Clinical,socio‐demographic and psychological characteristics in individuals with persistent psychotic experiences with and without a “need for care”

Individuals reporting persistent psychotic experiences (PEs) in the general population, but without a “need for care”, are a unique group of particular importance in identifying risk and protective factors for psychosis. We compared people with persistent PEs and no “need for care” (non‐clinical, N=92) with patients diagnosed with a psychotic disorder (clinical, N=84) and controls without PEs (N=83), in terms of their phenomenological, socio‐demographic and psychological features. The 259 participants were recruited from one urban and one rural area in the UK, as part of the UNIQUE (Unusual Experiences Enquiry) study. Results showed that the non‐clinical group experienced hallucinations in all modalities as well as first‐rank symptoms, with an earlier age of onset than in the clinical group. Somatic/tactile hallucinations were more frequent than in the clinical group, while commenting and conversing voices were rare. Participants in the non‐clinical group were differentiated from their clinical counterparts by being less paranoid and deluded, apart from ideas of reference, and having fewer cognitive difficulties and negative symptoms. Unlike the clinical group, they were characterized neither by low psychosocial functioning nor by social adversity. However, childhood trauma featured in both groups. They were similar to the controls in psychological characteristics: they did not report current emotional problems, had intact self‐esteem, displayed healthy schemas about the self and others, showed high life satisfaction and well‐being, and high mindfulness. These findings support biopsychosocial models postulating that environmental and psychological factors interact with biological processes in the aetiology of psychosis. While some PEs may be more malign than others, lower levels of social and environmental adversity, combined with protective factors such as intact IQ, spirituality, and psychological and emotional well‐being, may reduce the likelihood of persistent PEs leading to pathological outcomes. Future research should focus on protective factors and determinants of well‐being in the context of PEs, rather than exclusively on risk factors and biomarkers of disease states.     

Discovery of a novel series of quinolone α7 nicotinic acetylcholine receptor agonists

High throughput screening led to the identification of a novel series of quinolone α7 nicotinic acetylcholine receptor (nAChR) agonists. Optimization of an HTS hit (1) led to 4-phenyl-1-(quinuclidin-3-ylmethyl)quinolin-2(1H)-one, which was found to be potent and selective. Poor brain penetrance in this series was attributed to transporter-mediated efflux, which was in turn due to high pK_a. A novel 4-fluoroquinuclidine significantly lowered the pK_a of the quinuclidine moiety, reducing efflux as measured by a Caco-2 assay.     

Identifying biochemical phenotypic differences between cryptic species

Molecular genetic methods can distinguish divergent evolutionary lineages in what previously appeared to be single species, but it is not always clear what functional differences exist between such cryptic species. We used a metabolomic approach to profile biochemical phenotype (metabotype) differences between two putative cryptic species of the earthworm Lumbricus rubellus. There were no straightforward metabolite biomarkers of lineage, i.e. no metabolites that were always at higher concentration in one lineage. Multivariate methods, however, identified a small number of metabolites that together helped distinguish the lineages, including uncommon metabolites such as Nε-trimethyllysine, which is not usually found at high concentrations. This approach could be useful for characterizing functional trait differences, especially as it is applicable to essentially any species group, irrespective of its genome sequencing status.     

Long-term depression: a cell biological view

Recent studies of the molecular mechanisms of long-term depression (LTD) suggest a crucial role for the signalling pathways of apoptosis (programmed cell death) in the weakening and elimination of synapses and dendritic spines. With this backdrop, we suggest that LTD can be considered as the electrophysiological aspect of a larger cell biological programme of synapse involution, which uses localized apoptotic mechanisms to sculpt synapses and circuits without causing cell death.     

