Silence, like breathing
- Authors: Van der Nest, Megan
- Date: 2012
- Subjects: South African poetry (English) -- 21st century , Creative writing (Higher education) , Diaries -- Authorship , English language -- Writing
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:5980 , http://hdl.handle.net/10962/d1015246
- Description: In this collection of free verse lyric poems I have drawn inspiration from childhood memories, as well as from the natural world and encounters with the people around me. Each poem focuses on a small moment, presenting an emotive portrait of a memory or an experience. These small moments lead, cumulatively, to deeper insights into myself and the world around me. The collection is divided into four seasons, in part because the work is strongly influenced by the natural world, but also because the progression of the seasons mirrors something of the personal journey reflected in the poems.
- Full Text:
- Date Issued: 2012
- Authors: Van der Nest, Megan
- Date: 2012
- Subjects: South African poetry (English) -- 21st century , Creative writing (Higher education) , Diaries -- Authorship , English language -- Writing
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:5980 , http://hdl.handle.net/10962/d1015246
- Description: In this collection of free verse lyric poems I have drawn inspiration from childhood memories, as well as from the natural world and encounters with the people around me. Each poem focuses on a small moment, presenting an emotive portrait of a memory or an experience. These small moments lead, cumulatively, to deeper insights into myself and the world around me. The collection is divided into four seasons, in part because the work is strongly influenced by the natural world, but also because the progression of the seasons mirrors something of the personal journey reflected in the poems.
- Full Text:
- Date Issued: 2012
Small mammal communities at high altitude within the Sneeuberg Mountain complex, Eastern Cape Province, South Africa
- Authors: Kok, Armand du Preez
- Date: 2012
- Subjects: Mountain animals -- Research -- South Africa -- Eastern Cape , Mammal populations -- Research -- South Africa -- Eastern Cape , Mammals -- Research -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5766 , http://hdl.handle.net/10962/d1005454 , Mountain animals -- Research -- South Africa -- Eastern Cape , Mammal populations -- Research -- South Africa -- Eastern Cape , Mammals -- Research -- South Africa -- Eastern Cape
- Description: Due to their widespread and specious nature, small mammals are ideal for biogeographical studies. Small mammals also effectively connect various trophic levels by being both consumers and prey items for other animals. The Great Escarpment is the dominant mountain landscape in South Africa. Yet, very little small mammal research has been conducted on the Great Escarpment outside of the Main Drakensberg Mountains. This is surprising given the importance of mountains in shaping regional ecology. In this study, I assessed the diversity and community composition of small mammals at three high altitude (>1700m) sites within the Sneeuberg Mountain Complex (SMC) from June 2009 to May 2010. I also tested the effectiveness of five different bait types for measuring small mammal diversity (i.e. number of individuals caught, species richness, Shannon diversity index and Simpson index of diversity). Out of a total of 423 captures, 292 individuals of 12 small mammal species (one shrew, one elephant shrew and 10 rodents) were recorded over 5280 trap nights. The species richness and diversity of small mammals captured at the three sites were similar and this homogeneity was probably related to the regional processes (e.g. climate and latitude) that govern species richness and diversity. The most effective bait type in terms of capture success, species richness and diversity measurements was peanut butter and oats. In addition, the use of richness estimators revealed that peanut butter and oats was the most effective bait for sampling the species richness of small mammals. The effectiveness of peanut butter and oats was related to this bait having a more attractive scent, when compared to the other bait types. Future studies should focus on researching the range of local and regional processes that drive small mammal diversity at high altitudes in South Africa. I also recommend the use of more than one bait type when planning to survey small mammal communities.
