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Mechanosensing Mechanisms for Sensing Mechanical Stress Including Gravitational Changes

Planned Research

Project Area"LIVING IN SPACE" - Integral Understanding of life-regulation mechanism from "SPACE"
Project/Area Number 15H05936
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionOkayama University

Principal Investigator

Naruse Keiji  岡山大学, 医歯薬学総合研究科, 教授 (40252233)

Co-Investigator(Kenkyū-buntansha) 曽我部 正博  名古屋大学, 医学系研究科, 研究員 (10093428)
小林 剛  名古屋大学, 医学系研究科, 講師 (40402565)
高橋 賢  岡山大学, 医歯薬学総合研究科, 助教 (50432258)
Project Period (FY) 2015-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥95,030,000 (Direct Cost: ¥73,100,000、Indirect Cost: ¥21,930,000)
Fiscal Year 2019: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2018: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2017: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2015: ¥28,470,000 (Direct Cost: ¥21,900,000、Indirect Cost: ¥6,570,000)
Keywords宇宙 / 宇宙生物学 / 宇宙医学 / メカノバイオロジー / 重力 / 圧力 / 回転蛍光顕微鏡 / YAP / PKC / 血管内皮細胞 / 機械刺激受容チャネル / 機械刺激 / 遠心顕微鏡 / 模擬微小重力 / iPS細胞 / 微小重力 / 過重力 / 細胞内シグナル伝達 / メカノセンシング / 力学的ストレス / 動物細胞
Outline of Final Research Achievements

This study developed a centrifugal fluorescence microscope system that can observe the gravity response of cells in real time. In this way, we succeeded in live imaging of morphological changes of cells due to gravitational stimulation by rotation for several tens of minutes.
We also discovered a new mechanism for the gravity sensing of cells. In space, the bone density of astronauts decreases. In agreement with this, simulated microgravity acts as a suppressive factor in bone differentiation of mesenchymal stem cells. Our results suggest that the activity of the mechanosensitive ion channel TRPV4 is reduced in the simulated microgravity environment, and the activity of the protein kinase C is subsequently reduced to suppress the nuclear translocation of the transcriptional cofactor YAP. In addition, we have also developed a statistical method for uniformly analyzing gene expression levels among different species.

Academic Significance and Societal Importance of the Research Achievements

本研究は遠心蛍光顕微鏡システムの開発により、重力による細胞内小器官の形態的変化をリアルタイムで捉える技術を確立した。これにより、筋、骨、心血管系など、あらゆる細胞の重力感知機構を明らかにするためのプラットフォームが与えられた。
また重力が間葉系幹細胞の骨分化に影響を及ぼすメカニズムの一端を解明した。これにより、長期宇宙滞在による骨密度低下を抑制する方法の手がかりが得られた。
さらに、本研究は異種間の遺伝子発現量解析を統一的に行う手法も開発した。DNAアレイやRNA-seqのデータは高価だが、既存のデータベースのデータを活用することにより、宇宙医学の発展が加速すると期待される。

Report

(6 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (128 results)

All 2020 2019 2018 2017 2016 2015 Other

All Journal Article (35 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 29 results,  Open Access: 21 results,  Acknowledgement Compliant: 1 results) Presentation (83 results) (of which Int'l Joint Research: 29 results,  Invited: 57 results) Book (6 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Increased hydrostatic pressure induces nuclear translocation of DAF-16/FOXO in C.elegans2020

    • Author(s)
      Watanabe Naoshi、Morimatsu Masatoshi、Fujita Ayano、Teranishi Mika、Sudevan Surabhi、Watanabe Masaru、Iwasa Hiroaki、Hata Yutaka、Kagi Hiroyuki、Nishiyama Masayoshi、Naruse Keiji、Higashitani Atsushi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 523 Issue: 4 Pages: 853-858

    • DOI

      10.1016/j.bbrc.2020.01.047

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] L-type calcium channel modulates mechanosensitivity of the cardiomyocyte cell line H9c22019

    • Author(s)
      Ken Takahashi, Shogo Hayashi, Mari Miyajima, Marei Omori, Jing Wang, Keiko Kaihara, Masatoshi Morimatsu, Chen Wang, Jian Chen, Gentaro Iribe, Keiji Naruse, Masahiro Sokabe
    • Journal Title

      Cell Calcium

      Volume: 79 Pages: 68-74

    • DOI

      10.1016/j.ceca.2019.02.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Real-Time Single-Molecule Kinetic Analyses of AIP1-Enhanced Actin Filament Severing in the Presence of Cofilin.2019

    • Author(s)
      Hayakawa, K., C. Sekiguchi, M. Sokabe, S. Ono, and H. Tatsumi
    • Journal Title

      J Mol Biol.

