5 research outputs found

    MERRF/MELAS overlap syndrome: A double pathogenic mutation in mitochondrial tRNA genes

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    Background : Myoclonic epilepsy with ragged-red fibres (MERRF) and mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are established phenotypes of mitochondrial encephalomyopathy. The m.8356T>C transition in the mitochondrial tRNALys gene is a pathogenic mutations of MERRF. The m.3243A>G transition in the mitochondrial tRNALeu gene is detected in most MELAS patients. Although previous analyses of double mutations in mitochondrial DNA (mtDNA) were useful for discussing their nature, many unsolved questions remain. Objective : To describe the clinical and genetic features of a family with the above mtDNA double-point mutations and discuss the role of double mtDNA mutations in diverse clinical features in the family. Patients and methods : The proband was a 23-year-old woman with MERRF harbouring m.8356T>C and m.3243A>G transitions in mitochondrial tRNA genes. We assessed clinical aspects of her and those of her three relatives and performed mutation analyses on their mtDNA. Results : Phenotypes of the four patients were MERRF, MERRF/MELAS overlap syndrome and asymptomatic carrier. We hypothesise that the course of the phenotype of this family begins with MERRF and is followed by MELAS. This double mutation was heteroplasmic in blood of all four patients but with different rates in each patient, while m.8356T>C appeared homoplasmic and m.3243A>G was heteroplasmic in muscle of the two examined cases. No other mutations were detected in the total mtDNA sequence in this family. Conclusions : This is the first reported case of a double-point mutation in mtDNA, both of which were heteroplasmic and pathogenic for the established phenotypes

    Sex Differences in Salivary Oxytocin and Cortisol Concentration Changes during Cooking in a Small Group

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    Background: Oxytocin (OT), a neuropeptide, has positive effects on social and emotional processes during group activities. Because cooking is an integrated process in the cognitive, physical, and socio-emotional areas, cooking in a group is reported to improve emotion and cognition. However, evidence for efficacy in group cooking has not been well established at the biological level. Methods: To address this shortcoming, we first measured salivary levels of OT and cortisol (CORT), a biomarker of psychological stress, before and after group cooking for approximately 1 h by people who know each other in healthy married or unmarried men and women. We then compared the initial OT and CORT concentrations with those during individual non-cooking activities in isolation. Results: Baseline OT concentrations before group and non-group sessions did not significantly differ and OT levels increased after both types of activity in men and women. In men, however, the percentage changes of OT levels in the first over the second saliva samples were significantly small during cooking compared with those in individual activities. In women, however, such a difference was not observed. In contrast, the mean salivary CORT concentrations after group cooking were significantly decreased from the baseline level in both sexes, though such decreases were not significant after individual activity sessions. The sex-specific differences were marital-status independent. Conclusion: These results indicate that OT and CORT concentrations after two activity sessions by a familiar group changed in opposite directions in a sex-specific manner. This suggests that, because cooking is experience-based, we need to consider the sex-specific features of group cooking if we apply it for intervention

    Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles

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    Prion-like domains (PLDs) are low complexity sequences found in RNA binding proteins associated with the neurodegenerative disorder amyotrophic lateral sclerosis. Recently, PLDs have been implicated in mediating gene regulation via liquid-phase transitions that drive ribonucleoprotein granule assembly. In this paper, we report many PLDs in proteins associated with paraspeckles, subnuclear bodies that form around long noncoding RNA. We mapped the interactome network of paraspeckle proteins, finding enrichment of PLDs. We show that one protein, RBM14, connects key paraspeckle subcomplexes via interactions mediated by its PLD. We further show that the RBM14 PLD, as well as the PLD of another essential paraspeckle protein, FUS, is required to rescue paraspeckle formation in cells in which their endogenous counterpart has been knocked down. Similar to FUS, the RBM14 PLD also forms hydrogels with amyloid-like properties. These results suggest a role for PLD-mediated liquid-phase transitions in paraspeckle formation, highlighting this nuclear body as an excellent model system for understanding the perturbation of such processes in neurodegeneration