A reflection on the process of research and writing on human rights violations in Venda

Paper presented at the Wits History Workshop: The TRC; Commissioning the Past, 11-14 June, 199

An implantable nano-enabled bio-robotic intracranial device for targeted and prolonged drug delivery

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the degree of Doctor of PhilosophyAlzheimer’s disease (AD) is the most prevalent and progressive neurodegenerative disorder (ND). It is characterized by a progressive decline of cognitive function, complete loss of memory, deterioration of visual capacity and the inability to function independently. According to the World Health Organization (WHO) it is estimated that about 26 million people suffer with AD worldwide. Although the etiology of AD is not fully understood, the aggregation of β-amyloidal (A) peptides that are associated with the formation of extracellular neurotoxin senile plaques and neurofibrillary tangles comprising hyperphosphorylated tau proteins have been recognized as the primary constituents that play a crucial role in AD. Several potential neurotherapeutic agents that can improve the management of AD such as metal chelators and alkaloid drugs have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Metal chelators [e.g. histidine, Ethylenediaminetetraacetic acid (EDTA) and zinc acetate (ZnAc)] are the main therapy used for modulating Aβ peptide aggregation with biological metals (such as zinc and copper ions) which is associated with promoting neurotoxicity in AD. While alkaloid drugs, such as donepezil, galantamine and rivastigmine, are used to inhibit the enzyme acetylcholinesterase (AChE); memantine is used to block the N-methyl-D-aspartate (NMDA) receptors associated with pathological activation. Despite the availability of these indispensable drugs, the clinical utility of these drugs is hampered by their poor retention and difficulty in bypassing the highly restrictive Blood Brain Barrier (BBB). Therefore this study aimed at developing novel nanoliposomes (NLPs) surface-engineered with chelating and synthetic peptides that are capable of crossing the BBB thus improving delivery efficacy and modulating the extracellular neurotoxicity associated with β-Amyloid aggregates of AD. Furthermore, since this system was designed for a chronic condition, a temporary depot-based polymeric system was integrated for further enhancement of the liposomal half-life, storage and prolonged drug delivery over a period of 50 days. The surface-engineered NLPs produced were spherical in shape, 100-149±28nm ~ size, with a zeta potential range of -9.59 to -37.3mV and a polydispersity index (PdI) of 0.02-0.2. A Box-Behnken experimental design was employed for maximizing the ligand coupling efficiency (40-78%) and drug entrapment efficiency (DEE) that ranged from 42-79%. The optimized peptide-based ligand NLP formulation showed sustained drug release (30% of drug released within 48 hours). Chelating ligands on the surface of NLPs showed 50-68% modulation of neurotoxicity on PC12 neuronal cells induced by ZnAβ (1-42) or CuAβ (1-42) aggregates. When drug-loaded functionalized NLPs were embedded within the temporal hydrophilic hydrogel network/scaffold as an implantable nano-enabled bio-robotic intracranial device (BICD), the physicomechanical and physicochemical dynamics showed improvement of liposomal structure such as the stability, and homogeneity in distribution of the liposomes within the internal core of the hydrogel networks and post-lyophilized scaffold. In vitro studies in simulated cerebrospinal fluid (CSF) showed prolonged release behavior of the drug-loaded functionalized NLPs from the BICD with 50-70% released over 50 days. Scanning Electron Microscopy (SEM) and confocal microscopy confirmed intact liposomal structures within the temporal polymeric scaffold/depot post-fixation and post-lyophilization. Ex vivo studies confirmed cell proliferation and a low level of lactate dehydrogenase (LDH), which is associated with cell membrane damage/injury, after PC12 neuronal cells were exposed to the BICD. In addition, when PC12 neuronal cells were exposed to the BICD high accumulation of galantamine (GAL) into these PC12 neuronal cells was observed post-cultivation. This outcome indicated that the released drug-loaded functionalized NLPs from the BICD were still in their intact form and capable of serving as bio-robotic markers for the delivery of GAL into the neuronal cells in response to AD. Furthermore, intracellular activity validated that the synthetic peptide has the potency for targeted delivery of the drug-loaded NLPs post-release of the BICD in ex vivo studies. Overall, results from this study revealed that the BICD device had superior cytocompatibility and may be suitable for application as a prolonged and targeted delivery system for GAL into neuronal cells to treat AD

