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<!DOCTYPE html><html lang="en"><head><title data-react-helmet="true">Liliana M. Sanmarco scite author profile</title> <meta data-react-helmet="true" name="viewport" content="width=device-width, initial-scale=1, maximum-scale=5, viewport-fit=cover"/><meta data-react-helmet="true" property="og:site_name" content="scite.ai"/><meta data-react-helmet="true" property="og:type" content="website"/><meta data-react-helmet="true" property="og:url" content="https://scite.ai"/><meta data-react-helmet="true" property="twitter:card" content="summary_large_image"/><meta data-react-helmet="true" name="twitter:site" content="@scite"/><meta data-react-helmet="true" property="title" content="Liliana M. Sanmarco scite author profile"/><meta data-react-helmet="true" property="og:title" content="Liliana M. Sanmarco scite author profile"/><meta data-react-helmet="true" property="twitter:title" content="Liliana M. Sanmarco scite author profile"/><meta data-react-helmet="true" name="description" content="Supporting: 16 - Contrasting: 1 - Mentioning: 668 - Smart Citations for Liliana M. Sanmarco"/><meta data-react-helmet="true" property="og:description" content="Supporting: 16 - Contrasting: 1 - Mentioning: 668 - Smart Citations for Liliana M. Sanmarco"/><meta data-react-helmet="true" property="twitter:description" content="Supporting: 16 - Contrasting: 1 - Mentioning: 668 - Smart Citations for Liliana M. 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Sanmarco</h3><div class="Author__widgetContainer___Hnm_W"><div class="Notification__notificationContainer___N06uS " style="opacity:1;pointer-events:auto"><div role="button" class="Notification__notification___rIkeZ" tabindex="0"><div class="Notification__bellIcon___IKprf fa fa-bell"></div><div class="Notification__tooltip___DjoOa Tooltip__reference___hgPSY"><span class="Notification__setNotification___dsjeh">Sign up to set email alerts</span></div></div></div>|<div class="SharingWidget__container___UnD9v"><a class="SocialIcon__socialIcon___gm1fE SharingWidget__icon___Rek8d Link__link___plGt2 SocialIcon__socialIcon___gm1fE SharingWidget__icon___Rek8d" href="https://twitter.com/intent/tweet?text=scite%20Author%20Profile%20-%20Liliana%20M.%20Sanmarco&url=" tabindex="0" role="link" target="_blank" rel="noopener noreferrer" aria-label="https://twitter.com/scite"><i class="icon icon-twitter-new"></i></a><a class="SocialIcon__socialIcon___gm1fE SharingWidget__icon___Rek8d Link__link___plGt2 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style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div></div><div class="ProgressBar__bg___UVITD"><div class="ProgressBar__bar___AvWIq" style="width:0%"><div class="ProgressBar__inner___tiC7F ProgressBar__blue___VMO9o"></div></div></div></div><div style="opacity:0;pointer-events:none"><div class="PublicationInfo__articleCitationCountWrapper___fzJaN"><div class="PublicationInfo__countGroup___XGB7z"><span class="PublicationInfo__count___Dl63P">3</span><span class="PublicationInfo__countLabel___qOq41">Publications</span></div><div class="PublicationInfo__countGroup___XGB7z"><span class="PublicationInfo__count___Dl63P">685</span><span class="PublicationInfo__countLabel___qOq41">Citation Statements<!-- --> Received</span></div><div class="PublicationInfo__countGroup___XGB7z"><span class="PublicationInfo__count___Dl63P">308</span><span class="PublicationInfo__countLabel___qOq41">Citation Statements<!