Epigenetic regulation of neural stem cell fate by histone demethylase Fbxl11

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 吉田 進昭, 東京大学教授 井上 純一郎, 東京大学准教授 佐藤 均, 東京大学教授 宮島 篤, 東京大学特任教授 渡邉 すみ子University of Tokyo(東京大学

バンドウ フリョ シュウヨウジョ ノ ドイツヘイ ガ オオアサヒコ ジンジャ ケイダイ ニ ツクッタ ハシ ト コウエン

German prisoners in the Bandō prisoner-of-war (POW) camp made bridges and a park in the forest of the Ooasahiko-Jinja Shrine during 1917-1919. Details of the constructions were a 15 m-long wood bridge and five small wood bridges, four stone bridges, road with a total length of 1,130 m, stone embankments, slopes, two flights of stone steps with a length of 8 m and 3 m according to the record written by Adolf Deutschmann who planned and directed the work. Two stone bridges called Doitsu-bashi (German bridge) and Megane-bashi (glasses bridge) remain and the Doitsu-bashi has been designated as a cultural asset of Tokushima prefecture. However, other constructions have been disappeared or became unclear now. In this study, we tried to clarify their precise place and history using an old map of the Ooasahiko-Jinja Shrine, photos and pictures of German prisoners, and interview to an old resident who participated in improvement of the forest around 1970. Results indicated that the road and the stone bridge still remain in some part. In addition to Adolf Deutschmann we found that Max Bunge was an important member of the work. He has not been noticed in previous studies of the Bandō POW camp, although he was a famous person in the German community in Qingdao by some heroic behaviors, and that he became a mayor of his hometown Heiligenhafen after he was released from the camp. He wrote about beautiful nature of the shrine’s forest and about his sympathy to faith of Japanese pilgrims who he saw during construction work

Control of phosphate appetite in young rats

In the present study, we investigated whether a diet deficient in inorganic phosphate (Pi) stimulates an ingestive behavior to seek sources of Pi. Male Wistar rats were placed in individual cages with unrestricted access to tap water and a low (LPD, 0.02% Pi) or normal (NPD, 0.6% Pi) Pi diet for 6 days. On day 7, LDP rats were given unlimited access to a solution of 25 mM potassium phosphate water (Pi-water) for 9 additional days. Rats fed LPD consumed 70-100% more Pi-water then those fed NPD. The increase in Pi-water intake resulted in a marked rise in the growth rate of rats fed LPD during day 9. A similar intake of Pi was induced after only 2 days of LPD and was associated with significant reductions in both plasma and cerebrospinal fluid (CSF) levels of Pi ; these levels remained low throughout Pi restriction, despite a significant intake of Pi-water. Replenishment with a high-Pi diet rapidly quenched the appetite for Pi-water and was associated with restoration of both plasma and CSF Pi levels. These findings suggest that an appetite for Pi can be induced in rats, perhaps through lowered plasma and CSF Pi levels

Clinical and genetic characteristics of autoimmune polyglandular syndrome type 3 variant in the Japanese population

Objective: Type 1 diabetes (T1D) iscommonlyassociated withautoimmunethyroid disease (AITD),and the occurrence of both T1D and AITD in a patient is defined as autoimmune polyglandular syndrome type 3 variant (APS3v). We aimed to clarify the differences in the clinical and genetic characteristics of APS3v patients and T1D patients without AITD [T1D/AITD(-)] in the Japanese population. Design/Patients: Our subjects were 54 APS3v patients and 143 T1D/AITD(-) patients who were consecutively diagnosed at Nagasaki University Hospital from 1983 to the present. Results: A remarkable female predominance, a slow and older age onset of T1D, and a higher prevalence of glutamic acid decarboxylase autoantibodies were observed in APS3v patients compared to T1D/AITD(-) patients. The older onset age of T1D in APS3v patients was associated with a higher proportion of slow-onset T1D. Among the two major susceptible human leukocyte antigen (HLA) class II haplotypes in Japanese T1D, DRB1*0405- DQB1*0401, but not DRB1*0901-DQB1*0303, was associated with APS3v patients. Furthermore, DRB1*0803-DQB1*0601 was not protective in patients with APS3v. The frequencies of the GG genotype in +49G>A and +6230G>A polymorphism in the CTLA4 gene were significantly higher in T1D/AITD(-) patients, but not in APS3v patients, compared to control subjects. Conclusions: In conclusion, we found notable differences in the clinical and genetic characteristics of APS3v patients and T1D/AITD(-) patients in the Japanese population, and the differences in the clinical characteristics between the two groups may reflect distinct genetic backgrounds including the HLA DRB1-DQB1 haplotypes and CTLA4 gene polymorphisms

Language vs individuals in cross-linguistic corpus typology

Published as a special publication of Language Documentation & Conservation (No. 25).Peer reviewe

Effect of dietary components on renal inorganic phosphate (Pi) excretion induced by a Pi-depleted diet

