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Tauopathiestau-positive. mutations in tau. . . cause expression of splice variants or missense mutantsaffect microtuble binding capacity. pathophysiologicalalterations. Fig. 1B. Chromosome 17-linked FTLD. tau pathology. TDP-43 proteinopathiestau-negative, ubiquitin-positive. etiology.

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Sporadic ad

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icon-ok-sign" title="You have access" style="display:none;"></i></span></div> <a href="http://emboj.embopress.org/content/early/2014/06/05/embj.201387549" class="highwire-cite-linked-title"><div class="highwire-cite-title">The SNARE protein vti1a functions in dense‐core vesicle biogenesis</div><div class="highwire-cite-subtitle"></div></a> <div class="highwire-cite-snippet"><div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" id="content-block" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article precis-view "><span class="highwire-journal-article-marker-start"></span><div class="contributors"><ol class="contributor-list" id="contrib-group-1"><li class="contributor" id="contrib-1"><span class="name">Alexander M Walter</span><a id="xref-aff-1-1" class="xref-aff" href="#aff-1"><sup>1</sup></a><span class="xref-sep">,</span><a id="xref-aff-2-1" class="xref-aff" href="#aff-2"><sup>2</sup></a><span class="xref-sep">,</span><a id="xref-fn-1-1" class="xref-fn" href="#fn-1"><sup>†</sup></a>, </li><li class="contributor" id="contrib-2"><span class="name">Julia Kurps</span><a id="xref-aff-2-2" class="xref-aff" href="#aff-2"><sup>2</sup></a><span class="xref-sep">,</span><a id="xref-fn-1-2" class="xref-fn" href="#fn-1"><sup>†</sup></a>, </li><li class="contributor" id="contrib-3"><span class="name">Heidi de Wit</span><a id="xref-aff-2-3" class="xref-aff" href="#aff-2"><sup>2</sup></a>, </li><li class="contributor" id="contrib-4"><span class="name">Susanne Schöning</span><a id="xref-aff-3-1" class="xref-aff" href="#aff-3"><sup>3</sup></a>, </li><li class="contributor" id="contrib-5"><span class="name">Trine L Toft‐Bertelsen</span><a id="xref-aff-1-2" class="xref-aff" href="#aff-1"><sup>1</sup></a>, </li><li class="contributor" id="contrib-6"><span class="name">Juliane Lauks</span><a id="xref-aff-2-4" class="xref-aff" href="#aff-2"><sup>2</sup></a>, </li><li class="contributor" id="contrib-7"><span class="name">Iwona Ziomkiewicz</span><a id="xref-aff-4-1" class="xref-aff" href="#aff-4"><sup>4</sup></a>, </li><li class="contributor" id="contrib-8"><span class="name">Annita N Weiss</span><a id="xref-aff-5-1" class="xref-aff" href="#aff-5"><sup>5</sup></a>, </li><li class="contributor" id="contrib-9"><span class="name">Alexander Schulz</span><a id="xref-aff-4-2" class="xref-aff" href="#aff-4"><sup>4</sup></a>, </li><li class="contributor" id="contrib-10"><span class="name">Gabriele Fischer von Mollard</span><a id="xref-aff-3-2" class="xref-aff" href="#aff-3"><sup>3</sup></a>, </li><li class="contributor" id="contrib-11"><span class="name">Matthijs Verhage</span><a id="xref-aff-2-5" class="xref-aff" href="#aff-2"><sup>2</sup></a> and </li><li class="last" id="contrib-12"><span class="name">Jakob B Sørensen</span><a id="xref-corresp-1-1" class="xref-correspondence-address" href="#corresp-1">*</a><span class="xref-sep">,</span><a id="xref-aff-1-3" class="xref-aff" href="#aff-1"><sup>1</sup></a><span class="xref-sep">,</span><a id="xref-aff-6-1" class="xref-aff" href="#aff-6"><sup>6</sup></a></li></ol><ol class="affiliation-list"><li class="aff"><a id="aff-1" name="aff-1"></a><address><sup>1</sup><span class="named-content organisation-division" id="named-content-1">Neurosecretion Group</span>, <span class="named-content organisation-division" id="named-content-2">Department of Neuroscience and Pharmacology</span>, <span class="named-content organisation-division" id="named-content-3">Faculty of Health and Medical Sciences</span>, University of Copenhagen, <span class="named-content city" id="named-content-4">Copenhagen</span>, Denmark</address></li><li class="aff"><a id="aff-2" name="aff-2"></a><address><sup>2</sup><span class="named-content organisation-division" id="named-content-5">Department of Functional Genomics and Clinical Genetics</span>, <span class="named-content organisation-division" id="named-content-6">Center for Neurogenomics and Cognitive Research</span>, VU University Amsterdam and VU Medical Center, <span class="named-content city" id="named-content-7">Amsterdam</span>, The Netherlands</address></li><li class="aff"><a id="aff-3" name="aff-3"></a><address><sup>3</sup><span class="named-content organisation-division" id="named-content-8">Biochemie III</span>, <span class="named-content organisation-division" id="named-content-9">Fakultät für Chemie</span>, Universität Bielefeld, <span class="named-content city" id="named-content-10">Bielefeld</span>, Germany</address></li><li class="aff"><a id="aff-4" name="aff-4"></a><address><sup>4</sup><span class="named-content organisation-division" id="named-content-11">Department of Plant and Environmental Sciences</span>, University of Copenhagen, <span class="named-content city" id="named-content-12">Frederiksberg</span>, Denmark</address></li><li class="aff"><a id="aff-5" name="aff-5"></a><address><sup>5</sup><span class="named-content