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    Increased ectodomain shedding of lung-epithelial cell adhesion molecule 1 as a cause of increased alveolar cell apoptosis in emphysema

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    研究代表者publisher研究種目:若手研究(B); 研究期間:2013~2014; 課題番号:25860302; 研究分野:実験病理; 科研費の分科・細目:研究成果の概要(和文): 肺気腫の原因である蛋白分解酵素活性上昇と肺胞上皮アポトーシスを結び付ける分子機序は不明であった. 肺胞上皮の接着分子CADM1の機能的制御に細胞外切断(shedding)がある. ウエスタン法にて肺気腫ではsheddinが亢進し, TUNEL法にて肺胞上皮アポトーシスの上昇が判明した. ヒト肺上皮細胞株NCI-H441細胞においてCADM1のsheddingを惹起させた所, shedding産物であるαCTFがミトコンドリアに局在し, アポトーシスが上昇することを見出した. 肺気腫ではCADM1のsheddingが亢進し, αCTFがミトコンドリアに集積して肺胞上皮アポトーシスを促進していると考えられた. 研究成果の概要(英文): Alveolar epithelial cell apoptosis and proteolysis play central roles in the pathogenesis of emphysema, but molecular mechanisms underlying these two events are not yet clearly understood. CADM1 is a lung-epithelial cell adhesion molecule and generates membrane-associated C-terminal fragments (CTFs) through protease-mediated ectodomain shedding. Western blot analyses revealed that CADM1-CTFs increased in human emphysematous lungs in association with increased ectodomain shedding. Increased apoptosis of alveolar epithelial cells in emphysematous lungs was confirmed by TUNEL assays. NCI-H441 lung epithelial cells expressing mature CADM1 but not CTFs were induced to express αCTF by shedding inducers; phorbol ester and trypsin. Immunofluorescence and TUNEL assays revealed that CADM1-αCTF was localised to mitochondria and increased cell apoptosis. CADM1 shedding appeared to cause alveolar cell apoptosis in emphysematous lungs by producing αCTF that accumulated in mitochondria

    Approach from muscle to bone and cartilage regeneration and development of the treatment of diseases

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    研究代表者publisher研究種目:若手研究(B); 研究期間:2013~2014; 課題番号:25861347; 研究分野:医歯薬学; 科研費の分科・細目:研究成果の概要(和文): 本研究では筋組織が骨・軟骨再生を誘導する機序を明らかにすることを目的として, 筋組織での異所性骨化を破骨細胞形成の観点から検討した. 筋組織では皮下組織と比較して, 筋芽細胞とBMP-2の移植による異所性骨化が増加し, また破骨細胞の増加が見られた. さらに, 進行性骨化性線維異形成症の原因遺伝子である活性型BMP受容体を強制発現させた筋芽細胞はin vivoおよびin vitroにおいてTGF-βの発現を増加させ破骨細胞分化を促進することが明らかとなった. 以上より, 筋芽細胞が破骨細胞形成を促進して骨・軟骨再生を誘導することが示唆された. 研究成果の概要(英文): We investigated the role of osteoclasts during heterotopic bone formation in muscle tissue. The implantation of myoblasts with BMP-2 induced robust heterotopic ossification with an increase in the formation of osteoclasts in the muscle tissues than subcutaneous tissues. Moreover, the causal mutation transfection of fibrodysplasia ossification progressive in myoblasts enhanced the formation of osteoclasts through TGF-β in vivo and in vitro. This study demonstrated that the causal mutation transfection of fibrodysplasia ossification progressive in myoblasts enhances bone and cartilage regeneration through formation of osteoclasts from its precursor in muscle tissues

    表紙・目次・ほか 4(1) 2015

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    publisher表紙デザイン(前田, 大介

    〈論文〉総合依存, 国際機構とスマートパワー--ネオリベラル世界におけるオバマのネオリベラル外交

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    publisher専攻: 異文化コミュニケーション・国際関係(Abstract) The fall of the Berlin Wall has ushered in a neoliberal world order characterized by the rise of a number of powerful state and non-state actors. The fundamental liberal principles of the old Post World War II order remain the same including open trade, support for the rule of law and a commitment to human rights. However, financial and technology revolutions have transformed the global order in that multiple actors now have numerous channels to interact with each other. This paper argues, given this new global order, that the neoliberal theoretical framework and its respective policies tools adopted by the Obama administration are appropriate. The main tenets of the neoliberal framework and its policy instruments as outlined here are interdependence, institutions and smart power. Neoliberal theory contends that the agenda of analysis for international relations has expanded far beyond the narrow confines of security policy to fields such as economics, environment, health and sociocultural interchange. In fact, the impact of these areas on security policy, particularly in a context of high interdependence, has substantially diminished the value of hard power as a foreign policy tool. Obama has recognized the changing nature of the global order and adopted the use of economic interdependence, institutions and smart power to modify the behavior of other states. The main challenge confronting the United States is to retain its central role within the neoliberal order while managing the peaceful rise of other states

