成体マウス脳の成熟および未成熟オリゴデンドロサイトにおけるコルチコイステロイドレセプタ−の分布

The expression of glucocorticoid receptors (GRs) was investigated immunohistochemically in two different lineages of oligodendrocytes, using carbonic anhydrase (CA) II and neuron glial antigen (NG) 2 as markers of mature oligodendrocytes and oligodendrocyte progenitors, respectively. We focused on the gray matter regions, including CA1, CA3 and the dentate gyrus of the hippocampus, the primary somatosensory cortex barrel field and the basolateral amygdala, and the white matter regions, including the corpus callosum, external capsule and fimbria of the hippocampus. More than 80% of CAII-immunoreactive (IR) cells and more than 95% of NG2-IR cells expressed GRs in various regions of the brain. In contrast, neither CAII-IR cells nor NG2-IR cells expressed mineralocorticoid receptors (MRs) in the same regions. The intensity of GR expression was drastically reduced in CA II-IR cells and NG2-IR cells in the same regions in adrenalectomized mice. Finally, steroid receptor co-activator (SRC)-1 and p300, both of which are cofactors for GR, were expressed in the gray and white matter regions in NG2-IR cells, but not in CAII-IR cells. These results suggest that the expression of GRs in oligodendrocytes and their progenitor cells mediates several functions in vivo, including differentiation and myelination, as a major target of glucocorticoids and their cofactors.博士（医学）・甲620号・平成26年3月17日Copyright © 2014 by The Histochemical Societ

母子分離ストレスが報酬探索行動に及ぼす影響と側坐核におけるドーパミンD1受容体のDNAのメチル化機構を介した発現変化について

Early-life stress has long-lasting effects on the stress response, emotions, and behavior throughout an individual’s life. Clinical reports have demonstrated that child abuse victims exhibit impairments in reward-associated behavior; yet, the mechanism for this effect remains unclear. Maternal separation (MS) or MS coupled with social isolation (SI) (MS + SI) is widely used as a model for early-life stress in rodent studies. We employed mice subjected to MS + SI to clarify the long-term effect of early-life stress on reward-seeking involving palatable foods by a conditioned place-preference (CPP) paradigm. Prior MS + SI experience decreased exploration time in a chocolate-paired compartment in adult female mice, but not in male mice. We then focused on the mesolimbic dopamine pathway associated with reward-seeking behavior and measured both mRNA and protein levels of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and dopamine D1 and D2 receptors in the nucleus accumbens (NAc). MS + SI female mice had significantly lower D1 receptor mRNA and protein levels than controls, whereas the expression of TH and the D2 receptor was similar in the 2 groups. All mRNA and protein levels were unchanged in MS + SI male mice. When attempting to elucidate the mechanism underlying downregulation of the D1 receptor in the NAc of MS + SI females, we found hypermethylation of the Drd1a promoter region. These results suggest that early-life stress affects reward-seeking behavior in female mice, which may be associated with the downregulation of D1 receptor in the NAc via epigenetic modification of its promoter region.博士（医学）・甲第672号・平成29年6月28日Copyright © 2017 Elsevier B.V. All rights reserved

骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。

OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats. METHODS BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemical analyses using anti-Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale. RESULTS The BMSC sheets promoted axonal regeneration at 2 weeks after transplantation, but there was no significant difference in the number of Tuj1-positive axons between the sheet- and GS-transplanted groups. At 8 weeks after transplantation, Tuj1-positive axons elongated across the sheet, and their numbers were significantly greater in the sheet group than in the GS group. The areas of GFAP-positive glial scars in the sheet group were significantly reduced compared with those of the GS group at both time points. Finally, hindlimb locomotor function was ameliorated in the sheet group at 4 and 8 weeks after transplantation. CONCLUSIONS The results of the present study indicate that an ascorbic acid-induced BMSC sheet is effective in the treatment of SCI and enables autologous transplantation without requiring a scaffold.博士（医学）・甲第656号・平成28年11月24日© Copyright 2016 American Association of Neurological SurgeonsThe definitive version is available at " http://dx.doi.org/10.3171/2016.8.SPINE16250

Screening for resistance against Pseudomonas syringae in rice-FOX Arabidopsis lines identified a putative receptor-like cytoplasmic kinase gene that confers resistance to major bacterial and fungal pathogens in Arabidopsis and rice

Approximately 20 000 of the rice-FOX Arabidopsis transgenic lines, which overexpress 13 000 rice full-length cDNAs at random in Arabidopsis, were screened for bacterial disease resistance by dip inoculation with Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). The identities of the overexpressed genes were determined in 72 lines that showed consistent resistance after three independent screens. Pst DC3000 resistance was verified for 19 genes by characterizing other independent Arabidopsis lines for the same genes in the original rice-FOX hunting population or obtained by reintroducing the genes into ecotype Columbia by floral dip transformation. Thirteen lines of these 72 selections were also resistant to the fungal pathogen Colletotrichum higginsianum. Eight genes that conferred resistance to Pst DC3000 in Arabidopsis have been introduced into rice for overexpression, and transformants were evaluated for resistance to the rice bacterial pathogen, Xanthomonas oryzae pv. oryzae. One of the transgenic rice lines was highly resistant to Xanthomonas oryzae pv. oryzae. Interestingly, this line also showed remarkably high resistance to Magnaporthe grisea, the fungal pathogen causing rice blast, which is the most devastating rice disease in many countries. The causal rice gene, encoding a putative receptor-like cytoplasmic kinase, was therefore designated as BROAD-SPECTRUM RESISTANCE 1. Our results demonstrate the utility of the rice-FOX Arabidopsis lines as a tool for the identification of genes involved in plant defence and suggest the presence of a defence mechanism common between monocots and dicots

An easy-to-machine electrochemical flow microreactor: efficient synthesis of isoindolinone and flow functionalization

Flow electrochemistry is an efficient methodology to generate radical intermediates. An electrochemical flow microreactor has been designed and manufactured to improve the efficiency of electrochemical flow reactions. With this device only little or no supporting electrolytes are needed, making processes less costly and enabling easier purification. This is demonstrated by the facile synthesis of amidyl radicals used in intramolecular hydroaminations to produce isoindolinones. The combination with inline mass spectrometry facilitates a much easier combination of chemical steps in a single flow proces

地域特性からみた人々の生活を支援する保健医療の課題

地域特性からみた住民の生活と保健医療の課題を明らかにするため文献検討した。農村部、島嶼部、都市部は、共通して「終活に向けての取り組み」「高齢者の健康や生活状況」「地域住民の交流」「地域住民の見守りや支援ネットワーク」「保健医療福祉の資源とケアシステム」の５つのカテゴリが抽出された。また、この他、農村部と都市部は「精神保健上の支援と課題」のカテゴリも抽出され、６つのカテゴリに収束した。その中で農村部は、広い圏域をカバーするため、専門職の人材確保に加え、住民の中の仔細な支援関係に柔軟に対応できる専門職の力量形成が求められる。都市部は、孤独死防止等の課題もあるため、見守り活動等の住民協働による新たな地域包括ケアシステムの構築が望まれる。島嶼部は、限られた医療環境の中で実践するため、保健医療職の知識や技術の向上を目指した取り組みや住民の暮らしを維持するための包括的・継続的な保健医療の支援が求められる

PlGF Repairs Myocardial Ischemia through Mechanisms of Angiogenesis, Cardioprotection and Recruitment of Myo-Angiogenic Competent Marrow Progenitors

Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM) cells, recent clinical trials have revealed less benefit from these therapies than expected.We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF), a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity.Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1(+)/Lin(-) (SL) BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage.Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease

Belle II Technical Design Report

The Belle detector at the KEKB electron-positron collider has collected almost 1 billion Y(4S) events in its decade of operation. Super-KEKB, an upgrade of KEKB is under construction, to increase the luminosity by two orders of magnitude during a three-year shutdown, with an ultimate goal of 8E35 /cm^2 /s luminosity. To exploit the increased luminosity, an upgrade of the Belle detector has been proposed. A new international collaboration Belle-II, is being formed. The Technical Design Report presents physics motivation, basic methods of the accelerator upgrade, as well as key improvements of the detector.Comment: Edited by: Z. Dole\v{z}al and S. Un