1,333 Works

A role for microRNA-29a mediating ER stress-induced apoptosis in neuronal cells in the mouse central nervous system.

Katie Nolan
A role for microRNA-29a mediating ER stress-induced apoptosis in neuronal cells in the mouse central nervous system Disturbances in the folding of proteins within the endoplasmic reticulum (ER) lead to the accumulation of mis-folded and aggregated proteins and the activation of the ER stress response and has been implicated in neurodegenerativo diseases such as amyotrophic lateral sclerosis. MicroRNAs are small ribonucleic acids which can modulate the expression of proteins post-translationally and in recent years have...

The epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and an investigation of a novel therapeutic peptide conjugate.

Liam Burke
Herein we studied the epidemiology of two species of ESBL-producing Enterobacteriaceae causing clinical infections and investigated the potential of a novel host defence peptide conjugate as a therapeutic agent against these infections. We first characterised 100 ESBL-producing E. coli (ESBL-EC) collected over two years that caused infections in patients of Beaumont Hospital and in community patients attending general practitioners or residing in long-term care facilities (LTCFs) in North Dublin. Using molecular typing techniques, we found...

The epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and an investigation of a novel therapeutic peptide conjugate.

Liam Burke
Herein we studied the epidemiology of two species of ESBL-producing Enterobacteriaceae causing clinical infections and investigated the potential of a novel host defence peptide conjugate as a therapeutic agent against these infections. We first characterised 100 ESBL-producing E. coli (ESBL-EC) collected over two years that caused infections in patients of Beaumont Hospital and in community patients attending general practitioners or residing in long-term care facilities (LTCFs) in North Dublin. Using molecular typing techniques, we found...

Genome-wide mapping of markers for epilepsy predisposition and treatment.

Mark McCormack
There is an increasing amount of evidence to suggest genetics plays a large role in governing an individual's risk for developing epilepsy and their response to anti-epileptic drug treatment. Responses can range from seizure control with first drug, complete resistance and serious idiopathic and doserelated adverse events occurring upon exposure to specific drugs. This thesis consists of five studies with a common aim of identifying novel genetic influences on epilepsy predisposition and treatment. A candidate...

Individual Platelet Adhesion (iPA): A novel assay of platelet function

Ana Lopez Alonso
Cardiovascular disease is the leading cause of mortality in the developed countries and platelet related thrombosis the main complication in this condition. Anti-platelet agents are commonly used in the prevention of acute cardiovascular events. According to the American Heart Association and the American College of Cardiology (Circulation 2012), a class IIb recommendation is given for the use of platelet function test. This approach has been implemented in several clinical trials in order to improve outcomes...

The Impact of a Changed Approach to Analgesia and Sedation Management in the Paediatric Intensive Care Unit

Claire Magner
Background International best practice endorses the use of a standardised approach in the management of analgesic and sedative drugs in the Paediatric Intensive Care Unit (PICU). In adult intensive care settings incorporating analgesia and sedation guidelines has been associated with significant patient benefits including a reduction in the amounts of analgesia and sedative drugs used and a decrease in the duration of mechanical ventilation. In contrast, the evidence to support this change in practice in...

Anatomists and geometers : a selection from the published work.

A short commentary, not exceeding one thousand words, indicating how each publication contributes to the total corpus of the candidate’s research BIOENGINEERING The majority of bioengineering papers deal with bone, the detection of microdamage within it, its remodelling and adaptation in health and disease and its behaviour as a material in both theory and practice. The exception (B21) involves mechanical testing of vascular tissue. Paper B1 introduces a new fluorescence-aided technique for quantifying fuchsin-stained microdamage...

Molecular signalling pathways involved in AMPK-mediated neuronal preconditioning and optimisation of a high content screening assay to monitor excitotoxic neuronal death.

Neuronal preconditioning is a phenomenon where a previous exposure to a sublethal stress stimulus increases the resistance of neurons towards a second, normally lethal stress stimulus. Activation of the energy stress sensor, AMP-activated protein kinase (AMPK) has been shown to contribute to the protective effects of ischemic and mitochondrial uncoupling-induced preconditioning in neurons, however the molecular basis of AMPK-mediated preconditioning have been less well characterised. First, we investigated the effect of AMPK preconditioning using 5-aminoimidazole-4-carboxamide...

The role of IGF-I signalling in the pathogenesis of breast cancer : therapeutic potential of a protease resistant IGF binding protein 4 (IGFBP4)

Yvonne E. Smith
The insulin-like growth factor (IGF) pathway promotes breast cancer and disease progression through cellular processes including proliferation, differentiation, invasion, migration and angiogenesis. Due to its involvement in breast cancer, targeting this pathway may prove beneficial in treating this disease. This thesis investigates the importance of the IGF-IR in breast cancer progression, the characterisation of preclinical mouse models of breast cancer using classification and prognostic markers of the human disease, and preclinical evaluation of a novel...

