Paradoxical dominant negative activity of an immunodeficiency-associated activating variant.

encodes three regulatory subunits of class IA phosphoinositide 3-kinase (PI3K), each associating with any of three catalytic subunits, namely p110α, p110β, or p110δ. Constitutional mutations cause diseases with a genotype-phenotype relationship not yet fully explained: heterozygous loss-of-function mutations cause SHORT syndrome, featuring insulin resistance and short stature attributed to reduced p110α function, while heterozygous activating mutations cause immunodeficiency, attributed to p110δ activation and known as APDS2. Surprisingly, APDS2 patients do not show features of p110α hyperactivation, but do commonly have SHORT syndrome-like features, suggesting p110α hypofunction.

Effects of disturbances on aboveground biomass of alpine meadow in the Yellow River Source Zone, Western China.

A field experiment quantifies the impacts of two external disturbances (mowing-simulated grazing and number of pika) on aboveground biomass (AGB) in the Yellow River Source Zone from 2018 to 2020. AGB was estimated from drone images for 27 plots subject to three levels of each disturbance (none, moderate, and severe). The three mowing severities bear a close relationship with AGB and its annual change.

Insulin at 100 years - is rebalancing its action key to fighting obesity-related disease?

One hundred years ago, insulin was purified and administered to people with diabetes to lower blood glucose, suppress ketogenesis and save lives. A century later, insulin resistance (IR) lies at the heart of the obesity-related disease pandemic. Multiple observations attest that IR syndrome is an amalgamation of gain and loss of insulin action, suggesting that IR is a misnomer.