Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein
Identifieur interne : 000057 ( Pmc/Checkpoint ); précédent : 000056; suivant : 000058Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein
Auteurs : Ali Makky [France] ; Luc Bousset [France] ; Jérôme Polesel-Maris [Luxembourg (pays)] ; Ronald Melki [France]Source :
- Scientific Reports [ 2045-2322 ] ; 2016.
Abstract
Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson’s disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs. The latter exhibited differences in their shape, their structure but also in their functional properties. We have conducted an AFM study at high resolution and performed a statistical analysis of fibrillar α-Syn shape and thermal fluctuations to calculate the persistence length to further assess the nanomechanical properties of α-Syn polymorphs. Herein, we demonstrated quantitatively that distinct polymorphs made of the same protein (wild-type α-Syn) show significant differences in their morphology (height, width and periodicity) and physical properties (persistence length, bending rigidity and axial Young’s modulus).
Url:
DOI: 10.1038/srep37970
PubMed: 27901068
PubMed Central: 5128817
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein</title><author><name sortKey="Makky, Ali" sort="Makky, Ali" uniqKey="Makky A" first="Ali" last="Makky">Ali Makky</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, University Paris-Saclay</institution>, 92296 Châtenay-Malabry,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bousset, Luc" sort="Bousset, Luc" uniqKey="Bousset L" first="Luc" last="Bousset">Luc Bousset</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay</institution>, 91190 Gif-sur-Yvette,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Polesel Maris, Jerome" sort="Polesel Maris, Jerome" uniqKey="Polesel Maris J" first="Jérôme" last="Polesel-Maris">Jérôme Polesel-Maris</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Luxembourg Institute of Science and Technology (LIST), Materials Research and Technology (MRT)</institution>, L-4422 Belvaux,<country>Luxembourg</country></nlm:aff><country xml:lang="fr">Luxembourg (pays)</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Melki, Ronald" sort="Melki, Ronald" uniqKey="Melki R" first="Ronald" last="Melki">Ronald Melki</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay</institution>, 91190 Gif-sur-Yvette,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27901068</idno><idno type="pmc">5128817</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5128817</idno><idno type="RBID">PMC:5128817</idno><idno type="doi">10.1038/srep37970</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000194</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000194</idno><idno type="wicri:Area/Pmc/Curation">000193</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000193</idno><idno type="wicri:Area/Pmc/Checkpoint">000057</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000057</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein</title><author><name sortKey="Makky, Ali" sort="Makky, Ali" uniqKey="Makky A" first="Ali" last="Makky">Ali Makky</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, University Paris-Saclay</institution>, 92296 Châtenay-Malabry,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bousset, Luc" sort="Bousset, Luc" uniqKey="Bousset L" first="Luc" last="Bousset">Luc Bousset</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay</institution>, 91190 Gif-sur-Yvette,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Polesel Maris, Jerome" sort="Polesel Maris, Jerome" uniqKey="Polesel Maris J" first="Jérôme" last="Polesel-Maris">Jérôme Polesel-Maris</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Luxembourg Institute of Science and Technology (LIST), Materials Research and Technology (MRT)</institution>, L-4422 Belvaux,<country>Luxembourg</country></nlm:aff><country xml:lang="fr">Luxembourg (pays)</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Melki, Ronald" sort="Melki, Ronald" uniqKey="Melki R" first="Ronald" last="Melki">Ronald Melki</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay</institution>, 91190 Gif-sur-Yvette,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson’s disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs. The latter exhibited differences in their shape, their structure but also in their functional properties. We have conducted an AFM study at high resolution and performed a statistical analysis of fibrillar α-Syn shape and thermal fluctuations to calculate the persistence length to further assess the nanomechanical properties of α-Syn polymorphs. Herein, we demonstrated quantitatively that distinct polymorphs made of the same protein (wild-type α-Syn) show significant differences in their morphology (height, width and periodicity) and physical properties (persistence length, bending rigidity and axial Young’s modulus).