Large-Scaled Chain Stores versus Small-Scaled Local Stores of the Local Production for Local Consumption

* Revised： [15-16, 2015]* Revised：Large-Scaled Chain Stores versus Small-Scaled Local Stores [15-16-Rev., 2015]* Revised： [15-16-Rev.2, 2015

Large-Scaled Chain Stores versus Small-Scaled Local Stores of the Local Production for Local Consumption

* Revised： [15-16, 2015]* Revised：Large-Scaled Chain Stores versus Small-Scaled Local Stores [15-16-Rev., 2015]* Revised： [15-16-Rev.2, 2015

自己集合する足場タンパク質を用いた汎用的なP450活性化システムの構築

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 長棟 輝行, 東京大学教授 高井 まどか, 東京大学教授 津本 浩平, 東京大学教授 岡本 晃充, 東京大学准教授 伊藤 大知University of Tokyo(東京大学

Neurophysiological Analysis of Intermanual Transfer in Motor Learning

The purpose of this study was to examine the effect of motor training on motor imagery (MI), by comparing motor performance and motor cortex excitability changes with and without intermanual transfer of motor learning. Intermanual transfer was investigated in terms of excitability changes in the motor cortex and motor performance from right hand training to left hand performance. Participants were assigned to a transfer training group and a control group. We recorded motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS), applied to the left extensor carpi radialis (ECR) both with and without intermanual transfer. The results showed that after learning by the right hand, MEPs decreased during left hand MI. MEPs during MI were significantly decreased by unilateral training in the transfer training group. Since intermanual transfer plays an important role in stabilizing performance by the contralateral side, this result suggests that unilateral training decreases MEPs during MI on the contralateral side. In the control group, without right hand training, MEPs significantly increased after left hand training during MI. In the trained side, we found increased excitability in the agonist muscle area of the primary motor cortex. However, in the untrained side, excitability decreased in the homonymous muscle area of the primary motor cortex. This constitutes an increase in inhibitory effects and suggests that excitability changes in the respective neural circuit contribute to skilled performance by the ipsilateral and contralateral sides in the same motor task

Anti-CENP-C Antibody-Based Immunofluorescence Dicentric Assay: Radiation Dose-Response, Validation Studies, and Radiation Dose-Dependency on Sister Centromere Fluorescence

Dicentric chromosome assay (DCA) is the most accepted cytological technique for the purpose of biological dosimetry in radiological and nuclear accidents, however, it is not always easy to evaluate dicentric chromosomes because of the technical difficulty in identifying dicentric chromosomes on Giemsa-stained metaphase chromosome samples. Here, we applied an antibody recognizing centromere protein (CENP) C, CENP-C, whose antigenicity is resistant to the fixation with Carnoy\u27s solution. Normal human diploid cells were irradiated with various doses of 137Cs γ rays at 1 Gy/ min, treated with hypotonic solution, fixed with Carnoy\u27s fixative, and metaphase chromosome spreads were stained with anti-CENP-C antibody. Dose-dependent induction of dicentric chromosomes was confirmed between 1 and 10 Gy of γ rays, and the results were compatible with those obtained by the conventional Giemsa-stained chromosome samples. The CENP-C assay also uncovered the difference in the fluorescence from the sister centromeres on the same chromosome, which was more pronounced after radiation exposure. Although the underlying mechanism is still to be determined, the result suggests a novel effect of radiation on centromeres. The innovative protocol for CENP-C-based DCA, which enables ideal visualization of centromeres, is simple, effective and reliable. It does not require skilled examiners, so that it may be an alternative method, avoiding uneasiness of the current DCA using Giemsa-stained metaphase chromosome samples

High Mobility Group Box 1 Expression in Oral Inflammation and Regeneration

High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein of about 30 kDa. It is released from a variety of cells into the extracellular milieu in response to inflammatory stimuli and acts on specific cell-surface receptors, such as receptors for advanced glycation end-products (RAGE), Toll-like receptor (TLR)2, TLR4, with or without forming a complex with other molecules. HMGB1 mediates various mechanisms such as inflammation, cell migration, proliferation, and differentiation. On the other hand, HMGB1 enhances chemotaxis acting through the C-X-C motif chemokine ligand (CXCL)12/C-X-C chemokine receptor (CXCR)4 axis and is involved in regeneration. In the oral cavity, high levels of HMGB1 have been detected in the gingival tissue from periodontitis and peri-implantitis patients, and it has been shown that secreted HMGB1 induces pro-inflammatory cytokine expression, such as interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha, which prolong inflammation. In contrast, wound healing after tooth extraction or titanium dental implant osseointegration requires an initial acute inflammation, which is regulated by secreted HMGB1. This indicates that secreted HMGB1 regulates angiogenesis and bone remodeling by osteoclast and osteoblast activation and promotes bone healing in oral tissue repair. Therefore, HMGB1 can prolong inflammation in the periodontal tissue and, conversely, can regenerate or repair damaged tissues in the oral cavity. In this review, we highlight the role of HMGB1 in the oral cavity by comparing its function and regulation with its function in other diseases. We also discuss the necessity for further studies in this field to provide more specific scientific evidence for dentistry

Postnatal lethality and chondrodysplasia in mice lacking both chondroitin sulfate N-acetylgalactosaminyltransferase-1 and -2

