Global citizens: Who are they?

A growing desire to instigate global citizenship programmes in Higher Education (HE) has led to the development of optional structured opportunities for students to engage in prosocial activities. One of the challenges facing such programmes is to demonstrate and plan for the personal growth of those students. This paper reports the dispositional, prosocial and attitudinal characteristics; knowledge and skills; and perceptions of social justice that students who undertake these activities bring to their initial participation. The findings indicate, that in comparison to a control group, the students differ significantly in a number of important ways (e.g. conscientiousness, extraversion, openness; Machiavellianism, prosocial behaviour; self-esteem; skills relating to social action and tolerance and understanding and their concern regarding social problems). However, consideration should be given to the ways in which those students can be developed within a framework for social justice. Further, recruitment procedures for citizenship programmes in general should encourage the participation of a more diverse group of students than currently appears to be the case

Direct evidence for the ring opening of monosaccharide anions in the gas phase: photodissociation of aldohexoses and aldohexoses derived from disaccharides using variable-wavelength infrared irradiation in the carbonyl stretch region

a b s t r a c t All eight D-aldohexoses and aldohexoses derived from the non-reducing end of disaccharides were investigated by variable-wavelength infrared multiple-photon dissociation (IRMPD) as anions in the negative-ion mode. Spectroscopic evidence supports the existence of a relatively abundant open-chain configuration of the anions in the gas phase, based on the observation of a significant carbonyl absorption band near 1710 cm À1 . The abundance of the open-chain configuration of the aldohexose anions was approximately 1000-fold or greater than that of the neutral sugars in aqueous solution. This provides an explanation as to why it has not been possible to discriminate the anomeric configuration of aldohexose anions in the gas phase when derived from the non-reducing sugar of a disaccharide. Evidence from photodissociation spectra also indicates that the different aldohexoses yield product ions with maximal abundances at different wavelengths, and that the carbonyl stretch region is useful for differentiation of sugar stereochemistries. Quantum-chemical calculations indicate relatively low energy barriers to intramolecular proton transfer between hydroxyl groups and adjacent alkoxy sites located on open-chain sugar anions, suggesting that an ensemble of alkoxy charge locations contributes to their observed photodissociation spectra. Ring opening of monosaccharide anions and interconversion among configurations is an inherent property of the ions themselves and occurs in vacuo independent of solvent participation

Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth

The A20 protein is a known inhibitor of apoptosis that here is shown to be a novel cancer stem cell-promoting factor associated with poor glioma patient survival

Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E–09 and 4.10E–18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.publishedVersio

Genetics of rheumatoid arthritis contributes to biology and drug discovery

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Brain structural differences between 73- and 92-year olds matched for childhood intelligence, social background, and intracranial volume

Fully characterizing age differences in the brain is a key task for combating aging-related cognitive decline. Using propensity score matching on 2 independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age of 92 years (n = 42) to very similar participants at mean age of 73 years (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in gray and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural aging, in which brains from the 8th and 10th decades of life differ widely despite the same cognitive, socioeconomic, and brain-volumetric starting points

A glow discharge ion source with Fourier transform ion cyclotron resonance mass spectrometric detection

AbstractA glow discharge (GD) ion source has been coupled to a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer using a four-element electrostatic lens to accelerate and focus ions generated external to the instrument's high magnetic field into its analyzer cell. Like other GD mass spectrometers, GD-FT-ICR can provide a quantitative measure of bulk analyte concentration with good precision and accuracy. Although detection limits currently attainable are several orders of magnitude higher than the commercially available magnetic sector-based instrument, GD-FT-ICR holds promise for ultrahigh resolving power elemental mass analysis. Several schemes are proposed to lower the detection limits of the technique while still providing high enough resolution to resolve isobaric interferences