Catálogo de publicaciones - revistas

<jats:title>Plasmid Partitioning</jats:title> <jats:p> Bacterial plasmids need to be able to partition faithfully into daughter cells. Combining structural data and advanced microscopy, <jats:bold> Gayathri <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="1334" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1229091">1334</jats:related-article> , published online 25 October; see the cover) describe how actin-like ParM filaments form a bipolar spindle for the faithful segregation of low-copy-number plasmids to the two cell poles of <jats:italic>Escherichia coli</jats:italic> , despite being polar, with two distinct ends. ParM filaments are elongated by a small adaptor protein ParR that physically links the filament end(s) to a centromere-like region on the plasmid. Antiparallel filament bundling and sliding appear to produce a bipolar spindle made of filaments that elongate unidirectionally so that all the plasmids are segregated together in one large bundle. </jats:p>

<jats:title>Dissecting Wnt Signaling</jats:title> <jats:p> The Wnt signaling pathway plays a key role in regulating a broad range of functions from development to cancer. But a precise understanding of how Wnt proteins act through their receptors (Frizzled proteins) has been elusive. By paring the system down to its core reactions and performing kinetic analysis in cultured cells, <jats:bold> Hernández <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="1337" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1228734">1337</jats:related-article> , published online 8 November) were able to deduce the mechanism of Wnt action without invoking any previous assumptions. Such quantitative analysis of mass balance may offer a way to identify essential control points in other complicated signaling systems, and thus help define targets for therapeutic intervention. </jats:p>

<jats:title>Seeing the Light</jats:title> <jats:p> Rhodopsins respond to a range of electromagnetic radiation—allowing visual perception over a broad wavelength range in animals and facilitating light-driven ion transport and phototaxis in microorganisms. All rhodopsins contain an embedded retinal chromophore in which absorbance is tuned by the protein environment. To gain insight into how the protein tunes absorbance, <jats:bold> Wang <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="1340" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1226135">1340</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6112" page="1299" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1231589">Sakmar</jats:related-article> </jats:bold> ) turned to a smaller soluble protein, cellular retinol binding protein II. They engineered the protein to fully encapsulate and covalently bind all- <jats:italic>trans</jats:italic> -retinal as a Schiff base. From this starting point, they used rational mutagenesis to vary the absorption maximum over a range of more than 200 nanometers by altering the electrostatic environment of the protein-binding pocket. </jats:p>

<jats:title>Sewing Up DNA Repair</jats:title> <jats:p> All cells have a battery of DNA-repair pathways to help ensure genome maintenance and stability, including stress-induced DNA break repair in <jats:italic>Escherichia coli.</jats:italic> Similar pathways—which can be mutagenic—are known in yeast and human cells and have the potential to accelerate evolution. Sixteen proteins are known to be required for the pathway in <jats:italic>E. coli.</jats:italic> <jats:bold> Al Mamun <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="1344" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1226683">1344</jats:related-article> ) analyzed the <jats:italic>E. coli</jats:italic> pathway to determine the full complement of protein contributions to the pathway. Ninety-three genes were found to be required for stress-induced DNA break repair. One-third of the proteins identified in the network were involved in electron transfer, functioning in oxidative phosphorylation, and acting through the σ <jats:sup>s</jats:sup> stress response pathway, which thus represents a critical hub in the network. </jats:p>

<jats:title>Platelets Poison Parasites</jats:title> <jats:p> Activated platelets bound to malaria parasite–infected red blood cells were once thought to contribute to pathogenesis, but recently the platelets have been found to have a protective effect. <jats:bold> McMorran <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="1348" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1228892">1348</jats:related-article> ; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6112" page="1304" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1232439">Engwerda and Good</jats:related-article> ) extended this discovery to show that platelet activation releases intracellular granules containing a chemokine, PF4, which is internalized by <jats:italic>Plasmodium falciparum</jats:italic> –infected red cells. Subsequently, mature parasites within the cells die. The Duffy blood-group factor on red blood cells is known to act as a nonspecific receptor for chemokines, such as PF4, as well as a receptor for cell invasion by other species of malaria parasite. When the Duffy antigen was blocked by antibody treatment, platelets and PF4 were less able to kill the <jats:italic>P. falciparum</jats:italic> parasites within. </jats:p>

