Catálogo de publicaciones - revistas

<jats:title>Three Fluorines at Once</jats:title> <jats:p> The trifluoromethyl (CF <jats:sub>3</jats:sub> ) group is playing an increasingly important role in the design of pharmaceutical and agrochemical compounds. CF <jats:sub>3</jats:sub> is a powerful attractor of electron density within a given molecular framework, and recently fluorine-hydrocarbon interactions have emerged as a distinct complement to the more traditional hydrophilic/hydrophobic interplay that governs docking between small molecules and proteins. <jats:bold> Cho <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="1679" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1190524">1679</jats:related-article> ) now present an efficient method for appending CF <jats:sub>3</jats:sub> groups to a broad range of aryl substrates. A carefully optimized palladium catalyst was able to speed up a critical elimination step that has plagued previous efforts to realize a general solution to this synthetic challenge. </jats:p>

<jats:title>Hydrated Minerals on Martian Northern Plains</jats:title> <jats:p> The presence of hydrated minerals on the surface of Mars implies that the crust of the planet was once altered by the action of liquid water. This conclusion is well established for the ancient southern highlands of Mars, but the situation in the northern lowlands, which are thought to have been resurfaced by lava flows during the Hesperian period about 3 billion years ago, is not so clear. <jats:bold> Carter <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="328" xlink:href="10.1126/science.1189013">1682</jats:related-article> ) report the detection of hydrated minerals in nine northern plain craters, which are thought to have exposed the ancient, pre-Hesperian crust. The results suggest that the degree of alteration of the ancient martian crust is more extensive than previously assumed. </jats:p>

<jats:title>Glacial Gas</jats:title> <jats:p> Intracellular bacterial pathogens, such as a series of sudden and large warming episodes, called Dansgaard-Oeschger events, interrupted the cold conditions of the last glacial period. Large increases in the concentration of atmospheric methane accompanied the events, whose causes have remained the object of much speculation. <jats:bold> Bock <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="1686" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1187651">1686</jats:related-article> ) report measurements of the hydrogen isotopic composition of methane recovered in the North Greenland Ice Core Project. The excess atmospheric methane accompanying two Dansgaard-Oeschger events did not come from marine clathrates; instead, the methane probably came from increased fluxes from boreal wetlands, another major source of methane. </jats:p>

<jats:title>Inhibiting Leukocytosis</jats:title> <jats:p> Leukocytosis—an elevated white blood cell count—contributes by unknown mechanisms to the pathogenesis of atherosclerosis and associated coronary heart disease. Now, <jats:bold> Yvan-Charvet <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="328" xlink:href="10.1126/science.1189731">1689</jats:related-article> , published online 20 May; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5986" page="1641" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1191663">Hansson and Björkholm</jats:related-article> </jats:bold> ) show that the adenosine triphosphate–binding cassette transporters ABCA1 and ABCG1 are critical suppressors of atherosclerosis-associated leukocytosis. Mice deficient in both transporters in blood-producing hematopoietic cells possessed increased levels of hematopoietic stem and multipotential progenitor cells and accelerated atherosclerosis. ABCA1 and ABGA1 protect against atherosclerosis by promoting cholesterol efflux from cholesterol-laden macrophage foam cells to lipid-poor high-density lipoprotein (HDL) and apolipoprotein A-1. The leukocytosis and atherosclerosis in ABCA1- and ABG1-deficient mice were reversed in the presence of high amounts of HDL. Thus, signaling already known to inhibit atherosclerosis by reducing cholesterol in atherosclerotic plaques also reduces atherosclerosis-associated leukocytosis. </jats:p>

<jats:title>No Dicer for Me</jats:title> <jats:p> MicroRNAs (miRNAs) are small noncoding RNAs found in most eukaryotes. Most are processed from primary transcripts in the nucleus by the microprocessor enzyme complex, which includes the nuclease Drosha, with a small number being generated by the messenger RNA splicing machinery. All pre-miRNAs are then exported into the cytoplasm where they are cleaved further by a second nuclease, Dicer, into the mature, functional miRNA. <jats:bold> Cifuentes <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="1694" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1190809">1694</jats:related-article> , published online 6 May), now show that in a Dicer mutant fish at least one miRNA, miR-451, is still formed from pre-miR-451. The processing of pre-miR-451 requires the slicing activity of another protein in the miRNA pathway, Argonaute2. The unusual secondary structure of the pre-miR-451 determines its noncanonical processing pathway, which suggests that other miRNAs might also be processed in this way. </jats:p>

