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Molecular physiological basis of modulation and repair by oxidative stress in oral/gut/ brain chemosensory-endocrine interaction for dietary regulation.

Research Project

Project/Area Number 18H02968
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57010:Oral biological science-related
Research InstitutionKyushu University

Principal Investigator

Ninomiya Yuzo  九州大学, 五感応用デバイス研究開発センター, 特任教授 (50076048)

Co-Investigator(Kenkyū-buntansha) 吉田 竜介  岡山大学, 医歯薬学総合研究科, 教授 (60380705)
岩田 周介  九州大学, 歯学研究院, 助教 (60780062)
安松 啓子  九州大学, 五感応用デバイス研究開発センター, 特任准教授 (50380704)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords酸化ストレス / 味覚 / シグナル伝達 / 内分泌 / 神経科学
Outline of Final Research Achievements

Leptin and angiotensin II are hormones that regulate eating and drinking cravings in the brain, and sweet and salt taste sensitivities in the peripheral taste organ and contribute to energy and Na+ homeostasis. Also, the hormones at high concentrations are known to act as oxidative stress inducers in their target organs. This study investigated potential effects of oxidative stress on taste cells and target molecules based on analyses of mouse neural and behavioral taste responses and molecular expression. The results showed that oxidative stress agents increased sweet responses and decreased sodium responses and their targets of oxidative stress may be at intracellular region of KATP (sweet taste) known as a leptin target, and at extracellular region of ENaCs (sodium taste) known as an angiotensin II target.

Academic Significance and Societal Importance of the Research Achievements

本研究は、肥満・高血圧者増加の一因を成す甘味・塩味感受性のレプチン、アンギオテンシンII内分泌調節系の酸化ストレスによる変調について、マウス味神経・行動応答と味細胞の遺伝子・分子発現を基に検索した。その結果、内分泌系が高濃度で誘導する酸化ストレスは、代謝センサー(KATP)発現味細胞を介して甘味上昇を、Naセンサー(ENaC)発現細胞を介して塩味低下を導き、摂取を促進させることを見出した。この酸化ストレスによる甘味塩味感受性・摂取行動変化の発見は、味高嗜好性形成原理の一端を明らかにし、食の健全化への今後の新たな研究展開への起点となり、学際的意義のみならず社会的意義をもたらすものと思われる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(63 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (44 results) (of which Int'l Joint Research: 17 results,  Invited: 16 results) Book (2 results) Remarks (6 results)

  • [Int'l Joint Research] モネル化学感覚研究所(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] モネル化学感覚研究所(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] モネル化学感覚研究所(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Phosphatidylinositol‐3 kinase mediates the sweet suppressive effect of leptin in mouse taste cells2021

    • Author(s)
      Yoshida Ryusuke、Margolskee Robert F.、Ninomiya Yuzo
    • Journal Title

      Journal of Neurochemistry

      Volume: - Pages: 1-13

    • DOI

      10.1111/jnc.15268

    • NAID

      120007180828

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The sweet taste receptor, glucose transporters, and the ATP-sensitive K+ (KATP) channel: sugar sensing for the regulation of energy homeostasis2021

    • Author(s)
      Yoshida Ryusuke、Yasumatsu Keiko、Ninomiya Yuzo
    • Journal Title

      Current Opinion in Physiology

      Volume: 20 Pages: 57-63

    • DOI

      10.1016/j.cophys.2021.01.009

    • NAID

      120007185585

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of characteristic compounds of moderate volatility in breast cancer cell lines2020

    • Author(s)
      Tanaka Mitsuru、Hsuan Chung、Oeki Masataka、Shen Weilin、Goda Asuka、Tahara Yusuke、Onodera Takeshi、Sanematsu Keisuke、Rikitake Tomotsugu、Oki Eiji、Ninomiya Yuzo、Kurebayashi Rintaro、Sonoda Hideto、Maehara Yoshihiko、Toko Kiyoshi、Matsui Toshiro
    • Journal Title

      PLOS ONE

      Volume: 15(6) Pages: 0235442-0235456

    • DOI

      10.1371/journal.pone.0235442

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sodium‐glucose cotransporter 1 as a sugar taste sensor in mouse tongue2020

    • Author(s)
      Yasumatsu Keiko、Ohkuri Tadahiro、Yoshida Ryusuke、Iwata Shusuke、Margolskee Robert F.、Ninomiya Yuzo
    • Journal Title

      Acta Physiol (Oxf).

