Paracrine and autocrine regulation of gene expression by Wnt-inhibitor Dickkopf in wild-type and mutant hepatocytes

BACKGROUND: Cells are able to communicate and coordinate their function within tissues via secreted factors. Aberrant secretion by cancer cells can modulate this intercellular communication, in particular in highly organised tissues such as the liver. Hepatocytes, the major cell type of the liver, secrete Dickkopf (Dkk), which inhibits Wnt/β-catenin signalling in an autocrine and paracrine manner. Consequently, Dkk modulates the expression of Wnt/β-catenin target genes. We present a mathematical model that describes the autocrine and paracrine regulation of hepatic gene expression by Dkk under wild-type conditions as well as in the presence of mutant cells. RESULTS: Our spatial model describes the competition of Dkk and Wnt at receptor level, intra-cellular Wnt/β-catenin signalling, and the regulation of target gene expression for 21 individual hepatocytes. Autocrine and paracrine regulation is mediated through a feedback mechanism via Dkk and Dkk diffusion along the porto-central axis. Along this axis an APC concentration gradient is modelled as experimentally detected in liver. Simulations of mutant cells demonstrate that already a single mutant cell increases overall Dkk concentration. The influence of the mutant cell on gene expression of surrounding wild-type hepatocytes is limited in magnitude and restricted to hepatocytes in close proximity. To explore the underlying molecular mechanisms, we perform a comprehensive analysis of the model parameters such as diffusion coefficient, mutation strength and feedback strength. CONCLUSIONS: Our simulations show that Dkk concentration is elevated in the presence of a mutant cell. However, the impact of these elevated Dkk levels on wild-type hepatocytes is confined in space and magnitude. The combination of inter- and intracellular processes, such as Dkk feedback, diffusion and Wnt/β-catenin signal transduction, allow wild-type hepatocytes to largely maintain their gene expression

VLT Diffraction Limited Imaging and Spectroscopy in the NIR: Weighing the black hole in Centaurus A with NACO

We present high spatial resolution near-infrared spectra and images of the nucleus of Centaurus A (NGC 5128) obtained with NAOS-CONICA at the VLT. The adaptive optics corrected data have a spatial resolution of 0.06" (FWHM) in K- and 0.11" in H-band, four times higher than previous studies. The observed gas motions suggest a kinematically hot disk which is orbiting a central object and is oriented nearly perpendicular to the nuclear jet. We model the central rotation and velocity dispersion curves of the [FeII] gas orbiting in the combined potential of the stellar mass and the (dominant) black hole. Our physically most plausible model, a dynamically hot and geometrically thin gas disk, yields a black hole mass of M_bh = (6.1 +0.6/-0.8) 10^7 M_sun. As the physical state of the gas is not well understood, we also consider two limiting cases: first a cold disk model, which completely neglects the velocity dispersion; it yields an M_bh estimate that is almost two times lower. The other extreme case is to model a spherical gas distribution in hydrostatic equilibrium through Jeans equation. Compared to the hot disk model the best-fit black hole mass increases by a factor of 1.5. This wide mass range spanned by the limiting cases shows how important the gas physics is even for high resolution data. Our overall best-fitting black hole mass is a factor of 2-4 lower than previous measurements. With our revised M_bh estimate, Cen A's offset from the M_bh-sigma relation is significantly reduced; it falls above this relation by a factor of ~2, which is close to the intrinsic scatter of this relation. (Abridged)Comment: 12 pages, 14 figures, including minor changes following the referee report; accepted for publication in The Astrophysical Journa

Measurement and Compensation of Horizontal Crabbing at the Cornell Electron Storage Ring Test Accelerator

In storage rings, horizontal dispersion in the rf cavities introduces horizontal-longitudinal (xz) coupling, contributing to beam tilt in the xz plane. This coupling can be characterized by a "crabbing" dispersion term {\zeta}a that appears in the normal mode decomposition of the 1-turn transfer matrix. {\zeta}a is proportional to the rf cavity voltage and the horizontal dispersion in the cavity. We report experiments at the Cornell Electron Storage Ring Test Accelerator (CesrTA) where xz coupling was explored using three lattices with distinct crabbing properties. We characterize the xz coupling for each case by measuring the horizontal projection of the beam with a beam size monitor. The three lattice configurations correspond to a) 16 mrad xz tilt at the beam size monitor source point, b) compensation of the {\zeta}a introduced by one of two pairs of RF cavities with the second, and c) zero dispersion in RF cavities, eliminating {\zeta}a entirely. Additionally, intrabeam scattering (IBS) is evident in our measurements of beam size vs. rf voltage.Comment: 5 figures, 10 page

Nonlinear transport of Bose-Einstein condensates through mesoscopic waveguides

We study the coherent flow of interacting Bose-condensed atoms in mesoscopic waveguide geometries. Analytical and numerical methods, based on the mean-field description of the condensate, are developed to study both stationary as well as time-dependent propagation processes. We apply these methods to the propagation of a condensate through an atomic quantum dot in a waveguide, discuss the nonlinear transmission spectrum and show that resonant transport is generally suppressed due to an interaction-induced bistability phenomenon. Finally, we establish a link between the nonlinear features of the transmission spectrum and the self-consistent quasi-bound states of the quantum dot.Comment: 23 pages, 16 figure

A brown dwarf companion to the intermediate-mass star HR6037

In the course of an imaging survey we have detected a visual companion to the intermediate-mass star HR 6037. In this letter, we present two epoch observations of the binary with NACO/VLT, and near-IR spectroscopy of the secondary with ISAAC/VLT. The NACO observations allow us to confirm HR 6037B as a co-moving companion. Its J and H band ISAAC spectra suggest the object has an spectral type of M9+-1, with a surface gravity intermediate between that of 10 Myr dwarfs and field dwarfs with identical spectral type. The comparison of its Ks-band photometry with evolutionary tracks allows us to derive a mass, effective temperature, and surface gravity of 62+-20 MJup, Teff = 2330+-200 K, and log g = 5.1+-0.2, respectively. The small mass ratio of the binary, -0.03, and its long orbital period, -5000 yr, makes HR 6037 a rare and uncommon binary system.Comment: (5 pages, 4 figures, accepted for publication in A&A Letters

Analyzing Somatic DNA Repair in Arabidopsis Meiotic Mutants

Meiotic and somatic recombination share a common set of factors. Thus, the analysis of somatic DNA repair in meiotic mutant lines should be of special interest. Growth defects of mutant plants induced by specific genotoxins can thereby hint to DNA repair functions of the affected proteins. Here, we describe two kinds of approaches to characterize deficiencies in DNA repair in mutant lines of Arabidopsis thaliana, after genotoxin treatment