<jats:title>Awakening a Life Cycle</jats:title> <jats:p> Sleeping sickness continues to afflict populations in sub-Saharan Africa, but for the past 100 years, research on the <jats:italic>Trypanosoma brucei</jats:italic> protozoan parasite has been hampered by an inaccessibility of the insect vector stages to modern research tools. <jats:bold> Kolev <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="1352" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1229641">1352</jats:related-article> ) have identified an RNA-binding protein (RBP6) as a master regulator that drives the entire developmental program of the trypanosome through all its life-cycle stages. The ability to perform this transformation in vitro will allow study of the many biochemical and morphological changes as parasites change from dividing noninfectious forms to infectious nondividing antigenically variable forms. </jats:p>

<jats:title>The Good Side of Inflammation</jats:title> <jats:p> The zebrafish brain is much more adept than the human brain at recovering after traumatic injury. <jats:bold> Kyritsis <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="1353" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1228773">1353</jats:related-article> , published online 8 November; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6112" page="1303" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1232331">Stella</jats:related-article> </jats:bold> ) investigated the cellular events that support regeneration in the zebrafish brain. Although inflammation is part of the response in both settings, the zebrafish brain goes on to initiate proliferation of replacement neurons. By inciting inflammation without neuronal damage, radial glial cells could be pushed into neurogenesis. </jats:p>

<jats:title>Androgen-Driven Sequestration</jats:title> <jats:p> Male and female mice differ in the neuronal patterns that serve the mammary glands. <jats:bold> Yin Liu <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="1357" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1228258">1357</jats:related-article> ) now describe how gonadal hormones drive development of distinct male and female sensory innervations. Although both male and female mammary glands develop their sensory innervation similarly in early embryogenesis, once the androgens take effect, the developmental trajectories diverge. By birth, the rich network of sensory neurons present in the female is absent in the male. Androgens cause a switch from expression of the full-length neurotrophin receptor TrkB to its truncated form, TrkB.T1, both of which are expressed on the neurons. In males, truncated TrkB.T1 sequesters brain-derived neurotrophic factor (BDNF) from further activity, whereas in females, full-length TrkB binds BDNF and supports neuronal development. </jats:p>

<jats:title>From Man to Mouse</jats:title> <jats:p> Genome-wide association studies of humans have identified single-nucleotide polymorphisms (SNPs) that increase an individual's risk of developing common diseases like cancer. Most of these SNPs have only a modest effect on risk, and many map to noncoding regions of the genome. <jats:bold> Sur <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="1360" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1228606">1360</jats:related-article> , published online 1 November; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6112" page="1301" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1231733">Lewis and Tomlinson</jats:related-article> ) used a mouse model to study the functional impact of a particular SNP that resides 300 kilobases upstream of the <jats:italic>MYC</jats:italic> oncogene on human chromosome 8q24 and has been linked to cancer risk in humans. When a sequence encompassing this SNP was deleted in mice that were predisposed to develop intestinal tumors, the mice displayed fewer tumors than control mice. This SNP may thus play a causal role in human cancer, presumably through altered regulation of <jats:italic>MYC.</jats:italic> </jats:p>

<jats:title>Swapping Recombination Proteins</jats:title> <jats:p> Crossing over is a means by which organisms create genetic diversity through the mixing of gene complexes. The primary meiotic crossover pathway in budding yeast, mice, nematodes, and plants requires the Msh4–Msh5 heterodimer, which promotes crossovers by blocking anticrossover activities of the Bloom syndrome helicase. However, some fly species, including members of the genus <jats:italic>Drosophila</jats:italic> , have lost Msh4–Msh5. <jats:bold> Kohl <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="1363" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1228190">1363</jats:related-article> ) now show that <jats:italic>Drosophila</jats:italic> have evolved a minichromosome maintenance (MCM)–like protein, dubbed mei-MCM, that performs the same function as Msh4–Msh5. Furthermore, these genes appear to have evolved under positive selection, possibly as a result of their repurposing to this novel function. </jats:p>