The World Council of Churches and its programme to combat racism: the evolution and development of their fight against apartheid, 1969–1994

This historical study explores the development of the World Council of Churches’ (WCC) Programme to Combat Racism (PCR), 1969–1994, and its campaign against apartheid in South Africa. It demonstrates how church-state relations can be understood as ‘resistance’, but takes the analysis further by arguing that the PCR, as an external transnational, ecumenical lobby with intimate links to South African political radicalism, as well as exiled militant formations among the liberation movements, sanctified revolutionary action in dealing with white supremacy. It succeeded in marshalling a broad range of international opinion by creating an agency dedicated to the eradication of racism within the structures of the WCC. Increasingly diverse membership enabled it to act decisively outside the constraints of pre-eminent Western interests, theology and diplomacy, drawing more directly on strands of Liberation Theology and the politics of non-alignment. The thesis, based on extensive archival research in Geneva and South Africa, covers the growing activism of the PCR in the 1970s and 1980s, tracing its aims, projects and achievements under the various WCC general Assemblies at Uppsala, Nairobi, Vancouver and Canberra between 1968 and 1991. The PCR applied multiple strategies to attack apartheid, including special funding to the African National Congress, Pan Africanist Congress and South African Congress of Trade Unions, action research and anti-racism programmes to inform and influence churches in different parts of the world to join the anti apartheid struggle. The WCC and PCR provided a space for debate across a range of ideological contestation. This was a function of its location in Geneva, its broad ecumenism and its openness to representing the interests of oppressed communities. Its attraction to political action, civil society lobbies and philanthropic enterprises contributed to its effectiveness as a ‘think tank’ for liberation, distinct from defined party-political forums or secular international human rights agencies. It therefore represented a ‘clearing house’ for ideas about democratic transformation and social change. Even though the PCR drew fire for its support of armed struggle, it succeeded in fostering dialogue among liberals and radicals, opposing political factions and competing international interests in rethinking South Africa’s future between 1969 and 1994.HistoryD. Litt. et Phil

Inhibition of hepatitis B virus subgenotype A1 replication using activators of RNA interference

ABSTRACT Infection with the hepatitis B virus (HBV) is still a major global health problem with an estimated 6% of the world’s population chronically infected with the virus. Chronic infection with HBV subgenotype A1, which is hyperendemic to southern Africa, is associated with a particularly high incidence of liver cancer and cirrhosis. Understanding HBV replication and developing effective HBV treatment to prevent liver cancer remain important medical priorities. Although there is a preventative vaccine for HBV, efficacy of currently available treatment of established infection is limited. Exploiting the RNA interference (RNAi) pathway through the use of small interfering (siRNA) and short hairpin RNA (shRNA) is an attractive new approach for the development gene therapies against HBV infection. Our laboratory has designed and demonstrated the efficacy both in vitro and in vivo of several shRNAs designed to target the X open reading frame (ORF) of HBV. Thus, the objective of this study was to construct a replication competent plasmid vector of the A1 subgenotype, a reporter plasmid vector of HBV and to assess the efficacy of RNAi effecters against these vectors both in vitro and in vivo. The first HBV replication competent vector, pCR-HBVA1 1.3x, containing the sequence of an HBV subgenotype A1 isolate, was successfully constructed by generating a greater than genome length sequence of HBV, that starts just upstream of endogenous HBV basic core promoter (BCP) and ends just downstream of the unique HBV polyadenylation (pA) site. Human hepatoma (Huh7) cells transfected with this plasmid secreted HBV surface antigen (HBsAg) into Abstract viii culture supernatants. In the murine hydrodynamic injection model of HBV replication, serum HBsAg, hepatitis B e antigen (HBeAg) and viral particle levels as well as relative surface and core mRNA levels were shown to be significantly elevated as compared to mock-injected mice. The second HBV vector, pCH-FLuc, was successfully generated by replacing the surface ORF with the sequence encoding Firefly Luciferase. The ability of pCH-FLuc to express Firefly Luciferase was demonstrated in a liver cell line (Huh7 cells). Co-transfection of the reporter plasmid, pCH-FLuc, with shRNAs targeted to HBV caused a significant reduction in Luciferase expression. Co-transfection/injection of the pCR-HBVa1 1.3x with shRNAs caused significant inhibition in the level of viral antigens (HBsAg, HBeAg and hepatitis B core antigen (HBcAg) as well as relative surface and core mRNA levels. This was observed both in vitro and in vivo. Our results demonstrate the potential this model allows for the study of HBV replication as well as the assessment of potential therapeutic strategies in a regionally significant subgenotype of HBV

