International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

In vitro investigations into the role of human intrahepatic biliary epithelial cells as targets in primary biliary cirrhosis

The work in this thesis examines several aspects of the role of human intrahepatic biliary epithelial cells (HIBECs) as target structures in primary biliary cirrhosis (PBC). HIBECs have been successfully isolated and established in cell culture using the method of Joplin, 1989. A panel of monoclonal antibodies have been generated that stain bile ducts of different sizes in frozen sections of liver tissue. The pattern of staining varies between normal adult human liver tissue and diseased tissue. The pattern of staining seen in these tissue secretions and those of normal foetal liver tissue highlights the heterogeneity of the biliary tree. These findings support the hypothesis that proliferating bile ductules seen in diseases such as PBC might be derived from periseptal hepatocytes. A 51chromium release cytotoxicity assay has been established and validated. The assay has been used to assess the relative cytotoxicity of a range of bile salts to HIBECs in vitro. Although chenodeoxycholic acid was found to be the most toxic of the bile salts assayed, ursodeoxycholic acid was also toxic to biliary epithelial cells. Furthermore,, ursodeoxycholic acid did not protect from the toxic effects of chenodeoxycholic acid to HIBECs as has been demonstrated for hepatocytes. Expression of intercellular adhesion molecule-1 (ICAM-1) and HLA class I and II has been demonstrated on HIBECs in vitro. Enhanced expression of ICAM-1 is seen in vitro following stimulation with the proinflammatory cytokines, tumour necrosis factor-α (TNFα), interferon gamma (IFNγ) and interleukin-1 (ILi). Corticosteroids stimulated culture. Expression of HLA class II was also increased following stimulation with proinflammatory cytokines although to a lesser degree. Enhancement of HLA class I expression with cytokines was weak.</p

The Iowa Homemaker vol.17, no.3

A Royal Welcome by Genevieve Fisher, page 2 A Royal Honor for Iowa State by Mary Ellen Lynch, page 2 Hi, There! by Jane Helser, page 3 It’s Smart to Be Smart by Peggy Schenk, page 4 Eating My Way Abroad by Reuben Hall, page 5 Sally, Style Snoop by Beth Johnson and Ronnie Ronningen, page 6 My Latchstring Is Out by Alvina Iverson, page 8 Done With Dolls by Gaynold Carroll, page 9 Canning Cautions, page 9 From Corn-Fed to Fruit-Minded by Katheryn Ayres Proper, page 10 Alumnae Page, page 11 What’s New in Home Economics, page 12 Spookie Doings by Harriet Knudson, page 14 October Dates, page 14 Rush News by Gay Starrak and Betty Grant, page 15 Behind Bright Jackets, page 16 Not All Lessons Come in Textbooks by Mary Louise Duthrie, page 18 Honoraries – The Fruits of Labor, page 21 An Eggy Tale, page 21 The School Bell Has a Different Ring by Leah Scott, page 22 Hay – Ka Choo – Fever by Jean Sigmond, page 24</p

Taxation, redistribution and observability in social dilemmas

International audienceIn the presence of social dilemmas, cooperation is more difficult to achieve when populations are heterogeneous because of conflicting interests within groups. We examine cooperation in the context of a non-linear common pool resource game, in which individuals have unequal extraction capacities and have to decide on their extraction of resources from the common pool. We introduce monetary and nonmonetary policy instruments in this environment. One instrument is based on two variants of a mechanism that taxes extraction and redistributes the tax revenue. The other instrument varies the observability of individual decisions. We find that the two tax and redistribution mechanisms reduce extraction, increase efficiency and decrease inequality within groups. The scarcity pricing mechanism, which is a per-unit tax equal to the marginal extraction externality, is more effective at reducing extraction than an increasing block tax that only taxes units extracted above the social optimum. In contrast, observability impacts only the Baseline condition by encouraging free-riding instead of creating moral pressure to cooperate

Comprehensive proteomic analysis of human bile.

Item does not contain fulltextBile serves diverse functions from metabolism to transport. In addition to acids and salts, bile is composed of proteins secreted or shed by the hepatobiliary system. Although there have been previous efforts to catalog biliary proteins, an in-depth analysis of the bile proteome has not yet been reported. We carried out fractionation of non-cancerous bile samples using a multipronged approach (SDS-PAGE, SCX and OFFGEL) followed by MS analysis on an LTQ-Orbitrap Velos mass spectrometer using high resolution at both MS and MS/MS levels. We identified 2552 proteins - the largest number of proteins reported in human bile till date. To our knowledge, there are no previous studies employing high-resolution MS reporting a more detailed catalog of any body fluid proteome in a single study. We propose that extensive fractionation coupled to high-resolution MS can be used as a standard methodology for in-depth characterization of any body fluid. This catalog should serve as a baseline for the future studies aimed at discovering biomarkers from bile in gallbladder, hepatic, and biliary cancers.1 december 201