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Modular organization of the spinal motor system is thought to reduce the cognitive complexity of simultaneously controlling the large number of muscles and joints in the human body. Although modular organization has been confirmed in the hindlimb control system of several animal species, it has yet to be established in the forelimb motor system or in primates. Expanding upon experiments originally performed in the frog lumbar spinal cord, we examined whether costimulation of two sites in the macaque monkey cervical spinal cord results in motor activity that is a simple linear sum of the responses evoked by stimulating each site individually. Similar to previous observations in the frog and rodent hindlimb, our analysis revealed that in most cases (77% of all pairs) the directions of the force fields elicited by costimulation were highly similar to those predicted by the simple linear sum of those elicited by stimulating each site individually. A comparable simple summation of electromyography (EMG) output, especially in the proximal muscles, suggested that this linear summation of force field direction was produced by a spinal neural mechanism whereby the forelimb motor output recruited by costimulation was also summed linearly. We further found that the force field magnitudes exhibited supralinear (amplified) summation, which was also observed in the EMG output of distal forelimb muscles, implying a novel feature of primate forelimb control. Overall, our observations support the idea that complex movements in the primate forelimb control system are made possible by flexibly combined spinal motor modules., 腕の自由自在な動きをつくりだす多機能な神経細胞群の発見 --運動の方向と大きさを同時にコントロールする神経メカニズムの解明--. 京都大学プレスリリース. 2020-10-14., Primates aren't quite frogs. 京都大学プレスリリース. 2020-10-19.

Various studies on autonomous robots that perform physical tasks in living environments are being conducted at present to solve the social problems of an aging society with a low birth rate. Howeve...

In 2012, a large number of myositis cases with anti-mitochondrial M2 (AMA-M2) antibody, which had well been known as the serological hallmark for primary biliary cholangitis (PBC), were reported in Japan. Recently, some case series from Japan, France, America, China and India have shown that approximately 2.5% to 19.5% of patients with myositis have AMA-M2 antibody. The objective of this study was to clarify the prevalence, clinical features, treatment outcome, and severity determinants of AMA-M2 positive myositis.This study was a multicenter observational study. We enrolled patients who were diagnosed with myositis during a ten-year period between 2012 and 2021.Of the total of 185 patients with inflammatory myopathy, 17 patients were positive for AMA-M2 antibody. The typical symptoms were weakness mainly involving paravertebral muscles, weight loss, respiratory failure, and cardiac complications. Thirteen of the 17 patients had cardiac complications. A strong correlation was found between respiratory failure and modified Rankin Scale (mRS) score. A strong correlation was also found between respiratory failure and body weight, indicating that weight loss can be an indicator of potential progression of respiratory failure. Six of the 17 patients were complicated by malignancy.This study showed significant correlations between % vital capacity (VC), body mass index (BMI), and mRS score in patients with AMA-M2-positive myositis. Immunotherapy often improved CK level and respiratory dysfunction. We therefore propose that %VC and BMI should be monitored as disease indicators in treatment of AMA-M2-positive myositis.

The identification of true substrates of an E3 ligase is biologically important but biochemically difficult. In recent years, several techniques for identifying substrates have been developed, but these approaches cannot exclude indirect ubiquitination or have other limitations. Here we develop an E3 ligase substrate-trapping strategy by fusing a tandem ubiquitin-binding entity (TUBE) with an anti-ubiquitin remnant antibody to effectively identify ubiquitinated substrates. We apply this method to one of the RBR-type ligases, Parkin, and to one of the RING-type ligases, TRIM28, and identify previously unknown substrates for TRIM28 including cyclin A2 and TFIIB. Furthermore, we find that TRIM28 promotes cyclin A2 ubiquitination and degradation at the G1/S phase and suppresses premature entry into S phase. Taken together, the results indicate that this method is a powerful tool for comprehensively identifying substrates of E3 ligases., Watanabe et al. combine two previously developed strategies to identify E3 ubiquitin ligase substrates into a method, TR-TUBE that is subsequently used to identify substrates of the Parkin and TRIM28 ligases. They identify known substrates, validating the utility of the approach, and find that TRIM28 targets Cyclin A and TFIIB for degradation.

To explore non-motor comorbidities of myasthenia gravis (MG), we present two cases of thymoma-associated MG patients. Alopecia, pure red cell aplasia, and thymoma- associated multiorgan autoimmunity were observed in Case 1, and alopecia, thrombocytopenia, hypogammaglobulinemia and nephrotic syndrome were observed in Case 2. In both cases, autoreactive T lymphocytes inappropriately stimulated by thymus tissue may have played key roles in generating the various autoimmune-associated symptoms. Consequently, systemic immunological involvement due to the thymoma-associated breakdown of immunoregulations in both motor and non-motor systems should be considered in MG patients.

Robots are designed to tackle specific problems or are designed as a multipurpose platform that achieves a concept. In this letter, we approach the hardware design problem from practice and evaluation through numerous competitions including the Darpa Robotics Challenge, the Amazon Picking Challenge, and other competitions that were held in Japan. The paper aims to answer the question what hardware design would we achieve if we continuously refine designs through competitions? We show that competitions lead to a more compact but capable platform design that is durable and has more end effector solutions. We also point out the limitations and benefits of using competitions for designing robot platforms. Our platform began from a human-inspired design for teleoperation and has evolved to mix both human-like and industrial robot structure.

