Characterisation of infections in patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent.

We investigated the incidence of invasive fungal infections (IFIs) and other infectious complications in patients receiving venetoclax and hypomethylating agent therapy for acute myeloid leukaemia (AML). This retrospective, multicentre cohort study included adult patients with AML who received at least one cycle of venetoclax and either azacitidine or decitabine between January 2016 and August 2020. The primary outcome was the incidence of probable or confirmed IFI.

Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females.

Impaired estrogen receptor α (ERα) action promotes obesity and metabolic dysfunction in humans and mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal and oxidative metabolism, we established that reduced ERα expression in muscle is associated with glucose intolerance and adiposity in women and female mice. To test this relationship, we generated muscle-specific ERα knockout (MERKO) mice.

Parathyroid-hormone-related protein signaling mechanisms in lung carcinoma growth inhibition.

Parathyroid hormone-related protein (PTHrP) inhibits proliferation of several lung cancer cell lines, but the signaling mechanism has not been established. This study tested the hypotheses that growth inhibition is mediated through the PTHrP receptor, PTH1R, and that the process is modified by ERK activation. PTHrP-positive and negative clones of H1944 lung adenocarcinoma cells underwent stable PTH1R knockdown with lentiviral shRNA or transient transfection with ERK1 and ERK2 siRNA.

Genetic architecture of insulin resistance in the mouse.

Insulin resistance (IR) is a complex trait with multiple genetic and environmental components. Confounded by large differences between the sexes, environment, and disease pathology, the genetic basis of IR has been difficult to dissect. Here we examine IR and related traits in a diverse population of more than 100 unique male and female inbred mouse strains after feeding a diet rich in fat and refined carbohydrates.

HSP72 is a mitochondrial stress sensor critical for Parkin action, oxidative metabolism, and insulin sensitivity in skeletal muscle.

Increased heat shock protein (HSP) 72 expression in skeletal muscle prevents obesity and glucose intolerance in mice, although the underlying mechanisms of this observation are largely unresolved. Herein we show that HSP72 is a critical regulator of stress-induced mitochondrial triage signaling since Parkin, an E3 ubiquitin ligase known to regulate mitophagy, was unable to ubiquitinate and control its own protein expression or that of its central target mitofusin (Mfn) in the absence of HSP72. In wild-type cells, we show that HSP72 rapidly translocates to depolarized mitochondria prior to Parkin recruitment and immunoprecipitates with both Parkin and Mfn2 only after specific mitochondrial insult.