- Full Text:
- Date Issued: 2012
- Authors: Kok, Armand du Preez
- Date: 2012
- Subjects: Mountain animals -- Research -- South Africa -- Eastern Cape , Mammal populations -- Research -- South Africa -- Eastern Cape , Mammals -- Research -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5766 , http://hdl.handle.net/10962/d1005454 , Mountain animals -- Research -- South Africa -- Eastern Cape , Mammal populations -- Research -- South Africa -- Eastern Cape , Mammals -- Research -- South Africa -- Eastern Cape
- Description: Due to their widespread and specious nature, small mammals are ideal for biogeographical studies. Small mammals also effectively connect various trophic levels by being both consumers and prey items for other animals. The Great Escarpment is the dominant mountain landscape in South Africa. Yet, very little small mammal research has been conducted on the Great Escarpment outside of the Main Drakensberg Mountains. This is surprising given the importance of mountains in shaping regional ecology. In this study, I assessed the diversity and community composition of small mammals at three high altitude (>1700m) sites within the Sneeuberg Mountain Complex (SMC) from June 2009 to May 2010. I also tested the effectiveness of five different bait types for measuring small mammal diversity (i.e. number of individuals caught, species richness, Shannon diversity index and Simpson index of diversity). Out of a total of 423 captures, 292 individuals of 12 small mammal species (one shrew, one elephant shrew and 10 rodents) were recorded over 5280 trap nights. The species richness and diversity of small mammals captured at the three sites were similar and this homogeneity was probably related to the regional processes (e.g. climate and latitude) that govern species richness and diversity. The most effective bait type in terms of capture success, species richness and diversity measurements was peanut butter and oats. In addition, the use of richness estimators revealed that peanut butter and oats was the most effective bait for sampling the species richness of small mammals. The effectiveness of peanut butter and oats was related to this bait having a more attractive scent, when compared to the other bait types. Future studies should focus on researching the range of local and regional processes that drive small mammal diversity at high altitudes in South Africa. I also recommend the use of more than one bait type when planning to survey small mammal communities.
- Full Text:
- Date Issued: 2012
Smashing the crystal ball: post-structural insights associated with contemporary anarchism and the revision of blueprint utopianism
- Authors: Alexander, Tarryn Linda
- Date: 2012
- Subjects: Social change , Utopian socialism -- Philosophy , Utopias -- Philosophy , Anarchism
- Language: English
- Type: Thesis , Masters , MSocSc
- Identifier: vital:3311 , http://hdl.handle.net/10962/d1003099 , Social change , Utopian socialism -- Philosophy , Utopias -- Philosophy , Anarchism
- Description: This thesis is an exploration of the images which define revolution's meaning. It suggests a possible shifting of emphasis from the scientific imaginary which centres on identifying the correct way to totalising revolution, towards a post-structuralist-anarchistic imaginary which privileges prefigurative radicalisations of social relations in the here and now. It looks specifically at how the field of post-structuralism intertwines with historically anarchist concepts to generate an horizon of social change animated by experimental and open-ended transformations. While the thesis offers positive characterisations of the types of contemporary movements, tactics and principles which embody the change from closed to open utopianism, it is chiefly a commentary on the role of theory in depicting the complexity of relations on the ground and the danger of proposing one totalising pathway from one state of society to another. It asks the reader to consider, given the achievements of movements and given the insights of post-structuralism, whether it is still worthwhile to proclaim certainty when sketching the possibilities for transcendence toward emancipation, an aim, which in itself, is always under construction. I engage this by firstly establishing a practical foundation for the critique of endpoints in theory by exploring the horizontal and prefigurative nature of a few autonomous movements today. Secondly I propose the contemporary theory of post-structuralist anarchism as concomitant with conclusions about transformation made in the first chapter. Finally I recommend a few initial concepts to start debate about the way forward from old objectivist models of transformation. The uncertainties of daily life, crumbling of economic powers and rapid pace of change in the twenty-first century have opened up fantastic spaces for innovative thought. Reconsidering old consensus around what constitutes a desirable image of revolution is of considerable importance given today's burgeoning bottom-up political energy and the global debate surrounding the possibilities for bottom-up revolutionisation of society. I submit that theories which portray stories of permanent, pure and natural end-points to revolution are deficient justifications for radical action.
