Volume 22 Issue 8, August 2016

Little is known about the regulatory mechanisms of antifungal host defense. Two complementary studies show that the E3 ubiquitin ligase CBLB targets dectin-1 and dectin-2 for degradation, and thus exerts a strong anti-inflammatory effect.

A new study in mice shows that activation of the brain's reward system boosts beneficial antibacterial immunity in the periphery. These findings provide biological insights into the association between psychological and physical well-being.

Two recent studies have shown that alterations in muscle stem cell–niche interactions during aging underlie the functional decline in regenerative potential. The reconstitution of this communication restores stem cell function and enhances skeletal muscle repair.

The International AIDS Society Towards a Cure Working Group lays out its scientific strategy to achieve a cure for HIV.

DeNardo and colleagues report that inhibiting focal adhesion kinase in pancreatic ductal adenocarcinoma (PDAC) in mice reduces fibrosis and improves the efficacy of tumor immunotherapy. These findings suggest an approach to overcome the immunosuppressive tumor microenvironment of PDAC.

Silencing expression of the long noncoding RNA NEAT1 prevents paraspeckle formation and sensitizes neoplastic cells to DNA-damage-induced cell death. NEAT1 expression also predicts chemotherapy response in ovarian cancer patients.

ALS-associated mutations in TDP-43 enhance its localization to mitochondria, and the inhibition of mitochondrial targeting reduces neuronal toxicity and alleviates motor phenotypes induced by TDP-43 expression in mice in vivo.

The naturally occurring compound urolithin A has been found to promote mitophagy, thereby increasing lifespan in worms and improving skeletal muscle activity in rodents.

β1-integrin in the niche contributes to muscle stem cell maintenance via Fgf2 signaling, and during aging, stimulation of this integrin promotes muscle stem cell responsiveness to this growth factor and improved muscle regeneration.

During aging, the levels of fibronectin in the muscle stem cell niche decline, contributing to age-related frailty, and supplementation restores youth-like muscle regeneration in mice.

Jian Zhang and colleagues identify the E3 ubiquitin ligase CBLB as a major inhibitor of host defense against Candida albicans infection and show that targeting CBLB can protect mice from lethal candidiasis.

Wirnsberger et al. report that an E3 ubiquitin ligase, CBLB, impairs immune control of Candida albicans and that targeting CBLB protects mice from lethal fungal infection.

A variant of coagulation factor Xa reverses the anticoagulant effects of clinically used inhibitors of factor Xa and thrombin in mice, pointing to the potential use of this agent as a general reversal agent for direct oral anticoagulants.

A new study by Jane Visvader, Geoff Lindeman and colleagues reports on the potential role of RANK signaling in pre-neoplastic breast tissue from BRCA1-mutation carriers and in a mouse model of Brca1-deficient mammary cancer, suggesting that targeting RANK could be explored as an approach to prevent growth of tumors harboring mutated BRCA1.

Chemogenetic activation of central nervous system reward circuitry in the mouse VTA is shown to strengthen immunological host defenses against subsequent bacterial exposure and infection.

Damaged erythrocytes accumulate in various pathological conditions, such as hemolytic anemia, anemia of inflammation, and sickle cell disease. In mice challenged with damaged erythorcytes, a monocyte subset migrates to the liver (but not to the spleen), and this subset differentiates into a transient macrophage population that removes the damaged erythrocytes, thus preventing organ damage.

A systematic analysis reveals some genetic variation underpinning the heterogeneity in pathogen-induced cytokine production by blood cells from a cohort of healthy individuals.