Molecular mechanisms of complex-type N-glycan breakdown and metabolism by the human intestinal bacterium Barnesiella intestinihominis.

Intestinal bacteria play a crucial role in human health, for example, by maintaining immune and metabolic homeostasis and protecting against pathogens. Survival in the human intestine depends on the bacterium's ability to utilize complex carbohydrates. Some species are known to use host-derived glycans; for example, Bifidobacteria can utilize O-glycan of mucin.

A DUF3844 domain-containing protein is required for vacuolar protein sorting in Schizosaccharomyces pombe.

Protein trafficking to vacuoles in plants and fungi, and to lysosomes in animals, is essential for the maintenance of cellular homeostasis. In Saccharomyces cerevisiae, the vacuolar protein sorting (VPS) pathway has been well studied by using vacuolar carboxypeptidase Y (CPY) as a model, and many VPS genes have been identified. By contrast, the vacuolar protein trafficking pathway in Schizosaccharomyces pombe remains poorly understood.

Genetic and pathophysiological insights from autopsied patient with primary familial brain calcification: novel MYORG variants and astrocytic implications.

Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled.

Live cell imaging of β-tubulin mRNA reveals spatiotemporal expression dynamics in the filamentous fungus Aspergillus oryzae.

In filamentous fungi, microtubules are important for polar growth and morphological maintenance and serve as rails for intracellular trafficking. The molecular mechanisms associated with microtubules have been analyzed. However, little is known about when and where tubulin, a component of microtubules, is biosynthesized in multinuclear and multicellular filamentous fungi.

Polarity-dependent expression and localization of secretory glucoamylase mRNA in filamentous fungal cells.

In multinuclear and multicellular filamentous fungi little is known about how mRNAs encoding secreted enzymes are transcribed and localized spatiotemporally. To better understand this process we analyzed mRNA encoding GlaA, a glucoamylase secreted in large amounts by the industrial filamentous fungus Aspergillus oryzae, by the MS2 system, in which mRNA can be visualized in living cells. We found that glaA mRNA was significantly transcribed and localized near the hyphal tip and septum, which are the sites of protein secretion, in polarity-dependent expression and localization manners.

A novel homozygous HPDL variant in Japanese siblings with autosomal recessive hereditary spastic paraplegia: case report and literature review.

Biallelic variants of 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene have been linked to neurodegenerative disorders ranging from severe neonatal encephalopathy to early-onset spastic paraplegia. We identified a novel homozygous variant, c.340G > T (p.

Characterization of novel endo-β-N-acetylglucosaminidases from intestinal Barnesiella intestinihominis that hydrolyze multi-branched complex-type N-glycans.

Endo-β-N-acetylglucosaminidases (ENGases) are enzymes that hydrolyze N-linked glycans. Many ENGases have been characterized, but few have been identified with hydrolytic activity towards multi-branched complex-type N-glycans. In this study, three candidate ENGases were identified from Barnesiella intestinihominis based on database searches and phylogenetic analysis.

Writer's Cramps as an Initial Symptom of Spinocerebellar Ataxia Type 14.

Spinocerebellar ataxia type 14 (SCA14) is a rare form of autosomal dominant cerebellar ataxia caused by mutations in PRKCG. We herein report a case of SCA14 presenting with writer's cramp that predated the onset of progressive ataxia by four years. A 47-year-old Japanese woman had an 11-year history of writer's cramps, followed by unsteadiness.

[A case of myofibrillary myopathy due to Bcl2-Associated Athanogene 3 (BAG3) mutation complicated by peripheral neuropathy].

A 19-year-old female, normal at birth, grew up without neck movement when getting up. She needed a handrail to climb stairs since the age of 10 years old, and walked slowly since the age of 16 years old. Neurological examination revealed loss of deep tendon reflexes, decreased vibratory sensation, weakness of distal muscles of the lower extremities, and weakness of mainly cervical trunk muscles suspected to be due to myopathy.

[A case of Charcot-Marie-Tooth disease type 2 caused by homozygous MME gene mutation].

The patient is a 44-year-old man. His parents are consanguineous. He experienced muscle weakness in his toe and distal tingling sensation in his feet at 42 years of age, which gradually progressed.

Dystonia and Parkinsonism in COA7-related disorders: expanding the phenotypic spectrum.

