Preliminary Evaluation of the Group Teen Triple P Program for Parents of Teenagers Making the Transition to High School

Group Teen Triple P is a brief group parenting program for parents of teenagers. It is based on the successful Triple P – Positive Parenting Program for parents of children aged from 0 to 12, with a focus on helping parents manage the transition from late childhood to early adolescence. This paper describes the initial evaluation of a universal trial of the program offered to all parents of students entering their first year of high school at age 12 in a regional north Queensland school. Twenty-seven parents completed a battery of self-report questionnaires immediately before and after participating in the 8-week program. Participating parents reported significant reductions in conflict with their teenager, and on measures of laxness, over-reactivity, and disagreements with their partner over parenting issues. These are well-established parenting risk factors. In addition, parents reported significant improvements on measures of self-regulation, including self-efficacy, selfsufficiency, and self-management, and reductions on measures of depression, anxiety, and stress. It was concluded that a preliminary evaluation of the Group Teen Triple P program achieved its goals of reducing targeted risk factors associated with the development of behavioural and emotional problems in teenagers. The paper concludes with an examination of issues around parent recruitment and engagement which are crucial for the successful provision of effective and timely advice and support for parents of teenagers

Dopamine perturbation of gene co-expression networks reveals differential response in schizophrenia for translational machinery.

The dopaminergic hypothesis of schizophrenia (SZ) postulates that positive symptoms of SZ, in particular psychosis, are due to disturbed neurotransmission via the dopamine (DA) receptor D2 (DRD2). However, DA is a reactive molecule that yields various oxidative species, and thus has important non-receptor-mediated effects, with empirical evidence of cellular toxicity and neurodegeneration. Here we examine non-receptor-mediated effects of DA on gene co-expression networks and its potential role in SZ pathology. Transcriptomic profiles were measured by RNA-seq in B-cell transformed lymphoblastoid cell lines from 514 SZ cases and 690 controls, both before and after exposure to DA ex vivo (100 μM). Gene co-expression modules were identified using Weighted Gene Co-expression Network Analysis for both baseline and DA-stimulated conditions, with each module characterized for biological function and tested for association with SZ status and SNPs from a genome-wide panel. We identified seven co-expression modules under baseline, of which six were preserved in DA-stimulated data. One module shows significantly increased association with SZ after DA perturbation (baseline: P = 0.023; DA-stimulated: P = 7.8 × 10-5; ΔAIC = -10.5) and is highly enriched for genes related to ribosomal proteins and translation (FDR = 4 × 10-141), mitochondrial oxidative phosphorylation, and neurodegeneration. SNP association testing revealed tentative QTLs underlying module co-expression, notably at FASTKD2 (top P = 2.8 × 10-6), a gene involved in mitochondrial translation. These results substantiate the role of translational machinery in SZ pathogenesis, providing insights into a possible dopaminergic mechanism disrupting mitochondrial function, and demonstrates the utility of disease-relevant functional perturbation in the study of complex genetic etiologies

Near Infrared Adaptive Optics Imaging of QSO Host Galaxies

We report near-infrared (primarily H-band) adaptive optics (AO) imaging with the Gemini-N and Subaru Telescopes, of a representative sample of 32 nearby (z<0.3) QSOs selected from the Palomar-Green (PG) Bright Quasar Survey (BQS), in order to investigate the properties of the host galaxies. 2D modeling and visual inspection of the images shows that ~36% of the hosts are ellipticals, \~39% contain a prominent disk component, and ~25% are of undetermined type. 30% show obvious signs of disturbance. The mean M_H(host) = -24.82 (2.1L_H*), with a range -23.5 to -26.5 (~0.63 to 10 L_H*). At <L_H*, all hosts have a dominant disk component, while at >2 L_H* most are ellipticals. "Disturbed" hosts are found at all M_H(host), while "strongly disturbed" hosts appear to favor the more luminous hosts. Hosts with prominent disks have less luminous QSOs, while the most luminous QSOs are almost exclusively in ellipticals or in mergers (which presumably shortly will be ellipticals). At z<0.13, where our sample is complete at B-band, we find no clear correlation between M_B(QSO) and M_H(host). However, at z>0.15, the more luminous QSOs (M_B<-24.7), and 4/5 of the radio-loud QSOs, have the most luminous H-band hosts (>7L_H*), most of which are ellipticals. Finally, we find a strong correlation between the "infrared-excess", L_IR/L_BB, of QSOs with host type and degree of disturbance. Disturbed and strongly disturbed hosts and hosts with dominant disks have L_IR/L_BB twice that of non-disturbed and elliptical hosts, respectively. QSOs with "disturbed" and "strongly-disturbed" hosts are also found to have morphologies and mid/far-infrared colors that are similar to what is found for "warm" ultraluminous infrared galaxies, providing further evidence for a possible evolutionary connection between both classes of objects.Comment: 80 pages, accepted for publication in ApJ Supp

