AMPK alpha 1-induced RhoA phosphorylation mediates vasoprotective effect of estradiol

OBJECTIVE: Estradiol (E2) mediates numerous beneficial effects assigned to estrogens, but whereas mechanisms have been described at the endothelial level, direct effects on vascular smooth muscle cells (VSMC) are poorly documented. As evidence accumulates regarding the role of RhoA in vascular pathophysiology and the benefit of RhoA-Rho associated protein kinase (Rock) pathway inhibition, we analyzed if E2 could inhibit it in VSMC. METHODS AND RESULTS: We show that in VSMC, E2 inhibits the RhoA-Rock pathway in a time- and concentration-dependent manner. The inhibition of RhoA-Rock pathway results from E2-induced phosphorylation of the Ser188 of RhoA. Using pharmacological, transfection, and in vitro phosphorylation experiments, we demonstrate that AMP-activated protein kinase subunit alpha 1 (AMPKalpha1) is activated by estrogen receptor stimulation and catalyzes RhoA phosphorylation induced by E2. Ex vivo, ovariectomy leads to an increase in the amplitude of phenylephrine- or serotonine-induced contractions of aortic rings in wild-type mice but not in AMPKalpha1-knock-out mice or E2-supplemented animals. These functional effects were correlated with a reduced level of RhoA phosphorylation in the aorta of ovariectomized female, male, and AMPKalpha1 knock-out mice. CONCLUSION: Our work thus defines AMPKalpha1 as (1) a new kinase for RhoA and (2) a new mediator of the vasoprotective effects of estrogen

Diabetes-Related Antibody-Testing is a Valuable Screening Tool for Identifying Monogenic Diabetes – A Survey from the Worldwide SWEET Registry

Aims: To evaluate access to screening tools for monogenic diabetes in paediatric diabetes centres across the world and its impact on diagnosis and clinical outcomes of children and youth with genetic forms of diabetes. Methods: 79 centres from the SWEET diabetes registry including 53,207 children with diabetes participated in a survey on accessibility and use of diabetes related antibodies, c-peptide and genetic testing. Results: 73, 63 and 62 participating centres had access to c-peptide, antibody and genetic testing, respectively. Access to antibody testing was associated with higher proportion of patients with rare forms of diabetes identified with monogenic diabetes (54 % versus 17 %, p = 0.01), lower average whole clinic HbA1c (7.7[Q1,Q2: 7.3-8.0]%/61[56-64]mmol/mol versus 9.2[8.6-10.0]%/77[70-86]mmol/mol, p < 0.001) and younger age at onset (8.3 [7.3-8.8] versus 9.7 [8.6-12.7] years p < 0.001). Additional access to c-peptide or genetic testing was not related to differences in age at onset or HbA1c outcome. Conclusions: Clinical suspicion and antibody testing are related to identification of different types of diabetes. Implementing access to comprehensive antibody screening may provide important information for selecting individuals for further genetic evaluation. In addition, worse overall clinical outcomes in centers with limited diagnostic capabilities indicate they may also need support for individualized diabetes management.info:eu-repo/semantics/publishedVersio

The XXL Survey VII: A supercluster of galaxies at z=0.43

The XXL Survey is the largest homogeneous and contiguous survey carried out with XMM-Newton. Covering an area of 50 square degrees distributed over two fields, it primarily investigates the large-scale structures of the Universe using the distribution of galaxy clusters and active galactic nuclei as tracers of the matter distribution. Given its depth and sky coverage, XXL is particularly suited to systematically unveiling the clustering of X-ray clusters and to identifying superstructures in a homogeneous X-ray sample down to the typical mass scale of a local massive cluster. A friends-of-friends algorithm in three-dimensional physical space was run to identify large-scale structures. In this paper we report the discovery of the highest redshift supercluster of galaxies found in the XXL Survey. We describe the X-ray properties of the clusters members of the structure and the optical follow-up. The newly discovered supercluster is composed of six clusters of galaxies at a median redshift z around 0.43 and distributed across approximately 30 by 15 arc minutes (10 by 5 Mpc on sky) on the sky. This structure is very compact with all the clusters residing in one XMM pointing; for this reason this is the first supercluster discovered with the XXL Survey. Spectroscopic follow-up with WHT (William Herschel Telescope) and NTT (New Technology Telescope) confirmed a median redshift of z = 0.43. An estimate of the X-ray mass and luminosity of this supercluster and of its total gas mass put XLSSC-e at the average mass range of superclusters; its appearance, with two members of equal size, is quite unusual with respect to other superclusters and provides a unique view of the formation process of a massive structure.Comment: A&A, accepted; special XXL issu

