COVER The substantial grapevine diversity in the world, showcased here by the vigorous ‘Saperavi’ variety in the Kakheti region of Georgia, reveals secrets about human agricultural history. A genomic survey uncovers two concurrent domestication origins of this essential vine. It also shows how Western Asian table grapes diversified along human migration trails into muscat and unique western wine grapes. See pages 880 and 892.

Photo: Anna Bogush/Zoonar GmbH/Alamy

ONLINE COVER An ammonia molecule depicted in a grid-based model. Modeling the dynamics of atomic systems is a promising application of quantum computing, but current quantum computing lacks the necessary number of near-perfect qubits, the basic unit of quantum information, to perform this task. Chan et al. employed quantum computer emulations to model 2D and 3D atoms and molecules. Their first-quantized grid-based simulation represents the molecule’s wave function—the mathematical description of its state in a quantum system—in a manner similar to a grid of pixels representing an image. These simulation techniques can be generalized to model other complex systems.

ONLINE COVER Glycoengineering the Tip of the Spear. This month’s cover depicts cellular soldiers (blue myeloid cells at the left and green T cells at the right) rushing to battle cancer cells. Leading the charge is an Fc-enhanced form of an anti–PD-L1 checkpoint blockade antibody. Using mice humanized to express human Fcγ receptors (FcγRs), Saban et al. found that the in vivo antitumor activity of anti–PD-L1 antibodies was enhanced by removing fucose residues from glycans on the human IgG1 Fc region to promote binding to activating FcγRs on myeloid cells. Treatment with afucosylated anti–PD-L1 enabled depletion of immunosuppressive PD-L1⁺ cells in the tumor microenvironment and blocked inhibitory signaling in PD-1⁺ T cells. These findings suggest that modifications in the Fc scaffold of currently used anti–PD-L1 immunotherapy drugs could yield a boost in their antitumor activity.

ONLINE COVER Quick Reaction. Exoskeleton suits can improve standing balance by quickly reacting to postural perturbations. Beck et al. have developed a wearable ankle exoskeleton suit, ExoBoot, that can generate artificially fast torque before the onset of the user’s physiological reaction. ExoBoot was validated with human participants, preventing the users’ ankle joint from dorsiflexion and improving their standing balance when the surface they were stood on was displaced. This month’s cover is a multi-exposure image of a user wearing the ankle ExoBoot that is able to correct their standing balance following postural perturbation.

ONLINE COVER This week, Lee et al. report that Indian Hedgehog and Sonic Hedgehog make distinct contributions to the intercellular interactions that drive the endometrial remodeling necessary for establishing pregnancy in mice. The image shows a section of human endometrium, which is composed of a layer of epithelial cells and the underlying stromal cells.

ONLINE COVER Eyeing up DMD. This image of a rat eyeball demonstrates the histological structure of the extraocular muscles, or EOMs (embryonic myosin heavy chain, green; laminin, red). The EOMs tend to be spared in patients with Duchenne muscular dystrophy (DMD), but it is not clear why this is the case. Here Taglietti et al. studied a rat model of DMD, along with human tissue samples, to better understand this phenomenon. They found that up-regulation of the thyroid-stimulating hormone receptor (TSHR) protected EOMs from injury by reducing senescence in muscle stem cells and that forskolin administration could induce protective effects in limb skeletal muscles of affected rats. These findings suggest that inhibition of senescence could potentially be exploited to treat DMD.