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Analysis of Function and Mechanism of nuclear transport carrier Hikeshi

Research Project

Project/Area Number 26251021
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Imamoto Naoko  国立研究開発法人理化学研究所, 今本細胞核機能研究室, 主任研究員 (20202145)

Co-Investigator(Renkei-kenkyūsha) KOSE Shingo  国立研究開発法人理化学研究所, 今本細胞核機能研究室, 専任研究員 (90333278)
MAMADA Hiroshi  国立研究開発法人理化学研究所, 今本細胞核機能研究室, 特別研究員 (90568734)
Research Collaborator TAKAGI Masatoshi  国立研究開発法人理化学研究所, 今本細胞核機能研究室, 専任研究員
KIMURA Makato  国立研究開発法人理化学研究所, 今本細胞核機能研究室, 専任研究員
OGAWA Yutaka  国立研究開発法人理化学研究所, 今本細胞核機能研究室, 研究員
LEE Soo Jae  Chungbuk National University, College of Pharmacy, Professor
EPELEG Orly  Hebrew University Medical Center, Professor
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥40,690,000 (Direct Cost: ¥31,300,000、Indirect Cost: ¥9,390,000)
Fiscal Year 2016: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2015: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2014: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Keywords核-細胞質間輸送 / 熱ストレス / 分子シャペロンHsp70 / Hikeshi / HSF1 / タンパク質毒性ストレス / タンパク質恒常性 / 核ー細胞質間輸送 / 熱ショックストレス / 神経遺伝性疾患 / 蛍光相互相関法 / グルコース飢餓 / ノックアウトマウス
Outline of Final Research Achievements

Stresses significantly affect nuclear transport systems. Many of the well-characterized Importin nuclear transport pathways that are active under normal conditions are down regulated in response to stress.Under such stress condition, a nuclear transport carrier named Hikeshi drives nuclear import of molecular chaperone Hsp70.
Hikeshi is an evolutionarily conserved protein, and its function has not been previously characterized. We analyzed Hikeshi homologues from several organisms and found biochemical nature of Hikeshi homologues is conserved. Hikeshi is not an essential protein in lower eukaryotes although it affects stress sensitivity. However, dysfunction of Hikeshi has lethal effects in higher eukaryotes. Our analysis reveals that Hikeshi is involved in a regulation of HSF1, not only under stress condition but also under normal condition. We suggest Hikeshi is crucial for the maintenance of proteostasis at basal level in cells, which affect variety of organismal function.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (57 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (3 results) Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 14 results,  Open Access: 4 results,  Acknowledgement Compliant: 15 results) Presentation (27 results) (of which Int'l Joint Research: 4 results,  Invited: 13 results) Book (7 results) Remarks (5 results)

  • [Int'l Joint Research] Hebrew University Medical Center(イスラエル)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Hebrew University Medical Center(イスラエル)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Chungbuk National University(韓国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Extensive cargo identification reveals distinct biological roles of the 12 Importin2017

    • Author(s)
      Kimura, M., Morinaka, Y., Imai, K., Kose, S, Horton, P, Imamoto, N
    • Journal Title

      eLife

      Volume: 2017 Pages: 21184-21184

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ELYS regulates the localization of LBR by modulating its phosphorylation state.2016

    • Author(s)
      Mimura, Y., Takagi, M., Clever, M., Imamoto, N.
    • Journal Title

      J Cell Sci.

      Volume: 129 Pages: 4200-4212

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The perichromosomal protein Ki67 supports mitotic chromosome architecture.2016

    • Author(s)
      Takagi, M., Natsume, T., Kanemaki, M.T., Imamoto, N.
    • Journal Title

      Genes Cells

      Volume: 21 Pages: 1113-1124

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Leukoencephalopathy and early death associated with an Ashkenazi-Jewish founder mutation in the Hikeshi gene.2016

    • Author(s)
      Edvardson, S., Kose, S., Jalas, C., Fattal-Valevski, A., Watanabe, A., Ogawa, Y., Mamada, H., Fedick, A.M., Ben-Shachar, S., Treff, N.R., Shaag, A., Bale, S., Gartner, J., Imamoto, N., Elpeleg, O.
    • Journal Title

      J Med Genet

      Volume: 53 Pages: 132-137

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Leukoencephalopathy and early death associated with an Ashkenazi-Jewish founder mutation in the Hikeshi gene.2016

    • Author(s)
      Edvardson, S., Kose, S., Jalas, C., Fattal-Valevski, A., Watanabe, A., Ogawa, Y., Mamada, H., Fedick, A.M., Ben-Shachar, S., Treff, N.R., Shaag, A., Bale, S., Gärtner, J., Imamoto, N., Elpeleg, O.
    • Journal Title

