Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
In a mouse model of cerebral cavernous malformation, deletion of the gene PDCD10 leads to vascular defects in the central nervous system as a result of increased UNC13-mediated exocytosis and secretion of angiopoietin-2 by endothelial cells.
Cheng-Lung Ku and colleagues report that anti-interferon (IFN)-γ autoantibodies in patients with disseminated mycobacterial infections recognize the C-terminus of IFN-γ, and suggest that autoantibodies may arise by molecular mimicry. The authors propose a therapeutic strategy to treat patients using a modified IFN-γ that escapes neutralization by autoantibodies.
An IL4R polymorphism associated with severe asthma drives conversion of regulatory T cells to TH17 cells; this can be inhibited by neutralizing interleukin-6.
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.
In macrophages, Nox4 drives fatty acid metabolism, which in turn activates the NLRP3 inflammasome. This pathway can be pharmacologically targeted in vivo by inhibiting Nox4 to reduce S. pneumoniae infection in mice.
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.
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.
The naturally occurring compound urolithin A has been found to promote mitophagy, thereby increasing lifespan in worms and improving skeletal muscle activity in rodents.
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.
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.
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.
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.
Genome-wide methylome sequencing of serial samples obtained from patients with acute myeloid leukemia reveals that epigenetic alleles and genetic alleles follow independent courses during disease evolution.
Thalidomide and its derivatives lenalidomide and pomalidomide, which are used to treat multiple myeloma and del(5q) myelodysplastic syndrome, have antitumor and teratogenic effects through a mechanism involving destabilization of the CD147 and MCT1 proteins.
Lenalidomide, which is used to treat myelodysplastic syndrome, kills mutation-bearing hematopoietic cells by increasing expression of the G-protein-coupled receptor GPR68, leading to increased intracellular calcium concentrations and calpain activation.
The co-repressor GPS2 acts in macrophages to regulate their activation in obesity-induced inflammation, and appropriate GPS2 function is required to maintain insulin sensitivity in mice and humans with obesity.
Vaccari et al. report that SIV vaccines formulated with two different adjuvants elicit distinct immune responses and effects on SIV acquisition in rhesus macaques.