Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma.

Metastatic melanoma remains a major clinical challenge. Large-scale genomic sequencing of melanoma has identified bona fide activating mutations in RAC1, which are associated with resistance to BRAF-targeting therapies. Targeting the RAC1-GTPase pathway, including the upstream activator PREX2 and the downstream effector PI3Kβ, could be a potential strategy for overcoming therapeutic resistance, limiting melanoma recurrence, and suppressing metastatic progression.

Ship collision risk threatens whales across the world's oceans.

After the near-complete cessation of commercial whaling, ship collisions have emerged as a primary threat to large whales, but knowledge of collision risk is lacking across most of the world's oceans. We compiled a dataset of 435,000 whale locations to generate global distribution models for four globally ranging species. We then combined >35 billion positions from 176,000 ships to produce a global estimate of whale-ship collision risk.

Lateralized nodose ganglia gene expression implicates cholecystokinin receptors in interoceptive reward signaling.

The vagus nerves are important carriers of sensory information from the viscera to the central nervous system. Emerging evidence suggests that sensory signaling through the right, but not the left, vagus nerve evokes striatal dopamine release and reinforces appetitive behaviors. However, the extent to which differential gene expression within vagal sensory neurons contributes to this asymmetric reward-related signaling remains unknown.

The GPCR adaptor protein Norbin controls the trafficking of C5aR1 and CXCR4 in mouse neutrophils.

Norbin (Neurochondrin, NCDN) is a G protein-coupled receptor (GPCR) adaptor protein known for its importance in neuronal function. Norbin works by binding to numerous GPCRs, controlling their steady-state trafficking and sometimes their agonist-induced internalization, as well as their signaling. We recently showed that Norbin is expressed in neutrophils, limits the surface levels of the GPCRs C5aR1 and CXCR4 in neutrophils, and suppresses neutrophil-mediated innate immunity.