Howellhardison7934

Animals respond to sleep loss with compensatory rebound sleep, and this is thought to be critical for the maintenance of physiological homeostasis. Sleep duration varies dramatically across animal species, but it is not known whether evolutionary differences in sleep duration are associated with differences in sleep homeostasis. The Mexican cavefish, Astyanax mexicanus, has emerged as a powerful model for studying the evolution of sleep. While eyed surface populations of A. mexicanus sleep approximately 8 hr each day, multiple blind cavefish populations have converged on sleep patterns that total as little as 2 hr each day, providing the opportunity to examine whether the evolution of sleep loss is accompanied by changes in sleep homeostasis. EGFR signaling pathway Here, we examine the behavioral and molecular response to sleep deprivation across four independent populations of A. mexicanus. Our behavioral analysis indicates that surface fish and all three cavefish populations display robust recovery sleep during the day following nighttime sleep deprivation, suggesting sleep homeostasis remains intact in cavefish. We profiled transcriptome-wide changes associated with sleep deprivation in surface fish and cavefish. While the total number of differentially expressed genes was not greater for the surface population, the surface population exhibited the highest number of uniquely differentially expressed genes than any other population. Strikingly, a majority of the differentially expressed genes are unique to individual cave populations, suggesting unique expression responses are exhibited across independently evolved cavefish populations. Together, these findings suggest sleep homeostasis is intact in cavefish despite a dramatic reduction in overall sleep duration. © 2020 Wiley Periodicals, Inc.In β-thalassaemia, anaemia results from ineffective erythropoiesis characterized by inhibition of late-stage erythroid differentiation. We earlier used luspatercept and RAP-536 protein traps for certain Smad2/3-pathway ligands to implicate Smad2/3-pathway overactivation in dysregulated erythroid differentiation associated with murine β-thalassaemia and myelodysplasia. Importantly, luspatercept alleviates anaemia and has been shown to reduce transfusion burden in patients with β-thalassaemia or myelodysplasia. Here, we investigated the molecular mechanisms underlying luspatercept action and pSmad2/3-mediated inhibition of erythroid differentiation. In murine erythroleukemic (MEL) cells in vitro, ligand-mediated overactivation of the Smad2/3 pathway reduced nuclear levels of GATA-1 (GATA-binding factor-1) and its transcriptional activator TIF1γ (transcription intermediary factor 1γ), increased levels of reactive oxygen species, reduced cell viability and haemoglobin levels, and inhibited erythroid differentiation. Co-treatment with luspatercept in MEL cells partially or completely restored each of these. In β-thalassaemic mice, RAP-536 up-regulated Gata1 and its target gene signature in erythroid precursors determined by transcriptional profiling and gene set enrichment analysis, restored nuclear levels of GATA-1 in erythroid precursors, and nuclear distribution of TIF1γ in erythroblasts. Bone marrow cells from β-thalassaemic mice treated with luspatercept also exhibited restored nuclear availability of GATA-1 ex vivo. Our results implicate GATA-1, and likely TIF1γ, as key mediators of luspatercept/RAP-536 action in alleviating ineffective erythropoiesis. © 2020 Acceleron Pharma Inc. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.Post-modification of reticular materials with well-defined catalysts is an appealing approach to produce new catalytic functional materials with improved stability and recyclability, but also to study the catalysis phenomena in confined spaces. A promising strategy to this end is the post-functionalization of crystalline and robust metal-organic frameworks (MOFs) exploiting the potential of crystal-to-crystal transformations for further the characterisation of catalysts. In this regard, two new photocatalytic materials, MOF-520-PC1 and MOF-520-PC2, are straightforwardly obtained by the post-functionalization of MOF-520 with perylene-3-carboxylic acid (PC1) and perylene-3-butyric acid (PC2). The single crystal-to-crystal transformation yielded the X-ray diffraction structure of catalytic MOF-520-PC2. The well-defined disposition of the perylenes inside the MOF served as suitable model systems to get insights into the photophysical properties and mechanism by combining steady-state, time-resolved and transient absorption spectroscopy. The resulting materials are active organophotoredox catalysts in the reductive dimerisation of aromatic aldehydes, benzophenones, and imines, under mild reaction conditions. Moreover, MOF-520-PC2 can be applied for synthesising gram-scale quantities of products in continuous-flow conditions under steady-state light irradiation. This work provides an alternative approach for the construction of well-defined metal-free MOF based catalysts. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND The incidence of childhood obesity and associated comorbidities are on an increasing trend worldwide. More than 340 million children and adolescents aged between 5 and 19 years old were overweight or had obesity in 2016, from which over 124 million children and adolescents (6% of girls and 8% of boys) had obesity. OBJECTIVE To describe the relationship between pancreas steatosis, body fat and the risk of metabolic syndrome, insulin resistance in Hong Kong Chinese adolescents with both obesity and non-alcoholic fatty liver disease (NAFLD). METHODS Fifty two adolescents with obesity and NAFLD were analysed (14-18 years), stratified into fatty and non-fatty pancreas groups using chemical shift encoded MRI-pancreas proton density fat fraction ≥5%. Pancreatic, abdominal subcutaneous adipose tissue (SAT)/visceral adipose tissue (VAT) volumes, biochemical and anthropometric parameters were measured. Mann-Whitney U test, multiple linear/binary logistic regression analyses and odds ratios were used. RESULTS Fifty percent had fatty pancreas, 38% had metabolic syndrome and 81% had insulin resistance.