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Oxygen uptake ( O2) kinetics determine the magnitude of the O2 deficit and the degree of metabolic perturbation and is considered to be an important determinant of exercise tolerance; however, there is limited empirical evidence to demonstrate that O2 kinetics is a direct determinant of exercise tolerance. The purpose of this thesis was to investigate O2 kinetics as a determinant of exercise tolerance and to consider its potential interaction with the maximum O2 ( O2max) and the W′ (the curvature constant of the hyperbolic power-duration relationship) in setting the tolerable duration of exercise. Recreationally-active adult humans volunteered to participate in the investigations presented in this thesis. Pulmonary O2 kinetics was assessed on a breath-by-breath basis and exercise tolerance was assessed by a time-to-exhaustion trial, with exhaustion taken as the inability to maintain the required cadence. A period of repeated sprint training (RST) resulted in faster phase II O2 kinetics (Pre: 29 ± 5, Post: 23 ± 5 s), a reduced O2 slow component (Pre: 0.52 ± 0.19, Post: 0.40 ± 0.17 L•min-1), an increased O2max (Pre: 3.06 ± 0.62, Post: 3.29 ± 0.77 L•min-1) and a 53% improvement in severe exercise tolerance. A reduced O2 slow component and enhanced exercise tolerance was also observed following inspiratory muscle training (Pre: 0.60 ± 0.20, Post: 0.53 ± 0.24 L•min-1; Pre: 765 ± 249, Post: 1061 ± 304 s, respectively), L-arginine (ARG) administration (Placebo: 0.76 ± 0.29 L•min-1 vs. ARG: 0.58 ± 0.23; Placebo: 562 ± 145 s vs. ARG: 707 ± 232 s, respectively) and dietary nitrate supplementation administered as nitrate-rich beetroot juice (BR) (Placebo: 0.74 ± 0.24 vs. BR: 0.57 ± 0.20 L•min-1; Placebo: 583 ± 145 s vs. BR: 675 ± 203, respectively). However, compared to a control condition without prior exercise, the completion of a prior exercise bout at 70% Δ (70% of the difference between the work rate at the gas exchange threshold [GET] and the work rate at the O2max + the work rate at the GET) with 3 minutes recovery (70-3-80) speeded overall O2 kinetics by 41% (Control: 88 ± 22 s, 70-3-80: 52 ± 13 s), but impaired exercise tolerance by 16% (Control: 437 ± 79 s, 70-3-80: 368 ± 48 s) during a subsequent exercise bout. When the recovery duration was extended to 20 minutes (70-20-80) to allow a more complete replenishment of the W′, overall kinetics was speeded to a lesser extent (by 23%; 70-20-80: 68 ± 19 s) whereas exercise performance was enhanced by 15% (70-20-80: 567 ± 125 s) compared to the control condition. In addition, the faster O2 kinetics observed when exercise was initiated with a fast start (FS; 35 ± 6 s), compared to an even start (ES; 41 ± 10 s) and slow start (SS; 55 ± 14 s) pacing strategy, allowed the achievement of O2max in a 3 minute trial and exercise performance was enhanced. Exercise performance was unaffected in a 6 minute trial with a FS, despite faster O2 kinetics, as the O2max was attained in all the variously paced trials. Therefore, the results of this thesis demonstrate that changes in exercise performance cannot be accounted for, purely, by changes in O2 kinetics. Instead, enhanced exercise performance appears to be contingent on the interaction between the factors underpinning O2 kinetics, the O2max and the W′, in support of the proposed ‘triad model’ of exercise performance.

In agriculture nitrogen fixation by rhizobial inocula is an environmentally and economically beneficial alternative to synthetic fertilization. The effectiveness of rhizobial inocula can be limited by the inability of inoculum strains to compete with indigenous strains for nodule occupancy. Sinorhizobium meliloti fixes nitrogen in a complex symbiotic relationship with legume hosts including the agriculturally important forage Medicago sativa and the model legume Medicago truncatula. The ability to utilize organic compounds has emerged as an important trait for competitiveness for nodule occupancy in S. meliloti and other rhizobia. This thesis describes the use of bacterial genetics to characterize two carbon metabolism loci in S. meliloti. A genetic locus for erythritol catabolism was characterized and shown to encode an ABC transporter that is required for the catabolism of erythritol, adonitol and L-arabitol, as well as the genes for the catabolism of these three polyols. The ability to utilize erythritol was not necessary for the ability to compete for nodule occupancy in S. meliloti, in contrast to Rhizobium leguminosarum. A genetic locus that encodes components of the De Ley-Doudoroff pathway of galactose catabolism was identified and also characterized. The inability to catabolize galactose resulted in an increased ability to compete for nodule occupancy in S. meliloti. Evidence is presented that is consistent with the hypothesis that increased competitiveness resulted from enhanced production of the symbiotic exopolysaccharide succinoglycan. Inferences are drawn that contribute to the broader understanding of rhizobium-legume symbiosis. / October 2014

