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New Development of Foods for Preventing Vascular Diseases-Search for Biomarkers for Disease Prevention on the plasma Exosomes-

Research Project

Project/Area Number 15K00809
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Eating habits
Research InstitutionJissen Women's University (2018-2019)
Gunma University (2015-2017)

Principal Investigator

Nakamura Akio  実践女子大学, 生活科学部, 教授 (30282388)

Co-Investigator(Kenkyū-buntansha) 岸 博子  山口大学, 大学院医学系研究科, 准教授 (40359899)
河原田 律子 (那須律子)  高崎健康福祉大学, 健康福祉学部, 講師 (60383147)
Project Period (FY) 2015-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords喫煙 / ニコチン / アテローム性動脈硬化症 / 血管平滑筋細胞 / 形質転換 / オミックス研究 / マイクロRNA / ヒト疾患モデル細胞 / ヒト血管平滑筋細胞 / 細胞分化・脱分化 / エクソソーム / プロテオーム / 細胞遊走 / マイクロRNA / 動脈硬化性疾患 / タバコ煙 / 網羅的遺伝子解析 / プロテオーム解析 / 脱分化 / 抗酸化物質 / 機能性食品
Outline of Final Research Achievements

We constructed the model cell of arteriosclerosis by exposing human vascular smooth muscle cells to the nicotine contained in the mainstream of cigarette smoke. Using this human disease model cell, the identification of molecules involved in the transformation of vascular smooth muscle cells from contraction type to migration/proliferation type was carried out focusing on exosomes secreted from the vascular smooth muscle cells. At first, we established an isolation method of exosomes secreted from vascular smooth muscle cells from the culture supernatant. Secondary, we analyzed the micro RNAs and peptides contained in this exosome. As a result, we found some characteristic microRNAs and peptides. In the future, we would like to search for candidates for disease biomarkers among them and apply them to search for compounds that prevent arteriosclerosis from food ingredients.

Academic Significance and Societal Importance of the Research Achievements

研究代表者は、喫煙において、タバコの主流煙に含まれるニコチンがアテローム性動脈硬化症の危険因子であり、このニコチンが血管平滑筋細胞を収縮型から増殖型に形質転換することでアテローム形成を促すことを明らかにした。近年、細胞が分泌するエクソソームと呼ばれる小胞に含まれる分子ががんの早期発見のための疾患バイオマーカーとして世界中で注目されている。我々は独自に構築したアテローム性動脈硬化症ヒト疾患モデル細胞を用いて、分泌されるエクソソームが運搬する分子をバイオマーカーとして利用し、動脈硬化性疾患に対して改善効果が期待されている機能性食品成分の科学的根拠を調べることで一次予防に貢献できると考えている。

Report

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

    (55 results)

All 2020 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (6 results) Journal Article (13 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Acknowledgement Compliant: 5 results) Presentation (29 results) (of which Int'l Joint Research: 10 results,  Invited: 4 results) Book (6 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Marshall University/Washington University(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Hunan University(中国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Marshall University(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Marshall UniversityHuntington(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Hunan University(中国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Marshall University(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Profiles of Physarum Microplasmodial Phosphatase Activity Crucial to Cytoplasmic Streaming and Spherule Formation2019

    • Author(s)
      Chisa Y Okada, Akio Nakamura, Kyoko Ogawa, Kazuhiro Kohama, Takako S Kaneko
    • Journal Title

      Cell Biochem Biophys

      Volume: 77 Issue: 4 Pages: 357-366

    • DOI

      10.1007/s12013-019-00885-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 子宮内高血糖がラット新生仔の神経細胞に与える影響2019

    • Author(s)
      河原田律子, 大上桜香, 小浜智子, 中村彰男
    • Journal Title

      糖尿病と妊娠

      Volume: 19 Pages: 79-81

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 糖尿病妊娠モデル動物を用いた子宮内高血糖環境が次世代に与える影響2019

    • Author(s)
      河原田律子, 小浜智子, 中村彰男
    • Journal Title

      糖尿病と妊娠

      Volume: 19 Pages: 49-52

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 妊娠糖尿病の食事の重要性─n-3系不飽和脂肪酸の役割2018

    • Author(s)
      河原田律子、中村彰男
    • Journal Title

      食品と開発【2018年2月号・特集】食品抗酸化能評価の最前線

      Volume: 53 Pages: 4-6

    • Related Report
      2018 Research-status Report
  • [Journal Article] 生活習慣病と子ども DOHaDの基礎 動物実験から2018

    • Author(s)
      中村彰男、河原田律子
    • Journal Title

      小児科診療

      Volume: 81 Pages: 1273-1277

    • Related Report
      2018 Research-status Report
  • [Journal Article] Intrauterine hyperglycemia-induced inflammatory signalling via the receptor for advanced glycation end products in the cardiac muscle of the infants of diabetic mother rats.2017

