Direct angiotensin AT2 receptor stimulation using a novel AT2 receptor agonist, compound 21, evokes neuroprotection in conscious hypertensive rats

Background: In this study, the neuroprotective effect of a novel nonpeptide AT2R agonist, C21, was examined in a conscious model of stroke to verify a class effect of AT2R agonists as neuroprotective agents. Methods and Results: Spontaneously hypertensive rats (SHR) were pre-treated for 5 days prior to stroke with C21 alone or in combination with the AT2R antagonist PD123319. In a separate series of experiments C21 was administered in a series of 4 doses commencing 6 hours after stroke. A focal reperfusion model of ischemia was induced in conscious SHR by administering endothelin-1 to the middle cerebral artery (MCA). Motor coordination was assessed at 1 and 3 days after stroke and post mortem analyses of infarct volumes, microglia activation and neuronal survival were performed at 72 hours post MCA occlusion. When given prior to stroke, C21 dose dependently decreased infarct volume, which is consistent with the behavioural findings illustrating an improvement in motor deficit. During the pre-treatment protocol C21 was shown to enhance microglia activation, which are likely to be evoking protection by releasing brain derived neurotrophic factor. When drug administration was delayed until 6 hours after stroke, C21 still reduced brain injury. Conclusion: These results indicate that centrally administered C21 confers neuroprotection against stroke damage. This benefit is likely to involve various mechanisms, including microglial activation of endogenous repair and enhanced cerebroperfusion. Thus, we have confirmed the neuroprotective effect of AT2R stimulation using a nonpeptide compound which highlights the clinical potential of the AT2R agonists for future development

Lateral Variation in Crustal Structure along the Lesser Antilles Arc from Petrology of Crustal Xenoliths and Seismic Receiver Functions

We reconstruct crustal structure along the Lesser Antilles island arc using an inversion approach combining constraints from petrology of magmatic crustal xenoliths and seismic receiver functions. Xenoliths show considerable island-to-island variation in xenolith petrology from plagioclase-free ultramafic lithologies to gabbros and gabbronorites with variable proportions of amphibole, indicative of changing magma differentiation depths. Xenoliths represent predominantly cumulate compositions with equilibration depths in the range 5 to 40 km. We use xenolith mineral modes and compositions to calculate seismic velocities () and density at the estimated equilibration depths. We create a five-layer model of crustal structure for testing against receiver functions (RF) from island seismic stations along the arc. Lowermost layer (5) comprises peridotite with physical characteristics of mantle xenoliths from Grenada. Uppermost layer (1) consists of 5 km of volcaniclastics and sediments, whose physical properties are determined via a grid inversion routine. The three middle layers (2) to (4) comprise igneous arc crust with compositions corresponding to the xenoliths sampled at each island. By inversion we obtain a petrological best-fit for the RF on each island to establish the nature and thicknesses of layers (2) to (4). Along the arc we see variations in the depth and strength of both Moho and mid-crustal discontinuity (MCD) on length-scales of tens of km. Moho depths vary from 25 to 37 km; MCD from 11 and 32 km. The Moho is the dominant discontinuity beneath some islands (St. Kitts, Guadeloupe, Martinique, Grenada), whereas the MCD dominates beneath others (Saba, St. Eustatius). Along-arc variability in MCD depth and strength is consistent with variation in estimated magmatic H2O contents and differentiations depths that, in turn, influence xenolith lithologies. A striking feature is steep, along-arc gradients in similar to those observed at other oceanic arcs. These gradients reflect abrupt changes in rates and processes of magma generation in the underlying crust and mantle. We find no evidence for large, interconnected bodies of partial melt beneath the Lesser Antilles. Instead, the crustal velocity structure is consistent with magma differentiation in vertically-extensive, crystal mush-dominated reservoirs. Along-arc variation in crustal structure may reflect heterogeneous upwelling within the mantle wedge, itself driven by variation in slab-derived H2O fluxes.This work was supported by Natural Environment Research Council grants NE/N001966/1, NE/K004883/1, NE/K014978/1 and NE/K010824/1 and ERC Advanced Grant CRITMAG (Blundy

Salmonella-associated Deaths, Sweden, 1997–2003

We examined excess deaths after infection with Salmonella in a registry-based matched cohort study of 25,060 persons infected abroad and 5,139 infected within Sweden. The domestically infected have an increased standardized mortality ratio, whereas those who acquired Salmonella infection abroad had no excess risk of death

Spatially extended absorption around the z=2.63 radio galaxy MRC 2025-218: outflow or infall?

