Catálogo de publicaciones - revistas

<jats:title>Genetic Clues to Meningioma</jats:title> <jats:p> Meningiomas are the most common primary brain tumors in adults. Located within the layer of tissue covering the brain, these tumors are usually slow-growing and benign but can cause serious neurological complications. About half of these tumors have mutations in the <jats:italic>neurofibromin 2</jats:italic> gene ( <jats:italic>NF2</jats:italic> ). To identify other genes that contribute to meningioma pathogenesis, <jats:bold> Clark <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="6123" page="1077" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1233009">1077</jats:related-article> , published online 24 January) performed genome sequence analysis on 300 tumors. Meningiomas fell into two general classes: benign tumors located at the skull base—which tend to harbor mutations in the <jats:italic>TRAF7, KLF4, AKT1</jats:italic> , and <jats:italic>SMO</jats:italic> genes—and higher-grade tumors located in the cerebral and cerebellar hemispheres harbor mutations in <jats:italic>NF2.</jats:italic> </jats:p>

<jats:title>Dissecting Disaggregation</jats:title> <jats:p> The excessive accumulation of misfolded protein aggregates can overwhelm the cell's "quality control" machinery, leading to cell death. The yeast Hsp104 protein and its bacterial homolog ClpB are molecular chaperones that can "rescue" aggregated proteins by coupling the force generated from adenosine triphosphate hydrolysis to the progressive unfolding and threading of extended polypeptide segments through axial channels in these large molecular machines. Unfolded polypeptides emerging from the channel are refolded with the aid of a second chaperone system, DnaK/DnaJ/GrpE. DnaK also plays an important role in bringing regions of polypeptides within aggregates to ClpB to begin the solubilization process. <jats:bold> Rosenzweig <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="6123" page="1080" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1233066">1080</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="6123" page="1040" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1236012">Saibil</jats:related-article> ) describe a nuclear magnetic resonance–derived structure of the ClpB-DnaK complex, and verified it through mutagenesis and functional assays. The work clarifies the roles of each of the molecular players in the disaggregation reaction and provides a structural basis for the DnaK-ClpB interaction. </jats:p>

<jats:title>Mighty Male Microbes</jats:title> <jats:p> Both genetic and environmental factors contribute to an individual's susceptibility to autoimmune disease, but the specific environmental influences are not well characterized. <jats:bold> Markle <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="6123" page="1084" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1233521">1084</jats:related-article> , published online 17 January; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6123" page="1044" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1236226"> <jats:bold> Flak <jats:italic>et al.</jats:italic> </jats:bold> </jats:related-article> ) explored how microbial factors, in particular the gut microbiota, influence susceptibility to type 1 diabetes in mice. In the non-obese diabetic (NOD) mouse model of type 1 diabetes, female mice are significantly more susceptible to disease than males; however, this difference was not apparent under germ-free conditions. Transfer of cecal contents from male NOD mice to female NOD mice prior to disease onset protected against pancreatic islet inflammation, autoantibody production, and the development of diabetes and was associated with increased testosterone in female mice. Blocking androgen receptor activity abrogated protection. Thus, the microbiota may be able to regulate sex hormones and influence an individual's susceptibility to autoimmunity. </jats:p>

<jats:title>A Role for IFN-ɛ</jats:title> <jats:p> Type I interferons (IFNs) are critical cytokines involved in host defense against pathogens, particularly viruses. IFN-ɛ is an IFN-like gene encoded within the type I IFN locus in mice and humans whose function has not been characterized. <jats:bold> Fung <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="6123" page="1088" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1233321">1088</jats:related-article> ) created mice with a genetic deletion in <jats:italic>Ifn</jats:italic> -ɛ and found that, like other type I IFNs, IFN-ɛ signals through the IFN-α receptors 1 and 2. However, unlike these other cytokines, which are primarily expressed by immune cells and are induced upon immune cell triggering, IFN-ɛ was expressed exclusively by epithelial cells of the female reproductive tract in both mice and humans and its expression was hormonally regulated. IFN-ɛ–deficient mice were more susceptible to infection with herpes simplex virus 2 and <jats:italic>Chlamydia muridarum</jats:italic> , two common sexually transmitted pathogens. </jats:p>

<jats:title>How Migraine Develops</jats:title> <jats:p> Migraine is a common medical disorder. Unfortunately, how and why migraine headache is initiated is unclear. <jats:bold> Karatas <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="6123" page="1092" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1231897">1092</jats:related-article> ) now describe a signaling pathway between stressed neurons and meningeal trigeminal afferents, which may explain how migraine headaches can be generated. </jats:p>

<jats:title>Double Whammy</jats:title> <jats:p> Psychopathologies that cannot be explained by simple genetic or environmental circumstances may sometimes result from complex interplay between multiple inputs. <jats:bold> Giovanoli <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="6123" page="1095" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1228261">1095</jats:related-article> ) analyzed the interactions between prenatal and postnatal stressors in mice to see what synergies give rise to psychopathologies in the adult mice. The results suggest that susceptibilities arise when mice are exposed to prenatal infection and also exposed to stressors around puberty. Stressors delivered later in adolescence did not seem to produce the same susceptibility. Although the mechanisms that impose the delay between stressors and psychopathology remain obscure, the timing and sequence of the triggers hint at possible cellular causes. </jats:p>

<jats:p>Science in India is on the move in a big way. The government has initiated multibillion dollar investments to kick start research, education, and innovation over the next five years. Though several challenging issues remain for the country, India's best and brightest expats living in the United States and Europe are being enticed back to 'Mother India' with the promise of world-class research infrastructure and solid funding.</jats:p>

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