Objectives The aim of the present study was to determine the relation of urinary dysfunction with motor symptoms and nigrostriatal neuron loss in drug-naive patients with Parkinson's disease (PD). We therefore examined the relation of overactive bladder (OAB) symptoms with motor symptoms and striatal dopamine transporter (DAT) binding measured by [123-Iodine]-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenylnortropane) dopamine transporter single-photon emission computed tomography (123I-FP-CIT SPECT). Patients and methods Thirty-one untreated PD patients (12 men and 19 women with a mean age of 71.2 ± 6.7 years) were included in this study. Patients were evaluated with overactive bladder symptom score (OABSS) and divided into an OAB group and Non-OAB group. They underwent clinical assessments and 123I-FP-CIT SPECT imaging. Motor symptoms were assessed using Unified Parkinson's Disease Rating Scale (UPDRS). Results The results showed that UPDRS motor score (p = 0.01) and akinetic-rigid score (p = 0.002) were higher and that striatal DAT availability (p = 0.01) was lower in the OAB group than in the Non-OAB group. However, tremor score, age, and duration of PD showed no significant differences between the OAB group and Non-OAB group. Conclusions Urinary dysfunction in untreated PD is related with increase in motor symptoms (especially bradykinesia and axial symptoms) and reduction of striatal DAT availability.

Higuchi et al. identify recessive mutations in the mitochondrial gene, cytochrome c oxidase assembly factor 7 (COA7) in four unrelated patients with an axonal-type motor and sensory neuropathy with ataxia. Genetic, histopathological, radiological and functional data support a causative role for loss-of-function COA7 mutations in the observed phenotype., Several genes related to mitochondrial functions have been identified as causative genes of neuropathy or ataxia. Cytochrome c oxidase assembly factor 7 (COA7) may have a role in assembling mitochondrial respiratory chain complexes that function in oxidative phosphorylation. Here we identified four unrelated patients with recessive mutations in COA7 among a Japanese case series of 1396 patients with Charcot-Marie-Tooth disease (CMT) or other inherited peripheral neuropathies, including complex forms of CMT. We also found that all four patients had characteristic neurological features of peripheral neuropathy and ataxia with cerebellar atrophy, and some patients showed leukoencephalopathy or spinal cord atrophy on MRI scans. Validated mutations were located at highly conserved residues among different species and segregated with the disease in each family. Nerve conduction studies showed axonal sensorimotor neuropathy. Sural nerve biopsies showed chronic axonal degeneration with a marked loss of large and medium myelinated fibres. An immunohistochemical assay with an anti-COA7 antibody in the sural nerve from the control patient showed the positive expression of COA7 in the cytoplasm of Schwann cells. We also observed mildly elevated serum creatine kinase levels in all patients and the presence of a few ragged-red fibres and some cytochrome c oxidase-negative fibres in a muscle biopsy obtained from one patient, which was suggestive of subclinical mitochondrial myopathy. Mitochondrial respiratory chain enzyme assay in skin fibroblasts from the three patients showed a definitive decrease in complex I or complex IV. Immunocytochemical analysis of subcellular localization in HeLa cells indicated that mutant COA7 proteins as well as wild-type COA7 were localized in mitochondria, which suggests that mutant COA7 does not affect the mitochondrial recruitment and may affect the stability or localization of COA7 interaction partners in the mitochondria. In addition, Drosophila COA7 (dCOA7) knockdown models showed rough eye phenotype, reduced lifespan, impaired locomotive ability and shortened synaptic branches of motor neurons. Our results suggest that loss-of-function COA7 mutation is responsible for the phenotype of the presented patients, and this new entity of disease would be referred to as spinocerebellar ataxia with axonal neuropathy type 3.

To date, the only instance of tick-borne encephalitis (TBE) in Japan was reported from the southern part of Hokkaido Island in 1993; no other cases have been reported since then. We herein report the first case of TBE reported in the central part of Hokkaido Island, and describe the fatal clinical course of a patient who presented with meningoencephalomyelitis, which partly involved the nerve root. Magnetic resonance imaging (MRI) of the patient's cranium and spine revealed characteristic central nervous system involvement. Our case report is extremely relevant to efforts to protect public health and for precautions against TBE pandemics.

Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those of individuals with multiple system atrophy and Alzheimer’s disease. The neuropathological findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral degeneration and hippocampal sclerosis. Whole-exome analysis of this family identified a novel missense mutation in BSN. Within the pedigree, the detected BSN mutation was found only in affected individuals. Further genetic analyses were conducted in probands from four other pedigrees with PSP-like syndrome and in 41 sporadic cases. Three missense mutations in BSN that are very rarely listed in databases of healthy subjects were found in four sporadic cases. Western blot analysis of tau following the overexpression of wild-type or mutated BSN revealed the possibility that wild-type BSN reduced tau accumulation, while mutated BSN lost this function. An association between BSN and neurological diseases has not been previously reported. Our results revealed that the neurodegenerative disorder associated with the original proband’s pedigree is a novel tauopathy, differing from known dementia and parkinsonism syndromes, including PSP.