      Volume: 230

    • DOI

      10.1111/apha.13529

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparative analysis of enteroendocrine cells and their hormones between mouse intestinal organoids and native tissues2020

    • Author(s)
      Ohki Junko、Sakashita Akihiko、Aihara Eitaro、Inaba Akihiko、Uchiyama Hironobu、Matsumoto Masahito、Ninomiya Yuzo、Yamane Takumi、Oishi Yuichi、Iwatsuki Ken
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 84(5) Pages: 936-942

    • DOI

      10.1080/09168451.2020.1713043

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of Renin-Angiotensin System Components in the Taste Organ of Mice2019

    • Author(s)
      Shigemura Noriatsu、Takai Shingo、Hirose Fumie、Yoshida Ryusuke、Sanematsu Keisuke、Ninomiya Yuzo
    • Journal Title

      Nutrients.

      Volume: 11 Pages: 1-18

    • DOI

      10.3390/nu11092251

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of insulin signaling on mouse taste cell proliferation2019

    • Author(s)
      Takai Shingo、Watanabe Yu、Sanematsu Keisuke、Yoshida Ryusuke、Margolskee Robert F.、Jiang Peihua、Atsuta Ikiru、Koyano Kiyoshi、Ninomiya Yuzo、Shigemura Noriatsu
    • Journal Title

      PLoS One.

      Volume: 14 Pages: 0225190-0225190

    • DOI

      10.1371/journal.pone.0225190

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fatty acid taste quality information via GPR120 in the anterior tongue of mice2018

    • Author(s)
      Yasumatsu Keiko、Iwata Shusuke、Inoue Mayuko、Ninomiya Yuzo
    • Journal Title

      Acta Physiologica

      Volume: 226

    • DOI

      10.1111/apha.13215

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Signal detection and transmission pathways for sugars and fatty acids in the mouse peripheral taste system.2020

    • Author(s)
      Ninomiya Y, Yasumatsu K, Iwata S, Yoshida R.
    • Organizer
      ISOT2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Insulin-mTOR signaling may regulate mouse taste cell generation.2020

    • Author(s)
      Takai S, Watanabe Y, Margolskee RF, Jiang P, Ninomiya Y, Shigemura N.
    • Organizer
      ISOT2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] オルガノイド培養系を用いた味細胞分化メカニズム解明への新たなアプローチ2020

    • Author(s)
      髙井 信吾,渡邊 雄,Robert F. Margolskee,Peihua Jiang,二ノ宮 裕三,重村 憲徳.
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] アドレノメデュリンによるT1Rs 非依存性経路を介するマウス鼓索神経甘味応答増強効果2020

    • Author(s)
      岩田 周介,井上 真由子,吉田 竜介,重村 憲徳,二ノ宮 裕三.
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ラット嚥下反射に及ぼすオレキシンAとグルカゴン様ペプチド1の相互抑制作用2020

    • Author(s)
      小橋 基,美藤 純弘,吉田 竜介.
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 抗不整脈薬フレカイニドによる酸味感受性の増強2020

    • Author(s)
      川端 由子,髙井 信吾,吉田 竜介,實松 敬介,重村 憲徳.
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高度肥満症患者の空腸における味覚シグナル分子の伝令RNA 発現レベル2020

    • Author(s)
      安尾 敏明,硲 哲崇,二ノ宮 裕三.
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] アドレノメデュリンによるT1Rs 非依存性甘味受容機構を介したマウス鼓索神経甘味応答の増強2020

    • Author(s)
      岩田 周介,井上 真由子,吉田 竜介,重村 憲徳,二ノ宮 裕三.
    • Organizer
      日本味と匂学会 第54回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] レプチンによる甘味細胞応答抑制にはPI3K が関与する2020

    • Author(s)
      吉田 竜介,Robert F. Margolskee,二ノ宮 裕三.
    • Organizer
      日本味と匂学会 第54回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 甘味受容体感受性における低pHによる抑制効果の分子メカニズム2020

    • Author(s)
      實松 敬介,二ノ宮 裕三,重村 憲徳
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 低濃度塩添加によるヒト甘味認知閾値の低下2020

    • Author(s)
      吉田 竜介,實松 敬介,高井 信吾,岩田 周介,重村 憲徳
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Signal detection and transmission pathways for sugars and fatty acids in the peripheral taste systems.2019