Development of Nano- and Microparticle Technologies for Targeted Gene Silencing through RNA Interference Manipulation of the Immune Response in Inflammatory Lung Disease

Ciara Kelly
RNA Interference (RNAi) allows specific and potent knockdown of target genes and interest now lies beyond its use as a molecular biology tool and in its potential as a therapeutic to mediate gene silencing in diseased cells. Targeted local delivery of small interfering RNA (siRNA) to the lungs via inhalation offers a unique opportunity to treat a range of previously unbeatable or poorly controlled respiratory conditions. Alveolar macrophages are the first line of defence against...

Stereoselective Preparation of Enantiopure Abasic Nucleosides and 4-Nitroisoxazoles

Gea Bellini
Chapter 1. Stereoselective preparation of enantiopure abasic nucleosides The synthesis of artificial oligonucleotides capable of forming stable complexes with divalent Cu2+ ions and, by virtue of that, replacing the hydrogen-bonded natural base pairing in DNA has been recently reported. Based on these findings, a strategy for the development of novel C-nucleosides analogues bearing functional groups able to complex divalent metal ions, therefore avoiding the need of the natural nucleobase for the formation of a DNA...

Stereoselective Preparation of Enantiopure Abasic Nucleosides and 4-Nitroisoxazoles

Gea Bellini
Chapter 1. Stereoselective preparation of enantiopure abasic nucleosides The synthesis of artificial oligonucleotides capable of forming stable complexes with divalent Cu2+ ions and, by virtue of that, replacing the hydrogen-bonded natural base pairing in DNA has been recently reported. Based on these findings, a strategy for the development of novel C-nucleosides analogues bearing functional groups able to complex divalent metal ions, therefore avoiding the need of the natural nucleobase for the formation of a DNA...

The Role of HIF Hydroxylases in the Regulation of Colonic Epithelial Ion Transport

Joseph Bernard Jude Ward
The intestinal epithelium is a monolayer of cells that lines the entire surface of the gastrointestinal tract from mouth to anus. A key function of the intestinal epithelium is the absorption and secretion of fluids and electrolytes. The intestinal epithelium is primarily an absorptive tissue, but under normal conditions secretion also occurs. In conditions of disease the delicate balance between absorption and secretion can become dysregulated leading to the onset of diarrhoea. Chloride (Cl') secretion,...

Identification of novel biomarkers in postmenopausal osteoporosis

Laura Corrigan
Osteoporosis is a degenerative disorder characterised by a reduction in bone strength manifesting itself in fragility fractures. Current diagnosis relies on the measurement o f bone mineral density (BMD) generated by dual X-ray absorptiometry (DXA) scanners. Serological markers of disease or biomarkers, present themselves as a useful and potentially inexpensive methodology o f assessing disease status. Proteomic technologies utilised on biofluids have proven themselves as capable o f identifying candidate biomarkers of disease. The aim...

Communicable disease screening for asylum seekers and refugees in Ireland: an analysis of professional stakeholders’ insights into knowledge into action

Gemma Smith
Introduction Numerous countries employ migrant communicable disease screening programmes and initial health assessments (IHAs). Although the evidence base under-pinning screening policies has been criticised, relatively little is known about the extent to which screening policies, guidelines and programmes are implemented and practice is evidence-informed. Methods A case study design was employed to examine the development of communicable disease screening guidelines for asylum seekers and refugees in Ireland and the enacting of the guidelines and...

The \"humanisation\" of medicine? : the feminisation of medicine: a qualitative study of the career experiences of female doctors and implications for human resources management in Ireland.

Sara McAleese
The féminisation of medicine is an international phenomenon referring to increasing numbers of females undertaking medical education and entering the medical workforce. This phenomenon has been a hallmark of the medical profession in Ireland since the 1990s. Associated with this phenomenon are several trends that may have implications for human resources management of the medical workforce. These trends are: distinct variation in the distribution of female doctors across the medical specialties, under-representation of female doctors...

Controlled Release of Bioactive Molecules from Collagen-Based Scaffolds for Bone Repair

Elaine Quinlan
Although bone has an intrinsic capacity for self repair, the healing of large bone defects that typically present in humans often involves complications which can result in failure to heal, leading to delayed union or non-union of the defect. Due to limitations of current therapeutic approaches of autografting and allografting, the use of tissue engineered scaffolds has emerged. Despite some success with this approach, a major limitation is creating functionally vascularised constructs. In addition, scaffolds...