The Spitzer-South Pole Telescope Deep Field: Survey Design and IRAC Catalogs

The Spitzer-South Pole Telescope Deep Field (SSDF) is a wide-area survey using Spitzer's Infrared Array Camera (IRAC) to cover 94 square degrees of extragalactic sky, making it the largest IRAC survey completed to date outside the Milky Way midplane. The SSDF is centered at 23:30,-55:00, in a region that combines observations spanning a broad wavelength range from numerous facilities. These include millimeter imaging from the South Pole Telescope, far-infrared observations from Herschel/SPIRE, X-ray observations from the XMM XXL survey, near-infrared observations from the VISTA Hemisphere Survey, and radio-wavelength imaging from the Australia Telescope Compact Array, in a panchromatic project designed to address major outstanding questions surrounding galaxy clusters and the baryon budget. Here we describe the Spitzer/IRAC observations of the SSDF, including the survey design, observations, processing, source extraction, and publicly available data products. In particular, we present two band-merged catalogs, one for each of the two warm IRAC selection bands. They contain roughly 5.5 and 3.7 million distinct sources, the vast majority of which are galaxies, down to the SSDF 5-sigma sensitivity limits of 19.0 and 18.2 Vega mag (7.0 and 9.4 microJy) at 3.6 and 4.5 microns, respectively.Comment: Accepted by ApJS; this version updated to conform to refereed articl

Missing Baryons, from Clusters to Groups of Galaxies

From clusters to groups of galaxies, the powerful bremsstrahlung radiation L_X emitted in X rays by the intracluster plasma is observed to decline sharply with lowering virial temperatures T (i.e., at shallower depths of the gravitational wells) after a steep local L_X-T correlation; this implies increasing scarcity of diffuse baryons relative to dark matter, well under the cosmic fraction. We show how the widely debated issue concerning these `missing baryons' is solved in terms of the thermal and/or dynamical effects of the kinetic (at low redshifts z) and radiative (at high z) energy inputs from central active galactic nuclei, of which independent evidence is being observed. From these inputs we compute shape and z-evolution expected for L_X-T correlation which agree with the existing data, and provide a predictive pattern for future observations.Comment: 5 pages, 3 figures, uses REVTeX4 + emulateapj.cls and apjfonts.sty. Accepted on ApJ

The XMM-LSS Survey: A well controlled X-ray cluster sample over the D1 CFHTLS area

We present the XMM-LSS cluster catalogue corresponding to the CFHTLS D1 area. The list contains 13 spectroscopically confirmed, X-ray selected galaxy clusters over 0.8 deg2 to a redshift of unity and so constitutes the highest density sample of clusters to date. Cluster X-ray bolometric luminosities range from 0.03 to 5x10^{44} erg/s. In this study, we describe our catalogue construction procedure: from the detection of X-ray cluster candidates to the compilation of a spectroscopically confirmed cluster sample with an explicit selection function. The procedure further provides basic X-ray products such as cluster temperature, flux and luminosity. We detected slightly more clusters with a (0.5-2.0 keV) X-ray fluxes of >2x10^{-14} erg/s/cm^{-2} than we expected based on expectations from deep ROSAT surveys. We also present the Luminosity-Temperature relation for our 9 brightest objects possessing a reliable temperature determination. The slope is in good agreement with the local relation, yet compatible with a luminosity enhancement for the 0.15 < z< 0.35 objects having 1 < T < 2 keV, a population that the XMM-LSS is identifying systematically for the first time. The present study permits the compilation of cluster samples from XMM images whose selection biases are understood. This allows, in addition to studies of large-scale structure, the systematic investigation of cluster scaling law evolution, especially for low mass X-ray groups which constitute the bulk of our observed cluster population. All cluster ancillary data (images, profiles, spectra) are made available in electronic form via the XMM-LSS cluster database.Comment: 12 pages 5 figures, MNRAS accepted. The paper with full resolution cluster images is available at http://vela.astro.ulg.ac.be/themes/spatial/xmm/LSS/rel_pub_e.htm

Advanced glycation inhibition and protection against endothelial dysfunction induced by coumarins and procyanidins from Mammea neurophylla.

