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Glycoproteomic reasearch to reveal the frequency and diversity of the Congenital Disorders of Glycosylation

Research Project

Project/Area Number 23390081
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionResearch Institute, Osaka Medical Center for Maternal and Child Health

Principal Investigator

WADA Yoshinao  地方独立行政法人大阪府立病院機構大阪府立母子保健総合医療センター(研究所), その他部局等, 研究所長 (00250340)

Co-Investigator(Kenkyū-buntansha) TAJIRI Michiko  大阪府立母子保健総合医療センター(研究所), 代謝部門, 流動研究員 (70581312)
SHIBUKAWA Yukinao  大阪府立母子保健総合医療センター(研究所), 代謝部門, 主任研究員 (90393264)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2011: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords糖鎖 / 糖タンパク質 / 先天性代謝異常症 / 代謝異常 / 質量分析 / グライコプロテオミクス / 糖タンパク / プロテオーム / 診断
Outline of Final Research Achievements

A new mass spectrometric method for the diagnosis of congenital disorders of glycosylation (CDG) has been developed. The method effectively analyzed various types of CDG in international collaboration studies. A screening of CDG started in 2005 has found 11 families of CDG out of 1053 developmental delay patients of unknown cause. The incidence was approximately one percent in the Japanese cohort.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (55 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results,  Open Access: 1 results) Presentation (31 results) (of which Invited: 2 results) Book (3 results) Remarks (3 results)

  • [Journal Article] Mutations in COG2 encoding a subunit of the conserved oligomeric golgi complex cause a congenital disorder of glycosylation2015

    • Author(s)
      17.Kodera H, Ando N, Yuasa I, Wada Y, Tsurusaki Y, Nakashima M, Miyake N, Saitoh S, Matsumoto N, Saitsu H
    • Journal Title

      Clin Genet

      Volume: 87 Issue: 5 Pages: 455-460

    • DOI

      10.1111/cge.12417

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transferrin variants: Pitfalls in the diagnostics of Congenital disorders of glycosylation2015

    • Author(s)
      18.Zühlsdorf A, Park JH, Wada Y, Rust S, Reunert J, DuChesne I, Grüneberg M, Marquardt T
    • Journal Title

      Clin Biochem

      Volume: 1-2 Issue: 1-2 Pages: 11-13

    • DOI

      10.1016/j.clinbiochem.2014.09.022

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The novel transferrin E592A variant impairs the diagnostics of congenital disorders of glycosylation2014

    • Author(s)
      16.Park JH, Zühlsdorf A, Wada Y, Roll C, Rust S, Du Chesne I, Grüneberg M, Reunert J, Marquardt T.
    • Journal Title

      Clin Chim Acta

      Volume: 436C Pages: 135-139

    • DOI

      10.1016/j.cca.2014.05.011

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chondroitin sulfate proteoglycan tenascin-R regulates glutamate uptake by adult brain astrocytes2014

    • Author(s)
      Okuda H, Tatsumi K, Morita S, Shibukawa Y, Korekane H, Horii-Hayashi N, Wada Y, Taniguchi N, Wanaka A.
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 5 Pages: 2620-2631

    • DOI

      10.1074/jbc.m113.504787

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple phenotypes in phosphoglucomutase 1 deficiency2014

    • Author(s)
      Tegtmeyer LC, et al.
    • Journal Title

      N Engl J Med

      Volume: 370 Issue: 6 Pages: 533-542

    • DOI

      10.1056/nejmoa1206605

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interlaboratory Study on Differential Analysis of Protein Glycosylation by Mass Spectrometry: the ABRF Glycoprotein Research Multi-Institutional Study 20122013

    • Author(s)
      Leymarie N, et al.
    • Journal Title

      Mol Cell Proteomics

      Volume: 12 Issue: 10 Pages: 2935-2951

    • DOI

      10.1074/mcp.m113.030643

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in GMPPA Cause a Glycosylation Disorder Characterized by Intellectual Disability and Autonomic Dysfunction2013

