Catálogo de publicaciones - revistas

<jats:title>Move Over, TLR4</jats:title> <jats:p> The innate immune system senses bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 (TLR4) (see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6151" page="1184" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1243939">Kagan</jats:related-article> </jats:bold> ). However, <jats:bold> Kayagaki <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="6151" page="1246" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1240248">1246</jats:related-article> , published online 25 July) and <jats:bold> Hagar <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="6151" page="1250" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1240988">1250</jats:related-article> ) report that the hexa-acyl lipid A component of LPS from Gramnegative bacteria is able to access the cytoplasm and activate caspase-11 to signal immune responses independently of TLR4. Mice that lack caspase-11 are resistant to LPS-induced lethality, even in the presence of TLR4. </jats:p>

<jats:title>Joint Action</jats:title> <jats:p> Many small insects are impressive jumpers, but large leaps and small bodies pose biomechanical challenges. <jats:bold>Burrows and Sutton</jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6151" page="1254" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1240284">1254</jats:related-article> ) show that the nymphal planthopper <jats:italic>Issus</jats:italic> has interlocking gears on their hindleg trochanters that act together to cock the legs synchronously before triggering forward jumps. At the final molt, the gears are swapped for a high-performance friction-based mechanism because the risk of breaking a gear is high, the options for repair during molting are gone, and, moreover, the animal is bigger and stronger. </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:p>Listen to stories on DNA and disasters, new immunological weapons against HIV, Voyager's latest exit, and more,</jats:p>

<jats:p>Cancer is a highly complex disease that can encompass multiple genomic alterations in the progression from normal to diseased cell. Recent studies point to the significance of copy number aberrations in the etiology of cancer, with the number and complexity of these aberrations being indicative of overall prognosis. Additionally, the detection and characterization of subclones is also understood to be important for understanding clonal evolution of the cancer and thus patient monitoring and treatment decisions. Genome-wide copy number analysis is a powerful means to understand the genetic basis of solid tumors. With the majority of solid tumors typically stored as formalin-fixed, paraffin-embedded (FFPE) tissue, retrospectively analyzing these samples with available outcome data is a cost-effective route to prognostic and predictive biomarker discovery. Our expert panel will describe their research and discoveries, and how they have overcome the significant challenges of extracting copy number data from often degraded, heterogeneous FFPE samples.</jats:p>

<jats:title>Toward Synthetic Biology</jats:title> <jats:p> The detection of an appropriate point to intervene in a cellular pathway and minimize off-target effects on other cellular processes present problems for the design of circuits that control cellular signaling pathways and thus direct cell function. <jats:bold> Galloway <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/341/6152/1235005.full">1358</jats:ext-link> , published online 15 August; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6152" page="1349" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1243994">Sarkar</jats:related-article> </jats:bold> ) report progress on these challenges in the yeast <jats:italic>Saccharomyces cerevisiae</jats:italic> . A molecular control system was developed to direct the yeast cells to one of three cell fates. To avoid disruption of other cellular controls, exogenous ribozyme-based controllers that interfaced with the endogenous control circuits were used, which avoided genetic alteration to the cells. After enhancing the control circuits with feedback loops to make their behavior more reliable, the circuits were used to modulate the abundance of particular components that acted as critical regulators of yeast cell-fate decisions. This allowed direction of cell fate in response to a chosen chemical stimulus. These strategies may be adaptable to allow similar direction of the physiological state of mammalian cells, for example, to allow therapeutic applications of synthetic biology. </jats:p>

<jats:sec> <jats:title>Background</jats:title> <jats:p>Transition metal–catalyzed alkene metathesis has revolutionized organic synthesis during the last two decades, even though the commonly used catalysts do not provide kinetic control over the stereochemistry of the newly formed double bonds. It is of utmost importance to fix this shortcoming, because the olefin geometry not only determines the physical and chemical properties of the alkene products but is also innately linked to any biological activities that the olefins may have.</jats:p> </jats:sec> <jats:sec> <jats:title>Advances</jats:title> <jats:p> Recent progress in catalyst design led to the development of a first set of metal alkylidene complexes of ruthenium, molybdenum, and tungsten that allow a host of inter- and intramolecular alkene metathesis reactions to be performed with good to excellent levels of <jats:italic>Z</jats:italic> selectivity (see the figure). This marks a considerable advancement over prior art, even though inherently <jats:italic>E</jats:italic> -selective catalysts remain elusive. In the case of disubstituted olefins, this gap in coverage can be filled by a sequence of alkyne metathesis followed by stereoselective semi-reduction of the resulting acetylene derivatives, which provides highly selective access to either geometrical series. Because the required alkylidyne catalysts have also been greatly improved in terms of activity, functional group tolerance, and user-friendliness, this method constitutes a valuable preparative complement. </jats:p> </jats:sec> <jats:sec> <jats:title>Outlook</jats:title> <jats:p>It is expected that the new catalysts will be rapidly embraced by the synthetic community. Because the as-yet limited number of published case studies is very encouraging, it is reasonable to believe that more sophisticated applications to polyfunctionalized and/or industrially relevant targets will follow shortly. Such investigations will allow the selectivity and performance of the stereoselective metathesis catalysts to be scrutinized in great detail. In parallel, growing mechanistic insights into their mode of action will almost certainly be forthcoming that can then be translated into refined ligand design. The resulting feedback loops will likely result in the evolution of ever more selective and practical catalysts, the long-term impact of which on organic synthesis and materials science will surely be profound and lasting.</jats:p> </jats:sec>