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<jats:p>Hedrick brings up several potential concerns that he feels challenge or limit our main finding. Hedrick does not comment on our empirical results, but rather argues that several factors may confound or invalidate our conclusion. Many of these concerns focus on unknown ecological aspects of the translocated tortoises, but we believe there is no reason to conclude that they bias the results or interpretation as presented in our original paper.</jats:p>

<jats:title>A complete PIC-Mediator structure</jats:title> <jats:p> As a critical transcription coactivator, the multisubunit Mediator complex binds RNA polymerase II (Pol II), facilitates preinitiation complex (PIC) assembly, and stimulates transcription and phosphorylation of the Pol II C-terminal domain (CTD). However, how these critical transcriptional events are coordinated by Mediator is not fully understood. Chen <jats:italic>et al.</jats:italic> determined the structures of human Mediator and Mediator-bound PIC in distinct conformational states, the latter of which represents a complete PIC-Mediator complex assembled on the 14-subunit transcription factor IID (TFIID). The structures show that Mediator undergoes reorganization during PIC-Mediator assembly, sandwiches and facilitates phosphorylation of Pol II CTD, and works with TFIID to organize TFIIH in PIC for transcription initiation. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , abg0635, 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.abg0635">eabg0635</jats:related-article> </jats:p>

<jats:title>Doing astronomy with ripples in spacetime</jats:title> <jats:p>General relativity predicts that moving massive objects generate gravitational waves, ripples in spacetime that propagate at the speed of light. Direct detection of gravitational waves was first announced in February of 2016. Vitale reviews the scientific results of gravitational wave astronomy over the subsequent 5 years. About 50 events have been detected, mostly the mergers of binary black holes. The mass distribution of those events is unlike previously known black holes and constrains the evolution of massive stars. A binary neutron star merger was detected in both gravitational waves and electromagnetic radiation, a form of multi-messenger astrophysics. Tests of general relativity and cosmological measurements have also been performed.</jats:p> <jats:p> <jats:italic>Science</jats:italic> , abc7397, 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.abc7397">eabc7397</jats:related-article> </jats:p>

<jats:p> Hansson <jats:italic>et al</jats:italic> . argue that our main finding could provide an overly simplistic metric for maximizing genetic rescue. They agree that translocating the most genetically diverse individuals led to a large increase in translocated tortoise survival, but recommend instead moving individuals that have low genetic load and the greatest representation of metapopulation diversity. Their recommendation is based on specific model assumptions and fitness effects that are often unknown and are not generalizable to many endangered species applications. </jats:p>

<jats:p> Scott <jats:italic>et al</jats:italic> . (Reports, 27 November 2020, p. 1086) bring much-needed attention to species conservation by demonstrating heterozygote superiority among translocated tortoises. However, we believe that their recommended heterozygosity decision rule risks taking conservation genomics backward. We argue that their advice could misguide conservation management aimed at establishing viable populations, and that it can be improved by also assessing the genetic load. </jats:p>

<jats:p> Scott <jats:italic>et al</jats:italic> . (Reports, 27 November 2020, p. 1086) suggest, on the basis of conclusions obtained from a desert tortoise reintroduction program, that higher genomic heterozygosity should be used to identify individuals for successful translocation. I contend that this recommendation is questionable given these relocated tortoises’ unknown origin, their high mortality, insufficient data on resident tortoises and other components of fitness, and potential allelic dropout. </jats:p>

<jats:title>Making sense of TCR–pMHC topology</jats:title> <jats:p> Most T cells use a T cell receptor (TCR) that recognizes major histocompatibility complex molecules bound to peptides (pMHCs) derived from both self- and foreign antigens. Although there is great variability in the interface because of the diversity of both partners, this interaction displays a canonical docking topology for reasons that remain contested. Zareie <jats:italic>et al.</jats:italic> tested an assortment of both canonical and reversed-polarity TCRs that were all specific for the same cognate pMHC-I bearing a peptide derived from influenza A virus (IAV) (see the Perspective by Horkova and Stepanek). The authors determined that docking topology was the primary driver of in vivo T cell activation and recruitment when mice were infected with IAV. The canonical topology was required for the formation of a functional signaling complex, suggesting that T cell signaling constraints dictate how TCR and pMHC meet. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , abe9124, 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.abe9124">eabe9124</jats:related-article> ; see also abj2937, p. <jats:related-article issue="6546" page="1038" related-article-type="in-this-issue" vol="372">1038</jats:related-article> </jats:p>

<jats:p>The US Centers for Disease Control and Prevention (CDC) has had a rough few weeks. At first, it was criticized for being too cautious about its mask guidance for vaccinated individuals. Then, when it abruptly changed its mask recommendation for those who had been vaccinated, it was criticized for acting suddenly and without clearly explaining the reason for the new guidance and what it meant for the unvaccinated. Meanwhile, author Michael Lewis released a bestseller about problems at the CDC that go back decades, with local and state public health officials fighting pandemics in the face of inaction and confusion from the agency. The CDC is in a difficult position: In the course of carrying out its appointed task of communicating science and promoting the best health practices, it can also appear to be making policy—and that is not supposed to be its job. But where do you draw the line between proffering advice and promulgating policy? Maybe the CDC and the administration need to step back and consider if there is a better way for the agency to protect public health.</jats:p>

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