Project description:Between 6-20% of the cellular proteome is under circadian control and tunes mammalian cell function with daily environmental cycles. For cell viability, and to maintain volume within narrow limits, the daily variation in osmotic potential exerted by changes in the soluble proteome must be counterbalanced. The mechanisms and consequences of this osmotic compensation have not been investigated before. In cultured cells and in tissue we find that compensation involves electroneutral active transport of Na+, K+, and Cl- through differential activity of SLC12A family cotransporters. In cardiomyocytes ex vivo and in vivo, compensatory ion fluxes confer daily variation in electrical activity. Perturbation of soluble protein abundance has commensurate effects on ion composition and cellular function across the circadian cycle. Thus, circadian regulation of the proteome impacts ion homeostasis with substantial consequences for the physiology of electrically active cells such as cardiomyocytes.
Project description:Between 6-20% of the cellular proteome is under circadian control and tunes mammalian cell function with daily environmental cycles. For cell viability, and to maintain volume within narrow limits, the daily variation in osmotic potential exerted by changes in the soluble proteome must be counterbalanced. The mechanisms and consequences of this osmotic compensation have not been investigated before. In cultured cells and in tissue we find that compensation involves electroneutral active transport of Na+, K+, and Cl- through differential activity of SLC12A family cotransporters. In cardiomyocytes ex vivo and in vivo, compensatory ion fluxes confer daily variation in electrical activity. Perturbation of soluble protein abundance has commensurate effects on ion composition and cellular function across the circadian cycle. Thus, circadian regulation of the proteome impacts ion homeostasis with substantial consequences for the physiology of electrically active cells such as cardiomyocytes.
Project description:During production of the original article [1], there was a technical error that resulted in author corrections not being rendered in the PDF version of the article.
Project description:Postural stability is a multi-factorial skill maintained implicitly. Components of quiet standing can decline with Alcohol Use Disorder (AUD), cause instability, and disrupt activities of daily living (ADL). To examine how stability factors contribute to ADL and balance, 638 force platform testing sessions measured sway paths acquired during quiet standing in 151 AUD and 96 control men and women, age 25-75. Structural equation (seq) path analysis estimated contributions from age, diagnosis, and sensory perception to sway and measures of ADL and roadside ataxia testing. Whether eyes were open or closed, older AUD and control participants had longer sway paths than younger ones; older men had longer sway paths than older women. Although each sensory ability tested declined with aging, different factor constellations influenced ADL, ataxia scores, or sway path. Seq-path analysis indicated that ADL was strongly dependent on sensory (but not cognitive) systems with sway-path length accounting for upwards of 25% of variance. Within the AUD group, an index of historically-experienced withdrawal symptoms was a common predictor of stability regardless of vision condition. The greatest variance measured by the seq-path model was for predicting platform sway and simple ataxia testing of one-leg standing even though these measures were affected by different predictor variables: strong predictors of one-leg standing were diagnosis and age (R2 = 39.6%-43.2%), whereas strong predictors of sway-path length were sensory factors and withdrawal index (R2 = 22.0%-22.9%). These findings present evidence for appreciating selective factors that contribute to declining postural stability and to liability for compromised quality of life in AUD.
Project description:The HTML version of this Article incorrectly omits Supplementary Movie 1. Supplementary Movie 1 can be found as Supplementary Information associated with this Correction.
Project description:Type 2 diabetes mellitus, obesity and metabolic syndrome are becoming more prevalent worldwide and will present an increasingly challenging burden on healthcare systems. These interlinked metabolic abnormalities predispose affected individuals to a plethora of complications and comorbidities. Furthermore, diabetes is estimated by the World Health Organization to have caused 1.5 million deaths in 2019, with this figure projected to rise in coming years. This highlights the need for further research into the management of metabolic diseases and their complications. Studies on circadian rhythms, referring to physiological and behavioral changes which repeat approximately every 24 hours, may provide important insight into managing metabolic disease. Epidemiological studies show that populations who are at risk of circadian disruption such as night shift workers and regular long-haul flyers are also at an elevated risk of metabolic abnormalities such as insulin resistance and obesity. Aberrant expression of circadian genes appears to contribute to the dysregulation of metabolic functions such as insulin secretion, glucose homeostasis and energy expenditure. The potential clinical implications of these findings have been highlighted in animal studies and pilot studies in humans giving rise to the development of circadian interventions strategies including chronotherapy (time-specific therapy), time-restricted feeding, and circadian molecule stabilizers/analogues. Research into these areas will provide insights into the future of circadian medicine in metabolic diseases. In this review, we discuss the physiology of metabolism and the role of circadian timing in regulating these metabolic functions. Also, we review the clinical aspects of circadian physiology and the impact that ongoing and future research may have on the management of metabolic disease.