Regulatory Mechanisms for the quality of wound angiogenesis

• Project/Area Number: 21689047
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Plastic surgery
• Research Institution: Keio University
• Principal Investigator: KUBOTA Yoshiaki 慶應義塾大学, 医学部, 特任講師 (50348687)
• Project Period (FY): 2009 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥27,560,000 (Direct Cost: ¥21,200,000、Indirect Cost: ¥6,360,000); Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2010: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
• Keywords: 創傷治癒 / 血管 / マクロファージ / 形態学 / 血管新生 / CSF1 / 細胞・組織 / 循環器・高血圧 / 発現制御 / 臨床 / 発生・分化 / 細胞・組

Research Abstract

Recently it was recognized that vascular density (vascular “quantity”) does not necessarily correlate with oxygen delivery (vascular “quality”) to tissues. This study was performed to uncover the mechanism which determines the vascular quality. The group

Research Products

• [Journal Article] Pathological neoangiogenesis depends on oxidative stress regulation by ATM. (2012)
  • Author(s): Okuno Y, Nakamura-Ishizu A, Otsu K, SudaT and *Kubota Y.
  • Journal Title: Nat Med Volume: 18(8) Pages: 1208-1216
  • URL: http://www.keio.ac.jp/ja/press_release/2012/kr7a4300000artgk.html
  • Peer Reviewed
• [Journal Article] Tumor angiogenesis and anti-angiogenic therapy (2012)
  • Author(s): *Kubota Y.
  • Journal Title: Keio J Med. Volume: 61(2) Pages: 47-56
  • Peer Reviewed
• [Journal Article] The formation of an angiogenic astrocyte template is regulated by the neuroretina in a HIF-1-dependent manner. (2012)
  • Author(s): Nakamura-Ishizu A, Kurihara T, Okuno Y, Ozawa Y, Kishi K, Goda N, Tsubota K, Okano H, Suda T and *Kubota Y.
  • Journal Title: Dev Biol Volume: 363(1) Pages: 106-14
  • Peer Reviewed
• [Journal Article] Genome-wide identification of endothelial cell-enriched genes in the mouse embryo (2012)
  • Author(s): Takase H, Matsumoto K, Yamadera R, Kubota Y, Otsu A, Suzuki R, Ishitobi H, Mochizuki H, Kojima T, Takano S, UchidaK, Takahashi S, and *Ema M
  • Journal Title: Blood Volume: 120(4) Pages: 914-23
  • Peer Reviewed
• [Journal Article] Extracellular matrix protein Tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. (2012)
  • Author(s): Nakamura-Ishizu A, Okuno Y, Omatsu Y, Okabe K, Morimoto J, Uede T, Nagasawa T, Suda T and *Kubota Y.
  • Journal Title: Blood Volume: 119(23) Pages: 5429-5437
  • Peer Reviewed
• [Journal Article] Pathological neoangiogenesis depends on oxidative stress regulation by ATM. (2012)
  • Author(s): Yuji Okuno
  • Journal Title: Nature Medicine Volume: 18 Issue: 8 Pages: 1208-1216
  • DOI: 10.1038/nm.2846
  • Peer Reviewed
• [Journal Article] Extracellul- ar matrix protein Tenascin-C is req- uired in the bone marrow microenvio- nment primed for hematopoietic rege- neration (2012)
  • Author(s): Nakamura-Ishizu A, Okuno Y, Omatsu Y, Okabe K, Morimoto J, Uede T, Nagasa- wa T, Suda T, Kubota Y
  • Journal Title: Blood Volume: 119 Issue: 23 Pages: 5429-5437
  • DOI: 10.1182/blood-2011-11-393645
  • Peer Reviewed
• [Journal Article] Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero. (2011)
  • Author(s): *Kubota Y, Takubo K, Hirashima M, Nagoshi N, Kishi K, Okuno Y,Nakamura-Ishizu A, Sano K, Murakami M,Ema M, Omatsu Y, Takahashi S, Nagasawa T, Shibuya M, Okano H and *Suda T
  • Journal Title: J Exp Med Volume: 208(5) Pages: 949-60
  • URL: http://www.keio.ac.jp/ja/press_release/2011/kr7a4300000685ib-att/110511_2.pdf
  • Peer Reviewed
• [Journal Article] Bone marrow-derived cells serve as pro-angiogenic macrophages but notendothelial cells in wound healing. (2011)
  • Author(s): Okuno Y, Nakamura-Ishizu A, Kishi K, Suda T and *Kubota Y.