organisation-division" id="named-content-13">Department of Pharmacology</span>, University of Michigan, <span class="named-content city" id="named-content-14">Ann Arbor</span>, <span class="named-content state" id="named-content-15">MI</span>, USA</address></li><li class="aff"><a id="aff-6" name="aff-6"></a><address><sup>6</sup><span class="named-content organisation-division" id="named-content-16">Lundbeck Foundation Center for Biomembranes in Nanomedicine</span>, University of Copenhagen, <span class="named-content city" id="named-content-17">Copenhagen</span>, Denmark</address></li></ol><ol class="corresp-list"><li class="corresp" id="corresp-1"><a class="rev-xref" href="#xref-corresp-1-1">↵</a><span class="corresp-label">*</span>Corresponding author. Tel: +45 3532 7931; E‐mail: <span class="em-link"><span class="em-addr">jakobbs{at}sund.ku.dk</span></span></li></ol><ol class="fn-track"><li class="fn-equal" id="fn-1"><p id="p-10"><a class="rev-xref" href="#xref-fn-1-1">↵</a><span class="fn-label">†</span> These authors contributed equally to this paper</p></li></ol></div><div class="executive-summary"></div><div class="section precis" id="abstract-2"><p id="p-8">Neurotransmitter release depends on the SNARE protein vti1a, which is unexpectedly not required for final fusion of dense‐core vesicles, but for their generation.</p></div><div class="section graphic-abstract" id="abstract-1"><h2>Synopsis</h2><p id="p-1"><div class="graphic" id="boxed-text-1"><div class="graphic" id="graphic-1"><div class="graphic-inline anchor"><img xmlns:l="http://schema.highwire.org/Linking" xmlns:hwp="http://schema.highwire.org/Journal" src="pending:yes" l:ref-type="journal" hwp:journal="embojnl" hwp:article="embj.201387549" l:sub-ref="graphic-1" l:type="image/*" class="embedded" apath="/embojnl/early/2014/06/05/embj.201387549/embed/graphic-1.gif" frag-type="embed"></img></div></div></div></p><p id="p-2">Neurotransmitter release depends on the SNARE protein vti1a, which is unexpectedly not required for final fusion of dense‐core vesicles, but for their generation.</p><p></p><ul class="list-unord " id="list-1"><li id="list-item-1"><p id="p-4">In adrenal chromaffin cells, vti1a localizes to a compartment near the <em>trans</em>‐Golgi‐network, partly overlapping with syntaxin‐6, but is absent from secretory granules.</p></li><li id="list-item-2"><p id="p-5">In the absence of vti1a, secretory amplitude is reduced, fewer Ca<sup>2+</sup>‐channels are present in the plasma membrane, and the cells contain fewer vesicles of reduced size and synaptobrevin‐2/VAMP2 content.</p></li><li id="list-item-3"><p id="p-6">Release kinetics and Ca<sup>2+</sup>‐sensitivity remain unchanged in <em>vti1a</em> nulls, indicating that the final fusion reaction is independent of vti1a.</p></li><li id="list-item-4"><p id="p-7">Long‐term re‐expression of vti1a (days) is necessary for restoration of secretory capacity, consistent with vti1a involvement in an upstream step related to vesicle generation.</p></li></ul><p></p></div><ul class="kwd-group author-generated"><li class="kwd">adrenal chromaffin cells</li><li class="kwd">Ca<sup>2+</sup>‐channels</li><li class="kwd">exocytosis</li><li class="kwd">SNARE</li><li class="kwd">vesicle biogenesis</li></ul><ul class="history-list"><li xmlns:hwp="http://schema.highwire.org/Journal" class="received" hwp:start="2013-11-29"><span class="received-label">Received </span>November 29, 2013.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="rev-recd" hwp:start="2014-04-07"><span class="rev-recd-label">Revision received </span>April 7, 2014.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="accepted" hwp:start="2014-05-06"><span class="accepted-label">Accepted </span>May 6, 2014.</li></ul><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2014 The Authors</li></ul><span class="highwire-journal-article-marker-end"></span></div><span id="related-urls"></span></div></div></div> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Alexander M</span> <span class="nlm-surname">Walter</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Julia</span> <span class="nlm-surname">Kurps</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Heidi</span> <span class="nlm-surname">de Wit</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Susanne</span> <span class="nlm-surname">Schöning</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Trine L</span> <span class="nlm-surname">Toft‐Bertelsen</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Juliane</span> <span class="nlm-surname">Lauks</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Iwona</span> <span class="nlm-surname">Ziomkiewicz</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Annita N</span> <span class="nlm-surname">Weiss</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Alexander</span> <span class="nlm-surname">Schulz</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">Gabriele</span> <span class="nlm-surname">Fischer von Mollard</span></span>, <span class="highwire-citation-author" data-delta="10"><span class="nlm-given-names">Matthijs</span> <span class="nlm-surname">Verhage</span></span>, <span class="highwire-citation-author last" data-delta="11"><span class="nlm-given-names">Jakob B</span> <span class="nlm-surname">Sørensen</span></span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-type"><div class="toc-section">Article </div></span><span class="highwire-cite-metadata-date"><div>Published online 05.06.2014</div></span><ul class="links inline"><li class="membrane--intracellular-transport first"><a href="/collection/membrane-intracellular-transport">Membrane &amp; Intracellular Transport</a></li><li class="neuroscience last"><a href="/collection/neuroscience">Neuroscience</a></li></ul></div> </div></div></li><li class="even"><div class="highwire-article-citation" data-node-nid="171475"><div class="highwire-cite highwire-citation-jnl-embo-latest-online-citation clearfix"> <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="embojnl;embj.201489076" data-request-view="full"><i class="highwire-access-icon highwire-access-icon-user-access user-access icon-ok-sign" title="You have access" style="display:none;"></i></span></div> <a href="http://emboj.embopress.org/content/early/2014/06/05/embj.201489076" class="highwire-cite-linked-title"><div class="highwire-cite-title">STAP dance</div><div class="highwire-cite-subtitle"></div></a> <div class="highwire-cite-snippet"><div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" id="content-block" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article precis-view "><span class="highwire-journal-article-marker-start"></span><div class="contributors"><ol class="contributor-list" id="contrib-group-1"><li class="last" id="contrib-1"><span class="name">Bernd Pulverer</span><span class="address"> <span class="contrib-email">(<span class="em-link"><span class="em-addr">bernd.pulverer{at}embo.org</span></span>)</span></span><a id="xref-aff-1-1" class="xref-aff" href="#aff-1"><sup>1</sup></a></li></ol><ol class="affiliation-list"><li class="aff"><a id="aff-1" name="aff-1"></a><address><sup>1</sup>EMBO, <span class="named-content city" id="named-content-1">Heidelberg</span>, Germany</address></li></ol></div><div class="executive-summary"><p id="p-1">Systematic image screening at EMBO Press uncovers many problems, most of which can be resolved. Standardized pre‐publication image screening would make for a more reliable literature. Flagging putative image manipulation post‐publication remains an important control mechanism, but must not fall victim to an overzealous response. The STAP stem cell papers are a case in point.</p></div><div class="section precis" id="abstract-2"><p id="p-2">Systematic image screening at EMBO Press uncovers many irregularities, which are thereby prevented from entering the scientific literature. Such mechanisms may have helped thwart publication of manipulated images in recent high‐profile papers.</p></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2014 The Author</li></ul><span class="highwire-journal-article-marker-end"></span></div><span id="related-urls"></span></div></div></div> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first last" data-delta="0"><span class="nlm-given-names">Bernd</span> <span class="nlm-surname">Pulverer</span></span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-type"><div class="toc-section">Editorial </div></span><span class="highwire-cite-metadata-date"><div>Published online 05.06.2014</div></span></div> </div></div></li><li class="odd"><div class="highwire-article-citation" data-node-nid="171473"><div class="highwire-cite highwire-citation-jnl-embo-latest-online-citation clearfix"> <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="embojnl;embj.201488969" data-request-view="full"><i class="highwire-access-icon highwire-access-icon-user-access user-access icon-ok-sign" title="You have access" style="display:none;"></i></span></div> <a href="http://emboj.embopress.org/content/early/2014/06/03/embj.201488969" class="highwire-cite-linked-title"><div class="highwire-cite-title"><div xmlns="http://www.w3.org/1999/xhtml">NAD<sup>+</sup> controls neural stem cell fate in the aging brain</div></div><div class="highwire-cite-subtitle"></div></a> <div class="highwire-cite-snippet"><div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" id="content-block" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article precis-view "><span class="highwire-journal-article-marker-start"></span><div class="contributors"><ol class="contributor-list" id="contrib-group-1"><li class="contributor" id="contrib-1"><span class="name">Christopher Wiley</span><a id="xref-aff-1-1" class="xref-aff" href="#aff-1"><sup>1</sup></a> and </li><li class="last" id="contrib-2"><span class="name">Judith Campisi</span><span class="address"> <span class="contrib-email">(<span class="em-link"><span class="em-addr">jcampisi{at}lbl.gov</span></span>)</span></span><a id="xref-aff-1-2" class="xref-aff" href="#aff-1"><sup>1</sup></a><span class="xref-sep">,</span><a id="xref-aff-2-1" class="xref-aff" href="#aff-2"><sup>2</sup></a></li></ol><ol class="affiliation-list"><li class="aff"><a id="aff-1" name="aff-1"></a><address><sup>1</sup>Buck Institute for Research on Aging, <span class="named-content city" id="named-content-1">Novato</span>, <span class="named-content state" id="named-content-2">CA</span>, USA</address></li><li class="aff"><a id="aff-2" name="aff-2"></a><address><sup>2</sup>Lawrence Berkeley National Laboratory, <span class="named-content city" id="named-content-3">Berkeley</span>, <span class="named-content state" id="named-content-4">CA</span>, USA</address></li></ol></div><div class="executive-summary"><p id="p-1">Loss of the coenzyme NAD<sup>+</sup>, which is required for many energy‐dependent cellular processes, has emerged as a potentially unifying mechanism for age‐related conditions. A study in this issue of <em>The EMBO Journal</em> identifies a novel link between depletion of NAD<sup>+</sup> and age‐associated loss of proliferating adult neural stem/progenitor cells in the murine brain (Stein &amp; Imai, <a id="xref-ref-8-1" class="xref-ref" href="#ref-8">2014</a>). These data have important implications for how brain function might decline with age.