Matricellular protein CCN3 mitigates abdominal aortic aneurysm
Identifieur interne : 003279 ( Ncbi/Merge ); précédent : 003278; suivant : 003280Matricellular protein CCN3 mitigates abdominal aortic aneurysm
Auteurs : Chao Zhang [États-Unis, République populaire de Chine] ; Dustin Van Der Voort [États-Unis] ; Hong Shi [États-Unis] ; Rongli Zhang [États-Unis] ; Yulan Qing [États-Unis] ; Shuichi Hiraoka [Japon] ; Minoru Takemoto [Japon] ; Koutaro Yokote [Japon] ; Joseph V. Moxon [Australie] ; Paul Norman [Australie] ; Laure Rittié [États-Unis] ; Helena Kuivaniemi [Afrique du Sud] ; G. Brandon Atkins [États-Unis] ; Stanton L. Gerson [États-Unis] ; Guo-Ping Shi [États-Unis] ; Jonathan Golledge [Australie] ; Nianguo Dong [République populaire de Chine] ; Bernard Perbal [France] ; Domenick A. Prosdocimo [États-Unis] ; Zhiyong Lin [États-Unis]Source :
- The Journal of Clinical Investigation [ 0021-9738 ] ; ????.
Abstract
Abdominal aortic aneurysm (AAA) is a major cause of morbidity and mortality; however, the mechanisms that are involved in disease initiation and progression are incompletely understood. Extracellular matrix proteins play an integral role in modulating vascular homeostasis in health and disease. Here, we determined that the expression of the matricellular protein CCN3 is strongly reduced in rodent AAA models, including angiotensin II–induced AAA and elastase perfusion–stimulated AAA. CCN3 levels were also reduced in human AAA biopsies compared with those in controls. In murine models of induced AAA, germline deletion of
Url:
DOI: 10.1172/JCI82337
PubMed: 26974158
PubMed Central: 4811126
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<author><name sortKey="Zhang, Chao" sort="Zhang, Chao" uniqKey="Zhang C" first="Chao" last="Zhang">Chao Zhang</name>
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<affiliation wicri:level="1"><nlm:aff id="A2">Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.</nlm:aff>
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<author><name sortKey="Moxon, Joseph V" sort="Moxon, Joseph V" uniqKey="Moxon J" first="Joseph V." last="Moxon">Joseph V. Moxon</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Matricellular protein CCN3 mitigates abdominal aortic aneurysm</title>
<author><name sortKey="Zhang, Chao" sort="Zhang, Chao" uniqKey="Zhang C" first="Chao" last="Zhang">Chao Zhang</name>
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<author><name sortKey="Zhang, Rongli" sort="Zhang, Rongli" uniqKey="Zhang R" first="Rongli" last="Zhang">Rongli Zhang</name>
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<author><name sortKey="Qing, Yulan" sort="Qing, Yulan" uniqKey="Qing Y" first="Yulan" last="Qing">Yulan Qing</name>
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<author><name sortKey="Hiraoka, Shuichi" sort="Hiraoka, Shuichi" uniqKey="Hiraoka S" first="Shuichi" last="Hiraoka">Shuichi Hiraoka</name>
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<wicri:regionArea>Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo</wicri:regionArea>
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<author><name sortKey="Yokote, Koutaro" sort="Yokote, Koutaro" uniqKey="Yokote K" first="Koutaro" last="Yokote">Koutaro Yokote</name>
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<country xml:lang="fr" wicri:curation="lc">Japon</country>
<wicri:regionArea>Department of Medicine, Chiba University Graduate School of Medicine, Chiba</wicri:regionArea>
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<author><name sortKey="Moxon, Joseph V" sort="Moxon, Joseph V" uniqKey="Moxon J" first="Joseph V." last="Moxon">Joseph V. Moxon</name>
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<country xml:lang="fr" wicri:curation="lc">Australie</country>
<wicri:regionArea>The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, and The Department of Vascular and Endovascular Surgery, Townsville Hospital, Townsville, Queensland</wicri:regionArea>
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<author><name sortKey="Norman, Paul" sort="Norman, Paul" uniqKey="Norman P" first="Paul" last="Norman">Paul Norman</name>
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<author><name sortKey="Rittie, Laure" sort="Rittie, Laure" uniqKey="Rittie L" first="Laure" last="Rittié">Laure Rittié</name>
<affiliation wicri:level="2"><nlm:aff id="A8">Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>Department of Dermatology, University of Michigan, Ann Arbor, Michigan</wicri:regionArea>
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</placeName>
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<author><name sortKey="Kuivaniemi, Helena" sort="Kuivaniemi, Helena" uniqKey="Kuivaniemi H" first="Helena" last="Kuivaniemi">Helena Kuivaniemi</name>
<affiliation wicri:level="1"><nlm:aff id="A9">Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Afrique du Sud</country>
<wicri:regionArea>Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg</wicri:regionArea>
