We characterised the spatial structure of soil microbial communities in an unimproved grazed upland grassland in the Scottish Borders. A range of soil chemical parameters, cultivable microbes, ...protozoa, nematodes, phospholipid fatty acid (PLFA) profiles, community-level physiological profiles (CLPP), intra-radical arbuscular mycorrhizal community structure, and eubacterial, actinomycete, pseudomonad and ammonia-oxidiser 16S rRNA gene profiles, assessed by denaturing gradient gel electrophoresis (DGGE) were quantified. The botanical composition of the vegetation associated with each soil sample was also determined. Geostatistical analysis of the data revealed a gamut of spatial dependency with diverse semivariograms being apparent, ranging from pure nugget, linear and non-linear forms. Spatial autocorrelation generally accounted for 40–60% of the total variance of those properties where such autocorrelation was apparent, but accounted for 97% in the case of nitrate-N. Geostatistical ranges extending from approximately 0.6–6 m were detected, dispersed throughout both chemical and biological properties. CLPP data tended to be associated with ranges greater than 4.5 m. There was no relationship between physical distance in the field and genetic similarity based on DGGE profiles. However, analysis of samples taken as close as 1 cm apart within a subset of cores suggested some spatial dependency in community DNA-DGGE parameters below an 8 cm scale. Spatial correlation between the properties was generally weak, with some exceptions such as between microbial biomass C and total N and C. There was evidence for scale-dependence in the relationships between properties. PLFA and CLPP profiling showed some association with vegetation composition, but DGGE profiling did not. There was considerably stronger association between notional sheep urine patches, denoted by soil nutrient status, and many of the properties. These data demonstrate extreme spatial variation in community-level microbiological properties in upland grasslands, and that despite considerable numeric ranges in the majority of properties, overarching controlling factors were not apparent.
Cutaneous ageing is the result of two distinct, biological processes which may occur concurrently: (i) the passage of time, termed intrinsic ageing and (ii) environmental influences, termed extrinsic ...ageing. Intrinsic ageing of the skin is a slow process which causes changes in tissue structure and impairs function in the absence of additional biological, chemical and physical factors. The clinical features of intrinsically aged skin are not usually evident until old age when, although smooth and unblemished, the skin surface appears pale and is characterized by fine wrinkles with occasional exaggerated expression lines. Functionally, intrinsically aged skin is dry and less elastic than more youthful skin. In contrast, extrinsically aged skin is exemplified by deep, coarse wrinkles, mottled hyperpigmentation and a marked loss of elasticity and recoil. The two major environmental influences which induce extrinsic ageing are: (i) chronic exposure to solar ultraviolet (UV) irradiation (termed photoageing) and (ii) smoking. This review discusses the changes associated with the ageing process in the skin, with particular emphasis on the role played by the elastic fibre network in maintaining dermal function. The review concludes with a discussion of a short-term assay for independent assessment of the efficacy of anti-ageing cosmetic products using the elastic fibre component fibrillin-1 as a biomarker of extracellular matrix repair.
Context. The COSMOS survey is a multiwavelength survey aimed to study the evolution of galaxies, AGN and large scale structures. Within this survey XMM-COSMOS a powerful tool to detect AGN and galaxy ...clusters. The XMM-COSMOS is a deep X-ray survey over the full 2 deg2 of the COSMOS area. It consists of 55 XMM-Newton pointings for a total exposure of ~1.5 Ms with an average vignetting-corrected depth of 40 ks across the field of view and a sky coverage of 2.13 deg2. Aims. We present the catalogue of point-like X-ray sources detected with the EPIC CCD cameras, the $\log N - \log S$ relations and the X-ray colour–colour diagrams. Methods. The analysis was performed using the XMM-SAS data analysis package in the 0.5–2 keV, 2–10 keV and 5–10 keV energy bands. Source detection has been performed using a maximum likelihood technique especially designed for raster scan surveys. The completeness of the catalogue as well as $\log N -\log S$ and source density maps have been calibrated using Monte Carlo simulations. Results. The catalogs contains a total of 1887 unique sources detected in at least one band with likelihood parameter det_ml $>10$. The survey, which shows unprecedented homogeneity, has a flux limit of ~$1.7\times 10 ^{-15}$ erg cm-2 s-1, ~$9.3 \times 10 ^{-15}$ erg cm-2 s-1 and ~$1.3 \times 10^{-14}$ erg cm-2 s-1 over 90% of the area (1.92 deg2) in the 0.5–2 keV, 2–10 keV and 5–10 keV energy band, respectively. Thanks to the rather homogeneous exposure over a large area, the derived $\log N - \log S$ relations are very well determined over the flux range sampled by XMM-COSMOS. These relations have been compared with XRB synthesis models, which reproduce the observations with an agreement of ~10% in the 5–10 keV and 2–10 keV band, while in the 0.5–2 keV band the agreement is of the order of ~20%. The hard X-ray colors confirmed that the majority of the extragalactic sources in a bright subsample are actually type I or type II AGN. About 20% of the sources have a X-ray luminosity typical of AGN ($L_{\rm X}> 10^{42}$ erg/s) although they do not show any clear signature of nuclear activity in the optical spectrum.