      Volume: 431 Issue: 2 Pages: 308-322

    • DOI

      10.1016/j.jmb.2018.11.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tensile Loads on Tethered Actin Filaments Induce Accumulation of Cell Adhesion-Associated Proteins in Vitro.2019

    • Author(s)
      Kiyoshima, D., H. Tatsumi, H. Hirata, and M. Sokabe. 2018
    • Journal Title

      Langmuir

      Volume: 印刷中 Issue: 23 Pages: 7443-7451

    • DOI

      10.1021/acs.langmuir.8b02076

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanomedicine2018

    • Author(s)
      Naruse Keiji
    • Journal Title

      Biophysical Reviews

      Volume: 10 Issue: 5 Pages: 1257-1262

    • DOI

      10.1007/s12551-018-0459-7

    • NAID

      130007885104

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MECHANOMEDICINE: applications of mechanobiology to medical sciences and next-generation medical technologies2018

    • Author(s)
      NARUSE Keiji
    • Journal Title

      Journal of Smooth Muscle Research

      Volume: 54 Issue: 0 Pages: 83-90

    • DOI

      10.1540/jsmr.54.83

    • NAID

      130007483121

    • ISSN
      0916-8737, 1884-8796
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 特集:宇宙の極限環境から生命体の可塑性をさぐる--1.重力変動の生理機能への影響 細胞の重力応答機構--2018

    • Author(s)
      高橋 賢、佐々並三紗、長田 仁、成瀬恵治
    • Journal Title

      生体の科学

      Volume: 62 Pages: 106-109

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Planar compression of extracellular substrates induces S phase arrest via ATM-independent CHK2 activation2018

    • Author(s)
      Hayakawa H, Hirata H, Samsonov M, Sokabe M
    • Journal Title

      Biochim Biophys Res Commun

      Volume: 506(4) Issue: 4 Pages: 983-989

    • DOI

      10.1016/j.bbrc.2018.10.192

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biophysical mechanisms of membrane thickness dependent MscL gating: An all atom molecular dynamics study2018

    • Author(s)
      Katsuta H, Sawada Y, Sokabe M
    • Journal Title

      Langmuir

      Volume: - Issue: 23 Pages: 7432-7442

    • DOI

      10.1021/acs.langmuir.8b02074

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanoregulation and pathology of YAP/TAZ via Hippo and non-Hippo mechanisms2018

    • Author(s)
      Dobrokhotov O, Samsonov M, Sokabe M, Hirata H
    • Journal Title

      Clin Trans Med

      Volume: 7(1) Issue: 1 Pages: 23-23

    • DOI

      10.1186/s40169-018-0202-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reactive oxygen species up-regulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells.2018

    • Author(s)
      Yuushi Okumura et al.
    • Journal Title

      Am J Physiol Cell Physiol.

      Volume: 印刷中 Issue: 6 Pages: C721-C731

    • DOI

      10.1152/ajpcell.00184.2017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Post-injury stretch promotes recovery in a rat model of muscle damage induced by lengthening contractions2017

    • Author(s)
      Mori Tomohiro、Agata Nobuhide、Itoh Yuta、Inoue-Miyazu Masumi、Mizumura Kazue、Sokabe Masahiro、Taguchi Toru、Kawakami Keisuke
    • Journal Title

      The Journal of Physiological Sciences

      Volume: - Issue: 4 Pages: 1-10

    • DOI

      10.1007/s12576-017-0553-9

    • NAID

      40021574399

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Matrix stiffness regulates migration of human lung fibroblasts2017

    • Author(s)
      Asano Shuichi、Ito Satoru、Takahashi Kota、Furuya Kishio、Kondo Masashi、Sokabe Masahiro、Hasegawa Yoshinori
    • Journal Title

      Physiol Rep

      Volume: 5 Issue: 9 Pages: e13281-e13281

    • DOI

      10.14814/phy2.13281

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real-time imaging of mechanically and chemically induced ATP release in human lung fibroblasts2017

    • Author(s)
      Takahashi Kota、Ito Satoru、Furuya Kishio、Asano Shuichi、Sokabe Masahiro、Hasegawa Yoshinori
    • Journal Title

      Respir Physiol Neurobiol

      Volume: 242 Pages: 96-101

    • DOI

      10.1016/j.resp.2017.04.008

    • NAID

      120006343663

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantifying tensile force and ERK phosphorylation on actin stress fibers2017

    • Author(s)
      Hirata H, Gupta M, Vedula SRK, Lim CT, Ladoux B, Sokabe M.
    • Journal Title