We present an investigation into the absorber in front of the z=2.63 radio galaxy MRC 2025-218, using integral field spectroscopy obtained at the Very Large Telescope, and long slit spectroscopy obtained at the Keck II telescope. The properties of MRC 2025-218 are particularly conducive to study the nature of the absorbing gas, i.e., this galaxy shows bright and spatially extended Ly-alpha emission, along with bright continuum emission from the active nucleus. Ly-alpha absorption is detected across ~40x30 kpc^2, has a covering factor of ~1, and shows remarkably little variation in its properties across its entire spatial extent. This absorber is kinematically detached from the extended emission line region (EELR). Its properties suggest that the absorber is outside of the EELR. We derive lower limits to the HI, HII and H column densities for this absorber of 3x10^16, 7x10^17 and 2x10^18 cm^-2, respectively. Moreover, the relatively bright emission from the active nucleus has allowed us to measure a number of metal absorption lines: CI, CII, CIV, NV, OI, SiII, SiIV, AlII and AlIII. The column density ratios are most naturally explained using photoionization by a hard continuum, with an ionization parameter U~0.0005-0.005. Shocks or photoionization by young stars cannot reproduce satisfactorily the measured column ratios. Using the ratio between the SiII* and SiII column densities, we derive a lower limit of >10 cm^-3 for the electron density of the absorber. The data do not allow useful constraints to be placed on the metallicity of the absorber. We consider two possibilities for the nature of this absorber: the cosmological infall of gas, and an outflow driven by supernovae or the radio-jets.Comment: Accepted for publication in MNRA

The optical/X-ray connection: ICM iron content and galaxy optical luminosity in 20 galaxy clusters

X-ray observations of galaxy clusters have shown that the intra-cluster gas has iron abundances of about one third of the solar value. These observations also show that part (if not all) of the intra-cluster gas metals were produced within the member galaxies. We present a systematic analysis of 20 galaxy clusters to explore the connection between the iron mass and the total luminosity of early-type and late-type galaxies, and of the brightest cluster galaxies (BCGs). From our results, the intra-cluster medium (ICM) iron mass seems to correlate better with the luminosity of the BCGs than with that of the red and blue galaxy populations. As the BCGs cannot produce alone the observed amount of iron, we suggest that ram-pressure plus tidal stripping act together to enhance, at the same time, the BCG luminosities and the iron mass in the ICM. Through the analysis of the iron yield, we have also estimated that SN Ia are responsible for more than 50% of the total iron in the ICM. This result corroborates the fact that ram-pressure contributes to the gas removal from galaxies to the inta-cluster medium, being very efficient for clusters in the temperature range 2 < kT (keV)< 10Comment: Accepted for publication in MNRAS (11 pg, 9 figures and 3 tables

Sunyaev-Zel'dovich effect in the Virgo cluster from WMAP and ROSAT data

WMAP observations at mm wavelengths are sensitive to the Sunyaev-Zel'dovich effect in galaxy clusters. Among all the objects in the sky, the Virgo cluster is expected to provide the largest integrated signal. Based on models compatible with the X-ray emission observed in the ROSAT All Sky Survey, we predict a two-sigma detection of the SZ effect from Virgo in the WMAP 3-year data. Our analysis reveals a 3-sigma signal on scales of 5 degrees, although the frequency dependence deviates from the theoretical expectation for the SZ effect. The main sources of uncertainty are instrumental noise, and most importantly, possible contamination from point sources and diffuse back/foregrounds. In particular, a population of unresolved extragalactic sources in Virgo would explain the observed intensity and frequency dependence. In order to resolve this question one needs to wait for experiments like Planck to achieve the required accuracy.Comment: 11 pages. 10 figures. Submitted to MNRA

