COVER A donkey from Petra, Jordan, carries goods through the rugged landscape, as millions of others have done for millennia. Genetic analysis tracks their journey from a single domestic origin in Africa as early as 7000 years ago to rapid expansions through Eurasia 2500 years later. Ancient genomes also reveal trans-Mediterranean exchange, giant Roman beasts, and previously unknown diversity in the Levant. See page 1172.

Photo: Brit Büchner/EyeEm via Getty Images

ONLINE COVER A diabetic woman runs while wearing a continuous glucose monitor. Pillon et al. determined the effects of exercise on genomic and immunometabolic signatures in people with normal glucose tolerance and in those with type 2 diabetes. Their findings suggest exercise triggers a more pronounced inflammatory response in people with type 2 diabetes. This work shows the potential for therapies targeting inflammation to improve the benefits of exercise in type 2 diabetics.

ONLINE COVER Waves of IgA Regulate the Intestinal Microbiota. This month’s cover depicts the dynamic interplay between immunoglobulin A (IgA) and the commensal microbiota in the intestinal lumen. Penny and Domingues et al. report that secretory IgA exhibits daily rhythms in its release from lamina propria plasma cells into the intestinal tract, which are controlled by signals provided by food and the circadian clock. These “waves” of IgA regulate the daily oscillations in the relative abundance of commensal gut microbes to help maintain gut homeostasis.

ONLINE COVER Flexing Biomolecular Muscle. Actuation of soft microrobots can be achieved through the application of miniature motors, such as artificial muscles. However, the integration of such actuators within soft microrobots requires assembly processes that are often slow and require multiple steps. Wang et al. have developed a rapid and cost-effective in situ fabrication process that integrates artificial muscles composed of molecular motors in a variety of microrobots. This month’s cover shows a microrobot manipulating a ball; its arms are sequentially controlled by light-responsive artificial muscles.

ONLINE COVER This week, Oberkampf et al. show that degradation of the second messenger c-di-AMP protects the opportunistic pathogen Clostridioides difficile from hyperosmotic stress and the damaging effects of bile salts and is required for the bacterium to colonize the guts of antibiotic-treated mice. The image shows exponentially growing C. difficile cells in which the cell wall is fluorescently labeled.

ONLINE COVER Targeting Cancer Head On. Shown is an immunofluorescence microscopy image of a head and neck squamous cell carcinoma (HNSCC) patient-derived cell spheroid stained for keratin (red), epidermal growth factor receptor (green), and nuclei (blue). Gu et al. created a resource of 56 patient-derived cell spheroids and performed integrated genomic, transcriptomic, and pharmacological analysis to predict HNSCC biomarkers and gene-drug associations. The authors identified and validated one gene, ITGB1, as a predictive biomarker for responsiveness to docetaxel therapy, highlighting the use of this resource to identify and validate additional vulnerabilities in HNSCC to be exploited for targeted therapy.