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</affiliation>
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<author><name sortKey="Atkins, G Brandon" sort="Atkins, G Brandon" uniqKey="Atkins G" first="G. Brandon" last="Atkins">G. Brandon Atkins</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio, USA.</nlm:aff>
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<author><name sortKey="Gerson, Stanton L" sort="Gerson, Stanton L" uniqKey="Gerson S" first="Stanton L." last="Gerson">Stanton L. Gerson</name>
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<wicri:regionArea>Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="A6">The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, and The Department of Vascular and Endovascular Surgery, Townsville Hospital, Townsville, Queensland, Australia.</nlm:aff>
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<author><name sortKey="Dong, Nianguo" sort="Dong, Nianguo" uniqKey="Dong N" first="Nianguo" last="Dong">Nianguo Dong</name>
<affiliation wicri:level="1"><nlm:aff id="A2">Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
<wicri:noRegion>Wuhan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Perbal, Bernard" sort="Perbal, Bernard" uniqKey="Perbal B" first="Bernard" last="Perbal">Bernard Perbal</name>
<affiliation wicri:level="3"><nlm:aff id="A11">University of Paris Diderot — Paris 7, Paris, France.</nlm:aff>
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<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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<author><name sortKey="Prosdocimo, Domenick A" sort="Prosdocimo, Domenick A" uniqKey="Prosdocimo D" first="Domenick A." last="Prosdocimo">Domenick A. Prosdocimo</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio</wicri:regionArea>
<placeName><region type="state">Ohio</region>
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<author><name sortKey="Lin, Zhiyong" sort="Lin, Zhiyong" uniqKey="Lin Z" first="Zhiyong" last="Lin">Zhiyong Lin</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio, USA.</nlm:aff>
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<series><title level="j">The Journal of Clinical Investigation</title>
<idno type="ISSN">0021-9738</idno>
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<front><div type="abstract" xml:lang="en"><p>Abdominal aortic aneurysm (AAA) is a major cause of morbidity and mortality; however, the mechanisms that are involved in disease initiation and progression are incompletely understood. Extracellular matrix proteins play an integral role in modulating vascular homeostasis in health and disease. Here, we determined that the expression of the matricellular protein CCN3 is strongly reduced in rodent AAA models, including angiotensin II–induced AAA and elastase perfusion–stimulated AAA. CCN3 levels were also reduced in human AAA biopsies compared with those in controls. In murine models of induced AAA, germline deletion of <italic>Ccn3</italic>
resulted in severe phenotypes characterized by elastin fragmentation, vessel dilation, vascular inflammation, dissection, heightened ROS generation, and smooth muscle cell loss. Conversely, overexpression of CCN3 mitigated both elastase- and angiotensin II–induced AAA formation in mice. BM transplantation experiments suggested that the AAA phenotype of CCN3-deficient mice is intrinsic to the vasculature, as AAA was not exacerbated in WT animals that received CCN3-deficient BM and WT BM did not reduce AAA severity in CCN3-deficient mice. Genetic and pharmacological approaches implicated the ERK1/2 pathway as a critical regulator of CCN3-dependent AAA development. Together, these results demonstrate that CCN3 is a nodal regulator in AAA biology and identify CCN3 as a potential therapeutic target for vascular disease.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Invest</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Clin. Invest</journal-id>
<journal-id journal-id-type="publisher-id">J Clin Invest</journal-id>
<journal-title-group><journal-title>The Journal of Clinical Investigation</journal-title>
</journal-title-group>
<issn pub-type="ppub">0021-9738</issn>
<issn pub-type="epub">1558-8238</issn>
<publisher><publisher-name>American Society for Clinical Investigation</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26974158</article-id>
<article-id pub-id-type="pmc">4811126</article-id>
<article-id pub-id-type="publisher-id">82337</article-id>
<article-id pub-id-type="doi">10.1172/JCI82337</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Matricellular protein CCN3 mitigates abdominal aortic aneurysm</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Chao</given-names>
</name>
<email>cxz195@case.edu</email>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van der Voort</surname>
<given-names>Dustin</given-names>
</name>
