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Repurposing DrugBank compounds as potential Plasmodium falciparum class 1a aminoacyl tRNA synthetase multi-stage pan-inhibitors with a specific focus on mitomycin
Get PDFPlasmodium falciparum aminoacyl tRNA synthetases (PfaaRSs) are potent antimalarial targets essential for proteome fidelity and overall parasite survival in every stage of the parasite's life cycle. So far, some of these proteins have been singly targeted yielding inhibitor compounds that have been limited by incidences of resistance which can be overcome via pan-inhibition strategies. Hence, herein, for the first time, we report the identification and in vitro antiplasmodial validation of Mitomycin (MMC) as a probable pan-inhibitor of class 1a (arginyl(A)-, cysteinyl(C), isoleucyl(I)-, leucyl(L), methionyl(M), and valyl(V)-) PfaaRSs which hypothetically may underlie its previously reported activity on the ribosomal RNA to inhibit protein translation and biosynthesis. We combined multiple in silico structure-based discovery strategies that first helped identify functional and druggable sites that were preferentially targeted by the compound in each of the plasmodial proteins: Ins1-Ins2 domain in Pf-ARS; anticodon binding domain in Pf-CRS; CP1-editing domain in Pf-IRS and Pf-MRS; C-terminal domain in Pf-LRS; and CP-core region in Pf-VRS. Molecular dynamics studies further revealed that MMC allosterically induced changes in the global structures of each protein. Likewise, prominent structural perturbations were caused by the compound across the functional domains of the proteins. More so, MMC induced systematic alterations in the binding of the catalytic nucleotide and amino acid substrates which culminated in the loss of key interactions with key active site residues and ultimate reduction in the nucleotide-binding affinities across all proteins, as deduced from the binding energy calculations. These altogether confirmed that MMC uniformly disrupted the structure of the target proteins and essential substrates. Further, MMC demonstrated IC50 5 μM against the Dd2 and 3D7 strains of parasite making it a good starting point for malarial drug development. We believe that findings from our study will be important in the current search for highly effective multi-stage antimalarial drugs
South Africa-Africa trade: Continental Free Trade Area
No full textSouth Africa-Africa trade was examined for 2001-2021 and results show that Africa is an important market for South Africa's manufactured products and there is ease of market access for these products; its trade with Africa is highly complementary; and it has strong trade linkages with Africa's regional groups. Current South Africa-Africa trade is a foundation South Africa could utilise to consolidate, broaden and strengthen its role in intra-Africa trade with the AfCFTA in place as more complementary trade opportunities emerge; markets open more and current trade linkages with regional groups strengthen as trade barriers are reduced further; and regional value chains and production clusters initiatives emerge as market access improves with new and dynamic comparative advantages emerging
A Modern Guide to the Informal Economy, by Colin C. Williams
Get PDFColin C. Williams’ new book, A Modern Guide to the Informal Economy, offers a timely analysis of a segment of the global workforce that has received increasing atten tion in recent years. A range of different measures suggest that, globally, the vast majority (61 per cent) of all employment is informal.1 Once thought to be exclusive to labour markets in middle- and low-income countries, the rise of platform work and the gig economy in the economies of developed countries has spurred new inter est in the subject. Similarly, the uneven effects of the pandemic and its aftermath have drawn unprecedented attention to the resultant economic and social crisis, which has disproportionately affected workers in the informal economy.2 Using the most internationally comparable definition of the informal economy as comprising all workers without legal or social protection through their employment,3 the recent pandemic and continuing economic crisis has left the bulk of the global workforce without a safety net. Such a “moment” naturally raises questions about the structure of employment, the role and reach of social protection programmes and the policy options available in countries where informal employment is the norm
Assessing the status of the Barotse floodplain fishery and the implications of Australian redclaw crayfish Cherax quadricarinatus invasion on the fishery
Get PDFInland capture fisheries play an important role of supporting livelihoods of people in developing countries. Despite their significance these fisheries are often poorly monitored resulting in them being undervalued and often missing from policy and decision-making relating to food security and water use, particularly in third world countries. The Anthropocene has given rise to increased pressure on these systems, further justifying the need for monitoring activities to determine the ecosystem service provision status and the levels of existing and emerging threats to such services. This thesis focuses on the Barotse floodplain fishery of the Upper Zambezi system and the potential implications of the recent Cherax quadricarinatus invasion on the floodplain fishery. The thesis specifically assesses the current status of the fishery (Chapter 3), invasion dynamics