Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Evaluating the Use of Coded-Wire Tags in Individually Marking Odonata Larvae

This is an Accepted Manuscript of an article published by Cambridge University Press in The Canadian Entomologist in June 2015, available online: https://doi.org/10.4039/tce.2015.43We tested a potential new tool for marking Odonata larvae internally, evaluating the retention rates of injected coded-wire tags (CWT) and the effects of these tags on larval performance. Two species of dragonfly larvae (Epitheca canis McLachlan (Odonata: Corduliidae) and Leucorrhinia intacta Hagen (Odonata: Libellulidae)) were injected with CWT. Tag loss rates were assayed over experimental periods of 22 and 60 days, respectively for the two species. To assess whether tagging had negative effects on larvae, mortality, and growth of tagged larvae were compared to untagged larvae held in the same conditions. Tag retention rates were high (92–100%) and CWT were easily retrieved from preserved larvae via dissection, permitting most tagged larvae to be individually identified. There was 100% survival in larvae injected with CWT and tags do not appear to impair growth. The high retention and retrieval rates of this marking approach combined with no increase in mortality associated with tagging suggest that CWT are a useful means of individually labelling a large number of Odonata larvae in a time-efficient manner.Natural Sciences and Engineering Research Council of Canada Discovery Grant (RGPIN 435614-13) with funding from the Department of Biology, the University of Toronto Mississauga, awarded to SJM

Size-dependent predation alters interactions between parasites and predators

Increasing evidence indicates that parasites play an important role within many systems as prey for higher trophic levels. Predation on parasites can decrease their numbers and may affect host infection rates. Cercariae, a free-living infectious stage of trematode parasites, are abundant in freshwater systems and are directly consumed by a number of freshwater predators. However, few studies have tested whether predators exhibit a preference for cercariae when alternative prey are available or how these preferences vary across predator body sizes. We assessed whether dragonfly larvae, top predators in freshwater systems without fish, foraged preferentially when presented with two prey types, cercariae and zooplankton, and whether foraging preferences changed across predator body size. Body size of larval dragonfly predators was found to be significantly, and negatively, related to the fraction of cercariae in the diet. Larger bodied dragonfly larvae shifted their diet choice from cercariae to zooplankton. Changes in foraging selectivity as body size increases across a predatorâ s ontogeny can alter the strength of predator-prey interactions. Further investigation into size-selective foraging on parasites may provide new insights into the effects of predation on parasite abundance and transmission in natural systems.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Management impacts on the dissolved organic carbon release from deadwood, ground vegetation and the forest floor in a temperate oak woodland

The forest floor is often considered the most important source of dissolved organic carbon (DOC) in forest soils, yet little is known about the relative contribution from different forest floor layers, understorey vegetation and deadwood. Here, we determine the carbon stocks and potential DOC production from forest materials: deadwood, ground vegetation, leaf litter, the fermentation layer and top mineral soil (Ah horizon), and further assess the impact of management. Our research is based on long-term monitoring plots in a temperate deciduous woodland, with one set of plots actively managed by thinning, understorey scrub and deadwood removal, and another set that were not managed in 23 years. We examined long-term data and a spatial survey of forest materials to estimate the relative carbon stocks and concentrations and fluxes of DOC released from these different pools. Long-term soil water monitoring revealed a large difference in median DOC concentrations between the unmanaged (43.8 mg L−1) and managed (18.4 mg L−1) sets of plots at 10 cm depth over six years, with the median DOC concentration over twice as high in the unmanaged plots. In our spatial survey, a significantly larger cumulative flux of DOC was released from the unmanaged than the managed site, with 295.5 and 230.3 g m−2, respectively. Whilst deadwood and leaf litter released the greatest amount of DOC per unit mass, when volume of the material was considered, leaf litter contributed most to DOC flux, with deadwood contributing least. Likewise, there were significant differences in the carbon stocks held by different forest materials that were dependent on site. Vegetation and the fermentation layer held more carbon in the managed site than unmanaged, whilst the opposite occurred in deadwood and the Ah horizon. These findings indicate that management affects the allocation of carbon stored and DOC released between different forest materials

Brain morphology is differentially impacted by peripheral cytokines in schizophrenia-spectrum disorder

Deficits in brain morphology are one of the most widely replicated neuropathological features in schizophrenia-spectrum disorder (SSD), although their biological underpinnings remain unclear. Despite the existence of hypotheses by which peripheral inflammation may impact brain structure, few studies have examined this relationship in SSD. This study aimed to establish the relationship between peripheral markers of inflammation and brain morphology and determine whether such relationships differed across healthy controls and individuals with first episode psychosis (FEP) and chronic schizophrenia. A panel of 13 pro- and anti-inflammatory cytokines were quantified from serum in 175 participants [n = 84 Healthy Controls (HC), n = 40 FEP, n = 51 Chronic SCZ]. We first performed a series of permutation tests to identify the cytokines most consistently associated with brain structural regions. Using moderation analysis, we then determined the extent to which individual variation in select cytokines, and their interaction with diagnostic status, predicted variation in brain structure. We found significant interactions between cytokine level and diagnosis on brain structure. Diagnostic status significantly moderated the relationship of IFNγ, IL4, IL5 and IL13 with frontal thickness, and of IFNγ and IL5 and total cortical volume. Specifically, frontal thickness was positively associated with IFNγ, IL4, IL5 and IL13 cytokine levels in the healthy control group, whereas pro-inflammatory cytokines IFNγ and IL5 were associated with lower total cortical volume in the FEP group. Our findings suggest that while there were no relationships detected in chronic schizophrenia, the relationship between peripheral inflammatory markers and select brain regions are differentially impacted in FEP and healthy controls. Longitudinal investigations are required to determine whether the relationship between brain structure and peripheral inflammation changes over time.Liliana Laskaris, Sam Mancuso, Cynthia Shannon Weickert, Andrew Zalesky, Gursharan Chana, Cassandra Wannan ... et al