Catálogo de publicaciones - revistas

<jats:title>The Dependable Warmer</jats:title> <jats:p> During the middle of the Eocene, about 40 million years ago, a transient warming event interrupted the long-term cooling trend that had been in progress for the previous 10 million years. <jats:bold> Bijl <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="819" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1193654">819</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6005" page="763" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1197894">Pearson</jats:related-article> </jats:bold> ) constructed records of sea surface temperature and atmospheric CO <jats:sub>2</jats:sub> concentrations across the warming period. It appears that vast amounts of CO <jats:sub>2</jats:sub> were injected into the atmosphere, and a sea surface temperature increase of as much a 6°C accompanied the atmospheric CO <jats:sub>2</jats:sub> rise. </jats:p>

<jats:title>Gut Stem Cell Replacement</jats:title> <jats:p> Gut cell turnover is characteristically rapid and relies on stem cells in the crypts that lie between the intestinal villi. The prevailing view is that stem cell division is asymmetric with one daughter retaining a stem cell character; however, this pattern of stem cell turnover does not always apply. Using long-term lineage tracing, <jats:bold> Lopez-Garcia <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="822" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1196236">822</jats:related-article> , published online 23 September) showed that the loss of a stem cell was compensated for by the multiplication of a neighboring cell. The rate of stem-cell loss was found to be equivalent to the rate of cell division, indicating that symmetric cell division was the rule for gut stem cells and implying stochastic expansion, contraction, and extinction of clones occurs. </jats:p>

<jats:title>Keeping Fit</jats:title> <jats:p> Mutations may be deleterious, neutral, or advantageous. Understanding the relative effect of a new mutation on an organism's fitness is important for many systems from complex diseases to conservation biology. <jats:bold> Lind <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="825" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1194617">825</jats:related-article> ) used the bacterium <jats:italic>Salmonella typhimurium</jats:italic> to study the effects of random mutations in two ribosomal proteins on fitness. Most mutations, whether synonymous or nonsynonymous, had significant fitness costs, thus overturning the prevailing dogma that most point mutations are either neutral or lethal and indicating that the mutations influenced messenger RNA structure and/or stability. </jats:p>

<jats:title>Tumor Vaccination Success</jats:title> <jats:p> Vaccination with tumor-specific antigens is one of several attempted therapies seeking to harness the immune system, but—unfortunately—this strategy has been unsuccessful, possibly because of the immunosuppressive properties of the tumor microenvironment. <jats:bold> Kraman <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="827" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1195300">827</jats:related-article> ; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6005" page="761" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1198345"> <jats:bold>Schreiber and Rowley</jats:bold> </jats:related-article> ) have identified immunosuppressive cells of mesenchymal origin in mice comprising 2% of the tumor stromal cell population. They were identified by expression of the fibroblast activation protein–α. Deletion of these cells in lung or pancreatic cancers in mice allowed successful therapeutic vaccination against the tumors, which was dependent on the adaptive immune system and the cytokines interferon-γ and tumor necrosis factor–α. These findings reveal that multiple cell types contribute to the immunosuppressive tumor microenvironment and will inform therapeutic cancer vaccine design. </jats:p>

<jats:title>Blocking Interfering Microbes</jats:title> <jats:p> Irinotecan is a widely used anticancer pro-drug that is converted in the liver into the active form, but when it gets into the gut, the normally benign microbial flora can convert it into the toxic form, which kills the rapidly multiplying gut epithelium as it would kill rapidly dividing tumor cells, and thus causes diarrhea. <jats:bold> Wallace <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="831" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1191175">831</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6005" page="766" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1198310">Patel and Kaufmann</jats:related-article> </jats:bold> ) used high-throughput screening to identify inhibitors that target the offending bacterial enzyme, β-glucuronidase, without killing the bacteria or affecting orthologous mammalian enzymes. Crystal structures revealed the molecular basis of selectivity, and in vivo studies showed that an inhibitor protected mice from irinotecan-induced toxicity. </jats:p>

