A decomposition theorem for compact groups with application to supercompactness

We show that every compact connected group is the limit of a continuous inverse sequence, in the category of compact groups, where each successor bonding map is either an epimorphism with finite kernel or the projection from a product by a simple compact Lie group. As an application, we present a proof of an unpublished result of Charles Mills from 1978: every compact group is supercompact.Comment: 12 page

I Love Dat Man / music by E. J Simnes; words by Dan Packard

Cover: photo of Miss Alice Atherton, a Caucasian singer in front of a wall separating her from an African American vocal quartet; Musical Supplement of the New York Journal and Advertiser. July 10, 1898 description reads a coon song; Publisher: Mill Bros. (New York)https://egrove.olemiss.edu/sharris_a/1039/thumbnail.jp

A role for CaV1 and calcineurin signalling to depolarization-induced changes in neuronal DNA methylation

Copyright © 2015 The Authors Published by Elsevier Inc.Direct manipulations of neuronal activity have been shown to induce changes in DNA methylation (DNAm), although little is known about the cellular signaling pathways involved. Using reduced representation bisulfite sequencing, we identify DNAm changes associated with moderate chronic depolarization in dissociated rat hippocampal cultures. Consistent with previous findings, these changes occurred primarily in the vicinity of loci implicated in neuronal function, being enriched in intergenic regions and underrepresented in CpG-rich promoter regulatory regions. We subsequently used 2 pharmacological interventions (nifedipine and FK-506) to test whether the identified changes depended on 2 interrelated signaling pathways known to mediate multiple forms of neuronal plasticity. Both pharmacological manipulations had notable effects on the extent and magnitude of depolarization-induced DNAm changes indicating that a high proportion of activity-induced changes are likely to be mediated by calcium entry through L-type CaV1 channels and/or downstream signaling via the calcium-dependent phosphatase calcineurin.Wellcome TrustMRC 4-year PhD studentshipKCL CDN-SGDP collaborative seed fundin

Tradition and Prudence in Locke's Exceptions to Toleration

Why did Locke exclude Catholics and atheists from toleration? Not, I contend, because he was trapped by his context, but because his prudential approach and practica ljudgments led him to traditiona ltexts. I make this argumentfirst by outlining the connections among prudential exceptionality, practical judgments, and traditional texts. I then describe important continuities betweenc onventional English understandings of the relationship between state and religion and Locke's writings on toleration, discuss Locke's conception of rights, and illustrate his use of prudential exceptions and distinctions. I conclude by arguing that Locke's problems are relevant to assessingc ontemporary liberal discussions of tolerationa nd the separation of state and religion that lean heavily on practical justification

Epigenetic profiling of ADHD symptoms trajectories: a prospective, methylome-wide study

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent developmental disorder, associated with a range of long-term impairments. Variation in DNA methylation, an epigenetic mechanism, is implicated in both neurobiological functioning and psychiatric health. However, the potential role of DNA methylation in ADHD symptoms is currently unclear. In this study, we examined data from the Avon Longitudinal Study of Parents and Children (ALSPAC)-specifically the subsample forming the Accessible Resource for Integrated Epigenomics Studies (ARIES)-that includes (1) peripheral measures of DNA methylation (Illumina 450k) at birth (n=817, 49% male) and age 7 (n=892, 50% male) and (2) trajectories of ADHD symptoms (7-15 years). We first employed a genome-wide analysis to test whether DNA methylation at birth associates with later ADHD trajectories; and then followed up at age 7 to investigate the stability of associations across early childhood. We found that DNA methylation at birth differentiated ADHD trajectories across multiple genomic locations, including probes annotated to SKI (involved in neural tube development), ZNF544 (previously implicated in ADHD), ST3GAL3 (linked to intellectual disability) and PEX2 (related to perixosomal processes). None of these probes maintained an association with ADHD trajectories at age 7. Findings lend novel insights into the epigenetic landscape of ADHD symptoms, highlighting the potential importance of DNA methylation variation in genes related to neurodevelopmental and peroxisomal processes that play a key role in the maturation and stability of cortical circuits

Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide.