    • Author(s)
      Ninomiya Yuzo
    • Organizer
      39th Blankrnese Conferences.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 味細胞オルガノイドを用いた味細胞分化/増殖に影響を及ぼす因子の探索2019

    • Author(s)
      髙井 信吾,Robert F. Margolskee,Peihua Jiang,二ノ宮裕三,重村 憲徳
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 脂肪酸受容体の舌における部位的・時間的機能分担2019

    • Author(s)
      安松啓子,二ノ宮裕三
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] アドレノメデュリンによる T1Rs 非依存性経路を介するマウス鼓索神経糖 応答への影響2019

    • Author(s)
      岩田 周介,井上真由子,吉田 竜介,二ノ宮裕三
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス味細胞におけるmechanistic target of rapamycin (mTOR)の働き2019

    • Author(s)
      高井信吾,Margolskee Robert. F,Jiang Peihua ,二ノ宮裕三,重村 憲徳
    • Organizer
      日本味と匂学会第53回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] T1R3-KOマウスの鼓索神経単一神経記録および行動応答測定によるグルコースの味覚情報解析2019

    • Author(s)
      安松啓子,岩田周介,二ノ宮裕三
    • Organizer
      日本味と匂学会第53回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アドレノメデュリンによるT1Rs非依存性経路を介したマウス鼓索神経応答への影響2019

    • Author(s)
      岩田周介,井上真由子,吉田竜介,二ノ宮裕三
    • Organizer
      日本味と匂学会第53回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Taste Session:Overview2019

    • Author(s)
      Ninomiya Yuzo
    • Organizer
      The 48th Naito Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Contribution of SGLTs to sugar sensing as T1R-independent mechanisms in mouse gustatory tissues.2019

    • Author(s)
      Yasumatsu Keiko, Ohkuri Tadahiro, Iwata Shusuke, Margolskee Robert F, Ninomiya Y.uzo
    • Organizer
      The 18th ISMNTOP
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Signaling cascade for the sweet suppressive effect of leptin.2019

    • Author(s)
      Yoshida Ryusuke, Margolskee Robert F, Ninomiya Yuzo.
    • Organizer
      The 18th ISMNTOP
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The effect of Adrenomedullin on chorda tympani nerve responses to sugars via T1rs-independent pathway in mice.2019

    • Author(s)
      Iwata Shusuke, Inoue Mayuko, Yoshida Ryusuke, Ninomiya Yuzo.
    • Organizer
      The 18th ISMNTOP
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Insulin - mTOR signaling regulate taste bud organoid growth.2019

    • Author(s)
      Takai Shingo, Margolskee Robert F, Jiang Peihua, Ninomiya Yuzo, Shigemura Noriatsu.
    • Organizer
      The 18th ISMNTOP
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 未知の味・カロリーシグナル伝達経路の探索と食調節2019

    • Author(s)
      二ノ宮裕三
    • Organizer
      千里ライフサイエンスセミナーN4(感覚のサイエンス~豊かな社会の実現に向けて~)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Novel taste sensory pathways for sugars and fatty acids in the mouse periphery.2019

    • Author(s)
      Ninomiya Y, Yasumatsu K, Iwata S, Yoshida R.
    • Organizer
      FAOPS2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Involvement of phosphoinositide 3-kinase in leptin signaling in sweet sensitive taste cells.2019

    • Author(s)
      Yoshida R, Margolskee. RF, Ninomiya Y.
    • Organizer
      FAOPS2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The effects of insulin signaling on mouse taste bud organoid.2019

    • Author(s)
      Takai S, Jiang P, Margolskee RF, Ninomiya Y, Shigemura N.
    • Organizer
      FAOPS2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Adrenomedullin enhances chorda tympani nerve responses to sugars in mice.2019

    • Author(s)
      Iwata S, Inoue M, Yasumatsu K, Yoshida R, Ninomiya Y.
    • Organizer
      FAOPS2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Altered expression of taste signaling elements in jejunal tissue of obese patients.2019

    • Author(s)
      Yasuo T, Jiang P, Wood C, Chu Z, Benotti P, Still C, Rolston DD, Margolskee RF, Ninomiya Y.
    • Organizer
      FAOPS2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fatty acid-responding neurons in mouse glossopharyngeal nerve.2019

