Catálogo de publicaciones - revistas

<jats:title>Cryo-EM helps engineer enhanced IL-10</jats:title> <jats:p> Interleukin-10 (IL-10) binds to the IL-10 receptor (IL-10R), comprising two high-affinity α chains and two low-affinity β chains. Depending on the cellular context of its recognition, IL-10 can either suppress or activate immune responses. This pleiotropic behavior has complicated efforts to use IL-10 as an anti-inflammatory agent. Saxton <jats:italic>et al.</jats:italic> generated a high-affinity version of IL-10 (super-10), which allowed them to visualize IL-10 in complex with both IL-10Rα and IL-10Rβ by cryo–electron microscopy (cryo-EM). This enabled them to engineer additional variants of IL-10 with variable IL-10Rβ–binding affinities. Some of the partial agonists exhibited biased actions on myeloid cells, which exhibited anti-inflammatory properties without concomitant CD8 T cell activation. These findings may serve as a blueprint for future enhanced cytokine–based therapeutics. </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.abc8433">eabc8433</jats:related-article> </jats:p>

<jats:title>Satellite monitoring of development</jats:title> <jats:p> Recent years have witnessed rapid growth in satellite-based approaches to quantifying aspects of land use, especially those monitoring the outcomes of sustainable development programs. Burke <jats:italic>et al.</jats:italic> reviewed this recent progress with a particular focus on machine-learning approaches and artificial intelligence methods. Drawing on examples mostly from Africa, they conclude that satellite-based methods enhance rather than replace ground-based data collection, and progress depends on a combined approach. </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.abe8628">eabe8628</jats:related-article> </jats:p>

<jats:title>Eradicating the last vestiges of HIV</jats:title> <jats:p> After treatment with antiretroviral therapy, HIV-1 wild-type and escape variants can persist in a latent form, especially within CD4 <jats:sup>+</jats:sup> T cells, hindering efforts to eradicate the virus. Q. Wang <jats:italic>et al.</jats:italic> found that human CARD8, a member of the caspase recruitment domain (CARD)–containing family of innate immune sensors, is activatable by direct proteolysis of its N-terminus by HIV-1 protease. This cleavage should result in the programmed cell death of infected cells, but HIV-1 protease remains inactive and undetected as a subunit of the unprocessed Gag-Pol polyprotein. However, when infected cells were treated with non-nucleoside reverse transcriptase inhibitors, intracellular Gag-Pol dimerization was enhanced, resulting in CARD8-mediated caspase activation and pyroptosis. Targeting this pathway may be a promising way to eliminate residual HIV-1 in patients. </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.abe1707">eabe1707</jats:related-article> </jats:p>

<jats:title>Atomic structure of the minor spliceosome</jats:title> <jats:p> About 1% of the human genome contains the so-called U12-type introns, which are spliced by the minor spliceosome. Compared with the major spliceosome, the composition, assembly, functional states, activation, regulation, and structure of the minor spliceosome have been enigmatic. Bai <jats:italic>et al.</jats:italic> assembled the activated human minor spliceosome in an in vitro U12-type intron-splicing assay and determined the structure by cryo–electron microscopy at 2.9-angstrom resolution. They found a number of exciting and unanticipated features, including five new proteins that play an important role in the activated minor spliceosome. </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.abg0879">eabg0879</jats:related-article> </jats:p>

<jats:title>γδ T cells link immunity to nutrition</jats:title> <jats:p> Gamma delta (γδ) T cells are immune cells best known for host barrier defenses in epithelial tissues. Sullivan <jats:italic>et al.</jats:italic> discovered a previously unrecognized role for γδ T cells in sensing nutrient uptake in the small intestine (see the Perspective by Talbot and Littman). The researchers analyzed mice fed a high-carbohydrate versus a high-protein diet and observed remodeling of the small intestinal epithelium in response to dietary carbohydrates. Nutrient availability triggered an epithelial–immune cell circuit that was required for digestion and absorption of carbohydrates. Intestinal γδ T cells regulated the expression of a carbohydrate transcriptional program by limiting interleukin-22 production from type 3 innate lymphoid cells. These findings may also provide insights into how γδ T cells modulate metabolic disease. </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.aba8310">eaba8310</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6535" page="1202" related-article-type="in-this-issue" vol="371" xlink:href="10.1126/science.abg6455">1202</jats:related-article> </jats:p>

<jats:title>Keeping cGAS silent</jats:title> <jats:p> Cells detect microbial and self-DNA in the cytosol as a danger signal that triggers immune and inflammatory responses. Paradoxically, a large fraction of a DNA-sensing enzyme called cGAS is tightly associated with the chromatin, especially during mitosis. Li <jats:italic>et al.</jats:italic> uncovered two mechanisms that prevent cGAS from being activated by the chromatin DNA (see the Perspective by Ablasser). First, cGAS is hyperphosphorylated as cells enter mitosis, thereby inhibiting its DNA-binding and liquid-liquid phase separation, which promotes cGAS activation. Second, chromatin-bound cGAS is unable to oligomerize, a process required for its activation. Together, these mechanisms ensure cGAS inactivation during cell division to prevent autoimmune reactions. </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.abc5386">eabc5386</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6535" page="1204" related-article-type="in-this-issue" vol="371" xlink:href="10.1126/science.abg7422">1204</jats:related-article> </jats:p>

<jats:p>As countries grow eager to reignite their economies and people increasingly yearn for mobility and normalcy in life, pressure is mounting for some form of COVID-19 health status certificate that would support these desires. There has already been an explosion of COVID-19 passport initiatives for domestic use and international travel. But scientific, legal, and ethical concerns abound with such documentation. Given the high stakes, what is the path forward?</jats:p>

<jats:p> Walter Isaacson, one of America's foremost biographers, recently told me that he sees three fundamental units as the cornerstones of 20th-century innovation: the bit, the atom, and the gene. Having written about Steve Jobs and Albert Einstein—embodiments of the first two—in previous works, in his latest book, <jats:italic>The Code Breaker</jats:italic> , reviewed in this issue of <jats:italic>Science</jats:italic> (see page 1213), Isaacson's focus turns to the gene. His story centers on the life of biochemist Jennifer Doudna, who, together with Emmanuelle Charpentier, won the 2020 Nobel Prize in Chemistry for their pioneering work on the gene editing technology known as CRISPR-Cas9. The book is an extraordinarily detailed and revealing account of scientific progress and competition that grants readers behind-the-scenes access to the scientific process, which the COVID-19 pandemic has taught us remains opaque to the wider public. It also provides lessons in science communication that go beyond the story itself. </jats:p>

<jats:p>A roundup of weekly science policy and related news.</jats:p>