Catálogo de publicaciones - revistas

<jats:title>Reconstructing the Human Brain</jats:title> <jats:p> Reference brains have become a standard tool in human brain research. Reference brains presently in the public domain provide a spatial framework at the macroscopic level. <jats:bold> Amunts <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="6139" page="1472" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1235381">1472</jats:related-article> ) present a high-resolution (20 µm) three-dimensional reconstruction of a human brain. The tool will be freely available to help with interpreting functional neuroimaging studies, fiber tract analyses, and assigning molecular and gene expression data. </jats:p>

<jats:title>Dendritic Pruning</jats:title> <jats:p> During metamorphosis, <jats:italic>Drosophila</jats:italic> sensory neurons eliminate their dendritic trees, but axons and soma remain intact. <jats:bold> Kanamori <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="6139" page="1475" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1234879">1475</jats:related-article> , published online 30 May) demonstrate that compartmentalized calcium transients in dendrites function as the spatiotemporal cue for pruning of unwanted branches. Such a localized calcium signal, induced by a local elevation of branch excitability, activates calcium-dependent proteinases and eventually causes branch death. </jats:p>

<jats:p>Listen to stories on a new brain database, the 100th anniversary of Bohr's atomic theory, the fate of U.S. research powerhouses, and more.</jats:p>

<jats:p>Recent advances in technology and cost effectiveness of next generation sequencing has led to its progressively wider implementation in both research and clinical settings. The amount of data it produces, however, can be overwhelming—typically over three million variants per genome. The challenges for many researchers today are how to make sense of this huge volume of data in the context of the scientific question being asked, and how to identify those variants that provide meaningful and relevant information. In this webinar we will discuss current approaches to variant analysis and how they can be most effectively integrated into the next generation sequencing pipeline.</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:sec> <jats:title>Background</jats:title> <jats:p>Immediately after the Big Bang, the universe was uniform, homogeneous, and completely free of stars. The gravitational collapse of dark matter gathered gas with it that cooled, collapsed further, and formed stars. Observations over the past 20 years have revealed the dynamic star-formation history of the universe. The star-formation rate peaked 10 billion years ago, when stars formed an order of magnitude faster than in the modern universe. Deep observations have begun to reveal the early history of star formation, but how quickly star formation started remains controversial, with results from observations of early galaxies suggesting a slower start than distributions of distant gamma-ray bursts that trace young stars. However, simulations using standard prescriptions for energetic feedback from star formation (from stellar explosions and ionizing radiation) have tended to predict a substantially earlier peak than either of these methods shows.</jats:p> </jats:sec> <jats:sec> <jats:title>Advances</jats:title> <jats:p>Energetic feedback drives turbulence in diffuse gas that both promotes and inhibits star formation, with inhibition dominating over promotion, so that star formation does not efficiently trigger further star formation. Insufficient numerical resolution in simulations causes unphysical radiative cooling to occur in multiple ways, reducing the effectiveness of feedback in driving turbulence. Other mechanisms—such as magnetorotational instability, radiative heating, or accretion from the intergalactic medium—must also contribute to the observed gas velocity dispersions. Radiation pressure appears likely to be only modestly effective because of Rayleigh-Taylor instability in gas accelerated by it. Observed correlations between gas surface density and star-formation rate surface density can be reproduced by models including gravitational instability. Molecule formation may occur as a result of gravitational collapse rather than initiating it. Thus, gravitational instability seems to determine star formation, with the level of turbulence setting the critical density for instability.</jats:p> </jats:sec> <jats:sec> <jats:title>Outlook</jats:title> <jats:p> Determining the early history of star formation will require the efforts of the largest ground and space-based telescopes under construction, such as the James Webb Space Telescope <jats:italic>,</jats:italic> the European Extremely Large Telescope, and the Large Synoptic Survey Telescope. Progress in models requires both better algorithms and larger computers. Adaptive meshes, both structured and unstructured, will play a critical role, as will hybrid algorithms that can take full advantage of the shared memory nodes of massively parallel computer clusters. A clear picture of star formation will underpin our understanding of the evolution of galaxies, including our own Milky Way, and of the history of the production and distribution of the elements heavier than helium, including those necessary for planet formation and for life. </jats:p> </jats:sec>

