The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer

The most devastating aspect of cancer is the emergence of metastases. Thus, identification of potentially metastatic cells among a tumor cell population and the underlying molecular changes that switch cells to a metastatic state are among the most important issues in cancer biology. Here we show that, although normal human colonic epithelial cells lack the glycosphingolipid globotriaosylceramide (Gb(3)), this molecule is highly expressed in metastatic colon cancer. In addition, a subpopulation of cells that are greatly enriched in Gb(3) and have an invasive phenotype was identified in human colon cancer cell lines. In epithelial cells in culture, Gb(3) was necessary and sufficient for cell invasiveness. Transfection of Gb(3) synthase, resulting in Gb(3) expression in noncancerous polarized epithelial cells lacking endogenous Gb(3), induced cell invasiveness. Furthermore, Gb(3) knockdown by small inhibitory RNA in colon cancer epithelial cells inhibited cell invasiveness. Gb(3) is the plasma membrane receptor for Shiga toxin 1. The noncatalytic B subunit of Shiga toxin 1 causes apoptosis of human colon cancer cells expressing Gb(3). Injections of the B subunit of Shiga toxin 1 into HT29 human colon cancer cells engrafted into the flanks of nude mice inhibited tumor growth. These data demonstrate the appearance of a subpopulation of Gb(3) containing epithelial cells in the metastatic stage of human colon cancer and suggest their possible role in colon cancer invasiveness

Sequential Requisites Analysis: A New Method for Analyzing Sequential Relationships in Ordinal Data

This paper presents a new method inspired by evolutionary biology for analyzing longer sequences of requisites for the emergence of particular outcome variables across numerous combinations of ordinal variables in social science analysis. The approach involves repeated pairwise investigations of states in a set of variables and identifying what states in the variables that occur before states in all other variables. We illustrate the proposed method by analyzing a set of variables from version 6 of the V-Dem dataset (Coppedge et al. 2015a, b). With a large set of indicators measured over many years, the method makes it possible to explore long, complex sequences across many variables in quantitative datasets. This affords an opportunity, for example, to disentangle the sequential requisites of failing and successful sequences in democratization. For policy purposes this is instrumental: Which components of democracy are most exogenous and least endogenous and therefore the ideal targets for democracy promotion at different stages?This research project was supported by Riksbankens Jubileumsfond, Grant M13-0559:1, PI: Staffan I. Lindberg, V-Dem Institute, University of Gothenburg, Sweden; by Swedish Research Council, Grant C0556201, PIs: Staffan I. Lindberg, V-Dem Institute, University of Gothenburg, Sweden and Jan Teorell, Department of Political Science, Lund University, Sweden; by Knut and Alice Wallenberg Foundation to Wallenberg Academy Fellow Staffan I. Lindberg, Grant 2013.0166, V-Dem Institute, University of Gothenburg, Sweden; as well as by internal grants from the Vice-Chancellor’s office, the Dean of the College of Social Sciences, and the Department of Political Science at University of Gothenburg. We performed simulations and other computational tasks using resources provided by the Notre Dame Center for Research Computing (CRC) through the High Performance Computing section and the Swedish National Infrastructure for Computing (SNIC) at the National Supercomputer Centre in Sweden. We specifically acknowledge the assistance of In-Saeng Suh at CRC and Johan Raber at SNIC in facilitating our use of their respective systems

Direct Measurement of the Cu Oxidation Number of Cuprate Superconductor Ceramics

The Cu oxidation number in YBa2Cu3O7 has been measured directly by soft X-ray fluorescent spectroscopy both at room temperature and at liquid N2 temperature. The measurements are based on a calibration curve from different Ba-O compounds. The effect of changes in oxidation number above and below the transition temperature and its role in high T(c) superconductivity are discussed