The efficacy of topical sunscreens is currently assessed by crude, costly and time consuming in vivo assays. We have previously demonstrated that components of the dermal extracellular matrix (ECM), ...rich in UV-absorbing amino acids, are susceptible to damage by solar simulated radiation (SSR) in vitro. Here we developed an in vitro method to test the ability of sunscreens to protect fibrillin-rich microfibrils (FRM) and fibronectin, key components of the dermal ECM from UV-induced damage. Solutions of FRM or fibronectin were irradiated without protection, in the presence of a vehicle or a commercially-available flat-spectrum sunscreen. The effect of SSR on molecular structure was determined by atomic force microscopy (FRM) and SDS-PAGE (fibronectin). Following irradiation, FRM periodicity became bi-modally distributed (peaks: 40nm & 59nm) compared to the unimodal distribution in unexposed controls (peak: 50nm). Irradiation in the presence of flat-spectrum sunscreen protected against this change, maintaining the unimodal distribution. SSR induced significant aggregation of fibronectin (p=0.005), which was abrogated by sunscreen. These results demonstrate that this in vitro assay system is sufficiently sensitive to act as an initial/additional screen of sunscreen efficacy. We conclude that sunscreen can reduce UV-mediated damage of key dermal ECM in vitro and thereby prevent remodelling associated with photoageing.
•Current methods for SPF testing use crude measures of erythema on health volunteers.•UV-induced dermal matrix remodelling is a key hallmark of photoaged skin.•Skin extracted fibrillin microfibrils can be used as a biomarker of UV damage.•Fibronectin can used in a quick, easy in vitro assay to test sunscreen efficacy.•This in vitro assay shows sunscreens can also protect key dermal matrix components.
We present data analysis and X-ray source counts for the first season of XMM-Newton observations in the COSMOS field. The survey covers similar to 2 deg super(2) within the region of sky bounded by ...09 super(b) 57 super(m) 30 super(s) < R.A. < 10 super(b) 0S super(m) 30 super(s), 01 degree 27'30" < decl. < 02 degree 57'30" with a total net integration time of 504 ks. A maximum likelihood source detection was performed in the 0.5-2, 2-4.5, and 4.5-10 keV energy bands, and 1390 pointlike sources were detected in at least one band. Detailed Monte Carlo simulations were performed to fully test the source-detection method and to derive the sky coverage to be used in the computation of the log N -log S relations. These relations were then derived in the 0.5-2, 2-10, and 5-10 keV energy bands, down to flux limits of 7.2 x 10 super(-10) ergs cm super(-2) s super(-1), 4.0 x 10 super(-15) ergs cm super(-2) s super(-1), and 9.7 x 10 super(-15) ergs cm super(-2) s super(-1), respectively. Thanks to the large number of sources detected in the COSMOS survey, the log N -log S curves are tightly constrained over a range of fluxes which were poorly covered by previous surveys, especially in the 2-10 and 5-10 keV bands. The 0.5-2 and 2-10 keV differential log N -log S relations were fitted with a broken power-law model which revealed a Euclidean slope at the bright end and a flatter slope ( unk unk 1.5) at faint fluxes. In the 5-10 keV energy band a single power law provides an acceptable fit to the observed source counts with a slope alpha similar to 2.4. A comparison with the results of previous surveys shows good agreement in all the energy bands under investigation in the overlapping flux range. We also notice a remarkable agreement between our log N -log S relations and the most recent model of the X-ray background.
To conduct a pragmatic, randomized controlled trial to assess whether thiopurine methyltransferase (TPMT) genotyping prior to azathioprine reduces adverse drug reactions (ADRs).
A total of 333 ...participants were randomized 1:1 to undergo TPMT genotyping prior to azathioprine or to commence treatment without genotyping.
There was no difference in the primary outcome of stopping azathioprine due to an adverse reaction (ADR, p = 0.59) between the two study arms. ADRs were more common in older patients (p = 0.01). There was no increase in stopping azathioprine due to ADRs in TPMT heterozygotes compared with wild-type individuals. The single individual with TPMT variant homozygosity experienced severe neutropenia.