-- --> Given</span></div></div><div class="PublicationInfo__tallyWrapper___VYELt"><div class="PublicationInfo__profileTally___ZvSan"><span class="PublicationInfo__tallySubHeader___pW_2s">How they've been cited</span><a class="HorizontalTally__horizontalTally___gMrpx HorizontalTally__notClickable___L1uTA" disabled="" href="/"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">700</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">16</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">668</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">1</span></div></div></div></a></div><div class="PublicationInfo__profileTally___ZvSan"><span class="PublicationInfo__tallySubHeader___pW_2s">How they cite others</span><a class="HorizontalTally__horizontalTally___gMrpx HorizontalTally__notClickable___L1uTA" disabled="" href="/"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">285</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">13</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">295</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div></div></a></div></div></div></div></div></div><div class="Author__profileDetails___YUiVp"><div class="Author__affiliationSection___Ud0ZU"><div><div><div class="Tooltip__reference___hgPSY"><span class="Author__detailsHeader___uq1SB">Affiliations <i class="Author__infoIcon___IhHWw fa fa-info-circle"></i></span></div></div><a class="Author__affiliation___svQn9 Link__link___plGt2 Link__blueLink___BhE5_ Author__affiliation___svQn9" tabindex="0" href="/affiliations/brigham-and-women-s-hospital-6JX1">Brigham and Women's Hospital</a>, <a class="Author__affiliation___svQn9 Link__link___plGt2 Link__blueLink___BhE5_ Author__affiliation___svQn9" tabindex="0" href="/affiliations/harvard-university-NmzP">Harvard University</a>, <a class="Author__affiliation___svQn9 Link__link___plGt2 Link__blueLink___BhE5_ Author__affiliation___svQn9" tabindex="0" href="/affiliations/universidad-nacional-de-cordoba-yVGl">Universidad Nacional de C贸rdoba</a> </div></div><div class="Author__detailsContainer___rS4Du"><div class="Author__detailsHeader___uq1SB">Publications</div><div class="Author__setSort___wG8Ve"><style data-emotion="css 3iigni-container">.css-3iigni-container{pointer-events:none;position:relative;box-sizing:border-box;}</style><div class=" css-3iigni-container"><style data-emotion="css 7pg0cj-a11yText">.css-7pg0cj-a11yText{z-index:9999;border:0;clip:rect(1px, 1px, 1px, 1px);height:1px;width:1px;position:absolute;overflow:hidden;padding:0;white-space:nowrap;}</style><span id="react-select-175775-live-region" class="css-7pg0cj-a11yText"></span><span aria-live="polite" aria-atomic="false" aria-relevant="additions text" 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hlgwow">.css-hlgwow{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;display:grid;-webkit-flex:1;-ms-flex:1;flex:1;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-overflow-scrolling:touch;position:relative;overflow:hidden;padding:2px 8px;box-sizing:border-box;}</style><div class=" css-hlgwow"><div style="label:singleValue;grid-area:1 / 1 / 2 / 3;max-width:100%;overflow:hidden;text-overflow:ellipsis;white-space:nowrap;color:hsl(0, 0%, 60%);margin-left:2px;margin-right:2px;box-sizing:border-box">Order By: <!-- -->Most citations</div><style data-emotion="css 1mkvw8y">.css-1mkvw8y{visibility:hidden;-webkit-flex:1 1 auto;-ms-flex:1 1 auto;flex:1 1 auto;display:inline-grid;grid-area:1/1/2/3;grid-template-columns:0 min-content;margin:2px;padding-bottom:2px;padding-top:2px;color:hsl(0, 0%, 20%);box-sizing:border-box;}.css-1mkvw8y:after{content:attr(data-value) " 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css-0"></span><style data-emotion="css 1xc3v61-indicatorContainer">.css-1xc3v61-indicatorContainer{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-transition:color 150ms;transition:color 150ms;color:hsl(0, 0%, 80%);padding:8px;box-sizing:border-box;}.css-1xc3v61-indicatorContainer:hover{color:hsl(0, 0%, 60%);}</style><div class=" css-1xc3v61-indicatorContainer" aria-hidden="true"><style data-emotion="css 8mmkcg">.css-8mmkcg{display:inline-block;fill:currentColor;line-height:1;stroke:currentColor;stroke-width:0;}</style><svg height="20" width="20" viewBox="0 0 20 20" aria-hidden="true" focusable="false" class="css-8mmkcg"><path d="M4.516 7.548c0.436-0.446 1.043-0.481 1.576 0l3.908 3.747 3.908-3.747c0.533-0.481 1.141-0.446 1.574 0 0.436 0.445 0.408 1.197 0 1.615-0.406 0.418-4.695 4.502-4.695 4.502-0.217 