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Study on the neural mechanism of circadian output to female reproductive functions

Research Project

Project/Area Number 19K06360
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42010:Animal production science-related
Research InstitutionMeiji University

Principal Investigator

Nakamura Takahiro  明治大学, 農学部, 専任教授 (00581985)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords体内時計 / 視交叉上核 / 加齢 / 隔離術 / 性周期 / 神経回路 / 時計遺伝子 / 光遺伝学 / 化学・光遺伝学 / 生物時計 / 概日リズム / 睡眠
Outline of Research at the Start

概日リズムは生物が地球上で生存するために獲得・発達させてきた生命の基本機能である。哺乳類における概日時計中枢は脳・視床下部・視交叉上核(SCN)に存在するが、その時計中枢から出力される時刻情報がどのように各器官系が持つ生理機能に伝えられているか不明な点が多い。これまでの加齢変化をモデルとした研究成果により、各生理機能の概日リズムの変調は、SCNからの時刻情報の出力低下やそれに伴う脱同調状態が起因するという仮説に至っている。本研究では、概日時計出力様式の解明を主目的とし、マウスを用いこの概日時計出力の機能的コネクトームの解明、特に、雌性生殖機能に入力する時刻情報経路の解明に挑む。

Outline of Final Research Achievements

Circadian rhythm is a fundamental function that organisms have acquired and developed to survive on the earth. The central circadian clock of mammals exists in the suprachiasmatic nucleus (SCN) of the hypothalamus. However, it remains unclear how the timing signal from the SCN is transmitted to the physiological functions of each organ. In this study, we investigated the functional neural circuits from the SCN to female reproductive functions using mice as model animals. Using chemogenetics and optogenetics, it was revealed that the estrous cycle was disturbed when only the AVP neurons of the SCN were inactivated. In addition, the estrous cycle was disturbed even in mice where the efferent nerve of SCN was cut. These results indicate that the neural output of AVP neurons in the SCN plays an important role in female reproductive function.

Academic Significance and Societal Importance of the Research Achievements

本研究で行った正確な日内ダイナミクスを制御するSCN機能的出力経路の解明は、広く科学研究に寄与するとともに、健康分野では概日リズムの変調に起因する各種疾患の発生基盤の理解および対策の開発につながり、食糧生産分野では家畜の繁殖・育種の効率化に貢献する。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (58 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (6 results) Journal Article (16 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 14 results,  Open Access: 12 results) Presentation (32 results) (of which Int'l Joint Research: 12 results,  Invited: 3 results) Remarks (4 results)

  • [Int'l Joint Research] Barnard College of Columbia University/Washington University in St Louis/University of California Los Angeles(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Leiden University Medical Center(オランダ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Taipei Medical University(中国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Leibniz Institute(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] カリフォルニア大学ロサンゼルス校(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] ライデン大学(オランダ)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Oak extracts modulate circadian rhythms of clock gene expression in vitro and wheel-running activity in mice2022

    • Author(s)
      Haraguchi Atsushi、Du Yao、Shiraishi Rena、Takahashi Yuki、Nakamura Takahiro J.、Shibata Shigenobu
    • Journal Title

      Sleep and Biological Rhythms

      Volume: 20 Issue: 2 Pages: 255-266

    • DOI

      10.1007/s41105-021-00365-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of heterozygous and homozygous alleles in cryptochrome-deficient mice2022

    • Author(s)
      Oda Yoshiaki、Takasu Nana N.、Ohno Sachi N.、Shirakawa Yukie、Sugimura Mitsutaka、Nakamura Takahiro J.、Nakamura Wataru
    • Journal Title

      Neuroscience Letters

      Volume: 772 Pages: 136415-136415

    • DOI

      10.1016/j.neulet.2021.136415

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Secretin receptor-deficient mice exhibit robust food anticipatory activity2022

    • Author(s)
      Sugiyama Mizuki、Nishijima Ichiko、Nakamura Wataru、Nakamura Takahiro J.
    • Journal Title

      Neuroscience Letters

      Volume: 772 Pages: 136462-136462

    • DOI

      10.1016/j.neulet.2022.136462

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic methamphetamine uncovers a circadian rhythm in multiple-unit neural activity in the dorsal striatum which is independent of the suprachiasmatic nucleus2021

    • Author(s)
      Miyazaki Shota、Tahara Yu、Colwell Christopher S.、Block Gene D.、Nakamura Wataru、Nakamura Takahiro J.
    • Journal Title

      Neurobiology of Sleep and Circadian Rhythms

      Volume: 11 Pages: 100070-100070

    • DOI

      10.1016/j.nbscr.2021.100070

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Circadian clock regulates tear secretion in the lacrimal gland,2021

    • Author(s)
      Vu CHV, Kawashima M, Nakamura W, Nakamura TJ, Tsubota K.
    • Journal Title

      Exp Eye Res.

