Catálogo de publicaciones - revistas

<jats:title>Insights into Amyloidogenesis</jats:title> <jats:p> The amyloid-β (Aβ) peptides associated with Alzheimer's disease are generated by cleavage of the transmembrane C-terminal domain (C99) of the amyloid precursor protein by the enzyme γ-secretase. <jats:bold> Barrett <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="1168" related-article-type="in-this-issue" vol="336" xlink:href="10.1126/science.1219988">1168</jats:related-article> ) used nuclear magnetic resonance (NMR) and electron paramagnetic resonance spectroscopy to show that C99 contains surface-associated N- and C-terminal helices and a flexibly curved transmembrane helix that is well suited to processive cleavage by γ-secretase. Elevated cholesterol levels have been found to increase Aβ generation. NMR titration together with mutagenesis revealed a binding site for cholesterol within C99 that included a motif previously implicated in protein oligomerization. </jats:p>

<jats:title>Design and Build</jats:title> <jats:p> Self-assembling biomolecules are attractive building blocks in the development of functional materials. Sophisticated DNA-based materials have been developed; however, progress in designing protein-based materials has been slower. <jats:bold> King <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="1171" related-article-type="in-this-issue" vol="336" xlink:href="10.1126/science.1219364">1171</jats:related-article> ) describe a general computational method in which protein building blocks are first symmetrically docked onto a target architecture, and then binding interfaces that drive self-assembly of the building blocks are designed. As a proof of principle, trimeric building blocks were used to design self-assembling 12-subunit complexes with tetrahedral symmetry and 24-subunit complexes with octahedral symmetry. <jats:bold> Lai <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="1129" related-article-type="in-this-issue" vol="336" xlink:href="10.1126/science.1219351">1129</jats:related-article> ) were able to build a 12-subunit tetrahedral protein cage from fused oligomeric protein domains. </jats:p>

<jats:title>Predicting Catastrophic Collapse</jats:title> <jats:p> It is very difficult to predict the behavior of complex systems near tipping points, where a small change in conditions can lead to a large shift in the state of the system. Theory predicts that some generic statistical indicators can signal the approach of such tipping points, such as slower recoveries from perturbations of the system—a phenomenon called critical slowing down. Working with laboratory yeast populations, <jats:bold> Dai <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="1175" related-article-type="in-this-issue" vol="336" xlink:href="10.1126/science.1219805">1175</jats:related-article> ) provide an experimental measure for critical slowing down before catastrophic population collapse. This type of approach should help when trying to predict catastrophic thresholds in other complex systems, ranging from ecosystem transition to climate change, and even to crashes of financial markets. </jats:p>

<jats:title>So Selective</jats:title> <jats:p> The key elements for long-lived antibody-mediated immunity—memory B cells and plasmablasts—are generated in germinal centers, where B cells expressing high-affinity antigen receptors are selected for survival and proliferation in a process called affinity maturation. Unexpectedly, <jats:bold> Khalil <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="1178" related-article-type="in-this-issue" vol="336" xlink:href="10.1126/science.1213368">1178</jats:related-article> , published online 3 May; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6085" page="1120" related-article-type="in-this-issue" vol="336" xlink:href="10.1126/science.1223811"> <jats:bold>Bannard and Cyster</jats:bold> </jats:related-article> ) found that, in contrast to naïve B cells and B cells outside the germinal center, proximal signaling events are impaired downstream of the antigen receptor in mouse germinal center B cells. </jats:p>

<jats:title>Regaining Limb Movement</jats:title> <jats:p> Despite many years of intensive research, there is still an urgent need for novel treatments to help patients restore motor function after spinal cord injuries. <jats:bold> van den Brand <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="1182" related-article-type="in-this-issue" vol="336" xlink:href="10.1126/science.1217416">1182</jats:related-article> ) produced left and right hemisections at different levels of the rat thoracic spinal cord to cause complete hind limb paralysis mimicking the situation in humans with spinal cord injury. Systemic application of pharmacological agents, combined with a multisystem rehabilitation program including a robotic postural neuroprosthesis, restored voluntary movements of both hind limbs. </jats:p>

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