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<jats:p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo–electron microscopy and x-ray crystal structures of the spike protein and the receptor-binding domain bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a blueprint for understanding the marked reduction of binding of other therapeutic mAbs that leads to dampened neutralizing activity. Remodeling of interactions between the Omicron receptor-binding domain and human ACE2 likely explains the enhanced affinity for the host receptor relative to the ancestral virus.</jats:p>

<jats:p> Catalytic deracemization of α-branched aldehydes is a direct strategy to construct enantiopure α-tertiary carbonyls, which are essential to pharmaceutical applications. Here, we report a photochemical <jats:italic>E</jats:italic> / <jats:italic>Z</jats:italic> isomerization strategy for the deracemization of α-branched aldehydes by using simple aminocatalysts and readily available photosensitizers. A variety of racemic α-branched aldehydes could be directly transformed into either enantiomer with high selectivity. Rapid photodynamic <jats:italic>E</jats:italic> / <jats:italic>Z</jats:italic> isomerization and highly stereospecific iminium/enamine tautomerization are two key factors that underlie the enantioenrichment. This study presents a distinctive photochemical <jats:italic>E</jats:italic> / <jats:italic>Z</jats:italic> isomerization strategy for externally tuning enamine catalysis. </jats:p>

<jats:p>The observational signatures of black holes in x-ray binary systems depend on their masses, spins, accretion rate, and the misalignment angle between the black hole spin and the orbital angular momentum. We present optical polarimetric observations of the black hole x-ray binary MAXI J1820+070, from which we constrain the position angle of the binary orbital. Combining this with previous determinations of the relativistic jet orientation, which traces the black hole spin, and the inclination of the orbit, we determine a lower limit of 40° on the spin-orbit misalignment angle. The misalignment must originate from either the binary evolution or black hole formation stages. If other x-ray binaries have similarly large misalignments, these would bias measurements of black hole masses and spins from x-ray observations.</jats:p>

<jats:p> The accurate identification of antitumor T cell receptors (TCRs) represents a major challenge for the engineering of cell-based cancer immunotherapies. By mapping 55 neoantigen-specific TCR clonotypes (NeoTCRs) from 10 metastatic human tumors to their single-cell transcriptomes, we identified signatures of CD8 <jats:sup>+</jats:sup> and CD4 <jats:sup>+</jats:sup> neoantigen-reactive tumor-infiltrating lymphocytes (TILs). Neoantigen-specific TILs exhibited tumor-specific expansion with dysfunctional phenotypes, distinct from blood-emigrant bystanders and regulatory TILs. Prospective prediction and testing of 73 NeoTCR signature–derived clonotypes demonstrated that half of the tested TCRs recognized tumor antigens or autologous tumors. NeoTCR signatures identified TCRs that target driver neoantigens and nonmutated viral or tumor-associated antigens, suggesting a common metastatic TIL exhaustion program. NeoTCR signatures delineate the landscape of TILs across metastatic tumors, enabling successful TCR prediction based purely on TIL transcriptomic states for use in cancer immunotherapy. </jats:p>

<jats:p>Shaping the light emission characteristics of laser systems is of great importance in various areas of science and technology. In a typical lasing arrangement, the transverse spatial profile of a laser mode tends to remain self-similar throughout the entire cavity. Going beyond this paradigm, we demonstrate here how to shape a spatially evolving mode such that it faithfully settles into a pair of bi-orthogonal states at the two opposing facets of a laser cavity. This was achieved by purposely designing a structure that allows the lasing mode to encircle a non-Hermitian exceptional point while deliberately avoiding non-adiabatic jumps. The resulting state transfer reflects the unique topology of the associated Riemann surfaces associated with this singularity. Our approach provides a route to developing versatile mode-selective active devices and sheds light on the interesting topological features of exceptional points.</jats:p>

<jats:p>Treatment of bacterial infections currently focuses on choosing an antibiotic that matches a pathogen’s susceptibility, with less attention paid to the risk that even susceptibility-matched treatments can fail as a result of resistance emerging in response to treatment. Combining whole-genome sequencing of 1113 pre- and posttreatment bacterial isolates with machine-learning analysis of 140,349 urinary tract infections and 7365 wound infections, we found that treatment-induced emergence of resistance could be predicted and minimized at the individual-patient level. Emergence of resistance was common and driven not by de novo resistance evolution but by rapid reinfection with a different strain resistant to the prescribed antibiotic. As most infections are seeded from a patient’s own microbiota, these resistance-gaining recurrences can be predicted using the patient’s past infection history and minimized by machine learning–personalized antibiotic recommendations, offering a means to reduce the emergence and spread of resistant pathogens.</jats:p>

<jats:p>The natural product himastatin has an unusual homodimeric structure that presents a substantial synthetic challenge. We report the concise total synthesis of himastatin from readily accessible precursors, incorporating a final-stage dimerization strategy that was inspired by a detailed consideration of the compound’s biogenesis. Combining this approach with a modular synthesis enabled expedient access to more than a dozen designed derivatives of himastatin, including synthetic probes that provide insight into its antibiotic activity.</jats:p>

<jats:p> The 2022 Gordon Research Conference schedule was published on pages 900 to 927 of this issue of the print version of <jats:italic>Science</jats:italic> . The current schedule can also be found online at <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.grc.org/">www.grc.org/</jats:ext-link> . </jats:p>

<jats:p> Plants continuously form new organs in different developmental contexts in response to environmental cues. Underground lateral roots initiate from prepatterned cells in the main root, but cells can also bypass the root-shoot trajectory separation and generate shoot-borne roots through an unknown mechanism. We mapped tomato ( <jats:italic>Solanum lycopersicum</jats:italic> ) shoot-borne root development at single-cell resolution and showed that these roots initiate from phloem-associated cells through a unique transition state. This state requires the activity of a transcription factor that we named <jats:italic>SHOOTBORNE ROOTLESS</jats:italic> ( <jats:italic>SBRL</jats:italic> ) <jats:italic>.</jats:italic> Evolutionary analysis reveals that <jats:italic>SBRL</jats:italic> ’s function and cis regulation are conserved in angiosperms and that it arose as an ancient duplication, with paralogs controlling wound-induced and lateral root initiation. We propose that the activation of a common transition state by context-specific regulators underlies the plasticity of plant root systems. </jats:p>