Background And Objective: Biallelic mutations in the COA7 gene have been associated with spinocerebellar ataxia with axonal neuropathy type 3 (SCAN3), and a notable clinical diversity has been observed. We aim to identify the genetic and phenotypic spectrum of COA7-related disorders.

Methods: We conducted comprehensive genetic analyses on the COA7 gene within a large group of Japanese patients clinically diagnosed with inherited peripheral neuropathy or cerebellar ataxia.

Microbleed clustering in thalamus sign in CADASIL patients with R75P mutation.

Background And Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microvascular disease characterized by the development of vascular dementia and lacunar infarctions. This study aimed to identify the genetic and clinical features of CADASIL in Japan.

Methods: We conducted genetic analysis on a case series of patients clinically diagnosed with CADASIL.

[Involvement of autonomic nervous system since middle age in elderly patient with giant axonal neuropathy caused by novel genetic mutation].

A 69-year-old man began to experience difficulty with walking at the age of 5 years and started use of a cane at around 13 years, then finally started using a wheelchair at 17 years old. A diagnosis of Charcot-Marie-Tooth disease was previously determined at another hospital, though neither peripheral nerve biopsy nor gene analysis was conducted. He visited our institution at the age of 54 years and irregular outpatient examinations were started, which indicated slowly progressive muscle weakness and sensory disturbance of the limbs, leading to a decline in activities of daily living.

Siblings with Cockayne Syndrome B Type III Presenting with Slowly Progressive Cerebellar Ataxia.

Two patients, 48- and 50-year-old sisters, presented with a characteristic facial appearance with slowly progressive deafness and cerebellar ataxia starting in their 30s. Genetic testing identified compound heterozygous pathogenic variants in the ERCC6 gene: c.1583G>A (p.

Spatial Fluctuation of Central Nervous System Lesions in X-linked Charcot-Marie-Tooth Disease with a Novel GJB1 Mutation.

X-linked Charcot-Marie-Tooth disease type 1 (CMTX1), the most common form of CMTX, is caused by gap-junction beta 1 (GJB1) mutations. We herein report a 25-year-old Japanese man with disorientation, right hemiparesis, and dysarthria. Brain magnetic resonance imaging (MRI) showed high signal intensities in the bilateral cerebral white matter on diffusion-weighted imaging.

Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides.

N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins.

Anti-ganglionic acetylcholine receptor antibodies in functional neurological symptom disorder/conversion disorder.

Objective: Autoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by autonomic failure associated with the presence of anti-ganglionic acetylcholine receptor (gAChR) antibodies; however, several studies have reported that individuals with anti-gAChR antibodies present with central nervous system (CNS) symptoms such as impaired consciousness and seizures. In the present study, we investigated whether the presence of serum anti-gAChR antibodies correlated with autonomic symptoms in patients with functional neurological symptom disorder/conversion disorder (FNSD/CD).

Methods: Clinical data were collected for 59 patients presenting with neurologically unexplained motor and sensory symptoms at the Department of Neurology and Geriatrics between January 2013 and October 2017 and who were ultimately diagnosed with FNSD/CD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition.

Efficacy of l-Arginine treatment in patients with HTLV-1-associated neurological disease.

Objective: HTLV-1 infection causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), resulting in loss of motor function. In this Phase 2 trial, we assessed the efficacy and safety of l-arginine in patients with HAM/TSP.

Methods: This open-label, single-arm, Phase 2 study enrolled patients diagnosed with HAM/TSP.

Multi-type repeat expansions as the most common cause of hereditary sensory and autonomic neuropathy.

Non-coding repeat expansions within and genes have lately been linked to multisystem neurodegenerative diseases, which also shed light on yet undiagnosed patients with inherited peripheral neuropathies. The aim of this study was to identify the genetic basis of patients with hereditary sensory and autonomic neuropathy (HSAN). We collected 79 unrelated DNA samples clinically suspected with HSAN from multiple regions of Japan.

Galactosylation of cell-surface glycoprotein required for hyphal growth and cell wall integrity in Schizosaccharomyces japonicus.

Schizosaccharomyces japonicus is a dimorphic yeast, transiting between unicellular and hyphal growth. The glycoproteins of fission yeast contain, in addition to mannose (Man), a large number of galactose (Gal) residues. Previously, we reported that the cell-surface O-glycans of S.