COVER This image inspired by Bronze Age art depicts people of diverse cultures spreading their genes between West Asia and Southeast Europe. From left to right: Mycenaean, Minoan, Hittite, Armenian, and Urartian. A total of 1317 ancient genomes spanning 10,000 years were analyzed to reveal the manifold connections between these regions that are invisible in modern DNA. See pages 908, 922, 939, 940 and 982.

Credit: Oliver Uberti Creative

ONLINE COVER Closeup of FIND-IT barley. Global demand for food is driving improved agricultural productivity. Knudsen et al. demonstrate FIND-IT, an approach to rapidly develop resilient crop plants and improve microbial production systems. The method allows for selection and incorporation of domestication traits into the approximately 7000 undomesticated or semidomesticated crop plants that have superior drought tolerance, water tolerance, disease resistance and mineral use efficiency. Using cereal crop barley, the researchers show that FIND-IT can potentially serve as tool to help meet future food demands.

ONLINE COVER Exclusion of CD45 from a CAR-T Synapse. This month’s cover features a confocal microscopy image in which a human T cell expressing a CD19-targeting chimeric antigen receptor (CAR), stained in red, has formed an immunological synapse with a human Raji B cell lymphoma cell (blue). CD45 (green), a bulky tyrosine phosphatase enzyme that can inhibit CAR-T activation, is effectively excluded from the central portion of this synapse. Xiao et al. developed a size-exclusion model to explain how the relative sizes of the CAR construct and the CD45 isoform on a CAR-T cell and the target antigen on a tumor cell calibrate CD45’s dampening of antigen-triggered CAR-T activation at the synapse.

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, Zhang et al. report a regulatory loop between the intracellular domain of the amyloid precursor protein and the kinase LRRK2. The loop promoted neuronal loss and other disease markers in mouse models of Parkinson’s disease that were reduced with the APP-processing inhibitor itanapraced. The image shows staining for markers of autophagy (green) and dopaminergic neurons (red) in brain tissue from LRRK2-mutant mice.

ONLINE COVER Genetically Attenuated Parasites. The cover image shows a color-enhanced light micrograph of ring-stage Plasmodium falciparum (yellow), one of the species of Plasmodium that causes malaria in humans, inside of a human erythrocyte. A safe and effective malaria vaccine is essential to curb the morbidity and mortality caused by P. falciparum infection. Murphy et al. evaluated the safety, tolerability, and immunogenicity of a genetically attenuated P. falciparum with deletions of the P52, P36, and SAP1 genes (PfGAP3KO). Malaria-naïve volunteers were vaccinated with PfGAP3KO sporozoites via mosquito bite delivery. The authors found that PfGAP3KO vaccination provided protection against controlled human malaria infection, supporting further clinical evaluation of this vaccine candidate.