The development of novel siRNA nanoparticles for delivery to pulmonary epithelial cells

Alan J. Hibbitts
Local delivery of short-interfering RNA (siRNA) to the lungs represents a promising means of treating a range of pulmonary conditions such as acute lung injury (ALI) and chronic obstructive pulmonary disorder (COPD). However, effective pulmonary delivery of siRNA remains hampered by a range of host defence mechanisms. Furthermore, pharmaceutical issues that are currently impeding pulmonary siRNA therapy include cytotoxicity, inefficient rates of delivery and low levels of post-delivery siRNA stability. One strategy to overcome these...

Estrogen regulation of the Potassium Channel KCNQ1:KCNE3 in Colonic Epithelium

Raphael Rapetti-Mauss
Background: The KCNQ1:KCNE3 K+ channel is an essential component of the Cl" secretion machinery in the distal colon. This channel provides the driving force for apical Cl’ secretion by basolateral recycling of K+. The steroid hormone estrogen (17|3-estradiol, E2) has previously been reported to exert a female specific antisecretory response in colonic crypts through the inhibition of the KCNQ1:KCNE3 channel. The purpose of this study was to uncover and describe molecular mechanisms of estrogen regulation...

The role of osteoprotegerin and receptor activator of nuclear factor kappa-betta ligand in vascular calcification and the influence of insulin and liraglutide on this process in type 2 diabetes mellitus.

Colin Davenport
Background: The process of vascular calcification (VC) appears to involve certain vascular cell populations assuming an osteoblastic phenotype. Osteoprotegerin (OPG) has been proposed as an inhibitor of VC, potentially via blockade of either receptor activator of nuclear factor kappa-beta ligand (RANKL) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Treatments for type 2 diabetes mellitus (T2DM) such as insulin analogues and liraglutide are known to affect OPG, and may also affect VC. The aims of this...

Investigating novel mechanisms of metastasis in endocrine resistant breast cancer.

Breast cancer is the commonest solid tumour in European females. Treatment of breast cancer using anti-oestrogenic agents provides a template for the development of targeted therapies, both in breast cancer and other neoplastic diseases. Tamoxifen remains the treatment of choice for pre-menopausal breast cancer patients who express an oestrogen receptor, while a newer class of drug, aromatase inhibitors, are the first-line treatment for post-menopausal patients. In spite of these advances, up to 25% of breast...

Investigating novel mechanisms of metastasis in endocrine resistant breast cancer.

Breast cancer is the commonest solid tumour in European females. Treatment of breast cancer using anti-oestrogenic agents provides a template for the development of targeted therapies, both in breast cancer and other neoplastic diseases. Tamoxifen remains the treatment of choice for pre-menopausal breast cancer patients who express an oestrogen receptor, while a newer class of drug, aromatase inhibitors, are the first-line treatment for post-menopausal patients. In spite of these advances, up to 25% of breast...

Physiological Impact of Lipoxin A4 on Cystic Fibrosis Bronchial Epithelium

Gerard Higgins
This thesis reports a novel role of lipoxin A4 (LXA4) in mediating physiological effects within the airways of cystic fibrosis (CF) patients. CF is caused by a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This mutation leads to a dysfunctional chloride transport system resulting in dehydration of the airway surface liquid (ASL) layer, impaired mucociliary clearance, lung infection and inflammation. The eicosanoid LXA4 described as a signal of the resolution of inflammation...

A School-based Trial Protocol in Community Promotion of Solar Water Disinfection (SODIS): A Case Study of Ndagwe Sub County, Central Uganda

Improvement in microbial quality of drinking water by solar disinfection (SODIS) results in reduced diarrheal episodes among users. In this study, a randomized cluster stepped wedge study design was used to assess the use of primary school pupils as community promoters of SODIS technology in Ndagwe sub county, central Uganda. The intervention (SODIS) was introduced to pupils in the different school clusters at different time points throughout the year. Pupils were to only drink SODIS...

Development of Phase Transfer Catalysed Cyclopropanation and Related Processes

Claudia Del Fiandra
The aim of this research is to develop new Phase-Transfer catalysed Michael and Michael tandem reactions including bifunctional catalysed Michael reactions. We have brought our own contribution to this field by establishing a few highly enantioselective procedures that used the Michael reaction of enolisable starting materials. We describe a Michael-initiated ring closure (MIRC) reaction o f 2,3-disubstituted-1,1- cyclopropanediesters, obtained with good enantioselectivities, under operationally simple conditions and mild PTC catalysis. The study delivers a class...

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