of C. quadricarinatus (Chapter 4), economic impact of C. quadricarinatus on the fishery (Chapter 5) and fishers’ knowledge, awareness and perception of C. quadricarinatus (Chapter 6). To evaluate the current status of the fishery (Chapter 3), fisheries dependant surveys were conducted. The study revealed a multi-gear multi-species fishery with average catch rates of 5.83 kg per fisher per day and estimated annual harvest of 3123 tonnes per annum. The decline in catch rate, low mean sizes of species harvested, change in species composition, and predominant use of illegal fishing gear compared to previous surveys, suggested further overexploitation of fishery resources. The invasive C. quadricarinatus was identified as the most dominant by-catch species and more prevalent among fishers at the invasion core and in dry season. Analysis of the invasion dynamics of C. quadricarinatus (Chapter 4) involved extensive survey of the Barotse floodplain using collapsible promar traps. The study revealed significant up and down-stream spread from the 2019 range on the floodplain. Relative abundance was higher at the invasion core compared to the invasion edge while male to female sex ratio was not different between these zones, implying both sexes were acting as dispersers. Signals of environmental filtering were not detected while density dependent spatial sorting, and hydrological variation had a strong influence on C. quadricarinatus spread. To quantify economic impact C. quadricarinatus (Chapter 5) creel surveys were conducted during wet and dry season across the invasion range. The study showed that fish damage due to crayfish was limited to gillnets at the invasion core during the dry season and equated to the monetary loss of ~ US$ 21,000 per annum. In addition, gear damage and loss of time due to crayfish was experienced for various fishing gears but most prevalent at the invasion core and more so in dry season. Assessment of fishers’ awareness, knowledge and perception (Chapter 6) involved the use of social surveys administered at the invasion core. This component revealed that most of the respondents were aware of, but not knowledgeable about C. quadricarinatus. Respondents were not aware of any management information relating to C. quadricarinatus and consequently did not follow any management practices. The respondents were supportive of management interventions due to their perceived threat of C. quadricarinatus to the fishery. Age, education, and residence of respondents significantly influenced knowledge and perceptions of C. quadricarinatus. Findings from this study have important implications for the conservation of floodplain wetlands as it informs policy makers to put in place measures that address both overexploitation and aquatic invasive species dynamics to better facilitate sustainability of fisheries and conservation of biodiversity.Thesis (PhD) -- Faculty of Science, Zoology and Entomology, 202
A mechanistic and trait-based approach to investigating macroinvertebrates distribution and exposure to microplastics in riverine systems
Get PDFMicroplastics in rivers pose an ecological risk. Hydraulic biotopes form distinct flow patches that vary longitudinally along the river, potentially influencing the transport dynamics of microplastics. Macroinvertebrates exhibit adaptations to different hydraulic biotopes through their unique traits. These traits can mediate their exposure to microplastics, thereby imposing selective pressures on these organisms. Different taxa often demonstrate preferences for specific hydraulic biotopes characterized by distinct flow regimes. Understanding the transport dynamics of microplastics mediated by hydraulic biotopes and the potential exposure of macroinvertebrates at the hydraulic biotope scale is important for determining the fate of riverine microplastics and detecting species at risk. Both empirical and theoretical studies have highlighted the interconnectedness of hydrology, geomorphology, and microplastic transport in rivers, yet, there remains a gap in understanding how a hydro-geomorphological approach could enhance the understanding of the microplastic transport process. Little is known about the role of traits in driving macroinvertebrate exposure to microplastics at a scale relevant to ecological dynamics. This study addressed these gaps by applying a hydro-geomorphological approach to investigate the distribution of microplastics at the hydraulic biotope scale and assessed the potential exposure of macroinvertebrates using a trait-based approach. This study also explored the relationship between microplastic abundance and selected water physicochemical properties, as well as the influence of adjacent land use types. By integrating these aspects the research provided a comprehensive understanding of microplastics dynamics in river systems, shedding light on both environmental factors shaping their distribution and the potential impacts on aquatic organisms. The study was conducted over the wet and dry seasons (October 2021 – July 2022) at 10 sites located in the upper, middle, and lower reaches of the Swartkops and Buffalo River systems in the Eastern Cape Province of South Africa. The hydraulic biotopes (i.e., pools, runs, riffles) were grouped into two conceptualised forms, namely, sink and flush hydraulic zones and were characterized by hydraulic indices such as the Froude number and the Reynolds number. The flush hydraulic zone represents hydraulic biotopes where microplastics