Increasing the clinical psychiatric knowledge base about pathogenic copy number variation

Specific copy number variants (CNVs) have been robustly associated with intellectual disability, autism, and schizophrenia. Most of the literature focus has been on documenting the existence of these phenomena. There are few data to guide therapeutic choices for these “orphan” diseases. We call for systematic and longitudinal case reports which, if carefully conducted, may provide crucial initial knowledge to guide therapeutics. We provide a step-by-step overview, a tailored set of consensus criteria for high-quality case reports, and a specific set of learning resources

Optically Faint Radio Sources: Reborn AGN?

We have discovered a number of relatively strong radio sources in the field-of-view of SDSS galaxy clusters which present no optical counterparts down to the magnitude limits of the SDSS. The optically faint radio sources appear as double-lobed or core-jet objects on the FIRST radio images and have projected angular sizes ranging from 0.5 to 1.0 arcmin. We have followed-up these sources with near-infrared imaging using the wide-field imager HAWK-I on the VLT. K_s-band emitting regions, about 1.5 arcsec in size and coincident with the centers of the radio structures, were detected in all the sources, with magnitudes in the range 17-20 mag. We have used spectral modelling to characterize the sample sources. In general, the radio properties are similar to those observed in 3CRR sources but the optical-radio slopes are consistent with moderate to high redshift (z<4) gigahertz-peaked spectrum sources. Our results suggest that these unusual objects are galaxies whose black hole has been recently re-ignited but retain large-scale radio structures, signatures of previous AGN activity.Comment: Accepted for publication in A&

Municipal composts improve landscape plant establishment in compacted soil

Urban landscape soils are often compacted by construction activities, thereby restricting plant establishment. Common approaches to improve plant establishment on compacted soils are to till soil before plant installation, to apply compost, or to choose plants that can tolerate drought. This research was undertaken to evaluate the relative importance of remedial practices (tillage, compost application, and plant selection) on survival and growth of landscape plants in compacted, non-irrigated soil in a mediterranean climate (western Oregon, USA). In 2008, moist silt loam soil was compacted with a vibrating roller, followed by application of compost, tillage, and plant installation. Planting holes (25 cm deep x 15 cm diameter) for installation of transplants from 3.8-L pots were drilled into compacted soil using a power auger. We report soil and plant data for 2009. Pre-plant compost application increased plant growth and quality of both standard and drought-tolerant landscape plants. The first-year plant growth response to compost was the same for compost left on the soil surface or compost incorporated via roto-tilling. Apparently, enough compost fell into the planting holes on the “no till” plots to stimulate plant establishment. Biosolids compost provided more plant-available nitrogen than yard debris compost, but compost effects on plant growth and quality were similar for most plant varieties. Groundcover plants grew more with the biosolids compost than with the yard debris compost. We conclude that compost application is beneficial for plant establishment for all landscape species tested, and that it is not essential to incorporate the compost into soil before planting

Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia

The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 × 10-8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P=0.015, positive predictive value=35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect

Magnetic Reconnection with Asymmetry in the Outflow Direction

Magnetic reconnection with asymmetry in the outflow direction occurs in the Earth's magnetotail, coronal mass ejections, flux cancellation events, astrophysical disks, spheromak merging experiments, and elsewhere in nature and the laboratory. A control volume analysis is performed for the case of steady antiparallel magnetic reconnection with asymmetric downstream pressure, which is used to derive scaling relations for the outflow velocity from each side of the current sheet and the reconnection rate. Simple relationships for outflow velocity are presented for the incompressible case and the case of symmetric downstream pressure but asymmetric downstream density. Asymmetry alone is not found to greatly affect the reconnection rate. The flow stagnation point and magnetic field null do not coincide in a steady state unless the pressure gradient is negligible at the flow stagnation point.Comment: 12 pages, 8 figures. Submitted to JGR. Any comments will be appreciate

Problem gamblers share deficits in impulsive decision-making with alcohol-dependent individuals

Aims: Problem gambling has been proposed to represent a ‘behavioural addiction’ that may provide key insights into vulnerability mechanisms underlying addiction in brains that are not affected by the damaging effects of drugs. Our aim was to investigate the neurocognitive profile of problem gambling in comparison with alcohol dependence. We reasoned that shared deficits across the two conditions may reflect underlying vulnerability mechanisms, whereas impairments specific to alcohol dependence may reflect cumulative effects of alcohol consumption. Design: Cross-sectional study. Setting: Out-patient addiction treatment centres and university behavioural testing facilities. Participants: A naturalistic sample of 21 male problem and pathological gamblers, 21 male alcohol-dependent out-patients and 21 healthy male control participants. Measurements: Neurocognitive battery assessing decision-making, impulsivity and working memory. Findings: The problem gamblers and alcohol-dependent groups displayed impairments in risky decision-making and cognitive impulsivity relative to controls. Working memory deficits and slowed deliberation times were specific to the alcohol-dependent group. Conclusions: Gambling and alcohol-dependent groups shared deficits in tasks linked to ventral prefrontal cortical dysfunction. Tasks loading on dorsolateral prefrontal cortex were selectively impaired in the alcohol-dependent group, presumably as a consequence of long-term alcohol use

Ornamental bill color rapidly signals changing condition

Ornamental bill color is postulated to function as a condition-dependent signal of individual quality in a variety of taxonomically distant bird families. Most red, orange, and yellow bill colors are derived from carotenoid pigments, and carotenoid deposition in ornamentation may trade off with their use as immunostimulants and antioxidants or with other physiological functions. Several studies have found that bill color changes in response to physiological perturbations, but how quickly such changes can occur remains unclear. We tested the hypothesis that carotenoid-based orange bill color of American goldfinches Spinus tristis responds dynamically to rapid changes in physiological stress and reflects short-term changes in condition. We captured male and female goldfinches and measured bill color in the field and again under captive conditions several hours later. The following day, the captive birds were injected with either immunostimulatory lipopolysaccharide (LPS) or a control saline and changes in bill color were measured over a five day period. Yellow saturation of the bill decreased within 6.5 h between the field and captivity measures on the first day, presumably in response to capture stress. Over the longer experimental period, bill hue and luminance decreased significantly, whereas saturation significantly increased in both LPS and control groups. Bill hue and luminance decreased significantly more in birds treated with LPS than in control birds. Among LPS treated birds, individuals expressing high bill color at the beginning of the experiment lost more color than ‘low-color’ birds, but still retained higher color at the end of the experiment, suggesting that birds that invest heavily in bill coloration are able to sustain high costs in the face of a challenge. Bill color change may have resulted from rapid reallocation of carotenoids from ornamentation to immune function. However, the complex shifts in bill color over time suggest that bill color may be influenced by multiple carotenoid compounds and/or changes in blood flow or chemistry in vessels just beneath the translucent keratinized outer layer of the bill. We conclude that bill color is a dynamic, condition-dependent trait that strategically and reliably signals short-term fluctuations in physiological condition

Lack of Support for the Genes by Early Environment Interaction Hypothesis in the Pathogenesis of Schizophrenia

Ursini et al reported recently that the liability of schizophrenia explained by a polygenic risk score (PRS) derived from the variants most associated with schizophrenia was increased 5-fold in individuals who experienced complications during pregnancy or birth. Follow-up gene expression analysis showed that the genes mapping to the most associated genetic variants are highly expressed in placental tissues. If confirmed, these findings will have major implications in our understanding of the joint effect of genes and environment in the pathogenesis of schizophrenia. We examined the interplay between PRS and obstetric complications (OCs) in 5 independent samples (effective N = 2110). OCs were assessed with the full or modified Lewis-Murray scale, or with birth weight < 2.5 kg as a proxy. In a large cohort we tested whether the pathways from placenta-relevant variants in the original report were associated with case-control status. Unlike in the original study, we did not find significant effect of PRS on the presence of OCs in cases, nor a substantial difference in the association of PRS with case-control status in samples stratified by the presence of OCs. Furthermore, none of the PRS by OCs interactions were significant, nor were any of the biological pathways, examined in the Swedish cohort. Our study could not support the hypothesis of a mediating effect of placenta biology in the pathway from genes to schizophrenia. Methodology differences, in particular the different scales measuring OCs, as well as power constraints for interaction analyses in both studies, may explain this discrepancy