Catálogo de publicaciones - revistas

<jats:title>Distinguishing Ciliopathy</jats:title> <jats:p> Cilia were once thought to be evolutionary remnants, but structural defects reveal their importance in signaling pathways and human disease, such as Joubert syndrome. Either of the genes <jats:italic>TMEM138</jats:italic> and <jats:italic>TMEM216</jats:italic> can be found mutated in phenotypically indistinguishable ciliopathy patients. Interestingly, despite their lack of sequence homology, these genes have always been aligned in head-to-tail configuration during vertebrate evolution. The proteins expressed by these genes mark distinct tethered vesicles, which differentially carry ciliary proteins for assembly. <jats:bold> Lee <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="966" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1213506">966</jats:related-article> , published online 26 January; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6071" page="930" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1219301"> <jats:bold>Chakravarti and Kapoor</jats:bold> </jats:related-article> ) show that the coordinated expression of these adjacent genes depends upon a coevolved regulatory element in the noncoding intergenic region, which thus integrates the roles of both gene products. This discovery explains not only the indistinguishable pathogenesis of the patients' genotypes but also how the evolutionary clustering of genes unrelated in sequence may correlate with coordinated control of expression and function. </jats:p>

<jats:title>Death for Development</jats:title> <jats:p> Cell death is critical for animal development and for the promotion of gastrulation, as well as for sculpting tissues. Although cell death by apoptosis is essential in some invertebrates, genes promoting apoptosis in the mouse are not required for viability. This surprising observation prompted investigations by <jats:bold> Blum <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="970" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1215156">970</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="6071" page="926" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1219834">Link and Saldi</jats:related-article> </jats:bold> ), who have discovered a nonapoptotic developmental cell death process mediated by a polyglutamine-repeat protein in the nematode worm <jats:italic>Caenorhabditis elegans</jats:italic> . This form of cell death is morphologically similar to cell death occurring during vertebrate development, particularly cell death accompanying polyglutamine-dependent neurodegeneration. </jats:p>

<jats:title>Networks of Networks</jats:title> <jats:p> Quantitative networks, such as those represented by food webs, have become an important way of investigating the structure of ecological communities, but thus far only encompass a small subset of species. <jats:bold> Pocock <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="973" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1214915">973</jats:related-article> ) have linked seven different types of ecological networks to form a network of networks. They found that although networks varied in their robustness to species loss, they did not strongly co-vary; that is, what happens to one network is unrelated to what happens to another. The networks studied were identified from an agroecosystem in the southwestern UK, a habitat in which biodiversity has suffered substantially. This study succeeded in revealing which species are potential targets for restoration of ecological function in this and other systems. </jats:p>

<jats:title>Piercing Botulinum's Defense</jats:title> <jats:p> Botulinum neurotoxins (BoNTs) are poisons that cause muscle paralysis. In the acidic intestine, ingested BoNTs are protected within a progenitor toxin complex. The toxins are released on absorption into the neutral bloodstream. <jats:bold> Gu <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="977" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1214270">977</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="6071" page="928" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1219602">Adler</jats:related-article> </jats:bold> ) present the structure of a minimally functional progenitor toxin complex—BoNT in complex with a nontoxic, nonhemagglutinin protein at 2.7 angstrom resolution. The structure, together with biochemical studies, showed how complex assembly is regulated by pH and may be useful in guiding the development of delivery vehicles for oral administration of biologics and in the design of inhibitors for oral BoNT poisoning. </jats:p>

<jats:title>A Fraction of Folding</jats:title> <jats:p> An energy barrier has to be crossed as a protein transforms between folded and unfolded states. Molecular dynamic simulations have observed sharp transitions, with barrier crossing times of less than a microsecond, a fraction of the total folding time; however, this time range has been inaccessible to single-molecule experiments. <jats:bold> Chung <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="981" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1215768">981</jats:related-article> ) described single-molecule fluorescence experiments that allowed measurement of the transition-path time for a fast-folding protein and to reduce the upper bound for a slow-folding protein. Although the folding rates differed by a factor of 10,000, the transition-path times differ by less than a factor of 5, pointing to energy landscape theory for the explanation. </jats:p>

<jats:title>Sound the Alarm</jats:title> <jats:p> When small protein fragments or nucleic acids derived from an invading pathogen are detected by pattern recognition receptors on immune cells, the innate immune response is triggered. This event activates cells of the adaptive immune system, and together, both responses clear the infection. Infections also induce the release of “danger-associated molecular patterns,” or alarmins, from the host as a result of tissue damage. Whether these are also important for the ensuing immune response is less clear. <jats:bold> Bonilla <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="984" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1215418">984</jats:related-article> , published online 2 February) report that the alarmin, interleukin-33, is required for optimal cytotoxic CD8 <jats:sup>+</jats:sup> T cells responses and antiviral immunity in mice. In virus-infected mice deficient in IL-33 or its receptor, IL-33 is essential for signaling CD8 <jats:sup>+</jats:sup> T cells to expand, produce multiple cytokines and acquire cytotoxic capabilities. These results showed that endogenous material, independently of pathogen-derived molecules, are also required for antiviral immunity. </jats:p>

<jats:title>Curbing the Other Side</jats:title> <jats:p> The two hemispheres of the brain are connected via the corpus callosum; however, this pathway and its function are still not fully understood. <jats:bold> Palmer <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="989" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1217276">989</jats:related-article> ) used a combination of optogenetic, calcium-imaging, and electrophysiological methods to investigate the cellular mechanism of interhemispheric inhibition of the firing frequency of neocortical layer 5 pyramidal neurons in rats in vivo and in vitro. They discovered that this form of inhibition involved interneurons in the top layers of the cortex that suppressed active dendritic currents synergistically recruited by back-propagating action potentials. This mechanism depended upon a γ-aminobutyric acid type B receptor–mediated mechanism acting on specific ion channels in the dendrites of pyramidal neurons. </jats:p>

<jats:p>Not long ago, a clinically relevant and genomics-based model of disease meant an animal, but today's models also include cell lines and even computer-based simulations. Still, bioengineered mice and rats make up many of the models, and these genetically modified organisms provide increasingly accurate representations of how drugs treat human diseases. To get the most from genomics-based models for drug research, scientists can now combine information from bioengineered organisms, genomically modified cell lines, and computational models.</jats:p>

<jats:p>The show includes restoring ecological "networks of networks," climate change and early horse evolution, the state of science in India, and more.</jats:p>

<jats:p>A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.</jats:p>