can potentially be remobilized quickly into suspension, and the sink represents biotopes where microplastics can potentially accumulate and remobilisation is far slower. Fast-to-moderate flowing hydraulic biotopes were conceptualised as microplastics flush zones while slow-flowing to still biotopes as microplastic sink zones. Samples were collected at different depths in each hydraulic zone to quantify suspended and settled forms of microplastics. Microplastics targeted in this study ranged in size from 0.063 mm to less than 5 mm. Classification was achieved through microscopic observation, and confirmation via Fourier Transform Infrared Spectroscopy (FTIR-ATR) was conducted for samples ranging from 0.5 mm to less than 5 mm. At the site level, settled microplastics showed statistically significant spatial and temporal variations between the sites, and between the seasons (P < 0.05). The suspended microplastic varied only spatially. Fibres and fragments were the dominant microplastic shape, while polyethylene and polypropylene were the dominant microplastic polymers. Suspended microplastics showed statistically significant variation between urban land cover and other land cover categories (industrial, agricultural, rural, and natural land cover). Microplastics abundance was associated with high levels of turbidity, total suspended solids, total inorganic nitrogen, higher temperatures and increasing electrical conductivity. At the hydraulic biotope scale, the mean occurrence of suspended microplastics (1.76 ± 1.44 items/L; mean + SD) in the flush hydraulic zone was higher than that in the sink zone (1.54 ± 1.46 items/L), while settled microplastics were more abundant in the sink hydraulic zone (1.82 ± 1.98 items/L) than the flush hydraulic zone (1.32 ± 1.49 items/L). This observation was in line with the prediction in this study. The mean suspended and settled microplastics concentrations were higher during the wet season across the flush and sink hydraulic zones than in the dry season. Global multivariate analysis of variance (MANOVA) and two-way analysis of variance (ANOVA) revealed significant spatial and temporal variations in settled microplastics abundances between the flush and sink hydraulic zones. The results indicated that geomorphologically defined units such as riffles and moderate to fast runs (flush) generally contained lower amounts of settled microplastics compared to pools and backwaters (sink). However, this distinction between the flush and sink microplastic zones was observed only for settled microplastics and not for suspended microplastics. Suspended and settled microplastics showed a statistically significant relationship with the Froude number index. The generalised additive model indicated that settled microplastics abundance distribution decreased significantly with increasing Froude number value in the flush zone. Suspended microplastics decreased at low Froude number values and showed an increasing trend at higher Froude number values of about 0.75. The results indicate the usefulness of the hydraulic biotope scale microplastic monitoring approach in detecting microplastic hotspots and explaining variations in microplastics abundances driven by instream hydraulics. Four traits and ecological preferences of macroinvertebrates including body size, gill type, feeding habit, and velocity preferences were selected and resolved into 17 trait attributes. The sink hydraulic zones such as pools were indicated to favour exposure to and ingestion of microplastics compared to the flush zones such as riffles and fast runs. Large body size macroinvertebrates were associated with the sink zone. Taxa with a very small body size had a higher likelihood for microplastics ingestion than taxa with other body sizes. Collectorgathering macroinvertebrates taxa that have operculate gills with small body sizes were more prone to exposure to microplastics in hydraulic biotopes with slow to very slow velocities. Fibres were the most abundant plastic ingested by macroinvertebrates preferring the flush zone while fibres and fragments were mostly ingested by those preferring the sink zones. The binomial logistic model revealed a highly significant result for the likelihood of operculate gill shape to clog in the sink hydraulic zone. The result of the binomial logistic regression indicates the usefulness of the trait-based approach for predicting exposure to microplastics. Overall, the study reveals the influences of hydro-geomorphological features on the transport dynamics of microplastics and the usefulness of the trait-based approach in the ecological study of microplastics in riverine systems.Thesis (PhD) -- Faculty of Science, Institute for Water Research, 202
Selective and sensitive electrochemical detection of the Human Epidermal Growth Receptor 2 breast cancer biomarker, using Co (II) phthalocyanine-nanoparticle based platforms
