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Genomic analysis of Shati/Nat8l to protect use methamphetamine

Research Project

Project/Area Number 17K19801
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Society medicine, Nursing, and related fields
Research InstitutionUniversity of Toyama

Principal Investigator

Nitta Atsumi  富山大学, 大学院医学薬学研究部(薬学), 教授 (20275093)

Co-Investigator(Kenkyū-buntansha) 宇野 恭介  富山大学, 大学院医学薬学研究部(薬学), 助教 (30608774)
池田 和隆  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 分野長 (60281656)
西澤 大輔  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主席研究員 (80450584)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
KeywordsSHATI/NAT8L / DNAメチル化 / 覚醒剤乱用患者 / バイサルトファイト法 / SHATI/NAT8L / Shati/Nat8l / 覚醒剤 / 薬物乱用
Outline of Final Research Achievements

Methamphetamine abuse is a serious problem all over the world. We found that Shati/Nat8l protects addiction of methamphetamine. In this study, we investigated whether DNA mutation or modification of Shati/Nat8l in the patients with addiction. No differences of the genomic Shati/Nat8l in methamphetamine abuser. We found the change of DNA methylation in the CpG island, suggesting one possibility of new diagnosis methods for therapy for methamphetamine abusers. In near future, we attempt to check the methylation degree in the other substance abusers.

Academic Significance and Societal Importance of the Research Achievements

覚醒剤乱用は大きな社会問題であり、犯罪であることに加え、健康被害も大きい。最近では、違法薬物乱用も疾病ととらえ、医療の対象であると考えられている。遺伝子の修飾の程度で、薬物依存治療の進行の度合いが分かれば、治療法開発に対して大きな意義となる。そこで、本研究では、世界的にもほとんどない覚醒剤乱用患者の遺伝子バンクを使用して、調べたところ、覚醒剤患者に特徴的な遺伝子変異は見出されなかったが、Shati/Nat8lの遺伝子の発現調節部位での修飾の程度に有意な変化があることを分かった。これらの研究成果は、覚醒剤乱用患者の治療の進行程度を推測する方法につながると考えられる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (49 results)

All 2019 2018 2017 Other

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (35 results) (of which Int'l Joint Research: 16 results,  Invited: 6 results) Book (2 results) Remarks (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Inhibitory effects of Shati/Nat8l overexpression in the medial prefrontal cortex on methamphetamine‐induced conditioned place preference in mice2019

    • Author(s)
      Meriem Haddar, Kyosuke Uno, Katsunori Azuma, Shin‐ichi Muramatsu, Atsumi Nitta
    • Journal Title

      Addiction Biology

      Volume: 印刷中 Issue: 3

    • DOI

      10.1111/adb.12749

    • NAID

      120006941667

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shati/Nat8l knockout mice show behavioral deficits ameliorated by atomoxetine and methylphenidate2018

    • Author(s)
      Toriumi Kazuya、Tanaka Junko、Mamiya Takayoshi、Alkam Tursun、Kim Hyoung-Chun、Nitta Atsumi、Nabeshima Toshitaka
    • Journal Title

      Behavioural Brain Research

      Volume: 339 Pages: 207-214

    • DOI

      10.1016/j.bbr.2017.11.040

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Overexpression of transmembrane protein 168 in the mouse nucleus accumbens induces anxiety and sensorimotor gating deficit2017

    • Author(s)
      Fu Kequan、Miyamoto Yoshiaki、Sumi Kazuyuki、Saika Eriko、Muramatsu Shin-ichi、Uno Kyosuke、Nitta Atsumi
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 12 Pages: e0189006-e0189006

    • DOI

      10.1371/journal.pone.0189006

    • NAID

      120006402038

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination development2017

    • Author(s)
      Sumi Kazuyuki、Uno Kyosuke、Noike Hiroshi、Tomohiro Takenori、Hatanaka Yasumaru、Furukawa-Hibi Yoko、Nabeshima Toshitaka、Miyamoto Yoshiaki、Nitta Atsumi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 16872-16872

    • DOI

      10.1038/s41598-017-17151-1

    • NAID

      120006402037

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of the accumbal osteopontin-interacting transmembrane protein 168 in methamphetamine-induced place preference and hyperlocomotion in mice2017

    • Author(s)
      Fu Kequan、Miyamoto Yoshiaki、Otake Kazuya、Sumi Kazuyuki、Saika Eriko、Matsumura Shohei、Sato Naoki、Ueno Yuka、Seo Seunghee、Uno Kyosuke、Muramatsu Shin-ichi、Nitta Atsumi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 13084-13084

    • DOI

      10.1038/s41598-017-13289-0

    • NAID

      120006402035

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Striatal N-Acetylaspartate Synthetase Shati/Nat8l Regulates Depression-Like Behaviors via mGluR3-Mediated Serotonergic Suppression in Mice2017