  • Journal Title: Blood Volume: 117(19) Pages: 5264-72
  • Peer Reviewed
• [Journal Article] Sphere formation restores and confers hair-inducing capacity in cultured mesenchymal cells. (2011)
  • Author(s): Shimizu R, Okabe K, Kubota Y, Nakamura-Ishizu A, Nakajima H and *Kishi K.
  • Journal Title: Exp Dermatol Volume: 20(8) Pages: 679-81
  • Peer Reviewed
• [Journal Article] Vascularity of nongynecological leiomyosarcoma depends on colony-stimulating factor 1 but not on vascular endothelial growth factor (2011)
  • Author(s): *Kubota Y and Suda T
  • Journal Title: Am J Pathol Volume: 179(4) Pages: 1591-3
  • Peer Reviewed
• [Journal Article] The formation of an angiogenic astrocyte template is regulated by the neuroretina in a HIF-1-dependent manner (2011)
  • Author(s): Nakamura-Ishizu A, Kurihara T, Okuno Y, Ozawa Y, Kishi K, Goda N, Tsubota K, Okano H, Suda T, Kubota Y
  • Journal Title: Dev Biol Volume: 363 Issue: 1 Pages: 106-114
  • DOI: 10.1016/j.ydbio.2011.12.027
  • Peer Reviewed
• [Journal Article] Vascularity of nongynecological leiomyosarcoma depends on colony-stimulating factor 1 but not on vascular endothelial growth factor (2011)
  • Author(s): Kubota, et al
  • Journal Title: American Journal of Pathology Volume: 179 Pages: 1591-1593
  • Peer Reviewed
• [Journal Article] Sphere formation restores and confers hair-inducing capacity in cultured mesenchymal cells (2011)
  • Author(s): Shimizu, et al
  • Journal Title: Experimental Dermatology Volume: 20 Pages: 679-681
  • Peer Reviewed
• [Journal Article] Bone marrow-derived cells serve as proangiogenic macrophages but not endothelial cells in wound healing (2011)
  • Author(s): Okuno, et al.
  • Journal Title: Blood Volume: 117 Pages: 5264-5272
  • Peer Reviewed
• [Journal Article] von Hippel-Lindau protein regulates transition from fetal to adult circulatory system in retina (2010)
  • Author(s): Kurihara T, Kubota Y (equally first author), Ozawa Y, Takubo K, Noda K, Simon MC, Johnson RS, Suematsu M, Tsubota K, Ishida S, Goda N, *Suda T and *Okano H.
  • Journal Title: Development Volume: 137 Pages: 1563-1571
  • Peer Reviewed
• [Journal Article] Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver. (2010)
  • Author(s): *Iwasaki H, Arai F, Kubota Y, Dahl M and*Suda T.
  • Journal Title: Blood Volume: 116(4) Pages: 544-53
  • Peer Reviewed
• [Journal Article] Regulation of the HIF-1alpha Level Is Essential for Hematopoietic Stem Cells. (2010)
  • Author(s): *Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, Shima H, Johnson RS, Hirao A, Suematsu M,*Suda T.
  • Journal Title: Cell Stem Cell Volume: 7(3) Pages: 391-402
  • Peer Reviewed
• [Journal Article] von Hippel-Lindau protein regulates transition from fetal to adult circulatory system in retina. (2010)
  • Author(s): Kurihara, Kubota (equally first author), et al.