    • Author(s)
      Koehler K, et al.
    • Journal Title

      Am J Hum Genet

      Volume: 93 Issue: 4 Pages: 727-734

    • DOI

      10.1016/j.ajhg.2013.08.002

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy2013

    • Author(s)
      Kodera H, Nakamura K, Osaka H, Maegaki Y, Haginoya K, Mizumoto S, Kato M, Okamoto N, Iai M, Kondo Y, Nishiyama K, Tsurusaki Y, Nakashima M, Miyake N, Hayasaka K, Sugahara K, Yuasa I, Wada Y, Matsumoto N, Saitsu H.
    • Journal Title

      Hum Mutat

      Volume: 34 Issue: 12 Pages: 1708-1714

    • DOI

      10.1002/humu.22446

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decreased sialylation of IgA1 O-glycans associated with pneumococcal hemolytic uremic syndrome2013

    • Author(s)
      Aoki H, Shiomi M, Ikeda T, Ishii T, Shimizu N, Togawa M, Okamoto N, Kadoya K, Wada Y.
    • Journal Title

      Pediatr Int

      Volume: 55 Issue: 6

    • DOI

      10.1111/ped.12166

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of heregulin beta signaling by single N-glycan deletion mutant of soluble ErbB32013

    • Author(s)
      Takahashi M, Hasegawa Y, Ikeda Y, Wada Y, Tajiri M, Ariki S, Takamiya R, Nishitani C, Araki M, Yamaguchi Y, Taniguchi N, Kuroki Y.
    • Journal Title

      J Biol Chem

      Volume: 288 Issue: 46 Pages: 32910-32921

    • DOI

      10.1074/jbc.m113.491902

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for inflammatory bowel diseases.2012

    • Author(s)
      InoueT, Miyoshi E, et al.
    • Journal Title

      IBD Journal

      Volume: 18(9) Issue: 9 Pages: 1723-34

    • DOI

      10.1002/ibd.22876

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Absence of post-phosphoryl modification in dystroglycanopathy mouse models and wild-type tissues expressing a non-laminin binding form of α-dystroglycan2012

    • Author(s)
      Kuga A
    • Journal Title

      J Biol Chem

      Volume: 287 Issue: 12 Pages: 9560-9567

    • DOI

      10.1074/jbc.m111.271767

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-Glycans of SREC-I(scavenger receptorexpressed by endothelial cells): Essential role for ligand binding, traffickingand stability2012

    • Author(s)
      Sano, M., Korekane, H., Ohtsubo, K., Yamaguchi, Y., Kato, M., Shibukawa, Y., Tajiri, M., Adachi, H., Wada, Y., Asahi, M. and Taniguchi, N
    • Journal Title

      Glycobiology

      Volume: 22 Issue: 5 Pages: 714-724

    • DOI

      10.1093/glycob/cws010

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brd2 is required for cell cycle exit and neuronal differentiation through the E2F1 pathway in mouse neuroepithelial cells.2012

    • Author(s)
      Mami Tsume, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 425 Issue: 4 Pages: 762-768

    • DOI

      10.1016/j.bbrc.2012.07.149

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Label-Free Analysis of O-glycosylation Site-Occupancy Based on the Signal Intensity of Glycopeptide/Peptide Ions2012

    • Author(s)
      Wada Y
    • Journal Title

      Mass Spectrometry

      Volume: 1 Issue: 2 Pages: A0008-A0008

    • DOI

      10.5702/massspectrometry.A0008

    • NAID

      10031126345

    • ISSN
      2186-5116, 2187-137X
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mass spectrometry of apolipoprotein C-III, a simple analytical method for mucin-type O-glycosylation and its application to an autosomal reces sive cutis laxa type-2(ARCL2) patient2012

