Numerical simulations of the Warm-Hot Intergalactic Medium

In this paper we review the current predictions of numerical simulations for the origin and observability of the warm hot intergalactic medium (WHIM), the diffuse gas that contains up to 50 per cent of the baryons at z~0. During structure formation, gravitational accretion shocks emerging from collapsing regions gradually heat the intergalactic medium (IGM) to temperatures in the range T~10^5-10^7 K. The WHIM is predicted to radiate most of its energy in the ultraviolet (UV) and X-ray bands and to contribute a significant fraction of the soft X-ray background emission. While O VI and C IV absorption systems arising in the cooler fraction of the WHIM with T~10^5-10^5.5 K are seen in FUSE and HST observations, models agree that current X-ray telescopes such as Chandra and XMM-Newton do not have enough sensitivity to detect the hotter WHIM. However, future missions such as Constellation-X and XEUS might be able to detect both emission lines and absorption systems from highly ionised atoms such as O VII, O VIII and Fe XVII.Comment: 18 pages, 5 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 14; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Abundant Quantitative Trait Loci Exist for DNA Methylation and Gene Expression in Human Brain

A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We present a set of integrated experiments that investigate the effects of common genetic variability on DNA methylation and mRNA expression in four human brain regions each from 150 individuals (600 samples total). We find an abundance of genetic cis regulation of mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation across the genome. We show peak enrichment for cis expression QTLs to be approximately 68,000 bp away from individual transcription start sites; however, the peak enrichment for cis CpG methylation QTLs is located much closer, only 45 bp from the CpG site in question. We observe that the largest magnitude quantitative trait loci occur across distinct brain tissues. Our analyses reveal that CpG methylation quantitative trait loci are more likely to occur for CpG sites outside of islands. Lastly, we show that while we can observe individual QTLs that appear to affect both the level of a transcript and a physically close CpG methylation site, these are quite rare. We believe these data, which we have made publicly available, will provide a critical step toward understanding the biological effects of genetic variation

Food insecurity, school absenteeism and educational attainment of adolescents in Jimma Zone Southwest Ethiopia: a longitudinal study

<p>Abstract</p> <p>Background</p> <p>Food insecurity not only affects physical growth and health of children but also their intellectual development, school attendance and academic performance. However, most evidences are based on studies in high income countries. Although food insecurity is common in Ethiopia, to what extent it affects school attendance and educational attainment of adolescents is not explored. We hypothesized that food insecure adolescents would be more likely to be absent from school and have lower grades attained after 1 year compared to their food secure peers.</p> <p>Methods</p> <p>We used data from 2009 adolescents in the age group of 13-17 years from two consecutive surveys of a five year longitudinal family study in Southwest Ethiopia. A stratified random sampling was used to select participants. Regression analyses were used to compare school absenteeism and the highest grade attained after 1 year of follow-up in food secure and insecure adolescents. The analysis was adjusted for demographic factors, reported illness and workload.</p> <p>Results</p> <p>Significantly more (33.0%) food insecure adolescents were absent from school compared with their food secure peers (17.8%, P < 0.001). Multivariable logistic regression analyses showed that after adjusting for gender, place of residence and gender of the household head, adolescent food insecurity [OR 1.77 (1.34-2.33)], severe household food insecurity [OR 1.62 (1.27-2.06)], illness during the past one month before the survey [OR 2.26 (1.68-3.06)], the highest grade aspired to be completed by the adolescent [OR 0.92 (0.88-0.96)], and the number of days that the adolescent had to work per week [OR 1.16 (1.07-1.26)] were independent predictors of school absenteeism. Similarly after controlling for household income and gender of the household head, adolescent food insecurity(P < 0.001), severe household food insecurity(P < 0.001), illness during the last month(P < 0.001) and rural residence(P < 0.001) were inversely associated with highest grade attained, while age of the adolescent(P < 0.001), the highest grade intended to be completed(P < 0.001) and residence in semi urban area(P < 0.001) were positively associated with the highest grade attained.</p> <p>Conclusions</p> <p>Adolescent and household food insecurity are positively associated with school absenteeism and a lower educational attainment. Programs aiming to achieve universal access to primary education in food insecure environments should integrate interventions to ensure food security of adolescents.</p

Genotype, haplotype and copy-number variation in worldwide human populations

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups(1-3). Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms ( SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected-including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas-the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62552/1/nature06742.pd

GMC Collisions as Triggers of Star Formation. II. 3D Turbulent, Magnetized Simulations

We investigate giant molecular cloud (GMCs) collisions and their ability to induce gravitational instability and thus star formation. This mechanism may be a major driver of star formation activity in galactic disks. We carry out a series of three dimensional, magnetohydrodynamics (MHD), adaptive mesh refinement (AMR) simulations to study how cloud collisions trigger formation of dense filaments and clumps. Heating and cooling functions are implemented based on photo-dissociation region (PDR) models that span the atomic to molecular transition and can return detailed diagnostic information. The clouds are initialized with supersonic turbulence and a range of magnetic field strengths and orientations. Collisions at various velocities and impact parameters are investigated. Comparing and contrasting colliding and non-colliding cases, we characterize morphologies of dense gas, magnetic field structure, cloud kinematic signatures, and cloud dynamics. We present key observational diagnostics of cloud collisions, especially: relative orientations between magnetic fields and density structures, like filaments; 13CO(J=2-1), 13CO(J=3-2), and 12CO(J=8-7) integrated intensity maps and spectra; and cloud virial parameters. We compare these results to observed Galactic clouds

Exome chip analysis identifies low-frequency and rare variants in MRPL38 for white matter hyperintensities on brain MRI

International audienc

Diversity and Strain Specificity of Plant Cell Wall Degrading Enzymes Revealed by the Draft Genome of Ruminococcus flavefaciens FD-1

Peer reviewedPublisher PD

Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1,131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively. Mutations in TBK1 (1.5%) and other known FTLD genes (1.4%) were rare, and the disease in 57.7% of FTLD-TDP patients was unexplained by the known FTLD genes. To unravel the contribution of common genetic factors to the FTLD-TDP etiology in these patients, we conducted a two-stage association study comprising the analysis of whole-genome sequencing data from 517 FTLD-TDP patients and 838 controls, followed by targeted genotyping of the most associated genomic loci in 119 additional FTLD-TDP patients and 1653 controls. We identified three genome-wide significant FTLD-TDP risk loci: one new locus at chromosome 7q36 within the DPP6 gene led by rs118113626 (pvalue=4.82e-08, OR=2.12), and two known loci: UNC13A, led by rs1297319 (pvalue=1.27e-08, OR=1.50) and HLA-DQA2 led by rs17219281 (pvalue=3.22e-08, OR=1.98). While HLA represents a locus previously implicated in clinical FTLD and related neurodegenerative disorders, the association signal in our study is independent from previously reported associations. Through inspection of our whole genome sequence data for genes with an excess of rare loss-of-function variants in FTLD-TDP patients (n≥3) as compared to controls (n=0), we further discovered a possible role for genes functioning within the TBK1-related immune pathway (e.g. DHX58, TRIM21, IRF7) in the genetic etiology of FTLD-TDP. Together, our study based on the largest cohort of unrelated FTLD-TDP patients assembled to date provides a comprehensive view of the genetic landscape of FTLD-TDP, nominates novel FTLD-TDP risk loci, and strongly implicates the immune pathway in FTLD-TDP pathogenesis

p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC