Doctoral Theses (Life Sciences)
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Item Metabolic diversity in Campylobacter jejuni(Life Sciences, 2016-07) Alghafari, Wejdan Talal; Watson, Doctor Eleanor; Smith, Professor David G.E.; Morris, Doctor Peter; Mitchell, Doctor WilfAbstract and full text unavailable. Please refer to PDF.Item Auditory processing and its relation to cognitive and language ability across the autism spectrum(Life Sciences, 2015-04) Petrou, Alexandra Marie; Stewart, Doctor MaryIndividuals with autism spectrum conditions (ASC) often demonstrate enhanced discrimination of basic perceptual information such as pitch. This thesis investigated whether this enhanced perceptual tendency is limited to low-level acoustic stimuli or whether it occurs in higher-level linguistic stimuli in areas other than pitch and in speech-like sounds in adults with ASC who were individually matched on IQ to typically-developed adults. It tested whether differences in auditory discrimination and identification ability were related to aspects of language ability. It also tested whether IQ had an independent or an additive influence on performance differences and relationships. These effects were additionally explored with autistic traits in typically-developed adults in which IQ and linguistic skills are less variable than those within the ASC population. It was found that discrimination and identification ability of auditory stimuli were not enhanced but were related to IQ and some aspects of language ability. In ASC, previous reports of discrimination and identification differences may be attributable to an additive influence of IQ and some of the language difficulties may be explained by differences in the ability to discriminate and identify perceptual information in speech. These findings may impact on identifying and providing targeted language intervention in ASC.Item Retinal and choroidal oximetry using snapshot multispectral imaging(Life Sciences, 2015-04) Choudhary, Tushar R.; Ball, Professor Derek; Harvey, Professor AndyThe principal aim of the research was to validate and develop a non-invasive multispectral imaging technique of measuring oxygen saturation in retinal and choroidal vasculature. The Image replicating imaging spectrometer (IRIS) snapshot multispectral fundus camera used for retinal imaging, and image analysis protocols used to perform oximetry are described. In vitro and in vivo validation of oximetry techniques was performed. For in vitro validation an artificial eye containing blood at varying oxygenation was used. For in vivo validation the pig was used as an animal model. The calculated oxygen saturation was compared to blood gas analysis (gold standard) results and was found to be in close agreement. Retinal oximetry was performed on healthy human subjects. The average oxygen saturation value (± SD) for retinal arterioles and venules were 96.08% ± 1.9% and 68.04% ± 2.1%, respectively. The application of retinal oximetry technique was explored by conducting human hypoxia trials, in which the effect of acute mild hypoxia on retinal oxygenation and autoregulation was assessed on healthy human subjects. Hypoxic exposure resulted in a decline in both retinal arterial and venous saturation, as well as a significant increase in retinal vessel calibre, suggesting an autoregulatory response. This thesis also explored the possibility of exploiting fundus reflections to measure the choroidal oxygenation non-invasively. Fundus reflection intensity at two wavelengths, 780 nm and 800 nm (oxygen sensitive and isosbestic) were used to calculate intensity ratio (R), which is directly proportional to the blood oxygenation. A pilot study on 10 healthy humans was conducted. Fundus reflection was recorded at room air (normoxia) and 15% inspired oxygen (mild hypoxia). A significant reduction (P < 0.001) in intensity ratio was observed during hypoxia.Item Ecotoxicity of silver nanoparticles on estuarine and coastal bacterial communities(Life Sciences, 2015-05) Echavarri-Bravo, Virginia; Hartl, Doctor Mark; Paterson, Doctor LynnThe increasing use of silver nanoparticles (AgNPs) as a biocidal agent and their potential accumulation in coastal environments may threaten non-target natural environmental bacterial communities. For this reason the main aim of this PhD project was to examine the effects of AgNPs on the functioning of natural bacterial assemblages that inhabit estuaries and coastal areas including the mechanisms behind the recovery and resistance to AgNPs. The susceptibility of pure bacterial cultures to three different AgNP types, two standard reference materials (Sigma Aldrich AgNPs and the Organisation for Economic Co-operation and Development (OECD) NM-300 AgNPs) and a cleaning product purchased from Mesosilver containing AgNPs was examined. The Mesosilver AgNPs product exhibited the highest antibacterial activity followed by the NM-300 AgNPs. The higher toxicity exhibited by the Mesosilver AgNPs was associated with their smaller particle size and initially higher concentration of silver in ionic form. For all the AgNPs types tested, the toxicity was bacterial species-specific, Gram negative bacteria being more resistant than the Gram positive species. This initial work informed the design of the microcosm experiments established with sediments and water samples collected from the estuary to develop the exposure to AgNPs under more realistic environmental conditions. The results showed that a single pulse of NM-300 AgNPs (1 mg L-1) that led to sediment concentrations below 6 mg Ag kg dry weight-1 decreased the bacterial carbon utilization rate of environmentally relevant carbon substrates. Following a 24 hr exposure the functional diversity changed, but recovered after 120 hr. This recovery may be explained by a number of possible factors, such as the formation of compounds less toxic than AgNPs, or by the complexation of AgNPs with natural organic matter and sediments reducing their bioavailability, or also due to the presence of silver resistance genes or groups of organisms more resistant to silver. AgNPs did not affect the bacterial community structure based on the phospholipid fatty acids (PLFAs) analysis. The microcosm experiments suggested that AgNPs under environmentally relevant conditions can negatively affect bacterial function and provides an insight into the understanding of the bacterial community response and resilience to AgNPs. The results of this research project have improved the current knowledge about the toxicity of different silver nanoparticles and the bacterial response under more realistic environmental conditions and will support future risk assessments and regulation process of products containing silver nanoparticles.Item Subcellular dynamics of the Arabidopsis MPK4 signaling pathway(Life Sciences, 2016-06) Agarwal, Monica; Morris, Doctor Peter; Duncan, Professor RoryAbstract and full text unavailable. Please refer to PDF.Item Molecular analysis of starch utilization in solventogenic Clostridium(School of Life Sciences, 2018-01) Freeman, Richard J.; Mitchell, Doctor Wilf; Leslie, Doctor NickSolventogenic clostridia were commonly used in the 1900’s for the production of acetone, butanol and ethanol for various industries through ABE fermentation prior to being phased out in the late 1950’s and 60’s due to competition from cheaper oil based products. With the recent increase in interest in green technologies and the move away from oil, these solventogenic fermentations have again become industrially relevant. Particular interest has been shown in how clostridia break down a variety of industrial feedstocks, from cellulose to starch. Prior analysis of a protein secreted by C. saccharoperbutylacetonicum when grown in the presence of starch, revealed that it matched closely to a family of proteins called cyclodextrin glycosyltransferases (Cgt) responsible for breaking down starch into small ring-shaped polymers called cyclodextrins, a possibly novel method of starch metabolism for clostridial species. Further in-silico analysis identified a further 7 genes, encoding for possible starch degrading enzymes, transporter proteins and a putative operon regulator. The main aims of this project was to measure the expression of the genes of the starch operon when C. saccharoperbutylacetonicum was grown on different carbon sources. Expression levels were measured by qPCR and showed that the presence of starch had a significant effect on the expression of the genes of the starch operon. Further gene expression analysis carried out in a mutant strain of C. saccharoperbutylacetonicum which had a truncated version of the putative operon regulator lead to unregulated expression, no matter the carbon source suggesting that the putative regulator does indeed act on the expression of the operon. Further to the gene expression analysis, cloning and in-silico analysis was carried out to identify the function of the proteins expressed from the genes of the starch operon. Cloning efforts were focused on the three putative starch degrading proteins encoded by cgt, gdp, and aac, but efforts to clone any of the three genes into E. coli were unsuccessful. The in-silico analysis added further evidence to the role of several of the proteins, and found a possible function for the protein previously annotated as AAC, as part of a cyclodextrin degrading family of proteins called cyclodextrinase’s.Item Aquaculture site selection: A GIS-based approach to marine spatial planning in Scotland(Heriot-Watt University, 2015-05) McWhinnie, Lauren Helen; Fernandes, Professor T.; Briers, Doctor R.; Gubbins, Doctor M.; Davies, Doctor IThis thesis explores, tests and develops various methods and tools for implementing Marine Spatial Planning and aquaculture site selection within Scottish waters. Utilising geographically referenced data sets from numerous sources, a Geographical Information System (GIS) was used to map the spatial distribution of activities; their associated pressures, locations of marine environments and biological communities within Scotland’s sea area. Marine Zoning Schemes such as legislation based Multiple-Use Zoning Scheme and environmentally derived Marine Planning Frameworks have been applied and tested to support and inform the development of a new Prototype Zoning Scheme. The influence of inclusion of different data sets on zone coverage and extent has been explored with specific reference to the amount of protection the resultant zones provide to species and habitats that have significant conservation importance. Building on these zoning schemes, the application of GIS-based Multi-Criteria Analysis models has been appraised and their application investigated for both finfish cage and shellfish long-line aquaculture. This study has explored the suitability of alternative criteria and weighting configurations along with the feasibility of large sea-scale site selection models. In developing and investigating the viability of integrating these models within marine management frameworks such as zoning schemes, this study aims to inform planners, and both aid and inform decision making and management of future aquaculture developments. Together these studies contribute both practical recommendations for sustainable aquaculture development in the future and novel applications within the wider discipline of Marine Spatial Planning. They aim to contribute