Catálogo de publicaciones - revistas

<jats:title>Limited Stability</jats:title> <jats:p> Deep ocean circulation is thought to be stable during warm, interglacial periods. <jats:bold> Galaasen <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6175" page="1129" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1248667">1129</jats:related-article> , published online 20 February) constructed a highly resolved record of North Atlantic Deep Water production during the last interglacial period, around 128,000 to 116,000 years ago. The findings reveal large, centennial-scale reductions—in contrast to the prevailing paradigm. These changes occurred in an ocean warmer than that of today, but in a temperature regime similar to that expected because of global warming, raising the possibility that future ocean circulation, regional climate, and CO <jats:sub>2</jats:sub> sequestration pathways could be impacted. </jats:p>

<jats:p> Although substantial progress has been achieved in the structural analysis of exporters from the superfamily of adenosine triphosphate (ATP)–binding cassette (ABC) transporters, much less is known about how they selectively recognize substrates and how substrate binding is coupled to ATP hydrolysis. We have addressed these questions through crystallographic analysis of the Atm1/ABCB7/HMT1/ABCB6 ortholog from <jats:italic>Novosphingobium aromaticivorans</jats:italic> DSM 12444, <jats:italic>Na</jats:italic> Atm1, at 2.4 angstrom resolution. Consistent with a physiological role in cellular detoxification processes, functional studies showed that glutathione derivatives can serve as substrates for <jats:italic>Na</jats:italic> Atm1 and that its overexpression in <jats:italic>Escherichia coli</jats:italic> confers protection against silver and mercury toxicity. The glutathione binding site highlights the articulated design of ABC exporters, with ligands and nucleotides spanning structurally conserved elements to create adaptable interfaces accommodating conformational rearrangements during the transport cycle. </jats:p>

<jats:title>Crossing the Membrane</jats:title> <jats:p> Adenosine triphosphate (ATP)–binding cassette (ABC) transporters couple ATP hydrolysis to the translocation of a wide variety of substrates across cell membranes. <jats:bold> Srinivasan <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6175" page="1137" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1246729">1137</jats:related-article> ) describe the structure of a yeast mitochondrial transporter involved in Fe-S protein biogenesis. The structure reveals bound glutathione, which suggests that glutathione is part of the translocated substrate. <jats:bold> J. Y. Lee <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6175" page="1133" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1246489">1133</jats:related-article> ) describe the structure of a bacterial ABC transporter that confers protection against silver and mercury. This protein also binds glutathione derivatives. The structure provides insight into how ligand interactions are coupled to ATP hydrolysis. </jats:p>

<jats:title>Carbapenems Through the Looking Glass</jats:title> <jats:p> The carbapenem class of antibiotics is a critical weapon in the ongoing fight against drug-resistant bacteria. Microbial biosynthesis of these compounds, which contain a strained β-lactam ring motif, proceeds via a precursor that has the wrong configuration at one of the ring carbons. <jats:bold> Chang <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6175" page="1140" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1248000">1140</jats:related-article> ) combined x-ray crystallography with multiple spectroscopic probes to map out the mechanism by which the CarC enzyme inverts the precursor configuration to its mirror image. </jats:p>

<jats:p> Quantifying the impact of heritable epigenetic variation on complex traits is an emerging challenge in population genetics. Here, we analyze a population of isogenic <jats:italic>Arabidopsis</jats:italic> lines that segregate experimentally induced DNA methylation changes at hundreds of regions across the genome. We demonstrate that several of these differentially methylated regions (DMRs) act as bona fide epigenetic quantitative trait loci (QTL <jats:sup>epi</jats:sup> ), accounting for 60 to 90% of the heritability for two complex traits, flowering time and primary root length. These QTL <jats:sup>epi</jats:sup> are reproducible and can be subjected to artificial selection. Many of the experimentally induced DMRs are also variable in natural populations of this species and may thus provide an epigenetic basis for Darwinian evolution independently of DNA sequence changes. </jats:p>

<jats:title>Evolutionary Duality</jats:title> <jats:p> When ecological divergence involves traits that also contribute to mating behavior, such divergence could lead to rapid reproductive isolation and speciation. However, there are very few experimental demonstrations of such “dual” traits. <jats:bold> Chung <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6175" page="1148" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1249998">1148</jats:related-article> , published online 13 February) now demonstrate that specific cuticular hydrocarbons are a dual trait that affects both desiccation resistance and mate choice in the widely distributed Australian species <jats:italic>Drosophila serrata</jats:italic> . These compounds have largely been lost from its rainforest-restricted, desiccation-sensitive, closely related sibling <jats:italic>D. birchii</jats:italic> . </jats:p>

<jats:title>Keeping HIV at Bay?</jats:title> <jats:p> Preexposure prophylaxis involving daily doses of drugs can, with variable success rates, interrupt HIV transmission for individuals at high risk of acquiring HIV infection. However, one reason for the variability seen in the response to such drugs is a lack of adherence to the prescribed regimen. <jats:bold> Andrews <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6175" page="1151" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1248707">1151</jats:related-article> ) formulated a potent integrase inhibitor as a long-acting agent that protected macaques from repeated intrarectal challenges of simian HIV. Decay of plasma levels of drug were associated with increased susceptibility to infection after virus exposure. The drug levels required for a high degree of protection could potentially be achieved with quarterly injections in humans. </jats:p>

<jats:title>Altitude Sickness</jats:title> <jats:p> Whether the incidence of malaria will be (or has been) affected by the warming climate is poorly resolved. Global-scale analyses are fraught with technical difficulties, including problems with separating out changes resulting from destruction of mosquito habitat, insecticide use, and antimalarial drug use from multidecadal trends in climate change. <jats:bold> Siraj <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6175" page="1154" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244325">1154</jats:related-article> ) performed parallel analyses of highland malaria in Ethiopia and Colombia to ask whether interannual changes in temperature could explain variation in malaria incidence with altitude. Modeling the data confirmed that malaria moves up in elevation in warmer years and allowed estimates of how many more millions of cases could be expected in tropical highland areas if the mean temperature increased by 1° to 3°C. </jats:p>

<jats:p>Listen to stories on 100 years of crystallography, firming up the link between climate change and malaria, and more.</jats:p>

<jats:p>Researchers today have a many choices when deciding which sequencing technology to use for their clinical research. Sanger sequencing, long the "gold standard" in clinical research sequencing technology, has met significant competition with the advent of next generation sequencing (NGS). NGS technologies are now commonplace in clinical research laboratories where they have enabled rapid advances in the gathering and analysis of genetic information. However, with these advances have come additional challenges involving validation as these technologies become more widespread and move closer to future clinical application. In this webinar, our expert speakers will discuss the relative benefits of Sanger and NGS technologies and their application in different fields of clinical research.</jats:p>