A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus

Cell-cell contacts play a vital role in intracellular signaling, although the molecular mechanisms of these signaling pathways are not fully understood. E-cadherin, an important mediator of cell-cell adhesions, has been shown to be cleaved by γ-secretase. This cleavage releases a fragment of E-cadherin, E-cadherin C-terminal fragment 2 (E-cad/CTF2), into the cytosol. Here, we study the fate and function of this fragment. First, we show that coexpression of the cadherin-binding protein, p120 catenin (p120), enhances the nuclear translocation of E-cad/CTF2. By knocking down p120 with short interfering RNA, we also demonstrate that p120 is necessary for the nuclear localization of E-cad/CTF2. Furthermore, p120 enhances and is required for the specific binding of E-cad/CTF2 to DNA. Finally, we show that E-cad/CTF2 can regulate the p120-Kaiso-mediated signaling pathway in the nucleus. These data indicate a novel role for cleaved E-cadherin in the nucleus

Epidemiology of diabetes mellitus among 193,435 cats attending primary-care veterinary practices in England

BACKGROUND: Diabetes mellitus (DM) is a common endocrine disease of cats. The prevalence of DM in cats in England is not well‐defined. HYPOTHESIS/OBJECTIVES: To estimate the prevalence and identify risk factors for DM in a large population of cats attending primary‐care practices. ANIMALS: A cohort of 193,563 cats in the VetCompass Programme attending 118 primary‐care practices in England. METHODS: Cross‐sectional analysis of cohort clinical data. Data were extracted covering September 1st 2009 and August 31st 2014. Period prevalence of DM was calculated. Associations between risk factors and DM were assessed using logistic regression modelling. RESULTS: Of 1,128 DM cases were identified among 194,563 cats (period prevalence 0.58%; 95% confidence interval [CI] 0.54–0.61). Multivariable modelling indicated that Tonkinese (OR 4.1; 95% CI 1.8–9.6; P = .001), Norwegian Forest (odds ratio [OR] 3.5; 95% CI 1.3–9.6; P = .001) and Burmese (OR 3.0; 95% CI 2.0–4.4; P < .001) cats had increased odds of DM compared with crossbred cats. DM odds increased as bodyweight categories increased above 4 kg (P < .001), as cats aged beyond 6 years old (P < .001) and in insured cats (OR 2.0; 95% CI 1.6–2.4; P < .001) but sex was not significantly associated with DM. CONCLUSIONS AND CLINICAL IMPORTANCE: Diabetes mellitus is an important component of the primary‐care practice caseload with 1‐in‐200 cats affected. An increased risk of DM in certain cat breeds supports a genetic predisposition. These results can guide future research and preventative healthcare

Spontaneous superconducting islands and Hall voltage in clean superconductors

We study a clean superconductor in the Hall configuration, in the framework of a purely dissipative time-dependent Ginzburg--Landau theory. We find situations in which the order parameter differs significantly from zero in a set of islands that appear to form a periodic structure. When the pattern of islands becomes irregular, it moves in or against the direction of the current and a Hall voltage is found. Tiny differences in the initial state may reverse the sign of the Hall voltage. When the average Hall voltage vanishes, the local Hall voltage does not necessarily vanish. We examine the influence that several boundary conditions at the electrodes have on these effects.Comment: 6 pages, Includes additional cases and more detailed result

Processing and Transmission of Information

Contains research objectives and reports on three research projects.National Science Foundation (Grant G-16526)National Institutes of Health (Grant MH-04737-03)National Aeronautics and Space Administration (Grant NsG-496)Lincoln Laboratory, Purchase Order DDL BB-107U.S. Air Force under Contract AF 19(628)-50

The AMANDA Neutrino Telescope and the Indirect Search for Dark Matter

With an effective telescope area of order 10^4 m^2, a threshold of ~50 GeV and a pointing accuracy of 2.5 degrees, the AMANDA detector represents the first of a new generation of high energy neutrino telescopes, reaching a scale envisaged over 25 years ago. We describe its performance, focussing on the capability to detect halo dark matter particles via their annihilation into neutrinos.Comment: Latex2.09, 16 pages, uses epsf.sty to place 15 postscript figures. Talk presented at the 3rd International Symposium on Sources and Detection of Dark Matter in the Universe (DM98), Santa Monica, California, Feb. 199

Cryptococcal Meningitis Screening and Community-based Early Adherence Support in People With Advanced Human Immunodeficiency Virus Infection Starting Antiretroviral Therapy in Tanzania and Zambia: A Cost-effectiveness Analysis

BACKGROUND: A randomized trial demonstrated that among people living with late-stage human immunodeficiency virus (HIV) infection initiating antiretroviral therapy, screening serum for cryptococcal antigen (CrAg) combined with adherence support reduced all-cause mortality by 28%, compared with standard clinic-based care. Here, we present the cost-effectiveness. METHODS: HIV-infected adults with CD4 count <200 cells/μL were randomized to either CrAg screening plus 4 weekly home visits to provide adherence support or to standard clinic-based care in Dar es Salaam and Lusaka. The primary economic outcome was health service care cost per life-year saved as the incremental cost-effectiveness ratio (ICER), based on 2017 US dollars. We used nonparametric bootstrapping to assess uncertainties and univariate deterministic sensitivity analysis to examine the impact of individual parameters on the ICER. RESULTS: Among the intervention and standard arms, 1001 and 998 participants, respectively, were enrolled. The annual mean cost per participant in the intervention arm was US$339 (95$331-$347), resulting in an incremental cost of the intervention of US$77 (95% CI, $66-$88). The incremental cost was similar when analysis was restricted to persons with CD4 count <100 cells/μL. The ICER for the intervention vs standard care, per life-year saved, was US$70 (95$43-$211) for all participants with CD4 count up to 200 cells/μL and US$91 (95% CI, $49-$443) among those with CD4 counts <100 cells /μL. Cost-effectveness was most sensitive to mortality estimates. CONCLUSIONS: Screening for cryptococcal antigen combined with a short period of adherence support, is cost-effective in resource-limited settings

Patterned Irradiation of YBa_2Cu_3O_(7-x) Thin Films

We present a new experiment on YBa_2Cu_3O_{7-x} (YBCO) thin films using spatially resolved heavy ion irradiation. Structures consisting of a periodic array of strong and weak pinning channels were created with the help of metal masks. The channels formed an angle of +/-45 Deg with respect to the symmetry axis of the photolithographically patterned structures. Investigations of the anisotropic transport properties of these structures were performed. We found striking resemblance to guided vortex motion as it was observed in YBCO single crystals containing an array of unidirected twin boundaries. The use of two additional test bridges allowed to determine in parallel the resistivities of the irradiated and unirradiated parts as well as the respective current-voltage characteristics. These measurements provided the input parameters for a numerical simulation of the potential distribution of the Hall patterning. In contrast to the unidirected twin boundaries in our experiment both strong and weak pinning regions are spatially extended. The interfaces between unirradiated and irradiated regions therefore form a Bose-glass contact. The experimentally observed magnetic field dependence of the transverse voltage vanishes faster than expected from the numerical simulation and we interpret this as a hydrodynamical interaction between a Bose-glass phase and a vortex liquid.Comment: 7 pages, 8 Eps figures included. Submitted to PR

Self-consistent Green's function approaches

We present the fundamental techniques and working equations of many-body Green's function theory for calculating ground state properties and the spectral strength. Green's function methods closely relate to other polynomial scaling approaches discussed in chapters 8 and 10. However, here we aim directly at a global view of the many-fermion structure. We derive the working equations for calculating many-body propagators, using both the Algebraic Diagrammatic Construction technique and the self-consistent formalism at finite temperature. Their implementation is discussed, as well as the inclusion of three-nucleon interactions. The self-consistency feature is essential to guarantee thermodynamic consistency. The pairing and neutron matter models introduced in previous chapters are solved and compared with the other methods in this book.Comment: 58 pages, 14 figures, Submitted to Lect. Notes Phys., "An advanced course in computational nuclear physics: Bridging the scales from quarks to neutron stars", M. Hjorth-Jensen, M. P. Lombardo, U. van Kolck, Editor