In the course of systematic RNA interference (RNAi)-based screens with helicase-like genes in Caenorhabditis elegans , we have identified the drh-3 ( D2005.5 ) gene as a candidate gene for protection against X-ray irradiation. This gene encodes a novel RNA helicase-like protein that is similar to two nematode Dicer-related helicases (DRH). Here, we have showed the increased expression of drh-3 transcripts during maturation of larvae to adults, and characterized the phenotype of drh-3 -interferred nematodes using feeding RNAi method. RNAi-mediated depletion of the drh-3 transcripts caused embryonic lethality of F1 progeny and temperature-sensitive reproductive capacity but did not affect the nematode life span. F1 progeny from drh-3 ( RNAi ) animals exhibited increased lethality after X-ray irradiation or exposure to camptothecin. In drh-3 ( RNAi ) worms, aggregated chromosomes were observed in diakinesis oocyte nuclei. In developing early zygotic embryos from drh-3 ( RNAi ) worms, abnormally segregated chromosomes were observed and embryonic development was largely arrested at the mid-stages of embryogenesis. Finally, examination of checkpoint responses in mitotic germ cells with regards to replication arrest by hydroxyurea and X-ray-induced DNA damage suggested that both checkpoints function normally under these genotoxic stress conditions. Taken together, these results indicate that the drh-3 gene is essential for the development of germ-lines by maintaining chromosomal integrity in C. elegans .

Objectives To investigate the association of loneliness and its component subscales with the risk of dementia in a general Japanese older population. Method A total of 1,141 community-dwelling Japanese residents aged ≥65 years without dementia were prospectively followed up for a median 5.0 years. We evaluated any loneliness and its component subscales—namely, social and emotional loneliness—by using the 6-Item de Jong Gierveld Loneliness Scale. Cox proportional hazards models were used to estimate hazard ratios (HRs) of each loneliness type on the risk of dementia controlling for demographic factors, lifestyle factors, physical factors, social isolation factors, and depression. Results During the follow-up, 114 participants developed dementia. The age- and sex-adjusted incidence rate of dementia was significantly greater in participants with any loneliness and emotional loneliness than those without. The multivariable-adjusted HRs (95% confidence intervals) of participants with any loneliness and emotional loneliness on incident dementia were 1.61 (1.08-2.40) and 1.65 (1.07-2.54), respectively, as compared to those without. However, there was no significant association between social loneliness and dementia risk. In subgroup analyses of social isolation factors, excess risks of dementia associated with emotional loneliness were observed in participants who had a partner, lived with someone, or rarely communicated with relatives or friends, but such association was not significant in participants who had no partner, lived alone, or frequently communicated with friends or relatives. Discussion The present study suggested that loneliness, especially emotional loneliness, was a significant risk factor for the development of dementia in the general older population in Japan.

ObjectiveTo assess the association of regional grey matter atrophy with dementia risk in a general older Japanese population.MethodsWe followed 1158 dementia-free Japanese residents aged ≥65 years for 5.0 years. Regional grey matter volume (GMV) at baseline was estimated by applying voxel-based morphometry methods. The GMV-to-total brain volume ratio (GMV/TBV) was calculated, and its association with dementia risk was estimated using Cox proportional hazard models. We assessed whether the predictive ability of a model based on known dementia risk factors could be improved by adding the total number of regions with grey matter atrophy among dementia-related brain regions, where the cut-off value for grey matter atrophy in each region was determined by receiver operating characteristic curves.ResultsDuring the follow-up, 113 participants developed all-cause dementia, including 83 with Alzheimer’s disease (AD). Lower GMV/TBV of the medial temporal lobe, insula, hippocampus and amygdala were significantly/marginally associated with higher risk of all-cause dementia and AD (all p for trend ≤0.08). The risks of all-cause dementia and AD increased significantly with increasing total number of brain regions exhibiting grey matter atrophy (both p for trend <0.01). Adding the total number of regions with grey matter atrophy into a model consisting of known risk factors significantly improved the predictive ability for AD (Harrell’s c-statistics: 0.765–0.802; p=0.02).ConclusionsOur findings suggest that the total number of regions with grey matter atrophy among the medial temporal lobe, insula, hippocampus and amygdala is a significant predictor for developing dementia, especially AD, in the general older population.

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L-Leucine is known to stimulate protein synthesis in L6 myotubes. In the present study, we examined the possible involvement of calcium signaling pathways in the stimulation of protein synthesis induced by L-leucine in L6 myotubes. After 16 h of treatment with L-leucinedepleted medium, the re-addition of L-leucine for 4 h augmented protein synthesis by about 50% as compared with an L-leucine-depleted control. Ryanodine receptor antagonists almost completely abolished the stimulatory effect of L-leucine, while IP 3 receptor antagonists showed partial inhibition when added simultaneously with L-leucine. These results suggest the possibility that calcium signaling pathways are involved in L-leucinestimulated protein synthesis.