SNAI transcription factors mediate epithelial--mesenchymal transition in lung fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterised by accumulation of activated (myo)fibroblasts and excessive extracellular matrix deposition. The enhanced accumulation of (myo)fibroblasts may be attributed, in part, to the process of transforming growth factor \textgreekb1 (TGF\textgreekb1)-induced epithelial--mesenchymal transition (EMT), the phenotypic switching of epithelial to fibroblast-like cells. Although alveolar epithelial type II (ATII) cells have been shown to undergo EMT, the precise mediators and mechanisms remain to be resolved. The objective of this study is to investigate the role of SNAI transcription factors in the process of EMT and in IPF.Methods: Using quantitative reverse transcription-PCR (RT-PCR), immunofluorescence, immunohistochemistry, western blotting, as well as gain- and loss-of-function studies and functional assays, the role of SNAI1 and SNAI2 in TGF\textgreekb1-induced EMT in ATII cells in vitro was assessed; and the expression of SNAI transcription factors was analysed in experimental and human IPF in vivo.Results: TGF\textgreekb1 treatment increased the expression and nuclear accumulation of SNAI1 and SNAI2, in concert with induction of EMT in ATII cells. SNAI overexpression was sufficient to induce EMT, and small interfering RNA (siRNA)-mediated SNAI depletion attenuated TGF\textgreekb1-induced ATII cell migration and EMT. SNAI expression was elevated in experimental and human IPF and localised to hyperplastic ATII cells in vivo.Conclusions: The results demonstrate that TGF\textgreekb1-induced EMT in ATII cells is essentially controlled by the expression and nuclear translocation of SNAI transcription factors. Increased SNAI1 and SNAI2 expression in experimental and human IPF in vivo suggests that SNAI-mediated EMT may contribute to the fibroblast pool in idiopathic pulmonary fibrosis

Implementation of the Backlund transformations for the Ablowitz-Ladik hierarchy

The derivation of the Backlund transformations (BTs) is a standard problem of the theory of the integrable systems. Here, I discuss the equations describing the BTs for the Ablowitz-Ladik hierarchy (ALH), which have been already obtained by several authors. The main aim of this work is to solve these equations. This can be done in the framework of the so-called functional representation of the ALH, when an infinite number of the evolutionary equations are replaced, using the Miwa's shifts, with a few equations linking tau-functions with different arguments. It is shown that starting from these equations it is possible to obtain explicit solutions of the BT equations. In other words, the main result of this work is a presentation of the discrete BTs as a superposition of an infinite number of evolutionary flows of the hierarchy. These results are used to derive the superposition formulae for the BTs as well as pure soliton solutions.Comment: 20 page

Theory of Electron Spin Relaxation in ZnO

Doped ZnO is a promising material for spintronics applications. For such applications, it is important to understand the spin dynamics and particularly the spin coherence of this II-VI semiconductor. The spin lifetime $\tau_{s}$ has been measured by optical orientation experiments, and it shows a surprising non-monotonic behavior with temperature. We explain this behavior by invoking spin exchange between localized and extended states. Interestingly, the effects of spin-orbit coupling are by no means negligible, in spite of the relatively small valence band splitting. This is due to the wurtzite crystal structure of ZnO. Detailed analysis allows us to characterize the impurity binding energies and densities, showing that optical orientation experiments can be used as a characterization tool for semiconductor samples.Comment: 7 pages, 1 figure: minor changes Accepted by Phys. Rev.

Electron cooling by diffusive normal metal - superconductor tunnel junctions

We investigate heat and charge transport in NN'IS tunnel junctions in the diffusive limit. Here N and S are massive normal and superconducting electrodes (reservoirs), N' is a normal metal strip, and I is an insulator. The flow of electric current in such structures at subgap bias is accompanied by heat transfer from the normal metal into the superconductor, which enables refrigeration of electrons in the normal metal. We show that the two-particle current due to Andreev reflection generates Joule heating, which is deposited in the N electrode and dominates over the single-particle cooling at low enough temperatures. This results in the existence of a limiting temperature for refrigeration. We consider different geometries of the contact: one-dimensional and planar, which is commonly used in the experiments. We also discuss the applicability of our results to a double-barrier SINIS microcooler.Comment: 9 pages, 4 figures, submitted to Phys. Rev.

Std fimbriae-fucose interaction increases Salmonella-induced intestinal inflammation and prolongs colonization

Author summary The intestinal epithelium is a crucial biological interface, interacting with both commensal and pathogenic microorganisms. It’s lined with heavily glycosylated proteins and glycolipids which can act as both attachment sites and energy sources for intestinal bacteria. Fut2, the enzyme governing epithelial α1,2-fucosylation, has been implicated in the interaction between microbes and intestinal epithelial cells. Salmonella is one of the most important bacterial gastrointestinal pathogens affecting millions of people worldwide. Salmonella possesses fimbrial and non-fimbrial adhesins which can be used to adhere to host cells. Here we show that Salmonella expresses Std fimbriae in the gastrointestinal tract in vivo and exploit Std fimbriae to bind fucosylated structures in the mucus and on the intestinal epithelium. Furthermore, we demonstrate that the Std fimbriae-fucose interaction is necessary for bacterial colonization of the intestine and for triggering intestinal inflammation. These data lend new insights into bacterial adhesion-epithelial interactions which are essential for bacterial pathogenesis and key factors in determining tissue tropism and host susceptibility to infectious disease