Pharmacogenetics involves research into the hereditary basis for the different responses of individuals to drugs or other environmental pollutants. Several functional genetic polymorphisms of drug metabolising enzymes, transporters, receptors and other drug targets have been identified and characterised and these polymorphisms may be responsible for interethnic differences in drug disposition and disease risk. Few studies have focussed on ethnic African populations. Several genes that have known genetic polymorphism and have clinical implications for disease risk and/or treatment of patients were evaluated in a sample of the Ghanaian (West African) population. Catechol-O-methyltransferase (COMT) catalyses the 0-methylation of neurotransmitters, catechol hormones and drugs such as levodopa and methyldopa. Ethnic differences in COMT activity have been observed in several populations. Previous studies suggest that the homozygous low activity allele (COMT*L) is less common in individuals of African origin than Caucasians. COMT genotyping was performed using a mini-sequencing method in 195 healthy Ghanaians. The frequency of the homozygous low activity allele was 6%. In Caucasians it is 31%. This study provides confirmation that the low activity COMT allele is less common in individuals of African origin. This finding may be important clinically with regards to the treatment of many neuropsychiatric disorders and in the pathophysiology of various human disorders including oestrogen-induced cancers, Parkinson's disease, depression and hypertension. This thesis aimed to determine the allele frequency of therapeutically important genetic polymorphisms in an African (Ghanaian) population. The data was then compared to other ethnic populations. The marked racial and ethnic differences in the frequency of functional polymorphisms in these drug- and xenobiotic-metabolising enzymes, transporters, receptors and other drug targets shows that ethnic origin needs to be considered in studies aimed at discovering whether specific genotypes or phenotypes are associated with disease risk or drug toxicity. Genotyping prior to treatment may be essential, as 95% of the Ghanaian subjects genotyped had between one and four mutations in the therapeutically important genes analysed. Genotyping assays specific for predominant mutant alleles should be used in different ethnic groups.

Growth, feeding and metabolism in juvenile Atlantic salmon Salmo salar L. Growth, feeding and metabolism were studied during the juvenile growth phase of Atlantic salmon. Comparisons were made between the faster and slower growing members of sibling populations which formed the upper and lower modes of a bimodal growth distribution. Several new techniques were developed in order to investigate these parameters in small fish. Specific growth rates of marked individuals within the bimodal distribution followed the same pattern of development as the whole population, and appeared to be more closely related to changes in daylength than ambient water temperature. Morphometric assessment of the growth of the swimming musculature showed that both processes of cell enlargement (hypertrophy) and cellular proliferation (hyperplasia) were important. The relative importance of the two processes was dependent on developmental stage and season, although hyperplasia appeared to be more a characteristic of rapid growth than hypertrophy. Histochemical studies demonstrated the presence of "red", "white", and between them a diffuse band of "pink" muscle which appeared to become less evident during the freshwater growth period. Modal differences in food intake were found between October and March, with the upper mode fish feeding optimally whilst the lower mode fish fed at only maintenance levels. Although no differences were found in food turnover rate, upper mode fish demonstrated an elevated temperature specific food intake and gross conversion efficiency. Photoperiod was an important influence on feeding, affecting both the daily feeding pattern, which was suppressed in darkness; and evacuation rate, which was more rapid for fish experiencing an increasing rather than decreasing photoperiod. Upper mode fish and smolts had higher resting rates of oxygen consumption than lower mode fish at two of the experimental temperatures used. Smolts had larger gills than either modal group, although no differences were found between fish in the upper and lower modes. However, upper mode fish had larger hearts than those measured in the lower mode. The higher levels of metabolism usually associated with smolting appeared to be a normal characteristic of the upper growth mode. The parameters studied are discussed in relation to the energy budget, and it is concluded that the two growth modes comprise two distinct "physiological populations" within the sibling group. Photoperiod is considered to be a primary influence on growth, and it is suggested that differential responses to seasonal and daily changes in photoperiod by individuals may account for both the development of bimodality, and provide the means (through an increased daily and seasonal feeding opportunity) by which higher growth rates are sustained by the upper mode fish.

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