The convergence of nanotechnology, biotechnology and cancer medicine in the Fourth Industrial Revolution

Abstract: Please refer to full text to view abstrac

The media, Equal Education and school learners : an investigation of the possibility of 'political listening' in the South African education crisis

This study sets out to investigate democratic participation in South Africa and the role that media play and can potentially play within this context. It considers a social movement, as one way in which citizens can organise themselves and make their voices heard to improve their chances of making a meaningful contribution to democracy. It employs Susan Bickford's theory of 'political listening', which offers a potential solution to the lack of political representativeness and inclusiveness, by focusing on the way citizens relate to each other through speaking, listening and dialogue. This study examines whether the interaction between learners and the social movement Equal Education could be considered 'political listening', and the current and possible role of the media within this context of participation. The study also attempts to develop and make a contribution to the language of description for the theory of political listening in order to map it onto the data. Using evidence or data gathered through observation of Equal Education's youth group meetings with learners and in-depth interviews with learners, youth group facilitators, Equal Education staff members and journalists, this study shows how the interaction amongst learners and between Equal Education and learners could be considered political listening and how the social movement works as a democratic project which offers learners an opportunity to exercise their citizenship. Furthermore, it also details the current role of the media and possible role of the media as perceived by Equal Education, learners and by journalists who report on Equal Education's activities. The study does not make conclusive claims about whether 'political listening' occurs between Equal Education and learners and the media because the study is exploratory in nature and involves a lot of trial and error when it comes to applying the theory of political listening to interview and textual data, which is a communication context that the theory is only beginning to chart

An examination of activism and ‘political listening’ during the year of student protest at the University of Cape Town from 9 March 2015 to 9 March 2016

This study sets out to examine democratic participation in South Africa and the role that ‘political listening’ could play in making participation more equitable. It considers protest action on a South African university campus, which at times not only resulted in significant and swift concessions from the university leadership but also sparked national political action which got an equally swift response from the South African government. It considers the social movement, the RhodesMustFall movement (RMF), as one way in which students can organise themselves to get a better hearing from the University of Cape Town (UCT) management in their attempt to make a meaningful contribution to the university’s micro democracy. This study examines whether the interaction between the UCT management and RMF could be considered ‘political listening’, and the possible role of the Cape Times newspaper within this context of participation. Using data gathered through interviews, written communications, observation and newspaper articles, the study shows that in all of the interactions between RMF and the UCT management, both groups were seldom willing to forego their power to engage in genuine listening. Instead, the two parties guessed at what power the other party might have and acted to reduce that power. It is in this context of guessing at and figuring what power the other party has that listening occurs. Furthermore, the study shows that during the RMF protest, the UCT management viewed their responsibility for the institution mainly through the lens of Private Property Law which framed protest as something to be dealt with by restoring law and order. The study also details the role of the Cape Times newspaper in the interactions between RMF and the UCT management and considers if this role could be political listening. The study is exploratory and demonstrates how political listening could work more optimally in real-life instances.Thesis (PhD) -- Faculty of Humanities, Journalism and Media Studies, 202

A Review on Composite Liposomal Technologies for Specialized Drug Delivery

The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications