed by a distal muscle twitch after nerve stimulation proximal to the nerve fusion site. Sciatic nerve conduction velocity (SNCV) across the repair site and the force generated by tibialis anterior muscle (TAM) contraction were also compared between the 2SR and 5SR groups. Success rates were 100% for the 2SR and the 5SR groups. No statistically significant differences in SNCV (P = 0.444) or isometric tetanic TAM contractile force (P = 0.820) were observed between 2SR and 5SR in the setting of PEG fusion. These findings demonstrate no significant difference in successful PEG fusion between the 2SR and 5SR groups. In addition, the findings demonstrate no statistically significant differences in SNCV or isometric tetanic TAM contractile force following sciatic nerve transection when performing a 2SR or 5SR PN in the setting of PEG fusion. Successful PEG fusion can be achieved acutely with either a two or five-epineural suture repair in a rat model.

Accuracy of EMG linear envelope in identifying the peak of muscular activity during walking

BackgroundThe linear-envelope peak (LEP) of surface EMG signal is widely used in gait analysis to characterize muscular activity, especially in clinics. Research questionThis study is designed to evaluate LEP accuracy in identifying muscular activation and assessing activation timing during walking. MethodsSurface EMG signals from gastrocnemius lateralis (GL) and tibialis anterior (TA) were analyzed in 100 strides per subject (31 healthy subjects) during ground walking. Signals were full-wave rectified and low-pass filtered (cut-off frequency=5 Hz) to extract the linear envelope. LEP accuracy in identifying muscle activations and the associated error in peak detection were assessed by direct comparison with a reference method based on wavelet transform. LEP accuracy in identifying the timing of higher signalenergy levels was also assessed, increasing the reference-algorithm selectivity. ResultsThe detection error (percentage number of times when LEP falls outside the correspondent reference activation interval) is close to zero. Detection error increases up to 70% for intervals including only signal energy higher than 90% of energy peak. Mean absolute error (MAE, the absolute value of the distance between LEP timing and the correspondent actual timing of the sEMG-signal peak computed by reference algorithm) is 54.1±20.0 ms. Detection error and MAE are significantly higher (p<0.05) in TA data compared to GL signals. Differences among MAE values detected adopting different values for LE cut-off frequency are not statistically significant. SignificanceLEP was found to be accurate in identifying the number of muscle activations during walking. However, the use of LEP to assess the timing of highest sEMG-signal energy (signal peak) should be considered carefully. Indeed, it could introduce a relevant inaccuracy in muscle-activation identification and peak-timing quantification. The type of muscle to analyze could also influence LEP performances, while the cut-off frequency chosen for envelope extraction appears to have a limited impact.

Muscle Activation Frequency Relationship with Cost of Transport at Increasing Walking Speed in Preliminary Study Reveals Interplay of Both Active and Passive Dynamics

Metabolic cost plays a critical role in gait biomechanics, particularly in rehabilitation. Several factors influence metabolic cost during walking. Therefore, this study aimed to examine the relationship between metabolic cost and muscle activity, focusing on the frequency of EMG signals during walking. We recruited nine participants (five male and four female, age range 20–48 years) who walked for four minutes at six different speeds (ranging from 1.8 to 5.9 mph). EMG data were collected from the dominant lower leg muscles, specifically the lateral gastrocnemius (GAS-L) and the anterior tibialis (AT). Oxygen respiration was measured using open-circuit spirometry. Energy expenditure was estimated as the cost of transport (COT). The EMG data were analyzed using frequency domain features, such as the area under the curve of power spectral density (PSD-AUC) and the maximal distance between two points before and after the peak of the power spectral density curve (MDPSD). The results indicated that PSD-AUC is a better measure than MDPSD for understanding the relationship between activation frequency and COT. PSD-AUC demonstrated an increasing curvilinear trend (R2 = 0.93 and 0.77, second order polynomial fit), but the AT displayed higher variability. MDPSD exhibited more nonlinearity (R2 = 0.17–28, second order polynomial fit), but MDPSD demonstrated statistically significant differences (p &lt; 0.05, t-test independent) in frequency between the GAS-L (64–237 Hz) and AT (114–287 Hz) during slow walking. Additionally, the relationship between COT and PSD-AUC revealed a U-shaped curve, suggesting that high COT is a function of both active and passive dynamics during walking. These findings will be valuable in rehabilitating individuals who suffer from gait-related disorders, especially those related to muscle inefficiency.

