Catálogo de publicaciones - revistas

<jats:title>Observing Protein Dynamics</jats:title> <jats:p> Following the dynamics of protein conformational changes over the relatively long periods of time typical of enzyme kinetics can be challenging. <jats:bold> Choi <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="319" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1214824">319</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="6066" page="300" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1217170">Lu</jats:related-article> </jats:bold> ) were able to observe changes in lysozyme conformation, which changes its electrostatic potential, by using a carbon-nanotube field-effect transistor. Slower hydrolysis steps were compared with faster, but unproductive, hinge motion, and changes in lysozyme activity that occur with pH were shown to arise from differences in the relative amount of time spent in processive versus nonprocessive states. </jats:p>

<jats:title>Star Grazing</jats:title> <jats:p> Some comets come perilously close to the Sun. <jats:bold> Schrijver <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="324" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1211688">324</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="6066" page="296" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1217168">Lisse</jats:related-article> </jats:bold> ) describe observations made by the Solar Dynamics Observatory of one such Sun-grazing comet, which penetrated into, fragmented, and completely sublimated within the solar atmosphere. More than 2000 Sun-grazing comets have been observed in the past 15 years but none could be followed into the Sun's atmosphere. By showing that comets can be observed at such small distances from the Sun, this study opens up new ways to study comets and also the solar atmosphere. </jats:p>

<jats:title>Dynamic Replication</jats:title> <jats:p> In all organisms, DNA replication involves a multiprotein complex called the replisome. Active <jats:italic>Escherichia coli</jats:italic> replisomes contain three copies of DNA polymerase III (Pol III). <jats:bold> Lia <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="328" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1210400">328</jats:related-article> , published online 22 December) used single-molecule spectroscopy to probe the dynamics of single proteins during <jats:italic>E. coli</jats:italic> replication in vivo. The results confirmed the presence of three Pol III molecules in the active replisome, with regular exchange of one of these Pol III's with one from the pool. Coordination with single-stranded DNA content suggests the Pol III that performs lagging-strand synthesis is exchanged so that a new Pol III is used for the synthesis of each Okazaki fragment. </jats:p>

<jats:title>Shunning Shiga</jats:title> <jats:p> Infection with bacteria harboring Shiga toxin is responsible for more than 1 million deaths annually worldwide. Antidotes for the toxin are not available, and treatment with antibiotics is contraindicated because it increases the risk of toxin release (from dead bacteria) and leads to severe forms of the disease. Manganese is an essential nutrient and its toxicology in humans is well studied; it inhibits the normal trafficking of Shiga toxin in tissue culture cells. <jats:bold>Mukhopadhyay and Linstedt</jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="332" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1215930">332</jats:related-article> ) found that levels of Mn <jats:sup>2+</jats:sup> that caused no deleterious effects to normal cellular processes nevertheless altered intracellular trafficking of Shiga toxin so that it was degraded in lysosomes. This conferred very high levels of protection of cultured cells against toxin-induced death and made mice completely resistant to Shiga toxin–induced paralysis and death. </jats:p>

<jats:title>Trick of the Eye of the Beholder</jats:title> <jats:p> Male bowerbirds build elaborate bowers, or display areas, that consist of an avenue where the female stands and an arena where the male displays. Males decorate their arenas meticulously with stones, flowers, and found objects. Previous work has shown that these bowers induce forced perspective illusions in the observing females. Now <jats:bold>Kelley and Endler</jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="335" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1212443">335</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="6066" page="292" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1217451">Anderson</jats:related-article> </jats:bold> ) show that mating success is based on components of the illusion, rather than the physical nature of the bower. Thus, females choose their mates based on a visual illusion painstakingly constructed and maintained by the displaying male. </jats:p>

