Abundant Synthesis of Netrin-1 in Satellite Cell-Derived Myoblasts Isolated from EDL Rather Than Soleus Muscle Regulates Fast-Type Myotube Formation

Resident myogenic stem cells (satellite cells) are attracting attention for their novel roles in myofiber type regulation. In the myogenic differentiation phase, satellite cells from soleus muscle (slow fiber-abundant) synthesize and secrete higher levels of semaphorin 3A (Sema3A, a multifunctional modulator) than those derived from extensor digitorum longus (EDL; fast fiber-abundant), suggesting the role of Sema3A in forming slow-twitch myofibers. However, the regulatory mechanisms underlying fast-twitch myotube commitment remain unclear. Herein, we focused on netrin family members (netrin-1, -3, and -4) that compete with Sema3A in neurogenesis and osteogenesis. We examined whether netrins affect fast-twitch myotube generation by evaluating their expression in primary satellite cell cultures. Initially, netrins are upregulated during myogenic differentiation. Next, we compared the expression levels of netrins and their cell membrane receptors between soleus- and EDL-derived satellite cells; only netrin-1 showed higher expression in EDL-derived satellite cells than in soleus-derived satellite cells. We also performed netrin-1 knockdown experiments and additional experiments with recombinant netrin-1 in differentiated satellite cell-derived myoblasts. Netrin-1 knockdown in myoblasts substantially reduced fast-type myosin heavy chain (MyHC) expression; exogenous netrin-1 upregulated fast-type MyHC in satellite cells. Thus, netrin-1 synthesized in EDL-derived satellite cells may promote myofiber type commitment of fast muscles.

Plantar Mechanical Stimulation Maintains Slow Myosin Expression in Disused Rat Soleus Muscle via NO-Dependent Signaling

It was observed that gravitational unloading during space missions and simulated microgravity in ground-based studies leads to both transformation of slow-twitch muscle fibers into fast-twitch fibers and to the elimination of support afferentation, leading to the “switching-off” of postural muscle motor units electrical activity. In recent years, plantar mechanical stimulation (PMS) has been found to maintain the neuromuscular activity of the hindlimb muscles. Nitric oxide (NO) was shown to be one of the mediators of muscle fiber activity, which can also promote slow-type myosin expression. We hypothesized that applying PMS during rat hindlimb unloading would lead to NO production upregulation and prevention of the unloading-induced slow-to-fast fiber-type shift in rat soleus muscles. To test this hypothesis, Wistar rats were hindlimb suspended and subjected to daily PMS, and one group of PMS-subjected animals was also treated with nitric oxide synthase inhibitor (L-NAME). We discovered that PMS led to sustained NO level in soleus muscles of the suspended animals, and NOS inhibitor administration blocked this effect, as well as the positive effects of PMS on myosin I and IIa mRNA transcription and slow-to-fast fiber-type ratio during rat hindlimb unloading. The results of the study indicate that NOS activity is necessary for the PMS-mediated prevention of slow-to-fast fiber-type shift and myosin I and IIa mRNA transcription decreases during rat hindlimb unloading.

Three Individuals with PURA Syndrome in a Cohort of Patients with Neuromuscular Disease

Pur-α protein (PURA) syndrome manifests in early childhood with core features such as neurodevelopmental and speech delay, feeding difficulties, epilepsy, and hypotonia at birth. We identified three cases with PURA syndrome in a cohort of patients with unexplained muscular weakness, presenting with a predominantly neuromuscular and ataxic phenotype. We further characterize the clinical presentation of PURA syndrome including myopathic facies and muscular weakness as the main clinical symptoms in combination with elevated serum creatine kinase levels. Furthermore, we report two novel variants located in the conservative domains PUR-I and PUR-II. For the first time, we present the muscle biopsies of PURA syndrome patients, showing myopathic changes, fiber size variability, and fast fiber atrophy as the key features. PURA syndrome should be taken into consideration as a differential diagnosis in pediatric patients with unexplained muscle weakness.

Titanium Disulfide Based Saturable Absorber for Generating Passively Mode-Locked and Q-Switched Ultra-Fast Fiber Lasers

In our work, passively mode-locked and Q-switched Er-doped fiber lasers (EDFLs) based on titanium disulfide (TiS2) as a saturable absorber (SA) were generated successfully. Stable mode-locked pulses centred at 1531.69 nm with the minimum pulse width of 2.36 ps were obtained. By reducing the length of the laser cavity and optimizing the cavity loss, Q-switched operation with a maximum pulse energy of 67.2 nJ and a minimum pulse duration of 2.34 µs was also obtained. Its repetition rate monotonically increased from 13.17 kHz to 48.45 kHz with about a 35 kHz tuning range. Our experiment results fully indicate that TiS2 exhibits excellent nonlinear absorption performance and significant potential in acting as ultra-fast photonics devices.

Impact of overweight and obesity on women with urinary incontinence: pilot study

IntroductionTo assess whether obesity has a greater impact than overweight on urinary incontinence severity, pelvic floor muscle function, and quality of life in women with urinary incontinence. MethodsA pilot cross-sectional study using a convenience sample. Twenty-six volunteers were evaluated and divided into: Overweight Group (n=11) with BMI (body mass index) between 25.0-29.9kg/m²; Obesity Group (n=15) BMI≥30.0kg/m². The volunteers performed the urogynecological evaluation, Incontinence Severity Index (ISI), the King’s Health Questionnaire (KHQ), 1-hour pad test and evaluation of pelvic floor muscle function. Statistical analysis: Shapiro–Wilk test and the Mann-Whitney test for intergroup analysis. The significance level: p≤0.05. ResultsThe average age was 61.09(12.51) in the Overweight Group and 55.93(9.03) years in the Obesity Group. The Overweight Group presented better fast fiber contraction (p=0.03) of the pelvic floor muscle. There were no differences in the ISI and quality of life between the groups. ConclusionsThere was no difference in the impact caused by being overweight or obese in relation to urinary incontinence severity, pelvic floor muscle function and quality of life, except for fast fiber contraction in which Overweight Group showed better results.