Dietary inorganic phosphate (Pi) is the most important factor in the regulation of renal Pi excretion. Recent studies suggest the presence of an enteric-renal signaling axis for dietary Pi as well as the existence of a mechanism by which the intestine detects changes in luminal Pi concentrations. The mechanisms of intestinal Pi sensing, however, are unknown. In the present study, we focused on Pi depletion signals and investigated the effects of dietary components on intestinal Pi sensing. After feeding rats experimental diets for 3 days, we investigated urinary Pi excretion and plasma biochemical parameters. Renal Pi excretion was suppressed in rats fed a low-Pi diet (0.02% Pi). Elimination of dietary calcium (Ca) completely blocked the suppression of Pi excretion, suggesting that the presence of Ca is essential for the Pi depletion signal. Furthermore, a minimum Ca content of more than 0.02% was necessary for the Pi depletion signal. Magnesium, lanthanum, and strontium, which are agonists of calcium sensing receptor, instead of Ca, reduced Pi excretion.Therefore, dietary Ca appears to be important for the Pi depletion-sensing mechanism in the gastrointestinal tract. In addition, the calcium sensing receptor may be involved in the Pi depletion signal

Polygenic architecture informs potential vulnerability to drug-induced liver injury

Drug-Induced-Liver-Injury (DILI) is a leading cause of termination in drug development programs and removal of drugs from the market, and this is partially due to the inability to identify patients who are at risk1. Here, we developed a polygenic risk score (PRS) for DILI by aggregating effects of numerous genome-wide loci identified from previous large-scale genome-wide association studies (GWAS)2. The PRS predicted the susceptibility to DILI in patients treated with fasiglifam, amoxicillin-clavulanate or flucloxacillin, and in primary hepatocytes and stem cell-derived organoids from multiple donors treated with over 10 different drugs. Pathway analysis highlighted processes previously implicated in DILI, including unfolded protein responses and oxidative stress. In silico screening identified compounds that elicit transcriptomic signatures present in hepatocytes from individuals with elevated PRS, supporting mechanistic links and suggesting a novel screen for safety of new drug candidates. This genetic-, cellular-, organoid- and human-scale evidence underscored the polygenic architecture underlying DILI vulnerability at the level of hepatocytes, thus facilitating future mechanistic studies. Moreover, the proposed “polygenicity-in-a-dish” strategy might potentially inform designs of safer, more efficient, and robust clinical trials

作業療法士と歯科衛生士を目指す学生の高齢者に対する意識調査 : 祖父母との同居経験の有無から

近年の学生と関わるなかで,人と関わる経験を積み重ねていないと感じることがある.現に,入学後に初めて異年齢交流を経験する学生も多く存在する.また,現代の核家族化などにより高齢者とかかわる経験が非常に乏しくなっている.リハビリの専門職である作業療法士や口腔ケアの専門職である歯科衛生士を目指す学生としては,高齢社会の現状を把握し高齢者に対応できる人材となる必要がある.今回,学生たちの高齢社会に対する意識を知るために高齢者との「交流経験」と「交流に対する今後の意識」といった具体的な交流経験を含んだ質問紙によるアンケート調査を行なった.その結果,同居の有無や作業療法学生と歯科衛生学生に関係はなく,高齢者との具体的な交流内容により経験や意識に違いがあることが分かった.In recent interactions with students, the feeling has emerged that today\u27s students have not accumulated experiences of social contact with others. In fact, it has become clear that many students do not experience interaction with individuals outside their own age group until they have completed their education. However, students pursuing a career as an occupational therapist or dental hygienist are expected to develop the ability to understand the condition of elderly individuals and respond appropriately and adequately. Although students in such programs receive appropriate practical training and education, further training is obviously required. In order to identify students\u27 attitudes towards the elderly, a study was conducted using a questionnaire containing items regarding specific social interactions, such as the experience of interacting with elderly individuals, and attitudes about meeting elderly individuals in the future. The results indicated that regardless of whether students are living with their grandparents or not, or whether students are studying occupational therapy or dental hygiene, their experiences and attitudes depend on their actual current social contact with elderly individuals. Based on these results, the present article discusses the type of training and education regarding the elderly that should be provided for students

介護老人保健施設入所高齢者の作業提示方法の違い : 逆唱検査結果と作業効率の違いについて

本研究では、介護老人保健施設に6ケ月以上入所している高齢者に、作業提示方法による作業効率の違いを検討した. 作業の遂行に一時的必要となる作業記憶にも着眼した. 作業記憶を簡便に評価できる数字の逆唱を対象者におこない、対象者を逆唱の良好群と不良群の2群に分けた. 各群の対象者に4種類の作業構成の作業と、1種類の作業を繰り返しおこなう、2つの作業を提示し期間をあけて実施した. 2つの作業の作業効率の違いを検討するために、作業実施後にTMT-A、TMT-B、作業の実施前後にフリッカー検査をおこなって分析した. 不良群は2つの作業間でのTMT-Bに有意な正の相関を認めず、2つの作業提示方法において作業効率に違いがあると推察した. 逆唱が不良な高齢者に作業活動を提示する場合、組織だった行為を要する、簡単な複数の作業を一貫して順番に提示することが作業効率に違いがあることが示唆された.In the present study, the difference of the work efficiency according to the method of presenting work to senior citizen who had been the be imprisoned for six months or more to the geriatric health service facility was examined. It aimed it also at the working memory that became temporary necessary for accomplishing work. Reverse-backward of the figure that was handily appreciable of the working memory was done to the object person. The object person was divided into two crowds an excellent group and a defective group of reverse-backward. Two work done to each crowd\u27s object person repeating the work of four kinds of work compositions and one kind of work was presented, and the period was opened and executed. After work is executed, TMT-A, TMT-B to examine the difference of the work efficiency of two work. It analyzed it inspecting the flicker before and after the execution of work. A defective group is TMT-B between two work. It was guessed that a significant, positive correlation was not admitted in TMT-B, and there was a difference in the work efficiency in the method of presenting two work