    • Author(s)
      Kawaharada R, Masuda H, Chen Z, Blough E, Kohama T, Nakamura A.
    • Journal Title

      European journal of nutrition

      Volume: 印刷中 Issue: 8 Pages: 2701-2712

    • DOI

      10.1007/s00394-017-1536-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Role of ω-3 Unsaturated Fatty Acids to Protect the Fetal Heart from the Intrauterine Hyperglycemia2017

    • Author(s)
      中村彰男、河原田律子
    • Journal Title

      KAGAKU TO SEIBUTSU

      Volume: 55 Issue: 5 Pages: 319-325

    • DOI

      10.1271/kagakutoseibutsu.55.319

    • NAID

      130006712110

    • ISSN
      0453-073X, 1883-6852
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 妊娠中のω-3系不飽和脂肪酸の摂取とその有益な効果2017

    • Author(s)
      河原田律子、小浜智子、中村彰男
    • Journal Title

      糖尿病と妊娠

      Volume: 17 Pages: 7-14

    • NAID

      40021119725

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 妊娠中のω-3系不飽和脂肪酸摂取とその有用な効果2017

    • Author(s)
      河原田律子・小浜智子・中村彰男
    • Journal Title

      糖尿病と妊娠

      Volume: 17 Pages: 91-95

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] NOX1/NADPH Oxidase Expressed in Colonic Macrophages Contributes to the Pathogenesis of Colonic Inflammation in Trinitrobenzene Sulfonic Acid-Induced Murine Colitis2017

    • Author(s)
      Yokota H, Tsuzuki A, Shimada Y, Imai A, Utsumi D, Tsukahara T, Matsumoto M, Amagase K, Iwata K, Nakamura A, Yabe-Nishimura C, Kato S
    • Journal Title

      The Journal of Pharmacology and Experimental Therapeutics

      Volume: 360(1) Issue: 1 Pages: 192-200

    • DOI

      10.1124/jpet.116.235580

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Calcium-mediated regulation of recombinant hybrids of full-length Physarum myosin heavy chain with Physarum/scallop myosin light chains.2016

    • Author(s)
      Zhang, Y., Kawamichi, H., Kohama, K., and Nakamura, A.
    • Journal Title

      Acta. Biochim. Biophys. Sin.

      Volume: 48 Issue: 6 Pages: 536-543

    • DOI

      10.1093/abbs/gmw031

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Oral administration of Dictyostelium differentiation-inducing factor 1 lowers blood glucose levels in streptozotocin- induced diabetic rats.2016

    • Author(s)
      Kawaharada, R., Nakamura, A., Takahashi, K., Kikuchi, H., Oshima, Y., and Kubohara, Y.
    • Journal Title

      Life Sci.

      Volume: 155 Pages: 56-62

    • DOI

      10.1016/j.lfs.2016.04.032

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Calcium-mediated regulation of recombinant hybrids of full-length Physarum myosin heavy chain with Physarum/scallop myosin light chains2016

    • Author(s)
      Zhang, Y., Kawamichi, H., Kohama, K., and Nakamura, A
    • Journal Title

      Acta Biochimica et Biophysica Sinica

      Volume: 印刷中

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Effects of AGEs on the rat neuronal cells in the intrauterine hyperglycaemic environment.2020

    • Author(s)
      Nakamura, A., Okami, H., Shimizu, M., Ooi, S., Tokunaga, Y., Sasaki, Y., and Kawaharada, R.
    • Organizer
      93rd Annual Meeting of The Japanese Pharmacological Society(Yokohama, Japan)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of saturated fatty acids on skeletal muscle differentiation in an intrauterine hyperglycemic environment.2020

    • Author(s)
      Tokunaga, Y., Kawaharada, R., Ishida, C., and Nakamura, A.
    • Organizer
      93rd Annual Meeting of The Japanese Pharmacological Society(Yokohama, Japan)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 子宮内高血糖環境が胎児の神経グリア細胞に及ぼす影響に関して2019

    • Author(s)
      中村彰男、大上桜香、清水愛美、徳永弥生、大井聡美、河原田律子
    • Organizer
      第8回日本DOHaD学会学術集会(東京)
    • Related Report
      2019 Annual Research Report
  • [Presentation] ミオシン軽鎖キナーゼのアクチン連関による非キナーゼ活性について2019

    • Author(s)
      中村彰男、小濱一弘
    • Organizer
      第61回日本平滑筋学会総会(名古屋)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Effects of intrauterine hyperglycaemia on brain neurons in neonatal rats2019

    • Author(s)
      Ritsuko Kawaharada and Akio Nakamura
    • Organizer
      The 14th International Conference on Alzheimer's & Parkinson's Diseases (AD/PD 2019)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 子宮内高血糖環境が新生仔ラットの神経細胞に及ぼす影響2018