      Methods Mol Biol

      Volume: XX Pages: 223-234

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Actomyosin contractility provokes contact inhibition in E-cadherin-ligated keratinocytes2017

    • Author(s)
      Hirata Hiroaki、Samsonov Mikhail、Sokabe Masahiro
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 46326-46326

    • DOI

      10.1038/srep46326

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hyperforin/HP-β-cyclodextrin enhances mechanosensitive Ca2+ signaling to improve wound healing in HaCaT keratinocytes and atopic dermatitis in ex vivo skin2017

    • Author(s)
      Takada H, Yonekawa J, Matsumoto M, Furuya K, Sokabe M
    • Journal Title

      Biomed Res Internatl

      Volume: 2017 Pages: 8701801-8701801

    • DOI

      10.1155/2017/8701801

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantifying tensile force and ERK phosphorylation on actin stress fibers2017

    • Author(s)
      Hirata H, Gupta M, Vedula SRK, Lim CT, Ladoux B, Sokabe M
    • Journal Title

      Methods Mol Biol

      Volume: 1487 Pages: 223-234

    • DOI

      10.1007/978-1-4939-6424-6_16

    • ISBN
      9781493964222, 9781493964246
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Training at non-damaging intensities facilitates recovery from muscle atrophy.2017

    • Author(s)
      Itoh Y, Murakami T, Mori T, Agata N, Kimura N, Inoue-Miyazu M, Hayakawa K, Hirano T, Sokabe M, Kawakami K
    • Journal Title

      Muscle and Nerve

      Volume: 55(2) Issue: 2 Pages: 243-253

    • DOI

      10.1002/mus.25218

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Induced NCX1 overexpression attenuates pressure overload-induced pathological cardiac remodelling2016

    • Author(s)
      Ujihara Y, Iwasaki K, Takatsu S, Hashimoto K, Naruse K, Mohri1 M, Katanosaka Y
    • Journal Title

      Cardiovasc Res

      Volume: 111(4) Issue: 4 Pages: 348-361

    • DOI

      10.1093/cvr/cvw113

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Response to mechanical stimulus and cardiovascular homeostasis.2016

    • Author(s)
      Takahashi K, Naruse K
    • Journal Title

      Clin Calcium

      Volume: 26(12) Pages: 1671-1676

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Voltage dependent inactivation of MscS occurs independently of positively charged residues in the transmembrane domain2016

    • Author(s)
      Nomura T, Sokabe M, Yoshimura Y
    • Journal Title

      Biomed Res Internatl

      Volume: 2016 Pages: 2401657-2401657

    • DOI

      10.1155/2016/2401657

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real time imaging of inflation-induced ATP release the ex-vivo rat lung2016

    • Author(s)
      Furuya K, Tan JJ, Boudreault F, Sokabe M, Berthiaume Y, Grygorczyk R
    • Journal Title

      Am J Physiol:Lung Cell Mol Physiol

      Volume: 311(5) Issue: 5 Pages: L956-L969

    • DOI

      10.1152/ajplung.00425.2015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility2016

    • Author(s)
      Hirata H, Ku WC, Yip AK, Ursekar CP, Kawauchi K, Roy A, Guo AK, Vedula SR, Harada I, Chiam KH, Ishihama Y, Lim CT, Sawada Y, Sokabe M
    • Journal Title

      J Cell Sci

      Volume: 129(19) Issue: 19 Pages: 3574-3582

    • DOI

      10.1242/jcs.189415

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cellular ATP release in the lung and airway2016

    • Author(s)
      Ito S, Furuya K, Sokabe M, Hasegawa Y
    • Journal Title

      AIMS Biophysics

      Volume: 3(4) Issue: 4 Pages: 571-584

    • DOI

      10.3934/biophy.2016.4.571

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] メカノバイオロジーはどのようにして生まれたのか2016

    • Author(s)
      曽我部正博
    • Journal Title

      Clin Calcium

      Volume: 26(12) Pages: 1659-1669

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 伸展・圧縮センシング2016

    • Author(s)
      平田宏聡、曽我部正博
    • Journal Title

      医学のあゆみ

      Volume: 257(10) Pages: 1001-1007

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 接着構造/細胞骨格のメカノセンシング2016

    • Author(s)
      平田宏聡、曽我部正博
    • Journal Title

      血管医学

      Volume: 17(1) Pages: 77-85

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Molecular dynamics study on protein-water interplay in the mechanogating of the bacterial mechanosensitive channel MscL2015

    • Author(s)
      Sawada Y, Sokabe M
    • Journal Title

      Eur J Biophys

      Volume: 44 Issue: 7 Pages: 531-43

    • DOI

      10.1007/s00249-015-1065-2

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unidirectional incorporation of a bacterial mechanosensitive channel into liposomal membranes2015

    • Author(s)
      Nomura T, Cox CD, Bavi N, Sokabe M and Martinac B
    • Journal Title

      FASEB J.