0.223-0.502 0.335-0.787 0.335s-0.57-0.112-0.789-0.335c0 0-4.287-4.084-4.695-4.502s-0.436-1.17 0-1.615z"></path></svg></div></div></div></div></div></div><div class="Author__papers___ZUSjf"><div class="Author__paper___WaOSw Result__result___NPjx7"><div class="PaperCard__paperCard___Tkx_L"><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/mafg-driven-astrocytes-promote-cns-inflammation-68ZWDAMX"><h3 class="Paper__title___WkJQP">MAFG-driven astrocytes promote CNS inflammation</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/michael-a-wheeler-8G4OAM"><span>Wheeler</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/brigham-and-women-s-hospital-6JX1">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/iain-c-clark-ejOnM6"><span>Clark</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/brigham-and-women-s-hospital-6JX1">2</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/emily-tjon-2NV3XZ"><span>Tjon</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/brigham-and-women-s-hospital-6JX1">3</a></sup></div><span> </span></div><span class="Authors__link___k07oy">et al.</span><span> <!-- -->2020</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/nature-wmGvz"><em>Nature</em></a></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/mafg-driven-astrocytes-promote-cns-inflammation-68ZWDAMX"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">334</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">9</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">374</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.1038/s41586-020-1999-0" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr PaperCard__abstract___lR5RS Paragraph__body____m5FY"><span><span>Multiple sclerosis is a chronic inflammatory disease of the CNS 1 . Astrocytes contribute to the pathogenesis of multiple sclerosis 2 , but little is known about the heterogeneity of astrocytes and its regulation. Here we report the analysis of astrocytes in multiple sclerosis and its preclinical model experimental autoimmune encephalomyelitis (EAE) by single-cell RNA sequencing in combination with cell-specific Ribotag RNA profiling, assay for transposase-accessible chromatin with sequencing (ATAC-seq), chromatin immunoprecipitation with sequencing (ChIP-seq), genome-wide analysis of DNA methylation and in vivo CRISPR-Cas9-based genetic perturbations. We identified astrocytes in EAE and multiple sclerosis that were characterized by decreased expression of NRF2 and increased expression of MAFG, which cooperates with MAT2伪 to promote DNA methylation and represses antioxidant and anti-inflammatory transcriptional programs. Granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling in astrocytes drives the expression of MAFG and MAT2伪 and pro-inflammatory transcriptional modules, contributing to CNS pathology in EAE and, potentially, multiple sclerosis. Our results identify candidate therapeutic targets in multiple sclerosis.</span></span></p></div></div></div><div class="PaperCard__menu___wXkM0"><a class="PaperCard__textButton___ncs_Z" tabindex="0">show abstract</a><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div></div><div class="Author__paper___WaOSw Result__result___NPjx7"><div class="PaperCard__paperCard___Tkx_L"><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/gut-licensed-ifn纬-nk-cells-drive-4LbRWj5E"><h3 class="Paper__title___WkJQP">Gut-licensed IFN纬+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/liliana-m-sanmarco-ZGKyAp"><span>Sanmarco</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/brigham-and-women-s-hospital-6JX1">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/michael-a-wheeler-8G4OAM"><span>Wheeler</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/brigham-and-women-s-hospital-6JX1">2</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/cristina-gutierrez-vazquez-mOVZRg"><span>Guti茅rrez-V谩zquez</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/brigham-and-women-s-hospital-6JX1">3</a></sup></div><span> </span></div><span class="Authors__link___k07oy">et al.