Novel implications of Lingo-1 signaling in the prefrontal cortex and hippocampus of perinatal phencyclidine treated rats in a neurodevelopmental model of schizophrenia

Abstract of a poster presentation

Amplified Concern for Social Risk in Adolescence: Development and Validation of a New Measure.

In adolescence, there is a heightened propensity to take health risks such as smoking, drinking or driving too fast. Another facet of risk taking, social risk, has largely been neglected. A social risk can be defined as any decision or action that could lead to an individual being excluded by their peers, such as appearing different to one's friends. In the current study, we developed and validated a measure of concern for health and social risk for use in individuals of 11 years and over (N = 1399). Concerns for both health and social risk declined with age, challenging the commonly held stereotype that adolescents are less worried about engaging in risk behaviours, compared with adults. The rate of decline was steeper for social versus health risk behaviours, suggesting that adolescence is a period of heightened concern for social risk. We validated our measure against measures of rejection sensitivity, depression and risk-taking behaviour. Greater concern for social risk was associated with increased sensitivity to rejection and greater depressed mood, and this association was stronger for adolescents compared with adults. We conclude that social risks should be incorporated into future models of risk-taking behaviour, especially when they are pitted against health risks

The corporate constitution of national culture:The mythopoeia of 1966

Focussing on corporatized and mediated imaginings of nation - as highly political, public and pedagogic processes - we aim within this paper to address important questions of cultural identification and discursive address. Our focus is on the ubiquity of the year 1966 in popular narratives of Englishness in the immediacy of major football tournaments: connoting far more than football, we argue that the mythopoesis of 1966 - as a somewhat artificial, powerful myth-making mnemonic - is a historically situated toponym that conjures up the supremacy of England on the international stage. Further, through the performance of an aesthetic of selective silence, we propose that the mythopoeia of 1966 reasserts a utopic abstraction of nation, and acceptance and enactment of, and acquiescence to, mythical English 'values'. © 2014 © 2014 Taylor & Francis

Prenatal Insecticide Exposures and Birth Weight and Length among an Urban Minority Cohort

We reported previously that insecticide exposures were widespread among minority women in New York City during pregnancy and that levels of the organophosphate chlorpyrifos in umbilical cord plasma were inversely associated with birth weight and length. Here we expand analyses to include additional insecticides (the organophosphate diazinon and the carbamate propoxur), a larger sample size (n = 314 mother–newborn pairs), and insecticide measurements in maternal personal air during pregnancy as well as in umbilical cord plasma at delivery. Controlling for potential confounders, we found no association between maternal personal air insecticide levels and birth weight, length, or head circumference. For each log unit increase in cord plasma chlorpyrifos levels, birth weight decreased by 42.6 g [95% confidence interval (CI), −81.8 to −3.8, p = 0.03] and birth length decreased by 0.24 cm (95% CI, −0.47 to −0.01, p = 0.04). Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were also inversely associated with birth weight and length (p < 0.05). Birth weight averaged 186.3 g less (95% CI, −375.2 to −45.5) among newborns with the highest compared with lowest 26% of exposure levels (p = 0.01). Further, the associations between birth weight and length and cord plasma chlorpyrifos and diazinon were highly significant (p ≤ 0.007) among newborns born before the 2000–2001 U.S. Environmental Protection Agency’s regulatory actions to phase out residential use of these insecticides. Among newborns born after January 2001, exposure levels were substantially lower, and no association with fetal growth was apparent (p > 0.8). The propoxur metabolite 2-isopropoxyphenol in cord plasma was inversely associated with birth length, a finding of borderline significance (p = 0.05) after controlling for chlorpyrifos and diazinon. Results indicate that prenatal chlorpyrifos exposures have impaired fetal growth among this minority cohort and that diazinon exposures may have contributed to the effects. Findings support recent regulatory action to phase out residential uses of the insecticides

Genetic and epigenetic regulation in Lingo-1 : Effects on cognitive function and white matter microstructure in a case-control study for schizophrenia

Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) plays a vital role in a large number of neuronal processes underlying learning and memory, which are known to be disrupted in schizophrenia. However, Lingo-1 has never been examined in the context of schizophrenia. The genetic association of a single-nucleotide polymorphism (SNP, rs3144) and methylation (CpG sites) in the Lingo-1 3′-UTR region was examined, with the testing of cognitive dysfunction and white matter (WM) integrity in a schizophrenia case-control cohort (n = 268/group). A large subset of subjects (97 control and 161 schizophrenia subjects) underwent structural magnetic resonance imaging (MRI) brain scans to assess WM integrity. Frequency of the rs3144 minor allele was overrepresented in the schizophrenia population (p = 0.03), with an odds ratio of 1.39 (95% CI 1.016–1.901). CpG sites surrounding rs3144 were hypermethylated in the control population (p = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (p < 0.05), in addition to having associations with WM integrity (p = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in Lingo-1 in schizophrenia. Both of these genetic and epigenetic alterations may also have associations with cognitive dysfunction and WM integrity in the context of the schizophrenia pathophysiology

Proteomic analysis of Plasmodium falciparum histone deacetylase 1 complex proteins

Plasmodium falciparum histone deacetylases (PfHDACs) are an important class of epigenetic regulators that alter protein lysine acetylation, contributing to regulation of gene expression and normal parasite growth and development. PfHDACs are therefore under investigation as drug targets for malaria. Despite this, our understanding of the biological roles of these enzymes is only just beginning to emerge. In higher eukaryotes, HDACs function as part of multi-protein complexes and act on both histone and non-histone substrates. Here, we present a proteomics analysis of PfHDAC1 immunoprecipitates, identifying 26 putative P. falciparum complex proteins in trophozoite-stage asexual intraerythrocytic parasites. The co-migration of two of these (P. falciparum heat shock proteins 70-1 and 90) with PfHDAC1 was validated using Blue Native PAGE combined with Western blot. These data provide a snapshot of possible PfHDAC1 interactions and a starting point for future studies focused on elucidating the broader function of PfHDACs in Plasmodium parasites

