Catálogo de publicaciones - revistas

<jats:p>Human bestrophin-1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where mutations are associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a sensitive control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activation by mutations at the cytoplasmic exit. A homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.</jats:p>

<jats:p> The conserved heat shock transcription factor–1 (HSF-1) is essential to cellular stress resistance and life-span determination. The canonical function of HSF-1 is to regulate a network of genes encoding molecular chaperones that protect proteins from damage caused by extrinsic environmental stress or intrinsic age-related deterioration. In <jats:italic>Caenorhabditis elegans</jats:italic> , we engineered a modified HSF-1 strain that increased stress resistance and longevity without enhanced chaperone induction. This health assurance acted through the regulation of the calcium-binding protein PAT-10. Loss of <jats:italic>pat-10</jats:italic> caused a collapse of the actin cytoskeleton, stress resistance, and life span. Furthermore, overexpression of <jats:italic>pat-10</jats:italic> increased actin filament stability, thermotolerance, and longevity, indicating that in addition to chaperone regulation, HSF-1 has a prominent role in cytoskeletal integrity, ensuring cellular function during stress and aging. </jats:p>

<jats:p> T cells that mediate autoimmune diseases such as rheumatoid arthritis (RA) are difficult to characterize because they are likely to be deleted or inactivated in the thymus if the self antigens they recognize are ubiquitously expressed. One way to obtain and analyze these autoimmune T cells is to alter T cell receptor (TCR) signaling in developing T cells to change their sensitivity to thymic negative selection, thereby allowing their thymic production. From mice thus engineered to generate T cells mediating autoimmune arthritis, we isolated arthritogenic TCRs and characterized the self antigens they recognized. One of them was the ubiquitously expressed 60 <jats:italic>S</jats:italic> ribosomal protein L23a (RPL23A), with which T cells and autoantibodies from RA patients reacted. This strategy may improve our understanding of the underlying drivers of autoimmunity. </jats:p>

<jats:p>This webinar is the first in a series focusing on the pathways that allow for cancer development and progression, the emerging research in identifying and targeting these pathways, and the innovations in the development of cancer treatment options. Recent advances in our understanding of cancer have revealed that the disease cannot be understood through simple analysis of genetic mutations within cancerous cells. Instead, tumors should be considered complex tissues in which the cancer cells evolve and communicate with the surrounding cellular microenvironment to promote their own survival and dissemination. Although therapies against specific signaling proteins or pathways have been remarkably successful at treating certain cancers, the tumors frequently develop resistance, leading to even more aggressive forms of the disease.</jats:p> <jats:p>This webinar will focus on how rewiring of signaling pathways in response to drug treatment contributes to resistance and how this knowledge can be leveraged to develop more effective treatment strategies.</jats:p>

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

<jats:p>On this week's show: Connecting carnivores with plants and a daily news roundup.</jats:p>

<jats:p>First-in-class drugs and drought-resistant seeds may not seem to have much in common but the transformative technologies being developed to produce these game-changing products do. At the heart of those discoveries are the companies, identified by the 2014 Science Careers Top Employer Survey, that foster a spirit of innovation. These 20 biotechnology and pharmaceutical companies have their eyes on transformative prizes and invest in the intellectual capital needed to get there. From encouraging risky research to bolstering academic collaborations, keeping employees engaged and excited about their research is priority number one.</jats:p>

<jats:title>How to stop after copying the genome</jats:title> <jats:p> Replication is highly regulated: Failure to copy any part of the genome or copying parts of it more than once can cause genome instability with potentially disastrous consequences. Maric <jats:italic>et al.</jats:italic> and Priego Moreno <jats:italic>et al.</jats:italic> show that the DNA replication machinery, which stably encircles DNA during the duplication process, is actively disassembled once replication is complete (see the Perspective by Bell). The protein ring encircling the DNA is covalently modified, which allows it to be opened and the whole replication complex to be removed from DNA by a special disassembly complex. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" related-article-type="in-this-issue" xlink:href="10.1126/science.1253596">10.1126/science.1253596</jats:related-article> , p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6208" page="477" related-article-type="in-this-issue" vol="346" xlink:href="10.1126/science.1253585">477</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6208" page="418" related-article-type="in-this-issue" vol="346" xlink:href="10.1126/science.1261245">418</jats:related-article> </jats:p>

<jats:title>Experimental platforms for probing bacteria</jats:title> <jats:p>Bacteria respond to a host of changing cues provided by their environment. Hol and Dekker review how microfluidic and nanofabricated devices can provide a platform to deliver different stimuli in a variety of environments. Bacterial quorum sensing and electron transport are among the problems that can be studied in this way.</jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" related-article-type="in-this-issue" xlink:href="10.1126/science.1251821">10.1126/science.1251821</jats:related-article> </jats:p>