Catálogo de publicaciones - revistas

<jats:title>Beyond the Greatwall</jats:title> <jats:p> Protein phosphorylation and dephosphorylation provide a central mechanism that controls the eukaryotic cell division cycle and entry of cells into mitosis. A form of protein phosphatase 2A (PP2A) has an important role inhibiting phosphorylation-dependent activation of cyclin-dependent kinase 1 (CDK1) itself and also dephosphorylating substrates of the active CDK1 that promote mitosis. PP2A activity is inhibited when another protein kinase, known as Greatwall, is activated (see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6011" page="1638" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1199898"> <jats:bold>Virshup and Kaldis</jats:bold> </jats:related-article> ). <jats:bold> Mochida <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="1670" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1195689">1670</jats:related-article> ) and <jats:bold> Gharbi-Ayachi <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="1673" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1197048">1673</jats:related-article> ) searched for substrates of Greatwall that might participate in the cell cycle regulatory machinery. When phosphorylated by Greatwall, a pair of small related proteins, Arpp19 and α-endosulfine, inhibited activity of PP2A. These effects were critical for regulation of mitosis in <jats:italic>Xenopus</jats:italic> egg extracts and in human cancer cells. Greatwall itself is phosphorylated and activated by CDK1—thus, apparently contributing to a feed-forward loop that contributes to the switchlike commitment of cells to mitosis. </jats:p>

<jats:title>Beyond the Greatwall</jats:title> <jats:p> Protein phosphorylation and dephosphorylation provide a central mechanism that controls the eukaryotic cell division cycle and entry of cells into mitosis. A form of protein phosphatase 2A (PP2A) has an important role inhibiting phosphorylation-dependent activation of cyclin-dependent kinase 1 (CDK1) itself and also dephosphorylating substrates of the active CDK1 that promote mitosis. PP2A activity is inhibited when another protein kinase, known as Greatwall, is activated (see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6011" page="1638" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1199898"> <jats:bold>Virshup and Kaldis</jats:bold> </jats:related-article> ). <jats:bold> Mochida <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="1670" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1195689">1670</jats:related-article> ) and <jats:bold> Gharbi-Ayachi <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="1673" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1197048">1673</jats:related-article> ) searched for substrates of Greatwall that might participate in the cell cycle regulatory machinery. When phosphorylated by Greatwall, a pair of small related proteins, Arpp19 and α-endosulfine, inhibited activity of PP2A. These effects were critical for regulation of mitosis in <jats:italic>Xenopus</jats:italic> egg extracts and in human cancer cells. Greatwall itself is phosphorylated and activated by CDK1—thus, apparently contributing to a feed-forward loop that contributes to the switchlike commitment of cells to mitosis. </jats:p>

<jats:title>Few But Powerful</jats:title> <jats:p> Drug activation of the different types of acetylcholine receptors in cholinergic neurons often generates opposing or conflicting effects. Using optogenetic techniques in transgenic mice, <jats:bold> Witten <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="1677" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1193771">1677</jats:related-article> ) investigated the function of a rather enigmatic subpopulation of cholinergic neurons, the giant interneurons of the nucleus accumbens. Their excitation paradoxically reduced neighboring medium spiny neuron firing, while their inhibition increased medium spiny neuron firing. Furthermore, the giant interneurons were directly activated by cocaine, and silencing their drug-induced activity during cocaine exposure in freely behaving animals disrupted cocaine reward. </jats:p>

<jats:title>Essential and New</jats:title> <jats:p> Genes can be broadly grouped into two sets on the basis of their contribution to fitness: those that are essential to the life of an organism and those that can be dispensed with. However, the degree of essentiality in evolutionarily “new” genes—genes that have originated in the recent past—is unknown. <jats:bold> Chen <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="1682" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1196380">1682</jats:related-article> ) investigated the origination and evolution of new genes within 12 <jats:italic>Drosophila</jats:italic> species and found, surprisingly, that over one-third of genes that have originated within the last 3.5 million years show essential function and that these functions are overrepresented during larval development. Approximately the same proportion of older genes was essential, although many of these genes also appear to show enrichment at later developmental stages. These findings challenge conventional wisdom that would claim that essential genes are ancient and conserved among animal taxa. </jats:p>