Epigallocatechin gallate protects against fat and muscle atrophy in B16BL6 melanoma-bearing mice on a high-fat diet

AimsEpidemiological evidence indicates that there is a substantial association between body mass index (BMI) and at least ten forms of cancer, including melanoma, and BMI imbalance contributes to the poor survival rate of cancer patients before and after therapy. Nevertheless, few pharmacological studies on models of obesity and cancer have been reported. In this study, we administered epigallocatechin gallate (EGCG) to B16BL6 tumor-bearing mice that received a high-fat diet (HFD) to examine its impact. MethodsB16BL6 tumor-bearing mice were fed a HFD. Body weight and food intake were documented every week. We conducted a Western blot analysis to examine the protein levels in the tumor, gastrocnemius (GAS), and tibialis anterior (TA) muscles, as well as the inguinal and epididymal white adipose tissues (iWAT and eWAT). Key findingsEGCG has been shown to have anti-cancer effects equivalent to those of cisplatin, a chemotherapy drug. Furthermore, EGCG protected against the loss of epidydimal white adipose tissue by regulating protein levels of lipolysis factors of adipose triglyceride lipase and hormone-sensitive lipase as well as WAT browning factors of uncoupling protein 1, as opposed to cisplatin. EGCG was shown to reduce the protein levels of muscular atrophy factors of muscle RING-finger protein-1, whereas cisplatin did not contribute to rescuing the atrophy of TA and GAS muscles. ConclusionTaken together, our findings indicate that EGCG has a preventive effect against cachexia symptoms and has anti-cancer effects similar to those of cisplatin in tumor-bearing mice fed a high-fat diet.

Repair of Sciatic Nerve Defect in Rats With Acellular Nerve Allograft Carrying Vascular Endothelial Cells.

Acellular nerve allografts (ANAs) were developed to replace the autologous nerve grafts (ANGs) to fill the peripheral nerve defects. Poor vascularization relative to ANGs has been a limitation of application of ANAs. A total of 60 female Sprague-Dawley rats were assigned 3 groups. The rats in A group received ANGs, the rats in B group received ANAs, and the rats in C group were transplanted with ANA carrying endothelial cells (ANA + ECs). In the 1st, 2nd, 4th, and 12th postoperative weeks, 5 rats were selected from each group for evaluating sciatic function index (SFI), electrophysiology, maximum tetanic force recovery rate, tibialis anterior muscle weights recovery rate, and microvessel density. In the 12th postoperative week, the nerves were harvested and stained with toluidine blue and observed under an electron microscope to compare nerve fibers, myelin width, and G-ratio. All the rats survived. In the first and second postoperative weeks, more microvessels were found in the ANA + EC group. In the 12th postoperative week, the nerve fibers were more numerous, and G-ratio was smaller in the C group compared with the B group. The compound muscle action potential and maximum tetanic force recovery rate in the tibialis anterior muscle in the C group were better than those in the B group in the 12th postoperative week. The A group showed better performances in electrophysiology, maximum tetanic force, muscle wet weight, and nerve regeneration. ANA + ECs can promote early angiogenesis, promoting nerve regeneration and neurological function recovery.

Tibiofemoral bone configuration is not associated with hamstring muscle strength in male and female patients with ACL reconstruction.

Previous evidence indicated that the tibiofemoral bone configuration might elevate the risk of an anterior cruciate ligament (ACL) injury. Furthermore, a low hamstring-to-quadriceps muscle ratio predisposes especially females to unfavourable knee kinematics. The primary objective of the present study was to investigate sex-specific associations between tibiofemoral bone geometry and isokinetic knee flexion torque in patients with primary ACL injury followed by ACL reconstruction. N = 100 patients (72 = male, 28 = female, age = 31.3 ± 10.2, body mass index = 25.3 ± 3.6) with primary ACL rupture with isokinetic knee flexion torque assessments before and 6 months after ACL reconstruction surgery were analysed. Magnetic resonance imaging scans were analysed for medial posterior tibial slope (MPTS) and lateral posterior tibial slope, notch width index (NWI) and lateral femoral condyle index (LFCI). Additionally, isokinetic knee flexion torque (60°/s) and hamstring-quadriceps ratios were evaluated. Subsequently, functional parameters were correlated with imaging data for gender subgroups. The findings showed that presurgical isokinetic knee flexion torque was not associated with any marker of femoral or tibial bone geometry. Further, while significant differences were observed between female (0.883 ± 0.31 Nm/kg) and male (1.18 ± 0.35 Nm/kg) patients regarding preoperative normalized knee flexion torque (p < 0.001), no significant sex differences were found for percentage increases in normalized knee flexion torque from presurgery to postsurgery. Generally, female patients demonstrated significantly higher MPTS magnitudes (p < 0.05) and lower LFCI values (p < 0.05) compared to men. The present results demonstrated no association between tibial or femoral bone geometry and muscle strength of the hamstrings in patients with ACL reconstruction, indicating an important mismatch of muscular compensation to deviations in bone geometry. There were no sex-specific differences in tibiofemoral bone parameters. Level III.