</span><span> <!-- -->2021</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/nature-wmGvz"><em>Nature</em></a></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/gut-licensed-ifn纬-nk-cells-drive-4LbRWj5E"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">217</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">3</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">154</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.1038/s41586-020-03116-4" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr PaperCard__abstract___lR5RS Paragraph__body____m5FY"><span><span>Astrocytes are glial cells that are abundant in the central nervous system (CNS) and that have important homeostatic and disease-promoting functions1. However, little is known about the homeostatic anti-inflammatory activities of astrocytes and their regulation. Here, using high-throughput flow cytometry screening, single-cell RNA sequencing and CRISPR-Cas9-based cell-specific in vivo genetic perturbations in mice, we identify a subset of astrocytes that expresses the lysosomal protein LAMP12 and the death receptor ligand TRAIL3. LAMP1+TRAIL+ astrocytes limit inflammation in the CNS by inducing T cell apoptosis through TRAIL-DR5 signalling. In homeostatic conditions, the expression of TRAIL in astrocytes is driven by interferon-(IFN) produced by meningeal natural killer (NK) cells, in which IFN expression is modulated by the gut microbiome. TRAIL expression in astrocytes is repressed by molecules produced by T cells and microglia in the context of inflammation. Altogether, we show that LAMP1+TRAIL+ astrocytes limit CNS inflammation by inducing T cell apoptosis, and that this astrocyte subset is maintained by meningeal IFN+ NK cells that are licensed by the microbiome.</span></span></p></div></div></div><div class="PaperCard__menu___wXkM0"><a class="PaperCard__textButton___ncs_Z" tabindex="0">show abstract</a><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div></div><div class="Author__paper___WaOSw Result__result___NPjx7"><div class="PaperCard__paperCard___Tkx_L"><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/metabolic-control-of-astrocyte-pathogenic-e6JVGr2"><h3 class="Paper__title___WkJQP">Metabolic Control of Astrocyte Pathogenic Activity via cPLA2-MAVS</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/chun-cheih-chao-8DrvQ"><span>Chao</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/brigham-and-women-s-hospital-6JX1">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/cristina-gutierrez-vazquez-mOVZRg"><span>Guti茅rrez-V谩zquez</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/brigham-and-women-s-hospital-6JX1">2</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/veit-rothhammer-68R2QE"><span>Rothhammer</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/brigham-and-women-s-hospital-6JX1">3</a></sup></div><span> </span></div><span class="Authors__link___k07oy">et al.</span><span> <!-- -->2019</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/cell-pnm4z"><em>Cell</em></a></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/metabolic-control-of-astrocyte-pathogenic-e6JVGr2"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">149</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">4</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">140</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">1</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.1016/j.cell.2019.11.016" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr PaperCard__abstract___lR5RS Paragraph__body____m5FY"><span><span>Highlights d Sphingolipid drives astrocyte pathogenic activities via cPLA2-MAVS-NF-kB d cPLA2 displaces HK2 from MAVS, limiting the metabolic support of neurons by astrocytes d Miglustat suppresses astrocyte cPLA2-MAVS-NF-kB proinflammatory signaling d Miglustat is a candidate drug for repurposing to treat secondary progressive