    • Author(s)
      河原田律子、大上桜香、中野美穂、石田千聡、柿澤 朱音、辻野 真衣、柳 美帆、中村彰男
    • Organizer
      日本糖尿病学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Molecular imaging and biochemical analysis for the Physarum starvation response2018

    • Author(s)
      Chisa Y Okada, Akio Nakamura, Susumu Takekoshi, Kazuhiro Kohama and Takako S
    • Organizer
      第91回 日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 糖尿病妊婦から生まれてきた子供はアルツハイマー型認知症を発症するか?2018

    • Author(s)
      大上桜香、河原田律子、中村彰男
    • Organizer
      第65回 日本栄養改善学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 子宮内高血糖がラット新生仔の脳神経細胞にあたえる影響2018

    • Author(s)
      河原田律子, 小浜智子, 中村彰男
    • Organizer
      第34回日本糖尿病・妊娠学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 子宮内高血糖環境が胎児心筋細胞に与える影響2017

    • Author(s)
      中村彰男、野口玲於奈、河原田律子
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都女子大学(京都府)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] EPAは子宮内高血糖により誘発される糖尿病の母親の仔の心臓のインシュリンシグナル異常を改善した2017

    • Author(s)
      中村彰男・河原田律子
    • Organizer
      第90回 日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎県)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] ニコチンは血管平滑筋細胞に直接作用し、収縮型から遊走・増殖型に形質転換させる2017

    • Author(s)
      中村彰男、陳震一、吉山伸司、河原田律子、小濱一弘
    • Organizer
      2017年 生体運動研究合同班会議
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2017-01-06
    • Related Report
      2016 Research-status Report
  • [Presentation] 酸化ストレスにより生じたヒト大動脈平滑筋細胞のカルボニル修飾タンパク質の機能プロテオーム解析2017

    • Author(s)
      中村 彰男、岸 博子、河原田 律子、小林 誠、小濱 一弘
    • Organizer
      第59回日本平滑筋学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Intrauterine hyperglycemia induced the inflammatory signalling in the cardiac muscle of the infants of diabetic mother rats2017

    • Author(s)
      Nakamura, A., Imai, M., Inoue, A., Okami H., Sato, A., Yano, A., Kawaharada, R.,
    • Organizer
      10th World Congress on Development Origins of Health and Disease
    • Related Report
      2017 Research-status Report
  • [Presentation] 子宮内高血糖環境はAGEs/RAGEシグナルによる心筋細胞の慢性炎症を引き起こす。2017

    • Author(s)
      中村彰男, 今井美緒, 井上梓, 大上桜香, 佐藤亜耶, 矢野杏菜, 河原田律子
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規ホスファターゼが担う飢餓ストレス応答機構解明に向けた分子イメージング手法の開発2017

    • Author(s)
      岡田 千沙、中村 彰男、小濱 一弘、金子 堯子
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] 高グルコース培地中でのラット心筋芽細胞における EPAの影響2016

    • Author(s)
      野口 礼於奈、大沢 湧雅、齋藤 和真、河原田 律子、中村 彰男
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] The effect of maternal eicosapentaenoic acid supplementation on infant cardiovascular disease.2016

    • Author(s)
      Nakamura, A., and Kawaharada, R.
    • Organizer
      5th Annual Global Health Conference
    • Place of Presentation
      Kaohsiung, Taiwan
    • Year and Date
      2016-11-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Intrauterine hyperglycemia induced impaired insulin signaling and insulin resistance on the cardiac muscle in infant of diabetic mothers.2016

    • Author(s)
      Nakamura, A., and Kawaharada, R.
    • Organizer
      5th Conference on Prenatal Programming and Toxicity
    • Place of Presentation
      Kitakyushu, Japan
    • Year and Date
      2016-11-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of Protein modification by the active ingredient from nicotine- and tar- free cigarette smoke extract.2016

    • Author(s)
      Nakamura, A., Kishi, H., Kawaharada, R., Kobayashi, S. and Kohama, K.
    • Organizer
      19th International Vascular Biology Meeting
    • Place of Presentation
      Boston, U.S.A.
    • Year and Date
      2016-10-30
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高血糖環境のラット心筋細胞におけるEPAの影響2016

    • Author(s)
      河原田律子・中村彰男
    • Organizer
      第63回日本栄養改善学会学術総会
    • Place of Presentation
      ホテル青森(青森県)
    • Year and Date
      2016-09-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Myocardial protection by fish oil on infants of diabetic mother.2016

    • Author(s)
      Nakamura, A., and Kawaharada, R.
    • Organizer
      18th World Congress of Food Science and Technology
    • Place of Presentation
      Dublin, Ireland
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高血糖環境がラット心筋細胞のインスリンシグナル伝達に及ぼす影響2016