UBE2C promotes myoblast differentiation and skeletal muscle regeneration through the Akt signaling pathway.

Ubiquitin-conjugation enzyme E2C (UBE2C) is a crucial component of the ubiquitin-proteasome system that is involved in numerous cancers. In this study, we find that UBE2C expression is significantly increased in mouse embryos, a critical stage during skeletal muscle development. We further investigate the function of UBE2C in myogenesis. Knockdown of UBE2C inhibits C2C12 cell differentiation and decreases the expressions of MyoG and MyHC, while overexpression of UBE2C promotes C2C12 cell differentiation. Additionally, knockdown of UBE2C, specifically in the tibialis anterior muscle (TA), severely impedes muscle regeneration in vivo. Mechanistically, we show that UBE2C knockdown reduces the level of phosphorylated protein kinase B (p-Akt) and promotes the degradation of Akt. These findings suggest that UBE2C plays a critical role in myoblast differentiation and muscle regeneration and that UBE2C regulates myogenesis through the Akt signaling pathway.

POSTURAL CONTROL IMPAIRED IN MYOARTHROKINETIC AND NEURO-SENSORY DISORDERS

Interdependent subsystems involved in dynamic posture and locomotion are represented by osteoarticular, neuromuscular, sensory systems. Postural control is maintained by somato-sensory, visual vestibular feedback, integrated at the level of the locomotor system and the central nervous system. Postural stability is disturbed in mio-arthro-kinetic disorders. In proprioceptive loss, the automatic postural responses are diminished in amplitude and delayed in time; stretch reflexes in soleus and medial gastrocnemius are severely diminished; balance-correcting responses in tibialis anterior are diminished and delayed; backward motion of the trunk is reduced; movement strategies and synergies are disturbed. In peripheral vestibular loss, there are increased trunk responses to disruptive stimuli, with hypermetric trunk muscle responses and hypometric knee responses, but unchanged synergies; pathological changes to the modulation depth are produced; the amplitude of balance correcting responses in ankle muscles is severely reduced. Visual input serves to decrease the stiffness of the musculoskeletal system; it can be accomplished by decreasing the level of muscular activity across the joints of the lower limbs (in eyes-open subjects) or by reducing the gains of the other postural feedback mechanisms, the proprioceptive or vestibular systems (in eyes-closed subjects). Keywords: postural control, proprioceptive insufficiency, vestibular impairment.

Velocity-compensated intravoxel incoherent motion of the human calf muscle.

To determine whether intravoxel incoherent motion (IVIM) describes the blood perfusion in muscles better, assuming pseudo diffusion (Bihan Model 1) or ballistic motion (Bihan Model 2). IVIM parameters were measured in 18 healthy subjects with three different diffusion gradient time profiles (bipolar with two diffusion times and one with velocity compensation) and 17 b-values (0-600 s/mm2) at rest and after muscle activation. The diffusion coefficient, perfusion fraction, and pseudo-diffusion coefficient were estimated with a segmented fit in the gastrocnemius medialis (GM) and tibialis anterior (TA) muscles. Velocity-compensated gradients resulted in a decreased perfusion fraction (6.9% ± 1.4% vs. 4.4% ± 1.3% in the GM after activation) and pseudo-diffusion coefficient (0.069 ± 0.046 mm2/s vs. 0.014 ± 0.006 in the GM after activation) compared to the bipolar gradients with the longer diffusion encoding time. Increased diffusion coefficients, perfusion fractions, and pseudo-diffusion coefficients were observed in the GM after activation for all gradient profiles. However, the increase was significantly smaller for the velocity-compensated gradients. A diffusion time dependence was found for the pseudo-diffusion coefficient in the activated muscle. Velocity-compensated diffusion gradients significantly suppress the IVIM effect in the calf muscle, indicating that the ballistic limit is mostly reached, which is supported by the time dependence of the pseudo-diffusion coefficient.