</p><p id="p-3"><span class="fn-associated-article">See also: <a href="http://dx.doi.org/10.1002/embj.201386917">LR Stein &amp; S Imai</a> (June 2014)</span></p></div><div class="section precis" id="abstract-2"><p id="p-2">Age‐associated loss of NAD<sup>+</sup> or Nampt, the rate‐limiting biosynthetic step for this coenzyme, accounts for the loss of neural stem/progenitor cells self‐renewal and differentiation.</p></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2014 The Authors</li></ul><span class="highwire-journal-article-marker-end"></span></div><span id="related-urls"></span></div></div></div> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Christopher</span> <span class="nlm-surname">Wiley</span></span>, <span class="highwire-citation-author last" data-delta="1"><span class="nlm-given-names">Judith</span> <span class="nlm-surname">Campisi</span></span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-type"><div class="toc-section">Have you seen? </div></span><span class="highwire-cite-metadata-date"><div>Published online 03.06.2014</div></span><ul class="links inline"><li class="metabolism first"><a href="/collection/metabolism">Metabolism</a></li><li class="neuroscience"><a href="/collection/neuroscience">Neuroscience</a></li><li class="stem-cells last"><a href="/collection/stem-cells">Stem Cells</a></li></ul></div> </div></div></li><li class="even"><div class="highwire-article-citation" data-node-nid="171460"><div class="highwire-cite highwire-citation-jnl-embo-latest-online-citation clearfix"> <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="embojnl;embj.201488117" data-request-view="full"><i class="highwire-access-icon highwire-access-icon-user-access user-access icon-ok-sign" title="You have access" style="display:none;"></i></span></div> <a href="http://emboj.embopress.org/content/early/2014/06/03/embj.201488117" class="highwire-cite-linked-title"><div class="highwire-cite-title"><div xmlns="http://www.w3.org/1999/xhtml">Paternal RNA contributions in the <em>Caenorhabditis elegans</em> zygote</div></div><div class="highwire-cite-subtitle"></div></a> <div class="highwire-cite-snippet"><div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" id="content-block" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article precis-view "><span class="highwire-journal-article-marker-start"></span><div class="contributors"><ol class="contributor-list" id="contrib-group-1"><li class="contributor" id="contrib-1"><span class="name">Marlon Stoeckius</span><a id="xref-aff-1-1" class="xref-aff" href="#aff-1"><sup>1</sup></a><span class="xref-sep">,</span><a id="xref-fn-1-1" class="xref-fn" href="#fn-1"><sup>†</sup></a>, </li><li class="contributor" id="contrib-2"><span class="name">Dominic Grün</span><a id="xref-aff-1-2" class="xref-aff" href="#aff-1"><sup>1</sup></a><span class="xref-sep">,</span><a id="xref-fn-1-2" class="xref-fn" href="#fn-1"><sup>†</sup></a> and </li><li class="last" id="contrib-3"><span class="name">Nikolaus Rajewsky</span><a id="xref-corresp-1-1" class="xref-correspondence-address" href="#corresp-1">*</a><span class="xref-sep">,</span><a id="xref-aff-1-3" class="xref-aff" href="#aff-1"><sup>1</sup></a></li></ol><ol class="affiliation-list"><li class="aff"><a id="aff-1" name="aff-1"></a><address><sup>1</sup><span class="named-content organisation-division" id="named-content-1">Systems Biology of Gene Regulatory Elements</span>, Max Delbrück Center Berlin, <span class="named-content city" id="named-content-2">Berlin</span>, Germany</address></li></ol><ol class="corresp-list"><li class="corresp" id="corresp-1"><a class="rev-xref" href="#xref-corresp-1-1">↵</a><span class="corresp-label">*</span>Corresponding author. Tel: +49 30 9406 2999; E‐mail: <span class="em-link"><span class="em-addr">rajewsky{at}mdc-berlin.de</span></span></li></ol><ol class="fn-track"><li class="fn-equal" id="fn-1"><p id="p-10"><a class="rev-xref" href="#xref-fn-1-1">↵</a><span class="fn-label">†</span> Contributed equally.</p></li></ol></div><div class="executive-summary"></div><div class="section precis" id="abstract-2"><p id="p-8">This paper establishes significant paternal RNA contributions in <em>C. elegans</em> zygotes, a result with major bearings on their potential functional relevance.</p></div><div class="section graphic-abstract" id="abstract-1"><h2>Synopsis</h2><p id="p-1"><div class="graphic" id="boxed-text-1"><div class="graphic" id="graphic-1"><div class="graphic-inline anchor"><img xmlns:l="http://schema.highwire.org/Linking" xmlns:hwp="http://schema.highwire.org/Journal" src="pending:yes" l:ref-type="journal" hwp:journal="embojnl" hwp:article="embj.201488117" l:sub-ref="graphic-1" l:type="image/*" class="embedded" apath="/embojnl/early/2014/06/03/embj.201488117/embed/graphic-1.gif" frag-type="embed"></img></div></div></div></p><p id="p-2">This paper establishes significant paternal RNA contributions in <em>C. elegans</em> zygotes, a result with major bearings on their potential functional relevance.