I hereby declare that the work presented in this document is based on research carried out by me, and that no part has previously been submitted for a degree in this or any other university

Inhibitors of known transport processes, in conjunction with ion substitution were used in biochemical, physiological and microelectrode studies to investigate the mechanisms underlying ion and fluid secretion across the Malpighian tubules of Locusta migratoria. Immunocytochemical localization and cell fractionation methods used in conjunction with biochemical analyses demonstrate the presence of Na(^+)/K(^+)-ATPase activity on the basal cell membranes and HCO(_3)(^-)-stimulated and V-type ATPase activities on apical cell membranes. The biochemical properties of the HCO(_3)(^-)-stimulated and V-type ATPase activities are compared and the results discussed. Specific inhibitors of Na(^+)/K(^+)-ATPase and V-type ATPases inhibited fluid secretion whilst cAMP was found to stimulate fluid secretion. The continued secretion of K(^+) when tubules were bathed in K(^+)-free saline was attributed to the presence of mineral concretions shown in ultrastructural studies to be distributed throughout the cytoplasm. The effects of ouabain, NEM and cAMP on the cationic composition of the "urine" were studied. In control saline, ouabain and NEM increased the level of Na(^+) in the "urine" whereas cAMP caused an increase in the amount of K(^+) secreted. In Rb(^+)-saline, ouabain caused "urine" levels of Na(^+) to increase and levels of Rb(^+) to fall whereas cAMP and NEM had no effect on the cationic composition of the "urine". Ion substitution experiments used in conjunction with intracellular microelectrodes suggest the basal cell membrane contains an inward rectifying K(^+) channel. Blocking the basal inward rectifier with Rb(+) drove the potential of this membrane towards the emf of the apical membrane potential. In the presence of Rb(^+), bafilomycin A(_1), a specific V-type ATPase inhibitor, reduced this potential suggesting the apical membrane potential is produced by a V-type ATPase. The results are discussed and a hypothetical model is proposed to account for the mechanisms of ion and fluid movement across apical and basal cell surfaces

The relationship between amyloid structure and cytotoxicity

Self-assembly of proteins and peptides into amyloid structures has been the subject of intense and focused research due to their association with neurodegenerative, age-related human diseases and transmissible prion diseases in humans and mammals. Of the disease associated amyloid assemblies, a diverse array of species, ranging from small oligomeric assembly intermediates to fibrillar structures, have been shown to have toxic potential. Equally, a range of species formed by the same disease associated amyloid sequences have been found to be relatively benign under comparable monomer equivalent concentrations and conditions. In recent years, an increasing number of functional amyloid systems have also been found. These developments show that not all amyloid structures are generically toxic to cells. Given these observations, it is important to understand why amyloid structures may encode such varied toxic potential despite sharing a common core molecular architecture. Here, we discuss possible links between different aspects of amyloidogenic structures and assembly mechanisms with their varied functional effects. We propose testable hypotheses for the relationship between amyloid structure and its toxic potential in the context of recent reports on amyloid sequence, structure, and toxicity relationships

Readers’ experiences of Braille in an evolving technological world

This paper investigates people’s experiences and opinions of Braille as a reading method. It aims to explore how Braille’s role may be evolving in a world with an increased range of technological alternatives for reading. Two participant studies with people with visual impairments are reported. Firstly, a survey (Study A) explores current reading experiences and preferences. Secondly, building on the survey findings, a series of in-depth interviews (Study B) explores individual reading experiences of different artefacts. The findings show how particular assistive technologies may be deemed more or less appropriate for different reading contexts and purposes and highlights issues of production and standardization for reading artefacts. This suggests that providing people with visual impairments with access to a range of resources could support more inclusive practices. The findings also suggest that in some contexts, such as information presented in public spaces and on packaging, greater standardization of Braille could be of benefit to people with visual impairments