Catálogo de publicaciones - revistas

<jats:title>How to model hallucinations in mice</jats:title> <jats:p> There has not been enough progress in our understanding of the basic mechanisms underlying psychosis. Studying psychotic disorders in animal models is difficult because the diagnosis relies on self-reported symptoms that can only be assessed in humans. Schmack <jats:italic>et al.</jats:italic> developed a paradigm to probe and rigorously measure experimentally controlled hallucinations in rodents (see the Perspective by Matamales). Using dopamine-sensor measurements and circuit and pharmacological manipulations, they demonstrated a brain circuit link between excessive dopamine and hallucination-like experience. This could potentially be useful as a translational model of common psychotic symptoms described in various psychiatric disorders. It may also help in the development of new therapeutic approaches based on anatomically selective modulation of dopamine function. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <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.abf4740">eabf4740</jats:related-article> ; see also p. <jats:related-article issue="6537" page="33" related-article-type="in-this-issue" vol="372">33</jats:related-article> </jats:p>

<jats:title>Resolving genomic structural variation</jats:title> <jats:p> Many human genomes have been reported using short-read technology, but it is difficult to resolve structural variants (SVs) using these data. These genomes thus lack comprehensive comparisons among individuals and populations. Ebert <jats:italic>et al.</jats:italic> used long-read structural variation calling across 64 human genomes representing diverse populations and developed new methods for variant discovery. This approach allowed the authors to increase the number of confirmed SVs and to describe the patterns of variation across populations. From this dataset, they identified quantitative trait loci affected by these SVs and determined how they may affect gene expression and potentially explain genome-wide association study hits. This information provides insights into patterns of normal human genetic variation and generates reference genomes that better represent the diversity of our species. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <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.abf7117">eabf7117</jats:related-article> </jats:p>

<jats:title>Integrating form and function for design</jats:title> <jats:p> Antibodies are broadly used in therapies and as research tools because they can be generated against a wide range of targets. Efficacy can often be increased by clustering antibodies in multivalent assemblies. Divine <jats:italic>et al.</jats:italic> designed antibody nanocages from two components: One is an antibody-binding homo-oligomic protein and the other is the antibody itself. Computationally designed proteins drive the assembly of antibody nanocages in a range of architectures, allowing control of the symmetry and the antibody valency. The multivalent display enhances antibody-dependent signaling, and nanocages displaying antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein effectively neutralize pseudovirus. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <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.abd9994">eabd9994</jats:related-article> </jats:p>

<jats:title>CAR-T cells rest to get back in the race</jats:title> <jats:p> Chimeric antigen receptor (CAR)–T cells, which are engineered to target specific tumor antigens, are increasingly used as an immunotherapy. CAR-T cells have shown promising results in patients, particularly in hematologic cancers, but their anticancer activity can be limited by the onset of exhaustion and the loss of effectiveness. Weber <jats:italic>et al.</jats:italic> characterized the phenotypic and epigenomic changes associated with CAR-T cell exhaustion caused by continuous activity and the beneficial effects of transient rest periods (see the Perspective by Mamonkin and Brenner). The authors tested different approaches for providing these rest periods, such as using the drug dasatinib to temporarily suppress T cell activity, which helped to prevent exhaustion and improved antitumor activity in mouse models. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <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.aba1786">eaba1786</jats:related-article> ; see also p. <jats:related-article issue="6537" page="34" related-article-type="in-this-issue" vol="372">34</jats:related-article> </jats:p>