<email>thedustv@aol.com</email>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shi</surname>
<given-names>Hong</given-names>
</name>
<email>hshi1990@gmail.com</email>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0001-5178-7278</contrib-id>
<name><surname>Zhang</surname>
<given-names>Rongli</given-names>
</name>
<email>rongli.zhang@case.edu</email>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Qing</surname>
<given-names>Yulan</given-names>
</name>
<email>yxq3@case.edu</email>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hiraoka</surname>
<given-names>Shuichi</given-names>
</name>
<email>shuichi.hiraoka@gmail.com</email>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Takemoto</surname>
<given-names>Minoru</given-names>
</name>
<email>minoru.takemoto@faculty.chiba-u.jp</email>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yokote</surname>
<given-names>Koutaro</given-names>
</name>
<email>kyokote@faculty.chiba-u.jp</email>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moxon</surname>
<given-names>Joseph V.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Norman</surname>
<given-names>Paul</given-names>
</name>
<email>paul.norman@uwa.edu.au</email>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rittié</surname>
<given-names>Laure</given-names>
</name>
<email>lrittie@umich.edu</email>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0001-5753-8766</contrib-id>
<name><surname>Kuivaniemi</surname>
<given-names>Helena</given-names>
</name>
<email>hkuivaniemi@sun.ac.za</email>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Atkins</surname>
<given-names>G. Brandon</given-names>
</name>
<email>gbrandonatkins@gmail.com</email>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gerson</surname>
<given-names>Stanton L.</given-names>
</name>
<email>slg5@case.edu</email>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shi</surname>
<given-names>Guo-Ping</given-names>
</name>
<email>gshi@rics.bwh.harvard.edu</email>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Golledge</surname>
<given-names>Jonathan</given-names>
</name>
<email>jonathan.golledge@jcu.edu.au</email>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dong</surname>
<given-names>Nianguo</given-names>
</name>
<email>dongnianguo@hotmail.com</email>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Perbal</surname>
<given-names>Bernard</given-names>
</name>
<email>bperbal@gmail.com</email>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Prosdocimo</surname>
<given-names>Domenick A.</given-names>
</name>
<email>Domenick.Prosdocimo@case.edu</email>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Lin</surname>
<given-names>Zhiyong</given-names>
</name>
<email>zhiyong.lin@case.edu</email>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio, USA.</aff>
<aff id="A2"><label>2</label>
Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.</aff>
<aff id="A3"><label>3</label>
Division of Hematology and Oncology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.</aff>
<aff id="A4"><label>4</label>
Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan.</aff>
<aff id="A5"><label>5</label>
Department of Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.</aff>
<aff id="A6"><label>6</label>
The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, and The Department of Vascular and Endovascular Surgery, Townsville Hospital, Townsville, Queensland, Australia.</aff>
<aff id="A7"><label>7</label>
School of Surgery, University of Western Australia, Perth, Western Australia, Australia.</aff>
<aff id="A8"><label>8</label>
Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.</aff>
<aff id="A9"><label>9</label>
Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.</aff>
<aff id="A10"><label>10</label>
Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.</aff>
<aff id="A11"><label>11</label>
University of Paris Diderot — Paris 7, Paris, France.</aff>
<author-notes><corresp>Address correspondence to: Zhiyong Lin, Case Cardiovascular Research Institute, 2103 Cornell Road, Room 4-541, Cleveland, Ohio 44106, USA. Phone: 216.368.0767; E-mail: <email>Zhiyong.lin@case.edu</email>
.</corresp>
</author-notes>
<pub-date date-type="pub" publication-format="electronic" iso-8601-date="2016-03-14"><day>14</day>
<month>3</month>
<year>2016</year>
</pub-date>
<pub-date date-type="pub" publication-format="print" iso-8601-date="2016-04-01"><day>1</day>
<month>4</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>7</month>
<year>2016</year>
</pub-date>
<pmc-comment> PMC Release delay is 3 months and
0 days and was based on the . </pmc-comment>
<volume>126</volume>
<issue>4</issue>
<fpage>1282</fpage>
<lpage>1299</lpage>
<history><date date-type="received"><day>16</day>
<month>4</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>28</day>
<month>1</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2016, American Society for Clinical Investigation</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>American Society for Clinical Investigation</copyright-holder>