information to ensure both the sustainability and success of the Scottish aquaculture industry as well as the continued improvement and development of ecosystem-based marine planning and management.Item Studies towards the asymmetric synthesis of cyclochiral rotaxanes and Au(III)-oxo complexes as catalysts(Heriot-Watt University, 2015-05) O'Neill, James Alan ThomasThe work reported in this thesis consists of studies towards the asymmetric synthesis of mechanically planar chiral rotaxanes via desymmetrisation approach. It describes the synthesis of a novel macrocycle and the investigation of this macrocycle as a potential ligand in the Cadiot-Chodkiewicz and CuAAC ‘click’ reactions as part of the study towards the synthesis of asymmetric planar chiral rotaxanes. Furthermore, the use of Au(III)-oxo complexes as potential catalysts in a model hydroamination reaction are described. The thesis is divided into four chapters: Chapter one is an introduction to rotaxanes and includes an overview of the synthesis of rotaxanes and chirality in rotaxanes. Chapter two is an account of the synthesis of a novel macrocycle and details attempts to implement this macrocycle towards the synthesis of a rotaxane using the Cadiot-Chodkiewicz and CuAAC ‘click’ reactions. Chapter three describes optimisation and multi-gram scale-up of the synthetic route towards a novel C1-symmetric bi (oxazoline) macrocycle first synthesised in our group by Pauline Glen. Chapter four describes our investigation into the use of Au(III)-oxo complexes for use as catalysts in a model hydroamination reaction.Item Tissue markers of alveolar macrophage accumulations in inhaled drug development(Heriot-Watt University, 2016-07) Hildebrand, Deon Dieter; Stone, Professor VickiAlveolar macrophage accumulations in the lungs of rodents and dogs that have been exposed to inhaled new drug candidates is an important cause of attrition during preclinical drug development because it is very difficult to decide whether the accumulations are adverse or nonadverse. The expression of markers of alveolar macrophage endocytosis, alveolar macrophage activation and lung inflammation were investigated by means of reverse transcriptase-polymerase chain reaction, immunohistochemistry and in situ hybridisation in samples of formalin fixed paraffin embedded lungs from male rats. Messenger RNA levels of CD68, a marker of endocytosis, were increased 1.4 to 2.4-fold in lungs that contained alveolar macrophage accumulations. Cytoplasmic immunostaining related to the CD68 protein was increased 1.43 to 5.66-fold when the alveolar macrophage accumulations were numerous, large and associated with neutrophils and lymphocytes. In contrast, the immunostaining was not increased (range 0.67 to 1.21-fold) when only small and sparse alveolar macrophage accumulations that consisted entirely out of macrophages were present. Messenger RNA levels of resistin like molecule alpha and acidic mammalian chitinase – markers of wound healing (M2) activated macrophages – were found to be increased 3.9 to 8.2-fold and 1.8 to 2.4-fold respectively, in samples of lungs that contained alveolar macrophage accumulations. Messenger RNA levels of inducible nitric oxide synthase, a marker of classical (M1) activated macrophages was found to be increased 4.1-fold when neutrophils and lymphocytes were present amongst the accumulated alveolar macrophages. Messenger RNA levels of pro-inflammatory genes (such as E selectin) were found to be increased 2.2 to 4.4-fold in samples of lungs that contained alveolar macrophage accumulations but only when neutrophils and lymphocytes were visible amongst the accumulated macrophages in histological lung sections. Measuring the markers in FFPE lung samples can potentially help investigators discriminate adverse from nonadverse drug-induced alveolar macrophage accumulations with greater clarity and scientific rigour.Item The use of Saccharomyces cerevisiae as a model system to study the mechanism of action of chemical antioxidants(Heriot-Watt University, 2016-07) Chumnanka, Chuleeporn; Jamieson, Doctor Derek J.Butylated hydroxyanisole (BHA) is a synthetic substance commonly used as dietary antioxidant which plays an important role in protecting foods from oxidation. It has been reported that this compound caused an increase in glutathione-s-transferase specific activity, which is responsible for resistance to oxidative stress, i.e., there was some evidence that it could act as a pro-oxidant. In the present study, BHA was found to be toxic towards yeast and this was investigated further by determining its effect on the viability of a variety of yeast mutants lacking key genes required for resistance to oxidative stress. The results showed that the cell viability of the mutants was not significantly different from the wild type parental strains. This suggests that BHA toxicity was unlikely to involve reactive oxygen species (O2 - and H2O2) and might not directly involve the classical oxidant stress responses found in yeast cells. Interestingly, the pre-treatment of yeast cells with low concentrations of BHA (0.2 mM) and subsequent exposure to higher concentrations of either BHA or hydrogen peroxide (H2O2) resulted in pre-treated yeast cells becoming more resistant to both toxic levels of BHA and H2O2 than non pre-treated cells. These findings indicated that low level of BHA could induce an adaptive response to BHA and induce cross-protection against H2O2. A genetic approach was adopted to identify genes involved in this process, involving the isolation and characterisation of BHA sensitive mutants. The results demonstrated that the yeast genes TYR1, KRE6 and GPH1 play role in the cells response towards BHA.