https://hdl.handle.net/10646/769 2026-04-09T17:13:47Z https://hdl.handle.net/10646/4760 Title: Chemistry of Phorbol Ester Toxicity: A Computer Modelling Approach Authors: Wakandigara, ALbert Abstract: Phorbol esters are phytochemicals found in the Euphorbiaceae family, as the prime factors of toxicity in those plants. However, their degrees of toxicity vary from one compound to another, despite having closely similar structures. The aim of this research project was to determine toxicity characteristics, reactivity and chemical detoxification methods for phorbol esters, using computer modelling. Chemical stability was evaluated by calculating single-point energy and optimization, with the use of Density Functional Theory. Prediction of sites of metabolism and intrinsic reactivity was done to ascertain biological stabilities of the substances. Selected phorbol esters and diacylglycerol were modelled by docking the ligands onto the binding site of protein kinase C- and analyzing the ligand-protein interactions, as well as carrying out bond rotation studies. However, the availability of only one computationally-prepared, protein-ligand complex in literature was a major limitation, as other phorbol-ester targets could not be successfully studied. Reactions between phorbol esters and a chosen detoxifying reagent were carried out using quantum mechanical calculations, to assess feasibility. Findings from the study revealed that 12,13-phorbol esters are chemically more reactive, but biologically more stable than 13,16-phorbol esters. Although more toxic, the 12,13-phorbol esters would be easier to detoxify using chemical reagents than 13,16-phorbol esters. The toxicity of a phorbol ester is influenced by its ability to bind to the target protein, provide a hydrophobic cover on the binding site and its resistance to hydrolyze the ester linkages. Jatropha phorbol esters were found to be too big to fit into the binding pocket of the target protein under study and are predicted to interact with other phorbol-ester targets, by the same mechanism. It can be concluded that computer modelling is an effective tool in determining the toxicity factors, stability and detoxification mechanisms of phorbol esters. 2020-01-01T00:00:00Z https://hdl.handle.net/10646/4759 Title: Genetic analysis of 27 Y-Chromosome short tandem repeat (Y-STR) Loci of the Zimbabwean shona ethnic group Authors: Shonhai, Mandipa Abstract: Population genetic data about modern DNA profiles, specifically for Zimbabweans, was almost non-existent aside from that of 55 individuals’ DNA profiles contributed on the YHRD international database, under accession number YA003884. The aim of this research was to bridge the gap by the addition of this type of data for the Shona ethnic group from Zimbabwe. From 373 voluntary participants located in Harare province initially recruited under this research study, only 200 unrelated Zimbabwean males were considered for genetic population data due to the limitation of the analysis kit used. Epithelial cell samples from the inner side of the participants’ cheeks were taken and processed to produce each individuals Y-chromosomal DNA profile. Thirty-six of the same type of samples known as buccal swabs were utilised for a separate pilot study analysing related Zimbabwean Shona males. A 5-dye SureID® 27Y Human STR Identification Kit was used to perform multiplex polymerase chain reactions (PCR) and generate these Y-chromosomal DNA profiles for each participant from the unrelated and related Zimbabwean Shona male studies. This kit targets markers DYS456, DYS576, DYS570, DYS481, DYF387S1, DYS627, DYS393, DYS391, DYS390, DYS635, DYS449, DYS533, DYS438, DYS389I, DYS448, DYS389II, DYS19, GATA-H4, DYS518, DYS458, DYS460, DYS437, DYS439, DYS392, and DYS385, similar to the Yfiler® Plus Amplification Kit, another popular kit used to generate Y-chromosomal DNA profiles. Under the unrelated males’ genetic analysis, a total of 161 Y-chromosomal DNA profiles were generated with the PowerPlex® Y system which looks at 12 out of the 25 above markers, whereas 159 were generated for the Yfiler® Plus system (targets all 25 marker). The ratio of the number of unique DNA profiles to the total number of DNA profiles observed known as the Haplotype Discrimination Capacity (DC) with the Yfiler® Plus system was determined to be 0.9686. While the Genetic Diversity (GD) or variation in the genetic composition of the targeted marker ranged from 0.03748 at DYS392 with the least, to 0.867239 at DYS449 with the highest. One DNA profile or haplotype contained the triallelic pattern 37, 38, and 39 at DYF387S1. One marker, DYS448 was blank (had a null allele) in nine of the 159 DNA profiles, while microvariant alleles (alleles with decimal points) were seen in 13 of these DNA profiles. Pairwise genetic distances between this study population compared with data sets of 22 reference African populations as well as 51 reference non-African populations’ data sets showed significant genetic variation with the Shona population and each reference population. For the preliminary investigation of the individualizing capacity of the SureID® 27Y Human STR Identification Kit with Shona male brother pairs, 36Y-chromosomal DNA profiles were generated with the same procedure as for unrelated males. Of the 18 brother pairs analysed, 22.2% were distinguishable from each other at one maker, either marker DYS481, DYS393, DYS458 or DYS518. Variation at makers DYS518 and DYS481 could be explained by previously reported high genetic diversity for Shona unrelated males. Whereas, variation at makers DYS393 and DYS458 could be explained by their relatively smaller PCR products which resulted in detectable small changes in the DNA profiles. In addition, an