      Volume: 29 Issue: 10 Pages: 4334-45

    • DOI

      10.1096/fj.15-275198

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Ion channels activated by mechanical forces in bacterial and eukaryotic cells2015

    • Author(s)
      Sokabe M, Sawada M, Kobayashi T
    • Journal Title

      Subcell Biochem

      Volume: 72 Pages: 613-626

    • DOI

      10.1007/978-94-017-9918-8_28

    • ISBN
      9789401799171, 9789401799188
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 発展するメカノセンシング研究2015

    • Author(s)
      曽我部正博
    • Journal Title

      血管医学

      Volume: 16 Pages: 73-85

    • Related Report
      2015 Annual Research Report
  • [Journal Article] オピニオン:メカノバイオロジーの可能性2015

    • Author(s)
      曽我部正博
    • Journal Title

      ファルマシア

      Volume: 51 Pages: 1025-1025

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The Actin Filament as a Mechanosensor2015

    • Author(s)
      辰巳仁史、早川公英、曽我部正博
    • Journal Title

      Seibutsu Butsuri

      Volume: 55 Issue: 4 Pages: 187-191

    • DOI

      10.2142/biophys.55.187

    • NAID

      130005090035

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 骨と筋におけるメカノセンシングとメカノシグナリング2015

    • Author(s)
      小林剛、曽我部正博
    • Journal Title

      The BONE

      Volume: 29(35) Pages: 45-53

    • Related Report
      2015 Annual Research Report
  • [Presentation] Chondrocyte dynamics under high hydrostatic pressure2020

    • Author(s)
      Morimatsu M, Teramachi K, Nishiyama M, Naruse K
    • Organizer
      64th Annual Meeting of the Biophysical Society
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Role of nucleotide signalling in mechano-sensitive responses of organelle and cellular mechanics2019

    • Author(s)
      Iribe G, Kaihara K, Naruse K
    • Organizer
      The 8th International Workshop on Cardiac Mechano-Electric Coupling and Arrhythmias
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] メカノメディスン:メカノバイオロジーを駆使した医学研究・臨床応用2019

    • Author(s)
      成瀬恵治
    • Organizer
      第38回日本認知症学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Direct observation of cell mechanics under high hydrostatic pressure2019

    • Author(s)
      Morimatsu M, Naruse K
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Direct observation of cell mechanics under the physiological high hydrostatic pressure condition2019

    • Author(s)
      Morimatsu M, Nishiyama M, Naruse K
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] メカノメディスン:メカノバイオロジーを駆使した医学研究・臨床応用2019

    • Author(s)
      成瀬恵治
    • Organizer
      2019年次世代メディカルトーク
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] メカノメディスン:メカノバイオロジーを駆使した医学・医療への新展開2019

    • Author(s)
      成瀬恵治
    • Organizer
      ものづくりライフイノベーションシンポジウム2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 高静水圧負荷による軟骨細胞の圧力受容応答メカニズムの解明2019

    • Author(s)
      寺町一希、森松賢順、藤田彩乃、西山雅洋、成瀬恵治
    • Organizer
      生体医工学シンポジウム2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] 重力変化を含む力学的ストレスに対するメカノセンシング機構2019

    • Author(s)
      成瀬恵治
    • Organizer
      新領域学術研究「宇宙に生きる」2019年度 第1回全体会議
    • Related Report
      2019 Annual Research Report
  • [Presentation] 周期的伸展刺激と静水圧刺激に対するヒト歯根膜細胞の形態と配向の変化2019

    • Author(s)
      藤田彩乃、森松賢順、西山雅祥、高柴 正悟、 成瀬恵治
    • Organizer
      第58回日本生体医工学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Direct observation of cell mechanics under high hydrostatic pressure.2019

    • Author(s)
      Morimatsu M, Naruse K
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Mechanomedicine.2019

    • Author(s)
      Naruse K
    • Organizer
      9th Federation of the Asian and Oceanian Physiological Societies Congress (FAOPS2019)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell Mechanosensing.2019

    • Author(s)
      Naruse K
    • Organizer
      International Symposiumu on LIVING iIN SPACE 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] メカノメディスン2019

    • Author(s)
      成瀬恵治
    • Organizer
      日本学術会議「心と脳など新しい領域検討小委員会」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 重力変化を含む力学的ストレスに対するメカノセンシング機構2019