</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bousset, L" uniqKey="Bousset L">L. Bousset</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spillantini, M G" uniqKey="Spillantini M">M. G. Spillantini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spillantini, M G" uniqKey="Spillantini M">M. G. Spillantini</name></author><author><name sortKey="Crowther, R A" uniqKey="Crowther R">R. A. Crowther</name></author><author><name sortKey="Jakes, R" uniqKey="Jakes R">R. Jakes</name></author><author><name sortKey="Hasegawa, M" uniqKey="Hasegawa M">M. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27901068</article-id><article-id pub-id-type="pmc">5128817</article-id><article-id pub-id-type="pii">srep37970</article-id><article-id pub-id-type="doi">10.1038/srep37970</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Makky</surname><given-names>Ali</given-names></name><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bousset</surname><given-names>Luc</given-names></name><xref ref-type="corresp" rid="c2">b</xref><xref ref-type="aff" rid="a2">2</xref></contrib><contrib contrib-type="author"><name><surname>Polesel-Maris</surname><given-names>Jérôme</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Melki</surname><given-names>Ronald</given-names></name><xref ref-type="aff" rid="a2">2</xref></contrib><aff id="a1"><label>1</label><institution>Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, University Paris-Saclay</institution>, 92296 Châtenay-Malabry,<country>France</country></aff><aff id="a2"><label>2</label><institution>Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay</institution>, 91190 Gif-sur-Yvette,<country>France</country></aff><aff id="a3"><label>3</label><institution>Luxembourg Institute of Science and Technology (LIST), Materials Research and Technology (MRT)</institution>, L-4422 Belvaux,<country>Luxembourg</country></aff></contrib-group><author-notes><corresp id="c1"><label>a</label><email>ali.makky@u-psud.fr</email></corresp><corresp id="c2"><label>b</label><email>luc.bousset@cnrs.fr</email></corresp></author-notes><pub-date pub-type="epub"><day>30</day><month>11</month><year>2016</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>6</volume><elocation-id>37970</elocation-id><history><date date-type="received"><day>01</day><month>07</month><year>2016</year></date><date date-type="accepted"><day>03</day><month>11</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2016, The Author(s)</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>The Author(s)</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link></license-p></license></permissions><abstract><p>Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson’s disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs. The latter exhibited differences in their shape, their structure but also in their functional properties. We have conducted an AFM study at high resolution and performed a statistical analysis of fibrillar α-Syn shape and thermal fluctuations to calculate the persistence length to further assess the nanomechanical properties of α-Syn polymorphs. Herein, we demonstrated quantitatively that distinct polymorphs made of the same protein (wild-type α-Syn) show significant differences in their morphology (height, width and periodicity) and physical properties (persistence length, bending rigidity and axial Young’s modulus).</p></abstract></article-meta></front><floats-group><fig id="f1"><label>Figure 1</label><caption><title>TEM images of the different α-Syn fibrillar polymorphs.</title><p>Electron micrographs of α-Syn (<bold>a</bold>) fibrils, (<bold>b</bold>) ribbons, (<bold>c</bold>) fibrils-65, (<bold>d</bold>) fibrils-91 assemblies adsorbed onto carbon coated copper grid stained with Uranyl acetate. Scale bar 200 nm.