Dominance reversal protects large-effect resistance polymorphisms in temporally varying environments.

A central challenge in evolutionary biology is to uncover mechanisms maintaining functional genetic variation in heterogeneous environments . Population genetics theory suggests that beneficial reversal of dominance, where alleles are dominant when beneficial and recessive when deleterious, can help maintain such variation in temporally varying environments . However, empirical examples are scarce due to difficulties in measuring dominance in fitness in field experiments .

Small Molecule-mediated Insulin Hypersecretion Induces Transient ER Stress Response and Loss of Beta Cell Function.

Pancreatic islet beta cells require a fine-tuned endoplasmic reticulum (ER) stress response for normal function; abnormal ER stress contributes to diabetes pathogenesis. Here, we identified a small molecule, SW016789, with time-dependent effects on beta cell ER stress and function. Acute treatment with SW016789 potentiated nutrient-induced calcium influx and insulin secretion, while chronic exposure to SW016789 transiently induced ER stress and shut down secretory function in a reversible manner.