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 A glowing orange taste bud highlighted in a mouse’s tongue. The perception of taste allows one to assess whether ingested substances are nutritious or potentially hazardous, but this sense is frequently impaired in case of pathology or following chemotherapy. Vercauteren Drubbel et al. identify taste buds clustered in the mouse esophagus and compared mechanisms regulating development of taste receptor cells in the tongue and esophagus at single cell resolution. They provide an understanding of what gives rise to these receptors, and insights into the mechanisms involved in the generation of each taste bud cell type.

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, Watanabe et al. report that the timing of the peak abundance of the mycobacterial component receptors Dectin-2 and Mincle determines the signaling pathways activated by the common subunit FcRγ and, consequently, the gene expression profile and cytokine output of dendritic cells (see also the Focus by Blamberg and Lang). The colored scanning electron micrograph image shows human dendritic cells.

ONLINE COVER mRNA Vaccines for Cancer. This light micrograph shows cells from a cervical smear that are infected with human papillomavirus (HPV), characterized by clear cytoplasm and enlarged nuclei. Persistent HPV infections can cause cervical cancer, a major cause of cancer-related death in women, as well as several other types of cancer. In this issue, Ramos da Silva et al. performed a head-to-head comparison of three mRNA vaccine platforms designed to treat HPV-associated cancer. The vaccines exhibited different efficacy in murine tumor models, but all three vaccines outperformed both a DNA-based vaccine and a protein-based vaccine. Together, these data highlight the promise of mRNA vaccines for HPV-associated cancers.