Biochim Biophys Acta Mol Basis Dis
June 2024
Loss of prolyl endopeptidase-like (PREPL) encoding a serine hydrolase with (thio)esterase activity leads to the recessive metabolic disorder Congenital Myasthenic Syndrome-22 (CMS22). It is characterized by severe neonatal hypotonia, feeding problems, growth retardation, and hyperphagia leading to rapid weight gain later in childhood. The phenotypic similarities with Prader-Willi syndrome (PWS) are striking, suggesting that similar pathways are affected.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder, characterized by selective loss of motor neurons (MNs). A number of causative genetic mutations underlie the disease, including mutations in the fused in sarcoma (FUS) gene, which can lead to both juvenile and late-onset ALS. Although ALS results from MN death, there is evidence that dysfunctional glial cells, including oligodendroglia, contribute to neurodegeneration.
View Article and Find Full Text PDFBackground: Critical illness is hallmarked by severe stress and organ damage. Fibroblast growth factor 21 (FGF21) has been shown to rise during critical illness. FGF21 is a pleiotropic hormone that mediates adaptive responses to tissue injury and repair in various chronic pathological conditions.
View Article and Find Full Text PDFThe integrity of ER-mitochondria appositions ensures transfer of ions and phospholipids (PLs) between these organelles and exerts crucial effects on mitochondrial bioenergetics. Malfunctions within the ER-mitochondria contacts altering lipid trafficking homeostasis manifest in diverse pathologies, but the molecular effectors governing this process remain ill-defined. Here, we report that PERK promotes lipid trafficking at the ER-mitochondria contact sites (EMCS) through a non-conventional, unfolded protein response-independent, mechanism.
View Article and Find Full Text PDFJ Behav Ther Exp Psychiatry
September 2015
Background And Objectives: Learned fear can generalize to neutral events due their perceptual and conceptual similarity with threat relevant stimuli. This study simultaneously examined these forms of generalization to model the expansion of fear in anxiety disorders.
Methods: First, artificial categories involving sounds, nonsense words and animal-like objects were established.
The present study compared the impact of symbolic equivalence and opposition relations on fear generalisation. In a procedure using nonsense words, some stimuli became symbolically equivalent to an aversively conditioned stimulus while others were symbolically opposite. The generalisation of fear to symbolically related stimuli was then measured using behavioural avoidance, retrospective unconditioned stimulus expectancy and stimulus valence ratings.
View Article and Find Full Text PDFAdaptive anxiety relies on a balance between the generalization of fear acquisition and fear extinction. Research on fear (extinction) generalization has focused mostly on perceptual similarity, thereby ignoring the importance of conceptual stimulus relations in humans. The present study used a laboratory procedure to create de novo conceptual categories of arbitrary stimuli and investigated fear and extinction generalization among these stimuli.
View Article and Find Full Text PDF