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Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies.
2019
Cohesin complex disruption alters gene expression, and cohesin mutations are common in myeloid neoplasia, suggesting a critical role in hematopoiesis. Here, we explore cohesin dynamics and regulation of hematopoietic stem cell homeostasis and differentiation. Cohesin binding increases at active regulatory elements only during erythroid differentiation. Prior binding of the repressive Ets transcription factor Etv6 predicts cohesin binding at these elements and Etv6 interacts with cohesin at chromatin. Depletion of cohesin severely impairs erythroid differentiation, particularly at Etv6-prebound loci, but augments self-renewal programs. Together with corroborative findings in acute myeloid le…
A Predictive Model of the Prevalence of Delirium in Elderly Subjects Admitted to Nursing Homes.
2017
INTRODUCTION Delirium is common in geriatric patients admitted to nursing homes, with an incidence of 22-79% among long-term residents. AIM To establish a predictive model of the risk of delirium episodes in a sample of elderly people living in nursing homes. MATERIAL AND METHODS A retrospective, cross-sectional case-control study covering a period of 12 consecutive months (April 2014 - March 2015) was carried out. The included cases had suffered at least one episode of delirium during the study period. Sociodemographic and clinical variables as well as risk factors predisposing to or triggering episodes of delirium were recorded. RESULTS A total of 193 cases and 123 controls were recruited…
The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system
2019
International audience; Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-l…
Mitochondrial Fatty Acid β-Oxidation Inhibition Promotes Glucose Utilization and Protein Deposition through Energy Homeostasis Remodeling in Fish.
2020
BACKGROUND: Fish cannot use carbohydrate efficiently and instead utilize protein for energy supply, thus limiting dietary protein storage. Protein deposition is dependent on protein turnover balance, which correlates tightly with cellular energy homeostasis. Mitochondrial fatty acid β-oxidation (FAO) plays a crucial role in energy metabolism. However, the effect of remodeled energy homeostasis caused by inhibited mitochondrial FAO on protein deposition in fish has not been intensively studied. OBJECTIVES: This study aimed to identify the regulatory role of mitochondrial FAO in energy homeostasis maintenance and protein deposition by studying lipid, glucose, and protein metabolism in fish. M…
Nonacidic Farnesoid X Receptor Modulators.
2017
As a cellular bile acid sensor, farnesoid X receptor (FXR) participates in regulation of bile acid, lipid and glucose homeostasis, and liver protection. Clinical results have validated FXR as therapeutic target in hepatic and metabolic diseases. To date, potent FXR agonists share a negatively ionizable function that might compromise their pharmacokinetic distribution and behavior. Here we report the development and characterization of a high-affinity FXR modulator not comprising an acidic residue.
Adipocyte cannabinoid receptor CB1 regulates energy homeostasis and alternatively activated macrophages.
2017
Dysregulated adipocyte physiology leads to imbalanced energy storage, obesity, and associated diseases, imposing a costly burden on current health care. Cannabinoid receptor type-1 (CB1) plays a crucial role in controlling energy metabolism through central and peripheral mechanisms. In this work, adipocyte-specific inducible deletion of the CB1 gene (Ati-CB1- KO) was sufficient to protect adult mice from diet-induced obesity and associated metabolic alterations and to reverse the phenotype in already obese mice. Compared with controls, Ati-CB1-KO mice showed decreased body weight, reduced total adiposity, improved insulin sensitivity, enhanced energy expenditure, and fat depot-specific cell…
Preferred Music Listening Intervention in Nursing Home Residents with Cognitive Impairment: A Randomized Intervention Study.
2019
Background The current trend in addressing symptoms of dementia comprises non-pharmacological strategies such as music interventions for the management and improvement of cognitive function, memory, agitation, depression, or anxiety. Objective To determine the impact of a preferred music listening group intervention upon the functional, cognitive, and emotional dimensions in nursing home residents. Methods A randomized intervention study was carried out. The study was conducted from June to August 2015, and involved a preferred music listening group intervention lasting 60 minutes, 5 days/week during 8 weeks. A total of 119 adults aged ≥65 years, with annual permanent residence in the nursi…
Delirium Predisposing and Triggering Factors in Nursing Home Residents: A Cohort Trial-Nested Case-Control Study.
2019
Background Delirium is a common geriatric syndrome, with a prevalence of between 15-70% among older long-term care residents. It is associated with adverse outcomes, and its onset may prove imperceptible to health professionals. Few studies in institutionalized older people have analyzed the predictors of delirium. Objective The aim of the present study was to identify delirium predisposing and triggering factors, and develop a predictive model. Methods A cohort trial-nested case-control study covering a period of 12 consecutive months (April 2015 - March 2016) was carried out. Predisposing and triggering episodes of delirium were recorded. Results A total of 443 older persons were recruite…
Can a Prebiotic Formulation Reduce Frailty Levels in Older People?
2019
Objective: The purpose of this study was to examine whether a prebiotic formulation reduces frailty index (FI) levels in older people. Design: We conducted secondary analysis of a placebo-controlled, randomized, double-blind design study. Setting/Participants: The study included non-demented people over the age of 65 who were living in nursing homes and were able to walk. Fifty participants completed the study (75.3±7.3 years, 70% females). Intervention: Participants were randomly assigned to either a group who received daily Darmocare Pre® (inulin and fructooligosaccharides) for 13 weeks or a placebo group (maltodextrin). Measurement: The primary outcome in this secondary analysis was chan…
Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity
2017
Iron, copper and zinc are transition metals essential for life because they are required in a multitude of biological processes. Organisms have evolved to acquire metals from nutrition and to maintain adequate levels of each metal to avoid damaging effects associated with its deficiency, excess or misplacement. Interestingly, the main components of metal homeostatic pathways are conserved, with many orthologues of the human metal-related genes having been identified and characterized in Drosophila melanogaster. Drosophila has gained appreciation as a useful model for studying human diseases, including those caused by mutations in pathways controlling cellular metal homeostasis. Flies have m…