Engaging children in meaningful charity: opening-up the spaces within which children learn to give

This paper presents qualitative evidence from an in-depth, participative action research project with 150 children aged 4-8 years old, exploring their experiences, perceptions and preferences regarding charitable giving. Most children positively engage in charitable giving through home, school and their community, however less than 20% are aware of the cause area they are being asked to support, and most have little decision-making in their giving. Children’s willingness to engage increases when they critically examine the cause area and are facilitated to lead on giving decisions, often resulting in increased and sustained efforts to support cause areas that matter to them

The Genetic Effect of Copy Number Variations on the Risk of Type 2 Diabetes in a Korean Population

BACKGROUND: Unlike Caucasian populations, genetic factors contributing to the risk of type 2 diabetes mellitus (T2DM) are not well studied in Asian populations. In light of this, and the fact that copy number variation (CNV) is emerging as a new way to understand human genomic variation, the objective of this study was to identify type 2 diabetes-associated CNV in a Korean cohort. METHODOLOGY/PRINCIPAL FINDINGS: Using the Illumina HumanHap300 BeadChip (317,503 markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 275 patients with type 2 diabetes mellitus (T2DM) and 496 nondiabetic subjects (Total n = 771). To increase the sensitivity of CNV identification, we incorporated multiple factors using PennCNV, a program that is based on the hidden Markov model (HMM). To assess the genetic effect of CNV on T2DM, a multivariate logistic regression model controlling for age and gender was used. We identified a total of 7,478 CNVs (average of 9.7 CNVs per individual) and 2,554 CNV regions (CNVRs; 164 common CNVRs for frequency>1%) in this study. Although we failed to demonstrate robust associations between CNVs and the risk of T2DM, our results revealed a putative association between several CNVRs including chr15:45994758-45999227 (P = 8.6E-04, P(corr) = 0.01) and the risk of T2DM. The identified CNVs in this study were validated using overlapping analysis with the Database of Genomic Variants (DGV; 71.7% overlap), and quantitative PCR (qPCR). The identified variations, which encompassed functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the development process, in cell communication, in signal transduction, and in biological regulation. CONCLUSION/SIGNIFICANCE: We expect that the methods and findings in this study will contribute in particular to genome studies of Asian populations

Neurexin-1 and Frontal Lobe White Matter: An Overlapping Intermediate Phenotype for Schizophrenia and Autism Spectrum Disorders

Background: Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown. Method/Principal Findings: 53 healthy individuals between 18–59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject’s sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 39 untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia. Conclusions: Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brai

Rare Copy Number Deletions Predict Individual Variation in Intelligence

Phenotypic variation in human intellectual functioning shows substantial heritability, as demonstrated by a long history of behavior genetic studies. Many recent molecular genetic studies have attempted to uncover specific genetic variations responsible for this heritability, but identified effects capture little variance and have proven difficult to replicate. The present study, motivated an interest in “mutation load” emerging from evolutionary perspectives, examined the importance of the number of rare (or infrequent) copy number variations (CNVs), and the total number of base pairs included in such deletions, for psychometric intelligence. Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77) had been administered the Wechsler Abbreviated Scale of Intelligence (WASI). After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = −.30, p = .01). As prior studies have indicated greater heritability in individuals with relatively higher parental socioeconomic status (SES), we also examined the impact of ethnicity (Anglo/White vs. Other), as a proxy measure of SES; these groups did not differ on any genetic variable. This categorical variable significantly moderated the effect of length of deletions on intelligence, with larger effects being noted in the Anglo/White group. Overall, these results suggest that rare deletions (between 5% and 1% population frequency or less) adversely affect intellectual functioning, and that pleotropic effects might partly account for the association of intelligence with health and mental health status. Significant limitations of this research, including issues of generalizability and CNV measurement, are discussed

A national clinical decision support infrastructure to enable the widespread and consistent practice of genomic and personalized medicine

<p>Abstract</p> <p>Background</p> <p>In recent years, the completion of the Human Genome Project and other rapid advances in genomics have led to increasing anticipation of an era of genomic and personalized medicine, in which an individual's health is optimized through the use of all available patient data, including data on the individual's genome and its downstream products. Genomic and personalized medicine could transform healthcare systems and catalyze significant reductions in morbidity, mortality, and overall healthcare costs.</p> <p>Discussion</p> <p>Critical to the achievement of more efficient and effective healthcare enabled by genomics is the establishment of a robust, nationwide clinical decision support infrastructure that assists clinicians in their use of genomic assays to guide disease prevention, diagnosis, and therapy. Requisite components of this infrastructure include the standardized representation of genomic and non-genomic patient data across health information systems; centrally managed repositories of computer-processable medical knowledge; and standardized approaches for applying these knowledge resources against patient data to generate and deliver patient-specific care recommendations. Here, we provide recommendations for establishing a national decision support infrastructure for genomic and personalized medicine that fulfills these needs, leverages existing resources, and is aligned with the <it>Roadmap for National Action on Clinical Decision Support </it>commissioned by the U.S. Office of the National Coordinator for Health Information Technology. Critical to the establishment of this infrastructure will be strong leadership and substantial funding from the federal government.</p> <p>Summary</p> <p>A national clinical decision support infrastructure will be required for reaping the full benefits of genomic and personalized medicine. Essential components of this infrastructure include standards for data representation; centrally managed knowledge repositories; and standardized approaches for leveraging these knowledge repositories to generate patient-specific care recommendations at the point of care.</p

Citizenship Norms in Eastern Europe

Research on Eastern Europe stresses the weakness of its civil society and the lack of political and social involvement, neglecting the question: What do people themselves think it means to be a good citizen? This study looks at citizens’ definitions of good citizenship in Poland, Slovenia, the Czech Republic and Hungary, using 2002 European Social Survey data. We investigate mean levels of civic mindedness in these countries and perform regression analyses to investigate whether factors traditionally associated with civic and political participation are also correlated with citizenship norms across Eastern Europe. We show that mean levels of civic mindedness differ significantly across the four Eastern European countries. We find some support for theories on civic and political participation when explaining norms of citizenship, but also demonstrate that individual-level characteristics are differently related to citizenship norms across the countries of our study. Hence, our findings show that Eastern Europe is not a monolithic and homogeneous bloc, underscoring the importance of taking the specificities of countries into account

RNA-Seq of Human Neurons Derived from iPS Cells Reveals Candidate Long Non-Coding RNAs Involved in Neurogenesis and Neuropsychiatric Disorders

Genome-wide expression analysis using next generation sequencing (RNA-Seq) provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs) provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients