Catálogo de publicaciones - revistas

<jats:title>Coordinating Metabolism</jats:title> <jats:p> Growth factors help to coordinate metabolism with growth in part by stimulating the activity of the protein kinase mTORC1 (mechanistic target of rapamycin complex 1). <jats:bold> Ben-Sahra <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="6125" page="1323" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1228792">1323</jats:related-article> , published online 21 February) and <jats:bold> Robitaille <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="6125" page="1320" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1228771">1320</jats:related-article> , published online 21 February) independently identified a key target of mTORC1—carbamolyl-phosphate synthase 2, or CAD, the rate-limiting enzyme for de novo synthesis of pyrimidines. Metabolomic profiling and phosphoproteomic analyses of normal cells and cells lacking signaling by mTORC1 converged on CAD as a key point at which growth-promoting signals also ramp up production of nucleic acids. </jats:p>

<jats:title>Mitochondrial Makeup Mapped</jats:title> <jats:p> Because mass spectrometry (MS) cannot be performed on living cells, biologists currently recover spatial information indirectly, by purifying organelles or protein complexes prior to MS analysis. These purifications often yield false positives because of sample contamination and false negatives because of material loss. <jats:bold> Rhee <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="6125" page="1328" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1230593">1328</jats:related-article> , published online 31 January) present an approach that bridges microscopy and proteomics to produce a spatially and temporally resolved proteomic map of mitochondria from living cells. A nonspecific labeling enzyme (peroxidase) was genetically targeted to the mitochondria within live cells, where it tagged endogenous proteins in a spatially restricted manner within a 1-minute window, for subsequent identification and analysis by MS. This rapid and straightforward technology provides the ability to access otherwise inaccessible cellular regions and requires a very small amount of starting material. </jats:p>

<jats:title>Mercury Methylating Microbes</jats:title> <jats:p> Mercury (Hg) most commonly becomes bioavailable and enters the food web as the organic form methylmercury, where it induces acute toxicity effects that can be magnified up the food chain. But most natural and anthropogenic Hg exists as inorganic Hg <jats:sup>2+</jats:sup> and is only transformed into methylmercury by anaerobic microorganisms—typically sulfur-reducing bacteria. Using comparative genomics, <jats:bold> Parks <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="6125" page="1332" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1230667">1332</jats:related-article> , published online 7 February; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6125" page="1280" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1235591"> <jats:bold>Poulain and Barkay</jats:bold> </jats:related-article> ) identified two genes that encode a corrinoid and iron-sulfur proteins in six known Hg-methylating bacteria but were absent in nonmethylating bacteria. In two distantly related model Hg-methylating bacteria, deletion of either gene—or both genes simultaneously—reduced the ability for the bacteria to produce methylmercury but did not impair cellular growth. The presence of this two-gene cluster in several other bacterial and lineages for which genome sequences are available suggests the ability to produce methylmercury may be more broadly distributed in the microbial world than previously recognized. </jats:p>

<jats:title>Unusual Aggregates</jats:title> <jats:p> Several recent papers have revealed the unexpected genetic and pathological overlap between frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The most common genetic cause is the GGGGCC hexanucleotide repeat expansion upstream of the <jats:italic>C9orf72</jats:italic> coding region affecting about 10% of all patients. It is currently unknown how repeat expansion might lead to neurodegeneration. <jats:italic>C9orf72</jats:italic> patients show two distinct types of ubiquitinated inclusions in the central nervous system, one of which was identified as phosphorylated TDP-43 protein. However, all inclusions in the cerebellum and most inclusions in the hippocampus and neocortex lack TDP-43, and the actual disease protein is unknown. <jats:bold> Mori <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="6125" page="1335" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1232927">1335</jats:related-article> , published online 7 February; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6125" page="1282" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1236450">Taylor</jats:related-article> </jats:bold> ) discovered that most of these characteristic inclusions contain poly-(Gly-Ala) and, to a lesser extent, poly-(Gly-Pro) and poly-(Gly-Arg) dipeptide-repeat proteins that are generated by non-ATG–initiated translation from the expanded GGGGCC repeats in three reading frames. The findings yield mechanistic insight into the pathogenesis of FTLD/ALS with <jats:italic>C9orf72</jats:italic> repeat expansions and directly link this common mutation to the characteristic pathology. </jats:p>

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