    • Author(s)
      河原田律子・中村彰男
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 高グルコース状態でのラット心筋細胞のシグナル伝達におけるEPAの影響.2015

    • Author(s)
      中村彰男, 河原田律子
    • Organizer
      第23回 日本血管生物医学会学術集会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Eicosapentaenoic acid has improved the impaired insulin-signaling pathway of the cardiac muscle of infants2015

    • Author(s)
      Nakamura, A., and Kawaharada, R.
    • Organizer
      International Conference on Lipid Science & Technology 2015
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2015-11-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Eicosapentaenoic acid supplementation during pregnancy improved the insulin signalling pathway in the cardiac muscles of infants of diabetic mothers.2015

    • Author(s)
      Kawaharada R, and Nakamura A.
    • Organizer
      International Conference on Lipid Science & Technology 2015
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2015-11-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高グルコース状態でのラット心筋芽細胞の分化過程におけるEPAの影響.2015

    • Author(s)
      河原田律子, 飯塚祐里, 石川春香, 中村碧乃, 横山未歩, 小浜智子, 中村彰男
    • Organizer
      第31回 日本糖尿病・妊娠学会学術集会
    • Place of Presentation
      リーガロイヤルホテル東京
    • Year and Date
      2015-11-20
    • Related Report
      2015 Research-status Report
  • [Presentation] ニコチンは血管平滑筋細胞に直接作用して形質転換を引き起こす2015

    • Author(s)
      中村彰男, 吉山伸司, 陳震一, 河原田律子, 小濱一弘
    • Organizer
      第57回日本平滑筋学会総会
    • Place of Presentation
      山口大学 医学部
    • Year and Date
      2015-08-25
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Eicosapentaenoic acid may improve the impaired signaling pathway of the cardiac muscle of infants.2015

    • Author(s)
      Kawaharada R, Ichikawa S, Kofude C, Yajima M, Muramoto M, Nakamura A.
    • Organizer
      12th Asian Congress of Nutrition
    • Place of Presentation
      横浜 みなとみらい
    • Year and Date
      2015-05-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] 生化学 (サクセス管理栄養士・栄養士養成講座)第4版2019

    • Author(s)
      中村彰男
    • Total Pages
      192
    • Publisher
      第一出版
    • Related Report
      2019 Annual Research Report
  • [Book] Fish Oil and Cardiac Akt/mTOR-Mediated Insulin Resistance in Infants with Maternal Diabetes:Nutrition and Diet in Maternal Diabetes2018

    • Author(s)
      Akio Nakamura and Ritsuko Kawaharada
    • Total Pages
      514
    • Publisher
      Humana Press, Cham
    • ISBN
      9783319564388
    • Related Report
      2018 Research-status Report
  • [Book] Effects of Nicotine Contained in Tobacco Mainstream Smoke on Vascular Smooth Muscle Cells; Atherosclerosis - Yesterday, Today and Tomorrow2018

    • Author(s)
      Akio Nakamura
    • Total Pages
      118
    • Publisher
      IntechOpen
    • Related Report
      2018 Research-status Report
  • [Book] Fish Oil and Cardiac Akt/mTOR-Mediated Insulin Resistance in Infants with Maternal Diabetes. In: “Nutrition and Diet in Maternal Diabetes: An Evidence-Based Approach (Nutrition and Health)”. Edited by Rajkumar Rajendram, Victor R. Preedy, Vinood B. Patel.2017

    • Author(s)
      Nakamura, A., and Kawaharada, R.
    • Total Pages
      14
    • Publisher
      Springer Press,
    • ISBN
      9783319564388
    • Related Report
      2017 Research-status Report
  • [Book] The Long-Term Cardiovascular Effects and Safety of Fish Oil among Women with Diabetes and Their Infants.;Fish Oil: Uses, Properties and Role in Human Healt. Edited by Frankie Burton.2016

    • Author(s)
      Nakamura, A., and Kawaharada, R.
    • Publisher
      Nova publisher
    • Related Report
      2016 Research-status Report
  • [Book] The Long-Term Cardiovascular Effects and Safety of Fish Oil among Women with Diabetes and Their Infants. In “Fish Oil: Uses, Properties and Role in Human Health“. Edited by Frankie Burton.2016

    • Author(s)
      Nakamura, A., and Kawaharada, R.
    • Publisher
      Nova Science Publishers, Inc.New York.
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 後発酵茶由来の血圧上昇抑制作用を有する剤並びにそれを含む飲食品及び医薬2015

    • Inventor(s)
      中村彰男、吉山伸司、田中夏女、河原田律子
    • Industrial Property Rights Holder
      中村彰男、吉山伸司、田中夏女、河原田律子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015
    • Acquisition Date
      2018
    • Related Report
      2017 Research-status Report

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Published: 2015-04-16   Modified: 2022-02-16  

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