MS</span></span></p></div></div></div><div class="PaperCard__menu___wXkM0"><a class="PaperCard__textButton___ncs_Z" tabindex="0">show abstract</a><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div></div><div class="Author__paginatorLayout___ZeycX"><div class="Author__paginatorLoading___Zgmtf layouts__absoluteCenter___zke7Q" style="opacity:0;pointer-events:auto"><div data-testid="circle-spinner" class="CircleSpinner__sciteLoadingRing___nlTrH" style="width:64px;height:64px"><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:51.2px;height:51.2px;margin:6.4px;border-width:6.4px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent 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Sanmarco","affiliations":[{"affiliation":"Brigham and Women's Hospital","affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationId":9610,"count":17},{"affiliation":"Harvard University","affiliationSlug":"harvard-university-NmzP","affiliationId":14927,"count":16},{"affiliation":"Universidad Nacional de C贸rdoba","affiliationSlug":"universidad-nacional-de-cordoba-yVGl","affiliationId":14620,"count":14},{"affiliation":"Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas","affiliationSlug":"consejo-nacional-de-investigaciones-cientificas-Qrbw","affiliationId":14160,"count":13},{"affiliation":"Research Centre in Biological Chemistry of C贸rdoba","affiliationSlug":"research-centre-in-biological-chemistry-4Zl8P","affiliationId":267186,"count":8},{"affiliation":"Centro Cient铆fico Tecnol贸gico - San Juan","affiliationSlug":"centro-cientifico-tecnologico-san-8V4Ja","affiliationId":314265,"count":2},{"affiliation":"Centro Cient铆fico Tecnol贸gico - Tucum谩n","affiliationSlug":"centro-cientifico-tecnologico-tucuman-0akEP","affiliationId":213212,"count":2}],"lastKnownAffiliationId":9610,"loading":true,"papers":[{"id":7403668754,"doi":"10.1038\u002Fs41586-020-1999-0","slug":"mafg-driven-astrocytes-promote-cns-inflammation-68ZWDAMX","type":"journal-article","title":"MAFG-driven astrocytes promote CNS inflammation","abstract":"Multiple sclerosis is a chronic inflammatory disease of the CNS 1 . Astrocytes contribute to the pathogenesis of multiple sclerosis 2 , but little is known about the heterogeneity of astrocytes and its regulation. Here we report the analysis of astrocytes in multiple sclerosis and its preclinical model experimental autoimmune encephalomyelitis (EAE) by single-cell RNA sequencing in combination with cell-specific Ribotag RNA profiling, assay for transposase-accessible chromatin with sequencing (ATAC-seq), chromatin immunoprecipitation with sequencing (ChIP-seq), genome-wide analysis of DNA methylation and in vivo CRISPR-Cas9-based genetic perturbations. We identified astrocytes in EAE and multiple sclerosis that were characterized by decreased expression of NRF2 and increased expression of MAFG, which cooperates with MAT2伪 to promote DNA methylation and represses antioxidant and anti-inflammatory transcriptional programs. Granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling in astrocytes drives the expression of MAFG and MAT2伪 and pro-inflammatory transcriptional modules, contributing to CNS pathology in EAE and, potentially, multiple sclerosis. Our results identify candidate therapeutic targets in multiple sclerosis.","authors":[{"family":"Wheeler","given":"Michael A.","affiliation":"Brigham and Women's Hospital","authorSlug":"michael-a-wheeler-8G4OAM","authorName":"Michael A. Wheeler","authorID":"6321865","authorLastKnownAffiliationId":9610,"authorSequenceNumber":1,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Clark","given":"Iain C.","affiliation":"Brigham and Women's Hospital","authorSlug":"iain-c-clark-ejOnM6","authorName":"Iain C. Clark","authorID":"6740099","authorLastKnownAffiliationId":19129,"authorSequenceNumber":2,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Tjon","given":"Emily","affiliation":"Brigham and Women's Hospital","authorSlug":"emily-tjon-2NV3XZ","authorName":"Emily