Possible involvement of iron-induced oxidative insults in neurodegeneration.

Involvement of iron in the development of neurodegenerative disorders has long been suggested, and iron that cannot be stored properly is suggested to induce iron toxicity. To enhance iron uptake and suppress iron storage in neurons, we generated transgenic (Tg) mice expressing iron regulatory protein 2 (IRP2), a major regulator of iron metabolism, in a neuron-specific manner. Although very subtle, IRP2 was expressed in all regions of brain examined. In the Tg mice, mitochondrial oxidative insults were observed including generation of 4-hydroxynonenal modified proteins, which appeared to be removed by a mitochondrial quality control protein Parkin. Inter-crossing of the Tg mice to Parkin knockout mice perturbed the integrity of neurons in the substantia nigra and provoked motor symptoms. These results suggest that a subtle, but chronic increase in IRP2 induces mitochondrial oxidative insults and accelerates neurodegeneration in a mouse model of Parkinson's disease. Thus, the IRP2 Tg may be a useful tool to probe the roles of iron-induced mitochondrial damages in neurodegeraration research

〈報告〉中上級日本語学習者のための作文ガイドブックの開発

本稿では、中上級学習者のアカデミック・ジャパニーズのための作文学習を支援する作文ガイドブック作成に至る過程を概説し、試作した作文ガイドブックについて報告する。作文学習の際、日本語レベルを超えて共有すべき学習項目を特定し、レベル縦断の内容として各レベルの学習者が必要に応じて参照できれば、より学習効果が上がると考える。そこで、大学の補講日本語コースの中上級作文クラスにおいて、コースシラバス作成、レベルチェック作文分析の結果を踏まえて、作文ガイドブックの作成を行った。複数のレベルで誤用が見られる文体と文脈に関わる文法的な表現の中で学習項目として、文体、引用、接続詞・接続助詞、疑問文、文末表現、「る・た・ている」テンス・アスペクトという６項目を取り上げ、パワーポイント資料を作成した。共有できる学習資源として、作文授業を担当する教師や作文を書く学習者が利用しやすい内容や形式にして公開していくことが重要である。This paper outlines the process leading up to the preparation of a composition guidebook to support intermediate-advanced level learners learning composition for academic Japanese, and reports on the guidebook development. We hypothesize that during the composition learning process, learning will be more effective if learners, regardless of their levels, can refer to a set of essential learning items. Therefore, we prepared a composition guidebook based on the results of course syllabi and level check composition analysis in the intermediate-advanced composition classes of the supplementary Japanese language course of our university. At multiple learner levels, we observed errors related to style and context in grammar expression. Based on the errors, we selected six learning items, namely writing style, quotation, conjunction and conjunctive particles, interrogative sentences, sentence-ending expressions, and tense and aspect. We then created PowerPoint materials. As a learning resource that can be shared, it is important to make it accessible to both the teachers who are in charge of writing composition and to the learners who write compositions, in an easy-to-use content and format

BHLHA15-Positive Secretory Precursor Cells Can Give Rise to Tumors in Intestine and Colon in Mice

Background & Aims: The intestinal epithelium is maintained by long-lived intestinal stem cells (ISCs) that reside near the crypt base. Above the ISC zone, there are short-lived progenitors that normally give rise to lineage-specific differentiated cell types but can dedifferentiate into ISCs in certain circumstances. However, the role of epithelial dedifferentiation in cancer development has not been fully elucidated. Methods: We performed studies with Bhlha15-CreERT, Lgr5-DTR-GFP, Apc flox/flox , LSL-Notch (IC), and R26-reporter strains of mice. Some mice were given diphtheria toxin to ablate Lgr5-positive cells, were irradiated, or were given 5-fluorouracil, hydroxyurea, doxorubicin, or dextran sodium sulfate to induce intestinal or colonic tissue injury. In intestinal tissues, we analyzed the fate of progeny that expressed Bhlha15. We used microarrays and reverse-transcription PCR to analyze gene expression patterns in healthy and injured intestinal tissues and in tumors. We analyzed gene expression patterns in human colorectal tumors using The Cancer Genome Atlas data set. Results: Bhlha15 identified Paneth cells and short-lived secretory precursors (including pre-Paneth label-retaining cells) located just above the ISC zone in the intestinal epithelium. Bhlha15 + cells had no plasticity after loss of Lgr5-positive cells or irradiation. However, Bhlha15 + secretory precursors started to supply the enterocyte lineage after doxorubicin-induced epithelial injury in a Notch-dependent manner. Sustained activation of Notch converts Bhlha15 + secretory precursors to long-lived enterocyte progenitors. Administration of doxorubicin and expression of an activated form of Notch resulted in a gene expression pattern associated with enterocyte progenitors, whereas only sustained activation of Notch altered gene expression patterns in Bhlha15 + precursors toward those of ISCs. Bhlha15 + enterocyte progenitors with sustained activation of Notch formed intestinal tumors with serrated features in mice with disruption of Apc. In the colon, Bhlha15 marked secretory precursors that became stem-like, cancer-initiating cells after dextran sodium sulfate–induced injury, via activation of Src and YAP signaling. In analyses of human colorectal tumors, we associated activation of Notch with chromosome instability-type tumors with serrated features in the left colon. Conclusions: In mice, we found that short-lived precursors can undergo permanent reprogramming by activation of Notch and YAP signaling. These cells could mediate tumor formation in addition to traditional ISCs

Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2‐mutation carriers

The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients

プールの健康教室に参加することによる心身への影響―低身体活動高齢女性の実態調査―

目的：群馬県内のAプールが実施している健康教室に参加することが心身に及ぼす影響を明らかにすることを目的とした． 方法：研究参加に同意した65歳以上の低身体活動の女性11名を対象者とした．教室参加前に年齢，健康状態，気分を，教室当日に運動前，中，後の血圧・脈拍，主観的運動強度を，教室終了後に気分を調査した．任意で体力測定を行った． 結果：体力測定の結果は，握力，上体起こし，長座体前屈，開眼片足立ち，10m障害物歩行の全てで全国平均よりも低かった．気分は，教室参加後に緊張・不安が有意に低下した．収縮期血圧は運動後では運動前よりも有意に上昇し，脈拍は運動前よりも有意に低下した．主観的運動強度は運動前よりも有意に上昇した． 結論：対象者は，肥満，筋力低下傾向にあるが，集団で実施する水中運動の強度は適度であった．健康教室により，緊張・不安が改善し，適度な運動強度においても血圧や脈拍の有意な変動が認められた．Objectives: The purpose of this study was to investigate the effects of a health class offered at a swimming pool. Methods: The subjects were 11 women aged 65 years or older who had low active mass. We investigated age, health condition, and mood before the health class. On the day of the health class, we measured blood pressure, pulse, and perceived exertion before, during, and after aquatic exercise. We then investigated mood after the health class. We also offered an optional physical fitness test to the subjects. Results: Scores for grip strength, sit-ups, toe touching, one-leg standing with eyes open, and 10-m obstacle walking test results were below healthy levels. The mood test showed that tension and anxiety were improved. Systolic blood pressure was significantly higher, pulse was significantly lower, and the rate of perceived exertion was significantly higher after exercise than before. Conclusions: The subjects were obese and had muscle weakness, but the exercise was of moderate intensity. Tension and anxiety improved after the health class. Significant changes in blood pressure and pulse were found after exercise.原

Multicenter retrospective and comparative study of 5-minute versus 15-second endoscopic papillary balloon dilation for removal of bile duct stones

Background and study aims Endoscopic papillary balloon dilation (EPBD) is a method of bile duct stone removal that has a better long-term outcome but a high risk of post-ERCP pancreatitis (PEP). Recent studies have suggested that 5-minute EPBD can reduce the incidence of PEP. This study aimed to examine the safety and effectiveness of longer duration EPBD compared with shorter duration EPBD (5 minutes vs. 15 seconds after disappearance of the waist of a dilation catheter). Patients and methods Patients without a history of endoscopic sphincterotomy or EPBD who underwent EPBD to remove bile duct stones were selected retrospectively from five centers. The incidence of PEP, other early adverse events, and outcomes of EPBD were compared between the groups. A multivariable analysis of risk factors for PEP was performed. Results: A total of 607 patients (157 and 450 in the 5-minute and 15-second EPBD groups, respectively) were included. There were no statistically significant differences between the groups in terms of the incidence of PEP (8.3 % and 8.9 % in the 5-minute and 15-second EPBD groups, respectively; P = 0.871) and the incidence of overall early adverse events ( P = 0.999). Although 5-minute EPBD elongated the procedure time (45 vs. 37 minutes, P < 0.001), it increased the rate of complete stone removal during a single session ( P < 0.001) and decreased the use of lithotripsy ( P < 0.001). Conclusions: Compared with 15-second EPBD, 5-minute EPBD did not reduce the incidence of PEP