Get PDFBreast cancer is the world’s leading cause of cancer related deaths in women worldwide. The main reason lies in its late detection, mostly in the metastatic stage resulting in poor after-therapy prognosis, despite advances in methods of diagnosis and therapy. The reason for late-stage detection, is because breast cancer like any other cancers is asymptomatic in its early stages. Significant and characterizable features present in the later stages. Furthermore, conventional methods for breast cancer detection are more useful in the identification of the phenotypic features of cancer cells that arise at a later stage of the disease. Another issue with conventional methods where cancer diagnosis is concerned is that they tend to be specialist-dependent, time consuming and costly. Thus, easy, fast and inexpensive detection methods need to be developed urgently. Biomarker-based cancer diagnosis has emerged as one of the most promising strategies for early diagnosis, monitoring disease progression, and subsequent cancer treatment. This thesis focuses on the design and development of novel electrochemical biosensor platforms towards the low cost, efficient, sensitive and simple detection of early-stage breast cancer biomarker, human epidermal growth factor 2 (HER2). The electrochemical method is preferred because of its moderate cost, rapid response, ease of operation, readily quantifiable signal as well as high sensitivity and selectivity with lower detection limits. This thesis reports on two strategies towards signal amplification and sensitive detection of HER2, namely signal based amplification and target-based amplification. The former focuses on electrode or transducer modification techniques for improved signal to noise ratio. In which case; novel nanocomposites of phthalocyanines, graphene quantum dots, gold nanoparticles and cerium oxide nanoparticles are used for electrode modification for signal amplification and biorecognition element immobilization. The biorecognition elements of choice, are an aptamer and antibody known to be specific to the HER2 antigen for an enhanced sensor sensitivity and specificity. The second strategy focuses on increasing the number of detectable targets on the electrode surface towards enhanced sensitivity, precision and sensor accuracy. In which case; the performance of the aptamer and the antibody as recognition elements was explored. Furthermore, the effect of arrangement of these recognition elements on the electrode surface is investigated and reported upon. The strategies covered in this thesis are expected to result in novel biosensor platforms that can detect the HER2 biomarker with high precision, reproducibility, sensitivity and stability; towards low cost and effective early-stage breast cancer diagnostic tools.Thesis (PhD) -- Faculty of Science, Chemistry, 202
Meerkat polarimetric observations of Pictor A
Get PDFPictor A is one of the brightest and closest radio galaxies in the Southern Hemisphere, offering a unique opportunity for in-depth studies of the astrophysics of radio galaxies and their interactions with their environments. Many multi-wavelength studies of this source have been done. However, the most comprehensive radio frequency study of Pictor A’s morphological components was conducted by Perley et al. (1997) using the Very Large Array (VLA) located in the Northern Hemisphere. To date, that work remains the most detailed study of Pictor A. In this thesis, we conducted a spectropolarimetric study of Pictor A using new L-band data obtained in 2019 from the high-sensitivity MeerKAT telescope, which provides the deepest and most sensitive data of this source at a continuous and finely sampled frequency coverage in the L-band. Thus, due to Pictor A’s proximity, high luminosity, and the MeerKAT’s high sensitivity, the data delivers a unique dataset for our study of the magnetic field structure of Pictor A and allows for a detailed study of the source’s morphological structures. We presented the steps taken during our calibration and data reduction, leading to polarimetryready images. During the first phase of calibration, excision of data corrupted by instrumental effects and radio frequency interference (RFI) resulted in only 50% useable data. Pictor A’s exceptionally bright western hotspot introduced significant artefacts in our images, mitigated in the second calibration phase through direction-dependent calibration. The calibrated data resulted in a multi-frequency synthesis (MFS) Stokes I image of Pictor A at 7.5′′ in resolution with an offsource RMS noise of ∼22 Jy/beam. The off-source noise in the Stokes Q and U sub-band images ranged between 95 – 278 Jy/beam and 41 – 233 Jy/beam, respectively. Additionally, we briefly highlighted the effects of RFI in the L-band on polarimetry, particularly the considerable loss of 2 coverage of ∼50%. All the calibration recipes used for this work were made available in this thesis. Using Pictor A’s data as a testbed, we introduced a Python-based tool, Smops, developed during the calibration stages of our work. Smops was designed for an intermediate post-processing step. It interpolates input sub-band model FITS images (such as those produced by WSClean) into finely channelized sub-band model FITS images, thereby generating model images at a higher frequency resolution. Smops reduces the need to generate model images with numerous sub-bands, which is computationally intensive and time-consuming. A higher resolution in frequency of the models facilitates more efficient model subtraction during self-calibration. We then presented the total intensity features of Pictor A, which the calibrated data reveals. We confirmed the presence of Pictor A’s radio jet extending from its core to the western hotspot. Notably, this feature, faint and barely visible in previous radio images, is now distinctly observed. The counterjet remains undetectable. Furthermore, we demonstrated the coexistence of radio emission, which is expected to align with previously observed X-ray diffuse emission. This observation confirmed the inverse Compton