</p></caption><graphic xlink:href="srep37970-f1"></graphic></fig><fig id="f2"><label>Figure 2</label><caption><p>(<bold>a,g</bold>) AM-AFM topography images in air mode of hydrated α-Syn fibrils and ribbons, respectively, adsorbed onto mica substrate. These images were used for fibrils height determination. (<bold>b,h</bold>) Histograms of fibrils and ribbons height distributions. (<bold>c,i</bold>) Contours of fibrils and ribbons imaged by AFM, where initial tangents were aligned. (<bold>d,j</bold>) PM-AFM topography images of α-Syn fibrils and ribbons, respectively, obtained with Ultrasharp probes in air mode. These images were used for fibrils width determination. (<bold>e,k</bold>) Histograms of α-Syn fibrils and ribbons width distributions. (<bold>f,l</bold>) End-to-end distance (R<sup>2</sup>) plots as a function of contour length for α-Syn fibrils and ribbons, respectively, adsorbed on mica (blue open circles). Least-square fits are shown as red lines.</p></caption><graphic xlink:href="srep37970-f2"></graphic></fig><fig id="f3"><label>Figure 3</label><caption><p>(<bold>a,g</bold>) AM-AFM topography images in air mode of hydrated α-Syn fibrils-65 and -91, respectively, adsorbed onto mica substrate. These images were used for fibrils-65 and -91 height determination. (<bold>b</bold>,<bold>h</bold>) Histograms of fibrils-65 and -91 height distributions. (<bold>c,i</bold>) Contours of fibrils-65 and -91 imaged by AFM, where initial tangents were aligned. (<bold>d,j</bold>) PM-AFM topography images of α-Syn fibrils-65 and -91, respectively, obtained with ultrasharp probes in air mode. These images were used for fibrils-65 and -91 width determination. (<bold>e,k</bold>) Histograms of α-Syn fibrils-65 and -91 width distributions. (<bold>f,l</bold>) End-to-end distance (R<sup>2</sup>) plots as a function of contour length for α-Syn fibrils-65 and -91, respectively, adsorbed on mica (blue open circles). Least-square fits are shown as red lines</p></caption><graphic xlink:href="srep37970-f3"></graphic></fig><fig id="f4"><label>Figure 4</label><caption><p>Scatter plots of α-Syn fibrils-65 and -91 periodicities are depicted in (<bold>b</bold>,<bold>f</bold>), respectively. Next to each plot are presented the histograms with the Gaussian fit of the periodicities distribution. The histograms of the height (<bold>a,e</bold>) and periodicity (<bold>c,g</bold>) distributions with the Gaussian fit (blue line) are also depicted. AFM images showing representative periodicities observed for α-Syn fibrils-65 (<bold>d</bold>) and fibrils-91 (<bold>h</bold>).</p></caption><graphic xlink:href="srep37970-f4"></graphic></fig><table-wrap position="float" id="t1"><label>Table 1</label><caption><title>Morphological and mechanical properties of the different fibrils type determined on either mica or HOPG substrates.</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50">Sample</th><th align="center" valign="top" charoff="50">Fibrils</th><th align="center" valign="top" charoff="50">Ribbons</th><th align="center" valign="top" charoff="50">Fibrils-65</th><th align="center" valign="top" charoff="50">Fibrils-91</th></tr></thead><tbody valign="top"><tr><td colspan="5" align="center" valign="top" charoff="50"><bold>Mica substrate</bold></td></tr><tr><td align="left" valign="top" charoff="50"><bold>Height (nm)</bold></td><td align="center" valign="top" charoff="50">6.4 ± 0.7</td><td align="center" valign="top" charoff="50">5.1 ± 0.8</td><td align="center" valign="top" charoff="50">6.7 ± 0.8</td><td align="center" valign="top" charoff="50">5.4 ± 1.5</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">(n = 110)</td><td align="center" valign="top" charoff="50">(n = 113)</td><td align="center" valign="top" charoff="50">(n = 144)</td><td align="center" valign="top" charoff="50">(n = 210)</td></tr><tr><td align="left" valign="top" charoff="50"><bold>Width (nm)</bold></td><td align="center" valign="top" charoff="50">15.0 ± 0.9</td><td align="center" valign="top" charoff="50">20.1 ± 0.7</td><td align="center" valign="top" charoff="50">21.9 ± 1.8</td><td align="center" valign="top" charoff="50">20.6 ± 1.7</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">(n = 61)</td><td align="center" valign="top" charoff="50">(n = 53)</td><td align="center" valign="top" charoff="50">(n = 45)</td><td align="center" valign="top" charoff="50">(n = 52)</td></tr><tr><td align="left" valign="top" charoff="50"><bold>Measured fibril length (μm)</bold></td><td align="center" valign="top" charoff="50">1.4 ± 0.5</td><td align="center" valign="top" charoff="50">1.1 ± 0.6</td><td align="center" valign="top" charoff="50">1.9 ± 0.7</td><td align="center" valign="top" charoff="50">1.7 ± 0.9</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">(n = 58)</td><td align="center" valign="top" charoff="50">(n = 73)</td><td align="center" valign="top" charoff="50">(n = 112)</td><td align="center" valign="top" charoff="50">(n = 56)</td></tr><tr><td align="left" valign="top" charoff="50"><bold>Persistence length (μm)</bold></td><td align="center" valign="top" charoff="50">14.2 ± 3.3</td><td align="center" valign="top" charoff="50">3.5 ± 1.0</td><td align="center" valign="top" charoff="50">6.5 ± 3.2</td><td align="center" valign="top" charoff="50">5.8 ± 1.7</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">(n = 58)</td><td align="center" valign="top" charoff="50">(n = 73)</td><td align="center" valign="top" charoff="50">(n = 112)</td><td align="center" valign="top" charoff="50">(n = 56)</td></tr><tr><td align="left" valign="top" charoff="50"><bold>Bending rigidity (×10</bold><sup><bold>−26</bold></sup><bold>N.m</bold><sup><bold>2</bold></sup>)</td><td align="center" valign="top" charoff="50">5.8 ± 1.3</td><td align="center" valign="top" charoff="50">1.4 ± 0.4</td><td align="center" valign="top" charoff="50">2.7 ± 1.3</td><td align="center" valign="top" charoff="50">2.4 ± 0.7</td></tr><tr><td align="left" valign="top" charoff="50"><bold>Second moment of area (×10</bold><sup><bold>−34</bold></sup><bold>m</bold><sup><bold>4</bold></sup><bold>) of ellipsoidal shape</bold></td><td align="center" valign="top" charoff="50">1.9</td><td align="center" valign="top" charoff="50">1.3</td><td align="center" valign="top" charoff="50">3.2</td><td align="center" valign="top" charoff="50">1.6</td></tr><tr><td align="left" valign="top" charoff="50"><bold>Young modulus (GPa) of ellipsoidal shape</bold></td><td align="center" valign="top" charoff="50">0.30</td><td align="center" valign="top" charoff="50">0.11</td><td align="center" valign="top" charoff="50">0.08</td><td align="center" valign="top" charoff="50">0.15</td></tr><tr><td align="left" valign="top" charoff="50"><bold>Second moment of area (×10</bold><sup><bold>−34</bold></sup><bold>m</bold><sup><bold>4</bold></sup><bold>) of tape shape</bold></td><td align="center" valign="top" charoff="50">3.3</td><td align="center" valign="top" charoff="50">2.2</td><td align="center" valign="top" charoff="50">5.4</td><td align="center" valign="top" charoff="50">2.7</td></tr><tr><td align="left" valign="top" charoff="50"><bold>Young modulus (GPa) of tape shape</bold></td><td align="center" valign="top" charoff="50">0.17</td><td align="center" valign="top" charoff="50">0.06</td><td align="center" valign="top" charoff="50">0.05</td><td align="center" valign="top" charoff="50">0.08</td></tr><tr><td colspan="5" align="center" valign="top" charoff="50"><bold>HOPG substrate</bold><hr></hr></td></tr><tr><td rowspan="2" align="left" valign="middle" charoff="50"><bold>Persistence length (μm)</bold></td><td align="center" valign="top" charoff="50">12.6 ± 3.3</td><td align="center" valign="top" charoff="50">4.1 ± 1.3</td><td align="center" valign="top" charoff="50">6.5 ± 1.0</td><td align="center" valign="top" charoff="50">5.5 ± 2.0</td></tr><tr><td align="center" valign="top" charoff="50">(n = 53)</td><td align="center" valign="top" charoff="50">(n = 61)</td><td align="center" valign="top" charoff="50">(n = 56)</td><td align="center" valign="top" charoff="50">(n = 38)</td></tr><tr><td align="left" valign="top" charoff="50"><bold>Bending rigidity (×10</bold><sup><bold>−26</bold></sup><bold>N.m</bold><sup><bold>2</bold></sup>)</td><td align="center" valign="top" charoff="50">5.2 ± 1.3</td><td align="center" valign="top" charoff="50">1.7 ± 0.6</td><td align="center" valign="top" charoff="50">2.7 ± 0.4</td><td align="center" valign="top" charoff="50">2.3 ± 0.8</td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list><country><li>France</li><li>Luxembourg (pays)</li></country></list><tree><country name="France"><noRegion><name sortKey="Makky, Ali" sort="Makky, Ali" uniqKey="Makky A" first="Ali" last="Makky">Ali Makky</name></noRegion><name sortKey="Bousset, Luc" sort="Bousset, Luc" uniqKey="Bousset L" first="Luc" last="Bousset">Luc Bousset</name><name sortKey="Melki, Ronald" sort="Melki, Ronald" uniqKey="Melki R" first="Ronald" last="Melki">Ronald Melki</name></country><country name="Luxembourg (pays)"><noRegion><name sortKey="Polesel Maris, Jerome" sort="Polesel Maris, Jerome" uniqKey="Polesel Maris J" first="Jérôme" last="Polesel-Maris">Jérôme Polesel-Maris</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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