Spectral characterization of human leg EMG signals from an open access dataset for the development of computational models.

Large-scale neuromusculoskeletal models have been used for predicting mechanisms underlying neuromuscular functions in humans. Simulations of such models provide several types of signals of practical interest, such as surface electromyographic signals (EMG), which are compared with experimental data for interpretations of neurophysiological phenomena under study. Specifically, realistic characterization of spectral properties of simulated EMG signals is important for achieving powerful inferences, whereas considerations should be taken for myoelectric signals of different muscles. In this study, we characterized spectral properties of surface interference pattern EMG signals and motor unit action potentials (MUAP) acquired from three plantar flexor muscles: Soleus (SO), Medial Gastrocnemius (MG), and Lateral Gastrocnemius (LG); and one dorsiflexor muscle: Tibialis Anterior (TA). Surface EMG signals were acquired from 20 participants using the same convention for electrode placement. Specifically, interference pattern EMG signals were obtained during isometric constant force contractions at 5%, 10% and 20% of maximum voluntary contraction (MVC), whereas surface MUAPs were decomposed from surface EMG signals obtained at low contraction forces. We compared the spectrum median frequency (MDF) estimated from interference pattern EMG signals across muscles and contraction intensities. Additionally, we compared MDF and durations of MUAPs between muscles. Our results showed that MDF of interference pattern EMG signals acquired from TA were higher compared to SO, MG, and LG for all contraction intensities i.e., 5%, 10%, and 20% MVC. Consistently, MUAPs acquired from TA also had higher MDF values and shorter durations compared to the other leg muscles. We provide herein a dataset with the surface MUAPs waveforms and interference pattern EMG signals obtained for this study, which should be useful for implementing and validating the simulation of myoelectrical signals of leg muscles. Importantly, these results indicate that spectral properties of myoelectrical signals should be considered for improving EMG modeling in large-scale neuromusculoskeletal models.

A comprehensive dataset on biomechanics and motor control during human walking with discrete mechanical perturbations.

Humans have a remarkable capability to maintain balance while walking. There is, however, a lack of publicly available research data on reactive responses to destabilizing perturbations during gait. Here, we share a comprehensive dataset collected from 10 participants who experienced random perturbations while walking on an instrumented treadmill. Each participant performed six 5-min walking trials at a rate of 1.2 m/s, during which rapid belt speed perturbations could occur during the participant's stance phase. Each gait cycle had a 17% probability of being perturbed. The perturbations consisted of an increase of belt speed by 0.75 m/s, delivered with equal probability at 10%, 20%, 30%, 40%, 50%, 60%, 70%, or 80% of the stance phase. Data were recorded using motion capture with 25 markers, eight inertial measurement units (IMUs), and electromyography (EMG) from the tibialis anterior (TA), soleus (SOL), lateral gastrocnemius (LG), rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), and gluteus maximus (GM). The full protocol is described in detail. We provide marker trajectories, force plate data, EMG data, and belt speed information for all trials and participants. IMU data is provided for most participants. This data can be useful for identifying neural feedback control in human gait, biologically inspired control systems for robots, and the development of clinical applications.

Concerted regulation of skeletal muscle metabolism and contractile properties by the orphan nuclear receptor Nr2f6.

