Class 3 PI3K coactivates the circadian clock to promote rhythmic de novo purine synthesis.

Metabolic demands fluctuate rhythmically and rely on coordination between the circadian clock and nutrient-sensing signalling pathways, yet mechanisms of their interaction remain not fully understood. Surprisingly, we find that class 3 phosphatidylinositol-3-kinase (PI3K), known best for its essential role as a lipid kinase in endocytosis and lysosomal degradation by autophagy, has an overlooked nuclear function in gene transcription as a coactivator of the heterodimeric transcription factor and circadian driver Bmal1-Clock. Canonical pro-catabolic functions of class 3 PI3K in trafficking rely on the indispensable complex between the lipid kinase Vps34 and regulatory subunit Vps15.

Class 3 phosphoinositide 3-kinase promotes hepatic glucocorticoid receptor stability and transcriptional activity.

Aim: Lipid kinase class 3 phosphoinositide 3-kinase (PI3K) and nuclear receptor transcription factor glucocorticoid receptor (GR) play essential physiological roles in metabolic adaptation to fasting by activating lysosomal degradation by autophagy and metabolic gene expression, yet their functional interaction is unknown. The requirement of class 3 PI3K for GR function was investigated in liver tissue.

Methods: Inactivation of class 3 PI3K was achieved through deletion of its essential regulatory subunit Vps15, by expressing Cre-recombinase in the livers of Vps15 mice.

Systemic Treatment With Nicotinamide Riboside Is Protective in a Mouse Model of Light-Induced Retinal Degeneration.

Purpose: Maintaining levels of nicotinamide adenine dinucleotide (NAD+), a coenzyme critical for cellular energetics and biosynthetic pathways, may be therapeutic in retinal disease because retinal NAD+ levels decline during retinal damage and degeneration. The purpose of this study was to investigate whether systemic treatment with nicotinamide riboside (NR), a NAD+ precursor that is orally deliverable and well-tolerated by humans, is protective in a mouse model of light-induced retinal degeneration.

Methods: Mice were injected intraperitoneally with vehicle or NR the day before and the morning of exposure to degeneration-inducing levels of light.

Xanthohumol Protects Morphology and Function in a Mouse Model of Retinal Degeneration.

Purpose: To investigate whether treatment with xanthohumol (XN), the principal prenylated chalconoid from Humulus lupulus (hops), is protective in a mouse model of light-induced retinal degeneration (LIRD).

Methods: Mice (129S2/SvPasCrl) were intraperitoneally injected with vehicle or XN prior to toxic light exposure and every 3 days thereafter. Retinal function was assessed by electroretinograms at 1, 2, and 4 weeks following toxic light exposure.

Post-reproductive parthenogenetic pea aphids () are visually identifiable and disproportionately positioned distally to clonal colonies.

The role of kin-selection in the evolution of post-reproductive life is controversial. While anthropological and demographic studies strongly suggest that humans and a few other species experience kin selection for significant post-reproductive survival, these results are necessarily correlational. Understanding could therefore be advanced by the development of a globally available, field and laboratory tractable experimental model of kin-selected post-reproductive survival.