  • Journal Title: Development Volume: 137 Pages: 1563-1571
  • Peer Reviewed
• [Journal Article] Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver. (2010)
  • Author(s): Iwasaki, et al.
  • Journal Title: Blood Volume: 116 Pages: 544-53
  • Peer Reviewed
• [Journal Article] Regulation of the HIF-1alpha Level Is Essential for Hematopoietic Stem Cells. (2010)
  • Author(s): Takubo, et al.
  • Journal Title: Cell Stem Cell Volume: 7 Pages: 391-402
  • Peer Reviewed
• [Journal Article] M-CSF inhibition selectively targets pathological angiogenesis andlymphangiogenesis. (2009)
  • Author(s): *Kubota Y, Takubo K, Shimizu T, Ohno H,Kishi K, Shibuya M, Saya H and *Suda T
  • Journal Title: J Exp Med Volume: 206 Pages: 1089-102
  • Peer Reviewed
• [Journal Article] Feedback mechanism between blood vessels and astrocytes in retinal vascular development. (2009)
  • Author(s): *Kubota Y and *Suda T.
  • Journal Title: Trends Cardiovasc Med Volume: 19 Pages: 38-43
  • Peer Reviewed
• [Journal Article] Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. (2009)
  • Author(s): Morikawa S, Mabuchi Y, Kubota Y, Nagai Y, Niibe K, Hiratsu E, Suzuki S, Miyauchi-Hara C, Nagoshi N, Sunabori T, Shimmura S, Miyawaki A, Nakagawa T, Suda T, Okano H and *Matsuzaki Y
  • Journal Title: J Exp Med Volume: 206 Pages: 2483-96
  • Peer Reviewed
• [Journal Article] M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis (2009)
  • Author(s): Kubota Y, et al.
  • Journal Title: J.Exp.Med. 206 Pages: 1089-1102
  • Peer Reviewed
• [Journal Article] Feedback mechanism between blood vessels and astrocytes in retinal vascular development. (2009)
  • Author(s): Kubota Y, et al.
  • Journal Title: Trends Cardiovasc.Med. 19 Pages: 38-43
  • Peer Reviewed
• [Presentation] Oxidative stress as a target for antiangiogenic therapy (2014)
  • Author(s): Yoshiaki Kubota
  • Organizer: Keystone Symposium “Metabolism and Angiogenesis
  • Place of Presentation: British Columbia, Canada
  • Invited
• [Presentation] 腫瘍血管特異的分子メカニズムの解明: Beyond VEGF blockade (2013)
  • Author(s): 久保田義顕
  • Organizer: 第9回宮崎サイエンスキャンプ
  • Place of Presentation: 宮崎
  • Invited
• [Presentation] 腫瘍血管特異的な血管新生分子メカニズム (2013)
  • Author(s): 久保田義顕
  • Organizer: 第4回Molecular Cardiovascular Conference II
  • Place of Presentation: 北海道キロロ
  • Invited
• [Presentation] 腫瘍血管特異的分子標的としての酸化ストレスシグナル (2013)
  • Author(s): 久保田義顕
  • Organizer: 第21回日本血管生物医学会学術集会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] 腫瘍血管特異的分子メカニズムの解明 (2012)
  • Author(s): 久保田義顕
  • Organizer: 千葉大学G-COEセミナー
  • Place of Presentation: 千葉
  • Year and Date: 2012-12-17
• [Presentation] Oxidative stress in pathological angiogenesis. (2012)
  • Author(s): Kubota Y
  • Organizer: Special Seminar in Biomedicum Helsinki.
  • Place of Presentation: Biomedicum Helsinki, Helsinki, Finland
  • Year and Date: 2012-10-24
• [Presentation] Tumor angiogenesis and oxidative stress. (2012)
  • Author(s): Kubota Y.
  • Organizer: Joint JSPS-Karolinska Institute (KI) Symposium.