Tjon","authorID":"6379776","authorLastKnownAffiliationId":9610,"authorSequenceNumber":3,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Li","given":"Zhaorong","affiliation":"Brigham and Women's Hospital","authorSlug":"zhaorong-li-ke8Krw","authorName":"Zhaorong Li","authorID":"6944024","authorLastKnownAffiliationId":213052,"authorSequenceNumber":4,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Zandee","given":"St茅phanie","affiliation":"Universit茅 de Montr茅al","authorSlug":"stephanie-zandee-K6N90d","authorName":"St茅phanie Zandee","authorID":"6599579","authorLastKnownAffiliationId":257904,"authorSequenceNumber":5,"affiliationSlug":"universite-de-montreal-nDKN","affiliationID":"10677"},{"family":"Couturier","given":"C茅line","affiliation":"Montreal Neurological Institute and Hospital","authorSlug":"celine-couturier-9OJlAG","authorName":"C茅line Couturier","authorID":"5916890","authorLastKnownAffiliationId":1578,"authorSequenceNumber":6,"affiliationSlug":"montreal-neurological-institute-and-hospital-O0Q","affiliationID":"1578"},{"family":"Watson","given":"Brianna R.","affiliation":"Harvard University","authorSlug":"brianna-r-watson-G5jxAx","authorName":"Brianna R. Watson","authorID":"8505457","authorLastKnownAffiliationId":210484,"authorSequenceNumber":7,"affiliationSlug":"harvard-university-NmzP","affiliationID":"14927"},{"family":"Scalisi","given":"Giulia","affiliation":"Brigham and Women's Hospital","authorSlug":"giulia-scalisi-Zxj0m2","authorName":"Giulia Scalisi","authorID":"8073575","authorLastKnownAffiliationId":13291,"authorSequenceNumber":8,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Alkwai","given":"Sarah","affiliation":"Brigham and Women's Hospital","authorSlug":"sarah-alkwai-vy14eJ","authorName":"Sarah Alkwai","authorID":"10131397","authorLastKnownAffiliationId":161459,"authorSequenceNumber":9,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Rothhammer","given":"Veit","affiliation":"Brigham and Women's Hospital","authorSlug":"veit-rothhammer-68R2QE","authorName":"Veit Rothhammer","authorID":"6174754","authorLastKnownAffiliationId":218663,"authorSequenceNumber":10,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Rotem","given":"Assaf","affiliation":"Harvard University","authorSlug":"assaf-rotem-EWxXnk","authorName":"Assaf Rotem","authorID":"6528461","authorLastKnownAffiliationId":14927,"authorSequenceNumber":11,"affiliationSlug":"harvard-university-NmzP","affiliationID":"14927"},{"family":"Heyman","given":"John A.","affiliation":"Harvard University","authorSlug":"john-a-heyman-pnL5pj","authorName":"John A. Heyman","authorID":"4544730","authorLastKnownAffiliationId":14927,"authorSequenceNumber":12,"affiliationSlug":"harvard-university-NmzP","affiliationID":"14927"},{"family":"Thaploo","given":"Shravan","affiliation":"Brigham and Women's Hospital","authorSlug":"shravan-thaploo-5Yv4yA","authorName":"Shravan Thaploo","authorID":"10415669","authorLastKnownAffiliationId":9610,"authorSequenceNumber":13,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Sanmarco","given":"Liliana M.","affiliation":"Brigham and Women's Hospital","authorSlug":"liliana-m-sanmarco-ZGKyAp","authorName":"Liliana M. Sanmarco","authorID":"7332975","authorLastKnownAffiliationId":9610,"authorSequenceNumber":14,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Ragoussis","given":"Jiannis","affiliation":"McGill University and G茅nome Qu茅bec Innovation Centre","authorSlug":"jiannis-ragoussis-NlQ4L9","authorName":"Jiannis Ragoussis","authorID":"5766527","authorLastKnownAffiliationId":155364,"authorSequenceNumber":15,"affiliationSlug":"mcgill-university-and-genome-quebec-6n98X","affiliationID":"274998"},{"family":"Weitz","given":"David A.","affiliation":"Harvard University","authorSlug":"david-a-weitz-zR23L3","authorName":"David A. Weitz","authorID":"4789806","authorLastKnownAffiliationId":14927,"authorSequenceNumber":16,"affiliationSlug":"harvard-university-NmzP","affiliationID":"14927"},{"family":"Petrecca","given":"Kevin","affiliation":"Montreal