    • Author(s)
      Yasumatsu K, Iwata S, Inoue M, Ninomiya Y.
    • Organizer
      FAOPS2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of sugar transporters and calorie sensors in taste cells.2018

    • Author(s)
      Ninomiya Y, Yasumatsu K, Yoshida R, Iwata S, Shigemura N.
    • Organizer
      ECRO2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] マウス舌咽神経における脂肪酸に対する単一神経応答の解析2018

    • Author(s)
      安松啓子,岩田周介,二ノ宮裕三
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] アドレノメデュリンによるマウス鼓索神経応答への影響2018

    • Author(s)
      岩田周介,安松啓子,吉田竜介,二ノ宮裕三
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 末梢における甘味の受容と調節メカニズム2018

    • Author(s)
      吉田竜介
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] グルカゴン様ペプチド-1 受容体遺伝子多型と甘味認知閾値との関連について2018

    • Author(s)
      實松敬介 井上真由子,髙井信吾,二ノ宮裕三
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] インスリンシグナルは味細胞の分化・増殖に関与する2018

    • Author(s)
      髙井信吾,Robert F. Margolskee,Peihua Jiang,二ノ宮裕三, 重村憲徳
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 味覚障害誘発薬剤がマウス味蕾オルガノイドへ与える影響2018

    • Author(s)
      川端由子,高井信吾,吉田竜介,實松敬介,重村憲徳
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 味細胞におけるレプチンシグナリング2018

    • Author(s)
      吉田竜介
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス舌咽神経単一神経記録による脂肪酸受容機構の解析2018

    • Author(s)
      安松啓子,岩田周介,井上真由子,二ノ宮裕三
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 低pH条件下における甘味受容体感受性の解析2018

    • Author(s)
      實松敬介,尾崎礼奈,中林開人,二ノ宮裕三,重村憲徳
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス味細胞の分化/増殖におけるインスリンの効果2018

    • Author(s)
      高井信吾,Margolskee Robert. F,Jiang Peihua ,二ノ宮裕三,重村 憲徳
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] アドレノメデュリンのマウス鼓索神経応答への影響2018

    • Author(s)
      岩田周介,安松啓子,井上真由子,吉田竜介,二ノ宮裕三
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Leptin signaling pathway linking from activation of leptin receptor to KATP channel activation in sweet sensitive taste cells in mice.2018

    • Author(s)
      Yoshida R, Margolskee RF ,Ninomiya Y.
    • Organizer
      17th ISMNTOP
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The potential effects of insulin signaling on mouse taste bud organoid.2018

    • Author(s)
      Takai S, Margolskee RF , Jiang P, Ninomiya Y, Shigemura N.
    • Organizer
      17th ISMNTOP
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] The Senses: A Comprehensive Reference 2nd Edition Vol. 3 Chemosenses: Olfaction and Taste 3-10 Sweet and Umami taste2021

    • Author(s)
      Yoshida R, Ninomiya Y.
    • Total Pages
      20
    • Publisher
      Elsevier
    • ISBN
      9780128054093
    • Related Report
      2020 Annual Research Report
  • [Book] 日本歯科評論 No.915 79/1 2019年1月号2019

    • Author(s)
      二ノ宮裕三
    • Total Pages
      5
    • Publisher
      ヒョーロン・パブリッシャーズ
    • Related Report
      2018 Annual Research Report
  • [Remarks] 九州大学 五感応用デバイス研究開発センター

    • URL

      https://www.rdctos.kyushu-u.ac.jp/

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      2020 Annual Research Report
  • [Remarks] 九州大学大学院 歯学研究院 口腔機能解析学分野

    • URL

      https://www.dent.kyushu-u.ac.jp/sosiki/a06/

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      2020 Annual Research Report
  • [Remarks] 岡山大学大学院医歯薬学総合研究科口腔生理学分野

    • URL

      http://www.cc.okayama-u.ac.jp/~oralphys/OralPhysiology.html

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      2020 Annual Research Report 2019 Annual Research Report
  • [Remarks] 九州大学 五感応用デバイス研究開発センター

    • URL

      http://www.rdctos.kyushu-u.ac.jp/

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] 九州大学大学院 歯学研究院 口腔機能解析学分野

    • URL

      http://www.dent.kyushu-u.ac.jp/sosiki/a06/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 九州大学大学院歯学研究院口腔機能解析学

    • URL

      http://www.dent.kyushu-u.ac.jp/sosiki/a06/

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      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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