<jats:p> <jats:bold>Introduction:</jats:bold> One of the most critical and complex steps of protein synthesis is the coupled translocation of mRNA and tRNAs (mRNA and tRNAs) through the ribosome, catalyzed by the guanosine triphosphatase (GTPase) elongation factor EF-G. Although several of the main steps have been identified, the underlying molecular mechanisms of translocation are poorly understood. A central question is how structural rearrangements in the ribosome are coupled to movement of mRNA and tRNA. </jats:p> <jats:p> <jats:bold>Methods:</jats:bold> We trapped and crystallized complexes of <jats:italic>Thermus thermophilus</jats:italic> ribosomes bound with EF-G, mRNA, and tRNA, using the antibiotic fusidic acid (which prevents release of EF-G after GTP hydrolysis) or the nonhydrolyzable GTP analog GDPNP, in intermediate states of translocation. Their crystal structures were determined to resolutions from 3.5 to 4.1 Å. </jats:p> <jats:p> <jats:bold>Results:</jats:bold> The structures of the fusidic acid complex (Fus) and two GDPNP complexes (GDPNP-I and GDPNP-II) reveal conformational changes occurring during intermediate states of translocation, including large-scale (15° to 18°) rotation of the 30 <jats:italic>S</jats:italic> subunit head and 3° to 5° rotation of the 30 <jats:italic>S</jats:italic> body. In all complexes, the tRNA acceptor end has moved from the 50 <jats:italic>S</jats:italic> subunit P site to the 50 <jats:italic>S</jats:italic> E site, while the anticodon stem loop (ASL) and mRNA move with the head of the 30 <jats:italic>S</jats:italic> subunit to positions between the P and E sites, forming chimeric pe*/E intermediate states. The elongated, mobile domain IV of EF-G moves to contact the head of the 30 <jats:italic>S</jats:italic> subunit and the backbone of the mRNA. Two universally conserved bases of 16 <jats:italic>S</jats:italic> rRNA that intercalate between bases of the mRNA may act as “pawls” of a translocational ratchet. In the GDPNP complexes, structuring of the conserved switch loop I segment, which was disordered in previous structures, completes the cage that encloses GDPNP and fixes the relative geometry of EF-G domains I, III, and V. In the Fus complex, the position of fusidic acid overlaps that of switch loop I, stabilizing contacts between domains I and III that are normally made by the structured switch loop. </jats:p> <jats:p> <jats:bold>Conclusion:</jats:bold> Our structures capture intermediate states of the rate-limiting step of translocation, in which movement of the tRNA ASL and mRNA is coupled to rotational movement of the 30 <jats:italic>S</jats:italic> subunit head. Slippage of the translational reading frame during reverse rotation of the head during translocation may be prevented by intercalation of bases C1397 and A1503 of 16 <jats:italic>S</jats:italic> rRNA, which project from the body of the 30 <jats:italic>S</jats:italic> subunit, between mRNA bases. The antibiotic fusidic acid appears to stabilize binding of EF-G to the ribosome in the GDP state by mimicking the structure of the conserved core of switch loop I of EF-G in the GTP state. </jats:p>

<jats:title>Revealed in Translation</jats:title> <jats:p> The ribosome, with the help of transfer RNAs (tRNAs), converts the triple genetic code in messenger RNA (mRNA) into protein. Upon decoding of a codon, the mRNA and associated tRNAs must be moved through the ribosome, so that the next codon can be read, with a new charged tRNA taken in at the A (aminoacyl-tRNA) site, the newly extended peptidyl-tRNA moved into the P (peptidyl-tRNA) site, and the deacylated tRNA removed from the exit site in the ribosome (see the Perspective by <jats:bold> <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.sciencemag.org/content/340/6140/1534.full">Rodnina</jats:ext-link> </jats:bold> ). Crystal structures from <jats:bold> Tourigny <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.sciencemag.org/content/340/6140/1235490.full">1235490</jats:ext-link> ), <jats:bold>Pulk and Cate</jats:bold> (p. <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.sciencemag.org/content/340/6140/1235970.full">1235970</jats:ext-link> ), and <jats:bold> Zhou <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.sciencemag.org/content/340/6140/1236086.full">1236086</jats:ext-link> ), variously capture the prokaryotic ribosome during this translocation phase, revealing the hybrid states of the tRNAs and the substantial motions of the 30S ribosomal subunit during the process, the role of elongation factor G, and suggest how the direction and reading frame of the mRNA is maintained. </jats:p>

<jats:title>Revealed in Translation</jats:title> <jats:p> The ribosome, with the help of transfer RNAs (tRNAs), converts the triple genetic code in messenger RNA (mRNA) into protein. Upon decoding of a codon, the mRNA and associated tRNAs must be moved through the ribosome, so that the next codon can be read, with a new charged tRNA taken in at the A (aminoacyl-tRNA) site, the newly extended peptidyl-tRNA moved into the P (peptidyl-tRNA) site, and the deacylated tRNA removed from the exit site in the ribosome (see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6140" page="1534" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1240090">Rodnina</jats:related-article> </jats:bold> ). Crystal structures from <jats:bold> Tourigny <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.sciencemag.org/content/340/6140/1235490.full">1235490</jats:ext-link> ), <jats:bold>Pulk and Cate</jats:bold> (p. <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.sciencemag.org/content/340/6140/1235970.full">1235970</jats:ext-link> ), and <jats:bold> Zhou <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.sciencemag.org/content/340/6140/1236086.full">1236086</jats:ext-link> ), variously capture the prokaryotic ribosome during this translocation phase, revealing the hybrid states of the tRNAs and the substantial motions of the 30S ribosomal subunit during the process, the role of elongation factor G, and suggest how the direction and reading frame of the mRNA is maintained. </jats:p>