</permissions>
<self-uri xlink:href="https://www.jci.org/articles/view/82337">This article is available online at https://www.jci.org/articles/view/82337</self-uri>
<abstract><p>Abdominal aortic aneurysm (AAA) is a major cause of morbidity and mortality; however, the mechanisms that are involved in disease initiation and progression are incompletely understood. Extracellular matrix proteins play an integral role in modulating vascular homeostasis in health and disease. Here, we determined that the expression of the matricellular protein CCN3 is strongly reduced in rodent AAA models, including angiotensin II–induced AAA and elastase perfusion–stimulated AAA. CCN3 levels were also reduced in human AAA biopsies compared with those in controls. In murine models of induced AAA, germline deletion of <italic>Ccn3</italic>
resulted in severe phenotypes characterized by elastin fragmentation, vessel dilation, vascular inflammation, dissection, heightened ROS generation, and smooth muscle cell loss. Conversely, overexpression of CCN3 mitigated both elastase- and angiotensin II–induced AAA formation in mice. BM transplantation experiments suggested that the AAA phenotype of CCN3-deficient mice is intrinsic to the vasculature, as AAA was not exacerbated in WT animals that received CCN3-deficient BM and WT BM did not reduce AAA severity in CCN3-deficient mice. Genetic and pharmacological approaches implicated the ERK1/2 pathway as a critical regulator of CCN3-dependent AAA development. Together, these results demonstrate that CCN3 is a nodal regulator in AAA biology and identify CCN3 as a potential therapeutic target for vascular disease.</p>
</abstract>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Afrique du Sud</li>
<li>Australie</li>
<li>France</li>
<li>Japon</li>
<li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Massachusetts</li>
<li>Michigan</li>
<li>Ohio</li>
<li>Région de Kantō</li>
<li>Île-de-France</li>
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<settlement><li>Paris</li>
<li>Tokyo</li>
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<name sortKey="Atkins, G Brandon" sort="Atkins, G Brandon" uniqKey="Atkins G" first="G. Brandon" last="Atkins">G. Brandon Atkins</name>
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<name sortKey="Lin, Zhiyong" sort="Lin, Zhiyong" uniqKey="Lin Z" first="Zhiyong" last="Lin">Zhiyong Lin</name>
<name sortKey="Prosdocimo, Domenick A" sort="Prosdocimo, Domenick A" uniqKey="Prosdocimo D" first="Domenick A." last="Prosdocimo">Domenick A. Prosdocimo</name>
<name sortKey="Qing, Yulan" sort="Qing, Yulan" uniqKey="Qing Y" first="Yulan" last="Qing">Yulan Qing</name>
<name sortKey="Rittie, Laure" sort="Rittie, Laure" uniqKey="Rittie L" first="Laure" last="Rittié">Laure Rittié</name>
<name sortKey="Shi, Guo Ping" sort="Shi, Guo Ping" uniqKey="Shi G" first="Guo-Ping" last="Shi">Guo-Ping Shi</name>
<name sortKey="Shi, Hong" sort="Shi, Hong" uniqKey="Shi H" first="Hong" last="Shi">Hong Shi</name>
<name sortKey="Van Der Voort, Dustin" sort="Van Der Voort, Dustin" uniqKey="Van Der Voort D" first="Dustin" last="Van Der Voort">Dustin Van Der Voort</name>
<name sortKey="Zhang, Rongli" sort="Zhang, Rongli" uniqKey="Zhang R" first="Rongli" last="Zhang">Rongli Zhang</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Zhang, Chao" sort="Zhang, Chao" uniqKey="Zhang C" first="Chao" last="Zhang">Chao Zhang</name>
</noRegion>
<name sortKey="Dong, Nianguo" sort="Dong, Nianguo" uniqKey="Dong N" first="Nianguo" last="Dong">Nianguo Dong</name>
</country>
<country name="Japon"><region name="Région de Kantō"><name sortKey="Hiraoka, Shuichi" sort="Hiraoka, Shuichi" uniqKey="Hiraoka S" first="Shuichi" last="Hiraoka">Shuichi Hiraoka</name>
</region>
<name sortKey="Takemoto, Minoru" sort="Takemoto, Minoru" uniqKey="Takemoto M" first="Minoru" last="Takemoto">Minoru Takemoto</name>
<name sortKey="Yokote, Koutaro" sort="Yokote, Koutaro" uniqKey="Yokote K" first="Koutaro" last="Yokote">Koutaro Yokote</name>
</country>
<country name="Australie"><noRegion><name sortKey="Moxon, Joseph V" sort="Moxon, Joseph V" uniqKey="Moxon J" first="Joseph V." last="Moxon">Joseph V. Moxon</name>
</noRegion>
<name sortKey="Golledge, Jonathan" sort="Golledge, Jonathan" uniqKey="Golledge J" first="Jonathan" last="Golledge">Jonathan Golledge</name>
<name sortKey="Norman, Paul" sort="Norman, Paul" uniqKey="Norman P" first="Paul" last="Norman">Paul Norman</name>
</country>
<country name="Afrique du Sud"><noRegion><name sortKey="Kuivaniemi, Helena" sort="Kuivaniemi, Helena" uniqKey="Kuivaniemi H" first="Helena" last="Kuivaniemi">Helena Kuivaniemi</name>
</noRegion>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Perbal, Bernard" sort="Perbal, Bernard" uniqKey="Perbal B" first="Bernard" last="Perbal">Bernard Perbal</name>
</region>
</country>
</tree>
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