COVER Streams of lava erupted by Mauna Loa in December 2022 flow toward Mauna Kea on the horizon. As this photograph was taken, Mauna Loa’s neighboring volcano Kīlauea was experiencing an eruption of its own. Analysis of small earthquakes detected deep beneath the surface revealed the details of Kīlauea’s and Mauna Loa’s intertwined magma plumbing systems. See pages 434 and 462.

Photo: Mike Mezeul II

ONLINE COVER Mass cytometry imaging of a rhabdomyosarcoma (RMS) tumor cell culture. RMS cancers attach to muscles and other soft tissues and are the most common pediatric soft tissue sarcomas. Danielli et al. generated a comprehensive profile to identify potential drug candidates to treat RMS. Their findings reveal opportunities for future development of RMS therapies to block tumor growth and restore muscle cell differentiation for normal muscle function and growth.

ONLINE COVER Tumor-infiltrating Lymphocytes on JET Patrol. This month’s cover depicts T lymphocytes specific for tumor neoantigens near a cancer cell (yellow) displaying neoantigen peptides on a subset of its cell-surface MHC molecules. JETs (Junctions between Exons and Transposable elements) are a new class of cancer-associated neoantigens made by tumor cells as a result of noncanonical mRNA splicing linking exons to transcripts from transposable elements. Merlotti et al. identified recurrent JETs in human lung tumors and the presence of CD8⁺ T cells specific for JET-encoded epitopes in cancer patients. In a companion paper, Burbage et al. used mouse models to demonstrate that tumor-specific expression of JETs is under epigenetic control.

ONLINE COVER Drones branch out. Continuous and systematic biomonitoring of natural environments could enable a better understanding of how the biosphere responds to environmental changes. Environmental DNA (eDNA) is a useful tool for assessing biodiversity levels, particularly in forests. Aucone et al. report a drone that can autonomously land and sample eDNA on tree branches with different stiffnesses. This month's cover is a photograph of the drone resting on a branch.

ONLINE COVER This week, Gamage et al. show that the deletion of a single amino acid (Glu²⁹⁶) reverses the pathophysiological effects of the disease-associated R304W mutation of the ER Ca²⁺ sensor STIM1 by restoring the intramolecular contacts required for the inactive conformation. The image shows μCT scans of cortical (top row) and trabecular (bottom row) bone in a wild-type mouse (left column), a mouse expressing the R304W mutant (center column), and a mouse expressing STIM1 with both the R304W mutation and Glu²⁹⁶ deletion (right column).

ONLINE COVER Averting Anaphylaxis. The cover image shows peanut butter and peanuts, both of which can cause anaphylaxis in peanut-allergic individuals. Strict dietary avoidance is the primary strategy to prevent anaphylaxis in those with food allergies, though accidental exposures can occur. Here, Alakhras et al. aimed to specifically prevent peanut allergen–driven responses in mice such that subsequent peanut exposure would not result in anaphylaxis. The authors developed a peanut Ara h 2 allergen-specific covalent heterobivalent inhibitor (cHBI) that blocked IgE-driven allergic responses. cHBI treatment prophylactically and therapeutically prevented anaphylaxis in peanut-sensitized humanized mice, with protection lasting as long as two weeks after cHBI treatment. These results highlight the potential clinical use of cHBI treatment as a preventative for peanut-specific allergic responses.