Increased fibrosis in a mouse model of anti-laminin 332 mucous membrane pemphigoid remains unaltered by inhibition of aldehyde dehydrogenase

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by autoantibodies against the basal membrane zone of skin and surface-close epithelia and predominant mucosal lesions. The oral cavity and conjunctivae are most frequently affected, albeit clinical manifestations can also occur on the skin. MMP-associated lesions outside the oral cavity typically lead to scarring. Mechanisms underlying scarring are largely unknown in MMP and effective treatment options are limited. Herein, we assessed the collagen architecture in tissue samples of an antibody-transfer mouse model of anti-laminin-332 MMP. In MMP mice, increased collagen fibril density was observed in skin and conjunctival lesions compared to mice injected with normal rabbit IgG. The extracellular matrix of MMP skin samples also showed altered post-translational collagen cross-linking with increased levels of both lysine- and hydroxylysine-derived collagen crosslinks supporting the fibrotic phenotype in experimental MMP compared to control animals. In addition, we evaluated a potential anti-fibrotic therapy in experimental anti-laminin-332 MMP using disulfiram, an inhibitor of the aldehyde dehydrogenase (ALDH), which has been implicated in immune-mediated mucosal scarring. In addition, disulfiram also acts as a copper chelator that was shown to block lysyl oxidase activity, an enzyme involved in formation of collagen crosslinks. Topical use of disulfiram (300 μM in 2 [w/v] methocel) did not improve ocular lesions in experimental MMP over the 12-day treatment period in disulfiram-treated mice compared to vehicle-treated mice (n=8/group). Furthermore, C57BL6/J mice (n=8/group) were treated prophylactically with 200 mg/kg p.o. disulfiram or the solvent once daily over a period of 12 days. Systemic treatment did not show any reduction in the severity of oral and ocular lesions in MMP mice, albeit some improvement in skin lesions was observed in disulfiram- vs. vehicle-treated mice (p=0.052). No reduction in fibrosis was seen, as assessed by immunohistochemistry. Whilst blocking of ALDH failed to significantly ameliorate disease activity, our data provide new insight into fibrotic processes highlighting changes in the collagenous matrix and cross-linking patterns in IgG-mediated MMP

Stellar Iron Abundances: non-LTE Effects

We report new statistical equilibrium calculations for Fe I and Fe II in the atmosphere of Late-Type stars. We used atomic models for Fe I and Fe II having respectively 256 and 190 levels, as well as 2117 and 3443 radiative transitions. Photoionization cross-sections are from the Iron Project. These atomic models were used to investigate non-LTE effects in iron abundances of Late-Type stars with different atmospheric parameters. We found that most Fe I lines in metal-poor stars are formed in conditions far from LTE. We derived metallicity corrections of about 0.3 dex with respect to LTE values, for the case of stars with [Fe/H] ~ -3.0. Fe II is found not to be affected by significant non-LTE effects. The main non-LTE effect invoked in the case of Fe I is overionization by ultraviolet radiation, thus classical ionization equilibrium is far to be satisfied. An important consequence is that surface gravities derived by LTE analysis are in error and should be corrected before final abundances corrections. This apparently solves the observed discrepancy between spectroscopic surface gravities derived by LTE analyses and those derived from Hipparcos parallaxes. A table of non-LTE [Fe/H] and log g values for a sample of metal-poor late-type stars is given.Comment: 22 pages, 9 figures, 1 table, ApJ style, accepte

The solar photospheric abundance of carbon.Analysis of atomic carbon lines with the CO5BOLD solar model

