A5017064295- Hemoglobin structure and function
- Hemoglobinopathies and Related Disorders
- Protein Interaction Studies and Fluorescence Analysis
- Mass Spectrometry Techniques and Applications
- Protease and Inhibitor Mechanisms
- Erythrocyte Function and Pathophysiology
- Monoclonal and Polyclonal Antibodies Research
- Blood groups and transfusion
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Advanced Proteomics Techniques and Applications
- Drug Transport and Resistance Mechanisms
- Blood properties and coagulation
- Cellular transport and secretion
- Pancreatitis Pathology and Treatment
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Diabetes and associated disorders
- Protein purification and stability
- Lipoproteins and Cardiovascular Health
- Neonatal Health and Biochemistry
- Metabolism and Genetic Disorders
- Blood Pressure and Hypertension Studies
- Blood Coagulation and Thrombosis Mechanisms
- Iron Metabolism and Disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
Health Research Board
2025
University College Dublin
2025
Cancer Trials Ireland
2025
Mater Misericordiae University Hospital
2024-2025
Ollscoil na Gaillimhe – University of Galway
2025
St. Vincent's University Hospital
2021-2022
Royal Perth Hospital
2022
Canterbury Health Laboratories
2002-2020
Christchurch Hospital
1994-2020
University of Stirling
2019
The primary structure of apolipoprotein E (apo E) was investigated in seven type III hyperlipoproteinemic patients with the apo E-2/2 phenotype. Six had identical two-dimensional tryptic peptide maps. These differed from normal E3 map by altered mobility a single peptide. Amino acid analysis and sequencing showed that E2 these substitution 158 Arg----Cys. presence this mutation six confirms is most common form E2. seventh patient unique new resulting 136 Arg----Ser. He heterozygous for more...
Reduced glutathione (GSH) is one of the most preferred biological substrates myeloperoxidase-derived hypochlorous acid and a likely target for neutrophil oxidants. We have used HPLC to show that oxidation GSH by gives two major, stable products in addition disulphide (GSSG). The prevalent product lacks free amine thiol groups, was shown electrospray MS molecular mass 337 Da. This corresponds with gain oxygen atoms loss hydrogen atoms, consistent being an internal sulphonamide. other novel...
Both normal antithrombin‐III (AT‐IIIα) and the high heparin affinity form (AT‐IIIβ) were isolated from pooled human plasma. AT‐IIIβ had a lower negative charge molecular mass than AT‐IIIα. Sialidase endo‐F digestion indicated that inherent difference resided in oligosaccharide component of molecule. CNBr fragmentation showed there was an sidechain missing between residues 104 251, subdigestion with trypsin Asn 135 not glycosylated AT‐IIIβ. Chromatography total tryptic digests on concanavalin...
Abstract Albumin has an average plasma half-life of three weeks and is thus attractive carrier to improve the pharmacokinetics fused therapeutics. The regulated by FcRn, a cellular receptor that protects against intracellular degradation. To tailor-design therapeutic use albumin, it crucial understand how structural alterations in albumin affect FcRn binding transport properties. In blood, last C-terminal residue (L585) may be enzymatically cleaved. Here we demonstrate removal L585 causes...
Human neutrophils, when stimulated with phorbol myristate acetate or fMet-Leu-Phe in the presence absence of cytochalasin B, released metalloproteinases that catalytically inactivated plasma serine proteinase inhibitor, alpha 1-antitrypsin. Inactivation, measured as loss elastase inhibitory capacity, was accompanied by cleavage a Mr 4,000 peptide from COOH-terminus. Cleavage 1-antitrypsin cell supernatants inhibited EDTA, o-phenanthroline, and DTT, but not inhibitors thiol proteinases....
Hypochlorous acid (HOCl) is a potent oxidant produced by myeloperoxidase that causes aggregation of many proteins. Treatment apohaemoglobin and apomyoglobin with HOCl regular series oligomer bands when the proteins were separated SDS/PAGE under reducing conditions. Aggregation was detectable at HOCl/protein molar ratio 0.5:1 maximal ratios 10:1–20:1. Dimers formed within 1 min adding HOCl, further occurred over next 30 min. No convincing evidence for covalent cross-linking obtained amino...
The yeast KEX2 protease is the only enzyme that has a proven role in activation of polypeptide hormones through cleavage at pairs basic residues. fulfils this higher eukaryotes yet to be unequivocally identified. In investigation, KEX2‐like calcium‐dependent been identified rat hepatic microsomes. membrane‐bound, pH optimum 5–6 and converts proalbumin albumin. More importantly, like protease, it meets two other exacting criteria defined by specific mutations humans. Namely, does not process...
Abstract Since 2000, virtually every major assessment of ocean policy has called for implementing an ecosystem approach to managing marine resources, yet crafting such proved difficult. Ecosystems today exhibit little the abundance and complexity found in past, populations over‐fished species have declined dramatically world‐wide, historical evidence been difficult assimilate into complex models. Here, we look testimony Gulf Maine fishermen insights on Atlantic cod ( Gadus morhua )...
High‐affinity binding of progesterone, testosterone, prostaglandin F 2α and l ‐thyroxine to five genetic variants human serum albumin with defined point mutations was investigated by equilibrium dialysis (pH 7.4). Endogenous A (Alb A) from each individual commercial were used as controls in case. The association constant for progesterone Alb Canterbury (Lys313 → Asn) 1.5 times that calculated the corresponding, endogenous A. In contrast, Niigata (Asp269 Gly), Roma (Glu321 Lys), Parklands...
Possible effects of single point mutations on the ligand-binding capabilities human serum albumin (Alb) were investigated by studying interactions between strongly bound drugs warfarin, salicylate, and diazepam five structurally characterized genetic variants protein. Equilibrium dialysis data, obtained with normal Alb, revealed pronounced reductions in high affinity binding all three ligands to Alb Canterbury (313 Lys----Asn) Parklands (365 Asp----His). By contrast, unchanged was found case...
Genomic rearrangements are a well-recognized cause of genetic disease and can be formed by variety mechanisms. We report complex rearrangement causing severe hemophilia A, identified further characterized using range PCR-based methods, confirmed array-comparative genomic hybridization (array-CGH). This consists 15.5-kb deletion/16-bp insertion located 0.6 kb from 28.1-kb deletion/263-kb at Xq28 is one the most described DNA sequence level. propose that was generated distinct but linked...
Habitat loss and fragmentation greatly affect biological diversity. Actions to counteract their negative effects include increasing the quality, amount connectivity of seminatural habitats at landscape scale. However, much scientific evidence underpinning restoration comes from studies habitat fragmentation, it is unclear whether ecological principles derived removal investigations are applicable creation. In addition, relative importance local- (e.g., improving quality) vs. landscape-level...
Abstract Phosphodiesterase−5 (PDE5) inhibitors have gained interest as a potential treatment for dementia. However, current evidence is limited to observational and pre-clinical studies. We conducted drug-target Mendelian randomization (MR) analysis investigate the on-target effects of pharmacological PDE5 inhibition on dementia subtypes related phenotypes. selected variants from around PDE5A locus associated with diastolic systolic blood pressure, well circulating levels, create three...
Therapies targeting the LPL (lipoprotein lipase) pathway are under development for cardiometabolic disease. Insights into their efficacy-both alone and in combination with existing lipid-lowering therapies-modes of action, safety these agents essential to inform clinical development. Using Mendelian randomization, we aimed (1) evaluate efficacy, (2) explore shared mechanisms, (3) assess additive effects approved drugs, (4) identify secondary indications potential adverse effects. We selected...