The construction and use of bacterial DNA microarrays based on an optimized two-stage PCR strategy

BACKGROUND: DNA microarrays are a powerful tool with important applications such as global gene expression profiling. Construction of bacterial DNA microarrays from genomic sequence data using a two-stage PCR amplification approach for the production of arrayed DNA is attractive because it allows, in principal, the continued re-amplification of DNA fragments and facilitates further utilization of the DNA fragments for additional uses (e.g. over-expression of protein). We describe the successful construction and use of DNA microarrays by the two-stage amplification approach and discuss the technical challenges that were met and resolved during the project. RESULTS: Chimeric primers that contained both gene-specific and shared, universal sequence allowed the two-stage amplification of the 3,168 genes identified on the genome of Synechocystis sp. PCC6803, an important prokaryotic model organism for the study of oxygenic photosynthesis. The gene-specific component of the primer was of variable length to maintain uniform annealing temperatures during the 1(st ) round of PCR synthesis, and situated to preserve full-length ORFs. Genes were truncated at 2 kb for efficient amplification, so that about 92% of the PCR fragments were full-length genes. The two-stage amplification had the additional advantage of normalizing the yield of PCR products and this improved the uniformity of DNA features robotically deposited onto the microarray surface. We also describe the techniques utilized to optimize hybridization conditions and signal-to-noise ratio of the transcription profile. The inter-lab transportability was demonstrated by the virtual error-free amplification of the entire genome complement of 3,168 genes using the universal primers in partner labs. The printed slides have been successfully used to identify differentially expressed genes in response to a number of environmental conditions, including salt stress. CONCLUSIONS: The technique detailed here minimizes the cost and effort to replicate a PCR-generated DNA gene fragment library and facilitates several downstream processes (e.g. directional cloning of fragments and gene expression as affinity-tagged fusion proteins) beyond the primary objective of producing DNA microarrays for global gene expression profiling

Sensitivity of a national coronial database for monitoring unnatural deaths among ex-prisoners in Australia

<p>Abstract</p> <p>Background</p> <p>The period immediately after release from custody is a time of marked vulnerability and increased risk of death for ex-prisoners. Despite this, there is currently no routine, national system for monitoring ex-prisoner mortality in Australia. This study subsequently aimed to evaluate the sensitivity of Australia's National Coroners Information System (NCIS) for identifying reportable deaths among prisoners and ex-prisoners.</p> <p>Findings</p> <p>Prisoner and ex-prisoner deaths identified through an independent search of the NCIS were compared with 'gold standard' records of prisoner and ex-prisoner deaths, generated from a national monitoring system and a state-based record linkage study, respectively. Of 294 known deaths in custody from 2001-2007, an independent search of the NCIS identified 229, giving a sensitivity of 77.9% (72.8%-82.3%). Of 677 known deaths among ex-prisoners from 2001-2007, an independent search of the NCIS identified 37, giving a sensitivity of 5.5% (4.0-7.4%). Ex-prisoner deaths that were detected were disproportionately drug-related, occurring within the first four weeks post-release, among younger prisoners and among those with more than two prior prison admissions.</p> <p>Conclusions</p> <p>Although a search of the NCIS detected the majority of reportable deaths among prisoners, it was only able to detect a small minority of reportable deaths among ex-prisoners. This suggests that the NCIS is not effective for monitoring mortality among ex-prisoners in Australia. Given the elevated rates of mortality among ex-prisoners in Australia and elsewhere, there remains an urgent need to establish a process for routine monitoring of ex-prisoner mortality, preferably through record linkage.</p

Potential for ecological nonlinearities and thresholds to inform Pacific salmon management

AbstractEcology is often governed by nonlinear dynamics. Nonlinear ecological relationships can include thresholds—incremental changes in drivers that provoke disproportionately large ecological responses. Among the species that experience nonlinear and threshold dynamics are Pacific salmon (Oncorhynchus spp.). These culturally, ecologically, and economically significant fishes are in many places declining and management focal points. Often, managers can influence or react to ecological conditions that salmon experience, suggesting that nonlinearities, especially thresholds, may provide opportunities to inform decisions. However, nonlinear dynamics are not always invoked in management decisions involving salmon. Here, we review reported nonlinearities and thresholds in salmon ecology, describe potential applications that scientists and managers could develop to leverage nonlinear dynamics, and offer a path toward decisions that account for ecological nonlinearities and thresholds to improve salmon outcomes. It appears that nonlinear dynamics are not uncommon in salmon ecology and that many management arenas may potentially leverage them to enable more effective or efficient decisions. Indeed, decisions guided by nonlinearities and thresholds may be particularly desirable considering salmon management arenas are often characterized by limited resources and mounting ecological stressors, practical constraints, and conservation challenges. More broadly, many salmon systems are data‐rich and there are an extensive range of ecological contexts in which salmon are sensitive to anthropogenic decisions. Approaches developed to leverage nonlinearities in salmon ecology may serve as examples that may inform analogous approaches in other systems and taxa

Polymorphism in M(H2PO2)3 (M = V, Al, Ga) compounds with the perovskite-related ReO3 structure.

Trivalent metal hypophosphites with the general formula M(H2PO2)3 (M = V, Al, Ga) adopt the ReO3 structure, with each compound displaying two structural polymorphs. High-pressure synchrotron X-ray studies reveal a pressure-driven phase transition in Ga(H2PO2)3 that can be understood on the basis of ab initio thermodynamics