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<jats:title>Jump starting pathogen evolution</jats:title> <jats:p> Mycobacteria are mostly environmental saprotrophs, but during human history, some have become our pathogens. In the past 50 years or so, intractable and virulent infections of <jats:italic>Mycobacterium abscessus</jats:italic> have emerged in people with cystic fibrosis. Bryant <jats:italic>et al.</jats:italic> investigated how these mycobacteria have evolved into human pathogens so quickly (see the Perspective by Brugha and Spencer). Chronic infections in the lung offer plenty of evolutionary scope for the emergence of virulent clones after horizontal gene transfer and hypermutation. Pathogens are acquired by environmental contamination, which leaves open a window for clinical control because the most virulent clones survive poorly outside the body. Therefore, immediate treatment and enhanced infection-control measures for <jats:italic>M. abscessus</jats:italic> cases could reduce opportunities for the evolution of direct person-to-person transmission. </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.abb8699">eabb8699</jats:related-article> ; see also p. <jats:related-article issue="6541" page="465" related-article-type="in-this-issue" vol="372">465</jats:related-article> </jats:p>

<jats:title>Viral peptide is key to T cell priming</jats:title> <jats:p> Simian immunodeficiency virus (SIV) vaccines containing a strain 68-1 rhesus cytomegalovirus (RhCMV) vector elicit strong CD8 <jats:sup>+</jats:sup> T cell responses that can control and clear SIV infections. The SIV peptides targeted by these T cells are presented on major histocompatibility complex (MHC) II and the nonclassical MHC-Ib molecule MHC-E rather than the more typical MHC-Ia. Verweij <jats:italic>et al.</jats:italic> show that the 68-1 RhCMV–encoded peptide VL9 drives intracellular transport of MHC-E and recognition of RhCMV-infected targets by MHC-E–restricted CD8 <jats:sup>+</jats:sup> T cells. Rhesus macaques vaccinated with a mutant 68-1 RhCMV lacking VL9 showed no priming of MHC-E–restricted CD8 <jats:sup>+</jats:sup> T cells and no protection against SIV. This work strongly suggests that future effective CMV-based HIV vaccines in humans will also require MHC-E–restricted CD8 <jats:sup>+</jats:sup> T cell priming. </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.abe9233">eabe9233</jats:related-article> </jats:p>

<jats:title>Small RNAs guard CRISPR-Cas</jats:title> <jats:p> The microbial adaptive immunity system CRISPR-Cas benefits microbes by warding off genetic invaders, but it also inflicts a fitness cost because of occasional autoimmune reactions, rendering CRISPR loci evolutionarily unstable. Li <jats:italic>et al.</jats:italic> identified previously unnoticed toxin-antitoxin RNA pairs embedded within diverse CRISPR-Cas loci. The antitoxin RNA mimics a CRISPR RNA and repurposes the CRISPR immunity effector to transcriptionally repress a toxin RNA that would otherwise arrest cell growth by sequestering a rare transfer RNA. These small RNAs thus form a symbiosis with CRISPR, rendering CRISPR addictive to the host despite its fitness cost. These findings reveal how CRISPR-Cas can operate as a selfish genetic element. </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.abe5601">eabe5601</jats:related-article> </jats:p>

<jats:title>Assembling for transcription initiation</jats:title> <jats:p> Eukaryotic transcription initiation by RNA polymerase II (Pol II) requires the assembly of a preinitiation complex (PIC) on core promoters. The binding of TATA box–binding protein (TBP) to the TATA box promoter has been thought to be a general rule in PIC assembly and transcription initiation. However, most coding genes lack a TATA box, and nearly all Pol II–mediated gene transcription requires the TBP-containing multisubunit complex transcription factor IID (TFIID). Chen <jats:italic>et al.</jats:italic> determined the structures of human TFIID-based PIC in sequential assembly states and revealed that TFIID supports distinct PIC assembly on TATA-containing and TATA-lacking promoters. The finding resolves the long-standing mystery of how one set of general transcription machinery initiates transcription on diverse promoters. </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.aba8490">eaba8490</jats:related-article> </jats:p>

<jats:title>The daily rhythms of agriculture</jats:title> <jats:p> Sunlight drives agriculture, and plant circadian rhythms tune the plant's response to daily light-dark cycles. Steed <jats:italic>et al.</jats:italic> discuss how agricultural productivity might be improved by consideration of how the plant's circadian rhythm alters plant responses to the challenges posed by its environment. </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.abc9141">eabc9141</jats:related-article> </jats:p>

<jats:p>One key way that many governments around the world incorporate scientific research into policy-making is through cost-benefit analysis (CBA). But despite well-established practices for rigorous estimation of the pros and cons of policies, there is room to improve, particularly in characterizing difficult-to-measure benefits and the distribution of the costs and benefits across different segments of society. In this regard, announcements by US President Biden, if brought to fruition, could have far-reaching implications for how CBA is used in government decision-making. But such promising (and familiar) rhetoric is no guarantee of real progress, and the devil, as always, is in the details. These details are where the scientific community has an important role to play to improve the use of CBA and to hold the administration accountable.</jats:p>

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

<jats:p>Early studies suggest COVID-19 vaccine protection varies by ailment and treatment.</jats:p>

<jats:p>Upcoming presidential election could stall efforts to restore Lake Urmia.</jats:p>