Implications of climate change for potamodromous fishes

There is little understanding of how climate change will impact potamodromous freshwater fishes. Since the mid 1970s, a decline in annual rainfall in south‐western Australia (a globally recognized biodiversity hotspot) has resulted in the rivers of the region undergoing severe reductions in surface flows (ca. 50%). There is universal agreement amongst Global Climate Models that rainfall will continue to decline in this region. Limited data are available on the movement patterns of the endemic freshwater fishes of south‐western Australia or on the relationship between their life histories and hydrology. We used this region as a model to determine how dramatic hydrological change may impact potamodromous freshwater fishes. Migration patterns of fishes in the largest river in south‐western Australia were quantified over a 4 year period and were related to a number of key environmental variables including discharge, temperature, pH, conductivity and dissolved oxygen. Most of the endemic freshwater fishes were potamodromous, displaying lateral seasonal spawning migrations from the main channel into tributaries, and there were significant temporal differences in movement patterns between species. Using a model averaging approach, amount of discharge was clearly the best predictor of upstream and downstream movement for most species. Given past and projected reductions in surface flow and groundwater, the findings have major implications for future recruitment rates and population viabilities of potamodromous fishes. Freshwater ecosystems in drying climatic regions can only be managed effectively if such hydro‐ecological relationships are considered. Proactive management and addressing existing anthropogenic stressors on aquatic ecosystems associated with the development of surface and groundwater resources and land use is required to increase the resistance and resilience of potamodromous fishes to ongoing flow reductions.     

Hybridisation,paternal leakage and mitochondrial DNA linearization in three anomalous fish (Scombridae)

Using mitochondrial DNA for species identification and population studies assumes that the genome is maternally inherited, circular, located in the cytoplasm and lacks recombination. This study explores the mitochondrial genomes of three anomalous mackerel. Complete mitochondrial genome sequencing plus nuclear microsatellite genotyping of these fish identified them as Scomberomorus munroi (spotted mackerel). Unlike normal S. munroi, these three fish also contained different linear, mitochondrial genomes of Scomberomorus semifasciatus (grey mackerel). The results are best explained by hybridisation, paternal leakage and mitochondrial DNA linearization. This unusual observation may provide an explanation for mtDNA outliers in animal population studies.     

Association of FCGR2A and FCGR2A-FCGR3A haplotypes with susceptibility to giant cell arteritis

The Fc gamma receptors have been shown to play important roles in the initiation and regulation of many immunological and inflammatory processes and to amplify and refine the immune response to an infection. We have investigated the hypothesis that polymorphism within the FCGR genetic locus is associated with giant cell arteritis (GCA). Biallelic polymorphisms in FCGR2A, FCGR3A, FCGR3B and FCGR2B were examined for association with biopsy-proven GCA (n = 85) and healthy ethnically matched controls (n = 132) in a well-characterised cohort from Lugo, Spain. Haplotype frequencies and linkage disequilibrium (D') were estimated across the FCGR locus and a model-free analysis performed to determine association with GCA. There was a significant association between FCGR2A-131RR homozygosity (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.12 to 3.77, P = 0.02, compared with all others) and carriage of FCGR3A-158F (OR 3.09, 95% CI 1.10 to 8.64, P = 0.03, compared with non-carriers) with susceptibility to GCA. FCGR haplotypes were examined to refine the extent of the association. The haplotype showing the strongest association with GCA susceptibility was the FCGR2A-FCGR3A 131R-158F haplotype (OR 2.84, P = 0.01 for homozygotes compared with all others). There was evidence of a multiplicative joint effect between homozygosity for FCGR2A-131R and HLA-DRB1*04 positivity, consistent with both of these two genetic factors contributing to the risk of disease. The risk of GCA in HLA-DRB1*04 positive individuals homozygous for the FCGR2A-131R allele is increased almost six-fold compared with those with other FCGR2A genotypes who are HLA-DRB1*04 negative. We have demonstrated that FCGR2A may contribute to the 'susceptibility' of GCA in this Spanish population. The increased association observed with a FCGR2A-FCGR3A haplotype suggests the presence of additional genetic polymorphisms in linkage disequilibrium with this haplotype that may contribute to disease susceptibility. These findings may ultimately provide new insights into disease pathogenesis.     