      J. Med. Genet.

      Volume: 53 Pages: 132-137

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Molecular mechanism by which acyclic retinoid induces nuclear localization of transglutaminase 2 in human hepatocellular carcinoma cells.2015

    • Author(s)
      Shrestha, R., Tatsukawa, H., Shrestha, R., Ishibashi, N., Matsuura, T., Kagechika, H., Kose, S., Hitomi, K., Imamoto, N., Kojima, S.
    • Journal Title

      Cell Death Disease

      Volume: 6

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Biallelic Mutations in Nuclear Pore Complex Subunit NUP107 Cause Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome.2015

    • Author(s)
      Miyake, N., Tsukaguchi, H., Koshimizu, E., Shono, A., Matsunaga, S., Shiina, M., Mimura, Y.......... Imamoto, N.( 29人中25番目)....... , Matsumoto, N.
    • Journal Title

      Am. J. Hum. Genet

      Volume: 97 Pages: 555-566

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structural and functional analysis of Hikeshi, a new nuclear transport receptor of Hsp70s.2015

    • Author(s)
      Song, J., Kose, S., Watanabe, A., Son, S.Y., Choi, S., Hong, H., Yamashita, E., Park, I.Y., Imamoto, N., Lee, S.J.
    • Journal Title

      Acta Crystallogr. D Biol. Crystallogr.

      Volume: 71 Pages: 473-483

    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structural and functional analysis of Hikeshi, a new nuclear transport receptor of Hsp70.2015

    • Author(s)
      Song J, *Kose S, Watanabe A, Son SY, Choi S, Hong H, Yamashita E, Park I Y, *Imamoto N, *Lee S J.
    • Journal Title

      Acta Cryst. D Biol. Crystallogr.

      Volume: 71(Pt3) Pages: 473-483

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Analytic 3D imaging of mammalian nucleus at nanoscale using coherent X-Rays and optical fluorescence microscopy.2014

    • Author(s)
      Song C, Takagi M, Park J, Xu R, Gallagher-Jones M, Imamoto N, Ishikawa T.
    • Journal Title

      Biophys. J.

      Volume: 107 Pages: 1074-1081

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Ki67 antigen contributes to the timely accumulation of protein phosphatase 1γ on anaphase chromosomes.2014

    • Author(s)
      Takagi M, Nishiyama Y, Taguchi A, *Imamoto N.
    • Journal Title

      J. Biol. Chem.

      Volume: 289 Pages: 22877-22887

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Nucleocytoplasmic transport under stress conditions and its role in HSP70 chaperone systems.2014

    • Author(s)
      Kose S, *Imamoto N.
    • Journal Title

      BBA-General Subjects

      Volume: 1840 Pages: 2953-2960

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Ki-67 is a PP1-interacting protein that organises the mitotic chromosome periphery.2014

    • Author(s)
      Booth D, Takagi M, Sanchez-Pulido L, Petfalski E, Vargiu G, Samejima K, Imamoto N, Ponting C P, Tollervey D, Earnshaw W, Vagnarelli P.
    • Journal Title

      eLife

      Volume: 3: e01641

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The Schizosaccharomyces pombe Hikeshi/Opi10 protein has similar biochemical functions to its human homolog but acts in different physiological contexts.2014

    • Author(s)
      Oda Y, Kimura M, Kose S, Fasken MB, Corbett AH, *Imamoto N.
    • Journal Title

      FEBS Lett.

      Volume: 588 Pages: 1899-1905

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Biological significance of the importin-β family-dependent nucleocytoplasmic transport pathways.2014

    • Author(s)
      Kimura M, Imamoto N.
    • Journal Title

      Traffic

      Volume: 15 Pages: 727-748

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Analysis of stress-induced nucleocytoplasmic Carrier Hikeshi2017

    • Author(s)
      Imamoto N.
    • Organizer
      University of Strasbourg-RIKEN Workshop on Membrane Lipidology
    • Place of Presentation
      Strasbourg, France
    • Year and Date
      2017-03-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞質から核への蛋白質輸送を担う12種類にimportinβファミリー輸送因子の基質の大規模同定2017

    • Author(s)
      木村誠、森中祐理子、今井賢一郎、小瀬真吾、Paul Horton、今本尚子
    • Organizer
      第34回染色体ワークショップ・第15回 核ダイナミクス研究会
    • Place of Presentation
      かずさアカデミアホール(千葉県木更津市)
    • Year and Date
      2017-01-11
    • Related Report
      2016 Annual Research Report
  • [Presentation] Importinβファミリーが構成するヒト細胞の核内輸送経路を網羅した基質蛋白質の解析2017