    • Author(s)
      Wada Y, Kadoya M, Okamoto N
    • Journal Title

      Glycobiology

      Volume: 22 Issue: 8 Pages: 1140-1144

    • DOI

      10.1093/glycob/cws086

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] O-glycosylated IgA rheumatoid factor induces IgA deposits and glomerulonephritis2012

    • Author(s)
      Otani M, Nakata J, Kihara M, Leroy V, Moll S, Wada Y, Izui S
    • Journal Title

      J Am Soc Nephrol

      Volume: 23 Issue: 3 Pages: 438-446

    • DOI

      10.1681/asn.2011070701

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Infrared matrix-assisted laser desorption/ionization mass spectrometry for quantification of glycosaminoglycans and gangliosides2011

    • Author(s)
      Tajiri M, Wada Y
    • Journal Title

      Int.J.Mass Spectrom.

      Volume: 305 Issue: 2-3 Pages: 164-169

    • DOI

      10.1016/j.ijms.2010.10.029

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Mass Spectrometric Screening of Congenital Disorders of Glycosylation in Japan2014

    • Author(s)
      Yoshinao Wada
    • Organizer
      ASMS 30th Asilomar Conference on Mass Spectrometry, Advances in Glycomics and Glycoproteomics: Methods and Applications
    • Place of Presentation
      Asilomar, CA, USA
    • Year and Date
      2014-10-10 – 2014-10-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mass spectrometric screening of congenital disorders of glycosylation2014

    • Author(s)
      Yoshinao Wada
    • Organizer
      5th Asia Oseania Mass Spectrometry Conference & the 33rd Chinese Mass spectrometry Society Annual Conference
    • Place of Presentation
      Beijing, China
    • Year and Date
      2014-07-15 – 2014-07-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 可溶型ErbB3糖鎖欠損変異体とラパチニブのヘレグリンシグナル抑制作用における相乗効果2013

    • Author(s)
      高橋素子,長谷川喜弘,有木茂,高宮里奈,和田芳直,田尻道子,黒木由夫
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] The More than Sixty-Year History of Mass Spectrometry in Japan2013

    • Author(s)
      Yoshinao Wada
    • Organizer
      61st Conference on Mass Spectrometry and Allied Topics
    • Place of Presentation
      ミネアポリス(米国)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Ion Mobility Mass Spectrometry of IgG Fc Glycopeptides from Different Subclasses2013

    • Author(s)
      Michiko Tajiri, Feifei Zhu, Maissa M. Gaya, Yoshinao Wada, David E. Clemmer
    • Organizer
      61st Conference on Mass Spectrometry and Allied Topics
    • Place of Presentation
      ミネアポリス(米国)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 糖ペプチドのイオンモビリティー質量分析と分子力学法を用いたコンフォメーション探索2013

    • Author(s)
      田尻道子,竹内孝江,Feifei Zhu,Maissa M. Gaya,本郷やよい,中村健道,廣瀬賢治,David E. Clemmer,和田芳直
    • Organizer
      第61回質量分析総合討論会
    • Place of Presentation
      つくば
    • Related Report
      2013 Annual Research Report
  • [Presentation] Ion mobility mass spectrometry and MM conformational search of glycopeptides2013

    • Author(s)
      Michiko Tajiri, Takae Takeuchi, Yoshinao Wada
    • Organizer
      5th JCS International Symposium on Theoretical Chemistry
    • Place of Presentation
      奈良
    • Related Report
      2013 Annual Research Report
  • [Presentation] 可溶型ErbB受容体によるヘレグリンシグナル抑制機構2012

    • Author(s)
      高橋素子、長谷川喜弘、西谷千明、有木茂、和田芳直、田尻道子、黒木由夫
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] 細胞融合制御因子カルポニン3の生理的役割の解明2012

    • Author(s)
      渋川幸直、山崎奈津子、大門江津子、木村-吉田千春、持田京子、松尾勲、和田芳直
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] GAPDHのTransglutaminase 2依存的脱アミド化によるBeWo細胞の細胞融合2012