</p><p></p><ul class="list-unord " id="list-1"><li id="list-item-1"><p id="p-4">Metabolic labeling of males shows that male RNA is transferred into the oocyte upon fertilization.</p></li><li id="list-item-2"><p id="p-5">We performed a cross of hybrid strains and sequenced RNA from the 1‐cell‐fertilized embryo.</p></li><li id="list-item-3"><p id="p-6">Computational analyses of these data allow to quantify maternal and paternal RNA in the fertilized embryo.</p></li><li id="list-item-4"><p id="p-7">We discover numerous mRNAs and different classes of non‐coding RNAs of paternal origin in the fertilized embryo.</p></li></ul><p></p></div><ul class="kwd-group author-generated"><li class="kwd">embryogenesis</li><li class="kwd">epigenetic inheritance</li><li class="kwd">paternal RNA</li><li class="kwd">transgenerational inheritance</li></ul><ul class="history-list"><li xmlns:hwp="http://schema.highwire.org/Journal" class="received" hwp:start="2014-02-04"><span class="received-label">Received </span>February 4, 2014.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="rev-recd" hwp:start="2014-05-01"><span class="rev-recd-label">Revision received </span>May 1, 2014.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="accepted" hwp:start="2014-05-06"><span class="accepted-label">Accepted </span>May 6, 2014.</li></ul><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2014 The Authors</li></ul><span class="highwire-journal-article-marker-end"></span></div><span id="related-urls"></span></div></div></div> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Marlon</span> <span class="nlm-surname">Stoeckius</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Dominic</span> <span class="nlm-surname">Grün</span></span>, <span class="highwire-citation-author last" data-delta="2"><span class="nlm-given-names">Nikolaus</span> <span class="nlm-surname">Rajewsky</span></span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-type"><div class="toc-section">Article </div></span><span class="highwire-cite-metadata-date"><div>Published online 03.06.2014</div></span><ul class="links inline"><li class="development--differentiation first"><a href="/collection/development-differentiation">Development &amp; Differentiation</a></li><li class="rna-biology"><a href="/collection/rna-biology">RNA Biology</a></li><li class="systems--computational-biology last"><a href="/collection/systems-computational-biology">Systems &amp; Computational Biology</a></li></ul></div> </div></div></li><li class="odd"><div class="highwire-article-citation" data-node-nid="170993"><div class="highwire-cite highwire-citation-jnl-embo-latest-online-citation clearfix"> <div class="highwire-cite-access"><span class="highwire-citation-access"><i class="highwire-access-icon highwire-access-icon-open-access open-access icon-unlock-alt" title="Open Access"></i></span></div> <a href="http://emboj.embopress.org/content/early/2014/05/28/embj.201488373" class="highwire-cite-linked-title"><div class="highwire-cite-title">Structural basis for Pan3 binding to Pan2 and its function in mRNA recruitment and deadenylation</div><div class="highwire-cite-subtitle"></div></a> <div class="highwire-cite-snippet"><div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" id="content-block" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article precis-view "><span class="highwire-journal-article-marker-start"></span><div class="contributors"><ol class="contributor-list" id="contrib-group-1"><li class="contributor" id="contrib-1"><span class="name">Jana Wolf</span><a id="xref-aff-1-1" class="xref-aff" href="#aff-1"><sup>1</sup></a><span class="xref-sep">,</span><a id="xref-fn-1-1" class="xref-fn" href="#fn-1"><sup>†</sup></a>, </li><li class="contributor" id="contrib-2"><span class="name">Eugene Valkov</span><a id="xref-aff-1-2" class="xref-aff" href="#aff-1"><sup>1</sup></a><span class="xref-sep">,</span><a id="xref-fn-1-2" class="xref-fn" href="#fn-1"><sup>†</sup></a>, </li><li class="contributor" id="contrib-3"><span class="name">Mark D Allen</span><a id="xref-aff-1-3" class="xref-aff" href="#aff-1"><sup>1</sup></a>, </li><li class="contributor" id="contrib-4"><span class="name">Birthe Meineke</span><a id="xref-aff-1-4" class="xref-aff" href="#aff-1"><sup>1</sup></a>, </li><li class="contributor" id="contrib-5"><span class="name">Yuliya Gordiyenko</span><a id="xref-aff-2-1" class="xref-aff" href="#aff-2"><sup>2</sup></a>, </li><li class="contributor" id="contrib-6"><span class="name">Stephen H McLaughlin</span><a id="xref-aff-1-5" class="xref-aff" href="#aff-1"><sup>1</sup></a>, </li><li class="contributor" id="contrib-7"><span class="name">Tayla M Olsen</span><a id="xref-aff-1-6" class="xref-aff" href="#aff-1"><sup>1</sup></a>, </li><li class="contributor" id="contrib-8"><span class="name">Carol V Robinson</span><a id="xref-aff-2-2" class="xref-aff" href="#aff-2"><sup>2</sup></a>, </li><li class="contributor" id="contrib-9"><span class="name">Mark Bycroft</span><a id="xref-aff-1-7" class="xref-aff" href="#aff-1"><sup>1</sup></a>, </li><li class="contributor" id="contrib-10"><span class="name">Murray