    • Author(s)
      成瀬恵治
    • Organizer
      新領域学術研究「宇宙に生きる」2018年度 第2回全体会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] メカノメディスン:基礎医学研究から不妊治療・再生医療への展開のアップデート2019

    • Author(s)
      成瀬恵治
    • Organizer
      日本生物物理学会北海道支部会講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Mechanomedicine.2018

    • Author(s)
      Naruse K
    • Organizer
      Mechanobiology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanomedicine and Piezobiology.2018

    • Author(s)
      Naruse K
    • Organizer
      The 10th International Conference on High Pressure Bioscience and Biotechnology (HPBB2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 重力変化を含む力学的ストレスに対するメカノセンシング機構2018

    • Author(s)
      成瀬恵治
    • Organizer
      新領域学術研究「宇宙に生きる」2018年度 第1回全体会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] Opening Remarks.2018

    • Author(s)
      成瀬恵治
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Active Mechanosensing at Cell-Substrate and Cell-Cell Adhesions2018

    • Author(s)
      Sokabe M, Kobayashi T, Hirata H
    • Organizer
      Asian Biophysics Association Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanobiology of Skin Cancer: Proliferation of Keratinocyte is Regulated by Mechanical Force Generated in the Cell2018

    • Author(s)
      Sokabe M, Hirata H
    • Organizer
      The 5th International Conference on Innovative Biology, Medicine and Engineering (ICIBME) in Vietnam
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Plant-Inspired Mechanobiology of Cell Gravi-Sensing in Animal Cells2018

    • Author(s)
      Sokabe M
    • Organizer
      Memorial Symposium for the Establishment of Institute of Space Nutrition in Tokushima University
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Mechanobiology of Wound-Repair and Contact-Inhibition/Cancer: Critical Role of Mechanical Forces2018

    • Author(s)
      Sokabe M
    • Organizer
      International Conference on Mechanobiology for Regeneration &1st NCKU-CUHK Joint Forum on Cell Therapy & Tissue Engineering
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Toward the Elucidation of Cell Gravi-Sensing in Space2018

    • Author(s)
      Sokabe M, Kobayashi T, Nikawa T, Naruse K, Higashibata A
    • Organizer
      15th Korea-Japan Joint Seminar on Space Environment Utilization Research
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] メカノバイオロジーの誕生と発展:分子/細胞から組織/器官への展開2018

    • Author(s)
      曽我部正博
    • Organizer
      JSPSナノテクノロジー第174委員会 第64回研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Mechanobiology of the Contact Inhibition in Cell Proliferation2018

    • Author(s)
      曽我部正博、平田宏聡
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ミルク放出、創傷治癒、がんのメカノバイオロジー:細胞力覚の実体としくみ2018

    • Author(s)
      曽我部正博
    • Organizer
      日本薬学会次世代を担う創薬・医療薬理シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Urgent problems to be solved in mechanobiology, Symposium: Mechanomedicine2018

    • Author(s)
      曽我部正博
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 再生医療とメカノバイオロジー、シンポジウム“再生医療における物理刺激の役割(メカノバイオロジーとメカノセラピー”2018

    • Author(s)
      曽我部正博
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 間葉系幹細胞の足場の硬さ感知における機械刺激受容チャネルTRPV4を介したYAP活性化2018

    • Author(s)
      田中瑞奈, 平野拓真, 曽我部正博, 小林 剛
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 線虫を用いた筋ミトコンドリア研究2018

    • Author(s)
      東谷篤志, 小林 剛
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 間葉系幹細胞の重力感知における機械刺激受容チャンネルTRPV4を介したシグナル伝達経路の役割2018

    • Author(s)
      加藤信靖, 田中瑞奈, 曽我部正博, 小林 剛
    • Organizer
      日本宇宙生物科学会第32回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ストレス線維の張力低下により誘導された接着斑解体におけるエンドサイトーシスの役割2018

    • Author(s)
      堀池由朗, 田中瑞奈, 加藤信靖, 成瀬恵治, 曽我部正博, 小林 剛
    • Organizer
      日本宇宙生物科学会第32回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Rotational microscope visualizes cell mechanics under high gravity condition.2018

    • Author(s)
      Morimatsu M, Naruse K
    • Organizer
      Biophysical Society 62st Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 重力変化を含む力学的ストレスに対するメカノセンシング機構2018

    • Author(s)
      成瀬恵治
    • Organizer
      新領域学術研究「宇宙に生きる」2017年度第2回全体会議
    • Related Report
      2017 Annual Research Report
  • [Presentation] 蛍光遠心顕微鏡プロジェクト2018