    • Author(s)
      岩井香織、渋川幸直、山崎奈津子、角谷真智子、和田芳直
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] プロゲステロン刺激によって脱落膜化する子宮内膜細胞株の樹立2012

    • Author(s)
      中村織江、和田芳直
    • Organizer
      第27回日本免疫学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2012-12-08
    • Related Report
      2012 Annual Research Report
  • [Presentation] 糖ペプチドのMALDI MSによるO型糖鎖付加率の算定とその応用2012

    • Author(s)
      和田芳直, 角谷真知子
    • Organizer
      第37回日本医用マススペクトル学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-10-25
    • Related Report
      2012 Annual Research Report
  • [Presentation] Electron transfer dissociation of protonated disulfide linked peptides and analogs without S-S bond2012

    • Author(s)
      Shigeo Hayakawa, Shinya Matsumoto, Michisato Toyoda, Yasushi Shigeri, Michiko Tajiri, Yoshinao Wada
    • Organizer
      19^<th> International Mass Spectrometry Conference
    • Place of Presentation
      京都
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] Ion mobility mass spectrometry of IgG Fc glycopeptides from different subclasses2012

    • Author(s)
      Michiko Tajiri, Yayoi Hongo, Takemichi Nakamura, Kenji Hirose, Yoshinao Wada
    • Organizer
      19^<th> International Mass Spectrometry Conference
    • Place of Presentation
      京都
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] Evaluation of Pt-deposited Porous Alumina Target Plate with MALDI Spiral-TOFMS2012

    • Author(s)
      Takafumi Sato, Kanae Teramoto, Yoshihisa Ueda, Tomohiko Tamura, Moriyuki Hamada, Ken-Ichiro Suzuki, Yoshinao Wada, Takashi Yanagishita, Hideki Masuda
    • Organizer
      19^<th> International Mass Spectrometry Conference
    • Place of Presentation
      京都
    • Year and Date
      2012-09-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] 糖タンパク質糖鎖プロファイルからの疾患解析2012

    • Author(s)
      和田芳直
    • Organizer
      第8回臨床プロテオーム研究会
    • Place of Presentation
      東京
    • Year and Date
      2012-05-12
    • Related Report
      2012 Annual Research Report
  • [Presentation] 紫外および赤外レーザーによるマトリックス支援レーザー脱離イオン化MALDIマススペクトルの特徴について2011

    • Author(s)
      和田芳直
    • Organizer
      日本質量分析学会第58回イオン反応研究会
    • Place of Presentation
      堺(招待講演)
    • Year and Date
      2011-12-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] O型糖鎖プロファイルの恒常性とその変化要因について2011

    • Author(s)
      和田芳直
    • Organizer
      第3回臨床メタボロミクス研究会
    • Place of Presentation
      神戸(招待講演)
    • Year and Date
      2011-10-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] Mass Spectrometry for Clinical Glycoproteomics2011

    • Author(s)
      Wada Y
    • Organizer
      The 14th Beijjing Conference and Exhibition on Instrumental Analysis
    • Place of Presentation
      中国北京(招待講演)
    • Year and Date
      2011-10-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖ペプチドの質量分析がひらく糖鎖生物学2011

    • Author(s)
      和田芳直
    • Organizer
      バイオ医薬品サミット
    • Place of Presentation
      品川(招待講演)
    • Year and Date
      2011-10-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] Fc領域IgG糖ペプチドのイオンモビリティー質量分析に見られるサブクラス間相違2011

    • Author(s)
      田尻道子、廣瀬賢次、竹内孝江、和田芳直
    • Organizer
      第59回質量分析総合討論会
    • Place of Presentation
      吹田
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 先天性糖鎖合成不全症の分子診断プログラム(第4報)2011

    • Author(s)
      和田芳直、角谷真知子、岡本伸彦
    • Organizer
      第36回日本医用マススペクトル学会年会
    • Place of Presentation
      吹田
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Classical label-free quantitation for glycomics and glycoproteomics2011