identical DNA profile was reported for four brother pairs (P14, P15, P17 and P18). The shared DNA profile observed suggested relatedness probably via common ancestors. Brother pair P17 and P18 shared the same totems or clan “Moyo” while P15 with the “Shava” totem might be explained by the common ancestry from the “Mbire” lineage. Taken as a whole, the findings from this research provided much needed insight on the DNA profiles observed for Zimbabweans of Shona origin and subsequently gave information on this population’s genetics. It provided statistical parameters based on the unrelated males which are crucial for proper statistical calculations in human identification work which looks at Shona males. While it also highlighted the possible limitations and strengths of the SureID® 27Y Human STR Identification Kit when used for human identification which may involve related Shona males. 2021-01-01T00:00:00Z https://hdl.handle.net/10646/4758 Title: Differentiations in post-colonial urban spatial planning in Zimbabwe and Zambia Authors: Chigudu, Andrew Abstract: This study investigates and compares the colonial spatial planning legacies of Zimbabwe and Zambia. It examines how and why the legacies of two countries with a seemingly common colonial background would produce different developmental outcomes. The research’s ultimate objective is that of proposing a sustainable framework and guidelines for addressing the spatial planning problems in urban areas of both countries. Zimbabwe and Zambia were chosen as the foci of the study since they demonstrate the problem of inherited British spatial planning legislation and urban sprawl in Southern Africa. The research employed a mixed methods approach involving several case studies of local authorities in Zimbabwe and Zambia. The thesis obtained data from 2842 (1424 in Zimbabwe and 1418 in Zambia) questionnaires, 65 key informant interviews, 10 focus group discussions, observations and extensive documents reviews were analysed. Spatial differentiations in both countries were elaborated through indicators of the adopted comparative framework. The spatial planning system inherited from the British colonialists does little to address urban challenges in Zimbabwe and Zambia. This spatial planning legislation was designed under the assumption that the population in towns and cities would always be controlled. However, post-independence rural to urban migration has increased at an alarming rate, leading to a corresponding upsurge in urbanisation of major cities. Urbanisation has resulted in a system overload and poor service provision, with demand exceeding supply in Zimbabwe and Zambia. Both countries face urban development challenges, including urban land management, acute housing shortage, economic and political constraints, aging urban infrastructure, increased corruption and lack of transparency in the management of funds by local authorities. The Zambian government has begun to tackle urban transport problems in the capital city through shopping mall development, traffic safety measures and investment in an advanced road network. Zimbabwe still follows the rigid master planning approach, while Zambia has migrated to the flexible and sustainable integrated development planning approach. The research put forth the contribution that legislation, such as the Housing Act in Zambia played a major role in the provision of low-income housing and regularisation of informal settlements. The other contribution the research made is that urban challenges vary in terms of local context and dynamics exist in managing them. Urbanisation problems could be effectively controlled if local planning authorities in both countries adopt appropriate, flexible and sustainable spatial planning systems. The study recommends the adoption of a sustainable framework to guide spatial planning and urban development. Finally, the study recommends further research into resilient cities, sustainable urban infrastructure maintenance and financing. 2021-01-01T00:00:00Z https://hdl.handle.net/10646/4721 Title: In vivo toxicological study of aqueous extracts of Vitex payos fruits Authors: Dube, Felicia Nonsikelelo Abstract: The plant Vitex payos is used in folk medicine to treat several ailments. Despite Vitex payos’, ethno medicinal benefits, very few studies have described the fruits’ potential toxicity. The aim of the present study was to evaluate the in vivo acute and subchronic toxicity of aqueous extracts of Vitex payos fruits which grow in Zimbabwe on Sprague Dawley rats. Aqueous extraction of Vitex payos fruits was performed by using standard routine methods. The extract administered at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the treated animals during the 14-day observation period. Therefore, the Lethal dose 50% of Vitex payos was estimated to be more than 5000 mg/kg. In the, 90 day repeated dose oral toxicity study, twenty (20) adult Sprague Dawley rats were uniformly divided into four groups of 5 rats each. Group 1 served as a control while groups 2, 3 and 4 were respectively orally administered with 100 mg/kg body weight, 400 mg/kg body weight and 800 mg/kg body weight of the Vitex payos aqueous extract daily. The results revealed no significant difference in food and water consumption, body weight change and biochemical parameters, compared to the control group which received only distilled water. Histopathology examinations of the liver and kidney did not reveal morphological alteration. Analysis of these results with the information of signs, health monitoring and behaviour, could lead to the conclusion that the long-term oral administration of Vitex payos aqueous extract for 90 days does not cause sub chronic toxicity. 2020-08-01T00:00:00Z