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Viral cancers show oncogene addiction to viral oncoproteins, which are required for survival and proliferation of the dedifferentiated cancer cell. Human Merkel cell carcinomas (MCCs) that harbor a clonally integrated Merkel cell polyomavirus (MCV) genome have low mutation burden and require viral T antigen expression for tumor growth. Here, we showed that MCV⁺ MCC cells cocultured with keratinocytes undergo neuron-like differentiation with neurite outgrowth, secretory vesicle accumulation, and the generation of sodium-dependent action potentials, hallmarks of a neuronal cell lineage. Cocultured keratinocytes are essential for induction of the neuronal phenotype. Keratinocyte-conditioned medium was insufficient to induce this phenotype. Single-cell RNA sequencing revealed that T antigen knockdown inhibited cell cycle gene expression and reduced expression of key Merkel cell lineage/MCC marker genes, including HES6, SOX2, ATOH1, and KRT20. Of these, T antigen knockdown directly inhibited Sox2 and Atoh1 expression. MCV large T up-regulated Sox2 through its retinoblastoma protein-inhibition domain, which in turn activated Atoh1 expression. The knockdown of Sox2 in MCV⁺ MCCs mimicked T antigen knockdown by inducing MCC cell growth arrest and neuron-like differentiation. These results show Sox2-dependent conversion of an undifferentiated, aggressive cancer cell to a differentiated neuron-like phenotype and suggest that the ontology of MCC arises from a neuronal cell precursor.

Little is known regarding the incidence of the shoulder instability in Japan. The aim of this study was to evaluate the incidence of traumatic shoulder instability among Japanese military cadets. A prospective cohort study was performed to capture all traumatic shoulder instability events between 2009 and 2012 among cadets in a military educational academy of the Japan Self Defense Forces. The total number of cadets in the cohort was 5,402 (average age 20.6 years). The incidence of instability events, including dislocation or subluxation, was calculated. Chronicity, demographics of participants, mechanism of injury, and athletic events were also evaluated. The incidence of traumatic dislocation was 4.1/1,000 person-years and that of subluxation was 6.1/1,000 person-years. The incidence of primary dislocation or subluxation was 5.4/1,000 person-years and that of recurrent dislocation or subluxation was 4.7/1,000 person-years. Of first dislocations or subluxations, 92% occurred during sports activities, including after-school sports activities, military training, and gym classes. In conclusion, the overall incidence of shoulder instability events among Japanese military cadets was 10.3/1,000 person-years, and was extremely high. Most shoulder instability events occurred during sports activities, and a program to prevent such injuries during sports activities is necessary for young participants.

Musician’s dystonia is a type of task specific dystonia for which the pathophysiology is not clear. In this study, we performed functional magnetic resonance imaging to investigate the motor-related brain activity associated with musician’s dystonia. We compared brain activities measured from subjects with focal hand dystonia and normal (control) musicians during right-hand, left-hand, and both-hands tapping tasks. We found activations in the thalamus and the basal ganglia during the tapping tasks in the control group but not in the dystonia group. For both groups, we detected significant activations in the contralateral sensorimotor areas, including the premotor area and cerebellum, during each tapping task. Moreover, direct comparison between the dystonia and control groups showed that the dystonia group had greater activity in the ipsilateral premotor area during the right-hand tapping task and less activity in the left cerebellum during the both-hands tapping task. Thus, the dystonic musicians showed irregular activation patterns in the motor-association system. We suggest that irregular neural activity patterns in dystonic subjects reflect dystonic neural malfunction and consequent compensatory activity to maintain appropriate voluntary movements.

BackgroundThe epidemiological patterns of musculoskeletal injuries or disorders in military personnel have not been well documented and a better understanding is required for proper preventative measures and treatment. Here, we investigated musculoskeletal injuries or disorders among members of the Japan Self-Defense Forces.MethodsAll orthopedic patients (n = 22,340) who consulted to Japan Self-Defense Forces Hospitals were investigated for their type of injury or disorder, the injured body part, the mechanism, and the cause of injuries.ResultsThirty-nine percent of the cases were classified as traumatic injuries, and 61% were classified as non-traumatic disorders. Of the traumatic injury patients, the injured body part was the upper extremity in 32%, the trunk in 23%, and the lower extremities in 45% of the cases. The most common injured body location was the knee followed by the hand/finger and ankle. Exercise was the most common cause of injury, followed by traffic accident and military training.Contusions were the most common traumatic injuries, followed by sprains and fractures. Of non-traumatic disorders, the lower extremities were reported as the injured part in 43% of the disorders. Lumbar spine disorders were the most common non-traumatic disorders, followed by tendon and joint disorders.ConclusionsOver one-third of orthopedic cases among members of the Japan Self-Defense Forces are traumatic injuries, with the knee being the body part most commonly injured and exercise being the leading cause of injury.

Cholera toxin (choleragen) dissociated into two types of subunit with molecular weights estimated to be 28,000 daltons (A) and 11,000 daltons (B); this dissociation was effected by gel filtration at acid pH with or without urea. Subunit A could be separated into two fragments, A1 (23,000 daltons) and A2 (about 2,500 daItons), after reduction and alkylation. Choleragenoid (68,000 daItons) appeared to be a polymerizedform of subunit B. A-specific antigen was found in choleragen as well as in A1 and A2 , while B-specific antigen was found in both choleragen and choleragenoid. In electron micrographs, the toxin molecule appeared as a particle of uniform size consisting of subunits in V- or Y-shape and in ring form. The dimensions coincided with the values calculated from the molecular weights.