    • Author(s)
      成瀬恵治
    • Organizer
      新領域学術研究「宇宙に生きる」2017年度第2回全体会議
    • Related Report
      2017 Annual Research Report
  • [Presentation] 重力変化を含む力学的ストレスに対するメカノセンシング機構2017

    • Author(s)
      成瀬恵治
    • Organizer
      2017年度 生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ワークショップ:ザ・メカノバイオロジー:分子から個体のメカノセンシング2017

    • Author(s)
      曽我部正博、澤田康之、小林剛
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 神経ステロイドDHEAはラット海馬歯状回におけるアストロサイトのグルタミン輸送体GLT-1の活性を促進する2017

    • Author(s)
      曽我部正博、田中基樹、陳玲
    • Organizer
      第26回海馬と高次機能学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Mechanobiology: Past achievements and future issues, Symposium 2SAI Development of methodology to explore the mechanobiology2017

    • Author(s)
      曽我部正博
    • Organizer
      第55回日本生物物理学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] メカノバイオロジーへの招待:細胞力覚研究のフロンティア2017

    • Author(s)
      曽我部正博
    • Organizer
      第3回日本筋学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] メカノバイオロジー入門:いのちを支える細胞力覚2017

    • Author(s)
      曽我部正博
    • Organizer
      日本医科大学大学院特別講演
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Introduction to the Symposium: The Impact of Mechanobiology in Physiology、Symposiumon the impact of mechanobiology in physiology2017

    • Author(s)
      曽我部正博
    • Organizer
      第94回日本生理学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] メカノバイオロジーへの招待:機械受容チャネルから再生医療まで2017

    • Author(s)
      曽我部正博
    • Organizer
      第3回HO(特別講演)NGO HEART CLUB
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Introduction to mechanobiology: Molecular and biophysical mechanisms of cell mechanosensing, Invited Lecture at the Platform for Dynamic Approaches to Living System2017

    • Author(s)
      曽我部正博
    • Organizer
      Approaches to Living System
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Coarse grained molecular dynamics simulation of mammalian mechanosensitive ion channel TRPV22017

    • Author(s)
      Takahashi K
    • Organizer
      3rd International Symposium on Mechanobiology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Force and rigidity sensing by talin and vinculin at focal adhesions2017

    • Author(s)
      Hirata H, Chiam KH, Tatsumi H, Lim CT, Sokabe, M
    • Organizer
      3rd International Symposium on Mechanobiology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Unloading induces reactive oxygen sprecies associated signal transduction toward atrophy in skeletal muscle cells2017

    • Author(s)
      Nikawa T, Uchida T, Kobayashi T, Sokabe M
    • Organizer
      3rd International Symposium on Mechanobiology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanobiology of multicellular system: Role of mechanosensitive ATP release in milk ejection and wound healing2017

    • Author(s)
      Sokabe M, Furuya K
    • Organizer
      Special Seminar at Nutrition & Sante
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Gravi-sensing and -response in cultured mesenchymal stem cells2017

    • Author(s)
      Sokabe M, Kobayashi T
    • Organizer
      2nd Japan / French Symposium on Space Nutrition
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Actin filaments work as a mechanosensor in cells: Underlying molecular and biophysical mechanisms2017

    • Author(s)
      Sokabe M, Hayakawa, Tatsumi H
    • Organizer
      Satellite Meeting for the 3rd International Symposium on Mechanobiology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of protein water interplay in the mechanogating of the bacterial mechanosensitive channel MscL2017

    • Author(s)
      Sokabe M, Sawada Y.
    • Organizer
      9th International Meeting on Biomolecules under Pressure (IMBP)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Actin works as a mechanosensor2016

    • Author(s)
      Sokabe M
    • Organizer
      IGER International Symposium
    • Place of Presentation
      Nagoya Japan
    • Year and Date
      2016-12-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanobiology of multicellular system: Mechanosensitive ATP release is a key mechanism that orchestrates collective cell behavior ATP release2016

    • Author(s)
      Sokabe M, Furuya K
    • Organizer
      The 16th ICBME
    • Place of Presentation
      Singapore
    • Year and Date
      2016-12-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] High hydrostatic pressure induces cytoskeletal organization and signal transduction.2016

    • Author(s)
      Morimatsu M, Fujita A, Takahashi K, Naruse K
    • Organizer
      2016 American Society for Cell Biology
    • Place of Presentation
      San Francisco
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] メカノ再生医療・生殖医療2016

    • Author(s)
      成瀬恵治
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ストレス線維の張力低下により誘導された接着斑解体におけるエンドサイトーシスの役割2016

    • Author(s)
      田中瑞奈、齋木貴博、島本祐哉、曽我部正博、小林 剛
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] メカノメディスン:メカノトランスダクション研究とその臨床応用2016