Stewart</span><a id="xref-aff-1-8" class="xref-aff" href="#aff-1"><sup>1</sup></a> and </li><li class="last" id="contrib-11"><span class="name">Lori A Passmore</span><a id="xref-corresp-1-1" class="xref-correspondence-address" href="#corresp-1">*</a><span class="xref-sep">,</span><a id="xref-aff-1-9" class="xref-aff" href="#aff-1"><sup>1</sup></a></li></ol><ol class="affiliation-list"><li class="aff"><a id="aff-1" name="aff-1"></a><address><sup>1</sup><span class="named-content organisation-division" id="named-content-1">Medical Research Council (MRC) Laboratory of Molecular Biology</span>, <span class="named-content city" id="named-content-2">Cambridge</span>, UK</address></li><li class="aff"><a id="aff-2" name="aff-2"></a><address><sup>2</sup><span class="named-content organisation-division" id="named-content-3">Chemistry Research Laboratory</span>, University of Oxford, <span class="named-content city" id="named-content-4">Oxford</span>, UK</address></li></ol><ol class="corresp-list"><li class="corresp" id="corresp-1"><a class="rev-xref" href="#xref-corresp-1-1">↵</a><span class="corresp-label">*</span>Corresponding author. Tel: +44 1223 267062; E‐mail: <span class="em-link"><span class="em-addr">passmore{at}mrc-lmb.cam.ac.uk</span></span></li></ol><ol class="fn-track"><li class="fn-equal" id="fn-1"><p id="p-11"><a class="rev-xref" href="#xref-fn-1-1">↵</a><span class="fn-label">†</span> These authors contributed equally to this work.</p></li></ol></div><div class="executive-summary"></div><div class="section precis" id="abstract-2"><p id="p-9">mRNA poly(A) tail removal by the Pan2 exonuclease requires association with homodimeric Pan3, which binds and supplies poly(A) RNA to Pan2.</p></div><div class="section graphic-abstract" id="abstract-1"><h2>Synopsis</h2><p id="p-2"><div class="graphic" id="boxed-text-1"><div class="graphic" id="graphic-1"><div class="graphic-inline anchor"><img xmlns:l="http://schema.highwire.org/Linking" xmlns:hwp="http://schema.highwire.org/Journal" src="pending:yes" l:ref-type="journal" hwp:journal="embojnl" hwp:article="embj.201488373" l:sub-ref="graphic-1" l:type="image/*" class="embedded" apath="/embojnl/early/2014/05/28/embj.201488373/embed/graphic-1.gif" frag-type="embed"></img></div></div></div></p><p id="p-3">Regulation of mRNA poly(A) tails constitutes an important layer of mRNA stability and translation control. Structural and biochemical studies of the conserved Pan2–Pan3 deadenylation complex now reveal how the non‐catalytic subunit Pan3 contributes to coordinate activities within the complex, and thus to remove poly(A) tails.</p><p></p><ul class="list-unord " id="list-1"><li id="list-item-1"><p id="p-5">Pan3 binds to poly(A) RNA through an N‐terminal zinc finger and its pseudokinase/C‐terminal domain.</p></li><li id="list-item-2"><p id="p-6">The exonuclease subunit Pan2 does not bind RNA by itself.</p></li><li id="list-item-3"><p id="p-7">A single Pan2 protein binds to an asymmetric Pan3 homodimer via an extensive, high‐affinity interaction.</p></li><li id="list-item-4"><p id="p-8">Pan3 functions to supply the exonuclease Pan2 with substrate poly(A) RNA, facilitating efficient mRNA deadenylation.</p></li></ul><p></p></div><ul class="kwd-group author-generated"><li class="kwd">gene expression</li><li class="kwd">mRNA deadenylation</li><li class="kwd">Pan2–Pan3</li><li class="kwd">polyA tail</li><li class="kwd">protein structure</li></ul><ul class="history-list"><li xmlns:hwp="http://schema.highwire.org/Journal" class="received" hwp:start="2014-03-03"><span class="received-label">Received </span>March 3, 2014.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="rev-recd" hwp:start="2014-04-25"><span class="rev-recd-label">Revision received </span>April 25, 2014.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="accepted" hwp:start="2014-05-03"><span class="accepted-label">Accepted </span>May 3, 2014.</li></ul><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2014 MRC Laboratory of Molecular Biology Published under the terms of the CC BY 4.0 licence</li></ul><div class="license" id="license-1"><p id="p-1">This is an open access article under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0</a> License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.</p></div><span class="highwire-journal-article-marker-end"></span></div><span id="related-urls"></span></div></div></div> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Jana</span> <span class="nlm-surname">Wolf</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Eugene</span> <span class="nlm-surname">Valkov</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Mark D</span> <span class="nlm-surname">Allen</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Birthe</span> <span class="nlm-surname">Meineke</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Yuliya</span> <span class="nlm-surname">Gordiyenko</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Stephen H</span> <span class="nlm-surname">McLaughlin</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Tayla M</span> <span class="nlm-surname">Olsen</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Carol V</span> <span class="nlm-surname">Robinson</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Mark</span> <span class="nlm-surname">Bycroft</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">Murray</span> <span