<jats:title>A Likely Conformation</jats:title> <jats:p> At several stages of protein synthesis, guanosine triphosphate hydrolyzing enzymes (GTPases) interact with the ribosome, and GTP hydrolysis is coupled to progression of synthesis. <jats:bold> Voorhees <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="835" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1194460">835</jats:related-article> ) have determined a 3.2-resolution structure of the GTPase, elongation factor Tu, which delivers amino-acyl transfer RNA (tRNA) to the ribosome. The GTPase and tRNA were bound to the ribosome and were stalled in an active conformation by a GTP analog. The structure revealed that activation of the enzyme only required small changes in conformation to move a catalytic histidine into the correct position for hydrolysis. A similar mechanism likely applies to the activation of other translational GTPases. </jats:p>

<jats:title>Kicking Out Introns</jats:title> <jats:p> Many genes in eukaryotes contain introns that must be removed from the messenger RNA for proper gene function. Humans have on average eight introns per gene, whereas more than 90% of the genes in the yeast species <jats:italic>Saccharomyces cerevisiae</jats:italic> and <jats:italic>Candida albicans</jats:italic> have none at all. To understand how introns can be lost from genes, <jats:bold> Mitrovich <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="838" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1194554">838</jats:related-article> ) compared non–protein-coding genes among the yeasts and found that genes for small nucleolar RNAs (snoRNAs) in <jats:italic>C. albicans</jats:italic> are intronic. By contrast in <jats:italic>S. cerevisiae</jats:italic> , snoRNAs are processed from unmodified RNA, suggesting a massive loss of snoRNAs—associated introns in the common ancestor of the <jats:italic>Saccharomyces</jats:italic> species. The introns seem to have been lost through splice-site degeneration, and associated compaction of linked exons resulted in nested splicing of some snoRNAs. </jats:p>

<jats:title>Primitive Origins for Microglia</jats:title> <jats:p> Microglia are the resident macrophages of the central nervous system and are associated with neurodegeneration and brain inflammatory diseases. Although the developmental origins of other tissue macrophage populations are well established, the origins of microglia remain controversial. <jats:bold> Ginhoux <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="841" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1194637">841</jats:related-article> , published online 21 October) used in vivo lineage tracing studies to show that microglia arise early in mouse development and derive from primitive macrophages in the yolk sac. This is in contrast to other cells of the mononuclear phagocyte system, which arise later in development from a distinct progenitor population. </jats:p>

<jats:title>Tuned for Faces</jats:title> <jats:p> The temporal lobe of macaques' brains contains six patches of face-selective cortex. This observation has prompted systems neuroscientists to ask, why so many and what do they do? <jats:bold>Freiwald and Tsao</jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="845" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1194908">845</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6005" page="764" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1198348">Connor</jats:related-article> </jats:bold> ) targeted four of these regions for single-unit recordings and found that the different face-selective patches in macaques have independent functions. The areas where earliest processing occurred were most sharply tuned for individual views and least sharply tuned for identity. The mid-level area was more sharply tuned for identity, and the highest processing stage was strongly tuned for identity in a strikingly view-invariant way. These results yield fundamental insights into the computational process of object recognition, the functional organization of the brain, and how representations are transformed through processing hierarchies. </jats:p>

<jats:p>Think there's nothing new in the world of flow cytometry? Think again. As industry powerhouses like BD Biosciences and Beckman Coulter continually redefine the technology's bleeding edge, upstarts have emerged with innovative technologies of their own. And not only upstarts. No less a corporate brand than Sony entered the fray this past February with the purchase of flow cytometry firm iCyt. As Richard Konz, director of the University of Massachusetts Medical School Flow Cytometry Core Facility, explains, the technology has shaken off its immunology roots to become a multidisciplinary tool. "Literally every department is using flow for something, and that for me is very exciting," Konz says. "It's basically never a dull moment."</jats:p>