- Full Text:
- Date Issued: 2012
- Authors: Alexander, Tarryn Linda
- Date: 2012
- Subjects: Social change , Utopian socialism -- Philosophy , Utopias -- Philosophy , Anarchism
- Language: English
- Type: Thesis , Masters , MSocSc
- Identifier: vital:3311 , http://hdl.handle.net/10962/d1003099 , Social change , Utopian socialism -- Philosophy , Utopias -- Philosophy , Anarchism
- Description: This thesis is an exploration of the images which define revolution's meaning. It suggests a possible shifting of emphasis from the scientific imaginary which centres on identifying the correct way to totalising revolution, towards a post-structuralist-anarchistic imaginary which privileges prefigurative radicalisations of social relations in the here and now. It looks specifically at how the field of post-structuralism intertwines with historically anarchist concepts to generate an horizon of social change animated by experimental and open-ended transformations. While the thesis offers positive characterisations of the types of contemporary movements, tactics and principles which embody the change from closed to open utopianism, it is chiefly a commentary on the role of theory in depicting the complexity of relations on the ground and the danger of proposing one totalising pathway from one state of society to another. It asks the reader to consider, given the achievements of movements and given the insights of post-structuralism, whether it is still worthwhile to proclaim certainty when sketching the possibilities for transcendence toward emancipation, an aim, which in itself, is always under construction. I engage this by firstly establishing a practical foundation for the critique of endpoints in theory by exploring the horizontal and prefigurative nature of a few autonomous movements today. Secondly I propose the contemporary theory of post-structuralist anarchism as concomitant with conclusions about transformation made in the first chapter. Finally I recommend a few initial concepts to start debate about the way forward from old objectivist models of transformation. The uncertainties of daily life, crumbling of economic powers and rapid pace of change in the twenty-first century have opened up fantastic spaces for innovative thought. Reconsidering old consensus around what constitutes a desirable image of revolution is of considerable importance given today's burgeoning bottom-up political energy and the global debate surrounding the possibilities for bottom-up revolutionisation of society. I submit that theories which portray stories of permanent, pure and natural end-points to revolution are deficient justifications for radical action.
- Full Text:
- Date Issued: 2012
Social capital and fisheries co-management in South Africa: the East Coast Rock Lobster Fishery in Tshani Mankozi, Wild Coast, Eastern Cape
- Authors: Kaminsky, Alexander
- Date: 2012
- Subjects: Social capital (Sociology) -- Economic aspects Human capital -- South Africa Fishery management -- South Africa Natural resources -- Co-management -- South Africa Rural poor -- South Africa Sustainable development -- South Africa
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:3322 , http://hdl.handle.net/10962/d1003110
- Description: It is evident that natural fish stocks are in rapid decline and that millions of people around the world rely on these resources for food and for securing a livelihood. This has brought many social scientists, biologists and fisheries experts to acknowledge that communities need to take more control in managing their natural resources. The paradigm shift in fisheries management from a top-down resource orientated control to a participatory people-centred control is now being advocated in many maritime nations in facilitating community-based natural resource management. At the heart of these projects is the establishment of institutions and social networks that allow for clear communication and information sharing, based on scientific data and traditional knowledge which ultimately allow empowered communities to collectively manage their resources in partnership with government, market actors and many other stakeholders. Central to the problem is the issue of access rights. In many situations where co-management of natural resources through community-government partnerships is advocated, the failure of coastal states to provide adequate legislature and regulatory frameworks has jeopardised such projects. A second issue is the failure of many states to provide adequate investments in social and human capital which will enable communities to become the primary stakeholder in the co-management of their natural resources. Whilst investments like capacity building, education, skills training and development, communications and institution building can initially require high financial investments, the regulatory costs for monitoring, controlling and surveying fish stocks along the coastline will go down as communities take ownership of their resources under sustainable awareness. The main unit of investment therefore is social capital which allows for the increase in trust, cooperativeness, assertiveness, collective action and general capabilities of natural resource governance. High levels of social capital require good social relations and interactions which ultimately create a social network of fishers, community members and leaders, government officials, market players, researchers and various other stakeholders. Co-management thus has an inherent network structure made up of social relations on a horizontal scale amongst community members as well as on a vertical scale with government and fisheries authorities. These bonding relations between people and the bridging relations with institutions provide the social capital currency that allows for a successful co-management solution to community-based natural resource governance. The South African coastline is home to thousands of people who harvest the marine resources for food security and securing a basic income. Fishing is a major cultural and historical component of the livelihoods of many people along the coastline, particularly along the Wild Coast of South Africa located on its South-eastern shoreline. Due to the geopolitical nature of South Africa’s apartheid past many people were located in former tribal lands called Bantustans. The Transkei, one of the biggest homelands, is home to some of South Africa’s poorest people, many of whom rely on the marine resources. By 1998 the government sought to acknowledge the previously unrecognised subsistence sector that lived along the South African coastline with the promulgation of the Marine Living Resources Act. The act sought to legalise access rights for fishers and provide opportunities for the development of commercial fisheries. The act and many subsequent policies largely called for co-management as a solution to the management of the subsistence sector. This thesis largely explains the administrative and legislative difficulties in transporting the participatory components of co-management to the ground level. As such co-management has largely remained in rhetoric whilst the government provides a contradictory policy regarding the management of subsistence and small-scale fishers. This thesis attempts to provide qualitative ethnographic research of the East Coast Rock Lobster fishery located in a small fishing village in the Transkei. The fishery falls somewhere on the spectrum between the small-scale and subsistence sector as there are a basket of high and low value resources being harvested. It will be argued that in order to economically and socially develop the fishery the social capital and social networks of the community and various stakeholders needs to be analysed in order to effectively create a co-management network that can create a successful collective management of natural resources thereby sustaining these communities in the future.
