COVER For the technological feat of its construction and launch and its vast promise for exploring the universe, JWST is Science's 2022 Breakthrough of the Year. In this illustration, one of its early images—showing the vast, star-forming clouds known as the Pillars of Creation—is depicted on the gold-plated segments that make up the space telescope's 6.5-meter mirror. See page 1145.

Credit: (Illustration) C. Bickel/Science; (Pillars of Creation, Science) NASA, ESA, CSA, STSCI; (Pillars of Creation, Image processing) Joseph Depasquale/STSCI, Anton M. Koekemoer/STSCI, Alyssa Pagan/STSCI

ONLINE COVER For flying insects like Drosophila, maintaining aerial stability is a constant balancing act that requires active feedback control. Using a combination of targeted neural manipulations and quantitative behavioral measurements in freely flying Drosophila, Whitehead et al. identified key roles for two prominent wing steering muscles that fruit flies use to actuate these control reflexes. The authors found that silencing each of these wing motor units led to distinct pathways in the flight controller circuit being “turned off.” The results point towards an organizational principle for implementing relatively simple but robust feedback control in a system combining sensors and motors.

ONLINE COVER IL-2 Mutein Passes an Acid Test. This month’s cover depicts a glycolytic tumor releasing lactic acid molecules, establishing an acidic tumor microenvironment (TME). The low pH of the TME suppresses antitumor immune responses and favors tumor growth. Gaggero and Martinez-Fabregas et al. report that cytokines are extremely sensitive to the acidic pH found in tumors and lymph nodes. The activity of IL-2, a cytokine central to T cell responses, is highly limited at acidic pH. Using in vitro evolution, they identify a new IL-2 variant, Switch-2, that exhibits enhanced activity at acidic pH but, surprisingly, exhibits reduced activity at the neutral pH found in healthy tissue. Switch-2 therapy in mice triggered potent antitumor responses while avoiding the severe systemic toxicity associated with current high-dose IL-2 therapies.

ONLINE COVER Robot on the Wall. Terrestrial robots that can operate on horizontal and vertical surfaces will enable more opportunities for their application in the real world. Hong et al. have developed a fast-climbing legged robot that can scale ferromagnetic walls and ceilings, maneuver over small obstacles, and carry payloads. The quadruped robot called MARVEL (Magnetically Adhesive Robot for Versatile and Expeditious Locomotion) climbs using specially designed feet based on electro-permanent magnets and magnetorheological elastomers. This month's cover is a photograph of MARVEL climbing on a ferromagnetic surface.

ONLINE COVER This week, Zhou et al. show that the histone deacetylase HDAC10 inhibits the antiviral immune response by interacting with the transcriptional regulator IRF3, preventing its activation. The image shows H&E staining of a lung section from a mouse infected with VSV, showing immune cell infiltration.

ONLINE COVER Mitigating Marburg Virus. This image shows a transmission electron micrograph of Marburg virus (MARV) particles. MARV is a filovirus that causes severe, often lethal hemorrhagic fever disease in humans and nonhuman primates and is a Priority Pathogen for vaccine development. Here, Hunegnaw et al. evaluated the efficacy of a chimpanzee adenovirus 3 (ChAd3)-MARV vaccine in nonhuman primates. The authors found that the vaccine, when administered as a single dose, conferred protection against lethal MARV challenge from as early as 7 days after vaccination to as late as 1 year after vaccination, with antigen-specific antibodies serving as a correlate of protection. Together, these results support further clinical development of the ChAd3-MARV vaccine.