The histone chaperone Spt6 controls chromatin structure through its conserved N-terminal domain.

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.

SMIM1 absence is associated with reduced energy expenditure and excess weight.

Background: 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.

Biofortification in Ethiopia: Opportunities and Challenges.

Background: Children younger than 5 years and women of reproductive age often suffer from micronutrient deficiencies. Biofortification, which involves enriching staple crops with micronutrients, is a nutritional intervention focused on addressing micronutrient deficiencies. It is equitable, sustainable, and costs less than other nutritional interventions.

Insights into Spt6: a histone chaperone that functions in transcription, DNA replication, and genome stability.

Transcription elongation requires elaborate coordination between the transcriptional machinery and chromatin regulatory factors to successfully produce RNA while preserving the epigenetic landscape. Recent structural and genomic studies have highlighted that suppressor of Ty 6 (Spt6), a conserved histone chaperone and transcription elongation factor, sits at the crux of the transcription elongation process. Other recent studies have revealed that Spt6 also promotes DNA replication and genome integrity.

Estimating acid soil effects on selected cereal crop productivities in Ethiopia: Comparing economic cost-effectiveness of lime and fertilizer applications.

Acid 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.

Combined genetic deletion of GDF15 and FGF21 has modest effects on body weight, hepatic steatosis and insulin resistance in high fat fed mice.

Objectives: Obesity in humans and mice is associated with elevated levels of two hormones responsive to cellular stress, namely GDF15 and FGF21. Over-expression of each of these is associated with weight loss and beneficial metabolic changes but where they are secreted from and what they are required for physiologically in the context of overfeeding remains unclear.

Methods: Here we used tissue selective knockout mouse models and human transcriptomics to determine the source of circulating GDF15 in obesity.

Recombinant annexin A6 promotes membrane repair and protects against muscle injury.

Membrane 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.

Deletion of Sulfonylurea Receptor 2 in the Adult Myocardium Enhances Cardiac Glucose Uptake and Is Cardioprotective.

The adult myocardium relies on oxidative metabolism. In ischemic myocardium, such as the embryonic heart, glycolysis contributes more prominently as a fuel source. The sulfonylurea receptor 2 (SUR2) was previously implicated in the normal myocardial transition from glycolytic to oxidative metabolism that occurs during adaptation to postnatal life.

Mental health liaison in a regional burns unit-Past, present and future.

Objective: To describe the epidemiology of patients assessed by a Psychiatric Liaison Team (PLT) on a Regional Burns Unit in London, UK.

Method: A case note review of all patients assessed by the PLT over a 4-year period was carried out. Data were extracted regarding whether the burn was sustained intentionally or non-intentionally, ICD-10 psychiatric diagnosis, alcohol use at the time of injury and mechanism of injury.

HZETRN radiation transport validation using balloon-based experimental data.

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.

Can we improve the outcome of hydrodilatation for adhesive capsulitis?

Background: Hydrodilatation (HD) has been shown to improve pain and function in patients with adhesive capsulitis (AC). There is no consensus concerning how HD should be performed or what volume should be injected. It has distinct advantages compared to surgery; however, it is a painful procedure and is often poorly tolerated.

A Computationally-Efficient Probabilistic Approach to Model-Based Damage Diagnosis.

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.

Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury.

Genetic 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.

STING-associated vasculopathy develops independently of IRF3 in mice.

Patients 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.

Intermittent Glucocorticoid Dosing Improves Muscle Repair and Function in Mice with Limb-Girdle Muscular Dystrophy.

The 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.

Intermittent glucocorticoid steroid dosing enhances muscle repair without eliciting muscle atrophy.

Glucocorticoid 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.

Ethiopian wheat yield and yield gap estimation: A spatially explicit small area integrated data approach.

Despite 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.

Enhanced Muscular Dystrophy from Loss of Dysferlin Is Accompanied by Impaired Annexin A6 Translocation after Sarcolemmal Disruption.

Dysferlin 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.

Comparison of service utilisation and costs of working age adults and older adults receiving treatment for psychosis and severe non-psychotic conditions in England: implications for commissioning.

Objective: 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.

How psychiatric trainees keep up to date: survey of psychiatric trainees' use of journals and other information sources.

Aims 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.

Old age psychiatry in the modern age.

Old age psychiatry services globally are under threat. The discipline enjoyed its heyday in the two decades bridging the millennium. More recently there has been a move to integrate old age services with those of working age adults, to create 'ageless' services.

Cost-effectiveness of exercise as a therapy for behavioural and psychological symptoms of dementia within the EVIDEM-E randomised controlled trial.

Objective: 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).

Kinetic Stability of MOF-5 in Humid Environments: Impact of Powder Densification, Humidity Level, and Exposure Time.

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.