News & Views in 2016

The quest to improve influenza vaccines is aided by research into the immune response that they generate. Two recent studies have focused their attention on the specificities of antibodies induced after vaccination with conventional inactivated influenza vaccines.

A recent study shows that spermidine has beneficial effects on health and lifespan in mice, and that these effects are the result of improved cardiovascular function. Similar effects of spermidine on humans are supported by epidemiological studies.

Tumors continue to escape therapies that target single signaling pathways. A recent study in mice shows that combination immunotherapy involving different arms of immune response can overcome this and cure intractable tumors.

A recent study confirms an association between vessel co-option and resistance to bevacizumab, an anti-vascular endothelial growth factor-A (VEGFA) antibody, in patients with liver metastases. The authors suggest a combined therapeutic strategy that reduces co-option in mice.

Misfolded and hyperphosphorylated forms of the microtubule-associated protein tau are thought to be responsible for some degree of neurodegeneration. The demonstration of a novel toxic cleavage of tau by caspase-2 opens up new therapeutic avenues.

A new study presents a protocol to differentiate human induced pluripotent stem cells (iPSCs) into microglia that closely resemble their in vivo counterparts. These cells offer an exciting new tool for learning more about the role of microglia in disease.

Aberrant injury responses in the distal lung likely underpin the development of idiopathic pulmonary fibrosis (IPF). A recent study shows that defective Toll-like receptor 4 (TLR4)-mediated hyaluronan binding impairs alveolar type 2 cell renewal, which may contribute to a dysregulated lung-injury response in IPF.

Tumors often overexpress enzymes that synthesize fatty acids, but the requirement for fatty acid synthesis in tumor growth is unclear. A new fatty acid–synthesis inhibitor blunts lung tumor growth in mice, which implicates this process as a targetable liability.

Two new studies show that high-resolution imaging can detect active tuberculosis (TB) in people otherwise diagnosed as healthy. Individuals with these signs of active infection with Mycobacterium tuberculosis (Mtb) were at an increased risk of developing clinical TB.

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.

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 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 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.

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 provides the first insights into epigenetic heterogeneity in AML. The study highlights a striking independence of genetic and epigenetic variation, and links the kinetics of epigenetic change to clinical outcome.

Reservoirs of virally infected cells that are resistant to standard antiretroviral therapy make HIV-1 infection an incurable disease. A new study shows that follicular T helper cells in lymph node germinal centers are prime niches for HIV-1 persistence during antiviral therapy.

Two recent studies provide novel insights into the mechanism of action of thalidomide analogs in multiple myeloma and del(5q) myelodysplastic syndrome. They show that the role of the chaperone function of cereblon, and a calcium- and calpain-dependent pathway, are important in anticancer functions.

A recent study has shown that a single dose of fibroblast growth factor (FGF) 1 into the central nervous system (CNS) of various mouse and rat models of type 2 diabetes results in profound and exceptionally long-lasting reductions in blood glucose. This work raises the possibility of truly revolutionary therapies for individuals with type 2 diabetes that target the brain FGF system.

Two new studies in mice show that the gut microbiota produces metabolites from dietary tryptophan that regulate inflammation in the gut and central nervous system.