Catálogo de publicaciones - revistas

<jats:title>Of Wnt, Prorenin Receptor, and V-ATPase</jats:title> <jats:p> The Wnt protein binds to receptors at the cell surface and regulates signaling pathways that control a wide range of critical biological processes from stem cell differentiation to generation of cancer. In a screen for components required for Wnt signaling, <jats:bold> Cruciat <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="459" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1179802">459</jats:related-article> ) discovered an unexpected partner, the prorenin receptor (PRR). PRR bound to the Wnt receptor proteins Fz8 and LRP6. The PRR protein could interact with the receptors and promote Wnt signaling without its cytoplasmic domain through which it initiates signaling in response to the prorenin protein. Its role in Wnt signaling appears to be rather different. The PRR binds to the vacuolar H <jats:sup>+</jats:sup> –adenosine triphosphatase (V-ATPase), a proton pump that can influence endocytosis by acidification of vesicles. The V-ATPase was also necessary for phosphorylation of LRP6 and Wnt. Thus, PRR may link the V-ATPase to the Wnt receptor protein LRP6, allowing acidification in the vicinity of the activated receptor, which appears to be necessary for phosphorylation of LRP6 and subsequent signaling. </jats:p>

<jats:title>Late-Running Clock Components</jats:title> <jats:p> Many mammalian cells contain a well-characterized biological clock with a 24-hour cycle. In the latter part of the day, transcription mediated by one of the clock components, the transcription factor made up of the CLOCK and BMAL1 proteins, is inhibited, but the mechanism of inhibition has been unclear. <jats:bold> Robles <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="463" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1180067">463</jats:related-article> ) used mass spectrometry to identify proteins that RACK1 (receptor for activated C kinase–1), a scaffold protein that brings protein kinase C–α (PKCα ) into contact with its substrates, caused to be associated with BMAL1 at the time of day when its transcription-activating function was inhibited. Further studies implicated PKCα and RACK1 as integral components of the clock, without which the clock's free-running period was shortened. </jats:p>

<jats:title>Garnering Information on Granulomas</jats:title> <jats:p> In tuberculosis, the tuberculous granuloma has been viewed traditionally as a host-protective structure that serves to “wall off” mycobacteria. However, recent work in the zebrafish embryo showed that mycobacteria convert the nascent granuloma into a vehicle for bacterial expansion and dissemination. Thus, intercepting granuloma formation could provide a strategy for treating tuberculosis, an urgent public health goal in light of the epidemic of extensively drug-resistant tuberculosis. Now <jats:bold> Volkman <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="466" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1179663">466</jats:related-article> , published online 10 December; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5964" page="417" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1185569">Agarwal and Bishai</jats:related-article> </jats:bold> ) present the molecular pathway by which mycobacteria induce granulomas in zebrafish. Inhibition of this pathway attenuates infection by reducing granuloma formation, suggesting a therapeutic target for tuberculosis treatment. </jats:p>

<jats:title>MRSA, Close and Personal</jats:title> <jats:p> Methods for differentiating pathogen isolates are essential for understanding their evolution and spread, as well as for the formulation of effective clinical strategies. Current typing methods for bacterial pathogens focus on a limited set of characteristics providing data with limited resolving power. <jats:bold> Harris <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="469" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1182395">469</jats:related-article> ) used a high-throughput genome sequencing approach to show that isolates of methicillin-resistant <jats:italic>Staphylococcus aureus</jats:italic> (MRSA) are precisely differentiated into a global geographic structure. The findings suggest that intercontinental transmission has occurred for nearly four decades. The method could also detect individual person-to-person transmission events of MRSA within a hospital environment. </jats:p>

<jats:title>Space and Spikelets</jats:title> <jats:p> In neurons, spikelets are voltage fluctuations of small amplitude with a spike-like waveform. Spikelets are difficult to detect with extracellular techniques traditionally used to record neuronal activity in freely moving animals. <jats:bold> Epsztein <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="474" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1182773">474</jats:related-article> ) used head-anchored whole-cell recordings to analyze spikelet activity during spatial exploration in freely moving rats. A high incidence of spikelets was often followed by action potentials. Like action potentials, spikelets were all-or-none, but had different kinetics and amplitude, and were clearly distinct from excitatory postsynaptic potentials and occurred to a different extent in different cells. In cells with clear place fields, spikelets had similar spatial firing preferences, as did regular action potentials. Thus, spatially modulated spikelets may be involved in information processing in cortical neuronal networks. </jats:p>

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