An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression.

Unlabelled: Although suppressed cAMP levels have been linked to cancer for nearly five decades, the molecular basis remains uncertain. Here, we identify endosomal pH as a novel regulator of cytosolic cAMP homeostasis and a promoter of transformed phenotypic traits in colorectal cancer. Combining experiments and computational analysis, we show that the Na+/H+ exchanger NHE9 contributes to proton leak and causes luminal alkalinization, which induces resting [Ca2+], and in consequence, represses cAMP levels, creating a feedback loop that echoes nutrient deprivation or hypoxia.

IL-32 Drives the Differentiation of Cardiotropic CD4+ T Cells Carrying HIV DNA in People With HIV.

Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms β and γ induce the generation of CCR4+CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells.

Constraints on the Decay of ^{180m}Ta.

^{180m}Ta is a rare nuclear isomer whose decay has never been observed. Its remarkably long lifetime surpasses the half-lives of all other known β and electron capture decays due to the large K-spin differences and small energy differences between the isomeric and lower-energy states. Detecting its decay presents a significant experimental challenge but could shed light on neutrino-induced nucleosynthesis mechanisms, the nature of dark matter, and K-spin violation.

Dark Matter Constraints from Isomeric ^{178m}Hf.

We describe a first measurement of the radiation from a ^{178m}Hf sample to search for dark matter. The γ flux from this sample, possessed by Los Alamos National Laboratory nuclear chemistry, was measured with a Ge detector at a distance of 1.2 m due to its high activity.

Dark Matter Annihilation inside Large-Volume Neutrino Detectors.

New particles in theories beyond the standard model can manifest as stable relics that interact strongly with visible matter and make up a small fraction of the total dark matter abundance. Such particles represent an interesting physics target since they can evade existing bounds from direct detection due to their rapid thermalization in high-density environments. In this work we point out that their annihilation to visible matter inside large-volume neutrino telescopes can provide a new way to constrain or discover such particles.