Seán J. Costelloe

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The evolutionary relationships of the thiamine pyrophosphate (TPP)-dependent family of enzymes was investigated by generation of a neighbor joining phylogenetic tree using sequences from the conserved pyrophosphate (PP) and pyrimidine (Pyr) binding domains of 17 TPP-dependent enzymes. This represents the most comprehensive analysis of TPP-dependent enzyme(More)
We have used active-site targeted directed evolution by saturation mutagenesis to improve the activity of E. coli transketolase towards non-phosphorylated substrates. Residues were selected for each set based on either structural proximity to substrate, or on phylogenetic variation. Each library was screened towards the reaction between hydroxypyruvate(More)
OBJECTIVE To assess the incidence of thyroid dysfunction (TD) in a UK cohort of patients with hepatitis C virus (HCV) infection treated with interferon-alpha (IFNalpha) and ribavirin combination therapy (IFN/RBV). DESIGN, PATIENTS AND MEASUREMENTS A retrospective study of 288 patients who received IFN/RBV for HCV during a 2-year period from January 2006(More)
BACKGROUND Copy number variants (CNVs) are a major form of genomic variation, which may be implicated in complex disease phenotypes. However, investigation of the role of CNVs in coronary heart disease (CHD) traits has been limited. METHODS AND RESULTS We examined the use of the cnvHap algorithm for CNV detection, using data for 2500 men from the Second(More)
Mutants of transketolase (TK) with improved substrate specificity towards the non-natural aliphatic aldehyde substrate propionaldehyde have been obtained by directed evolution. We used the same active-site targeted saturation mutagenesis libraries from which we previously identified mutants with improved activity towards glycolaldehyde, which is(More)
Preanalytical errors have previously been shown to contribute a significant proportion of errors in laboratory processes and contribute to a number of patient safety risks. Accreditation against ISO 15189:2012 requires that laboratory Quality Management Systems consider the impact of preanalytical processes in areas such as the identification and control of(More)
BACKGROUND Huntington's disease is an inherited neurodegenerative disorder characterised by motor, cognitive and psychiatric disturbances. Patients exhibit other symptoms including sleep and mood disturbances, muscle atrophy and weight loss which may be linked to hypothalamic pathology and dysfunction of hypothalamo-pituitary axes. METHODS We studied(More)
BACKGROUND Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III) and controls. METHODS Control (n = 15), premanifest (n = 14) and(More)
BACKGROUND Most errors in the clinical laboratory occur in the preanalytical phase. This study aimed to comprehensively describe the prevalence and nature of preanalytical quality monitoring practices in UK clinical laboratories. METHODS A survey was sent on behalf of the Association for Clinical Biochemistry and Laboratory Medicine Preanalytical Working(More)