      Volume: 108524 Pages: 108524-108524

    • DOI

      10.1016/j.exer.2021.108524

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior2021

    • Author(s)
      Maejima Takashi、Tsuno Yusuke、Miyazaki Shota、Tsuneoka Yousuke、Hasegawa Emi、Islam Md Tarikul、Enoki Ryosuke、Nakamura Takahiro J.、Mieda Michihiro
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 6 Pages: 1-18

    • DOI

      10.1073/pnas.2010168118

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Editorial: Development of Circadian Clock Functions2021

    • Author(s)
      Myung Jihwan、Nakamura Takahiro J.、Jones Jeff R.、Silver Rae、Ono Daisuke
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 735007-735007

    • DOI

      10.3389/fnins.2021.735007

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diurnal Variation in Trigeminal Pain Sensitivity in Mice2021

    • Author(s)
      Niiro Ayako、Ohno Sachi N.、Yamagata Kanae A.、Yamagata Kazuaki、Tomita Kazuo、Kuramoto Eriko、Oda Yoshiaki、Nakamura Takahiro J.、Nakamura Wataru、Sugimura Mitsutaka
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 703440-703440

    • DOI

      10.3389/fnins.2021.703440

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electrophysiological Approaches to Studying the Suprachiasmatic Nucleus2020

    • Author(s)
      Michel S, Nakamura TJ, Meijer JH, Colwell CS.
    • Journal Title

      Methods Mol Biol.

      Volume: 2130 Pages: 303-324

    • DOI

      10.1007/978-1-0716-0381-9_23

    • ISBN
      9781071603802, 9781071603819
    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Journal Article] Modeling circadian regulation of ovulation timing: age-related disruption of estrous cyclicity2020

    • Author(s)
      Ohara Takayuki、Nakamura Takahiro J.、Nakamura Wataru、Tokuda Isao T.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 16767-16767

    • DOI

      10.1038/s41598-020-73669-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reciprocal Expression Patterns of Placental Leucine Aminopeptidase/Insulin-Regulated Aminopeptidase and Vasopressin in the Murine Brain2020

    • Author(s)
      Goto Yoshikuni、Nakamura Takahiro J.、Ogawa Kenji、Hattori Akira、Tsujimoto Masafumi
    • Journal Title

      Frontiers in Molecular Biosciences

      Volume: 7 Pages: 168-168

    • DOI

      10.3389/fmolb.2020.00168

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A high-salt/high fat diet alters circadian locomotor activity and glucocorticoid synthesis in mice2020

    • Author(s)
      Yokoyama Yoko、Nakamura Takahiro J.、Yoshimoto Karen、Ijyuin Honoka、Tachikawa Naoyuki、Oda Haruka、Shiraishi Rena、Shinohara Kaori、Kumadaki Kayo、Honda Shiori、Nakamura Anna、Kitamura Naho、Tsubota Kazuo、Watanabe Mitsuhiro
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 5 Pages: e0233386-e0233386

    • DOI

      10.1371/journal.pone.0233386

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Secretin receptor-deficient mice exhibit altered circadian rhythm in wheel-running activity2020

    • Author(s)
      Sugiyama Mizuki、Nishijima Ichiko、Miyazaki Shota、Nakamura Takahiro J.
    • Journal Title

      Neuroscience Letters

      Volume: 722 Pages: 134814-134814

    • DOI

      10.1016/j.neulet.2020.134814

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppression of Blue Light at Night Ameliorates Metabolic Abnormalities by Controlling Circadian Rhythms2019

    • Author(s)
      Nagai Norihiro、Ayaki Masahiko、Yanagawa Tatsuo、Hattori Atsuhiko、Negishi Kazuno、Mori Takuro、Nakamura Takahiro J.、Tsubota Kazuo
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 60 Issue: 12 Pages: 3786-3793

    • DOI

      10.1167/iovs.19-27195

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of testosterone on circadian rhythmicity in old mice2019

    • Author(s)
      Atsuyoshi Hashimoto, Shingo Fujiki, Wataru Nakamura & Takahiro J. Nakamura
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 69 Issue: 5 Pages: 791-798

    • DOI

      10.1007/s12576-019-00695-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 環境時刻と概日リズムとの調和による不妊解消戦略2019

    • Author(s)
      中村渉、中村 孝博
    • Journal Title

      実験医学

      Volume: 37 Pages: 386-391

    • Related Report
      2019 Research-status Report
  • [Presentation] 雌性生殖機能におけるAVPニューロン特異的GABAシグナリングの役割2021

