Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Northern Ireland Peace Monitoring Report Number Six

This is the sixth in the series of Northern Ireland Peace Monitoring Reports,the first of which was published in February 2012. In each case the Community Relations Council has coordinated the project and published the report, with financial support from The Joseph Rowntree Charitable Trust. We are grateful to The Joseph Rowntree Charitable Trust (JRCT) for the long-term commitment to this project, without which these reports would not be possible.The independence of each report has been an important component of the process. As well as being independently funded, the report is independently authored; it collates data which is produced independently of the report; andit is overseen by an independent advisory panel which draws on a range of academic disciplines. The Panel was also independently chaired by the highly respected and experienced academic, Professor Emeritus Adrian Guelke(Queen’s University Belfast).The Community Relations Council would like to thank the report’s authors, Professor Ann Marie Gray (Ulster University) and her team: Dr. Paula Devine (Queen’s University Belfast), Dr. Jennifer Hamilton (Ulster University), Gareth Hetherington (Ulster University), Dr. Grainne Kelly (Ulster University), Dr. Brendan Lynn (Ulster University), Dr. Richard Martin (London School of Economics) and Dr. John Topping (Queen’s University Belfast) who carried the enormous burden for compiling, analysing and ordering the research. We are also grateful to Professor Guelke and those who served on the Advisory Panel for reading through many drafts and for contributing insights, critical reflection, and encouragement. The members of the Advisory Panel for this report were Professor Paddy Hillyard (Professor Emeritus, Queens University Belfast), Tony McCusker, (former Chair of CRC who did much to develop the original idea and create an understanding of the value of the Peace Monitoring Report), Kirsty McManus (Institute of Directors), Frank Gaffikin (Professor Emeritus, Queens University Belfast), Dr. Emily Stanton (Community Relations In Schools) and Tim Jones (JRCT), all of whom discussed the many challenging topics in a thoughtful and good-humoured way.Each report gathers and examines data on a wide range of topics relevant to our peace journey. The data is set out in an indicator framework which has four dimensions, this has been maintained throughout the series of reports. As the reports now span over a decade, the authors have ensured that the data is gathered in a largely consistent way, albeit that there are inevitably new and emerging events to be included, in this case for example, the pandemic. The consistency of the reports structure allows us to measure the distance travelled over time towards a peaceful and inclusive society or away from it (as movement towards peace here, as is the case everywhere, is not inevitable).As can be seen in this report, there are a myriad of actions and in actions across a wide range of themes that can affect stability and peace in large and small ways. This report reveals the complex picture of events, providing the opportunity to consider them in the context of deeper stresses in our society. This is a challenging task. Peace processes are not linear, this makes them difficult to monitor. They are multi-dimensional, acted on by event taking place now but also by deep memory and hurts passed from generation to generation. As a result, we inevitably end up with a kaleidoscopic, sometimes contradictory picture. The process of building and sustaining peace is dynamic; everyone is involved in large and small ways in shaping the future,whether they realise it or not. The Community Relations Council hopes this report will be a valuable tool for shaping plans and setting the course for the contribution we all make to sustaining peace. Focus and commitment remain vital, because as we have seen throughout the world, peace processes are not guaranteed.Following the publication of this report there will be a series of dissemination events at which the findings will be discussed. 2023 marked the 25th anniversary of the Belfast/Good Friday Agreement, this is a timely moment for a detailed account of the peace process – its weaknesses as well as its strengths. It continues to be our hope that the dispassionate analysis presented in this report will help those making the journey now or learning from it in the future.Dr. Jacqueline IrwinChief Executive OfficerCommunity Relations Council<br/

A short-echo-time proton magnetic resonance spectroscopic imaging study of temporal lobe epilepsy

Purpose: We used short-echo-time proton magnetic resonance spectroscopy imaging (MRSI) to study metabolite concentration variation through the temporal lobe in patients with temporal lobe epilepsy (TLE) with and without abnormal MRI.Methods: MRSI was performed at TE = 30 ms to study 10 control subjects, 10 patients with TLE and unilateral hippocampal sclerosis, and 10 patients with TLE and unremarkable MRI (MRI negative). We measured the concentrations of N-acetyl aspartate + N-acetyl aspartyl-glutamate (NAAt), creatine (Cr), choline (Cho), glutamate + glutamine (Glx), and myoinositol, in the anterior, middle, and posterior medial temporal lobe (MTL), and in the posterior lateral temporal lobe. Segmented volumetric T-1-weighted MRIs gave the tissue composition of each MRSI voxel. Normal ranges were defined as the control mean 3 SD,Results: In the hippocampal sclerosis group, seven of 10 had abnormally low NAAt in the ipsilateral anterior MTL. In the MRI-negative group. four of 10 had low NAAt in the middle MTL voxel ipsilateral to seizure onset. Metabolite ratios were less sensitive to abnormality than was the NAAt concentration. Group analysis showed low NAAt, Cr, and Cho in the anterior MTL in hippocampal sclerosis, Glx was elevated in the anterior voxel contralateral to seizure onset in the MRI-negative group. Metabolite concentrations were influenced by voxel position and tissue composition.Conclusions: (a) Low NAAt, Cr, and Cho were features of the anterior sclerotic hippocampus, whereas low NAAt was observed in the MRI-negative group in the middle MTL region. The posterior temporal lobe regions were not associated with significant metabolite abnormality; (b) The two patient groups demonstrated different metabolite profiles across the temporal lobe, with elevated Glx a feature of the MRI-negative groups and (c) Voxel tissue composition and position influenced obtained metabolite concentrations

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale