Includes abstract. / Includes bibliographical references. / T-box genes constitute an ancient family of developmentally important transcription factors that have gained prominence in cancer biology. For example, endogenous TBX2 is overexpressed in a growing list of cancers and when ectopically overexpressed it can bypass senescence and the tetraploidy checkpoints that protect against cancer. When the current study was initiated it was unclear as to whether the endogenous overexpression of TBX2 was a cause or consequence of the oncogenic process and whether it may be a suitable anti-cancer drug target. The objectives of this study were therefore (1) to explore the role of increased TBX2 levels in melanomagenesis by assessing the effect of knocking it down in melanoma cell lines, (2) to determine the mechanism by which TBX2 is upregulated by the UV-induced DNA damage pathway in melanoma cells and (3) to verify whether TBX2 is a suitable drug target by assessing the cellular sensitivity of control and TBX2-depleted cells in response to the chemotherapeutic drug cisplatin.

Includes abstract. / Includes bibliographical references (p. 185-201). / Measurements of muscle activity derived from surface EMG electrodes are variable due to both intrinsic and extrinsic factors. The intrinsic factors are endogenous in nature (features within the body) and include muscle fiber type, muscle fiber diameter and length, the amount of tissue between muscle and electrode, and depth and location of muscle with respect to the placement of electrodes (24). These biological factors vary between subjects and cannot be controlled. The extrinsic factors are experimental variables which are influenced by the researcher and can be controlled to some extent. Examples of extrinsic factors include the location, area, orientation, shape of electrodes and the distance between electrodes (interelectrode distance). In order to measure biological variation in the EMG signal, which is important in studies where surface EMG is used to gain understanding of physiological regulation, it is important to minimise the variation caused by these factors. This is in part achieved through the appropriate method of normalisation. The isometric maximal voluntary contraction (MVC) has been used as a standardmethod of normalisation for both static and dynamic exercises. However, researchers have recently improved the methods of normalisation by developing alternative techniques for the measurement of EMG during dynamic activities. By using the same type of movement for normalisation as during the trial, experimental errors can be reduced. The appropriate method of normalisation is defined as a method that is capable of showing repeatability, reliability (low intra-subject variation) and sensitivity to changes in EMG amplitude that is due to biological change and not the contribution of experimental factors. The aim of this thesis was to critically analyse alternative methods of EMG normalisation during dynamic exercise. The data should provide possible guidelines to researchers who are planning studies involving measurement of EMG activity during cycling, running and in clinical populations. Furthermore, the thesis aimed to illustrate that decisions regarding the most appropriate method of normalisation should be based on the study design, research question (absolute muscle activity or changes in muscle pattern) and the muscles being investigated.

Includes abstract. Includes bibliographical references (leaves 172-196).

Includes bibliographical references. / Respiratory motion of the heart is a problem for high-resolution cardiac MRI. Diaphragmatic navigator gating with a 5mm acceptance window is most commonly used to address this but has an inherently low respiratory efficiency that is further compromised by respiratory drift. A novel method is presented that uses data from multiple navigators prior to the imaging segment as input for a control system to predict the diaphragm position throughout the imaging segment and correct the slice position in real time.

Includes bibliography. / Despite the fact that the chicken embryo is a model system for developmental biologists, comparatively little is known about the regulation of avian melanogenesis. There has only been one report of the characterisation of the chicken tyrosinase gene promoter, and only one full-length chicken microphthalmia cDNA (cmi9) has been identified to date.

Includes abstract. / Includes bibliographical references (p. 197-215). / The primary aim of this thesis was to identify candidate genes that may be associated with ACL ruptures, and then use a genetic association approach following a case-control study design to identify specific sequence variants (single nucleotide polymorphisms, SNPs) within these candidate genes which may predispose individuals to ACL ruptures. Candidate genes (COL1A1, COL5A1 and COL12A1) were selected based on the biological function of their encoded proteins (type I, type V and type XII collagen respectively) within the basic structural and functional unit of ligaments, namely the collagen microfibril.

Includes bibliographical references (p. 182-205). / We investigated the effects of voluntary exercise on neuroprotection after unilateral lesions with 6-hydroxydopamine. Rats were divided into runners (had access to running wheel) and non-runners (their running wheels were immobilised). Two weeks after injection of the neurotoxin, the rats were injected with apomorphine and the number of ipsilateral and contralateral rotations was counted with contralateral rotations of greater than 150 considered to represent striatal dopamine neuron destruction of 70% or above.

Includes bibliographical references. / This main purpose of this thesis was therefore to investigate whether any specific genes on the tip of the long arm of chromosome 9 were associated with Achilles tendon injuries, using a case-control study design. The specific objectives were: (i) to identify all genes located in the 9q32-q34.3 locus in close proximity to the ABO gene, that could be involved in tendon injuries (Chapter 2) and (ii) to investigate the possible association of the identified candidate genes (COL5A1 and TNC with both Achilles tendon rupture and chronic Achilles tendinopathy (Chapter 3 and 4) and (iii) finally to investigate the possible interaction of these two genes with tendon function, namely the muscle-tendon unit flexibility (chapter 5) and structure, namely the morphological changes of the Achilles tendon (Chapter 6).

Includes bibliographical references / Skeletal age is a measure of biological maturation and is based on the stages of formation of bones. As age increases, skeletal maturation progresses and the various hard tissue changes which take place are uniquely identifiable and defining to each stage of development. Age assessment using skeletal maturation is a diagnostic tool used clinically and in forensic investigations. Radiographs of the hand and wrist are frequently used to estimate age (Greulich and Pyle,1959); however studies conducted in South Africa have shown that these methods are not applicable to South Africans since the method over estimates age in the 17 - 22 year olds(Dembetembe and Morris, 2013) and both over and underestimates age in 0 - 13 year old individuals (Speed, 2012). There currently is a lack of comprehensive data and studies on the union of the major joints in South African children despite the need for population specific data in age estimations. The LODOX Statscan system, which emits low dose radiation and full body radiographs in thirteen seconds, was used to assess radiographs of1891 individuals between the ages of 6 - 24 years. Union was classified in four stages ranging from one (non-union) to stage four (complete union). Radiographs were obtained from the Red Cross War Memorial hospital and Groote Schuur hospital in Cape Town and Tygerberg and Salt River mortuaries in Cape Town as well as the Chris Hani Baragwanathand Milpark hospitals in Johannesburg. The standards developed on radiographs were later used to conduct gross analysis of skeletal material obtained from the Raymond Dart Collection. Complete union was classified as the age at which 95% of the both males and females showed stage 4 of union. Complete union of all joints in females occurs by age 21 years and 24 years in males with the iliac crest being the last epiphysis to fuse in both males and females. Ordinal logistic regression found significant differences between males and females in the stages of union and age (p < 0.05). There is however no significant differences in stage of union and age between different ethnic groups and individuals from various socio-economic status backgrounds (p > 0.05).Data for union times in South African children show that maturity in females at the elbow, hip and ankle are achieved at approximately 15 years of age followed by the knee at 16 years, wrist at 18 years, and shoulder at 20 years. The radiographically visible epiphyses the iliac crest are the last epiphyses to complete union at 21 years. Males progress through union in the same sequence with the exception that there is a two year delay in age at maturity. The elbow in males completes union at approximately 17 years followed by the hip and ankle at 18 years, knee at 19 years, wrist at 20 years, and shoulder at 21 years and finally the iliac crest at 22 years. The methodology derived on radiographs was successfully applied to gross observations of skeletal material. It therefore provides a useful diagnostic tool for use in skeletonised forensic cases in the absence of skeletal material from which to derive such standards. The current work provides an alternative to the Greulich and Pyle (1959) method and is specifically tailored toward South African children.

Hearing impairment is a chronic condition for which limited screening and diagnostic services are available in low-and-middle income countries (LMICs). In addition to the conventional medical devices existing to screen for the condition, several smartphone- and tablet-based applications have been introduced as mobile health (mHealth) solutions. This study was aimed at reviewing the set of mobile health tools available for screening for hearing loss in both developed countries and LMICs. Furthermore, to consider the suitability of the screening tools identified in the first objective for use in developing countries. The research approach adopted for this study was that of a state-of-the-art review. Relevant literature on mobile technology solutions to assess hearing loss were identified in electronic databases and reviewed. The mHealth solutions were reviewed with a focus on: countries of origin and evaluation; devices, software platforms and hardware considerations; hearing loss characteristics of recruited populations; features of the tests conducted and of the testing environment; reference methods to which the mobile application was compared; application performance; feedback from users; and cost. Eighteen available smartphone- and tablet-based applications for hearing loss screening were reviewed. Studies on these applications included participants from a variety of ages and, with and without hearing loss. A variety of testing environments were used. Studies on the applications found 11 of them to have acceptable functionality for use in screening for hearing loss. These 11 applications are also potentially suitable for use in LMICs, although they have some limitations. While these applications are not able to replace the conventional audiometer, they have potential as a first point of access for referral to conventional audiometry, and to help increase access to hearing loss tests in resource-constrained health systems.