The disassembly and reassembly of nucleosomes by histone chaperones is an essential activity during eukaryotic transcription elongation. This highly conserved process maintains chromatin integrity by transiently removing nucleosomes as barriers and then restoring them in the wake of transcription. While transcription elongation requires multiple histone chaperones, there is little understanding of how most of them function and why so many are required.
View Article and Find Full Text PDFBackground: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors.
View Article and Find Full Text PDFAcid soils are a major constraint to agricultural productivity in many parts of sub-Saharan Africa, including Ethiopia. Restoring soil pH to optimal ranges for agriculture can have a significant impact on yields, particularly for acid intolerant crops like wheat and barley. The application of agricultural lime is the standard corrective, although the large application requirements, lack of farmer awareness, and weak or non-existent lime supply chains make this a complex problem to address at scale.
View Article and Find Full Text PDFMembrane repair is essential to cell survival. In skeletal muscle, injury often associates with plasma membrane disruption. Additionally, muscular dystrophy is linked to mutations in genes that produce fragile membranes or reduce membrane repair.
View Article and Find Full Text PDFLife Sci Space Res (Amst)
May 2018
The deterministic radiation transport code HZETRN (High charge (Z) and Energy TRaNsport) was developed by NASA to study the effects of cosmic radiation on astronauts and instrumentation shielded by various materials. This work presents an analysis of computed differential flux from HZETRN compared with measurement data from three balloon-based experiments over a range of atmospheric depths, particle types, and energies. Model uncertainties were quantified using an interval-based validation metric that takes into account measurement uncertainty both in the flux and the energy at which it was measured.
View Article and Find Full Text PDFInt J Progn Health Manag
November 2017
This work presents a computationally-efficient, probabilistic approach to model-based damage diagnosis. Given measurement data, probability distributions of unknown damage parameters are estimated using Bayesian inference and Markov chain Monte Carlo (MCMC) sampling. Substantial computational speedup is obtained by replacing a three-dimensional finite element (FE) model with an efficient surrogate model.
View Article and Find Full Text PDFGenetic disruption of the dystrophin complex produces muscular dystrophy characterized by a fragile muscle plasma membrane leading to excessive muscle degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the transforming growth factor β (TGFβ) pathway, osteopontin encoded by the SPP1 gene and latent TGFβ binding protein 4 (LTBP4). We now evaluated the functional effect of these modifiers in the context of muscle injury and repair to elucidate their mechanisms of action.
View Article and Find Full Text PDFPatients with stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) develop systemic inflammation characterized by vasculopathy, interstitial lung disease, ulcerative skin lesions, and premature death. Autosomal dominant mutations in STING are thought to trigger activation of IRF3 and subsequent up-regulation of interferon (IFN)-stimulated genes (ISGs) in patients with SAVI. We generated heterozygous STING N153S knock-in mice as a model of SAVI.
View Article and Find Full Text PDFThe muscular dystrophies are genetically diverse. Shared pathological features among muscular dystrophies include breakdown, or loss of muscle, and accompanying fibrotic replacement. Novel strategies are needed to enhance muscle repair and function and to slow this pathological remodeling.
View Article and Find Full Text PDFGlucocorticoid steroids such as prednisone are prescribed for chronic muscle conditions such as Duchenne muscular dystrophy, where their use is associated with prolonged ambulation. The positive effects of chronic steroid treatment in muscular dystrophy are paradoxical because these steroids are also known to trigger muscle atrophy. Chronic steroid use usually involves once-daily dosing, although weekly dosing in children has been suggested for its reduced side effects on behavior.
View Article and Find Full Text PDFDespite the routine collection of annual agricultural surveys and significant advances in GIS and remote sensing products, little econometric research has integrated these data sources in estimating developing nations' agricultural yields. In this paper, we explore the determinants of wheat output per hectare in Ethiopia during the 2011-2013 principal crop seasons at the kebele administrative area. Using a panel data approach, combining national agricultural field surveys with relevant GIS and remote sensing products, the model explains nearly 40% of the total variation in wheat output per hectare across the country.
View Article and Find Full Text PDFDysferlin is a membrane-associated protein implicated in membrane resealing; loss of dysferlin leads to muscular dystrophy. We examined the same loss-of-function Dysf mutation in two different mouse strains, 129T2/SvEmsJ (Dysf(129)) and C57BL/6J (Dysf(B6)). Although there are many genetic differences between these two strains, we focused on polymorphisms in Anxa6 because these variants were previously associated with modifying a pathologically distinct form of muscular dystrophy and increased the production of a truncated annexin A6 protein.
View Article and Find Full Text PDFObjective: Current plans in the English National Health Service are to replace block contracts for mental health providers with a single tariff for each 'cluster' of conditions. A single tariff will not take into account the potential additional complexity and costs inherent in caring for older people. To examine the basis for a uniform tariff, differences in service utilisation and costs between working age adults and older adults in two populous clusters (non-psychotic, psychotic) were investigated across five mental health healthcare providers in and around London.
View Article and Find Full Text PDFAims and method To gather information about psychiatric trainees' use of different information sources and academic materials, a questionnaire was distributed at the London Deanery Annual Psychiatry Trainee Conference and the training programmes of two teaching trusts. Results Participants returned 202 out of a total of 300 completed questionnaires (67%). Websites were the most commonly accessed information source ahead of textbooks, abstracts and journals.
View Article and Find Full Text PDFObjective: Although available evidence is modest, exercise could be beneficial in reducing behavioural and psychological symptoms of dementia. We aim to evaluate the cost-effectiveness of a dyadic exercise regimen for individuals with dementia and their main carer as therapy for behavioural and psychological symptoms of dementia.
Methods: Cost-effectiveness analysis within a two-arm, pragmatic, randomised, controlled, single-blind, parallel-group trial of a dyadic exercise regimen (individually tailored, for 20-30 min at least five times per week).
Metal-organic frameworks (MOFs) are an emerging class of microporous, crystalline materials with potential applications in the capture, storage, and separation of gases. Of the many known MOFs, MOF-5 has attracted considerable attention because of its ability to store gaseous fuels at low pressure with high densities. Nevertheless, MOF-5 and several other MOFs exhibit limited stability upon exposure to reactive species such as water.
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