<jats:title>Stochastic or Asymmetric Fate Determination?</jats:title> <jats:p> During an adaptive immune response, B lymphocytes rapidly divide and differentiate into effector cell populations, including antibody-secreting plasmablasts and memory B cells. Many also change the class of antibody they secrete, through a process called isotype switching. During this process, some cells die. Whether cells acquire these different fates in a stochastic or programmed manner, however, is unclear. <jats:bold> Duffy <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="338" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1213230">338</jats:related-article> , published online 5 January) used single-cell tracking to determine the times to division, differentiation into a plasmablast, isotype switching, and death of stimulated B lymphocytes. Statistical analysis and mathematical modeling revealed that these cell-fate decisions appear to be the result of random clocks: Which clock went off first (division, differentiation, or death), determined the fate of the cell. <jats:bold> Barnett <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="342" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1213495">342</jats:related-article> , published online 15 December) sought to determine whether asymmetrical cell division, which is thought to contribute to effector cell-fate decisions in T cells, may be at work in B lymphocytes. Indeed, factors important for the initiation and maintenance of germinal center B lymphocyte identity, along with an ancestral polarity protein, were asymmetrically distributed and maintained their asymmetry during cell division. </jats:p>

<jats:title>Stochastic or Asymmetric Fate Determination?</jats:title> <jats:p> During an adaptive immune response, B lymphocytes rapidly divide and differentiate into effector cell populations, including antibody-secreting plasmablasts and memory B cells. Many also change the class of antibody they secrete, through a process called isotype switching. During this process, some cells die. Whether cells acquire these different fates in a stochastic or programmed manner, however, is unclear. <jats:bold> Duffy <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="338" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1213230">338</jats:related-article> , published online 5 January) used single-cell tracking to determine the times to division, differentiation into a plasmablast, isotype switching, and death of stimulated B lymphocytes. Statistical analysis and mathematical modeling revealed that these cell-fate decisions appear to be the result of random clocks: Which clock went off first (division, differentiation, or death), determined the fate of the cell. <jats:bold> Barnett <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="342" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1213495">342</jats:related-article> , published online 15 December) sought to determine whether asymmetrical cell division, which is thought to contribute to effector cell-fate decisions in T cells, may be at work in B lymphocytes. Indeed, factors important for the initiation and maintenance of germinal center B lymphocyte identity, along with an ancestral polarity protein, were asymmetrically distributed and maintained their asymmetry during cell division. </jats:p>

<jats:title>Natural Killer Controls</jats:title> <jats:p> Cytolytic natural killer (NK) cells participate in both antimicrobial and antitumor immunity. Their responsiveness is tuned through signals received through a variety of inhibitory and activating receptors expressed on their cell surface. <jats:bold> Narni-Mancinelli <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="344" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1215621">344</jats:related-article> ) now show that signaling through the activating receptor NKp46 paradoxically keeps NK cell responses in check. NK cells from mice with disrupted NKp46 expression were hyperresponsive to stimulation and better protected against viral infection. NK cell responses, which are part of the early response to infection, may thus need to be carefully tuned to ensure optimal initiation of adaptive immunity and formation of protective long-lived memory cells. </jats:p>

<jats:title>Taking the Myc</jats:title> <jats:p> Despite nearly 30 years of research into the mechanisms by which Myc oncogene dysregulation contributes to tumorigenesis, there are still no effective therapies that inhibit Myc activity. <jats:bold> Kessler <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="348" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1212728">348</jats:related-article> , published online 8 December; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6066" page="293" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1217819">Evan</jats:related-article> </jats:bold> ) searched for gene products that support Myc-driven tumorigenesis. One pharmacologically tractable target that emerged from the screen was the SUMO-activating enzyme complex SAE1/2, which catalyzes a posttranslational modification (SUMOylation) that alters protein behavior and function. SUMOylation was found to control the Myc transcriptional response, and its inhibition caused mitotic defects and apoptosis in Myc-dependent breast cancer cells. </jats:p>

<jats:title>Coordinating Synapses</jats:title> <jats:p> Cortical microcircuits produce cell assemblies that emit spatiotemporally orchestrated spiking activity. These activity patterns are decoded by the dendrites of downstream neurons. Whether synaptic inputs are clustered or dispersed over target dendrites at a given time is critical for determining dendritic computational power. However, such subcellular dynamics are poorly understood. In rodent organotypic slice cultures, <jats:bold> Takahashi <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="353" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1210362">353</jats:related-article> ) found that dendritic spine activities were frequently synchronized within a group of spines in the immediate vicinity of one another. This local synchronization seems to reflect convergent synaptic inputs from intrinsically synchronized presynaptic neuron populations. </jats:p>