    • Author(s)
      Miyamoto Yoshiaki、Iegaki Noriyuki、Fu Kequan、Ishikawa Yudai、Sumi Kazuyuki、Azuma Sota、Uno Kyosuke、Muramatsu Shin-ichi、Nitta Atsumi
    • Journal Title

      International Journal of Neuropsychopharmacology

      Volume: 20 Issue: 12 Pages: 1027-1035

    • DOI

      10.1093/ijnp/pyx078

    • NAID

      120006402036

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The involvement of brain-derived neurotrophic factor in 3,4-methylenedioxymethamphetamine-induced place preference and behavioral sensitization2017

    • Author(s)
      Akihiro Mouri, Yukihiro Noda, Minae Niwa, Yurie Matsumoto, Takayoshi Mamiya, Atsumi Nitta, Kiyofumi Yamada, Shoei Furukawa, Tatsunori Iwamura, Toshitaka Nabeshima
    • Journal Title

      Behavioural Brain Research

      Volume: 329 Pages: 157-165

    • DOI

      10.1016/j.bbr.2017.04.052

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 薬物依存関連遺伝子Shati/Nat8l、Piccolo およびTMEM168の生理機能および薬物依存治療薬標的としての有用性2019

    • Author(s)
      新田淳美
    • Organizer
      第92回日本薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Attenuation of the formation of CPP by methamphetamine in Shati/Nat8l overexpressed mice in the prefrontal cortex2018

    • Author(s)
      Haddar M, Uno K, Muramatsu SI, Nitta A
    • Organizer
      CINP 31th World Congress (CINP2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Attenuation pharmacological effects of methamphetamine by Piccolo knockdown in the nucleus accombens in mice2018

    • Author(s)
      Kusui Y, Uno K, Ge B, Morishita S, Miyamoto Y, Muramatsu SI, Nitta A
    • Organizer
      CINP 31th World Congress (CINP2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Behavioral impairment via delay myelination development in the prefrontal cortex of SHATI/NAT8L knockout mice2018

    • Author(s)
      Nitta A, Sumi K, Noike H, Miyamoto Y, Uno K
    • Organizer
      CINP 31th World Congress (CINP2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sexual differences of cognitive impairment induced by deletion of Shati/Nat8l2018

    • Author(s)
      Uno K, Endo K, Sumi K, Hadda Mr, Muramatsu SI, Miyamoto Y, Nitta A
    • Organizer
      CINP 31th World Congress (CINP2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibitory effects of accumbal transmembrane protein 168 (TMEM168) on methamphetamine-induced place2018

    • Author(s)
      Nitta A, Fu K, Otake K, Sumi K, Saika E, Sato N, Ueno Y, Uno K, Muramatsu SI, Miyamoto Y
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018 Kyoto)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cognitive dysfunction induced by the deletion of NAA synthase Shati/NatSI in mice2018

    • Author(s)
      Uno K, EndoK, Sumi K, Meriem H, Miyamoto Y, Muramatsu SI, Nitta A
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018 Kyoto)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibitory effects of Shati/Nat81 overexpression in the medial prefrontal cortex on the methamphetamine induced-CPP in mice2018

    • Author(s)
      Haddar M, Uno K, Muramatsu SI, Nitta A
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018 Kyoto)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibitory effect of knockdown Piccolo on methamphetamine-induced behavioral changes via dopamine/GABA release in the nucleus accumbens of mice2018

    • Author(s)
      Kusui Y, Uno K, Ge B, Morishita S, Miyamoto Y, Muramatsu SI, Nitta A
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018 Kyoto)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Behavioral impairment associated with dysfunction of myelination by Shati/Nat8L deficit in mice2018

    • Author(s)
      Noike H, Sumi K, Uno K, Tomohiro T, Hatanaka Y, Miyamoto Y, Nitta A.
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018 Kyoto)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Vulnerability of social defeats in the overexpressed striatal SHATI/NATSL in mice2018

    • Author(s)
      Miyanishi H, Uno K, Miyazaki T, Sodeyama K, Fuziwara T, Muramatsu SI, Miyamoto SI, Nitta A
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018 Kyoto)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Behavioral and neurochemical analyses in the Piccolo knockdown mice as a new animal model for schizophrenia.2018

    • Author(s)
      Hamatani K, Miyamoto Y, Fu K, Inagaki R, Oketani Y, Muramatsu SI, Uno K, Nitta A
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018 Kyoto)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Attenuation of methamphetamine-induced CPP by Shati/Nat8l overexpression in medial prefrontal cortex of mice.2018