Mixed quark-nucleon phase in neutron stars and nuclear symmetry energy

The influence of the nuclear symmetry energy on the formation of a mixed quark-nucleon phase in neutron star cores is studied. We use simple parametrizations of the nuclear matter equation of state, and the bag model for the quark phase. The behavior of nucleon matter isobars, which is responsible for the existence of the mixed phase, is investigated. The role of the nuclear symmetry energy changes with the value of the bag constant B. For lower values of B the properties of the mixed phase do not depend strongly on the symmetry energy. For larger B we find that a critical pressure for the first quark droplets to form is strongly dependent on the nuclear symmetry energy, but the pressure at which last nucleons disappear is independent of it.Comment: 12 pages, 16 figures, Phys. Rev. C in pres

Quantum corrections to static solutions of Nahm equation and Sin-Gordon models via generalized zeta-function

One-dimensional Yang-Mills Equations are considered from a point of view of a class of nonlinear Klein-Gordon-Fock models. The case of self-dual Nahm equations and non-self-dual models are discussed. A quasiclassical quantization of the models is performed by means of generalized zeta-function and its representation in terms of a Green function diagonal for a heat equation with the correspondent potential. It is used to evaluate the functional integral and quantum corrections to mass in the quasiclassical approximation. Quantum corrections to a few periodic (and kink) solutions of the Nahm as a particular case of the Ginzburg-Landau (phi-in-quadro) and and Sin-Gordon models are evaluated in arbitrary dimensions. The Green function diagonal for heat equation with a finite-gap potential is constructed by universal description via solutions of Hermit equation. An alternative approach based on Baker-Akhiezer functions for KP equation is proposed . The generalized zeta-function and its derivative at zero point as the quantum corrections to mass is expressed in terms of elliptic integrals.Comment: Workshop Nonlinear Physics and Experiment; Gallipoli, 200

Mitochondrial Dynamics and Respiration Within Cells with Increased Open Pore Cytoskeletal Meshes

The cytoskeletal architecture directly affects the morphology, motility, and tensional homeostasis of the cell. In addition, the cytoskeleton is important for mitosis, intracellular traffic, organelle motility, and even cellular respiration. The organelle responsible for a majority of the energy conversion for the cell, the mitochondrion, has a dependence on the cytoskeleton for mobility and function. In previous studies, we established that cytoskeletal inhibitors altered the movement of the mitochondria, their morphology, and their respiration in human dermal fibroblasts. Here, we use this protocol to investigate applicability of power law diffusion to describe mitochondrial locomotion, assessment of rates of fission and fusion in healthy and diseased cells, and differences in mitochondria locomotion in more open networks either in response to cytoskeletal destabilizers or by cell line. We found that mitochondria within fibrosarcoma cells and within fibroblast cells treated with an actin-destabilizing toxin resulted in increased net travel, increased average velocity, and increased diffusion of mitochondria when compared to control fibroblasts. Although the mitochondria within the fibrosarcoma travel further than mitochondria within their healthy counterparts, fibroblasts, the dependence on mitochondria for respiration is much lower with higher rates ofhydrogen peroxide production and was confirmed using the OROBOROS O2K. We also found that rates of fission and fusion of the mitochondria equilibrate despite significant alteration of the cytoskeleton. Rates ranged from 15% to 25%, where the highest rates were observed within the fibrosarcoma cell line. This result is interesting because the fibrosarcoma cell line does not have increased respiration metrics including when compared to fibroblast. Mitochondria travel further, faster, and have an increase in percent mitochondria splitting or joining while not dependent on the mitochondria for a majority of its energy production. This study illustrates the complex interaction between mitochondrial movement and respiration through the disruption of the cytoskeleton

Diffusion controlled initial recombination

This work addresses nucleation rates in systems with strong initial recombination. Initial (or `geminate') recombination is a process where a dissociated structure (anion, vortex, kink etc.) recombines with its twin brother (cation, anti-vortex, anti-kink) generated in the same nucleation event. Initial recombination is important if there is an asymptotically vanishing interaction force instead of a generic saddle-type activation barrier. At low temperatures, initial recombination strongly dominates homogeneous recombination. In a first part, we discuss the effect in one-, two-, and three-dimensional diffusion controlled systems with spherical symmetry. Since there is no well-defined saddle, we introduce a threshold which is to some extent arbitrary but which is restricted by physically reasonable conditions. We show that the dependence of the nucleation rate on the specific choice of this threshold is strongest for one-dimensional systems and decreases in higher dimensions. We discuss also the influence of a weak driving force and show that the transport current is directly determined by the imbalance of the activation rate in the direction of the field and the rate against this direction. In a second part, we apply the results to the overdamped sine-Gordon system at equilibrium. It turns out that diffusive initial recombination is the essential mechanism which governs the equilibrium kink nucleation rate. We emphasize analogies between the single particle problem with initial recombination and the multi-dimensional kink-antikink nucleation problem.Comment: LaTeX, 11 pages, 1 ps-figures Extended versio

Direct observation of Levy flight of holes in bulk n-InP

We study the photoluminescence spectra excited at an edge side of n-InP slabs and observed from the broadside. In a moderately doped sample the intensity drops off as a power-law function of the distance from the excitation - up to several millimeters - with no change in the spectral shape.The hole distribution is described by a stationary Levy-flight process over more than two orders of magnitude in both the distance and hole concentration. For heavily-doped samples, the power law is truncated by free-carrier absorption. Our experiments are near-perfectly described by the Biberman-Holstein transport equation with parameters found from independent optical experiments.Comment: 4 pages, 3 figure