Chondroitin sulfate (CS) is a sulfated glycosaminoglycan (GAG) chain. In cartilage, CS plays important roles as the main component of the extracellular matrix (ECM), existing as side chains of the major cartilage proteoglycan, aggrecan. Six glycosyltransferases are known to coordinately synthesize the backbone structure of CS; however, their in vivo synthetic mechanism remains unknown. Previous studies have suggested that two glycosyltransferases, Csgalnact1 (t1) and Csgalnact2 (t2), are critical for initiation of CS synthesis in vitro. Indeed, t1 single knockout mice (t1 KO) exhibit slight dwarfism and a reduction in CS content in cartilage compared with wild-type (WT) mice. To reveal the synergetic roles of t1 and t2 in CS synthesis in vivo, we generated systemic single and double knockout (DKO) mice and cartilage-specific t1 and t2 double knockout (Col2-DKO) mice. DKO mice exhibited postnatal lethality, whereas t2 KO mice showed normal size and skeletal development. Col2-DKO mice survived to adulthood and showed severe dwarfism compared with t1 KO mice. Histological analysis of epiphyseal cartilage from Col2-DKO mice revealed disrupted endochondral ossification, characterized by drastic GAG reduction in the ECM. Moreover, DKO cartilage had reduced chondrocyte proliferation and an increased number of apoptotic chondrocytes compared with WT cartilage. Conversely, primary chondrocyte cultures from Col2-DKO knee cartilage had the same proliferation rate as WT chondrocytes and low GAG expression levels, indicating that the chondrocytes themselves had an intact proliferative ability. Quantitative RT-PCR analysis of E18.5 cartilage showed that the expression levels of Col2a1 and Ptch1 transcripts tended to decrease in DKO compared with those in WT mice. The CS content in DKO cartilage was decreased compared with that in t1 KO cartilage but was not completely absent. These results suggest that aberrant ECM caused by CS reduction disrupted endochondral ossification. Overall, we propose that both t1 and t2 are necessary for CS synthesis and normal chondrocyte differentiation but are not sufficient for all CS synthesis in cartilage

<資料>見えにくさを補う手段の違いが弱視学生支援に対する健常学生の態度に及ぼす効果

本研究は、弱視学生が見えにくさを補う手段（弱視レンズ条件・接近視条件・タブレット条件）を使いながら学習・生活する様子を画像で提示した場合に、それらが健常学生の態度に及ぼす効果の違いを検討した。382名の健常学生に対し、弱視学生の画像付き説明文に基づく3条件を無作為にひとつ提示し、障害者イメージ尺度（不便さ尺度・尊敬尺度）、弱視学生支援サービス尺度（授業支援尺度・成績評価尺度・組織支援尺度）への回答を求めた。その結果、タブレット条件と接近視条件のときの方が不便なイメージになったものの、弱視学生支援に関するすべての下位尺度でタブレット条件のときの方が他の条件よりも消極的な評価になった。また、健常学生は女子の方が男子よりも肯定的なイメージを持ち、弱視学生支援に対する態度もすべての下位尺度で肯定的であった。これらの結果が弱視学生の障害開示や援助要請を補助する手立ての手がかりになるものと示唆された。The purpose of the present study was to examine effects of difference in means to decrease visual difficulty (utilization of tablet, low vision aids, or close-proximity vision) on nondisabled college students\u27 attitudes toward academic supports for peers with low vision. Participants were instructed that they received disability disclosure and help seeking by student with low vision. After reading disability disclosure sentences, students without disabilities (N = 382) answered a questionnaire based on interpersonal image and attitude toward support service for students with low vision. The results showed that conditions of using tablet and close-proximity vision gave more difficult image than that of using low vision aids. However, condition of using tablet induced more negative attitude toward academic support for students with low vision than another conditions. On the other hand, women perceived positive image compared to men. Moreover, women also had more positive attitude toward support service for students with low vision. In conclusion, these results will help students with low vision to choose the method disability disclosure and help seeking

Nr5a1 suppression during the murine fetal period optimizes ovarian development by fine-tuning Notch signaling

The nuclear receptor NR5A1 is equally expressed and required for development of the gonadal primordia of both sexes, but, after sex determination, it is upregulated in XY testes and downregulated in XX ovaries. We have recently demonstrated, in mice, that this downregulation is mediated by forkhead box L2 (FOXL2) and hypothesized that adequate suppression of Nr5a1 is essential for normal ovarian development. Further, analysis of human patients with disorders/differences of sex development suggests that overexpression of NR5A1 can result in XX (ovo)testicular development. Here, we tested the role of Nr5a1 by overexpression in fetal gonads using a Wt1-BAC (bacterial artificial chromosome) transgene system. Enforced Nr5a1 expression compromised ovarian development in 46,XX mice, resulting in late-onset infertility, but did not induce (ovo)testis differentiation. The phenotype was similar to that of XX mice lacking Notch signaling. The expression level of Notch2 was significantly reduced in Nr5a1 transgenic mice, and the ovarian phenotype was almost completely rescued by in utero treatment with a NOTCH2 agonist. We conclude that suppression of Nr5a1 during the fetal period optimizes ovarian development by finetuning Notch signaling