class="nlm-surname">Stewart</span></span>, <span class="highwire-citation-author last" data-delta="10"><span class="nlm-given-names">Lori A</span> <span class="nlm-surname">Passmore</span></span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-type"><div class="toc-section">Article </div></span><span class="highwire-cite-metadata-date"><div>Published online 28.05.2014</div></span><ul class="links inline"><li class="rna-biology first"><a href="/collection/rna-biology">RNA Biology</a></li><li class="structural-biology last"><a href="/collection/structural-biology">Structural Biology</a></li></ul></div> </div></div></li><li class="even"><div class="highwire-article-citation" data-node-nid="170987"><div class="highwire-cite highwire-citation-jnl-embo-latest-online-citation clearfix"> <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="embojnl;embj.201488142" data-request-view="full"><i class="highwire-access-icon highwire-access-icon-user-access user-access icon-ok-sign" title="You have access" style="display:none;"></i></span></div> <a href="http://emboj.embopress.org/content/early/2014/05/27/embj.201488142" class="highwire-cite-linked-title"><div class="highwire-cite-title">miRNAs at the interface of cellular stress and disease</div><div class="highwire-cite-subtitle"></div></a> <div class="highwire-cite-snippet"><div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" id="content-block" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article precis-view "><span class="highwire-journal-article-marker-start"></span><div class="contributors"><ol class="contributor-list" id="contrib-group-1"><li class="contributor" id="contrib-1"><span class="name">Anna Emde</span><a id="xref-aff-1-1" class="xref-aff" href="#aff-1"><sup>1</sup></a> and </li><li class="last" id="contrib-2"><span class="name">Eran Hornstein</span><a id="xref-corresp-1-1" class="xref-correspondence-address" href="#corresp-1">*</a><span class="xref-sep">,</span><a id="xref-aff-1-2" class="xref-aff" href="#aff-1"><sup>1</sup></a></li></ol><ol class="affiliation-list"><li class="aff"><a id="aff-1" name="aff-1"></a><address><sup>1</sup><span class="named-content organisation-division" id="named-content-1">Department of Molecular Genetics</span>, Weizmann Institute of Science, <span class="named-content city" id="named-content-2">Rehovot</span>, Israel</address></li></ol><ol class="corresp-list"><li class="corresp" id="corresp-1"><a class="rev-xref" href="#xref-corresp-1-1">↵</a><span class="corresp-label">*</span>Corresponding author. Tel: +972 89346215; E‐mail: <span class="em-link"><span class="em-addr">eran.hornstein{at}weizmann.ac.il</span></span></li></ol></div><div class="executive-summary"></div><div class="section precis" id="abstract-1"><p id="p-1">Anna Emde and Eran Hornstein discuss the interplay between the miRNA machinery and the cellular stress pathway and how this contributes to disease risk.</p></div><ul class="kwd-group author-generated"><li class="kwd">cellular stress</li><li class="kwd">dicer</li><li class="kwd">disease</li><li class="kwd">micrornas</li><li class="kwd">stress granules</li></ul><ul class="history-list"><li xmlns:hwp="http://schema.highwire.org/Journal" class="received" hwp:start="2014-02-10"><span class="received-label">Received </span>February 10, 2014.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="rev-recd" hwp:start="2014-03-23"><span class="rev-recd-label">Revision received </span>March 23, 2014.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="accepted" hwp:start="2014-03-28"><span class="accepted-label">Accepted </span>March 28, 2014.</li></ul><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2014 The Authors</li></ul><span class="highwire-journal-article-marker-end"></span></div><span id="related-urls"></span></div></div></div> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Anna</span> <span class="nlm-surname">Emde</span></span>, <span class="highwire-citation-author last" data-delta="1"><span class="nlm-given-names">Eran</span> <span class="nlm-surname">Hornstein</span></span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-type"><div class="toc-section">Review </div></span><span class="highwire-cite-metadata-date"><div>Published online 27.05.2014</div></span><ul class="links inline"><li class="neuroscience first"><a href="/collection/neuroscience">Neuroscience</a></li><li class="rna-biology last"><a href="/collection/rna-biology">RNA Biology</a></li></ul></div> </div></div></li><li class="last odd"><div class="highwire-article-citation" data-node-nid="170926"><div class="highwire-cite highwire-citation-jnl-embo-latest-online-citation clearfix"> <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="embojnl;embj.201488031" data-request-view="full"><i class="highwire-access-icon highwire-access-icon-user-access user-access icon-ok-sign" title="You have access" style="display:none;"></i></span></div> <a href="http://emboj.embopress.org/content/early/2014/05/26/embj.201488031" class="highwire-cite-linked-title"><div class="highwire-cite-title"><div xmlns="http://www.w3.org/1999/xhtml">The number of <em>Neisseria meningitidis</em> type IV pili determines host cell interaction</div></div><div class="highwire-cite-subtitle"></div></a> <div