The maintenance of skeletal muscle plasticity upon changes in the environment, nutrient supply, and exercise depends on regulatory mechanisms that couple structural and metabolic adaptations. The mechanisms that interconnect both processes at the transcriptional level remain underexplored. Nr2f6, a nuclear receptor, regulates metabolism and cell differentiation in peripheral tissues. However, its role in the skeletal muscle is still elusive. Here, we aimed to investigate the effects of Nr2f6 modulation on muscle biology in vivo and in vitro. Global RNA-seq was performed in Nr2f6 knockdown C2C12 myocytes (N=4-5). Molecular and metabolic assays and proliferation experiments were performed using stable Nr2f6 knockdown and Nr2f6 overexpression C2C12 cell lines (N=3-6). Nr2f6 content was evaluated in lipid overload models in vitro and in vivo (N=3-6). In vivo experiments included Nr2f6 overexpression in mouse tibialis anterior muscle, followed by gene array transcriptomics and molecular assays (N=4), ex vivo contractility experiments (N=5), and histological analysis (N=7). The conservation of Nr2f6 depletion effects was confirmed in primary skeletal muscle cells of humans and mice. Nr2f6 knockdown upregulated genes associated with muscle differentiation, metabolism, and contraction, while cell cycle-related genes were downregulated. In human skeletal muscle cells, Nr2f6 knockdown significantly increased the expression of myosin heavy chain genes (two-fold to three-fold) and siRNA-mediated depletion of Nr2f6 increased maximal C2C12 myocyte's lipid oxidative capacity by 75% and protected against lipid-induced cell death. Nr2f6 content decreased by 40% in lipid-overloaded myotubes and by 50% in the skeletal muscle of mice fed a high-fat diet. Nr2f6 overexpression in mice resulted in an atrophic and hypoplastic state, characterized by a significant reduction in muscle mass (15%) and myofibre content (18%), followed by an impairment (50%) in force production. These functional phenotypes were accompanied by the establishment of an inflammation-like molecular signature and a decrease in the expression of genes involved in muscle contractility and oxidative metabolism, which was associated with the repression of the uncoupling protein 3 (20%) and PGC-1α (30%) promoters activity following Nr2f6 overexpression in vitro. Additionally, Nr2f6 regulated core components of the cell division machinery, effectively decoupling muscle cell proliferation from differentiation. Our findings reveal a novel role for Nr2f6 as a molecular transducer that plays a crucial role in maintaining the balance between skeletal muscle contractile function and oxidative capacity. These results have significant implications for the development of potential therapeutic strategies for metabolic diseases and myopathies.

Hindlimb myology in two piscivorous raptorial birds: a quantitative comparison of the osprey and the white‐tailed sea eagle (Aves, Accipitriformes)

AbstractThe hindlimbs of Accipitriformes are vital for capturing prey. Research on hindlimb musculature has primarily focused on species preferring avian and mammalian prey, whereas piscivorous species have received limited attention. This study aims to investigate the quantitative characteristics of hindlimb muscles in two piscivorous Accipitriformes, Pandion haliaetus and Haliaeetus albicilla, to discern potential muscular features associated with their specific food preference. The mass and proportion of all hindlimb muscles in both species were assessed based on their primary function (flexion or extension). A Kruskal‐Wallis test was employed to analyze possible differences in muscle mass between species. The allometric relationships between the muscles and body mass were explored with the reduced major axis method. Additionally, a study on the architectural parameters of the primary gripping muscles in P. haliaetus was conducted, using published information from other raptorial birds for comparison. The isometric scaling relationship predominated in the majority of individual muscles helping maintain a proportional relationship relative to body mass. Both species exhibited a similar pattern in terms of quantitative muscle features, implying a preservation of muscle characteristics linked to their predatory capabilities. The largest proportion of hindlimb muscle mass was dedicated to digit flexion in accordance with the grasping abilities of birds of prey. The muscles tibialis cranialis, flexor digitorum longus and flexor hallucis longus exhibited the greatest mass, high physiological cross‐sectional area values, and long fibre, categorizing them as high‐power specialists. These muscles are crucial in the flexion movements that produce the gripping action that characterizes birds of prey. Although no statistically significant differences were detected, each species displayed slightly distinct muscular characteristics, particularly in the architectural properties of the flexor muscles controlling digits II, III, and IV. These variations seem to be associated with differences in their prey preferences.

Nonlinear dynamics of postural control system under visual-vestibular habituation balance practice: evidence from EEG, EMG and center of pressure signals.

