COVER This image illustrates a transmembrane G protein–coupled receptor, GPR120, bound to an omega-3 fatty acid ligand, eicosapentaenoic acid, shown in bright orange. GPR120 recognizes unsaturated fatty acids, which contain cis double bonds, through a tight binding pocket within the membrane. Information about the identity of the ligand is propagated through the receptor to a G protein or to other signaling partners in the cell. See page eadd6220.

Illustration: C. Bickel/Science. Structural data: C. Mao et al, Science 380, eadd6220 (2023).

ONLINE COVER A 3D look at two neuronal precursor cells of a developing mouse brain connected by a thin link. Using electron microscopy and deep learning, Cordero Cervantes et al. unravel complex intercellular connections that bridge pairs of cerebellar granule cells throughout the external granular layer of the cerebellum. According to the study, granule cells in the cerebellum, which is responsible for complex motor functions, continue to divide and migrate after birth. Simultaneously, these cells can connect through thin tunnels that can be observed and studied using ultrahigh resolution electron microscopy.

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 Robust robots. The ability of robots to endure severe damage, as well as offer the possibility for repair, can enable their deployment in challenging settings. Kim et al. have developed aerial robots that can endure several punctures while sustaining controlled flight. The dielectric elastomer actuators on the robots were also designed to be repairable by using laser ablation to isolate the defects and recover their performance. This month’s cover is a photograph of the aerial robot showing one dielectric elastomer actuator pierced with fiberglass needles.

ONLINE COVER This week, Kjær et al. characterize signaling by GPR183, a GPCR for oxysterol ligands that mediates the migration and positioning of immune cells in tissues. The authors found that GPR183-dependent cell migration required receptor desensitization by β-arrestin proteins, but not receptor internalization. The image shows molecular dynamics simulations of potential interactions between the C tail of GPR183 (green) and β-arrestin-1.

ONLINE COVER A Curved Canal Conduit. The cover depicts a redesigned tympanostomy tube (green) implanted across the tympanic membrane to enable delivery of a drug (purple) to the middle ear. Implantable medical conduits such as tympanostomy tubes are commonly used for conditions such as ear infections but can result in burdens including device infection, obstruction, or displacement, as well as damage to surrounding tissue. Patel et al. used the Young-Laplace equation to redesign such tubes into a smaller, curved form, enabling faster drug delivery while preventing environmental water entry, adhesion and growth of pathogenic bacteria, and tissue ingrowth. Healthy chinchillas implanted with the curved tubes showed no signs of cochlear damage or hearing loss after device implantation and retrieval, indicating the safety of the approach.