Antioxidants restore store-operated Ca entry in patient-iPSC-derived myotubes with tubular aggregate myopathy-associated Ile484ArgfsX21 STIM1 mutation via upregulation of binding immunoglobulin protein.

Store-operated Ca entry (SOCE) is indispensable for intracellular Ca homeostasis in skeletal muscle, and constitutive activation of SOCE causes tubular aggregate myopathy (TAM). To understand the pathogenesis of TAM, we induced pluripotent stem cells (iPSCs) from a TAM patient with a rare mutation (c.1450_1451insGA; p.

Bone wax technique for full-endoscopic lumbar laminotomy.

Hemostatic procedures in endoscopic spine surgery have not yet been established, especially in full-endoscopic spine surgery (FESS) performed under continuous irrigation, which has been a major concern for surgeons. Chu had previously reported a technique to convey bone wax during full-endoscopic cervical spine surgery via intracorporeal route by using ball tip of the drill in 2018. However, to the best of our knowledge, there has been no report by surgeons to adopt bone wax as a hemostatic material in full-endoscopic lumbar surgery to date, probably because of difficulty in handling bone wax under continuous irrigation and through a narrow and long working channel in endoscope.

N-terminal domain on dystroglycan enables LARGE1 to extend matriglycan on α-dystroglycan and prevents muscular dystrophy.

Dystroglycan (DG) requires extensive post-translational processing and -glycosylation to function as a receptor for extracellular matrix (ECM) proteins containing laminin-G (LG) domains. Matriglycan is an elongated polysaccharide of alternating xylose (Xyl) and glucuronic acid (GlcA) that binds with high affinity to ECM proteins with LG domains and is uniquely synthesized on α-dystroglycan (α-DG) by like-acetylglucosaminyltransferase-1 (LARGE1). Defects in the post-translational processing or -glycosylation of α-DG that result in a shorter form of matriglycan reduce the size of α-DG and decrease laminin binding, leading to various forms of muscular dystrophy.

Step-bunching instability of growing interfaces between ice and supercooled water.

SignificanceStep-bunching instability (SBI) is one of the interfacial instabilities driven by self-organization of elementary step flow associated with crystal-growth dynamics, which has been observed in diverse crystalline materials. However, despite theoretical suggestions of its presence, no direct observations of SBI for simple melt growth have been achieved so far. Here, with the aid of a type of optical microscope and its combination with a two-beam interferometer, we realized quantitative in situ observations of the spatiotemporal dynamics of the SBI.

Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation.

α-Dystroglycan (α-DG) is a highly glycosylated basement membrane receptor that is cleaved by the proprotein convertase furin, which releases its N-terminal domain (α-DGN). Before cleavage, α-DGN interacts with the glycosyltransferase LARGE1 and initiates functional O-glycosylation of the mucin-like domain of α-DG. Notably, α-DGN has been detected in a wide variety of human bodily fluids, but the physiological significance of secreted α-DGN remains unknown.

Changes in oxidative stress severity and antioxidant potential during muscle atrophy and reloading in mice.

[Purpose] Changes in oxidative stress severity and antioxidant potential are routinely used as oxidative stress markers. While several studies have reported the relationship between these markers and exercise, little is known about the dynamic nature of these markers during muscle atrophy and reloading. Therefore, we examined changes in oxidative stress severity and antioxidant potential during muscle atrophy and reloading.

A new model of skeletal muscle atrophy induced by immobilization using a hook-and-loop fastener in mice.

[Purpose] To study muscle atrophy, the muscle atrophy model mice have been used frequently. In particular, cast immobilization is the most common method to induce muscle atrophy. However, it is time consuming and often causes adverse events including skin injury, edema, and necrosis.

Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle.

Dystroglycan (DG) is a highly expressed extracellular matrix receptor that is linked to the cytoskeleton in skeletal muscle. DG is critical for the function of skeletal muscle, and muscle with primary defects in the expression and/or function of DG throughout development has many pathological features and a severe muscular dystrophy phenotype. In addition, reduction in DG at the sarcolemma is a common feature in muscle biopsies from patients with various types of muscular dystrophy.

Tubular aggregate myopathy caused by a novel mutation in the cytoplasmic domain of STIM1.

Objective: To identify the gene mutation of tubular aggregate myopathy (TAM) and gain mechanistic insight into the pathogenesis of the disorder.

Methods: We described a family affected by autosomal dominant TAM and performed exome and Sanger sequencing to identify mutations. We further analyzed the functional significance of the identified mutation by expression studies and intracellular Ca(2+) measurements.

Overexpression of LARGE suppresses muscle regeneration via down-regulation of insulin-like growth factor 1 and aggravates muscular dystrophy in mice.

Several types of muscular dystrophy are caused by defective linkage between α-dystroglycan (α-DG) and laminin. Among these, dystroglycanopathy, including Fukuyama-type congenital muscular dystrophy (FCMD), results from abnormal glycosylation of α-DG. Recent studies have shown that like-acetylglucosaminyltransferase (LARGE) strongly enhances the laminin-binding activity of α-DG.

LARGE glycans on dystroglycan function as a tunable matrix scaffold to prevent dystrophy.