<jats:title>Making a Germ Cell</jats:title> <jats:p> When it comes to generating the germ line, animals fall into two classes: those, like mammals, which use inductive interactions to specify the germ line and those, like nematodes, which use germ plasm—a specialized egg cytoplasm that segregates asymmetrically in embryos. Germ plasm contains germ, or P, granules—RNA-protein aggregates that have been thought to harbor the germ line determinants. Now, <jats:bold> Gallo <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="1685" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1193697">1685</jats:related-article> , published online 2 December) describe a <jats:italic>Caenorhabditis elegans</jats:italic> mutant that challenges this belief. The germ line still formed even when germ granule components were missegregated. Thus, even in animals with germ plasm, germ granules appear to be a consequence, not a cause, of germ cell specification. </jats:p>

<jats:title>Metabolism Without Modification</jats:title> <jats:p> Obesity-associated metabolic disease has rapidly become a public health priority in the developed world and is being addressed through prevention strategies aimed at lifestyle changes and through pharmacological approaches. <jats:bold> Barnett <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="1689" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1196154">1689</jats:related-article> , published online 18 November) designed a drug that inhibits the action of ghrelin, a circulating peptide hormone that increases fat mass and food intake. The drug, a bisubstrate analog called GO-CoA-Tat, is a selective antagonist of ghrelin O-acyltransferase (GOAT), an enzyme that catalyzes a posttranslational modification that is essential for ghrelin activity. Injection of GO-CoA-Tat into wild-type mice on a high-fat diet improved glucose tolerance and reduced weight gain, probably through changes in metabolic activity. Because GO-CoA-Tat is a peptide-based drug that requires repeated injection, it is unsuitable for clinical use, but GOAT does represent a potentially valuable target for future drug development efforts in metabolic disease. </jats:p>

<jats:title>Size Matters</jats:title> <jats:p> Animals regulate their growth so that all organs are mutually proportional, even when growth occurs at different times. However, the mechanism by which this occurs is unknown. <jats:bold>Nijhout and Grunert</jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1693" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1197292">1693</jats:related-article> , published online 25 November) performed an analysis of relative wing growth in the tobacco hornworm, <jats:italic>Manduca</jats:italic> . Animals that were small owing to starvation had smaller wings, due to their slower growth rate, and they also stopped growing earlier than large, well-fed larvae. The insect hormone ecdysone was implicated in the process that governs this scaling relationship between adult wings and body size. </jats:p>

<jats:title>Lymphocytes Layer It On</jats:title> <jats:p> Cells of the immune system begin to develop from hematopoietic stem cells (HSCs) during fetal life. In the adult, HSCs continue to produce immune cells to replenish dying cells or in response to an infection. In mice and birds, immune cell development occurs in a “layered” manner, whereby distinct populations of HSCs that arise at different times during development generate distinct immune cell lineages. In contrast, development of human immune cells, and T lymphocytes in particular, is thought to be linear. <jats:bold> Mold <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="1695" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1196509">1695</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="6011" page="1635" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1200406">Betz</jats:related-article> </jats:bold> ) now show that T lymphocyte development in humans is also “layered,” and strategically so. T cells that arise from fetal HSCs are enriched in regulatory T cells, which promote immune tolerance, rather than classical T cells, which readily respond to foreign antigen. By favoring the development of regulatory T cell populations during fetal life, the immune system is perhaps better able to keep responses to maternal antigens in check. The development of large numbers of classical T cells is delayed until after birth when infectious agents represent a more imminent threat. </jats:p>

<jats:p>The show includes the top scientific breakthrough of 2010 and some of the big ideas of the past decade.</jats:p>

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