New results on the Galactic Center Helium stars

The cluster of helium stars around Sgr A* has been re‐observed with the BEAR spectro‐imager on CFHT, in the 2.06 μm helium line, at a spectral resolution of 52 km s^(–1) and on a field of ≃40″. This new analysis confirms and completes a previous study at a spectral resolution of 74 km s^(–1) and on a smaller field of 24″ , corresponding to the central parsec (Paumard et al. 2001). Nineteen stars are confirmed as helium stars. These observations led to a clear differentiation between two groups of hot stars based on their emission linewidth, their magnitude and their positions relative to Sgr A*. The first class of 6 members is characterized by narrow‐line profiles (FWHM ≃200 km s^(–1)) and by their brightness. The other, fainter in K by an average of 2 mag, has a much broader emission component of width ≃1,000 km s^(–1). Several of the emission lines show a P Cygni profile. From these results, we propose that the narrow‐line group is formed of stars in the LBV phase, while the broad‐line group is formed of stars in or near the WR phase. The division into two groups is also shown by their spatial distribution, with the narrow‐line stars in a compact central cluster (IRS 16) and the other group distributed at the periphery of the central cluster of hot stars. HST‐NICMOS data in Paα (1.87 μm) of the same field reveal a similar association. The identification of the Paα counterpart to the He I stars provides an additional element to characterize the two groups. Bright Paα emitters are found generally associated with the narrow‐line class stars while the weak Paαemitters are generally associated with the broad‐line stars. A few particular cases are discussed. This confirms the different status of evolution of the two groups of massive, hot stars in the central cluster. As a by‐product, about 20 additional candidate emission stars are detected in the central, high‐resolution 19″ field from the NICMOS data

The Galactic Center Source IRS 13E: a Star Cluster

High spatial resolution, near‐infrared observations of the Galactic Center source, close to Sgr A*, known historically as IRS13, are presented. These observations include ground‐based adaptive optics images in the H, K' and L bands, HST‐NICMOS observations in filters between 1.1 and 2.2 μm, and spectroimaging data in the He I 2.06 μm line and the Brγ line. Analysis of all these data has made possible the resolution of the main component, IRS 13E, into a cluster of seven individual stars within a projected diameter of ∼0.5″ (0.02 pc), and to build their SED. The main sources, 13E1, 13E2, 13E3 (a binary), and 13E4, are hot stars of different nature. 13E2 and 13E4 are emission line stars. The spectral type of the various members goes from O5I to WR, including dusty WRs like IRS 21 (Tanner et al. 2002). All these sources have a common westward proper motion. Two weaker sources, 13E5 and 13E6, are also detected within the compact cluster, with 13E5 proposed as another dusty WR and 13E6 as a O5V star. An extended halo seen around the cluster, part of the mini‐spiral of dust is particularly enhanced in the L band. It is interpreted as a contribution of the scattered light from the inner cluster and the thermal emission from the dust. IRS 13E is proposed to be the remaining core of a massive, young star cluster which was disrupted in the vicinity of Sgr A*, and hence, the possible source of the young stars in the central parsec, from the helium stars to the S stars

CCN3: a key growth regulator in Chronic Myeloid Leukaemia

Chronic Myeloid Leukaemia (CML) is characterized by expression of the constitutively active Bcr-Abl tyrosine kinase. We have shown previously that the negative growth regulator, CCN3, is down-regulated as a result of Bcr-Abl kinase activity and that CCN3 has a reciprocal relationship of expression with BCR-ABL. We now show that CCN3 confers growth regulation in CML cells by causing growth inhibition and regaining sensitivity to the induction of apoptosis. The mode of CCN3 induced growth regulation was investigated in K562 CML cells using gene transfection and treatment with recombinant CCN3. Both strategies showed CCN3 regulated CML cell growth by reducing colony formation capacity, increasing apoptosis and reducing ERK phosphorylation. K562 cells stably transfected to express CCN3 showed enhanced apoptosis in response to treatment with the tyrosine kinase inhibitor, imatinib. Whilst CCN3 expression was low or undetectable in CML stem cells, primary CD34+ CML progenitors were responsive to treatment with recombinant CCN3. This study shows that CCN3 is an important growth regulator in haematopoiesis, abrogation of CCN3 expression enhances BCR-ABL dependent leukaemogenesis. CCN3 restores growth regulation, regains sensitivity to the induction of apoptosis and enhances imatinib cell kill in CML cells. CCN3 may provide an additional therapeutic strategy in the management of CML

Parasite Zoonoses and Wildlife: Emerging Issues

The role of wildlife as important sources, reservoirs and amplifiers of emerging human and domestic livestock pathogens, in addition to well recognized zoonoses of public health significance, has gained considerable attention in recent years. However, there has been little attention given to the transmission and impacts of pathogens of human origin, particularly protozoan, helminth and arthropod parasites, on wildlife. Substantial advances in molecular technologies are greatly improving our ability to follow parasite flow among host species and populations and revealing valuable insights about the interactions between cycles of transmission. Here we present several case studies of parasite emergence, or risk of emergence, in wildlife, as a result of contact with humans or anthropogenic activities. For some of these parasites, there is growing evidence of the serious consequences of infection on wildlife survival, whereas for others, there is a paucity of information about their impact

Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer

Objective: To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2). Design: We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-Analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-Analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as â € positive' and â € less-credible positive' were further validated in three large GWAS consortia conducted in populations of European origin. Results: We initially identified 18 independent variants at 16 loci that were classified as â € positive' polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as â € less-credible positive' SNPs; 72.2% of the â € positive' SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to â € less-credible' positive (reducing the â € positive' variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-Analyses found no evidence to support their associations with CRC risk. Conclusion: The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility.</p

Localized Plasticity in the Streamlined Genomes of Vinyl Chloride Respiring Dehalococcoides

Vinyl chloride (VC) is a human carcinogen and widespread priority pollutant. Here we report the first, to our knowledge, complete genome sequences of microorganisms able to respire VC, Dehalococcoides sp. strains VS and BAV1. Notably, the respective VC reductase encoding genes, vcrAB and bvcAB, were found embedded in distinct genomic islands (GEIs) with different predicted integration sites, suggesting that these genes were acquired horizontally and independently by distinct mechanisms. A comparative analysis that included two previously sequenced Dehalococcoides genomes revealed a contextually conserved core that is interrupted by two high plasticity regions (HPRs) near the Ori. These HPRs contain the majority of GEIs and strain-specific genes identified in the four Dehalococcoides genomes, an elevated number of repeated elements including insertion sequences (IS), as well as 91 of 96 rdhAB, genes that putatively encode terminal reductases in organohalide respiration. Only three core rdhA orthologous groups were identified, and only one of these groups is supported by synteny. The low number of core rdhAB, contrasted with the high rdhAB numbers per genome (up to 36 in strain VS), as well as their colocalization with GEIs and other signatures for horizontal transfer, suggests that niche adaptation via organohalide respiration is a fundamental ecological strategy in Dehalococccoides. This adaptation has been exacted through multiple mechanisms of recombination that are mainly confined within HPRs of an otherwise remarkably stable, syntenic, streamlined genome among the smallest of any free-living microorganism

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

International audienc

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder