Differential Regulation of Growth-Promoting Signalling Pathways by E-Cadherin

Background: Despite the well-documented association between loss of E-cadherin and carcinogenesis, as well as the link between restoration of its expression and suppression of proliferation in carcinoma cells, the ability of E-cadherin to modulate growth-promoting cell signalling in normal epithelial cells is less well understood and frequently contradictory. The potential for E-cadherin to co-ordinate different proliferation-associated signalling pathways has yet to be fully explored. Methodology/Principal Findings: Using a normal human urothelial (NHU) cell culture system and following a calcium-switch approach, we demonstrate that the stability of NHU cell-cell contacts differentially regulates the Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-Regulated Kinase (ERK) and Phosphatidylinositol 3-Kinase (PI3-K)/AKT pathways. We show that stable cell contacts down-modulate the EGFR/ERK pathway, whilst inducing PI3-K/AKT activity, which transiently enhances cell growth at low density. Functional inactivation of E-cadherin interferes with the capacity of NHU cells to form stable calcium-mediated contacts, attenuates E-cadherin-mediated PI3-K/AKT induction and enhances NHU cell proliferation by allowing de-repression of the EGFR/ERK pathway and constitutive activation of beta-catenin-TCF signalling. Conclusions/Significance: Our findings provide evidence that E-cadherin can differentially and concurrently regulate specific growth-related signalling pathways in a context-specific fashion, with direct, functional consequences for cell proliferation and population growth. Our observations not only reveal a novel, complex role for E-cadherin in normal epithelial cell homeostasis and tissue regeneration, but also provide the basis for a more complete understanding of the consequences of E-cadherin loss on malignant transformation

A Completely Invariant SUSY Transform of Supersymmetric QED

We study the SUSY breaking of the covariant gauge-fixing term in SUSY QED and observe that this corresponds to a breaking of the Lorentz gauge condition by SUSY. Reasoning by analogy with SUSY's violation of the Wess-Zumino gauge, we argue that the SUSY transformation, already modified to preserve Wess-Zumino gauge, should be further modified by another gauge transformation which restores the Lorentz gauge condition. We derive this modification and use the resulting transformation to derive a Ward identitiy relating the photon and photino propagators without using ghost fields. Our transformation also fulfills the SUSY algebra, modulo terms that vanish in Lorentz gauge

Nonperturbative Vertices in Supersymmetric Quantum Electrodynamics

We derive the complete set of supersymmetric Ward identities involving only two- and three- point proper vertices in supersymmetric QED. We also present the most general form of the proper vertices consistent with both the supersymmetric and U(1) gauge Ward identities. These vertices are the supersymmetric equivalent of the non supersymmetric Ball-Chiu vertices.Comment: seventeen pages late

Short-Chained Oligo(Ethylene Oxide)-Functionalized Gold Nanoparticles: Realization Of Significant Protein Resistance

Protein corona formed on nanomaterial surfaces play an important role in the bioavailability and cellular uptake of nanomaterials. Modification of surfaces with oligoethylene glycols (OEG) are a common way to improve the resistivity of nanomaterials to protein adsorption. Short-chain ethylene oxide (EO) oligomers have been shown to improve the protein resistance of planar Au surfaces. We describe the application of these EO oligomers for improved protein resistance of 30 nm spherical gold nanoparticles (AuNPs). Functionalized AuNPs were characterized using UV-Vis spectroscopy, dynamic light scattering (DLS), and zeta potential measurements. Capillary electrophoresis (CE) was used for separation and quantitation of AuNPs and AuNP-protein mixtures. Specifically, nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) was employed for the determination of equilibrium and rate constants for binding between citrate-stabilized AuNPs and two model proteins, lysozyme and fibrinogen. Semi-quantitative CE analysis was carried out for mixtures of EO-functionalized AuNPs and proteins, and results demonstrated a 2.5-fold to 10-fold increase in protein binding resistance to lysozyme depending on the AuNP surface functionalization and a 15-fold increase in protein binding resistance to fibrinogen for both EO oligomers examined in this study

Higher Resolution VLBI Imaging with Fast Frequency Switching

Millimetre-VLBI is an important tool in AGN astrophysics, but it is limited by short atmospheric coherence times and poor receiver and antenna performance. We demonstrate a new kind of phase referencing for the VLBA, enabling us to increase the sensitivity in mm-VLBI by an order of magnitude. If a source is observed in short cycles between the target frequency, nu_t, and a reference frequency, nu_ref, the nu_t data can be calibrated using scaled-up phase solutions from self-calibration at nu_ref. We have demonstrated the phase transfer on 3C 279, where we were able to make an 86 GHz image with 90 % coherence compared to self-calibration at nu_t. We have detected M81, our science target in this project, at 86 GHz using the same technique. We describe scheduling strategy and data reduction. The main impacts of fast frequency switching are the ability to image some of the nearest, but relatively weak AGN cores with unprecedented high angular resolution and to phase-reference the nu_t data to the nu_ref core position, enabling the detection of possible core shifts in jets due to optical depth effects. This ability will yield important constraints on jet properties and might be able to discriminate between the two competing emission models of Blandford-Konigl jets and spherical advection-dominated accretion flows (ADAFs) in low-luminosity AGNs.Comment: 4 pages, 6 figures, appears in: Proceedings of the 6th European VLBI Network Symposium held on June 25th-28th in Bonn, Germany. Edited by: E. Ros, R.W. Porcas, A.P. Lobanov, and J.A. Zensu