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The potential to differentiate human embryonic stem cells (hESCs) in vitro to provide an unlimited source of human hepatocytes for use in biomedical research, drug discovery, and the treatment of liver diseases holds great promise. Here we describe a three-stage process for the efficient and reproducible differentiation of hESCs to hepatocytes by priming(More)
Robert D. Finn, Lesley A. McLaughlin, Sebastien Ronseaux, Ian Rosewell, J. Brian Houston, Colin J. Henderson, and C. Roland Wolf From the Cancer Research UK Molecular Pharmacology Unit, Biomedical Research Institute, Level 5, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom, Cancer Research UK Transgenic Services, Clare Hall(More)
Generation Scotland: the Scottish Family Health Study aims to identify genetic variants accounting for variation in levels of quantitative traits underlying the major common complex diseases (such as cardiovascular disease, cognitive decline, mental illness) in Scotland. Generation Scotland will recruit a family-based cohort of up to 50,000 individuals(More)
OBJECTIVES We have earlier shown that diet and xenobiotic metabolizing enzyme genotypes influence colorectal cancer risk, and now investigate whether similar associations are seen in patients with premalignant colorectal adenomas (CRA), recruited during the pilot phase of the Scottish Bowel Screening Programme. METHODS Nineteen polymorphisms in 13 genes(More)
The cause of 95% of Parkinson's disease (PD) cases is unknown. It is hypothesized that PD arises from an interaction of free-radical-generating agents with an underlying genetic susceptibility to these compounds. Here we use the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of parkinsonism to examine the role of a dual function protein, GSTpi, in(More)
The NF-E2 p45-related factor 2 (Nrf2) regulates cytoprotective genes that contain an antioxidant response element (ARE) in their promoters. To investigate whether anticancer drugs can induce ARE-driven gene expression, we have developed a stable human mammary MCF7-derived reporter cell line called AREc32, which contains a luciferase gene construct(More)
Bacillus subtilis strain 168 encodes two flavocytochromes P450, Cyp102A2 and Cyp102A3. The cyp102A3 gene is preceded by, and organized in an operon with, a gene for a transcriptional regulator, encoded by fatR. The paralogous gene, cyp102A2, is most likely transcribed as a mono-cistronic message. We show that fatR encodes a protein that binds to an operator(More)
Epidemiologic evidence suggests a role for folate, a critical component of the 1-carbon cycle, in colorectal adenoma and cancer pathogenesis. Low folate levels, along with genetic polymorphisms in key enzymes such as methylene tetrahydrofolate reductase (MTHFR), can cause DNA hypomethylation and aberrant CpG methylation, which have been associated with(More)
The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular(More)
OBJECTIVE To compare the efficacy and safety of adjunctive treatment with paroxetine or amitriptyline in patients with bipolar disorder who relapsed into a depressive episode during lithium maintenance therapy. METHODS Data from a randomized, double-blind trial comparing paroxetine (N=18) or amitriptyline (N=22) as adjunctive treatment for an episode of(More)