<jats:title>In, Out, Positive Charge About</jats:title> <jats:p> The mechanism by which multispanning, helix-bundle membrane proteins are inserted into their target membrane is not completely understood. EmrE is an <jats:italic>Escherichia coli</jats:italic> inner-membrane protein with four transmembrane helices that can take up two distinct topologies—with its amino terminus toward the cytosol, or away from the cytosol. <jats:bold> Seppälä <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="1698" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1188950">1698</jats:related-article> , published online 27 May; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5986" page="1644" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1193065">Tate</jats:related-article> </jats:bold> ) exploited the dual-topology property of EmrE to study the mechanism of membrane protein assembly in <jats:italic>Escherichia coli</jats:italic> . Systematically exploring the effects of positively charged residues on the topology of EmrE revealed that the membrane orientation of EmrE constructs with four or five transmembrane helices could be controlled by a single positively charged residue placed in different locations throughout the protein, including the very carboxyl terminus. Such global control of membrane protein topology raises important questions concerning how multispanning membrane proteins are handled by the membrane protein insertion machinery. </jats:p>

<jats:title>Breaking Hamilton's Rule</jats:title> <jats:p> Hamilton's rule states that the evolution of cooperation is correlated with the kin relationship between the actor and the recipient and the degree of the benefit. However, this approximation relies on several steps of simplification that are often violated in natural systems. <jats:bold> Smith <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="1700" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1189675">1700</jats:related-article> ) derived a non-additive model for the evolution of cooperation by kin selection that could be applied to all domains of life—not just animals. Experimental data examining the bacteria <jats:italic>Myxococcus xanthus</jats:italic> showed that nonlinear interactions among cells make bacterial cooperation surprisingly resistant to cheating. </jats:p>

<jats:title>Bacterial (Interferon)ce</jats:title> <jats:p> Intracellular bacterial pathogens, such as <jats:italic>Listeria monocytogenes</jats:italic> , are detected in the cytosol of host immune cells, where they induce a host response that is often dependent on microbial secretion systems. <jats:bold> Woodward <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="1703" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1189801">1703</jats:related-article> , published online 27 May) now show that <jats:italic>L. monocytogenes</jats:italic> produce and release cyclic diadenosine monophosphate into the host cytosol, which induces the production of host type I interferon. Because a number of intracellular pathogens contain the protein machinery to generate this nucleotide and also activate this same innate immune pathway, a common molecular mechanism may exist for host detection of cytosolic bacterial pathogens. </jats:p>

<jats:title>A Gut Feeling</jats:title> <jats:p> The mammalian gut is colonized by many nonpathogenic, commensal microbes. In order to prevent the body from mounting inappropriate immune responses to these microbes, plasma cells in the gut produce large amounts of immunoglobulin A (IgA) specific for commensal bacteria. Because of the difficulties of uncoupling IgA production from microbial colonization, how commensal bacteria shape the gut IgA response is not well understood. <jats:bold> Hapfelmeier <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="1705" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1188454">1705</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="5986" page="1646" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1192488">Cerutti</jats:related-article> </jats:bold> ) have now devised a way to get around this problem by developing a reversible system of gut bacterial colonization in mice. Commensal-specific IgA responses were able to persist for long periods of time in the absence of microbial colonization and required the presence of high microbial loads in the gut for their induction. IgA responses upon bacterial reexposure did not resemble the synergistic prime-boost effect seen in classical immunological memory responses but rather exhibited an additive effect that matched the current bacterial content present in the gut. The body thus constantly adapts the commensal-specific immune response to the microbial species present in the gut, which contrasts with the systemic immune response, which persists in the absence of pathogenic microbes. </jats:p>

<jats:title>Addicts Lose Plasticity</jats:title> <jats:p> What are the biological mechanisms associated with the transition from occasional drug use to addiction? In rats, like in humans, even after a prolonged period of drug intake, only a limited number of animals develop addiction-like behavior despite the amount of drug taken by all subjects being the same. <jats:bold> Kasanetz <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="1709" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1187801">1709</jats:related-article> ) compared the expression of <jats:italic>N</jats:italic> -methyl- <jats:sc>d</jats:sc> -aspartate (NMDA)–dependent long-term depression (NMDA-LTD) in the nucleus accumbens of addicted and nonaddicted rats. Initially, once drug self-administration had been learned and consolidated, but before the appearance of addiction-like behavior, LTD was suppressed in all animals independently of their vulnerability to addiction at a later stage. However, after 2 months, when addiction-like behavior appears, LTD was persistently lost in the addicted animals. In contrast, normal NMDA-LTD reappeared in animals that maintained a controlled drug intake without becoming addicted. </jats:p>