Mechanisms altering airway smooth muscle cell Ca(2+) homeostasis in two asthma models

Background: Asthma is characterized by airway remodeling, altered mucus production and airway smooth muscle cell (ASMC) contraction causing extensive airway narrowing. In particular, alterations of ASMC contractility seem to be of crucial importance. The elevation of the cytoplasmic Ca(2+) concentration is a key event leading to ASMC contraction and changes in the agonist- induced Ca(2+) increase in ASMC have been reported in asthma. Objective: The aim of this study was to investigate mechanisms underlying these changes. Methods: Murine tracheal smooth muscle cells (MTSMC) from T- bet KO mice and human bronchial smooth muscle cells (HBSMC) incubated with IL-13 and IL-4 served as asthma models. Acetylcholine- induced changes in the cytoplasmic Ca(2+) concentration were recorded using fluorescence microscopy and the expression of Ca(2+) homeostasis regulating proteins was investigated with Western blot analysis. Results: Acetylcholine- induced Ca(2+) transients were elevated in both asthma models. This correlated with an increased Ca(2+) content of the sarcoplasmic reticulum (SR). In MTSMC from T-bet KO mice, the expression of the SR Ca(2+) buffers calreticulin and calsequestrin was higher compared to wild- type mice. In HBSMC incubated with IL-13 or IL-4, the expression of ryanodine receptors, inositol-3-phosphate receptors and sarcoplasmic/ endoplasmic reticulum Ca 2+ ATPases 2 was increased compared to HBSMC without incubation with interleukins. The enlarged acetylcholine- induced Ca(2+) transients could be reversed by blocking inositol-3- phosphate receptors. Conclusions: We conclude that in the murine asthma model the SR Ca(2+) buffer capacity is increased, while in the human asthma model the expression of SR Ca(2+) channels is altered. The investigation of the Ca(2+) homeostasis of ASMC has the potential to provide new therapeutical options in asthma. Copyright (C) 2008 S. Karger AG, Basel

The properties of dynamically ejected runaway and hyper-runaway stars

Runaway stars are stars observed to have large peculiar velocities. Two mechanisms are thought to contribute to the ejection of runaway stars, both involve binarity (or higher multiplicity). In the binary supernova scenario a runaway star receives its velocity when its binary massive companion explodes as a supernova (SN). In the alternative dynamical ejection scenario, runaway stars are formed through gravitational interactions between stars and binaries in dense, compact clusters or cluster cores. Here we study the ejection scenario. We make use of extensive N-body simulations of massive clusters, as well as analytic arguments, in order to to characterize the expected ejection velocity distribution of runaways stars. We find the ejection velocity distribution of the fastest runaways (>~80 km s^-1) depends on the binary distribution in the cluster, consistent with our analytic toy model, whereas the distribution of lower velocity runaways appears independent of the binaries properties. For a realistic log constant distribution of binary separations, we find the velocity distribution to follow a simple power law; Gamma(v) goes like v^(-8/3) for the high velocity runaways and v^(-3/2) for the low velocity ones. We calculate the total expected ejection rates of runaway stars from our simulated massive clusters and explore their mass function and their binarity. The mass function of runaway stars is biased towards high masses, and depends strongly on their velocity. The binarity of runaways is a decreasing function of their ejection velocity, with no binaries expected to be ejected with v>150 km s^-1. We also find that hyper-runaways with velocities of hundreds of km s^-1 can be dynamically ejected from stellar clusters, but only at very low rates, which cannot account for a significant fraction of the observed population of hyper-velocity stars in the Galactic halo.Comment: Now matching published ApJ versio

The Anisotropic Spatial Distribution of Hypervelocity Stars

We study the distribution of angular positions and angular separations of unbound hypervelocity stars (HVSs). HVSs are spatially anisotropic at the 3-sigma level. The spatial anisotropy is significant in Galactic longitude, not in latitude, and the inclusion of lower velocity, possibly bound HVSs reduces the significance of the anisotropy. We discuss how the observed distribution of HVSs may be linked to their origin. In the future, measuring the distribution of HVSs in the southern sky will provide additional constraints on the spatial anisotropy and the origin of HVSs.Comment: 4 pages, accepted to ApJ Letter

Nucleon Polarizibilities for Virtual Photons

We generalize the sum rules for the nucleon electric plus magnetic polarizability $\Sigma=\alpha+\beta$ and for the nucleon spin-polarizability $\gamma$, to virtual photons with $Q^2>0$. The dominant low energy cross sections are represented in our calculation by one-pion-loop graphs of relativistic baryon chiral perturbation theory and the $\Delta(1232)$-resonance excitation. For the proton we find good agreement of the calculated $\Sigma_p(Q^2)$ with empirical values obtained from integrating up electroproduction data for $Q^2<0.4 GeV^2$. The proton spin-polarizability $\gamma_p(Q^2)$ switches sign around $Q^2= 0.4 GeV^2$ and it joins smoothly the "partonic" curve, extracted from polarized deep-inelastic scattering, around $Q^2=0.7 GeV^2$. For the neutron our predictions of $\Sigma_n(Q^2)$ and $\gamma_n(Q^2)$ agree reasonably well at $Q^2=0$ with existing determinations. Upcoming (polarized) electroproduction experiments will be able to test the generalized polarizability sum rules investigated here.Comment: 12 pages, 5 figures, submittes to Nuclear Physics

