A5054447572- Lysosomal Storage Disorders Research
- Carbohydrate Chemistry and Synthesis
- Glycogen Storage Diseases and Myoclonus
- Gut microbiota and health
- Trypanosoma species research and implications
- Clostridium difficile and Clostridium perfringens research
- Cellular transport and secretion
- Glycosylation and Glycoproteins Research
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Nosocomial Infections in ICU
- Chemical Analysis and Environmental Impact
- Thyroid Disorders and Treatments
- Research on Leishmaniasis Studies
- Complement system in diseases
- Bacterial Infections and Vaccines
- Coffee research and impacts
- Neonatal and fetal brain pathology
- Phytochemistry and Bioactive Compounds
- Gastrointestinal motility and disorders
- Receptor Mechanisms and Signaling
- Parasitic Diseases Research and Treatment
- Parkinson's Disease Mechanisms and Treatments
- Restless Legs Syndrome Research
- Cardiomyopathy and Myosin Studies
University College Cork
2016-2023
BioMarin (United States)
2013-2020
APC Microbiome Institute
2018-2020
National University of Ireland
2018-2019
Drug Discovery Laboratory (Norway)
2014
Adamas Pharmaceuticals (United States)
2012
Natural Environment Research Council
2007
London North West Healthcare NHS Trust
2006
Wellcome Trust
1998-2006
Northwick Park Hospital
2006
Background Neurodegenerative metabolic disorders such as mucopolysaccharidosis IIIB (MPSIIIB or Sanfilippo disease) accumulate undegraded substrates in the brain and are often unresponsive to enzyme replacement treatments due impermeability of blood barrier enzyme. MPSIIIB is characterised by behavioural difficulties, cognitive later motor decline, with death second decade life. Most these neurodegenerative lysosomal storage diseases lack effective treatments. We recently described...
Significance Mucopolysaccharidosis type IIIB (MPS IIIB) is a devastating and currently untreatable disease affecting mainly the brain. The cause lack of lysosomal enzyme, α– N -acetylglucosaminidase (NAGLU), storage heparan sulfate. Using mouse model MPS IIIB, we administered modified NAGLU by injection into left ventricle brain, bypassing blood–brain barrier. modification consisted fragment IGFII, which allows receptor-mediated uptake delivery to lysosomes. enzyme was taken up avidly cells...
There are complex interactions between aging, frailty, diet, and the gut microbiota; modulation of microbiota by diet could lead to healthier aging. The purpose this study was test effect diets differing in sugar, fat, fiber content upon mice humanized with from healthy or frail older people. We also performed a 6-month dietary supplementation three human cohorts representing distinct life-stages.Mice were colonized then underwent an 8-week intervention either high-fiber/low-fat typical...
Alteration of the gut microbiota by repeated antibiotic treatment increases susceptibility to Clostridioides difficile infection. Faecal transplantation from donors with a normal effectively treats C. infection.The study involved 10 patients recurrent infection, nine whom received transplants individual and one who donor unit stool bank (OpenBiome).All individuals demonstrated enduring post-transplant resolution difficile- associated diarrhoea. diversity recipients significantly increased,...
Abstract Background A hallmark feature of Parkinson's disease (PD) is the build‐up α‐synuclein protein aggregates throughout brain; however also expressed in enteric neurons. Gastrointestinal (GI) symptoms and pathology are frequently reported PD, including constipation, increased intestinal permeability, glial pathology, alterations to gut microbiota composition. can propagate through neuronal systems but site origin whether it be or brain, still unknown. Physical exercise associated with...
Recent investigations in neuroscience implicate the role of microbial-derived metabolites, such as short-chain fatty acids (SCFAs) brain health and disease. The SCFAs acetate, propionate butyrate have pleiotropic effects within nervous system. They are crucial for maturation brain's innate immune cells, microglia, modulate other glial cells through aryl-hydrocarbon receptor. Investigations preclinical clinical models find that exert neuroprotective antidepressant affects, while also...
Alterations in intestinal microbiota have been correlated with a growing number of diseases. Investigating the faecal is widely used as non-invasive and ethically simple proxy for biopsies. There an urgent need collection transport media that would allow sampling at distance from processing laboratory, obviating same-day DNA extraction recommended by previous studies freezing methods stool. We compared bacterial quality apparent phylogenetic composition derived using commercial kit stool...
Psychological stress affects maternal gastrointestinal (GI) permeability, leading to low-grade inflammation, which can negatively affect fetal development. We investigated a panel of circulating markers as biological signature this exposure in pregnant women with and without the stress-related GI disorder irritable bowel syndrome (IBS). Markers permeability inflammation were measured plasma from healthy IBS cohorts at 15 20 weeks' gestation. Biomarkers evaluated respect their degree...
The development of tuberculin skin test (TST) positivity following infection by Mycobacterium tuberculosis is not invariable and may depend on bacillary as well host factors.First, to compare the diagnostic performance TST a form in vitro IFN-gamma release assay (IFNGRA) circumstances contact investigation prompted an unusually severe index case infectious pulmonary tuberculosis. Second, investigate ability strain M. responsible induce cytokine secretion from monocytes vitro.A routine...
We isolated Candida dubliniensis from a nonhuman source, namely, tick samples an Irish seabird colony. The species was unambiguously identifi ed by phenotypic and genotypic means. Analysis of the 5.8S rRNA gene showed that environmental isolates belong to C. genotype 1.
Abstract BMN 250 is being developed as enzyme replacement therapy for Sanfilippo type B, a primarily neurological rare disease, in which patients have deficient lysosomal alpha- N -acetylglucosaminidase (NAGLU) activity. taken up target cells by the cation-independent mannose 6-phosphate receptor (CI-MPR, insulin-like growth factor 2 receptor), then facilitates transit to lysosome. dosed directly into central nervous system via intracerebroventricular (ICV) route, and objective of this work...
Mycobacterium tuberculosis is a significant threat to global health. bovis BCG vaccine provides only partial protection, and the skin test reagent used aid diagnosis of both active latent tuberculosis, purified protein derivative (PPD), lacks specificity sensitivity. The use genetically detoxified Bordetella pertussis adenylate cyclase toxin (CyaA) as delivery system for two immunodominant proteins M. that are greater than PPD, early-secreted antigenic target 6-kDa (ESAT-6) culture filtrate...
A series of hydrophobic mannosides were synthesized and tested for their ability to act as acceptor substrates mannosyltransferases in a Trypanosoma brucei cell-free system. The thiooctyl α-mannosides octyl all accepted single mannose residues α-linkage, judged by thin layer chromatography the products before after jack bean α-mannosidase digestion. mannosylation reactions inhibited amphomycin, suggesting that immediate donor was dolicholphosphate-mannose (Dol-P-Man) cases. transferred...