The use of hydrodynamical simulations, the selection of atomic data, and the computation of deviations from local thermodynamical equilibrium for the analysis of the solar spectra have implied a downward revision of the solar metallicity. We are in the process of using the latest simulations computed with the CO5BOLD code to reassess the solar chemical composition. We determine the solar photospheric carbon abundance by using a radiation-hydrodynamical CO5BOLD model, and compute the departures from local thermodynamical equilibrium by using the Kiel code. We measure equivalent widths of atomic CI lines on high resolution, high signal-to-noise ratio solar atlases. Deviations from local thermodynamic equilibrium are computed in 1D with the Kiel code. Our recommended value for the solar carbon abundance, relies on 98 independent measurements of observed lines and is A(C)=8.50+-0.06, the quoted error is the sum of statistical and systematic error. Combined with our recent results for the solar oxygen and nitrogen abundances this implies a solar metallicity of Z=0.0154 and Z/X=0.0211. Our analysis implies a solar carbon abundance which is about 0.1 dex higher than what was found in previous analysis based on different 3D hydrodynamical computations. The difference is partly driven by our equivalent width measurements (we measure, on average, larger equivalent widths with respect to the other work based on a 3D model), in part it is likely due to the different properties of the hydrodynamical simulations and the spectrum synthesis code. The solar metallicity we obtain from the CO5BOLD analyses is in slightly better agreement with the constraints of helioseismology than the previous 3D abundance results. (Abridged)Comment: Astronomy and Astrophysics, accepte

Formation of Zr I and II lines under non-LTE conditions of stellar atmospheres

The non-local thermodynaic equilibrium (non-LTE) line formation for the two ions of zirconium is considered through a range of spectral types when the Zr abundance varies from the solar value down to [Zr/H] = -3. The model atom was built using 148 energy levels of Zr I, 772 levels of Zr II, and the ground state of Zr III. It was shown that the main non-LTE mechnism for the minority species Zr I is ultraviolet overionization. Non-LTE leads to systematically depleted total absorption in the Zr I lines and positive abundance corrections, reaching to 0.33 dex for the solar metallicity models. The excited levels of Zr II are overpopulated relative to their thermodynamic equilibrium populations in the line formation layers due to radiative pumping from the low-excitation levels. As a result, the line source function exceeds the Planck function leading to weakening the Zr II lines and positive non-LTE abundance corrections. Such corrections grow towards lower metallicity and lower surface gravity and reach to 0.34 dex for Teff = 5500 K, log g = 2.0, [M/H] = -2. As a test and first application of the Zr I-Zr II model atom, Zr abundance was determined for the Sun on the basis of 1D LTE model atmosphere. Lines of Zr I and Zr II give consistent within the error bars non-LTE abundances, while the difference in LTE abundances amounts to 0.28 dex. The solar abundance of zirconium obtained with the MAFAGS solar model atmosphere is log eps(Zr) = 2.63+-0.07.Comment: published in Astron. Letters, 36, 664 (2010); Erratum was submitte

Non-LTE line formation for heavy elements in four very metal-poor stars

Stellar parameters and abundances of Na, Mg, Al, K, Ca, Sr, Ba, and Eu are determined for four very metal-poor stars (-2.66 < [Fe/H] < -2.15) based on non-LTE line formation and analysis of high-resolution (R ~60000 and 90000) high signal-to-noise (S/N > 200) observed spectra. A model atom for H I is presented. An effective temperature was obtained from the Balmer Halpha and Hbeta line wing fits, the surface gravity from the Hipparcos parallax if available and the non-LTE ionization balance between Ca I and Ca II. Based on the hyperfine structure affecting the Ba II resonance line, the fractional abundance of the odd isotopes of Ba was derived for HD 84937 and HD 122563 from a requirement that Ba abundances from the resonance line and subordinate lines of Ba II must be equal. For each star, non-LTE leads to a consistency of Teff from two Balmer lines and to a higher temperature compared to the LTE case, by up to 60 K. Non-LTE effects are important in spectroscopic determination of surface gravity from Ca I/Ca II. For each star with a known trigonometric gravity, non-LTE abundances from the lines of two ionization stages agree within the error bars, while a difference in the LTE abundances consists of 0.23 dex to 0.40 dex for different stars. Departures from LTE are found to be significant for the investigated atoms, and they strongly depend on stellar parameters. For HD 84937, the Eu/Ba ratio is consistent with the relative solar system r-process abundances, and the fraction of the odd isotopes of Ba, f_odd, equals 0.43+-0.14. The latter can serve as a constraint on r-process models. The lower Eu/Ba ratio and f_odd = 0.22+-0.15 found for HD 122563 suggest that the s-process or the unknown process has contributed significantly to the Ba abundance in this star.Comment: accepted for publication in A&A, November 16, 200

