Sequential peripheral enrichment of H2A.Zac and H3K9me2 during trophoblast differentiation in human embryonic stem cells

ES細胞分化過程において継時的に分布変化するヒストン修飾を同定 --ヒト幹細胞が分化する時、核では何が起こっているのか--. 京都大学プレスリリース. 2021-01-06.During the transition from pluripotency to a lineage-committed state, chromatin undergoes large-scale changes in structure, involving covalent modification of histone tails, use of histone variants and gene position changes with respect to the nuclear periphery. Here, using high-resolution microscopy and quantitative image analysis, we surveyed a panel of histone modifications for changes in nuclear peripheral enrichment during differentiation of human embryonic stem cells to a trophoblast-like lineage. We found two dynamic modifications at the nuclear periphery, acetylation of histone H2A.Z (H2A.Zac), and dimethylation of histone H3 at lysine 9 (H3K9me2). We demonstrate successive peripheral enrichment of these markers, with H2A.Zac followed by H3K9me2, over the course of 4 days. We find that H3K9me2 increases concomitantly with, but independently of, expression of lamin A, since deletion of lamin A did not affect H3K9me2 enrichment. We further show that inhibition of histone deacetylases causes persistent and increased H2A.Z acetylation at the periphery, delayed H3K9me2 enrichment and failure to differentiate. Our results show a concerted change in the nature of peripheral chromatin occurs upon differentiation into the trophoblast state

Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

Background Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was 1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC

Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients

Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001−3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01)

総合臨床実習における実習成績の分析

本学で使用する実習成績評価の信頼性を検証するとともに、実習成績結果から学生の特徴について明確にすることを目的とした. 実習成績評価は中項目、小項目ともにCronbachの α信頼係数は高値を示し、本学で作成した成績表の全ての項目内容は信頼性、内的整合性が保たれていることがわかった. Klaster分析によって実習成績別に良好群、中間群、不良群にわけることができた. 学生の特徴として、良好群は全ての中項目で60点以上の成績であった. 中間群は基本的態度、対人関係、対象者のオリエンテーションなどコミュニケーション能力に関係する中項目では60点以上の成績となっていたが、評価に関係する中項目においては60点を下回る成績であった. 不良群では全ての中項目において60点を下回る成績であった.As well as verify the authenticity of the grading clinical practice used by the University, we have intended to clarify characteristics of student results from grading clinical practice. Cronbach\u27s reliability coefficient α indicates the threshold in both middle items, small items, grading clinical practice, he was found to be maintained reliability, and internal consistency of the contents of all the items of the league table that you created in the university. I can be divided into good group, middle group, the poor control group performance by training by analysis klaster. The characteristics of the students, was a good group performance of more than 60 items of all. Intermediary group in the field, but had become a grade of at least 60 points in that relate to communication skills, such as orientation basic attitudes, interpersonal relations, of the subject, in the field he was a grade below 60 points in the related to the evaluation. Bad group it was 60 points lower than the results of all the items

Reconfiguring boundaries : Japanese women in Shanghai

This thesis explores migratory processes of Japanese women to Shanghai since the early 2000s. It sheds light on the -shifting meaning of boundaries between Japan and other Asian countries, particularly China, through these migratory processes. I argue that urbanization and opportunities associated with rapid economic growth in China, as well as growing economic ties between China and Japan, are central to their migration processes. Their acts of migration are part of the processes of redefining and renegotiating boundaries between Japan and other parts of Asia. In this regard, I stress that they are not passive recipients of transnational processes. Rather, I suggest that they are active participants in the dynamic processes of place making and negotiating borders as well as countering, questioning and re· imagining the state practices of demarcating boundaries. Transnational migration is a vital part of enacting such processes as it enables individual migrants to relate to the place, culture and/or people beyond "our" territory: an imagined community that is sustained through the acts of forgetting and remembering and of securitizing border-crossings as a threat to the secure and bounded community. By drawing attention to the migratory processes of Japanese women to Shanghai, I suggest that the global cities in the Asia· Pacific region may provide a significant space for critically interrogating the questions of boundaries, mobility and territoriality. I thus argue that the movement of people is vital to the reconfiguration of boundaries

Prevalence of temporomandibular disorders among junior high school students who play wind instruments

Objectives This study investigated whether playing wind instruments has adverse effects on musculoskeletal functions among junior high school students who play in music clubs. Material and Methods The study included 210 junior high school students (35 boys, 175 girls) belonging to 1 of 4 different school clubs that practiced playing wind instruments more than 6 days/week. The mean age of the participants was 14 years. The study was performed using a questionnaire survey and an electromyographic examination of jaw and cervical muscle activities during playing wind instruments. Results The prevalence of temporomandibular disorders (TMD) among the children playing woodwind (WW) or brass wind (BW) instruments was higher than in those playing non-wind (NW) instruments. Long duration of playing WW with a reed mouthpiece or BW with a small mouthpiece was suggested to affect the incidence of TMD, which was more marked in girls than in boys, irrespective of height or weight. Muscle activity in the masseter muscle during playing an instrument was significantly higher in the BW with a small mouthpiece group than in the NW group (p < 0.05). In cervical muscles, muscle activity of both the sternocleidomastoid and trapezius muscles was higher during playing BW than in the case of other instruments, and activity in the sternocleidomastoid muscle was significantly higher in the BW with a small mouthpiece group than in the case of other instrument groups (p < 0.05). Conclusions Playing wind instruments may have adverse effects on musculoskeletal functions among junior high school students playing in music clubs as compared with playing NW instruments. The prevalence of TMD among the students playing wind instruments was higher than in those playing other instruments. Long duration of playing those instruments affects musculoskeletal function, and this effect is more marked in girls than in boys, irrespective of height or weight