COVER Researchers have developed deep-learning methods to predict the structures of proteins in complex with small molecules, nucleic acids, and other nonprotein components and to design proteins to bind to small molecules. The illustration shows a background cloud of amino acids and short peptides coming together to form the central blue protein around a target ligand, heme, shown in orange. See eadl2528.

Image: C. Bickel/Science. Data: R. Krishna et al., Science 384, eadl2528 (2024).

ONLINE COVER A dry, cracked riverbed near Poyang Lake, China, October 2022. That year, the region suffered a record drought that persisted from July to October. Using observations and a suite of model experiments, Fu et al. showed that the drought was triggered by historic rainfall in Pakistan. Understanding the dynamic pathway linking flooding in Pakistan to East Asian heatwaves and droughts could improve subseasonal predictions of extreme weather events in East Asia.

ONLINE COVER Cultivating Memory B Cell Responses to a Plant-Based Vaccine. CoVLP (coronavirus virus-like particle) is a promising COVID-19 vaccine produced in the weed Nicotiana benthamiana. A squalene-based adjuvant, AS03, can enhance immune responses to CoVLP vaccination, but how AS03 affects memory B cell responses to CoVLP is unknown. Grigoryan et al. studied immune responses in healthy individuals who received two doses of CoVLP with or without AS03. They found that AS03 promoted the progressive maturation of memory B cell responses over time, leading to enhanced neutralization of SARS-CoV-2 and increased memory B cell breadth. This month’s cover illustration depicts a syringe containing a plant-based SARS-CoV-2 vaccine.

ONLINE COVER Special Issue on Legged Robots. Developing legged robots capable of complex motor skills is a major challenge for roboticists. Haarnoja et al. used deep reinforcement learning to train miniature humanoid robots, Robotis OP3, to play a game of one-versus-one soccer. The robots were capable of exhibiting not only agile movements, such as walking, kicking the ball, and rapid recovery from falls, but also emergent behaviors to adapt to the game scenario, such as subtle defensive moves and dynamic footwork in response to the opponent. This month’s cover is an image of the miniature humanoid robot kicking a ball.

ONLINE COVER This week, Nadjar et al. describe an optogenetic tool that facilitates the study of rapid inflammasome responses and pyroptosis. The image shows immortalized, bone marrow–derived macrophages observed by confocal microscopy.

ONLINE COVER Long Distance Relationships. The cover image shows an Aedes aegypti mosquito, the vector for the four serotypes of dengue virus (DENV). Secondary infections with DENV can cause severe disease, which is thought to be a result of sub-neutralizing antibodies that actually enhance infection. Prior studies have demonstrated that the order of infections with the four DENV serotypes influences disease risk, but this work has generally considered each of the serotypes as a single entity. To look more closely at how within- and between-serotype antigenic variability influences disease risk, Wang et al. evaluated 21 years of DENV surveillance data, coupling information on viral antigenic variation with patient outcomes. The authors found that severe disease risk was maximized when the first and second infecting viruses had an intermediate antigenic distance. These data suggest that monitoring DENV antigenic variation could be used to predict when severe disease might arise in a population.