The XMM Large Scale Structure Survey: Properties and Two-Point Angular Correlations of Point-like Sources

We analyze X-ray sources detected over 4.2 pseudo-contiguous sq. deg. in the 0.5-2 keV and 2-10 keV bands down to fluxes of 2x10^{-15} and 8x10^{-15} erg/s/cm^2 respectively, as part of the XMM Large Scale Structure Survey. The logN-logS in both bands shows a steep slope at bright fluxes, but agrees well with other determinations below ~2x10^{-14} erg/s/cm^2. The detected sources resolve close to 30 per cent of the X-ray background in the 2-10 keV band. We study the two-point angular clustering of point sources using nearest neighbours and correlation function statistics and find a weak, positive signal for ~1130 sources in the 0.5-2 keV band, but no correlation for ~400 sources in the 2-10 keV band below scales of 100 arcsec. A sub-sample of ~200 faint sources with hard X-ray count ratios, that is likely to be dominated by obscured AGN, does show a positive signal with the data allowing for a large scaling of the angular correlation length, but only at the ~2 (3) sigma level, based on re-sampling (Poisson) statistics. We discuss possible implications and emphasize the importance of wider, complete surveys in order to fully understand the large scale structure of the X-ray sky.Comment: A&A in press; High resolution version at http://www-xray.ast.cam.ac.uk/~pg/publications.htm

Galaxy Clusters in the Swift/BAT era II: 10 more Clusters detected above 15 keV

We report on the discovery of 10 additional galaxy clusters detected in the ongoing Swift/BAT all-sky survey. Among the newly BAT-discovered clusters there are: Bullet, Abell 85, Norma, and PKS 0745-19. Norma is the only cluster, among those presented here, which is resolved by BAT. For all the clusters we perform a detailed spectral analysis using XMM-Newton and Swift/BAT data to investigate the presence of a hard (non-thermal) X-ray excess. We find that in most cases the clusters' emission in the 0.3-200keV band can be explained by a multi-temperature thermal model confirming our previous results. For two clusters (Bullet and Abell 3667) we find evidence for the presence of a hard X-ray excess. In the case of the Bullet cluster, our analysis confirms the presence of a non-thermal, power-law like, component with a 20-100 keV flux of 3.4 \times 10-12 erg cm-2 s-1 as detected in previous studies. For Abell 3667 the excess emission can be successfully modeled as a hot component (kT=~13keV). We thus conclude that the hard X-ray emission from galaxy clusters (except the Bullet) has most likely thermal origin.Comment: Accepted for publication by Ap

XMM-Newton observations of Extremely Red Objects and the link with luminous, X-ray obscured Quasars

We present the results of a deep (about 80 ks) XMM-Newton survey of the largest sample of near-infrared selected Extremely Red Objects (R-K>5) available to date to K_S< 19.2. At the relatively bright X-ray fluxes (F_{2-10 keV}> 4x10^{-15} cgs) and near-infrared magnitude probed by the present observations, the fraction of AGN (i.e., X-ray detected) among the ERO population is small (~3.5%); conversely, the fraction of EROs among hard X-ray selected sources is much higher (~20%). The X-ray properties of EROs detected in our XMM-Newton observation indicate absorption in excess of 10^{22} cm^{-2} in a large fraction of them. We have also considered additional samples of X-ray detected EROs available in the literature. X-ray spectral analysis of the highest S/N sources unambiguously indicates that large columns of cold gas (even >10^{23} cm^{-2}) are the rule rather than the exception. The X-ray, optical, and near-infrared properties of those X-ray selected EROs with a spectroscopic or photometric redshift nicely match those expected for quasars 2, the high-luminosity, high-redshift obscured AGNs predicted in baseline XRB synthesis models. A close correlation is detected between X- and K-band fluxes. For the AGN EROs this is consistent, under reasonable assumptions, with the relation established locally between the host galaxies and their central black holes. This suggest that the majority of EROs are powered by massive black holes accreting, on average, at about 0.03-0.1 of the Eddington limit.Comment: 33 pages, 10 figures, to appear in A&

