ASD, Employment and Mental Health

Factsheet for HR Departments (and employers more generally). This leaflet is designed to help Human Resources departments understand Autism Spectrum Disorder (ASD) and the impact of mental health on individuals with ASD in the workplace. It provides information on how HR can help, and 'Top Tips' to support employees with ASD & mental health difficulties

Number sense in school mathematics: student performance in four countries

Since 1988 teams of researchers in the United States, Japan and Australia have been involved in a collaborative research project to assess the mental computation ability of their students. The results of this research have been reported elsewhere (Mcintosh, Bana & Farrell 1995; Mcintosh, Nohda, Reys & Reys 1995). The researchers involved were Professors Robert and Barbara Reys of the University of Missouri - Columbia, Professor Nobuhiko Nohda of the University of Tsukuba and Alistair Mcintosh, Jack Bana and Brian Farrell of Edith Cowan University, Perth, Western Australia. The United States and Australian researchers went on to assess the number sense of the same cohorts of students in their two countries. During this time, a doctoral student at the University of Missouri -Columbia, Der Ching Yang, was conducting research into the number sense of Taiwanese students, adapting some of the test items devised by the research teams. In 1995, while Professors Robert and Barbara Reys were at the University of Goteborg on Fulbright scholarships, a team of researchers including Goran Emanuelsson and Bengt Johansson used many of the items to test the number sense of Swedish students. This monograph, while focussing mainly on the United States and Australian data, also includes relevant Swedish and Taiwanese data, together with brief discussions kindly contributed by Goran Emanuelsson, Bengt Johansson and Der Ching Yang. The idea of the development of number sense as a central goal of school mathematics is a recent one, and broad agreement as to its scope is only beginning to emerge. The development of written group tests of number sense is even more embryonic, and indeed not all experts agree that pencil and paper tests, let alone tests including multiple choice items, are an appropriate mode of assessing number sense

Reaching and understanding

Individuals with Asperger syndrome, part of the autism spectrum, experience particular difficulties with social interaction and communication. Despite having average (or above average) intellectual ability, the vast majority of these individuals fail to secure, or maintain, long term employment. Furthermore, high rates of anxiety are common in this group and this further compounds employment difficulties. In this article we outline some of the difficulties experienced by those with Asperger syndrome in the workplace, as well as the role and responsibility of those working in HR Departments to support those with Asperger syndrome according to the Equality Act (2010). We provide specific ideas for interventions and support that may be appropriate to this group. The article links to the HR Factsheet also available (see http://eprints.gold.ac.uk/5624/)

Genome-wide association study of multisite chronic pain in UK Biobank

Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype ‘chronic pain grade’, have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual’s overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches

Selective Cholesterol Dynamics between Lipoproteins and Caveolae/Lipid Rafts

Although low-density lipoprotein (LDL) receptor-mediated cholesterol uptake through clathrin-coated pits is now well understood, the molecular details and organizing principles for selective cholesterol uptake/efflux (reverse cholesterol transport, RCT) from peripheral cells remain to be resolved. It is not yet completely clear whether RCT between serum lipoproteins and the plasma membrane occurs primarily through lipid rafts/caveolae or from non-raft domains. To begin to address these issues, lipid raft/caveolae-, caveolae-, and non-raft-enriched fractions were resolved from purified plasma membranes isolated from L-cell fibroblasts and MDCK cells by detergent-free affinity chromatography and compared with detergent-resistant membranes isolated from the same cells. Fluorescent sterol exchange assays between lipoproteins (VLDL, LDL, HDL, apoA1) and these enriched domains provided new insights into supporting the role of lipid rafts/caveolae and caveolae in plasma membrane/lipoprotein cholesterol dynamics:  (i) lipids known to be translocated through caveolae were detected (cholesteryl ester, triacylglycerol) and/or enriched (cholesterol, phospholipid) in lipid raft/caveolae fractions; (ii) lipoprotein-mediated sterol uptake/efflux from lipid rafts/caveolae and caveolae was rapid and lipoprotein specific, whereas that from non-rafts was very slow and independent of lipoprotein class; and (iii) the rate and lipoprotein specificity of sterol efflux from lipid rafts/caveolae or caveolae to lipoprotein acceptors in vitro was slower and differed in specificity from that in intact cellsconsistent with intracellular factors contributing significantly to cholesterol dynamics between the plasma membrane and lipoproteins

Plin2 Inhibits Cellular Glucose Uptake through Interactions with SNAP23, a SNARE Complex Protein

Although a link between excess lipid storage and aberrant glucose metabolism has been recognized for many years, little is known what role lipid storage droplets and associated proteins such as Plin2 play in managing cellular glucose levels. To address this issue, the influence of Plin2 on glucose uptake was examined using 2-NBD-Glucose and [(3)H]-2-deoxyglucose to show that insulin-mediated glucose uptake was decreased 1.7- and 1.8-fold, respectively in L cell fibroblasts overexpressing Plin2. Conversely, suppression of Plin2 levels by RNAi-mediated knockdown increased 2-NBD-Glucose uptake several fold in transfected L cells and differentiated 3T3-L1 cells. The effect of Plin2 expression on proteins involved in glucose uptake and transport was also examined. Expression of the SNARE protein SNAP23 was increased 1.6-fold while levels of syntaxin-5 were decreased 1.7-fold in Plin2 overexpression cells with no significant changes observed in lipid droplet associated proteins Plin1 or FSP27 or with the insulin receptor, GLUT1, or VAMP4. FRET experiments revealed a close proximity of Plin2 to SNAP23 on lipid droplets to within an intramolecular distance of 51 Å. The extent of targeting of SNAP23 to lipid droplets was determined by co-localization and co-immunoprecipitation experiments to show increased partitioning of SNAP23 to lipid droplets when Plin2 was overexpressed. Taken together, these results suggest that Plin2 inhibits glucose uptake by interacting with, and regulating cellular targeting of SNAP23 to lipid droplets. In summary, the current study for the first time provides direct evidence for the role of Plin2 in mediating cellular glucose uptake