WGS data were used from 347,630 individuals with European ancestry in the UK Biobank to obtain high-precision estimates of coding and non-coding rare variant heritability for 34 co...

Removal of type-I nNOS neurons decreased delta-band power in the LFP, lowered dilation to sustained stimulation, decreased the interhemispheric coherence of neural and hemodynamic signals, and reduced...

Feng, Luo and colleagues show that the combination of glucose and fructose, as found in sugar-sweetened beverages, promotes colorectal cancer metastasis through a mechanism involving sorbitol dehydrog...

Klag et al. identified that Turicibacter, a spore-forming bacteria, promotes leanness by producing unique lipids that suppress host ceramides and reduce fat uptake. High-fat diets lower Turicibacter l...

Autoimmune diseases arise from genetic and environmental factors that disrupt immune tolerance. Recent studies highlight the role of myeloid cell immunometabolism, particularly mitochondrial dysfuncti...

Franklin et al. profile DNA methylation during development and aging of the human cortex, identifying pronounced cell-type-specific changes during prenatal life. The authors confirm the importance of ...

The methylenomycins are highly functionalized cyclopentanone antibiotics produced by Streptomyces coelicolor A3(2). A biosynthetic pathway to the methylenomycins has been proposed based on sequence analysis of the proteins encoded by the methylenomycin biosynthetic gene cluster and the incorporation of labeled precursors. However, the roles played by putative biosynthetic enzymes remain experimentally uninvestigated. Here, the biosynthetic functions of enzymes encoded by mmyD, mmyO, mmyF, and mmyE were investigated by creating in-frame deletions in each gene and investigating the effect on methylenomycin production. No methylenomycin-related metabolites were produced by the mmyD mutant, consistent with the proposed role of MmyD in an early biosynthetic step. The production of methylenomycin A, but not methylenomycin C, was abolished in the mmyF and mmyO mutants, consistent with the corresponding enzymes catalyzing the epoxidation of methylenomycin C, as previously proposed. Expression of mmyF and mmyO in a S. coelicolor M145 derivative engineered to express mmr, which confers methylenomycin resistance, enabled the resulting strain to convert methylenomycin C to methylenomycin A, confirming this hypothesis. A novel metabolite (premethylenomycin C), which readily cyclizes to form the corresponding butanolide (premethylenomycin C lactone), accumulated in the mmyE mutant, indicating the corresponding enzyme is involved in introducing the exomethylene group into methylenomycin C. Remarkably, both premethylenomycin C and its lactone precursor were one to two orders of magnitude more active against various Gram-positive bacteria, including antibiotic-resistant Staphylococcus aureus and Enterococcus faecium isolates, than methylenomycins A and C, providing a promising starting point for the development of novel antibiotics to combat antimicrobial resistance.

In this primer, Patrick Haggard and Matthew Longo consider how sensory signals from receptors throughout the body are integrated to produce the sense of a coherent, continuous, sentient body that form...

Using a zebrafish-based screen, Civiletto and colleagues identify the herb-derived metabolites thymol and carvacrol as activators of autophagy and mitophagy, demonstrating their therapeutic potential ...

We found strong evidence that antidepressants differ markedly in their physiological effects, particularly for cardiometabolic parameters. Treatment guidelines should be updated to reflect differences...

Although a keto diet limits weight gain and evokes weight loss in obese mice, it impairs metabolic health in males and females.

Translational Psychiatry - Providing alternative fuel for the brain in anorexia nervosa: a review of the literature on ketones and their effects on metabolism and the brain

Purpose of Review Cancer is a disease influenced by both genetic and environmental factors, with dietary lipids being a significant contributing factor. This review summarizes the role of polyunsatura...

AbstractBackground. Infiltrating gliomas are progressive brain tumors with an invariably fatal prognosis. Nutritional interventions, such as the ketogenic

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Studies in mice show that acute stress activates hyperglycaemia via activation of a medial amygdala–ventral hypothalamic circuit that controls glucose metabolic responses in the liver, independently of adrenal and pancreatic hormones.