Transcriptome sequencing study implicates immune-related genes differentially expressed in schizophrenia: new data and a meta-analysis

We undertook an RNA sequencing (RNAseq)-based transcriptomic profiling study on lymphoblastoid cell lines of a European ancestry sample of 529 schizophrenia cases and 660 controls, and found 1058 genes to be differentially expressed by affection status. These differentially expressed genes were enriched for involvement in immunity, especially the 697 genes with higher expression in cases. Comparing the current RNAseq transcriptomic profiling to our previous findings in an array-based study of 268 schizophrenia cases and 446 controls showed a highly significant positive correlation over all genes. Fifteen (18%) of the 84 genes with significant (false discovery rateo0.05) expression differences between cases and controls in the previous study and analyzed here again were differentially expressed by affection status here at a genome-wide significance level (Bonferroni Po0.05 adjusted for 8141 analyzed genes in total, or Po ~ 6.1 × 10− 6), all with the same direction of effect, thus providing corroborative evidence despite each sample of fully independent subjects being studied by different technological approaches. Meta-analysis of the RNAseq and array data sets (797 cases and 1106 controls) showed 169 additional genes (besides those found in the primary RNAseq-based analysis) to be differentially expressed, and provided further evidence of immune gene enrichment. In addition to strengthening our previous array-based gene expression differences in schizophrenia cases versus controls and providing transcriptomic support for some genes implicated by other approaches for schizophrenia, our study detected new genes differentially expressed in schizophrenia. We highlight RNAseq-based differential expression of various genes involved in neurodevelopment and/or neuronal function, and discuss caveats of the approach

Compressed Sensing for Multidimensional Spectroscopy Experiments

Compressed sensing is a processing method that significantly reduces the number of measurements needed to accurately resolve signals in many fields of science and engineering. We develop a two-dimensional variant of compressed sensing for multidimensional spectroscopy and apply it to experimental data. For the model system of atomic rubidium vapor, we find that compressed sensing provides an order-of-magnitude (about 10-fold) improvement in spectral resolution along each dimension, as compared to a conventional discrete Fourier transform, using the same data set. More attractive is that compressed sensing allows for random undersampling of the experimental data, down to less than 5% of the experimental data set, with essentially no loss in spectral resolution. We believe that by combining powerful resolution with ease of use, compressed sensing can be a powerful tool for the analysis and interpretation of ultrafast spectroscopy data.Chemistry and Chemical Biolog

Dopamine perturbation of gene co-expression networks reveals differential response in schizophrenia for translational machinery

The dopaminergic hypothesis of schizophrenia (SZ) postulates that positive symptoms of SZ, in particular psychosis, are due to disturbed neurotransmission via the dopamine (DA) receptor D2 (DRD2). However, DA is a reactive molecule that yields various oxidative species, and thus has important non-receptor-mediated effects, with empirical evidence of cellular toxicity and neurodegeneration. Here we examine non-receptor-mediated effects of DA on gene co-expression networks and its potential role in SZ pathology. Transcriptomic profiles were measured by RNA-seq in B-cell transformed lymphoblastoid cell lines from 514 SZ cases and 690 controls, both before and after exposure to DA ex vivo (100 μM). Gene co-expression modules were identified using Weighted Gene Co-expression Network Analysis for both baseline and DA-stimulated conditions, with each module characterized for biological function and tested for association with SZ status and SNPs from a genome-wide panel. We identified seven co-expression modules under baseline, of which six were preserved in DA-stimulated data. One module shows significantly increased association with SZ after DA perturbation (baseline: P = 0.023; DA-stimulated: P = 7.8 × 10-5; ΔAIC = −10.5) and is highly enriched for genes related to ribosomal proteins and translation (FDR = 4 × 10−141), mitochondrial oxidative phosphorylation, and neurodegeneration. SNP association testing revealed tentative QTLs underlying module co-expression, notably at FASTKD2 (top P = 2.8 × 10−6), a gene involved in mitochondrial translation. These results substantiate the role of translational machinery in SZ pathogenesis, providing insights into a possible dopaminergic mechanism disrupting mitochondrial function, and demonstrates the utility of disease-relevant functional perturbation in the study of complex genetic etiologies