    • Author(s)
      杉山瑞樹、陳佳旭、三枝理博、中村孝博
    • Organizer
      第28回日本時間生物学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 概日リズムに駆動する液性出力候補因子BDNFの評価2021

    • Author(s)
      宮﨑翔太、中村渉、中村孝博
    • Organizer
      第28回日本時間生物学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 雌性生殖におけるAVPニューロンの役割2021

    • Author(s)
      陳佳旭、杉山瑞樹、三枝理博、中村孝博
    • Organizer
      第28回日本時間生物学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] CBA 系統マウスにおける概日リズムの亜系統差2021

    • Author(s)
      白石麗奈、橋本惇能、武井美澪、下村和宏、中村孝博
    • Organizer
      第28回日本時間生物学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 女子大学生における月経周期と概日リズムの相関2021

    • Author(s)
      小髙つぐみ、高須奈々、中村渉、 中村孝博
    • Organizer
      第28回日本時間生物学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] IVCシステム使用時の微生物モニタリングの一例2021

    • Author(s)
      佐古典久、市瀬誠一、直井実穂、中村孝博、加藤克彦
    • Organizer
      第55回日本実験動物技術者協会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] IVCシステム使用時の微生物モニタリング法の構築2021

    • Author(s)
      佐古典久、市瀬誠一、直井実穂、中村孝博、加藤克彦
    • Organizer
      静岡実験動物研究会 令和2-3年度大会(第50回総会及び第48回研究発表会)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 視交叉上核隔離が概日リズムに与える影響2020

    • Author(s)
      宮﨑翔太、前嶋大智、水田習斗、中村孝博
    • Organizer
      第15回環境生理学プレコングレス
    • Related Report
      2020 Research-status Report
  • [Presentation] 雌性生殖におけるAVPニューロンのGABAの役割2020

    • Author(s)
      陳佳旭、杉山瑞樹、三枝理博、中村孝博
    • Organizer
      第27回日本時間生物学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] セクレチン受容体欠損マウスにおける給餌予知活動2020

    • Author(s)
      杉山瑞樹、西島維知子、中村渉、中村孝博
    • Organizer
      第27回日本時間生物学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Effects of the isolation of suprachiasmatic nucleus on circadian rhythmicity2020

    • Author(s)
      Shota Miyazaki, Daichi Maejima, Shuto Mizuta, Wataru Nakamura, Takahiro J. Nakamura
    • Organizer
      SRBR 2020 Society for Research on Biological Rhythms
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Roles of GABA in suprachiasmatic AVP Neurons on Female Reproductive Function2020

    • Author(s)
      Jiaxu Chen, Mizuki Sugiyama, Michihiro Mieda, Takahiro J. Nakamura
    • Organizer
      SRBR 2020 Society for Research on Biological Rhythms
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Circadian Rhythms of Triglyceride Accumulation in Adipocytes2020

    • Author(s)
      Rena Shiraishi, Satomi Morita, Yoshikuni Goto, Hikari Yoshitane, Yoshimasa Asano, Yoshitaka Fukada, Yasushi Mizoguchi, Takahiro J. Nakamura
    • Organizer
      SRBR 2020 Society for Research on Biological Rhythms
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脳内メトアンフェタミン概日振動体の観察2020

    • Author(s)
      宮崎翔太、田原優、ColwellChristopher S、Block Gene D、中村渉、中村孝博
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] The circadian clock in mammals2019

    • Author(s)
      Takahiro J. Nakamura, Nana N. Takasu, Wataru Nakamura
    • Organizer
      ICMMA2019 International Conference on "Spatio-temporal patterns on various levels of the hierarchy of life"
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] In vivo monitoring reveals two different oscillators in methamphetamine treated mice2019

    • Author(s)
      Shota Miyazaki, Yu Tahara, Christopher S. Colwell, Gene D. Block, Wataru Nakamura, Takahiro J. Nakamura
    • Organizer
      ICMMA2019 International Conference on "Spatio-temporal patterns on various levels of the hierarchy of life"
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Roles of GABA in Suprachiasmatic AVP Neurons on Female Reproductive Functions2019

    • Author(s)
      Mizuki Sugiyama, Michihiro Mieda, Takahiro J. Nakamura, Roles of GABA in Suprachiasmatic AVP Neurons on Female Reproductive Functions
    • Organizer
      ICMMA2019 International Conference on "Spatio-temporal patterns on various levels of the hierarchy of life"
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Circadian Strategy for Female Reproduction2019