origin of Pictor A’s lobe emission. Employing the RM-synthesis technique for the spectropolarimetric study of Pictor A, we identified a relatively consistent rotation measure (RM) across its lobes, with an average RM of 48.06 ± 10.19 rad m−2 for the entire source. However, the eastern lobe displayed a wider RM dispersion than the western lobe. Moreover, our study affirmed the depolarisation asymmetry previously observed between the western and eastern lobes of Pictor A, where the eastern lobe exhibited significantly more depolarisation than its western counterpart. Most lines-of-sight across Pictor A displayed single-peaked Faraday spectra, indicating a single Faraday rotating screen. However, we also noted that several lines-of-sight (∼23%) showed more than one Faraday peak. An investigation into the ii possible causes of the multiple observed peaks using QU-fitting suggested that there is a possibility of a Faraday thick structure or multiple Faraday components along these paths. Furthermore, we estimated a Galactic RM contribution towards Pictor A of 23.57 ± 10.87 rad m−2. We concluded that while our Galaxy may contribute to the mean RM for this source, it cannot explain smallscale fluctuations, which suggests that some fraction of the observed rotation measures could result from some inter-galactic medium, X-ray gas near the shock boundary region (the sheath), or other unknown intervening material. We introduced Scrappy, a Python-based tool tailored for processing lines-of-sight data. Scrappy yields RM-synthesis diagnostic data products such as the data associated with each line-of-sight, and their corresponding plots in -space (e.g. cleaned and dirty Faraday spectra and RMTF), and 2-space (e.g. the fractional polarisation, and Stokes Q and U ). Scrappy further avails a Bash-based pipeline, showrunner.sh, that processes input sub-band Stokes images, automatically selects usable sub-bands, stacks images into Stokes cubes, generates lines-of-sight, processes their corresponding data, and produces diagnostic plots. Additionally, it creates per-pixel maps of fractional polarisation, RM, polarisation angle, peak FDF, and linear polarised intensity. The pipeline ensures reproducibility. To visualise the diagnostic plots from Scrappy, we developed PolarVis, a simple web-based tool that enables the visualisation of diagnostic plots associated with each available line-of-sight, thus facilitating the quick exploration of interesting lines-of-sight in regions across this source. This tool facilitates the visualisation of polarisation behaviour for specific lines-of-sight, enabling quick identification of interesting regions of the source. Furthermore, its interactivity promotes the exploration of line-of-sight data. Availing data to the public with this tool permits validation or comparison of results from varying techniques, hence fostering a sense of transparency. As a result, the 2389 lines-of-sight of Pictor A are presented using PolarVis and are available at https://pica.ratt.center.Thesis (PhD) -- Faculty of Science, Physics and Electronics, 202
Experimental and theoretical studies in the elucidation of chemical and biochemical reaction mechanisms
Get PDFAccess restricted. Exected release in 2026.Thesis (PhD) -- Faculty of Science, Chemistry, 202
Metal–organic framework-based heterogeneous catalysts with tailored active sites for precise oxidative transformations
No full textAccess restricted. Exected release in 2025.Thesis (PhD) -- Faculty of Science, Chemistry, 202
Ukuma njenge ndoda: the making of Xhosa masculinities in Mthatha, Eastern Cape
Get PDFThis study examines how young men construct their masculine identities in daily life through the collection of activities that happen throughout young men's lives in Mthatha, Eastern Cape. The aim of the research is to examine how black men construct their identity as men. It seeks to examine the everyday ways in which young men speak of their masculinity, how they understand themselves in relation to women and the causes of gender-based and sexual violence in South Africa. The study conceptualises Xhosa masculinities and manhood within the framework of masculinist violence and the state. It demonstrates the intersection of manhood violence and the state within the discipline of international relations which is characterised by ideas of state security and war. Interviews with Xhosa men in Mthatha illuminated that boys are raised to be men who stand, articulated as ukuma njenge ndoda (standing up as a man), for themselves, family and community. Ukuma operates as an assertion and protection of self, a demonstration of independence and being self-sustaining. It importantly speaks to the gendered division of labour where over and above standing up for oneself, it is a man’s duty and responsibility “ukumela izinto zekhaya” – to stand up for his home and family. This thesis shows that the different forms that ukuma carry with them expectations of dominance and control or at least maintain the appearance of it. Ultimately, the concept of ukuma serves as a way to legitimise the use of force or violence in certain instances where men feel that an act of violence constitutes ukuzimela (standing up for himself) or ukumela ikhaya (standing up for his family). The masculinising of this duty implicates not only the men it is bestowed upon the women and children who are the ones supposedly protected and provided for.Thesis (MSocSci) -- Faculty of Humanities, Political and International Studies, 202