A statistical analysis of the Two Dimensional XMM-Newton Group Survey: The impact of feedback on group properties

(abridged) We present a statistical analysis of 28 nearby galaxy groups from the Two-Dimensional XMM-Newton Group Survey (2dXGS). We focus on entropy and the role of feedback, dividing the sample into cool core (CC) and non cool core (NCC) systems, the first time the latter have been studied in detail in the group regime. The coolest groups have steeper entropy profiles than the warmest systems, and NCC groups have higher central entropy and exhibit more scatter than their CC counterparts. We compare the entropy distribution of the gas in each system to the expected theoretical distribution ignoring non-gravitational processes. In all cases, the observed maximum entropy far exceeds that expected theoretically, and simple models for modifications of the theoretical entropy distribution perform poorly. Applying initial pre-heating, followed by radiative cooling, generally fails to match the low entropy behaviour, and only performs well when the difference between the maximum entropy of the observed and theoretical distributions is small. Successful feedback models need to work differentially to increase the entropy range in the gas, and we suggest two basic possibilities. We analyse the effects of feedback on the entropy distribution, finding systems with a high measure of `feedback impact' to reach higher entropy than their low feedback counterparts and also to show significantly lower central metallicities. If low entropy, metal-rich gas has been boosted to large entropy in the high feedback systems, it must now reside outside 0.5r_500, to remain undetected. We find similar levels of enrichment in both high and low feedback systems, and argue that the lack of extra metals in the highest feedback systems points to an AGN origin for the bulk of the feedback, probably acting within precursor structures.Comment: 24 pages, 21 figures; accepted for publication in MNRA

Subduction initiation without magmatism:The case of the missing Alpine magmatic arc

Models of orogens identify subduction of oceanic crust as the key mechanism leading to continental collision. Such models, based inter alia on thermobarometric and geochronological evidence preserved in high-pressure metamorphic rocks and subduction-related magmatism, have been used to explain the convergence of Europe and Adria in the Cretaceous–Cenozoic and the subsequent Alpine orogen. Here, we review the metamorphic, igneous, and sedimentary record of the past 300 Ma of the Alpine orogen to show that there is no evidence of igneous activity during subduction initiation and prograde high-pressure metamorphism, leading to an ∼50 Ma hiatus in magmatism, or “arc gap.” The closure of rift basins forming the Piemont-Liguria ocean did not follow a classical Wadati-Benioff–type subduction. Instead, subduction initiation at passive margins allowed for the accretion of the hydrated portion of the subducting plate within an orogenic wedge as subduction of dry subcontinental lithosphere inhibited magmatism during subduction initiation and ocean closure.ISSN:0091-7613ISSN:1943-268

Enlightening the structure and dynamics of Abell 1942

We present a dynamical analysis of the galaxy cluster Abell 1942 based on a set of 128 velocities obtained at the European Southern Observatory. Data on individual galaxies are presented and the accuracy of the determined velocities is discussed as well as some properties of the cluster. We have also made use of publicly available Chandra X-ray data. We obtained an improved mean redshift value z = 0.22513 \pm 0.0008 and velocity dispersion sigma = 908^{+147}_{-139} km/s. Our analysis indicates that inside a radius of ~1.5 h_{70}^{-1} Mpc (~7 arcmin) the cluster is well relaxed, without any remarkable feature and the X-ray emission traces fairly well the galaxy distribution. Two possible optical substructures are seen at ~5 arcmin from the centre towards the Northwest and the Southwest direction, but are not confirmed by the velocity field. These clumps are however, kinematically bound to the main structure of Abell 1942. X-ray spectroscopic analysis of Chandra data resulted in a temperature kT = 5.5 \pm 0.5 keV and metal abundance Z = 0.33 \pm 0.15 Z_odot. The velocity dispersion corresponding to this temperature using the T_X-sigma scaling relation is in good agreement with the measured galaxies velocities. Our photometric redshift analysis suggests that the weak lensing signal observed at the south of the cluster and previously attributed to a "dark clump", is produced by background sources, possibly distributed as a filamentary structure.Comment: Accepted for publication in Astronomy & Astrophysics, 15 pages, 15 figures, table w/ positions, photometric data and redshift