    • Author(s)
      Sayuri Sakazume, Wataru Nakamura, Takahiro J. Nakamura
    • Organizer
      ICMMA2019 International Conference on "Spatio-temporal patterns on various levels of the hierarchy of life"
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of the isolation of suprachiasmatic nucleus on rhythms of body temperature and peripheral clocks2019

    • Author(s)
      Daichi Maejima, Shota Miyazaki, Shuto Mizuta, Wataru Nakamura, Takahiro J. Nakamura
    • Organizer
      ICMMA2019 International Conference on "Spatio-temporal patterns on various levels of the hierarchy of life"
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] サーカディアンリズム同調と性周期2019

    • Author(s)
      中村渉、中村孝博、織田善晃、高須奈々
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 時間給餌によるハンチントンモデル病モデルマウスの疾患予防効果2019

    • Author(s)
      田原優、Daniel S.Whittaker,Dawn H.Loh,Huei-Bin Wang,Christopher SH.Luk,Dika Kujis,中村孝博、Gene D.Block,Christopher S.Colwell
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 視交叉上核隔離が概日リズムに与える影響2019

    • Author(s)
      宮崎翔太、前嶋大智、水田習斗、中村孝博
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 雌性生殖機能に対する概日リズムストラテジー2019

    • Author(s)
      坂詰小百合、中村渉、中村孝博
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 雌性生殖機能における視交叉上核AVP細胞特異的GABAの役割2019

    • Author(s)
      杉山瑞樹、三枝理博、中村孝博
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 排卵タイミングの概日制御に関する数理モデル2019

    • Author(s)
      大原隆之、中村孝博、中村渉、徳田功
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 時間栄養学による神経変性疾患の予防2019

    • Author(s)
      田原 優, Daniel S. Whittaker, Dawn H. Loh, Huei-Bin Wang, Christopher SH. Luk, Dika Kuljis, 中村 孝博, 柴田 重信, Gene D. Block, Christopher S. Colwell
    • Organizer
      第6回時間栄養科学研究会/第14回NutriRhythm(ニュートリズム)検討会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of the isolation of suprachiasmatic nucleus on circadian rhythmicity2019

    • Author(s)
      Shota Miyazaki, Daichi Maejima, Shuto Mizuta, Wataru Nakamura, Takahiro J. Nakamura
    • Organizer
      16th Congress of the European Biological Rhythms Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Roles of GABA in Suprachiasmatic AVP Neurons on Female Reproductive Functions2019

    • Author(s)
      Mizuki Sugiyama, Michihiro Mieda, Takahiro J. Nakamura
    • Organizer
      6th Congress of the European Biological Rhythms Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Time-restricted feeding is effective in the BACHD mouse model of Huntington’s disease2019

    • Author(s)
      Yu Tahara, Daniel S. Whittaker, Dawn H. Loh, Huei-Bin Wang, Christopher S.H. Luk, Dika Kuljis, Takahiro J. Nakamura, Shigenobu Shibata, Gene D. Block, Christopher S. Colwell
    • Organizer
      16th Congress of the European Biological Rhythms Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Modeling circadian regulation of ovulation timing: Age-related disruption of estrous cyclicity2019

    • Author(s)
      Takayuki Ohara, Takahiro J. Nakamura, Wataru Nakamura, Isao T. Tokuda
    • Organizer
      16th Congress of the European Biological Rhythms Society
    • Related Report
      2019 Research-status Report
  • [Presentation] 体内時計が制御する睡眠覚醒リズムと加齢に伴う機能低下2019

    • Author(s)
      中村渉、中村孝博、高須奈々
    • Organizer
      日本睡眠学会第44回定期学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Effects of the isolation of suprachiasmatic nucleus on circadian rhythmicity2019

    • Author(s)
      Shota Miyazaki, Daichi Maejima, Shuto Mizuta, Wataru Nakamura, Takahiro J. Nakamura
    • Organizer
      V World Congress of Chronobiology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] 明治大学農学部動物生理学研究室

    • URL

      http://www.isc.meiji.ac.jp/~chrono/index.html

    • Related Report
      2021 Annual Research Report 2020 Research-status Report 2019 Research-status Report
  • [Remarks] 明治大学農学部生命科学科

    • URL

      https://meiji-lifesci.jp/master/nakamura/

    • Related Report
      2020 Research-status Report
  • [Remarks] 教員データベース

    • URL

      https://gyoseki1.mind.meiji.ac.jp/mjuhp/KgApp?kyoinId=ymddgogiggy

    • Related Report
      2020 Research-status Report
  • [Remarks] Researchmap

    • URL

      https://researchmap.jp/tjnakamura

    • Related Report
      2020 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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