Neurological Institute and Hospital","authorSlug":"kevin-petrecca-MVj0x0","authorName":"Kevin Petrecca","authorID":"6065408","authorLastKnownAffiliationId":1578,"authorSequenceNumber":17,"affiliationSlug":"montreal-neurological-institute-and-hospital-O0Q","affiliationID":"1578"},{"family":"Moffitt","given":"Jeffrey R.","affiliation":"Harvard University","authorSlug":"jeffrey-r-moffitt-dvyOr9","authorName":"Jeffrey R. Moffitt","authorID":"5971818","authorLastKnownAffiliationId":10282,"authorSequenceNumber":18,"affiliationSlug":"harvard-university-NmzP","affiliationID":"14927"},{"family":"Becher","given":"Burkhard","affiliation":"University of Zurich","authorSlug":"burkhard-becher-NayApg","authorName":"Burkhard Becher","authorID":"103112827","authorLastKnownAffiliationId":15057,"authorSequenceNumber":19,"affiliationSlug":"university-of-zurich-G2NZ","affiliationID":"15057"},{"family":"Antel","given":"Jack","affiliation":"Montreal Neurological Institute and Hospital","authorSlug":"jack-antel-n69lyn","authorName":"Jack Antel","authorID":"5814533","authorLastKnownAffiliationId":1578,"authorSequenceNumber":20,"affiliationSlug":"montreal-neurological-institute-and-hospital-O0Q","affiliationID":"1578"},{"family":"Prat","given":"Alexandre","affiliation":"Universit茅 de Montr茅al","authorSlug":"alexandre-prat-PQbYjk","authorName":"Alexandre Prat","authorID":"4894689","authorLastKnownAffiliationId":257904,"authorSequenceNumber":21,"affiliationSlug":"universite-de-montreal-nDKN","affiliationID":"10677"},{"family":"Quintana","given":"Francisco J.","affiliation":"Brigham and Women's Hospital","authorSlug":"francisco-j-quintana-1ZvWD0","authorName":"Francisco J. Quintana","authorID":"4869347","authorLastKnownAffiliationId":9610,"authorSequenceNumber":22,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"}],"keywords":[],"year":2020,"shortJournal":"Nature","publisher":"Springer Science and Business Media LLC","issue":"7796","volume":"578","page":"593-599","retracted":false,"memberId":297,"issns":["0028-0836","1476-4687"],"tally":{"total":384,"supporting":9,"contradicting":0,"mentioning":374,"unclassified":1,"doi":"10.1038\u002Fs41586-020-1999-0","citingPublications":334},"citingTally":{"total":53,"supporting":0,"contradicting":0,"mentioning":53,"unclassified":0,"sourceDoi":"10.1038\u002Fs41586-020-1999-0","numCitedPublications":100},"editorialNotices":[],"journalSlug":"nature-wmGvz","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},{"id":9980322542,"doi":"10.1038\u002Fs41586-020-03116-4","slug":"gut-licensed-ifn纬-nk-cells-drive-4LbRWj5E","type":"journal-article","title":"Gut-licensed IFN纬+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes","abstract":"Astrocytes are glial cells that are abundant in the central nervous system (CNS) and that have important homeostatic and disease-promoting functions1. However, little is known about the homeostatic anti-inflammatory activities of astrocytes and their regulation. Here, using high-throughput flow cytometry screening, single-cell RNA sequencing and CRISPR-Cas9-based cell-specific in vivo genetic perturbations in mice, we identify a subset of astrocytes that expresses the lysosomal protein LAMP12 and the death receptor ligand TRAIL3. LAMP1+TRAIL+ astrocytes limit inflammation in the CNS by inducing T cell apoptosis through TRAIL-DR5 signalling. In homeostatic conditions, the expression of TRAIL in astrocytes is driven by interferon-(IFN) produced by meningeal natural killer (NK) cells, in which IFN expression is modulated by the gut microbiome. TRAIL expression in astrocytes is repressed by molecules produced by T cells and microglia in the context of inflammation. Altogether, we show that LAMP1+TRAIL+ astrocytes limit CNS inflammation by inducing T cell apoptosis, and that this astrocyte subset is maintained by meningeal IFN+ NK cells that are licensed by the microbiome.","authors":[{"family":"Sanmarco","given":"Liliana M.","affiliation":"Brigham and Women's