Fbw7によるユビキチン依存的分解を介したGATA結合タンパク質2レベルの制御：GATA結合タンパク質2のスレオニン176のサイクリンB-サイクリン依存性キナーゼ1を介したリン酸化の関与

浜松医科大学学位論文　医博第700号（平成27年3月16日

Nucleophilic substitution reaction of 1-methoxy-6-nitro-indole

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学部Nucleophilic substitution reaction of 1-methoxy-6-nitroindole (1) was examined. In the reaction with sodium methoxide or sodium cyanide as a nucleophile, 2- and 3-methoxy-6-nitroindoles, and 7-cyano-6-nitroindole were obtained, respectively. A novel methylene homologation at the 3-position was found in the reaction of 1 with sodium methyl sulfide or potassium salt of diethyl malonate to give 3-methylthiomethytyl-6-nitroindole and its 2-methylthio derivative, and diethyl 2-(6-nitroindol-3-yl)methylmalonate, respectively. Possible reaction mechanism is discussed

Identification of hepta-histidine as a candidate drug for Huntington's disease by in silico-in vitro- in vivo-integrated screens of chemical libraries.

We identified drug seeds for treating Huntington's disease (HD) by combining in vitro single molecule fluorescence spectroscopy, in silico molecular docking simulations, and in vivo fly and mouse HD models to screen for inhibitors of abnormal interactions between mutant Htt and physiological Ku70, an essential DNA damage repair protein in neurons whose function is known to be impaired by mutant Htt. From 19,468 and 3,010,321 chemicals in actual and virtual libraries, fifty-six chemicals were selected from combined in vitro-in silico screens; six of these were further confirmed to have an in vivo effect on lifespan in a fly HD model, and two chemicals exerted an in vivo effect on the lifespan, body weight and motor function in a mouse HD model. Two oligopeptides, hepta-histidine (7H) and Angiotensin III, rescued the morphological abnormalities of primary neurons differentiated from iPS cells of human HD patients. For these selected drug seeds, we proposed a possible common structure. Unexpectedly, the selected chemicals enhanced rather than inhibited Htt aggregation, as indicated by dynamic light scattering analysis. Taken together, these integrated screens revealed a new pathway for the molecular targeted therapy of HD

Hornerin deposits in neuronal intranuclear inclusion disease : direct identification of proteins with compositionally biased regions in inclusions

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder, characterized by the presence of eosinophilic inclusions (NIIs) within nuclei of central and peripheral nervous system cells. This study aims to identify the components of NIIs, which have been difficult to analyze directly due to their insolubility. In order to establish a method to directly identify the components of NIIs, we first analyzed the huntingtin inclusion-rich fraction obtained from the brains of Huntington disease model mice. Although the sequence with expanded polyglutamine could not be identified by liquid-chromatography mass spectrometry, amino acid analysis revealed that glutamine of the huntingtin inclusion-rich fraction increased significantly. This is compatible with the calculated amino acid content of the transgene product. Therefore, we applied this method to analyze the NIIs of diseased human brains, which may have proteins with compositionally biased regions, and identified a serine-rich protein called hornerin. Since the analyzed NII-rich fraction was also serine-rich, we suggested hornerin as a major component of the NIIs. A specific distribution of hornerin in NIID was also investigated by Matrix-assisted laser desorption/ionization imaging mass spectrometry and immunofluorescence. Finally, we confirmed a variant of hornerin by whole-exome sequencing and DNA sequencing. This study suggests that hornerin may be related to the pathological process of this NIID, and the direct analysis of NIIs, especially by amino acid analysis using the NII-rich fractions, would contribute to a deeper understanding of the disease pathogenesis.Peer reviewe

Coping behaviors with the experience of outpatients with gynecological cancer during adjuvant chemotherapy

research repor

浜松市内における教員の作業療法の認知度と必要性に関する調査

実践報告Practical reports　本研究の目的は，浜松市内の教育現場における作業療法の認知度，教員が児童・生徒において困っていること，作業療法の必要性などを調査することである．調査方法は，浜松市内の公立小・中学校，特別支援学校に勤務している教員242 名に対し，アンケート調査を実施した．結果は，小・中学校，特別支援学校において半数以上の教員が作業療法を知っていた．また半数以上教員が気になる児童・生徒がいると回答し，行動面，学習面，対人関係，自立活動面において，困り感を感じていた．しかし，作業療法の必要性については，小・中学校では，「どちらともいえない」や未回答の回答が半数以上を占めていた．OT が学校に介入するためには，外部専門家としての知識や実践を学び，県士会等の組織的に学校教育現場に関わることが必要である．　This study examines the need for Occupational Therapy (OT) awareness and skills, and the real-life needs of Hamamatsu-based educators who face OT challenges with their students. 242 public elementary, junior high school, and special education teachers completed a questionnaire. More than half of the surveyed teachers had a basic understanding of Occupational Therapy. Additionally, more than half the surveyed teachers said they had students with OT needs. Many teachers face difficulties with student behavior, learning challenges, communications, and student independence. In contrast, nearly half of the surveyed teachers also answered that they did not perceive there to be any pressing need for OT services or OT professional help for their students. The study finds that it is necessary for OT professionals and the OT Association to be more proactive in understanding the needs for local school and students. To accomplish this, it is necessary for the local OT Association to be systematically involved in local schools

作業療法学生における臨床実習での学びの過程と省察 : テキストマイニングによる分析から

研究論文Original Articles　臨床実習における学びのプロセスを，探索的に明らかにすることを目的に，実習後に行われた振り返りの記述の分析を行った．　その結果，学生は自己内省が行えるようになり，基本的知識の習得だけでなく，エビデンスを求める思考，問題解決のために分析する思考が必要であると考えられるようになっていることが確認できた．この思考は，Dreyfus model では，熟練者レベルの思考である．初心者のレベルである学生が，熟練者レベルの思考に気付くことが出来たことは教員が振り返りシートの作成に関わっていることも要因であると考えられた．　また，コミュニケーションに課題を感じている学生は，物事の優先順位を付けた行動化も同様に課題と考えていることが分かった．優先順位を付けた行動化は，実習中に学ぶことが難しく，臨床実習前からの学内での指導が重要であることも示唆された．　For the purpose of exploratively identifying the process of learning in clinical practicum, written reflections from post-fieldwork students were analyzed.　The results confirmed that students became able to self-reflect, and became able to recognize the necessity of not only basic knowledge acquisition but also the type of thinking that seeks evidence as well as analytical thinking for problem solving. These kinds of thinking are considered as expert level in the Dreyfus model. Educators’ involvement in development of reflection sheets may have partly contributed to the fact that the students, who were at novice level, became able to recognize thinking at expert level.　Additionally, it was found that those students, who feel communication is a challenging task, considered doing things in order of priority is also challenging. As it is difficult to learn to act in order of priority during clinical practicum, it was also suggested that on-campus instruction prior to commencing the practicum is important