  • Place of Presentation: Karolinska Institute, Stockholm, Sweden
  • Year and Date: 2012-10-23
• [Presentation] マウス毛乳頭血管発生のメカニズム (2012)
  • Author(s): 久保田義顕
  • Organizer: 第2回細胞再生医療研究会
  • Place of Presentation: 神戸
  • Year and Date: 2012-07-29
• [Presentation] 血管パターニング制御機構と腫瘍血管新生. (2012)
  • Author(s): 久保田義顕
  • Organizer: 第39回NIH金曜会
  • Place of Presentation: Bethesda
  • Year and Date: 2012-06-01
• [Presentation] Pathological neoangiogenesis depends on oxidative stress regulation by ATM. (2012)
  • Author(s): Kubota Y.
  • Organizer: Mini Seminar in the Scripps Institute.
  • Place of Presentation: SanDiego, CA
  • Year and Date: 2012-03-12
• [Presentation] Atm function in angiogenesis (2012)
  • Author(s): 久保田義顕
  • Organizer: 第35回日本分子生物学会年会 ワークショップ「ATMファミリーキナーゼの多様な制御機構と組織・動物種特異的な役割」
  • Place of Presentation: 福岡
• [Presentation] Neuroretinal regulation of vascular patterning. (2012)
  • Author(s): Kubota Y
  • Organizer: Neuro-Vascular Wiring Symposium 2012
  • Place of Presentation: 奈良県新公会堂
• [Presentation] 抗腫瘍血管新生療法の新規標的 (2012)
  • Author(s): 久保田義顕
  • Organizer: Beyond VEGF blockade 第30回日本骨代謝学会学術集会
  • Place of Presentation: 東京
• [Presentation] Oxidative stress in pathological angiogenesis (2012)
  • Author(s): Yoshiaki Kubota
  • Organizer: Special Seminar in Biomedicum Helsinki
  • Place of Presentation: Helsinki, Finland
  • Invited
• [Presentation] Tumor angiogenesis and oxidative stress (2012)
  • Author(s): Yoshiaki Kubota
  • Organizer: Joint JSPS; Karolinska Institute (KI) Symposium
  • Place of Presentation: Stockholm, Sweden
  • Invited
• [Presentation] Atm function in angiogenesis (2012)
  • Author(s): 久保田義顕
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] 抗腫瘍血管新生療法の新規標的；Beyond VEGF blockade (2012)
  • Author(s): 久保田義顕
  • Organizer: 第30回日本骨代謝学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Pathological neoangiogenesis depends on oxidative stress regulation by ATM (2011)
  • Author(s): 久保田義顕
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川)(招待講演)
  • Year and Date: 2011-12-13
• [Presentation] 抗腫瘍血管新生療法の新規標的の探索 (2011)
  • Author(s): 久保田義顕
  • Organizer: Beyond VEGF blockade第42回 ニューロ・オンコロジィの会
  • Place of Presentation: 東京
  • Year and Date: 2011-12-03
• [Presentation] 形成外科と免疫組織学的解析 (2011)
  • Author(s): 久保田義顕、貴志和生
  • Organizer: 第20回日本形成外科基礎学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-10-06
• [Presentation] ATM drives pathological angiogenesis by suppressing oxidative stress (2011)
  • Author(s): 久保田義顕
  • Organizer: 9th Japan-Korea vascular biology symposium
  • Place of Presentation: Westin Hotel Busan, Busan, Korea(招待講演)
  • Year and Date: 2011-08-26
• [Presentation] ATM-mediated suppression of oxidative stress is required for pathological neovascular expansion (2011)
  • Author(s): 久保田義顕
  • Organizer: 8th International Symposium on the Biology of Endothelial Cells
  • Place of Presentation: ETH Zurich Main Campus, Zurich, Switzerland
