Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects

Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species

Preventive evidence into practice (PEP) study: implementation of guidelines to prevent primary vascular disease in general practice protocol for a cluster randomised controlled trial

There are significant gaps in the implementation and uptake of evidence-based guideline recommendations for cardiovascular disease (CVD) and diabetes in Australian general practice. This study protocol describes the methodology for a cluster randomised trial to evaluate the effectiveness of a model that aims to improve the implementation of these guidelines in Australian general practice developed by a collaboration between researchers, non-government organisations, and the profession.This study is funded by an Australian National Health and Medical Research Council (NHMRC) Partnership grant (ID 568978) together with the Australian National Heart Foundation, Royal Australian College of General Practitioners, and the BUPA Foundation. MH is supported by a NHMRC Senior Principle Research Fellowship

Wireless Mouth Motion Recognition System Based on EEG-EMG Sensors for Severe Speech Impairments

This study aims to demonstrate the feasibility of using a new wireless electroencephalography (EEG)–electromyography (EMG) wearable approach to generate characteristic EEG-EMG mixed patterns with mouth movements in order to detect distinct movement patterns for severe speech impairments. This paper describes a method for detecting mouth movement based on a new signal processing technology suitable for sensor integration and machine learning applications. This paper examines the relationship between the mouth motion and the brainwave in an effort to develop nonverbal interfacing for people who have lost the ability to communicate, such as people with paralysis. A set of experiments were conducted to assess the efficacy of the proposed method for feature selection. It was determined that the classification of mouth movements was meaningful. EEG-EMG signals were also collected during silent mouthing of phonemes. A few-shot neural network was trained to classify the phonemes from the EEG-EMG signals, yielding classification accuracy of 95%. This technique in data collection and processing bioelectrical signals for phoneme recognition proves a promising avenue for future communication aids

Neuroepigenomics: resources, obstacles, and opportunities

Long-lived postmitotic cells, such as most human neurons, must respond effectively to ongoing changes in neuronal stimulation or microenvironmental cues through transcriptional and epigenomic regulation of gene expression. The role of epigenomic regulation in neuronal function is of fundamental interest to the neuroscience community, as these types of studies have transformed our understanding of gene regulation in postmitotic cells. This perspective article highlights many of the resources available to researchers interested in neuroepigenomic investigations and discusses some of the current obstacles and opportunities in neuroepigenomics

Predicted impacts from offshore produced-water discharges on hypoxia in the gulf of Mexico

Summer hypoxia (dissolved oxygen < 2 mg/L) in the bottom waters of the northern Gulf of Mexico has received considerable scientific and policy attention because of potential ecological and economic impacts. This hypoxic zone forms off the Louisiana coast each summer and has increased from an average of 8,300 km2 in 1985-1992 to over 16,000 km2 in 1993-2001, reaching a record 22,000 km2 in 2002. The almost threefold increase in nitrogen load from the Mississippi River Basin (MRB) to the Gulf since the middle of the last century is the primary external driver for hypoxia. A goal of the 2001 Federal Action Plan is to reduce the 5-year running average size of the hypoxic zone to below 5,000 km2 by 2015. After the Action Plan was developed, a new question arose as to whether sources other than the MRB may also contribute significant quantities of oxygen-demanding substances. One very visible potential source is the hundreds of offshore oil and gas platforms located within or near the hypoxic zone, many of which discharge varying volumes of produced water. The objectives of this study were to assess the incremental impacts of produced water discharges on dissolved oxygen in the northern Gulf of Mexico, and to evaluate the significance of these discharges relative to loadings from the MRB. Predictive simulations were conducted with three existing models of Gulf hypoxia using produced water loads from an industry study. Scenarios were designed that addressed loading uncertainties, settleability of suspended constituents, and different assumptions on delivery locations for the produced water loads. Model results correspond to the incremental impacts of produced water loads, relative to the original model results, which included only loads from the MRB. The predicted incremental impacts of produced water loads on dissolved oxygen in the northern Gulf of Mexico from all three models were small. Even considering the predicted ranges between lower- and upper-bound results, these impacts are likely to be within the errors of measurement for bottomwater dissolved oxygen and hypoxic area at the spatial scale of the entire hypoxic zone

New insights and updated guidelines for epigenome-wide association studies

Epigenetic dysregulation in disease is increasingly studied as a potential mediator of pathophysiology. The epigenetic events are believed to occur in somatic cells, but the limited changes of DNA methylation in studies to date indicate that only subsets of the cells tested undergo epigenetic dysregulation. The recognition of this subpopulation effect indicates the need for care in design and execution of epigenome-wide association studies (EWASs), paying particular attention to confounding sources of variability. To maximize the sensitivity of the EWASs, ideally, the cell type mediating the disease should be tested, which is not always practical or ethical in human subjects. The value of using accessible cells as surrogates for the target, disease-mediating cell type has not been rigorously tested to date. In this review, participants in a workshop convened by the National Institutes of Health update EWAS design and execution guidelines to reflect new insights in the field