Identification of blue high proper motion objects in the Tycho-2 and 2MASS catalogues using Virtual Observatory tools

With available Virtual Observatory tools, we looked for new bright blue high proper motion objects in the entire sky: white dwarfs, hot subdwarfs, runaway OB stars, and early-type stars in nearby young moving groups. We performed an all-sky cross-match between the optical Tycho-2 and near-infrared 2MASS catalogues with Aladin, and selected objects with proper motions >50mas/yr and colours Vt-Ks<-0.5mag with TOPCAT. We also collected multi-wavelength photometry, constructed the spectral energy distributions and estimated effective temperatures from fits to atmospheric models with VOSA for the most interesting targets. We assembled a sample of 32 bright blue high proper motion objects, including ten sdO/B subdwarfs, nine DA white dwarfs, five young early-type stars (two of which are runaway stars), two blue horizontal branch stars, one star with poor information, and five objects reported for the first time in this work. These last five objects have magnitudes Bt~11.0-11.6mag, effective temperatures ~24,000-30,000K, and are located in the region of known white dwarfs and hot subdwarfs in a reduced proper motion-colour diagram. We confirmed the hot subdwarf nature of one of the new objects, Albus 5, with public far-ultraviolet spectroscopic data obtained with FUSE.Comment: Published in Astronomy & Astrophysic

Tritium O-Methylation of N-Alkoxy Maleimide Derivatives as Labeling Reagents for Biomolecules

An efficient procedure to access tritium-labeled maleimide derivatives in a high specific activity has been developed. N-Substituted maleimides containing the hydroxy functionality are O-methylated in a three-step synthesis route, including (1) Diels-Alder protection of the maleimide core, (2) O-methylation by the use of commercially available [3H]methyl nosylate, and (3) deprotection by retro-Diels-Alder reaction. With our procedure, N-hydroxyalkyl maleimide derivatives can be labeled in overall radiochemical yields of 13-15% and in &gt;98% radiochemical purity. The major advantage of N-alkoxy maleimides in comparison to N-alkylated maleimides such as N-ethylmaleimide is their lower volatility, which enables safer handling with respect to radiation-safety protection. Tritium-labeled maleimide building blocks allow subsequent Michael-type conjugation reactions of thiol-containing biomolecules for mechanistic in vitro or in vivo studies. </p

The Unseen Population of F to K-type Companions to Hot Subdwarf Stars

We present a method to select hot subdwarf stars with A to M-type companions using photometric selection criteria. We cover a wide range in wavelength by combining GALEX ultraviolet data, optical photometry from the SDSS and the Carlsberg Meridian telescope, near-infrared data from 2MASS and UKIDSS. We construct two complimentary samples, one by matching GALEX, CMC and 2MASS, as well as a smaller, but deeper, sample using GALEX, SDSS and UKIDSS. In both cases, a large number of composite subdwarf plus main-sequence star candidates were found. We fit their spectral energy distributions with a composite model in order to estimate the subdwarf and companion star effective temperatures along with the distance to each system. The distribution of subdwarf effective temperature was found to primarily lie in the 20,000 - 30,000 K regime, but we also find cooler subdwarf candidates, making up ~5-10 per cent. The most prevalent companion spectral types were seen to be main-sequence stars between F0 and K0, while subdwarfs with M-type companions appear much rarer. This is clear observational confirmation that a very efficient first stable Roche-lobe overflow channel appears to produce a large number of subdwarfs with F to K-type companions. Our samples thus support the importance of binary evolution for subdwarf formation.Comment: 30 pages, 10 figures, 11 tables. Accepted for publication in MNRA

Durchflusszytometrie als Methode zur Quantifizierung der Wirkung ionisierender Strahlen auf dreidimensionale Organkokulturen von humanem Bronchialepithel und einer Bronchialepithel-Tumorzelllinie

Monolayerkulturen von Normal- und Tumorzellen verhalten sich unter Bestrahlung substantiell unterschiedlich. Wir haben ein Ko-Kultursystem (COCs), bestehend aus dreidimensionalen Organkulturen von humanem Bronchialepithels (OCs') und der GFP-transfizierten Lungenkarzinom-Zelllinie EPLC entwickelt, und können in Kombination mit der Durchflusszytometrie den DNA-Gehalt getrennt für Tumor- und Normalzellen analysieren. Damit kann die Wirkung ionisierender Strahlung auf die Proliferation, die Apoptose und die Zellzahl im Verlauf quantifiziert werden. Die humane Bronchialepithel-Zelllinie BEAS-2-B zeigt im Monolayer gesteigerte Proliferation und erhöhte Strahlensenitivität im Vergleich zum normalen Bronchialepithel in der COC. Ebenso ist die Proliferation und Strahlensenitivität der Tumorzellen, wenn als Monolayer kultiviert, erhöht im Vergleich zu Tumorzellen in COCs. Normalepithel-Zellen zeigten mit Tumorzellen in COCs kultiviert, verminderte Proliferation und, nach Bestrahlung keine gesteigerte Apoptose. Diese Daten zeigen, dass mit COCs in Verbindung mit Durchflusszytometrie die Auswirkung ionisierender Strahlung in einem In-vivo-nahen System erfassbar ist und das sowohl die räumliche Organisation als auch die Interaktion von Normal- und Tumorzellen für die Wirksamkeit einer Antitumortherapie entscheidend sind