Hospital","authorSlug":"liliana-m-sanmarco-ZGKyAp","authorName":"Liliana M. Sanmarco","authorID":"7332975","authorLastKnownAffiliationId":9610,"authorSequenceNumber":1,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Wheeler","given":"Michael A.","affiliation":"Brigham and Women's Hospital","authorSlug":"michael-a-wheeler-8G4OAM","authorName":"Michael A. Wheeler","authorID":"6321865","authorLastKnownAffiliationId":9610,"authorSequenceNumber":2,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Guti茅rrez-V谩zquez","given":"Cristina","affiliation":"Brigham and Women's Hospital","authorSlug":"cristina-gutierrez-vazquez-mOVZRg","authorName":"Cristina Guti茅rrez-V谩zquez","authorID":"5263343","authorLastKnownAffiliationId":213283,"authorSequenceNumber":3,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Polonio","given":"Carolina Manganeli","affiliation":"Brigham and Women's Hospital","authorSlug":"carolina-manganeli-polonio-RVmORD","authorName":"Carolina Manganeli Polonio","authorID":"5225170","authorLastKnownAffiliationId":9610,"authorSequenceNumber":4,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Linnerbauer","given":"Mathias","affiliation":"Brigham and Women's Hospital","authorSlug":"mathias-linnerbauer-Zx3a3d","authorName":"Mathias Linnerbauer","authorID":"7906831","authorLastKnownAffiliationId":9610,"authorSequenceNumber":5,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Pinho鈥怰ibeiro","given":"Felipe A.","affiliation":"Harvard University","authorSlug":"felipe-a-pinho-ribeiro-W8py11","authorName":"Felipe A. Pinho鈥怰ibeiro","authorID":"5776348","authorLastKnownAffiliationId":19037,"authorSequenceNumber":6,"affiliationSlug":"harvard-university-NmzP","affiliationID":"14927"},{"family":"Li","given":"Zhaorong","affiliation":"Brigham and Women's Hospital","authorSlug":"zhaorong-li-ke8Krw","authorName":"Zhaorong Li","authorID":"6944024","authorLastKnownAffiliationId":213052,"authorSequenceNumber":7,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Giovannoni","given":"Federico","affiliation":"Brigham and Women's Hospital","authorSlug":"federico-giovannoni-xQWJy3","authorName":"Federico Giovannoni","authorID":"8088622","authorLastKnownAffiliationId":9610,"authorSequenceNumber":8,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Batterman","given":"Katelyn V.","affiliation":"Boston University","authorSlug":"katelyn-v-batterman-QyYK0V","authorName":"Katelyn V. Batterman","authorID":"8041016","authorLastKnownAffiliationId":7891,"authorSequenceNumber":9,"affiliationSlug":"boston-university-11nj","affiliationID":"7891"},{"family":"Scalisi","given":"Giulia","affiliation":"Brigham and Women's Hospital","authorSlug":"giulia-scalisi-Zxj0m2","authorName":"Giulia Scalisi","authorID":"8073575","authorLastKnownAffiliationId":13291,"authorSequenceNumber":10,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Zandee","given":"St茅phanie","affiliation":"Centre Hospitalier de l鈥橴niversit茅 de Montr茅al","authorSlug":"stephanie-zandee-K6N90d","authorName":"St茅phanie Zandee","authorID":"6599579","authorLastKnownAffiliationId":257904,"authorSequenceNumber":11,"affiliationSlug":"centre-hospitalier-de-l-universite-de-Wx80g","affiliationID":"257904"},{"family":"Heck","given":"Evelyn S.","affiliation":"Brigham and Women's Hospital","authorSlug":"evelyn-s-heck-0XZ3D0","authorName":"Evelyn S. Heck","authorID":"14376012","authorLastKnownAffiliationId":9610,"authorSequenceNumber":12,"affiliationSlug":"brigham-and-women-s-hospital-6JX1","affiliationID":"9610"},{"family":"Alsuwailm","given":"Moneera","affiliation":"Harvard University","authorSlug":"moneera-alsuwailm-ayRMRr","authorName":"Moneera Alsuwailm","authorID":"9446739","authorLastKnownAffiliationId":9610,"authorSequenceNumber":13,"affiliationSlug":"harvard-university-NmzP","affiliationID":"14927"},{"family":"Rosene","given":"Douglas L.","affiliation":"Boston University","authorSlug":"douglas-l-rosene-n659EV","authorName":"Douglas L. 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