    • Author(s)
      木村誠、今本尚子
    • Organizer
      蛋白研セミナー
    • Place of Presentation
      大阪大学蛋白質研究所(大阪府吹田市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 間期の核膜孔複合体形成と核膜サブドメインPore free island消失2016

    • Author(s)
      三村恭弘、竹本智子、横田秀夫、今本尚子
    • Organizer
      第39回 日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Analysis of thermal-stress induced nucleocytoplasmic transport carrier Hikeshi2016

    • Author(s)
      Imamoto N
    • Organizer
      Frontiers in aging research toward healthy longevity
    • Place of Presentation
      丸の内MY PLAZAホール(東京都千代田区)
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 分子シャペロンHsp70核内輸送運搬体Hikeshiの機能2016

    • Author(s)
      今本尚子
    • Organizer
      臨床ストレス応答学会
    • Place of Presentation
      山口大学(山口県宇部市)
    • Year and Date
      2016-11-11
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 核―細胞質タンパク質運搬体分子Hikeshi:熱ストレス時に活性化する分子シャペロンHsp70輸送機構とその生理機能2016

    • Author(s)
      小瀬真吾、今本尚子
    • Organizer
      第89回 日本生化学会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 細胞質・細胞核の温度センシング機構の解明2016

    • Author(s)
      今本尚子
    • Organizer
      第68回 日本細胞生物学会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Analysis of a stress activated nuclear import carrier, Hikeshi, using knockout mice.2016

    • Author(s)
      儘田 博志、小林 健太郎、小瀬 真吾、今本 尚子
    • Organizer
      第33回染色体ワークショップ・第14回核ダイナミクス研究会
    • Place of Presentation
      松島一の坊(宮城郡松島町)
    • Year and Date
      2016-01-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] SILAC法と蛋白質核輸送再構成系によるimportin-βファミリー輸送因子の輸送基質の大規模同定2015

    • Author(s)
      木村誠、 小瀬真吾、今本尚子
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会・合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Thermal stress induced nuclear transport pathway mediated by Hikeshi2015

    • Author(s)
      Naoko Imamoto
    • Organizer
      2015 Nuclear Transport Meeting
    • Place of Presentation
      Eden Roc Hotel(Sant Feliu de Guixols, Spain)
    • Year and Date
      2015-09-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 熱ストレスで駆動する核ー細胞質間輸送を担うHikeshi2015

    • Author(s)
      今本尚子
    • Organizer
      日本生物物理学会第53回年会
    • Place of Presentation
      金沢大学角間キャンパス(石川県金沢市)
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Large Scale Identification of Nuclear Transport Receptor Substrates Using a Novel Approach2015

    • Author(s)
      Naoko Imamoto
    • Organizer
      International Symposium on Chromatin Structure, Dynamics, and Function
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県淡路市)
    • Year and Date
      2015-08-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Function of nuclecytoplasmic transport carrier, Hikeshi2015

    • Author(s)
      今本尚子
    • Organizer
      第67回日本細胞生物学会大会
    • Place of Presentation
      タワーホール船堀(東京都江戸川区)
    • Year and Date
      2015-07-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Thermal stress induced nuclear transport mediated by Hikeshi: its mechanism and physiological significance2015

    • Author(s)
      Naoko Imamoto
    • Organizer
      HiHA 第4回 Workshop
    • Place of Presentation
      広島大学健康長寿研究拠点(広島県広島市)
    • Year and Date
      2015-06-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 核―細胞質間輸送運搬体Hikeshi機能の破綻で誘引されるヒト疾患とマウス発生異常2014

    • Author(s)
      今本尚子
    • Organizer
      第32回染色体ワークショップ・第13回核ダイナミクス研究会
    • Place of Presentation
      広島県廿日市
    • Year and Date
      2014-12-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Ki67抗原が分裂期染色体表層にPCFを樹立する分子機構2014

    • Author(s)
      高木昌俊
    • Organizer
      第32回染色体ワークショップ 第13回核ダイナミクス研究会 (共催)
    • Place of Presentation
      廿日市市、日本
    • Year and Date
      2014-12-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] SILAC法と核蛋白質輸送再構成系によるimportinβファミリー輸送因子の基質蛋白質の同定2014

    • Author(s)
      木村誠
    • Organizer
      第32回染色体ワークショップ/第13回核ダイナミクス研究会
    • Place of Presentation
      廿日市市、日本
    • Year and Date
      2014-12-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] SILAC法と蛋白質核輸送再構成系によるimportin-βファミリー輸送因子の輸送基質の同定2014

    • Author(s)
      木村誠
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜、日本
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] HSP70分子シャペロンシステムにおける核-細胞質間運搬体分子Hikeshiの機能解析2014

    • Author(s)
      小瀬真吾
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都市、日本
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Thermal-stress induced nuclear transport mediated by Hikeshi: its mechanism and physiological significance2014

    • Author(s)
      今本尚子
    • Organizer
      Internaional Meeting of the German Society for Cell Biology (DGZ)
    • Place of Presentation
      ポツダム ドイツ
    • Year and Date
      2014-07-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 核膜孔複合体と輸送運搬体によるimportin輸送制御:細胞核機能から高次生命へ2014

    • Author(s)
      今本尚子
    • Organizer
      新学術領域研究 動的クロマチン構造と機能 第二回班会議
    • Place of Presentation
      北海道上川郡、日本
    • Year and Date
      2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 間期Cyclin-CDK複合体によるPOM121のリン酸化の機能解析2014

    • Author(s)
      三村恭弘
    • Organizer
      第2回クロマチン動構造若手の会
    • Place of Presentation
      北海道上川郡、日本
    • Year and Date
      2014-07-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] 分子シャペロンHSP70運搬体分子Hikeshiの輸送機構とその機能解析2014

    • Author(s)
      小瀬真吾
    • Organizer
      第66回日本細胞生物学会大会
    • Place of Presentation
      奈良市、日本
    • Year and Date
      2014-06-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 細胞ストレスで駆動する核-細胞質間輸送:輸送運搬体Hikeshiの機能2014

    • Author(s)
      今本尚子
    • Organizer
      第66回日本細胞生物学会大会
    • Place of Presentation
      奈良市、日本
    • Year and Date
      2014-06-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 核ー細胞質間輸送運搬体分子Hikeshi (火消し)2014

    • Author(s)
      今本尚子
    • Organizer
      新学術領域研究 「クロマチン動構造と創薬」セミナー
    • Place of Presentation
      大阪府茨木市
    • Year and Date
      2014-05-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Hikeshiによる熱ストレス依存的HSP70核内移行2014

    • Author(s)
      小瀬真吾
    • Organizer
      理研シンポジウム「細胞システムの動態と論理 VI」
    • Place of Presentation
      和光市、日本
    • Year and Date
      2014-04-03 – 2014-04-04
    • Related Report
      2014 Annual Research Report
  • [Book] Encyclopaedia of Cell Biology2015

    • Author(s)
      Mimura, Y., Imamoto, N
    • Total Pages
      9
    • Publisher
      ELSEVIER
    • Related Report
      2015 Annual Research Report
  • [Book] Methods Mol. Biol.2015

    • Author(s)
      Kose, S., Funakoshi, T., Imamoto, N
    • Total Pages
      12
    • Publisher
      Springer Science
    • Related Report
      2015 Annual Research Report
  • [Book] Reconstitution of nucleocytoplasmic transport using digitonin-permeabilized cells.2015

    • Author(s)
      Kose S, Funakoshi T, *Imamoto N.
    • Publisher
      Methods Mol. Biol1262:
    • Related Report
      2014 Annual Research Report
  • [Book] Control of Nuclear Size by NPC proteins. In Cancer biology and Nuclear Envelope.2014

    • Author(s)
      Takagi M, *Imamoto N.
    • Publisher
      Adv. Exp. Med. Biol.773:
    • Related Report
      2014 Annual Research Report
  • [Book] Analysis of nucleocytoplasmic transport in digitonin-per meabilized cells under different cellular conditions.2014

    • Author(s)
      Furuta M, Kose S, Kehlenbach RH, *Imamoto N.
    • Publisher
      Methods Cell Biol.22:
    • Related Report
      2014 Annual Research Report
  • [Book] Cell fusion method to visualize interphase nuclear pore formation.2014

    • Author(s)
      Maeshima K, Funakoshi T, *Imamoto N.
    • Publisher
      Method Cell Biol.122:
    • Related Report
      2014 Annual Research Report
  • [Book] Novel approaches for identification of nuclear transport receptor substrates.2014

    • Author(s)
      Kimura M, Thakar K, Karaca S, Imamoto N, *Kehlenbach R.
    • Publisher
      Methods Cell Biol.122:
    • Related Report
      2014 Annual Research Report
  • [Remarks] 今本細胞核機能研究室/理化学研究所

    • URL

      http://www.riken.jp/research/labs/chief/cell_dyn/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 今本細胞核機能研究室

    • URL

      http://www.riken.jp/celldynamics/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 核タンパク質の輸送経路を大規模決定(プレスリリース)

    • URL

      http://www.riken.jp/pr/press/2017/20170202_1/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 理化学研究所の研究室ホームページ

    • URL

      http://www.riken.go.jp/research/labs/chief/cell_dyn/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.riken.jp/celldynamics/index.html

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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