Mutation of neuron-specific chromatin remodeling subunit BAF53b:rescue of plasticity and memory by manipulating actin remodeling

Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons. We generated transgenic mice lacking subdomain 2 of Baf53b (BAF53b Delta SB2). Long-term synaptic potentiation (LTP) and long-term memory, both of which are associated with phosphorylation of the actin severing protein cofilin, were assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically delivered into the hippocampus of BAF53b Delta SB2 mice in an effort to rescue LTP and memory. BAF53b Delta SB2 mutant mice show impairments in phosphorylation of synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory deficits are rescued by overexpression of a phosphorylation mimetic of cofilin. Baseline physiology and behavior were not affected by the mutation or the experimental treatment. This study suggests a potential link between nBAF function, actin cytoskeletal remodeling at the dendritic spine, and memory formation. This work shows that a targeted manipulation of synaptic function can rescue adult plasticity and memory deficits caused by manipulations of nBAF, and thereby provides potential novel avenues for therapeutic development for multiple intellectual disability disorders

Improved residue contact prediction using support vector machines and a large feature set

BACKGROUND: Predicting protein residue-residue contacts is an important 2D prediction task. It is useful for ab initio structure prediction and understanding protein folding. In spite of steady progress over the past decade, contact prediction remains still largely unsolved. RESULTS: Here we develop a new contact map predictor (SVMcon) that uses support vector machines to predict medium- and long-range contacts. SVMcon integrates profiles, secondary structure, relative solvent accessibility, contact potentials, and other useful features. On the same test data set, SVMcon's accuracy is 4% higher than the latest version of the CMAPpro contact map predictor. SVMcon recently participated in the seventh edition of the Critical Assessment of Techniques for Protein Structure Prediction (CASP7) experiment and was evaluated along with seven other contact map predictors. SVMcon was ranked as one of the top predictors, yielding the second best coverage and accuracy for contacts with sequence separation >= 12 on 13 de novo domains. CONCLUSION: We describe SVMcon, a new contact map predictor that uses SVMs and a large set of informative features. SVMcon yields good performance on medium- to long-range contact predictions and can be modularly incorporated into a structure prediction pipeline

Genome-Wide Identification of Bcl11b Gene Targets Reveals Role in Brain-Derived Neurotrophic Factor Signaling

B-cell leukemia/lymphoma 11B (Bcl11b) is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells

PathEx: a novel multi factors based datasets selector web tool

<p>Abstract</p> <p>Background</p> <p>Microarray experiments have become very popular in life science research. However, if such experiments are only considered independently, the possibilities for analysis and interpretation of many life science phenomena are reduced. The accumulation of publicly available data provides biomedical researchers with a valuable opportunity to either discover new phenomena or improve the interpretation and validation of other phenomena that partially understood or well known. This can only be achieved by intelligently exploiting this rich mine of information.</p> <p>Description</p> <p>Considering that technologies like microarrays remain prohibitively expensive for researchers with limited means to order their own experimental chips, it would be beneficial to re-use previously published microarray data. For certain researchers interested in finding gene groups (requiring many replicates), there is a great need for tools to help them to select appropriate datasets for analysis. These tools may be effective, if and only if, they are able to re-use previously deposited experiments or to create new experiments not initially envisioned by the depositors. However, the generation of new experiments requires that all published microarray data be completely annotated, which is not currently the case. Thus, we propose the PathEx approach.</p> <p>Conclusion</p> <p>This paper presents PathEx, a human-focused web solution built around a two-component system: one database component, enriched with relevant biological information (expression array, omics data, literature) from different sources, and another component comprising sophisticated web interfaces that allow users to perform complex dataset building queries on the contents integrated into the PathEx database.</p