    Analysis and evaluation of plastic ankle foot orthosis (PAFO) based on quantitative data

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    研究代表者publisher研究種目:基盤研究(C); 研究期間:2012~2014; 課題番号:24500666; 研究分野:人間医工学, 日本リハビリテーション科学・福祉工学; 科研費の分科・細目:研究成果の概要(和文): 本研究では, 健常者および装具使用者の歩行データから得られた装具にかかる荷重データをもとに, 取得した装具の3次元形状データと有限要素解析ソフトを用いて, 装具にかかる応力や変形を分析した. 初めに, 被験者の歩行中に装具にかかる力を装具脹脛部分に設置した6軸力覚センサを用いて健常者と装具使用者のデータを測定した. 測定の結果, 装具前後方向の荷重が健常者と装具使用者で異なることが分かり, 同データが評価指標となる可能性が見出された. ついで, スキャナで獲得した装具形状に対し同データを外力として加えた有限要素解析を実施した. さらに, 同手法を用いて装具をトリミングしたときの応力集中や変形などの状態を分析した. 研究成果の概要(英文): This study reports on an analysis of the deformation and stress on an orthosis using its 3D shape data and finite element analysis software. The analysis is based on orthosis load data obtained from ambulatory data of healthy participants and orthosis users. First, the forces acting on an orthosis during ambulation of participants were measured using a six-axis force torque sensor installed in the calf section. The data revealed that there is a significant difference in anterior-posterior loads, which may be an important evaluation index of orthotic ambulation, between orthosis users and healthy participants. These data were applied as an external force to the orthosis shape obtained using a scanner and subjected to finite element analysis. Then, we analyze stress concentrations and deformations of orthoses modified by trimming when a given load was applied to them

    Regulatory mechanisms of MAPK signaling and its application to chemicalgenomics

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    研究代表者研究分担者研究分担者研究分担者publisher研究種目:基盤研究(B); 研究期間:2011~2014; 課題番号:23390021; 研究分野:分子遺伝学, 細胞生物学, ゲノム薬理学, 分子細胞生物学, シグナル伝達, ゲノム創薬; 科研費の分科・細目:研究成果の概要(和文): 本研究は, 遺伝学的と薬理学を融合した独自のケミカルゲノミクスを展開し, その成果として, 細胞増殖とがん化の鍵を握るマップキナーゼ(MAPK)シグナルの調節機構を明らかにし, MAPKシグナルを標的とした創薬を展開した. 具体的には, MAPKの活性化に関わる遺伝子群や標的遺伝子の同定に加え、MAPKシグナルを制御できる化合物を発見した. さらに, 免疫抑制薬であるFK506, RapamycinやFTY720の感受性を決定する遺伝子群を同定し, これらの遺伝子とMAPK経路のクロストーク機構を明らかにした. これらの成果は, MAPKシグナルの破綻が引き起こすがんを始めとした疾患治療法開発に貢献する. 研究成果の概要(英文): The purpose of this research project was to elucidate novel regulatory mechanisms of the Pmk1 MAPK signaling pathway in fission yeast and its application to genome-based drug discovery. We performed chemicalgenomics screens, utilizing the functional interaction between MAPK and calcineurin, and identified regulators (such as Cwg2, Rho4 and Rho5) and targets of Pmk1 MAPK in addition to several compounds that modify the ERK MAPK signaling pathway in mammals. Furthermore, we performed genome-wide identification of the genes involved in the sensitivities to FK506, Rapamycin and FTY720 and elucidated as-yet-unidentified functional interactions between MAPK and these gene products. Collectively, our data will contribute to the development of novel and effective therapeutic approaches for diseases associated with abrogated MAPK signaling activity

    Application of inhibitory method of pancreatic cancer cell growth by the regulation of lumican glycosylation using therapeutic peptides.

