Phosphoinositides are lipid signals that control cellular processes and are particularly closely associated with the control of membrane trafficking. PtdIns(3,5) \(\char{cmmi10}{0x50}\)\(_2\) is the most recently identified phosphoinositide and was previously recognised as contr…
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The overarching aim of this thesis was to better understand the behavioural, cognitive, and neural corollaries of blunted cardiovascular and/or cortisol reactions to acute psychological stress. As such, it was also concerned to further test the proposition that blunted cardiovas…
Background: The non-invasive assessment of volume status in left ventricular systolic dysfunction (LVSD) is challenging. The main thesis objective was to establish the feasibility and potential clinical utility of repeated measures assessment of non-invasive biomarkers in defini…
In obesity, lipids stored in muscle as lipid droplets (LDs) lead to accumulation of fatty acid (FA) metabolites and insulin resistance. This research involves development of immunofluorescence microscopy methods to generate novel information on the subcellular content and distri…
Exercise training is known to increase endothelial function and provoke arterial remodelling both locally and systemically. This thesis was designed to further examine these relationships by investigating the acute response to different exercise intensities, with and without she…
Ptprq, a receptor-like phosphatase known to be associated with the shaft connectors of stereocilia, is a protein required for the maintenance of the hair-bundle structure. The extracellular domain of Ptprq has numerous potential sites for N-glycosylation and the cytoplasmic doma…
The sensory hair bundles of the cochlea are complex structures that are vital for hearing. Phosphorylation plays an important role in regulating actin in many cell types, but the role it plays in regulating the development and maintenance of the hair bundle has yet to be fully e…
Subclinical thyroid dysfunction (SCTD), characterised by abnormal serum thyrotrophin concentrations (TSH) with normal free thyroxine (FT\(_4\)), is regularly encountered in primary care. The clinical manifestations of SCTD are not well established, particularly in older individu…
In rheumatoid arthritis (RA), chronic inflammation and destruction of the joint is driven by local production of cytokines. My aims were to characterise cytokine mRNA expression in multiple synovial fluid cell populations in early and established RA and to study these, in additi…
Background: Quitting smokers gain weight, this offsets some advantages of quitting and may increase risk of type 2 diabetes above that of continuing smokers. The extent of weight gain, the associated characteristics, and management that will not hinder quit success are unclear. …
Cardiovascular control during exercise results from three main mechanisms, namely central command (descending neural input), skeletal muscle afferent feedback (metabo - and mechanoreflex) and the arterial baroreflex. The studies outlined in this thesis sought to examine the pote…
The availability of fully sequenced genomes of the model organisms including Drosophila, and their subsequent annotation has afforded seamless opportunities for reverse genetics in a complex model organism. With the advent of DNA microarrays to assay the levels of tens of thousa…
The purpose of this study was to investigate the stabilizing properties of osmolytes, specifically sugars on biomolecule such as protein. The strategy used in this study involved the utilisation of surfactant-rich micelles; where by the impact sugars have on the free energy of e…
The process through which new blood vessels are formed within the body is known as angiogenesis. An essential part of our survival, it has also been implicated more recently in many diseases both in terms of induced growth, and abnormal vascular structure. Angiogenesis is charac…
Drosophila melanogaster has been an important model organism for over a century, cumulating in a vast array of mutant and transgenic stocks, the publication of the genome, its subsequent annotation and more recently the production of the online gene expression database, FlyAtlas…
Purpose: To investigate the physiological, immunological and psychological response to an intense bout of exercise performed by highly trained individuals at 09:00 hs and 16:00 hs (Chapter 5) and at 09:00 hs and 18:00 hs (Chapter 6). Methods: Using a crossover randomized design,…
Globally, gastric cancer claims around 800,000 lives per year. As many patients present at an advanced stage of disease, prognosis remains poor for most patients, with five-year survival rates of less than 30%. As many patients show only limited short-term benefits from current …
The tumour microenvironment consists of a diverse range of cell types, which work together to create favorable conditions to support tumour growth and metastasis. It has been repeatedly reported that bone marrow-derived mesenchymal stem cells (MSCs), also referred to as multipot…
Molecular mechanisms governing the plasticity of cellular boundaries in confluent epithelial monolayers are poorly characterised. In this thesis, we report a drastic reorganisation of cellular boundaries, provoked by the prolonged withdrawal of EGF from non-malignant mammary epi…