class="highwire-cite-snippet"><div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" id="content-block" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article precis-view "><span class="highwire-journal-article-marker-start"></span><div class="contributors"><ol class="contributor-list" id="contrib-group-1"><li class="contributor" id="contrib-1"><span class="name">Anne‐Flore Imhaus</span><a id="xref-aff-1-1" class="xref-aff" href="#aff-1"><sup>1</sup></a><span class="xref-sep">,</span><a id="xref-aff-2-1" class="xref-aff" href="#aff-2"><sup>2</sup></a> and </li><li class="last" id="contrib-2"><span class="name">Guillaume Duménil</span><a id="xref-corresp-1-1" class="xref-correspondence-address" href="#corresp-1">*</a><span class="xref-sep">,</span><a id="xref-aff-1-2" class="xref-aff" href="#aff-1"><sup>1</sup></a><span class="xref-sep">,</span><a id="xref-aff-2-2" class="xref-aff" href="#aff-2"><sup>2</sup></a></li></ol><ol class="affiliation-list"><li class="aff"><a id="aff-1" name="aff-1"></a><address><sup>1</sup>INSERM U970 Paris Cardiovascular Research Center, <span class="named-content city" id="named-content-1">Paris</span>, France</address></li><li class="aff"><a id="aff-2" name="aff-2"></a><address><sup>2</sup><span class="named-content organisation-division" id="named-content-2">Faculté de Médecine Paris Descartes</span>, Université Paris Descartes, <span class="named-content city" id="named-content-3">Paris</span>, France</address></li></ol><ol class="corresp-list"><li class="corresp" id="corresp-1"><a class="rev-xref" href="#xref-corresp-1-1">↵</a><span class="corresp-label">*</span>Corresponding author. Tel: +33 1 53 98 80 49; Fax: +33 1 53 98 79 53; E‐mail: <span class="em-link"><span class="em-addr">guillaume.dumenil{at}inserm.fr</span></span></li></ol></div><div class="executive-summary"></div><div class="section precis" id="abstract-2"><p id="p-7">PilV and PilX pilins of <em>Neisseria meningitidis</em> type IV pili regulate pili number rather than their composition, suggesting that meningitidis infection‐associated adhesion and plasma membrane re‐organization require a minimum number of pili rather than specific sub‐types.</p></div><div class="section graphic-abstract" id="abstract-1"><h2>Synopsis</h2><p id="p-1"><div class="graphic" id="boxed-text-1"><div class="graphic" id="graphic-1"><div class="graphic-inline anchor"><img xmlns:l="http://schema.highwire.org/Linking" xmlns:hwp="http://schema.highwire.org/Journal" src="pending:yes" l:ref-type="journal" hwp:journal="embojnl" hwp:article="embj.201488031" l:sub-ref="graphic-1" l:type="image/*" class="embedded" apath="/embojnl/early/2014/05/26/embj.201488031/embed/graphic-1.gif" frag-type="embed"></img></div></div></div></p><p id="p-2">PilV and PilX pilins of <em>Neisseria meningitidis</em> type IV pili regulate pili number rather than their composition, suggesting that meningitidis infection‐associated adhesion and plasma membrane re‐organization require a minimum number of pili rather than specific subtypes.</p><p></p><ul class="list-unord " id="list-1"><li id="list-item-1"><p id="p-4">PilX and PilV minor pilins exert their effects for the periplasm rather than inserted in the pilus fiber.</p></li><li id="list-item-2"><p id="p-5">Inactivation of the <em>pilV</em> and <em>pilX</em> genes leads to altered pilus biogenesis resulting in a mild decrease in the number of pili.</p></li><li id="list-item-3"><p id="p-6">Decreasing the number of type IV pili is sufficient to recapitulate the defects observed in the <em>pilV</em> and <em>pilX</em> mutants.</p></li></ul><p></p></div><ul class="kwd-group author-generated"><li class="kwd">adhesion</li><li class="kwd">infectious disease</li><li class="kwd">meningitis</li><li class="kwd">septicemia</li><li class="kwd">type IV pili</li></ul><ul class="history-list"><li xmlns:hwp="http://schema.highwire.org/Journal" class="received" hwp:start="2014-01-27"><span class="received-label">Received </span>January 27, 2014.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="rev-recd" hwp:start="2014-03-21"><span class="rev-recd-label">Revision received </span>March 21, 2014.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="accepted" hwp:start="2014-04-15"><span class="accepted-label">Accepted </span>April 15, 2014.</li></ul><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2014 The Authors</li></ul><span class="highwire-journal-article-marker-end"></span></div><span id="related-urls"></span></div></div></div> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Anne‐Flore</span> <span class="nlm-surname">Imhaus</span></span>, <span class="highwire-citation-author last" data-delta="1"><span class="nlm-given-names">Guillaume</span> <span class="nlm-surname">Duménil</span></span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-type"><div class="toc-section">Article </div></span><span class="highwire-cite-metadata-date"><div>Published online 26.05.2014</div></span><ul class="links inline"><li class="cell-adhesion-polarity--cytoskeleton first"><a href="/collection/cell-adhesion-polarity-cytoskeleton">Cell Adhesion, Polarity &amp; Cytoskeleton</a></li><li class="microbiology-virology--host-pathogen-interaction last"><a href="/collection/microbiology-virology-host-pathogen-interaction">Microbiology, Virology &amp; Host Pathogen Interaction</a></li></ul></div> 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