Sex ratio dynamics of Gonatocerus ashmeadi,a parasitoid of the glassy‐winged sharpshooter in California

We examined whether Gonatocerus ashmeadi Girault (Hymenoptera: Mymaridae), a quasi‐gregarious egg parasitoid of Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae), produces precise sex ratios under a field setting. Under laboratory conditions, previous studies have shown that G. ashmeadi exhibits strongly female‐biased sex ratios with low variance in the number of males produced per host. Field‐collected G. ashmeadi tend to produce much less female‐biased sex ratios with high variance in male numbers. We found significant positive effects of proportion parasitism and host density on sex ratio. Proportion parasitism also had a positive effect on sex ratio variance. The findings of this study are discussed in the context of theoretical predictions.     

Optimization of an in vivo plant P450 monooxygenase system in Saccharomyces cerevisiae

Cytochrome P450s are heme-thiolate oxygenases involved in a wide number of reactions such as epoxidation, hydroxylation, and demethylation. Heterologously expressed eukaryotic P450s are potentially useful biocatalysts for stereospecific oxygenation reactions under mild conditions. Numerous factors, such as intracellular pH, cytochrome P450, cytochrome P450 reductase, NADPH, and oxygen concentration all influence the in vivo activity. To systematically examine these factors, we selected ferulate 5-hydroxylase (F5H), a plant P450, with the Saccharomyces cerevisiae WAT11 strain as an expression host. Two media compositions and two cultivation procedures were investigated to optimize the in vivo activity of F5H. We modified a previously published selective growth medium (Pompon et al. [1996] Methods Enzymol 272:51-64) that increased the specific growth rate and cell yield of the host strain. A cultivation procedure with separate growth and induction stages that each contained selective media resulted in a 45% increase of whole cell F5H specific activity. In a medium designed for simultaneous growth and induction, we observed a 2.6-fold higher specific F5H activity, but substantially lower cell yield. Surprisingly, in this medium the higher specific F5H activity did not correlate with a higher P450 concentration. The effects of addition of the first committed heme precursor, delta-aminolevulinic acid, and Fe(III) at the beginning of induction period were also studied for our two-stage procedure. A small, but significant (P < 0.05) increase in whole cell F5H activity was observed following ALA addition.     

Phylogeny of the gudgeons (Teleostei: Cyprinidae: Gobioninae)

The members of the cyprinid subfamily Gobioninae, commonly called gudgeons, form one of the most well-established assemblages in the family Cyprinidae. The subfamily is a species-rich group of fishes, these fishes display diverse life histories, appearances, and behavior. The phylogenetic relationships of Gobioninae are examined using sequence data from four loci: cytochrome b, cytochrome c oxidase I, opsin, and recombination activating gene 1. This investigation produced a data matrix of 4114 bp for 162 taxa that was analyzed using parsimony, maximum likelihood, and Bayesian inference methods. The phylogenies our analyses recovered corroborate recent studies on the group. The subfamily Gobioninae is monophyletic and composed of three major lineages. We find evidence for a Hemibarbus-Squalidus group, and the tribes Gobionini and Sarcocheilichthyini, with the Hemibarbus-Squalidus group sister to a clade of Gobionini-Sarcocheilichthyini. The Hemibarbus-Squalidus group includes those two genera; the tribe Sarcocheilichthyini includes Coreius, Coreoleuciscus, Gnathopogon, Gobiocypris, Ladislavia, Paracanthobrama, Pseudorasbora, Pseudopungtungia, Pungtungia, Rhinogobio, and Sarcocheilichthys; the tribe Gobionini includes Abbottina, Biwia, Gobio, Gobiobotia, Huigobio, Microphysogobio, Platysmacheilus, Pseudogobio, Romanogobio, Saurogobio, and Xenophysogobio. The monotypic Acanthogobio is placed into the synonymy of Gobio. We tentatively assign Belligobio to the Hemibarbus-Squalidus group and Mesogobio to Gobionini; Paraleucogobio and Parasqualidus remain incertae sedis. Based on the topologies presented, the evolution of swim bladder specializations, a distinctive feature among cyprinids, has occurred more than once within the subfamily.