This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. Suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers.We are grateful to all of the patients and control subjects who contributed to this study. The authors would like to acknowledge support of the Brain and Behaviour Research Foundation through a NARSAD Young Investigator Grant to TMM and from the UK Medical Research Council (MRC) (grant number MR/K013807/1) to JM. ZK would like to acknowledge funding from the NIH grant (grant number NIMH 1R21MH094771). The Douglas Bell Canada Brain Bank is supported by the FRQS through the Quebec Network on Suicide, Mood Disorders and Related Disorders, and by Brain Canada through an infrastructure grant. We acknowledge Niamh Mullins and Professor Catherine Lewis, King’s College London, for kindly supplying us with the suicide attempt GWAS data

Low X-Ray Luminosity Galaxy Clusters: Main goals, sample selection, photometric and spectroscopic observations

We present the study of nineteen low X-ray luminosity galaxy clusters (L$_X \sim$ 0.5--45 $\times$ $10^{43}$ erg s$^{-1}$), selected from the ROSAT Position Sensitive Proportional Counters (PSPC) Pointed Observations (Vikhlinin et al. 1998) and the revised version of Mullis et al. (2003) in the redshift range of 0.16 to 0.7. This is the introductory paper of a series presenting the sample selection, photometric and spectroscopic observations and data reduction. Photometric data in different passbands were taken for eight galaxy clusters at Las Campanas Observatory; three clusters at Cerro Tololo Interamerican Observatory; and eight clusters at the Gemini Observatory. Spectroscopic data were collected for only four galaxy clusters using Gemini telescopes. With the photometry, the galaxies were defined based on the star-galaxy separation taking into account photometric parameters. For each galaxy cluster, the catalogues contain the PSF and aperture magnitudes of galaxies within the 90\% completeness limit. They are used together with structural parameters to study the galaxy morphology and to estimate photometric redshifts. With the spectroscopy, the derived galaxy velocity dispersion of our clusters ranged from 507 km~s$^{-1}$ for [VMF98]022 to 775 km~s$^{-1}$ for [VMF98]097 with signs of substructure. Cluster membership has been extensively discussed taking into account spectroscopic and photometric redshift estimates. In this sense, members are the galaxies within a projected radius of 0.75 Mpc from the X-ray mission peak and with cluster centric velocities smaller than the cluster velocity dispersion or 6000 km~s$^{-1}$, respectively. These results will be used in forthcoming papers to study, among the main topics, the red cluster sequence, blue cloud and green populations; the galaxy luminosity function and cluster dynamics.Comment: 13 pages, 6 tables, 9 figures. Uses emulateapj. Accepted for publication in The Astronomical Journal. Some formatting errors fixe

The community of advantage

This paper gives an overview of my recently published book, The Community of Advantage: A Behavioural Economist’s Defence of the Market. I explain that my stance as author is that of a behavioural economist and an economic liberal. The book is an attempt to counter the widespread belief that the findings of behavioural economics justify regulatory interventions in the economy that would previously have been thought unacceptably paternalistic. I argue that competitive markets are desirable, not as an efficient means for satisfying the given preferences of assumedly rational individuals, but as an institutional structure that provides opportunities for whatever voluntary transactions people might want to make

Methylomic trajectories across human fetal brain development

Open access articleEpigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited. We quantified genome-wide patterns of DNA methylation at ∼ 400,000 sites in 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 d post-conception. We identified highly significant changes in DNA methylation across fetal brain development at >7% of sites, with an enrichment of loci becoming hypomethylated with fetal age. Sites associated with developmental changes in DNA methylation during fetal brain development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across brain development. Weighted gene comethylation network analysis (WGCNA) revealed discrete modules of comethylated loci associated with fetal age that are significantly enriched for genes involved in neurodevelopmental processes. This is, to our knowledge, the most extensive study of DNA methylation across human fetal brain development to date, confirming the prenatal period as a time of considerable epigenomic plasticity.MRCUniversity of Exeter Medical SchoolWellcome Trus

Clozapine-induced transcriptional changes in the zebrafish brain

Clozapine is an atypical antipsychotic medication that is used to treat schizophrenia patients who are resistant to other antipsychotic drugs. The molecular mechanisms mediating the effects of clozapine are not well understood and its use is often associated with severe side-effects. In this study, we exposed groups of wild-type zebrafish to two doses of clozapine ('low' (20 µg/L) and 'high' (70 µg/L)) over a 72-h period, observing dose-dependent effects on behaviour. Using RNA sequencing (RNA-seq) we identified multiple genes differentially expressed in the zebrafish brain following exposure to clozapine. Network analysis identified co-expression modules characterised by striking changes in module connectivity in response to clozapine, and these were enriched for regulatory pathways relevant to the etiology of schizophrenia. Our study highlights the utility of zebrafish as a model for assessing the molecular consequences of antipsychotic medications and identifies genomic networks potentially involved in schizophrenia.This article is freely available via Open Access. Click on the publisher URL to access it via the publisher's site.This work was supported by a Medical Research Council (MRC) Project Grant (MR/K013807/1) and Clinical Infrastructure Funding (MR/M008924/1) to JM. JV is funded by an RCUK/UKRI Rutherford Fund Fellowship (MR/R024987/1). We would like to acknowledge the use of the University of Exeter High-Performance Computing (HPC) facility in carrying out this work.published version, accepted version, submitted versio