Our work supports the strong evidence that individuals with TPMT variant homozygosity are at high risk of severe neutropenia, whereas TPMT heterozygotes are not at increased risk of ADRs at standard doses of azathioprine.
Vaccination with Bacille Calmette-Guérin (BCG) has traditionally been used for protection against disease caused by the bacterium Mycobacterium tuberculosis (M.tb). The efficacy of BCG, especially ...against pulmonary tuberculosis (TB) is variable. The best protection is conferred in temperate climates and there is close to zero protection in many tropical areas with a high prevalence of both tuberculous and non-tuberculous mycobacterial species. Although interferon (IFN)-γ is known to be important in protection against TB disease, data is emerging on a possible role for interleukin (IL)-17 as a key cytokine in both murine and bovine TB vaccine studies, as well as in humans. Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) is a novel TB vaccine designed to enhance responses induced by BCG. Antigen-specific IFN-γ production has already been shown to peak one week post-MVA85A vaccination, and an inverse relationship between IL-17-producing cells and regulatory T cells expressing the ectonucleosidease CD39, which metabolises pro-inflammatory extracellular ATP has previously been described. This paper explores this relationship and finds that consumption of extracellular ATP by peripheral blood mononuclear cells from MVA85A-vaccinated subjects drops two weeks post-vaccination, corresponding to a drop in the percentage of a regulatory T cell subset expressing the ectonucleosidase CD39. Also at this time point, we report a peak in co-production of IL-17 and IFN-γ by CD4(+) T cells. These results suggest a relationship between extracellular ATP and effector responses and unveil a possible pathway that could be targeted during vaccine design.
We present the results of the simultaneous deep XMM-Newton and Chandra observations of the bright Seyfert 1.9 galaxy MCG -5-23-16, which is thought to have one of the best known examples of a ...relativistically broadened iron K alpha line. The time-averaged spectral analysis shows that the iron K-shell complex is best modeled with an unresolved narrow emission component (FWHM < 5000 km s super(-1), EW similar to 60 eV) plus a broad component. This latter component has FWHM similar to 44.000 km s super(-1) and EW similar to 50 eV. Its profile is well described by an emission line originating from an accretion disk viewed with an inclination angle similar to 40 degree , with the emission arising from within a few tens of gravitational radii of the central black hole. The time-resolved spectral analysis of the XMM-Newton EPIC pn spectrum shows that both the narrow and broad components of the Fe K emission line appear to be constant in time within the errors. We detected a narrow sporadic absorption line at 7.7 keV, which appears to be variable on a timescale of 20 ks. If associated with Fe XXVI Ly alpha , this absorption is indicative of a possibly variable, high-ionization, high-velocity outflow. The variability of this absorption feature appears to rule out a local (z = 0) origin. The analysis of the XMM-Newton RGS spectrum reveals that the soft X-ray emission of MCG -5-23-16 is likely dominated by several emission lines superimposed on an unabsorbed scattered power-law continuum. The lack of strong Fe L-shell emission, together with the detection of a strong forbidden line in the O VII triplet, is consistent with a scenario in which the soft X-ray emission lines are produced in a plasma photoionized by the nuclear emission.
We present the results of a search for galaxy dusters in the first 36 XMM-Newton pointings on the Cosmic Evolution Survey (COSMOS) field. We reach a depth for a total cluster flux in the 0.5-2 keV ...band of 3 x 10 super(-15) ergs cm sub(-2) s sub(-1), having one of the widest XMM-Newton contiguous raster surveys, covering an area of 2.1 deg super(2). Cluster candidates are identified through a wavelet detection of extended X-ray emission. Verification of the cluster candidates is done based on a galaxy concentration analysis in redshift slices of thickness 0.1-0.2 in redshift, using the multiband photometric catalog of the COSMOS field and restricting the search to z < 1.3 and i sub(AB) < 25. We identify 72 clusters and derive their properties based on the X-ray cluster scaling relations. A statistical description of the survey in terms of the cumulative log (N > S) - logS distribution compares well with previous results, although yielding a somewhat higher number of clusters at similar fluxes. The X-ray luminosity function of COSMOS clusters matches well the results of nearby surveys, providing a comparably tight constraint on the faint-end slope of alpha = 1.03 plus or minus 0.04. For the probed luminosity range of (8 x 10 super(42))-(2 x 10 super(44)) ergs s sub(-1), our survey is In agreement with and adds significantly to the existing data on the cluster luminosity function at high redshifts and implies no substantial evolution at these luminosities to z = 1.3.
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