    • Author(s)
      Haddar M, Uno K, Azuma K, Muramatsu SI, Nitta A.
    • Organizer
      The Third International Symposium on Toyama-Asia-Africa Pharmaceutical Network
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Attenuation of methamphetamine-induced CPP by Shati/Nat8l overexpression in medial prefrontal cortex of mice2018

    • Author(s)
      Hamatani K, Miyamoto Y, Fu K, Inagaki R, Muramatsu SI, Uno K, Nitta A
    • Organizer
      The Third International Symposium on Toyama-Asia-Africa Pharmaceutical Network
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「AAVベクターによるTMEMの過剰発現は薬物依存関連行動と不安作用を変化させる」(Effects of overexpression of TMEM-induced by AAV on the behabioral changes of the drug dependence and anxiety2018

    • Author(s)
      新田淳美
    • Organizer
      第24回日本遺伝子細胞治療学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] SHATI/NAT8L欠損マウスにおける脳ミエリン形成遅延による社会性能力の低下2018

    • Author(s)
      新田淳美、鷲見和之、野池 悠、宮本嘉明、宇野恭介
    • Organizer
      第133回日本薬理学会近畿部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Requirement of postmortem brain research in the psycopharmacological study of a novel molecule, Piccolo2018

    • Author(s)
      新田淳美
    • Organizer
      第40回日本生物学的精神医学会・第61回日本神経化学会大会合同年会 2018KOBE
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] プレシナプス性細胞基質タンパク質Piccoloに着目した新規総合失調症モデル動物の開発 (シンポジウム2 精神疾患の次世代医療に向けて)2018

    • Author(s)
      宮本嘉明、濱谷康平、稲垣 良、傅 柯ぜん;、村松慎一、新田淳美
    • Organizer
      第69回日本薬理学会北部会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 新規薬物依存関連タンパク質TMEM168の生理機能解析.2018

    • Author(s)
      佐藤直輝、宮本嘉明、傅 柯ぜん;、大竹和弥、村松慎一、新田淳美
    • Organizer
      第69回日本薬理学会北部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウスへのメタンフェタミン連続投与で側坐核で発現量が増加するShati/Nat8l、PiccoloおよびTMEM168の薬物依存への影響および精神疾患との関連2018

    • Author(s)
      新田淳美
    • Organizer
      第28回日本臨床精神神経薬理学会・第48回日本神経精神薬理学会 合同年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 前頭前皮質Piccolo発現抑制マウスにおける統合失調症モデル動物開発に向けての行動薬理学及び神経化学的解析2018

    • Author(s)
      濱谷康平、稲垣 良、宮本嘉明、傅柯ぜん;、佐藤慶、桶谷 祐貴、村松 慎一、宇野 恭介、新田 淳美
    • Organizer
      日本薬学北陸支部 第130回例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 前頭前皮質 Piccolo 発現抑制による統合失調症モデルマウスにおける光遺伝学・マイクロダイアリシス法を用いた神経回路解明2018

    • Author(s)
      新田淳美
    • Organizer
      第29回マイクロダイアリシス研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] マウス嗅周皮質におけるプレシナプスタンパク質Piccoloのノックダウンは認知機能障害を引き起こす Piccolo knockdown in the perirhinal cortex induces cognitive dysfunction in the new schizophrenia mice2018

    • Author(s)
      桶谷 祐貴、宮本 嘉明、濱谷 康平、村松 慎一、新田 淳美
    • Organizer
      第92回日本薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SHATI/NAT8Lの血中DNAメチル化は未治療のうつ病患者において上昇する Increased DNA methylation of SHATI/NAT8L promotor sites in the blood from unmedicated patients with depression2018

    • Author(s)
      宮西 肇、宇野 恭介、岩田 美奈、菊池 佑、山森 英長、安田 由華、大井 一高、橋本 亮太、住吉 太幹、新田 淳美
    • Organizer
      第92回日本薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 前頭前皮質のShati/Nat8l過剰発現はメタンフェタミン誘発性の場所嗜好性を減弱する。 Methamphetamine-induced CPP inhibition by overexpression of Shati/Nat8l in the medial prefrontal cortex.2018

    • Author(s)
      HADDAR MERIEM、宇野 恭介、東 克憲、村松 慎一、新田 淳美
    • Organizer
      第92回日本薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 線条体のShati/Nat8lはうつ様症状発症の脆弱性を決定づける Vulnerability for onset of depression induced by striatal Shati/Nat8l in mice2018

    • Author(s)
      宇野 恭介、宮西 肇、宮崎 杜夫、袖山 健吾、藤原 俊幸、村松 慎一、新田 淳美
    • Organizer
      第92回日本薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス線条体のShati/Nat8l はうつ様症状発症に脆弱性を示す2018

    • Author(s)
      宇野 恭介, 宮西 肇, 宮崎 杜夫, 袖山 健吾, 藤原 俊幸, 村松 慎一, 宮本 嘉明, 新田 淳美
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] nduction system of Shati/Nat8L expression by methamphetamine via dopamine D1 signaling pathway2017