  • Year and Date: 2011-06-16
• [Presentation] 抗腫瘍血管新生療法の新規標的の探索 (2011)
  • Author(s): 久保田義顕
  • Organizer: 第80回北里記念式 北里賞受賞講演
  • Place of Presentation: 東京
  • Year and Date: 2011-06-10
• [Presentation] マクロファージを標的としたリンパ浮腫治療戦略 (2011)
  • Author(s): 久保田義顕、貴志和生
  • Organizer: 第54回日本形成外科学会総会・学術集会
  • Place of Presentation: あわぎんホール(徳島)(招待講演)
  • Year and Date: 2011-04-13
• [Presentation] ATM-mediated suppression of oxidative stress is required for pathological neovascular expansion (2011)
  • Author(s): 久保田義顕
  • Organizer: 新学術領域「血管-神経ワイヤリングにおける相互依存性の成立機構」班会議
  • Place of Presentation: 神戸
  • Year and Date: 2011-01-18
• [Presentation] Pathological neoangiogenesis depends on oxidative stress regulation by AT M (2011)
  • Author(s): 久保田義顕
  • Organizer: 第34回日本分子生物学会年会ワークショップ「Dynamic linkage of vascular system and organ functions -novel roles of blood vessels in health and disease」
  • Place of Presentation: 横浜
• [Presentation] Pathological neoangiogenesis depends on oxidative stress regulation by ATM. (2011)
  • Author(s): Kubota Y
  • Organizer: The Second Pacific Symposium on Vascular Biology.
  • Place of Presentation: Jeju, Korea
• [Presentation] ATM drives pathological angiogenesis by suppressing oxidative stress (2011)
  • Author(s): Kubota Y.
  • Organizer: 9th Japan-Korea vascular biology symposium.
  • Place of Presentation: Busan, Korea
• [Presentation] Postnatal tissue-resident vascular precursor cells marked by myelin protein zero. (2011)
  • Author(s): 久保田義顕
  • Organizer: 新学術領域「血管-神経ワイヤリングにおける相互依存性の成立機構」班会議
  • Place of Presentation: 熊本
• [Presentation] Role of Ataxia-telangiectasia mutated (ATM) in angiogenesis (2011)
  • Author(s): 久保田義顕
  • Organizer: 第7回Aso International Meeting
  • Place of Presentation: 熊本
• [Presentation] ATM-mediated suppression of oxidative stress is required for pathological neovascular expansion. (2011)
  • Author(s): Kubota Y.
  • Organizer: 8th International Symposium on the Biology of Endothelial Cells.
  • Place of Presentation: 8th International Symposium on the Biology of Endothelial Cells.
• [Presentation] マクロファージのリンパ管新生における役割 (2011)
  • Author(s): 久保田義顕
  • Organizer: 第35回日本リンパ学会総会
  • Place of Presentation: 東京
• [Presentation] マクロファージを標的としたリンパ浮腫治療戦略 (2011)
  • Author(s): 久保田義顕、貴志和生
  • Organizer: 第54回日本形成外科学会総会・学術集会
  • Place of Presentation: 徳島
• [Presentation] 組織血管前駆細胞(tissue-resident vascular precursors)の同定と機能解析 (2010)
  • Author(s): 久保田義顕
  • Organizer: 第11回 Organ Microcirculation Forum
  • Place of Presentation: 東京
  • Year and Date: 2010-11-04
• [Presentation] 組織血管前駆細胞(tissue-resident vascular precursors)の同定と機能解析 (2010)
  • Author(s): 久保田義顕
  • Organizer: 第11回Organ Microcirculation Forum
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-11-04
• [Presentation] 血管・リンパ管新生におけるマクロファージの役割 (2010)
  • Author(s): 久保田義顕、奥野祐次、須田年生、貴志和生
  • Organizer: 第19回日本形成外科学会基礎学術集会
