Structure of the human Bre1 complex bound to the nucleosome.

Histone H2B monoubiquitination (at Lys120 in humans) regulates transcription elongation and DNA repair. In humans, H2B monoubiquitination is catalyzed by the heterodimeric Bre1 complex composed of Bre1A/RNF20 and Bre1B/RNF40. The Bre1 proteins generally function as tumor suppressors, while in certain cancers, they facilitate cancer cell proliferation. To obtain structural insights of H2BK120 ubiquitination and its regulation, we report the cryo-electron microscopy structure of the human Bre1 complex bound to the nucleosome. The two RING domains of Bre1A and Bre1B recognize the acidic patch and the nucleosomal DNA phosphates around SHL 6.0-6.5, which are ideally located to recruit the E2 enzyme and ubiquitin for H2BK120-specific ubiquitination. Mutational experiments suggest that the two RING domains bind in two orientations and that ubiquitination occurs when Bre1A binds to the acidic patch. Our results provide insights into the H2BK120-specific ubiquitination by the Bre1 proteins and suggest that H2B monoubiquitination can be regulated by nuclesomal DNA flexibility.

Effects of cigarette smoking on the association between respiratory muscle strength and skeletal muscle mass in middle-aged and older adults: the Wakayama Study.

PURPOSE: This study aimed to examine whether cumulative smoking exposure affects the association between peak expiratory flow rate (PEFR) and skeletal muscle mass in middle-aged and older adults. METHODS: The study participants comprised 832 community-dwelling individuals aged 50-89 years (mean age: 69 years) without chronic obstructive pulmonary disease. Bioelectrical impedance analysis was performed to estimate the skeletal muscle mass of each participant. PEFR was assessed using an electronic spirometer. Cumulative smoking exposure was expressed in pack years, that is a product of the average number of packs of cigarettes smoked per day and smoking duration in years. RESULTS: The whole-body skeletal muscle mass progressively reduced with decreasing PEFR levels in both males and females. In the multiple regression analysis, PEFR was found to be significantly associated with skeletal muscle mass, independent of the potential confounding factors. When participants were stratified based on the cumulative smoking exposure, the association between low PEFR and reduced skeletal muscle mass persisted in individuals with non-smoking and light-to-moderate smoking exposure (< 30 pack-years). However, this association was not clearly observed in individuals with heavy smoking exposure (≥ 30 pack-years). CONCLUSION: The findings of this study support the notion that PEFR declines with a reduction in systemic skeletal muscle mass due to aging. However, chronic cigarette smoking induces respiratory dysfunction exceeding the expected values by age, and thus a low PEFR level may not be used as a marker of reduced muscle mass in older adults exposed to heavy smoking.

Excessive alcohol intake and liver fibrosis are associated with skeletal muscle mass reduction in elderly men: the Wakayama study.

BACKGROUND: Excessive alcohol intake complicated by liver dysfunction has been presumed to affect skeletal muscles. This study aimed to examine the association between excessive alcohol intake, liver fibrosis, and loss of skeletal muscle mass in elderly men. METHODS: The study participants comprised 799 community-dwelling elderly men (age, 71 ± 3 years) with no history of treatment for liver disease. Bioelectrical impedance analysis was performed to estimate the appendicular skeletal muscle mass (ASM) of each participant. The ASM values were also normalized for height (ASM index). Liver fibrosis was evaluated using the Fib4 index, which was calculated using participant age, AST level, ALT level, and platelet count. Usual alcohol intake was estimated based on the type of alcohol, frequency of drinking, and amount of alcohol consumed per day. RESULTS: Among the excess drinkers (≥ 20 g/day), the ASM index of the subgroup with liver fibrosis (Fib4 index ≥ 2.67) was significantly lower than that of the subgroup with no liver fibrosis (Fib4 index < 2.67). However, no significant difference between the subgroups was found in the non-drinkers and moderate drinkers (< 20 g/day). In multiple regression analysis, the Fib4 index was significantly associated with the ASM index, independent of potential confounding factors. The association between the Fib4 index and ASM index was more pronounced in excess drinkers than in non-drinkers and moderate drinkers. CONCLUSION: These results suggest that liver fibrosis is associated with loss of skeletal muscle mass in elderly men, and excessive alcohol intake combined with liver fibrosis may lead to greater muscle mass reduction than each individual condition.

Myositis-specific Autoantibodies Reacting to Both Tif1gamma and Mi-2 in a Patient with Juvenile Dermatomyositis.

is missing (Short communication).

Social development conditions and related factors for children in Japanese kindergarten in Shanghai, China.

OBJECTIVE: The aim of this study is to clarify the social development conditions and related factors for children in Japanese kindergarten in Shanghai, China. METHODS: The target schools were three Japanese kindergartens in Shanghai, three in Wakayama, Japan, and three in Osaka, Japan. The target kindergarten children were all 5- or 6-year-olds. We used an anonymous questionnaire to the guardian of the child. The question items related to social development, lifestyle and daily activities of the child, and rearing awareness and conditions of the guardian. Social development was scored by Strength and Difficulties Questionnaires (SDQ). RESULTS: The number of respondents was 246 (Shanghai group 72, Wakayama group 86, Osaka group 88). The median value of the score of total difficulties and prosocial behavior, SDQ subscale, and the proportion of children judged as low need showed no significant difference. Results of multiple logistic regression analysis showed that the frequency of eating fast-foods and the rearing condition "I become anxious or lose enthusiasm for childrearing when the child is recalcitrant" were the factors relevant to prosocial behavior in the Shanghai group. In the Wakayama group, the hours spent daily watching TV was designated as the relevant factor. In the Osaka group, hours spent daily playing outdoors was found to be the relevant factor. CONCLUSIONS: Social development of children in Japanese kindergarten in Shanghai was the same as that of those living in Japan. The factors relevant to prosocial behavior in the Shanghai group were different from those in the two cities in Japan. This study may show the important points to keep in mind for childrearing abroad.