    • Author(s)
      Uno K, Miyazaki T, Miyamoto Y, Nitta A
    • Organizer
      The 5th Congress of AsCNP 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The combination of presynaptic cytomatrix protein Piccolo knockdown in the prefrontal cortex and mild social defeat stress induces schizophrenia-like behaviors in mice2017

    • Author(s)
      3) Miyamoto Y, Hamatani K, Inagaki R, Sato K, Muramatu SI, Nabeshima T, Uno K, Nitta A
    • Organizer
      The 5th Congress of AsCNP 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel molecules, Shati/Nat8l, Piccolo and TMEM168, protect methamphetamine dependence in mice. Joint AsCNP-ASNP meeting (JM02 Addiction research collaborations in Asia)2017

    • Author(s)
      Nitta A
    • Organizer
      The 5th Congress of AsCNP 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Study of Teneurin-4 function to establish the bipolar disease mice model using CRISPR-Cas9 system2017

    • Author(s)
      Miyashita M, Uno K, Nakano F, Nishizono H, Muramatsu SI , Miyamoto Y, Nitta A
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Enhanced locomotor activity and impaired prepulse inhibition induced by presynaptic cytomatrix protein Piccolo knockdown in the amygdala of mice2017

    • Author(s)
      Hamatani K, Miyamoto Y, Oketani Y, Muramatsu SI , Uno K, Nitta A
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] マウス線条体でのShati/Nat8l過剰発現によるセロトニン神経系を介する情動性調節2017

    • Author(s)
      東 颯太, 宮本嘉明, 家垣典幸, 傅 かぜん, 鷲見和之, 石川雄大, 村松慎一, 宇野恭介, 新田淳美
    • Organizer
      第68回薬理学会北部会
    • Related Report
      2017 Research-status Report
  • [Presentation] 幼若期のミエリン形成の遅延による SHATI/NAT8L KOマウスの社会性低下や不安作用の増大2017

    • Author(s)
      15) 新田淳美, 鷲見和之, 友廣岳則, 畑中保丸, 日比陽子, 宮本嘉明, 鍋島俊隆, 宇野恭介
    • Organizer
      第39回 日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 依存性薬物の薬理作用発現を抑制する分子群 行動薬理学的・生化学的研究,シンポジウム19依存性薬物の光と影.2017

    • Author(s)
      新田淳美
    • Organizer
      第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会
    • Related Report
      2017 Research-status Report
  • [Book] Shati/Nat8l and N-acetylaspartate (NAA) have important roles in regulating nicotinic acetylcholine receptors in neuronal and psychiatric diseases in animal models and humans2018

    • Author(s)
      Atsumi Nitta, Hiroshi Noike, Kazuyuki Sumi, Hajime Miyanishi, Takuya Tanaka, Kazuya Takaoka, Miyuki Nagakura, Noriyuki Iegaki, Jin-ichiro Kaji,Yoshiaki Miyamoto, Shin-Ichi Muramatsu, Kyosuke Uno
    • Total Pages
      191
    • Publisher
      Springer
    • ISBN
      9789811084874
    • Related Report
      2018 Annual Research Report
  • [Book] Shati/Nat8l and N-acetylaspartate (NAA) have important roles in regulating nicotinic acetylcholine receptors in neuronal and psychiatric diseases in animal models and humans IN“Nicotinic Acetylcholine Receptor Signaling in Neuroprotection”2018

    • Author(s)
      Nitta A*, Noike H, Sumi K, Miyanishi H, Tanaka T, Nagakura M, Iegaki N, Kaji JI, Miyamoto Y, Muramatsu SI, Uno K.
    • Total Pages
      191
    • Publisher
      Springer Nature
    • ISBN
      9789811084874
    • Related Report
      2017 Research-status Report
  • [Remarks] 富山大学大学院医学薬学研究部(薬学)・薬物治療学研究室ホームページ

    • URL

      http://www.pha.u-toyama.ac.jp/yakuchi/top.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] こころの病気を探求する

    • URL

      http://sai-jisedai.jugem.jp/

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] 富山大学 教員総覧 新田淳美

    • URL

      http://evaweb.u-toyama.ac.jp/html/386_ja.html?k=%E6%96%B0%E7%94%B0

    • Related Report
      2018 Annual Research Report
  • [Remarks] 富山大学薬学部薬物治療学研究室ホームページ

    • URL

      http://www.pha.u-toyama.ac.jp/yakuchi/top.html

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 特許2017

    • Inventor(s)
      新田淳美、鷲見和之、野池悠、宇野恭介
    • Industrial Property Rights Holder
      国立大学法人富山大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Acquisition Date
      2018
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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