  • Place of Presentation: 横浜(一般講演)
  • Year and Date: 2010-09-17
• [Presentation] 毛周期・加齢に伴う毛包血管網リモデリング (2010)
  • Author(s): 久保田瀬、貴志和生
  • Organizer: 第19回日本形成外科学会基礎学術集会
  • Place of Presentation: 横浜(一般講演)
  • Year and Date: 2010-09-17
• [Presentation] 網膜幹細胞の血管ネットワーク形成における役割 (2010)
  • Author(s): 久保田義顕
  • Organizer: 新学術領域「血管-神経ワイヤリングにおける相互依存性の成立機構」キックオフミーティング
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-13
• [Presentation] 網膜幹細胞の血管ネットワーク形成における役割 (2010)
  • Author(s): 久保田義顕
  • Organizer: 新学術領域「血管-神経ワイヤリングにおける相互依存性の成立機構」キックオフミーティング
  • Place of Presentation: 大阪(招待講演)
  • Year and Date: 2010-09-13
• [Presentation] 血管・リンパ管新生におけるマクロファージの役割 (2010)
  • Author(s): 久保田義顕
  • Organizer: 第11回Pharmaco-Hematologyシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-06-19
• [Presentation] 血管・リンパ管新生におけるマクロファージの役割 (2010)
  • Author(s): 久保田義顕
  • Organizer: 第11回Pharmaco-Hematologyシンポジウム
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-06-19
• [Presentation] Role of macrophages in angiogenesis and lymphangiogenesis. (2010)
  • Author(s): 久保田義顕
  • Organizer: 第18回 日本血管生物医学会学術集会
  • Place of Presentation: 大阪
• [Presentation] M-CSF as a therapeutic target for tumor lymph/angiogenesis. (2010)
  • Author(s): Kubota Y
  • Organizer: 5th Gordon Research Conference (Endothelial Cell Phenotypes In health & Disease).
  • Place of Presentation: Biddeford, ME
• [Presentation] M-CSF as a therapeutic target for tumor lymph/angiogenesis. (2010)
  • Author(s): Kubota Y
  • Organizer: 5th Gordon Research Conference (Endothelial Cell Phenotypes In health & Disease)
  • Place of Presentation: Biddeford, ME(Invited speaker)
• [Presentation] Role of macrophages in angiogenesis and lymphangiogenesis. (2010)
  • Author(s): 久保田義顕
  • Organizer: 第18回 日本血管生物医学会学術集会
  • Place of Presentation: 大阪(招待講演)
• [Presentation] 血管・リンパ管新生におけるマクロファージの役割 (2009)
  • Author(s): 久保田義顕
  • Organizer: 第15回血液科学セミナー
  • Place of Presentation: 東京
  • Year and Date: 2009-11-22
• [Presentation] 血管・リンパ管新生におけるマクロファージの役割 (2009)
  • Author(s): 久保田義顕
  • Organizer: 第15回 血液科学セミナー
  • Place of Presentation: 東京
• [Presentation] M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. (2009)
  • Author(s): Kubota Y
  • Organizer: 5th International Conference on Tumor Microenvironment.
  • Place of Presentation: Versailles, France
• [Presentation] 発生期・腫瘍リンパ管新生におけるマクロファージの役割 (2009)
  • Author(s): 久保田義顕
  • Organizer: 第1回リンパ学に関する松本カンファランス
  • Place of Presentation: 松本
• [Book] 医学のあゆみ特集号「サイトカインと疾患-新たな病態モデルから治療へ」血管新生病とM-CSF阻害 (2010)
  • Author(s): 久保田義顕
  • Publisher: 医歯薬出版株式会社
• [Book] 実験医学増刊号「血管研究と血管治療」マクロファージによる血管新生の制御機構 (2010)
  • Author(s): 久保田義顕
  • Publisher: 羊土社
• [Remarks]
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• [Remarks]
  • URL: http://www.careerpath-prj.keio.ac.jp/kanrinmaru/scholar/kubota/index.html
• [Remarks]
  • URL: http://www.careerpath-prj.keio.ac.jp/kanrinmaru/scholar/kubota/index.html