Catálogo de publicaciones - revistas

<jats:title>Wnt–β-Catenin in Germ Cells</jats:title> <jats:p> The Wnt–β-catenin pathway contributes to many signaling mechanisms during organismal development and carcinogenesis by regulating both transcription and cell adhesion. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="294" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244512"> <jats:bold> Hamada-Kawaguchi <jats:italic>et al.</jats:italic> </jats:bold> </jats:related-article> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="294" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244512">294</jats:related-article> ) demonstrate that this pathway must be activated in ovarian somatic cells to stop proliferation of germ cells in <jats:italic>Drosophila.</jats:italic> Phosphorylation of a tyrosine residue on β-catenin by the tyrosine kinase Btk turns on signaling in the niche cells by promoting transcriptional activity of β-catenin. Failure in this process resulted in ovarian tumors in the flies. </jats:p>

<jats:title>Germline Pol I</jats:title> <jats:p> RNA polymerase I (Pol I)–directed ribosomal RNA (rRNA) transcription has been extensively studied in mammalian cell lines and yeast. However, the functional significance of cell-specific regulation of Pol I transcription within developmental contexts in vivo remains unclear. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="298" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1246384"> <jats:bold> Zhang <jats:italic>et al.</jats:italic> </jats:bold> </jats:related-article> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="298" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1246384">298</jats:related-article> ) characterized a <jats:italic>Drosophila</jats:italic> Pol I regulatory complex and found that germline stem cells (GSCs) of the ovary exhibited increased levels of rRNA transcription relative to their immediate daughter cells. High levels of rRNA expression promoted GSC proliferation, with attenuation of Pol I activity showing effects during early germ cell differentiation. </jats:p>

<jats:title>Drug With a (Re)Purpose</jats:title> <jats:p> Thalidomide, once infamous for its deleterious effects on fetal development, has re-emerged as a drug of great interest because of its beneficial immunomodulatory effects. A derivative drug called lenalidomide significantly extends the survival of patients with multiple myeloma, but the molecular mechanisms underlying its efficacy remain unclear (see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="256" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1249543">Stewart</jats:related-article> </jats:bold> ). Building on a previous observation that thalidomide binds to cereblon, a ubiquitin ligase, <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="305" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244917"> Lu <jats:italic>et al.</jats:italic> </jats:related-article> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="305" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244917">305</jats:related-article> , published online 28 November) and <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="301" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244851"> <jats:bold> Krönke <jats:italic>et al.</jats:italic> </jats:bold> </jats:related-article> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="301" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244851">301</jats:related-article> , published online 28 November) show that in the presence of lenalidomide, cereblon selectively targets two B cell transcription factors (Ikaros family members, IKZF1 and IKZF3) for degradation. In myeloma cell lines and patient cells, down-regulation of IKZF1 and IKZF3 was necessary and sufficient for the drug's anticancer activity. Thus, lenalidomide may act, at least in part, by “grepurposing” a ubiquitin ligase. </jats:p>

<jats:title>Drug With a (Re)Purpose</jats:title> <jats:p> Thalidomide, once infamous for its deleterious effects on fetal development, has re-emerged as a drug of great interest because of its beneficial immunomodulatory effects. A derivative drug called lenalidomide significantly extends the survival of patients with multiple myeloma, but the molecular mechanisms underlying its efficacy remain unclear (see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="256" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1249543">Stewart</jats:related-article> </jats:bold> ). Building on a previous observation that thalidomide binds to cereblon, a ubiquitin ligase, <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="305" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244917"> Lu <jats:italic>et al.</jats:italic> </jats:related-article> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="305" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244917">305</jats:related-article> , published online 28 November) and <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="301" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244851"> <jats:bold> Krönke <jats:italic>et al.</jats:italic> </jats:bold> </jats:related-article> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="301" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244851">301</jats:related-article> , published online 28 November) show that in the presence of lenalidomide, cereblon selectively targets two B cell transcription factors (Ikaros family members, IKZF1 and IKZF3) for degradation. In myeloma cell lines and patient cells, down-regulation of IKZF1 and IKZF3 was necessary and sufficient for the drug's anticancer activity. Thus, lenalidomide may act, at least in part, by “grepurposing” a ubiquitin ligase. </jats:p>

<jats:title>Identifying Drivers and Passengers</jats:title> <jats:p> Modern genomics is unearthing hundreds of genetic and epigenetic alterations associated with human cancers. It is important to delineate which of these alterations participate actively in tumor progression and/or metastases (driver mutations) and which are inconsequential (passenger mutations). To this end, <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="309" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1248627"> <jats:bold> Schramek <jats:italic>et al.</jats:italic> </jats:bold> </jats:related-article> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="309" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1248627">309</jats:related-article> ) conducted an in vivo RNA interference screen in mice to test simultaneously the functionality of putative cancer genes and down-regulated messenger RNAs associated with tumor-initiating cells of squamous cell carcinomas (SCCs). Several candidates, including nonmuscle myosin-IIa, not previously viewed as tumor suppressors were uncovered. </jats:p>

<jats:title>The Secret Life of a Vaccine</jats:title> <jats:p> Antigen-specific CD8 <jats:sup>÷</jats:sup> T cells play a central role in the adaptive immune response to viral infections and to cancer. <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="313" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1246829"> Ravindran <jats:italic>et al.</jats:italic> </jats:related-article> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6168" page="313" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1246829">313</jats:related-article> , published online 5 December) studied the successful yellow fever virus vaccine YF-17D to gain insight into its mechanism of action. The vaccine activated the nutrient deprivation sensor, GCN2 kinase, in dendritic cells. In transgenic mouse models, GCN2 activation promoted autophagy and antigen cross-presentation, enhancing the virus-specific CD8 <jats:sup>÷</jats:sup> T cell response. The findings suggest an important role for nutrient availability and autophagy in vaccine efficacy, which could aid more successful vaccine development. </jats:p>

<jats:p>The discovery of RNAi revealed an entire layer of previously unknown gene regulation; new tools are helping more scientists analyze and manipulate this system to probe the secret lives of cells.</jats:p>

<jats:p>A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.</jats:p>

<jats:p>Listen to stories on what we can learn from the gut bacteria of modern hunter-gatherers, testing the weathering speed limit, and more.</jats:p>

<jats:p>Sedimentary rocks examined by the Curiosity rover at Yellowknife Bay, Mars, were derived from sources that evolved from an approximately average martian crustal composition to one influenced by alkaline basalts. No evidence of chemical weathering is preserved, indicating arid, possibly cold, paleoclimates and rapid erosion and deposition. The absence of predicted geochemical variations indicates that magnetite and phyllosilicates formed by diagenesis under low-temperature, circumneutral pH, rock-dominated aqueous conditions. Analyses of diagenetic features (including concretions, raised ridges, and fractures) at high spatial resolution indicate that they are composed of iron- and halogen-rich components, magnesium-iron-chlorine–rich components, and hydrated calcium sulfates, respectively. Composition of a cross-cutting dike-like feature is consistent with sedimentary intrusion. The geochemistry of these sedimentary rocks provides further evidence for diverse depositional and diagenetic sedimentary environments during the early history of Mars.</jats:p>