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    研究代表者publisher研究種目:基盤研究(C); 研究期間:2012~2014; 課題番号:24591019; 研究分野:医歯薬科学; 科研費の分科・細目:研究成果の概要(和文): ルミカンの発現量と細胞増殖能には正の相関性があり, 細胞浸潤能とは負の相関性があることが報告されている. 今回, ルミカンが膵癌細胞の増殖や浸潤に関わる機構について検討するため, ルミカン発現調製細胞を用い, それらの細胞の発現タンパク質の変動を網羅的に解析した. その結果, 24種類のタンパク質がルミカンの発現と相関性があることが明らかとなった. この中にはアポトーシスのマーカーとして知られているタンパク質やMMP-9の活性化と関連があるタンパク質が含まれていたことから、ルミカンはアポトーシスやこれらのタンパク質の発現に関わることで細胞増殖や浸潤を制御していると考えられた. 研究成果の概要(英文): It has been reported that lumican expression level showed positive correlation with cell growth of pancreatic ductal adenocarcinoma (PDAC) cells and showed negative correlation with cell invasion of PDAC cells. In this study, we performed global shotgun proteomic analysis using lumican-regulated PANC-1 cells to examine the effect of lumican on cell growth and invasion in PDAC cells. As a result of proteomics, 24 proteins were identified as candidate proteins which expression was regulated by lumican, and these candidate proteins included protein which is known apoptosis marker and protein which regulate MMP-9 activation. Thus, lumican might be involved in cell growth and invasion to regulate cell apoptosis and these proteins expression

    Empirical studies on the diffusion and scope of dynamic externalities in geographical and technological space

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    研究代表者publisher研究種目:若手研究(B); 研究期間:2012~2014; 課題番号:24730231; 研究分野:地域経済学・都市経済学; 科研費の分科・細目:研究成果の概要(和文): 本研究では、第一に, 探索的空間データ分析の手法により「成長クラスター」(技術的に近接にある成長産業の地理的な集積)を検出した. 第二に, 検出された成長クラスターの形成に, どのようなタイプの動学的外部性が寄与しているのかを空間計量経済モデルを構築して分析した. 名古屋大都市圏を対象にした分析によれば, 成長クラスターのコア部の形成には, 輸送用機械と技術的に近接にある各種多様な製造業やサービス業の間での外部性の波及が寄与している. 一方でクラスター縁辺部は輸送用機械と電気機械のみにより形成されており, 同一産業内の外部性がクラスター内の広い範囲に波及してそれら産業の成長に寄与していることが分析された. 研究成果の概要(英文): In this study, we first apply the methods of exploratory spatial data analysis (ESDA) and investigate the geographical concentration of nterrelated growing industries, or “growth clusters,” by using data from the Nagoya metropolitan area in Japan. Second, by applying spatial econometric models, we examine whether and which type of knowledge externalities contribute to region-industry dynamics and to the formation of the detected growth cluster. The core of the cluster is made up of manufacturing industries, but also includes several service sectors. The periphery of the cluster has less variety, mainly including the transportation equipment and electrical machinery industries. We find that intra-industry externalities that diffuse over a broader area within the cluster help the steady growth of the transportation equipment industry. In the core of the cluster, the diversified interrelated structure also contributes to the growth of the auto-related manufacturingsectors

    〈Articles〉The Long-term Careers of Brazilian Migrant Workers in Japan--A Qualitative Analysis as a Pilot Study

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    publisher[概要]本研究の目的は, パイロット・インタビュー調査を通じて, 日系ブラジル人労働者の長期的なキャリアを考察することである. 日系ブラジル人労働者を対象としたキャリアの先行研究はほとんどなく, 彼らのキャリアにどのような特徴があるのか示されてこなかった. そこで, 実際に日本で働く日系ブラジル人労働者のキャリアを詳しく分析した. 彼らのキャリア段階は4つに分けることができ, それぞれの段階にその後のキャリア行動に影響を与える要因が関連していることがわかった. また, 彼らを取り巻く文脈的要因が重層的に関連しており, 外国人労働者のキャリア研究では, 文脈的観点から複数の要因の関連性を検討することが重要であることを示す. [Abstract]This article examines the long-term careers of Brazilian migrant workers in Japan from results of a pilot study. Previous studies haven't demonstrated the issues of their careers because few researches have been conducted. We investigated the actual work-life careers of Brazilian workers in Japanese factories and offices. The results suggest that they have four career stages, and multiple influences interact at each career stage. This article addresses the importance of considering the relevance among their influences from a contextual perspective

    [巻頭言] 「変わること, 変わらないこと」

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