The dense glycan coat that surrounds every cell is essential for cellular development and physiological function, and it is becoming appreciated that its composition is highly dynamic. Post-translational addition of the polysaccharide repeating unit [-3-xylose-α1,3-glucuronic acid-β1-]n by like-acetylglucosaminyltransferase (LARGE) is required for the glycoprotein dystroglycan to function as a receptor for proteins in the extracellular matrix. Reductions in the amount of [-3-xylose-α1,3-glucuronic acid-β1-]n (hereafter referred to as LARGE-glycan) on dystroglycan result in heterogeneous forms of muscular dystrophy.

[Emerging novel therapeutic strategy for α-dystroglycanopathy by Large].

The past decade of researches have revealed mutations of known or putative glycosyltransferases in several types of muscular dystrophy, including Fukuyama-type congenital muscular dystrophy. In these disorders, the function of α-dystroglycan is severely decreased, therefore they are called α-dystroglycanopathy. Recently, putative glycosyltransferase Large was shown to restore the defective function of α-dystroglycan, thus, it is an intriguing idea to apply this effect to the therapy of α-dystroglycanopathy.

Clinical and pathological characteristics of IgG4-related sclerosing sialadenitis.

Objectives/hypothesis: A new concept of IgG4-related sclerosing sialadenitis characterized by high serum IgG4 levels and tissue infiltration of IgG4-expressing plasmacytes has recently been proposed. To determine appropriate serum levels of IgG4 for monitoring disease activity, a total of 36 serum samples and eight tissue samples from patients with IgG4-related sclerosing sialadenitis were studied.

Study Design: A retrospective clinical study at Yamagata University School of Medicine.

Histone deacetylase inhibitor trichostatin A enhances myogenesis by coordinating muscle regulatory factors and myogenic repressors.

Histone deacetylase inhibitors (HDACIs) are known to promote skeletal muscle formation. However, their mechanisms that include effects on the expression of major muscle components such as the dystrophin-associated proteins complex (DAPC) or myogenic regulatory factors (MRFs) remain unknown. In this study, we investigated the effects of HDACIs on skeletal muscle formation using the C2C12 cell culture system.

Defective glycosylation of α-dystroglycan contributes to podocyte flattening.

In addition to skeletal muscle and the nervous system, α-dystroglycan is found in the podocyte basal membrane, stabilizing these cells on the glomerular basement membrane. Fukutin, named after the gene responsible for Fukuyama-type congenital muscular dystrophy, is a putative glycosyltransferase required for the post-translational modification of α-dystroglycan. Chimeric mice targeted for both alleles of fukutin develop severe muscular dystrophy; however, these mice do not have proteinuria.

Electromyographic response in inferior head of human lateral pterygoid muscle to anteroposterior postural change during opening and closing of mouth.

The purpose of this study was to investigate the influence of anteroposterior postural change on electromyography (EMG) activity in the lateral pterygoid muscle. Subjects consisted of 7 patients attending this hospital for close examination. The inferior heads of the lateral pterygoid and masseter muscles were chosen as evaluation sites.

Reduced proliferative activity of primary POMGnT1-null myoblasts in vitro.

Protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) is an enzyme that transfers N-acetylglucosamine to O-mannose of glycoproteins. Mutations of the POMGnT1 gene cause muscle-eye-brain (MEB) disease. To obtain a better understanding of the pathogenesis of MEB disease, we mutated the POMGnT1 gene in mice using a targeting technique.

UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase in nuclei and rimmed vacuoles of muscle fibers in DMRV (distal myopathy with rimmed vacuoles).

Background: UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is a key molecule in the pathogenesis of distal myopathy with rimmed vacuoles (DMRV) and hereditary inclusion body myopathy (HIBM) and almost all such patients have some mutations in GNE. However, subcellular localization of GNE and the mechanism of muscular damage have not been clarified.

Methods: A rabbit polyclonal antibody for GNE was prepared.

Processing and secretion of the N-terminal domain of alpha-dystroglycan in cell culture media.

Alpha-dystroglycan (alpha-DG) plays a crucial role in maintaining the stability of muscle cell membrane. Although it has been shown that the N-terminal domain of alpha-DG (alpha-DG-N) is cleaved by a proprotein convertase, its physiological significance remains unclear. We show here that native alpha-DG-N is secreted by a wide variety of cultured cells into the culture media.

Enhancement of nitric oxide synthase induction in alveolar macrophages by in vivo administration of docetaxel.

Effects of docetaxel, a taxane-derivative anti-cancer drug, on lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis were investigated in alveolar macrophages isolated from rats. LPS-induced NO production and inducible NO synthase (iNOS) expression were significantly enhanced in the macrophages isolated from rats injected intraperitoneally with docetaxel (4 mg/kg body weight per day for 5 consecutive days) compared with those in macrophages from control rats administrated a vehicle. In vivo administration of docetaxel augmented LPS-induced p38 activation but not extracellular signal-related kinase (ERK) activation in isolated macrophages.

Stress distribution in maxillary alveolar ridge according to finite element analysis using micro-CT.

The purpose of the present study was to evaluate stress distribution by finite element analysis in an accurate model simulating trabecular bone using micro-CT. Dentulous and edentulous maxillary jaws of Japanese adult cadavers were used (5 sides each; total, 10 sides). Imaging was performed using a micro-CT, followed by reconstruction with 3-D images.