    • Author(s)
      Y.Wada
    • Organizer
      2011 Annual meeting of the Korean Society for Mass Spectrometry and the 2nd Asian & Oceanic Mass Spectroemtry Conference
    • Place of Presentation
      釜山(招待講演)
    • Year and Date
      2011-08-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] Congenital disorder of glycosylation type Icの1女児例2011

    • Author(s)
      市川和志、角谷真知子、和田芳直、岡本伸彦
    • Organizer
      第34回日本小児遺伝学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2011-08-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Fc領域IgG糖ペプチドのイオンモビリティー質量分析にみられるサブクラス間相違2011

    • Author(s)
      田尻道子、廣瀬賢治、和田芳直
    • Organizer
      日本プロテオーム学会2011年大会
    • Place of Presentation
      新潟
    • Year and Date
      2011-07-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖ペプチドのイオンモビリティMS:N型糖鎖とタンパク骨格のアミノ酸依存的相互作用2011

    • Author(s)
      田尻道子、廣瀬賢治、和田芳直
    • Organizer
      第38回BMSコンファレンス
    • Place of Presentation
      箱根
    • Year and Date
      2011-07-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] それでもイメージングMSに紫外レーザーを使いますか?2011

    • Author(s)
      田尻道子、和田芳直
    • Organizer
      第38回BMSコンファレンス
    • Place of Presentation
      箱根
    • Year and Date
      2011-07-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖タンパク質糖鎖合成不全症の実態がMSによって明らかにされつつある2011

    • Author(s)
      和田芳直
    • Organizer
      第38回BMSコンファレンス
    • Place of Presentation
      箱根
    • Year and Date
      2011-07-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Ion mobility MS of glycopeptides from the Fc regions of different IgG subclasses2011

    • Author(s)
      Wada Y、Tajiri M、Hirose K
    • Organizer
      58th Conference on Mass Spectrometry and Allied Topics
    • Place of Presentation
      デンバー、米国
    • Year and Date
      2011-06-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] Matrix-assisted laser/desorption ionization using a pulsed infrared laser at 6 μm wavelength2011

    • Author(s)
      Wada Y、Tajiri M
    • Organizer
      国際分析科学会議ICAS2011
    • Place of Presentation
      京都(招待講演)
    • Year and Date
      2011-05-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖鎖合成不全症にみる糖鎖バイオマーカーへの視点2011

    • Author(s)
      和田芳直
    • Organizer
      第61回日本電気泳動学会シンポジウム・第7回日本臨床プロテオーム研究会2011連合大会
    • Place of Presentation
      山口(招待講演)
    • Year and Date
      2011-05-10
    • Related Report
      2011 Annual Research Report
  • [Book] Mass spectrometry of Glycoproteins2013

    • Author(s)
      Wada Y
    • Total Pages
      339
    • Publisher
      springer
    • Related Report
      2013 Annual Research Report
  • [Book] 現代質量分析学:基礎原理から応用研究まで(DOJIN ACADEMIC SERIES)2013

    • Author(s)
      高山光男(編集), 瀧浪欣彦(編集), 和田芳直(編集), 早川滋雄(編集)
    • Total Pages
      514
    • Publisher
      化学同人
    • Related Report
      2012 Annual Research Report
  • [Book] 先天代謝異常症diagnosis at a glance2011

    • Author(s)
      和田芳直
    • Total Pages
      172
    • Publisher
      診断と治療社
    • Related Report
      2011 Annual Research Report
  • [Remarks] 研究内容(大阪府立母子保健総合医療センター 研究所・代謝部門)

    • URL

      http://www.mch.pref.osaka.jp/research/molecular/content.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.much.pref.osaka.jp/laboratory/metabolism/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.mch.pref.osaka.jp/sub_about/news/hp_news_cdg.html

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

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