Human postural control system is inherently complex with nonlinear interaction among multiple subsystems. Accordingly, such postural control system has the flexibility in adaptation to complex environments. Previous studies applied complexity-based methods to analyze center of pressure (COP) to explore nonlinear dynamics of postural sway under changing environments, but direct evidence from central nervous system or muscular system is limited in the existing literature. Therefore, we assessed the fractal dimension of COP, surface electromyographic (sEMG) and electroencephalogram (EEG) signals under visual-vestibular habituation balance practice. We combined a rotating platform and a virtual reality headset to present visual-vestibular congruent or incongruent conditions. We asked participants to undergo repeated exposure to either congruent (n = 14) or incongruent condition (n = 13) five times while maintaining balance. We found repeated practice under both congruent and incongruent conditions increased the complexity of high-frequency (0.5-20 Hz) component of COP data and the complexity of sEMG data from tibialis anterior muscle. In contrast, repeated practice under conflicts decreased the complexity of low-frequency (<0.5 Hz) component of COP data and the complexity of EEG data of parietal and occipital lobes, while repeated practice under congruent environment decreased the complexity of EEG data of parietal and temporal lobes. These results suggested nonlinear dynamics of cortical activity differed after balance practice under congruent and incongruent environments. Also, we found a positive correlation (1) between the complexity of high-frequency component of COP and the complexity of sEMG signals from calf muscles, and (2) between the complexity of low-frequency component of COP and the complexity of EEG signals. These results suggested the low- or high-component of COP might be related to central or muscular adjustment of postural control, respectively.

Pannexin 1 dysregulation in Duchenne muscular dystrophy and its exacerbation of dystrophic features in mdx mice

BackgroundDuchenne muscular dystrophy (DMD) is associated with impaired muscle regeneration, progressive muscle weakness, damage, and wasting. While the cause of DMD is an X-linked loss of function mutation in the gene encoding dystrophin, the exact mechanisms that perpetuate the disease progression are unknown. Our laboratory has demonstrated that pannexin 1 (Panx1 in rodents; PANX1 in humans) is critical for the development, strength, and regeneration of male skeletal muscle. In normal skeletal muscle, Panx1 is part of a multiprotein complex with dystrophin. We and others have previously shown that Panx1 levels and channel activity are dysregulated in various mouse models of DMD.MethodsWe utilized myoblast cell lines derived from DMD patients to assess PANX1 expression and function. To investigate how Panx1 dysregulation contributes to DMD, we generated a dystrophic (mdx) mouse model that lacks Panx1 (Panx1−/−/mdx). In depth characterization of this model included histological analysis, as well as locomotor, and physiological tests such as muscle force and grip strength assessments.ResultsHere, we demonstrate that PANX1 levels and channel function are reduced in patient-derived DMD myoblast cell lines. Panx1−/−/mdx mice have a significantly reduced lifespan, and decreased body weight due to lean mass loss. Their tibialis anterior were more affected than their soleus muscles and displayed reduced mass, myofiber loss, increased centrally nucleated myofibers, and a lower number of muscle stem cells compared to that of Panx1+/+/mdx mice. These detrimental effects were associated with muscle and locomotor functional impairments. In vitro, PANX1 overexpression in patient-derived DMD myoblasts improved their differentiation and fusion.ConclusionsCollectively, our findings suggest that PANX1/Panx1 dysregulation in DMD exacerbates several aspects of the disease. Moreover, our results suggest a potential therapeutic benefit to increasing PANX1 levels in dystrophic muscles.

Ultrasound guided compressibility of the lower leg anterior tibial muscle compartment: a feasibility study

ABSTRACT Objectives Some young individuals participating in sports activities may encounter lower leg muscle pain and tightness, potentially indicating chronic exertional compartment syndrome (CECS). While muscle pressure measurement is typically recommended for diagnosis, it is invasive and associated with low sensitivity and specificity. Thus, there is a need for novel diagnostic approaches. Methods This feasibility study aims to assess whether an ultrasound-guided technique can effectively measure the compressibility of the anterior tibial muscle compartment, focusing on optimal leg positioning and identifying reliable external and internal anatomical landmarks. The compressibility of the anterior tibial muscle compartment was evaluated using ultrasound images obtained at 10 mmHg and 80 mmHg external pressure, with the drop in compartment thickness used to calculate the compressibility ratio. Measurements were conducted in various leg positions and utilizing different external and internal landmarks. Results Studies in healthy volunteers showed that knee and heel support positioning, measuring at the leg’s widest circumference, and using the interosseous membrane as an internal landmark yielded the lowest measurement variability with an intra class correlation of .977 (.764–1.000; 95%-confidence interval). Conclusion These findings suggest that ultrasound-guided techniques can feasibly determine the compressibility ratio of the anterior tibial muscle compartment, providing valuable insights for standardized protocols in future studies on suspected cases of chronic exertional compartment syndrome.