A primordial star in the heart of the Lion

Context: The discovery and chemical analysis of extremely metal-poor stars permit a better understanding of the star formation of the first generation of stars and of the Universe emerging from the Big Bang. aims: We report the study of a primordial star situated in the centre of the constellation Leo (SDSS J102915+172027). method: The star, selected from the low resolution-spectrum of the Sloan Digital Sky Survey, was observed at intermediate (with X-Shooter at VLT) and at high spectral resolution (with UVES at VLT). The stellar parameters were derived from the photometry. The standard spectroscopic analysis based on 1D ATLAS models was completed by applying 3D and non-LTE corrections. results: An iron abundance of [Fe/H]=--4.89 makes SDSS J102915+172927 one of the lowest [Fe/H] stars known. However, the absence of measurable C and N enhancements indicates that it has the lowest metallicity, Z<= 7.40x10^{-7} (metal-mass fraction), ever detected. No oxygen measurement was possible. conclusions: The discovery of SDSS J102915+172927 highlights that low-mass star formation occurred at metallicities lower than previously assumed. Even lower metallicity stars may yet be discovered, with a chemical composition closer to the composition of the primordial gas and of the first supernovae.Comment: To be published in A&

Consistent responses of soil microbial communities to elevated nutrient inputs in grasslands across the globe

Soil microorganisms are critical to ecosystem functioning and the maintenance of soil fertility. However, despite global increases in the inputs of nitrogen (N) and phosphorus (P) to ecosystems due to human activities, we lack a predictive understanding of how microbial communities respond to elevated nutrient inputs across environmental gradients. Here we used high-throughput sequencing of marker genes to elucidate the responses of soil fungal, archaeal, and bacterial communities using an N and P addition experiment replicated at 25 globally distributed grassland sites. We also sequenced metagenomes from a subset of the sites to determine how the functional attributes of bacterial communities change in response to elevated nutrients. Despite strong compositional differences across sites, microbial communities shifted in a consistent manner with N or P additions, and the magnitude of these shifts was related to the magnitude of plant community responses to nutrient inputs. Mycorrhizal fungi and methanogenic archaea decreased in relative abundance with nutrient additions, as did the relative abundances of oligotrophic bacterial taxa. The metagenomic data provided additional evidence for this shift in bacterial life history strategies because nutrient additions decreased the average genome sizes of the bacterial community members and elicited changes in the relative abundances of representative functional genes. Our results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide

The solar photospheric nitrogen abundance. Analysis of atomic transitions with 3D and 1D model atmospheres

CONTEXT: In recent years, the solar chemical abundances have been studied in considerable detail because of discrepant values of solar metallicity inferred from different indicators, i.e., on the one hand, the "sub-solar" photospheric abundances resulting from spectroscopic chemical composition analyses with the aid of 3D hydrodynamical models of the solar atmosphere, and, on the other hand, the high metallicity inferred by helioseismology. AIMS: After investigating the solar oxygen abundance using a CO5BOLD 3D hydrodynamical solar model in previous work, we undertake a similar approach studying the solar abundance of nitrogen, since this element accounts for a significant fraction of the overall solar metallicity, Z. METHOD: We used a selection of atomic spectral lines to determine the solar nitrogen abundance, relying mainly on equivalent width measurements in the literature. We investigate the influence on the abundance analysis, of both deviations from local thermodynamic equilibrium ("NLTE effects") and photospheric inhomogeneities ("granulation effects"). RESULTS: We recommend use of a solar nitrogen abundance of A(N)=7.86+-0.12 whose error bar reflects the line-to-line scatter. CONCLUSION: The solar metallicity implied by the CO5BOLD-based nitrogen and oxygen abundances is in the range 0.0145<= Z <= 0.0167. This result is a step towards reconciling photospheric abundances with helioseismic constraints on Z. Our most suitable estimates are Z=0.0156 and Z/X=0.0213.Comment: To be published on A&

Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic $ep$ scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil