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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.
Matthieu Perreau and colleagues show that HIV-infected lymph node PD-1+ and follicular helper T cells account for the major source of replication-competent HIV-1 in individuals who have been treated with antiretroviral drugs.
In Trp53-mutated hepatocellular carcinoma, conformation-changing aurora kinase A inhibitors disrupt aurora kinase A–MYC interactions, resulting in MYC degradation and suppression of tumor growth.
The pluripotency factor OCT4 is expressed in smooth muscle cells of atherosclerotic lesions in both mice and humans, and has atheroprotective effects in mice.
Jonathan Carlson and colleagues report that pre-adaptation of HIV to a recipient's major histocompatibility complex class I alleles impairs immune control of the virus.
eQTL analysis of human brain RNA-seq data targeted to genes within the 10q24.32 schizophrenia-associated locus reveals that the risk SNP in this region is selectively associated with expression of BORCS7 and a human-specific isoform of AS3MT across multiple independent samples. Expression of only the associated AS3MT isoform is higher in tissue from humans with schizophrenia than in healthy controls.
After upregulation of AHR in astrocytes by type I interferons, commensal-microbe-derived metabolites of dietary tryptophan act on astrocytes to suppress CNS inflammation.
Fifty-five percent of individuals vaccinated with an attenuated Plasmodium falciparum sporozoite vaccine remained without parasitemia after controlled human malaria infection one year later; immune correlate analysis in humans and non-human primates suggest a role for liver-resident T cells.