Transcriptomic signatures of schizophrenia revealed by dopamine perturbation in an ex vivo model

The dopaminergic hypothesis of schizophrenia (SZ) postulates that dopaminergic over activity causes psychosis, a central feature of SZ, based on the observation that blocking dopamine (DA) improves psychotic symptoms. DA is known to have both receptor- and non-receptor-mediated effects, including oxidative mechanisms that lead to apoptosis. The role of DA-mediated oxidative processes in SZ has been little studied. Here, we have used a cell perturbation approach and measured transcriptomic profiles by RNAseq to study the effect of DA exposure on transcription in B-cell transformed lymphoblastoid cell lines (LCLs) from 514 SZ cases and 690 controls. We found that DA had widespread effects on both cell growth and gene expression in LCLs. Overall, 1455 genes showed statistically significant differential DA response in SZ cases and controls. This set of differentially expressed genes is enriched for brain expression and for functions related to immune processes and apoptosis, suggesting that DA may play a role in SZ pathogenesis through modulating those systems. Moreover, we observed a non-significant enrichment of genes near genome-wide significant SZ loci and with genes spanned by SZ-associated copy number variants (CNVs), which suggests convergent pathogenic mechanisms detected by both genetic association and gene expression. The study suggests a novel role of DA in the biological processes of immune and apoptosis that may be relevant to SZ pathogenesis. Furthermore, our results show the utility of pathophysiologically relevant perturbation experiments to investigate the biology of complex mental disorders

Familiality of Gender Nonconformity Among Homosexual Men.

We examined whether recalled childhood gender nonconformity and self-reported adult gender nonconformity is familial, using data from 1154 families selected for having at least two homosexual brothers. Specifically, we examined the extent to which homosexual men's variation in gender nonconformity runs in families by examining pairs of genetic brothers who were both homosexual (N = 672-697 full sibling concordant pairs). We also examined similarity between homosexual and heterosexual brothers (N = 79-82 full sibling discordant pairs). Consistent with past studies, concordant pairs yielded modest positive correlations consistent with moderate genetic and/or familial environmental effects on gender nonconformity. Unlike results of smaller past studies, discordant pairs also yielded modest positive, though nonsignificant, correlations. Our results support the feasibility of supplementing genetic studies of male sexual orientation with analyses of gender nonconformity variation

The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction

Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5′ ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct

Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced Arthritis and Pathology

ABSTRACT Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis and arthralgia over the past decade. These include a recent outbreak in the Caribbean islands and the Americas that caused more than 1 million cases of viral arthralgia. Despite the major impact of CHIKV on global health, viral determinants that promote CHIKV-induced disease are incompletely understood. Most CHIKV strains contain a conserved opal stop codon at the end of the viral nsP3 gene. However, CHIKV strains that encode an arginine codon in place of the opal stop codon have been described, and deep-sequencing analysis of a CHIKV isolate from the Caribbean identified both arginine and opal variants within this strain. Therefore, we hypothesized that the introduction of the arginine mutation in place of the opal termination codon may influence CHIKV virulence. We tested this by introducing the arginine mutation into a well-characterized infectious clone of a CHIKV strain from Sri Lanka and designated this virus Opal524R. This mutation did not impair viral replication kinetics in vitro or in vivo . Despite this, the Opal524R virus induced significantly less swelling, inflammation, and damage within the feet and ankles of infected mice. Further, we observed delayed induction of proinflammatory cytokines and chemokines, as well as reduced CD4 + T cell and NK cell recruitment compared to those in the parental strain. Therefore, the opal termination codon plays an important role in CHIKV pathogenesis, independently of effects on viral replication. IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes significant outbreaks of viral arthralgia. Studies with CHIKV and other alphaviruses demonstrated that the opal termination codon within nsP3 is highly conserved. However, some strains of CHIKV and other alphaviruses contain mutations in the opal termination codon. These mutations alter the virulence of related alphaviruses in mammalian and mosquito hosts. Here, we report that a clinical isolate of a CHIKV strain from the recent outbreak in the Caribbean islands contains a mixture of viruses encoding either the opal termination codon or an arginine mutation. Mutating the opal stop codon to an arginine residue attenuates CHIKV-induced disease in a mouse model. Compared to infection with the opal-containing parental virus, infection with the arginine mutant causes limited swelling and inflammation, as well as dampened recruitment of immune mediators of pathology, including CD4 + T cells and NK cells. We propose that the opal termination codon plays an essential role in the induction of severe CHIKV disease