    • Author(s)
      成瀬恵治
    • Organizer
      自然科学研究機構岡崎統合バイオサイエンスセンターセミナー
    • Place of Presentation
      愛知県岡崎市
    • Year and Date
      2016-11-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 分子と細胞、そして細胞と組織をつなぐメカニカルシグナル、シンポジウム”原子からいのちへ:21世紀の新しい生命観を求めて”2016

    • Author(s)
      曽我部正博
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば市
    • Year and Date
      2016-11-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 自己集合性ペプチドゲルの医学・医療応用2016

    • Author(s)
      成瀬恵治
    • Organizer
      第25回ポリマー材料フォーラム
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2016-11-11
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Possible Mechanisms for Gravity Sensing in Single Cells2016

    • Author(s)
      Sokabe M
    • Organizer
      11th Asian Microgravity Symposium
    • Place of Presentation
      Sapporo, Japan
    • Year and Date
      2016-10-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Loss of Rigidity Sensing of Mesenchymal Stem Cells under Microgravity2016

    • Author(s)
      Kobayashi T, Tanaka M, Hashizume T, Higashibata A, Yano S, Nikawa T, Sokabe M
    • Organizer
      11th Asian Microgravity Symposium
    • Place of Presentation
      Sapporo, Japan
    • Year and Date
      2016-10-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] メカノ医工学:循環器・不妊治療を中心に2016

    • Author(s)
      成瀬恵治
    • Organizer
      大阪大学MEIプロフェッショナルコース
    • Place of Presentation
      大阪府
    • Year and Date
      2016-10-22
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Cellular Active Touch Sensing of Substrate Rigidity2016

    • Author(s)
      Kobayashi T, Sokabe M
    • Organizer
      5th Nagoya Biomimetics International Symposium
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      2016-10-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 微小重力環境における間葉系幹細胞のYAP/TAZの活性化抑制機構2016

    • Author(s)
      小林 剛、橋爪藤子、田中瑞奈、丸山昭洋、東端 晃、矢野幸子、成瀬恵治、二川 建、曽我部正博
    • Organizer
      第62回日本宇宙航空環境医学会大会・日本宇宙生物科学会第30回大会
    • Place of Presentation
      愛知県
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] High hydrostatic pressure induces signal transduction of MAPK pathway.2016

    • Author(s)
      Morimatsu M, Fujita A, Takahashi K, Naruse K
    • Organizer
      Biophysical Society
    • Place of Presentation
      Singapore
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TRPC3 participates in the angiotensin II type 1 receptor-dependent slow force response to stretch in mouse cardiomyocytes.2016

    • Author(s)
      Yamaguchi Y, Iribe G, Naruse K
    • Organizer
      7th International Workshop on Cardiac Mechano-Electric Coupling and Arrhythmias
    • Place of Presentation
      Germany
    • Year and Date
      2016-09-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TRPC3 participates in the angiotensin II type 1 receptor-dependent slow force response to stretch in mouse cardiomyocytes.2016

    • Author(s)
      Yamaguchi Y, Iribe G, Kaneko T, Takahashi K, Numaga-Tomita T, Nishida M, Birnbaumer L, Naruse K
    • Organizer
      45th European Muscle Conference
    • Place of Presentation
      France
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] メカノメディスン:メカノトランスダクション研究とその臨床応用2016

    • Author(s)
      成瀬恵治
    • Organizer
      医学研究の基礎を語り合う集い
    • Place of Presentation
      東京
    • Year and Date
      2016-07-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] メカノトランスダクションと生体界面:MS チャネル活性化における脂質/水、および接着分子/細胞骨格との相互作用2016

    • Author(s)
      曽我部正博
    • Organizer
      平成28年度生理研研究会「生体界面研究会」
    • Place of Presentation
      岡崎市
    • Year and Date
      2016-07-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 心筋細胞におけるTRPC3チャネルを介した伸展誘発遅発性カルシウム応答の制御機構2016

    • Author(s)
      山口陽平,入部玄太郎,成瀬恵治
    • Organizer
      第11回 TRPs and SOCs 研究会
    • Place of Presentation
      愛知県岡崎市
    • Year and Date
      2016-06-02
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] MECHANOMEDICINE:メカノバイオロジーを駆使した医学研究・医療応用への展開2016

    • Author(s)
      成瀬恵治
    • Organizer
      第186回横浜市立大学医学会講演会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Comprehensive analyses of gene expression patterns in early mouse early embryos experiencing chemical and mechanical stimuli.2016

    • Author(s)
      Asano Y, Matsuura K, Naruse K
    • Organizer
      Mechanobiology of Disease
    • Place of Presentation
      Singapore
    • Year and Date
      2016-04-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト精子が螺旋運動する流路条件の検討2016

    • Author(s)
      仁科 咲織、松浦 宏治、成瀬 恵治
    • Organizer
      第55回日本生体医工学会大会
    • Place of Presentation
      富山県富山市
    • Year and Date
      2016-04-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 重力変化を含む力学的ストレスに対するメカノセンシング機構2016

    • Author(s)
      高橋賢
    • Organizer
      新領域研究「宇宙に生きる」2016ワークショップ
    • Place of Presentation
      東京
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞の重力感知機構2016

    • Author(s)
      奥村浩基、佐々並三紗
    • Organizer
      新領域研究「宇宙に生きる」2016ワークショップ
    • Place of Presentation
      東京
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] メカノバイオロジーを使って組織の再生力を制御する2016

    • Author(s)
      曽我部正博
    • Organizer
      平成28年度 再生医療サポートビジネス懇話会-再生医療におけるモノづくりビジネスはここから始まる-
    • Place of Presentation
      京都
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 科学的筋治療を目指して:骨格筋の生理学 III - 感覚入力による骨格筋の制御2016

    • Author(s)
      曽我部正博
    • Organizer
      深層筋治療セミナー
    • Place of Presentation
      横浜市
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Initial Step of Gravi-Sensing in Mesenchymal Stem Cells2016

    • Author(s)
      Kobayashi T, Sokabe M
    • Organizer
      the 13th Korea -Japan Joint Seminar on Space Environment Utilization Research, Hokkaido University, Graduate School of Engineering
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanobiology of Wound Healing: Effects of force and extracellular ATP2015

    • Author(s)
      Sokabe M
    • Organizer
      The 4th International Conference on Innovative Biology
    • Place of Presentation
      Hanoi Vietnam
    • Year and Date
      2015-10-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞から自分を眺める:メカノバイオロジーへの招待2015

    • Author(s)
      曽我部正博
    • Organizer
      日本心理学会第79回大会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-09-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Molecular and biophysical mechanisms underlying force dependent dynamics (breakdown) of actin cytoskeletons2015

    • Author(s)
      Sokabe M
    • Organizer
      7th WACBE World Congress on Bioengineering
    • Place of Presentation
      Singapore
    • Year and Date
      2015-07-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] Mechanobiology2017

    • Author(s)
      Takahashi K, Piao H, Naruse K
    • Total Pages
      14
    • Publisher
      Wiley-Blackwell
    • ISBN
      9781118966143
    • Related Report
      2017 Annual Research Report
  • [Book] 細胞のマルチスケールメカノバイオロジー2017

    • Author(s)
      佐藤 正明、安達 泰治、松下 慎二、井上 康博、平田 宏聡、曽我部 正博、出口 真次、安藤 譲二、山本 希美子、谷下 一夫、須藤 亮
    • Total Pages
      160
    • Publisher
      森北出版
    • ISBN
      9784627691414
    • Related Report
      2017 Annual Research Report
  • [Book] メカノバイオロジーの誕生と今後の展望2017

    • Author(s)
      曽我部正博
    • Total Pages
      3
    • Publisher
      日本機械学会
    • Related Report
      2017 Annual Research Report
  • [Book] メカノバイオロジー:基礎から医療への展開2017

    • Author(s)
      曽我部正博
    • Total Pages
      6
    • Publisher
      医薬ジャーナル
    • Related Report
      2017 Annual Research Report
  • [Book] Mechanobiology: Exploitation for Medical Benefit2017

    • Author(s)
      Takahashi K, Piao H, Naruse K
    • Total Pages
      410
    • Publisher
      Blackwell Publishing
    • Related Report
      2016 Annual Research Report
  • [Book] メカノバイオロジー2015

    • Author(s)
      曽我部正博
    • Total Pages
      332
    • Publisher
      化学同人
    • Related Report
      2015 Annual Research Report
  • [Remarks] 宇宙に生きる:宇宙からひも解く新たな生命制御機構の統合的理解

    • URL

      https://living-in-space.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 宇宙に生きる宇宙からひも解く新たな生命制御機構の統合的理解

    • URL

      http://living-in-space.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 宇宙に生きる・宇宙からひも解く新たな生命制御機構の統合的理解

    • URL

      http://living-in-space.jp/

    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 蛍光遠心顕微鏡2016

    • Inventor(s)
      成瀬恵治、高橋 賢、森松賢順
    • Industrial Property Rights Holder
      成瀬恵治、高橋 賢、森松賢順
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-043814
    • Filing Date
      2016-03-07
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2015-07-02   Modified: 2022-11-04  

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