Generating snoRNA-guided Programmable 2'- -methylation.

Small nucleolar RNAs (snoRNAs) are critical in guiding post-transcriptional modifications like 2'- -methylation (Nm), which play crucial roles in downstream processes such as splicing and translation. This study tests a novel method for Nm validation, addressing a significant gap in modern Nm research, and offers insight into the intricacies of snoRNA-guided Nm. While mapping of Nm modifications has seen significant improvement within the past decade, no major techniques have been able to validate these potential sites.

Improved Methods for Deamination-Based mA Detection.

-methyladenosine (mA) is a critical regulator of gene expression and cellular function. Much of our knowledge of mA has been enabled by the identification of mA sites transcriptome-wide. However, global mA profiling methods require high amounts of input RNA to accurately identify methylated RNAs, making mA profiling from rare cell types or scarce tissue samples infeasible.

PGC-1α promotes nitric oxide antioxidant defenses and inhibits FOXO signaling against cardiac cachexia in mice.

Chronic heart failure often results in catabolic muscle wasting, exercise intolerance, and death. Oxidative muscles, which have greater expression of the metabolic master gene peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and its target genes, are more resistant to catabolic wasting than are glycolytic muscles; however, the underlying mechanism is unknown. To determine the functional role of PGC-1α in oxidative phenotype-associated protection, skeletal muscle-specific PGC-1α transgenic mice were crossbred with cardiac-specific calsequestrin transgenic mice, a genetic model of chronic heart failure.

PGC-1alpha plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle.

Endurance exercise stimulates peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) expression in skeletal muscle, and forced expression of PGC-1alpha changes muscle metabolism and exercise capacity in mice. However, it is unclear if PGC-1alpha is indispensible for endurance exercise-induced metabolic and contractile adaptations in skeletal muscle. In this study, we showed that endurance exercise-induced expression of mitochondrial enzymes (cytochrome oxidase IV and cytochrome c) and increases of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31)-positive endothelial cells in skeletal muscle, but not IIb-to-IIa fiber-type transformation, were significantly attenuated in muscle-specific Pgc-1alpha knockout mice.

p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice.

Regular endurance exercise induces skeletal muscle contractile and metabolic adaptations, conferring salutary health benefits, such as protection against the metabolic syndrome. The plasticity of skeletal muscle has been extensively investigated, but how the adaptive processes are precisely controlled is largely unknown. Using muscle-specific gene deletion in mice, we now show that p38gamma mitogen-activated protein kinase (MAPK), but not p38alpha and p38beta, is required for endurance exercise-induced mitochondrial biogenesis and angiogenesis, whereas none of the p38 isoforms are required for IIb-to-IIa fiber-type transformation.

Ceramide induces endothelial cell senescence.

Ceramide has been proposed to be a mediator of replicative senescence. Our aim was to determine whether ceramide induces senescence in vascular endothelial cells. Human umbilical vein endothelial cells were cultured to different population doubling levels and ceramide levels were quantitated.

Involvement of cholinergic neuronal systems in intravenous cocaine self-administration.

Recent studies suggest the participation of cholinergic neurons in the brain processes underlying reinforcement. The involvement of cholinergic neurons in cocaine self-administration has been recently demonstrated in studies using muscarinic and nicotinic agonists and antagonists, microdialysis, assessment of choline acetyltransferase activity and acetylcholine (ACh) turnover rates. The present experiment was initiated to identify subsets of cholinergic neurons involved in the brain processes that underlie cocaine self-administration by lesioning discrete populations with a selective neurotoxin.