Volume 22 Issue 9, September 2016

A new study shows that withaferin A, a steroidal lactone isolated from Withania somnifera, can exert profound metabolic benefits in mice, including body-weight loss, reduced hepatic steatosis and improved glucose control.

A new study has proposed a mechanism for the pathogenesis of cerebral cavernous malformation (CCM) that links endothelial CCM3 deficiency to increased secretion of the vascular destabilizing protein angiopoietin-2 (ANGPT2).

A recent study suggests that exposure to the mold Aspergillus induces the production of antibodies that neutralize interferon-γ (IFN-γ), which increases the risk of mycobacterial disease.

Patterns of splicing are frequently altered in cancer, and genes that encode splicing regulatory factors are often mutated. Thus, recent strategies have emerged to target splicing alterations in cancer, which are reviewed here.

CRISPR–Cas9-mediated insertion of a naturally occurring benign mutation in blood cell progenitors from patients with sickle cell disease increases fetal hemoglobin expression to levels sufficient to ameliorate the pathological morphology observed in erythrocytes differentiated from these cells.

Low-dose IL-2 treatment alters the abundance of regulatory T cells, IL-17-producing T cells and follicular helper T cells, but not of T helper type 1 and 2 cells, in patients with SLE.

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.

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.

An IL4R polymorphism associated with severe asthma drives conversion of regulatory T cells to T_H17 cells; this can be inhibited by neutralizing interleukin-6.

Withaferin A is a naturally occurring compound that has potent antidiabetic and anti-obesity properties in mice.

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.

Bruner et al. report that defective HIV-1 proviruses predominate in early infection, even when antiretroviral therapy is initiated in the first months after infection. The results highlight challenges in estimating the reservoir of intact, replication-competent virus that may influence cure strategies.

The ability of transplanted neural stem cells to ameliorate neuropathological and behavioral phenotypes after experimental stroke in mice is enhanced by co-treatment with 3K3A-APC, which acts to stimulate neuronal differentiation and functional integration within the host circuitry.

Mutation or downregulation of cohesin components confer ERK reactivation and resistance to BRAF or MEK inhibitors in melanoma cells expressing BRAF or NRAS activating mutations.