がん検診啓発活動を通しての看護学生の学び

がん医療の向上に向けて、地域でがんの検診啓発活動に取り組む看護学生の自主グループが誕生し、正課外活動として取り組んでいる。地域の健康課題「がん」に関する、啓発活動に取り組む看護学生の学びをインタビューから質的に分析し、明らかにした。学生は〈関係づくりとしてのネットワーク構築の重要性〉〈専門職者を目指した自己研鑽〉〈コミュニケーション能力の向上〉〈問題発見・解決と企画力の向上〉〈倫理観・責任感を伴った行動の必要性〉〈社会性形成と自己理解〉の6カテゴリー、30サブカテゴリーについて学んでいた。授業時間以外の自主的な学習を促進する正課外活動の重要性が示唆された

First Data Release of the Hyper Suprime-Cam Subaru Strategic Program

The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is a three-layered imaging survey aimed at addressing some of the most outstanding questions in astronomy today, including the nature of dark matter and dark energy. The survey has been awarded 300 nights of observing time at the Subaru Telescope and it started in March 2014. This paper presents the first public data release of HSC-SSP. This release includes data taken in the first 1.7 years of observations (61.5 nights) and each of the Wide, Deep, and UltraDeep layers covers about 108, 26, and 4 square degrees down to depths of i~26.4, ~26.5, and ~27.0 mag, respectively (5sigma for point sources). All the layers are observed in five broad bands (grizy), and the Deep and UltraDeep layers are observed in narrow bands as well. We achieve an impressive image quality of 0.6 arcsec in the i-band in the Wide layer. We show that we achieve 1-2 per cent PSF photometry (rms) both internally and externally (against Pan-STARRS1), and ~10 mas and 40 mas internal and external astrometric accuracy, respectively. Both the calibrated images and catalogs are made available to the community through dedicated user interfaces and database servers. In addition to the pipeline products, we also provide value-added products such as photometric redshifts and a collection of public spectroscopic redshifts. Detailed descriptions of all the data can be found online. The data release website is https://hsc-release.mtk.nao.ac.jp/.Comment: 34 pages, 20 figures, 7 tables, moderate revision, accepted for publication in PAS

川崎医科大学におけるブース形式診療科別説明会の学内開催

川崎医科大学は,中核市の倉敷市内と政令指定都市の岡山市内に二つの附属病院を有している。両病院の卒後臨床研修プログラムは独立しているが,研修は両方の病院の診療科から選択することが可能である。平成27年7月,初めて川崎医科大学生を対象にした大学附属病院診療科の説明会をブース形式で学内開催した。研修プログラム説明会とは趣を異にし,各診療科の特徴や業務内容を広報することを目的とした。1年生から6年生までの学生が参加し,アンケート調査に回答した52名全員が将来の研修病院の選択に役に立ったと答え,うち27%は非常に役立ったと高い満足度を示した。また,研修医だけで計画した学生向けのミニシンポジウムも同時に開催し,来場した約70%の学生が参加し貴重な情報収集の場となった。次年度以降も改善を加えながら,学生が身近に附属病院スタッフや先輩研修医と交流できるイベントとして育てていきたい。Kawasaki Medical School has one hospital in Kurashiki City, a core city, and another in Okayama City, an ordinance-designated city. These hospitals have independent postgraduate clinical training programs. However, departments of both hospitals can be selected for training. In July 2015, a boothtype meeting regarding Kawasaki Medical School Hospital departments was held for Kawasaki Medical School students for the first time. The intent of the meeting differed from that of other training program meetings, and its goal was to provide information on the characteristics and tasks of each department. First- to sixth-year students participated in the meeting. All 52 students who responded to a questionnaire survey answered that the meeting was useful in helping them select a hospital for their future training, and 27% of them reported that the meeting was very useful and showed high levels of satisfaction. A mini symposium for students planned only by residents was also held at the same time. About 70% of visiting students participated in the symposium and were given a valuable opportunity to gather information. By making improvements, we will cultivate the meeting as an event in which students can have contact with hospital staff and junior residents from the next year