Advanced glycation end-products (AGEs) are associated with many pathogenic disorders such as pathogenesis of diabetes or endothelial dysfunction leading to cardiovascular events. Therefore, the identification of new anti-AGE molecules or extracts aims at preventing such pathologies. Many Clusiaceae and Calophyllaceae species are used in traditional medicines to treat arterial hypertension as well as diabetes. Focusing on these plant families, an anti-AGE plant screening allowed us to select Mammea neurophylla for further phytochemical and biological studies. Indeed, both DCM and MeOH stem bark extracts demonstrated in vitro their ability to prevent inflammation in endothelial cells and to reduce vasoconstriction. A bioguided fractionation of these extracts allowed us to point out 4-phenyl- and 4-(1-acetoxypropyl)coumarins and procyanidins as potent inhibitors of AGE formation, potentially preventing endothelial dysfunction. The fractionation steps also led to the isolation of two new compounds, namely neurophyllols A and B from the DCM bark extract together with thirteen known mammea A and E coumarins (mammea A/AA, mammea A/AB, mammea A/BA, mammea A/BB, mammea A/AA cycloD, mammea A/AB cycloD, disparinol B, mammea A/AB cycloE, ochrocarpin A, mammea A/AA cycloF, mammea A/AB cycloF, mammea E/BA, mammea E/BB) as well as δ-tocotrienol, xanthones (1-hydroxy-7-methoxyxanthone, 2-hydroxyxanthone) and triterpenes (friedelin and betulinic acid). During this study, R,S-asperphenamate, previously described from fungal origin was also purified

The XMM-LSS survey: the Class 1 cluster sample over the initial 5 square degrees and its cosmological modelling

We present a sample of 29 galaxy clusters from the XMM-LSS survey over an area of some 5deg2 out to a redshift of z=1.05. The sample clusters, which represent about half of the X-ray clusters identified in the region, follow well defined X-ray selection criteria and are all spectroscopically confirmed. For all clusters, we provide X-ray luminosities and temperatures as well as masses. The cluster distribution peaks around z=0.3 and T =1.5 keV, half of the objects being groups with a temperature below 2 keV. Our L-T(z) relation points toward self-similar evolution, but does not exclude other physically plausible models. Assuming that cluster scaling laws follow self-similar evolution, our number density estimates up to z=1 are compatible with the predictions of the concordance cosmology and with the findings of previous ROSAT surveys. Our well monitored selection function allowed us to demonstrate that the inclusion of selection effects is essential for the correct determination of the evolution of the L-T relation, which may explain the contradictory results from previous studies. Extensive simulations show that extending the survey area to 10deg2 has the potential to exclude the non-evolution hypothesis, but that constraints on more refined ICM models will probably be limited by the large intrinsic dispersion of the L-T relation. We further demonstrate that increasing the dispersion in the scaling laws increases the number of detectable clusters, hence generating further degeneracy [in addition to sigma8, Omega_m, L(M,z) and T(M,z)] in the cosmological interpretation of the cluster number counts. We provide useful empirical formulae for the cluster mass-flux and mass-count-rate relations as well as a comparison between the XMM-LSS mass sensitivity and that of forthcoming SZ surveys.Comment: Accepted for publication by MNRAS. Full resolution images as well as additional cluster data are available through a dedicated database at http://l3sdb.in2p3.fr:8080/l3sdb

The XMM large scale structure survey: optical vs. X-ray classifications of active galactic nuclei and the unified scheme

Our goal is to characterize AGN populations by comparing their X-ray and optical classifications. We present a sample of 99 spectroscopically identified X-ray point sources in the XMM-LSS survey which are significantly detected in the [2-10] keV band, and with more than 80 counts. We performed an X-ray spectral analysis for all of these 99 X-ray sources. Introducing the fourfold point correlation coefficient, we find only a mild correlation between the X-ray and the optical classifications, as up to 30% of the sources have differing X-ray and optical classifications: on one hand, 10% of the type 1 sources present broad emission lines in their optical spectra and strong absorption in the X-rays. These objects are highly luminous AGN lying at high redshift and thus dilution effects are totally ruled out, their discrepant nature being an intrinsic property. Their X-ray luminosities and redshifts distributions are consistent with those of the unabsorbed X-ray sources with broad emission lines. On the other hand, 25/32 are moderate luminosity AGN, which are both unabsorbed in the X-rays and only present narrow emission lines in their optical spectra. The majority of them have an optical spectrum which is representative of the host galaxy. We finally infer that dilution of the AGN by the host galaxy seems to account for their nature. 5/25 have been defined as Seyfert 2. In conclusion, most of these 32 discrepant cases can be accounted for by the standard AGN unified scheme, as its predictions are not met for only 12% of the 99 X-ray sources. ABRIDGEDComment: 25 pages, 19 figures, Accepted for publication in A&

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