The Accumulation of Tissue Cholesterol and Its Relationship to Bile Acid and Sterol Turnover

Normal and hypophysectomized rats were divided into equal homogeneous groups to determine the effect of cholestyramine, corn oil and cholesterol on the excretion of fecal bile acids and sterols. Bile acid turnover rates, pool sizes, and spectrums were studied and compared

Application area for multiple software product lines in automotive development

International audienceSince today’s well known software product lines (SPL) approaches [1] [2] [4] [5] [6] [7] [8] [9] [12] focus on one single SPL, a methodology for connection and adjustment of multiple product lines is needed. The paper will shortly survey existing processes and methods e.g. FODA [4] for product lines and show adaptations to automotive industry. The focus of the paper will be an adapted process for automotive functional development, which is based on multiple software product lines (MSPL) and particularly regards customer-supplier relationship. It will propose a general SPL interface to manage using MSPL. The interface consists of a SPL Interface Methodology which defines steps for the adjustment of two or more different SPLs as well as a data interface (SPL Interface Data) which defines a data format for the exchange between different SPL tools. The SPL adjustment is demonstrated with a case study of an imaginary advanced driver assistance system called mobilSoft Adaptive Cruise Control (MCC), which consists of three product lines, one for the whole MCC and two for the subsystems linear tracking and traverse control

Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia

Copyright @ 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.Muscular Dystrophy Association (USA), the National Health and Medical Research Council (Australia), the Friedreich’s Ataxia Research Alliance (USA), the Brockhoff Foundation (Australia), the Friedreich Ataxia Research Association (Australasia), Seek A Miracle (USA) and the Victorian Government’s Operational Infrastructure Support Program

Role of OmpA2 surface regions of Porphyromonas gingivalis in host-pathogen interactions with oral epithelial cells

Outer membrane protein A (OmpA) is a key outer membrane protein found in Gram-negative bacteria that contributes to several crucial processes in bacterial virulence. In Porphyromonas gingivalis, OmpA is predicted as a heterotrimer of OmpA1 and OmpA2 subunits encoded by adjacent genes. Here we describe the role of OmpA and its individual subunits in the interaction of P. gingivalis with oral cells. Using knockout mutagenesis, we show that OmpA2 plays a significant role in biofilm formation and interaction with human epithelial cells. We used protein structure prediction software to identify extracellular loops of OmpA2, and determined these are involved in interactions with epithelial cells as evidenced by inhibition of adherence and invasion of P. gingivalis by synthetic extracellular loop peptides and the ability of the peptides to mediate interaction of latex beads with human cells. In particular, we observe that OmpA2-loop 4 plays an important role in the interaction with host cells. These data demonstrate for the first time the important role of P. gingivalis OmpA2 extracellular loops in interaction with epithelial cells, which may help design novel peptide-based antimicrobial therapies for periodontal disease

The Role of Lipid Metabolism in B Cell Immune Functions

Evidence indicates that lipid accumulation due to obesity triggers a low-grade, chronic inflammation, which is correlated with the occurrence of Type 2 diabetes (T2D). Recent studies provide evidence for the essential role that B cells play in obesity-induced inflammation and the development of insulin resistance. In visceral adipose tissue (VAT), B cells generate self-reactive antibodies (autoantibodies), which increase their pathogenicity. They also activate the production of cytokines by T cells through antigen presentation. Lastly, B cells themselves increase the production of inflammatory cytokines while decreasing the production of the anti-inflammatory cytokine IL-10. We hypothesize that neutral lipid accumulation exclusively in B cells will cause them to infiltrate VAT, trigger autoantibody production, and develop an autoimmune pathology. Preliminary research has led to the generation of a B cell-specific CGI-58 knockout (BKO) mice model in order to induce neutral lipid accumulation in B cells. It was found that increased accumulation of triglycerides in CGI-58 BKO mice significantly increased the levels of spontaneous activation in B cells, shown by the increases in the number of germinal center B cells, the surface expression levels of B cell activation markers, and the number of infiltrated lymphocytes in VAT, compared to Flox controls. The goal of this project is to determine the mechanism by which B cell lipid metabolism regulates B cell activation and pathogenicity in obesity-associated insulin resistance.Maryland Summer Scholars Progra

A Rapid Flexible Method for Determining Bile Lipids

A rapid flexible method has been developed for the quantitative determination of bile lipids In gallbladder and hepatic bile and duodenal aspirates. Quantification of bile salts involves separation of bile salt conjugates from one another and other bile lipids by thin layer chromatography. The separated salts are determined using 3-hydroxysteroid dehydrogenase and gas liquid chromatography. Cholesterol is determined in petroleum ether extracts of saponified bile by application of the Lieberman-Burchard reaction. Phospholipid phosphorus is determined in purified bile lipid extracts by oxidation followed by application of Bartlett\u27s modification of the Fiske- SubbaRow method

X-Ray Diffraction Powder Data for Steroids: Supplement IX

This supplement continues a series of publications which began with a separate section, in the December, 1958 issue. All supplements are listed in the references

X-Ray Diffraction Powder Data for Steroids: Supplement VIII

This supplement continues a series of publications which began as a separate section, with the Dec. 1958 issue, and has been supplemented periodically since then. Other publications have been March 1961 (Supplement I) Sept. 1962 (Supp. II): March 1963 (Supp. Ill): March 1964 (Supp. IV): Dec. 1964 (Supp. V): Sept. 1965 (Supp. VI) and Dec. 1966 (Supp. VII)