- Full Text:
- Date Issued: 2012
- Authors: Kaminsky, Alexander
- Date: 2012
- Subjects: Social capital (Sociology) -- Economic aspects Human capital -- South Africa Fishery management -- South Africa Natural resources -- Co-management -- South Africa Rural poor -- South Africa Sustainable development -- South Africa
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:3322 , http://hdl.handle.net/10962/d1003110
- Description: It is evident that natural fish stocks are in rapid decline and that millions of people around the world rely on these resources for food and for securing a livelihood. This has brought many social scientists, biologists and fisheries experts to acknowledge that communities need to take more control in managing their natural resources. The paradigm shift in fisheries management from a top-down resource orientated control to a participatory people-centred control is now being advocated in many maritime nations in facilitating community-based natural resource management. At the heart of these projects is the establishment of institutions and social networks that allow for clear communication and information sharing, based on scientific data and traditional knowledge which ultimately allow empowered communities to collectively manage their resources in partnership with government, market actors and many other stakeholders. Central to the problem is the issue of access rights. In many situations where co-management of natural resources through community-government partnerships is advocated, the failure of coastal states to provide adequate legislature and regulatory frameworks has jeopardised such projects. A second issue is the failure of many states to provide adequate investments in social and human capital which will enable communities to become the primary stakeholder in the co-management of their natural resources. Whilst investments like capacity building, education, skills training and development, communications and institution building can initially require high financial investments, the regulatory costs for monitoring, controlling and surveying fish stocks along the coastline will go down as communities take ownership of their resources under sustainable awareness. The main unit of investment therefore is social capital which allows for the increase in trust, cooperativeness, assertiveness, collective action and general capabilities of natural resource governance. High levels of social capital require good social relations and interactions which ultimately create a social network of fishers, community members and leaders, government officials, market players, researchers and various other stakeholders. Co-management thus has an inherent network structure made up of social relations on a horizontal scale amongst community members as well as on a vertical scale with government and fisheries authorities. These bonding relations between people and the bridging relations with institutions provide the social capital currency that allows for a successful co-management solution to community-based natural resource governance. The South African coastline is home to thousands of people who harvest the marine resources for food security and securing a basic income. Fishing is a major cultural and historical component of the livelihoods of many people along the coastline, particularly along the Wild Coast of South Africa located on its South-eastern shoreline. Due to the geopolitical nature of South Africa’s apartheid past many people were located in former tribal lands called Bantustans. The Transkei, one of the biggest homelands, is home to some of South Africa’s poorest people, many of whom rely on the marine resources. By 1998 the government sought to acknowledge the previously unrecognised subsistence sector that lived along the South African coastline with the promulgation of the Marine Living Resources Act. The act sought to legalise access rights for fishers and provide opportunities for the development of commercial fisheries. The act and many subsequent policies largely called for co-management as a solution to the management of the subsistence sector. This thesis largely explains the administrative and legislative difficulties in transporting the participatory components of co-management to the ground level. As such co-management has largely remained in rhetoric whilst the government provides a contradictory policy regarding the management of subsistence and small-scale fishers. This thesis attempts to provide qualitative ethnographic research of the East Coast Rock Lobster fishery located in a small fishing village in the Transkei. The fishery falls somewhere on the spectrum between the small-scale and subsistence sector as there are a basket of high and low value resources being harvested. It will be argued that in order to economically and socially develop the fishery the social capital and social networks of the community and various stakeholders needs to be analysed in order to effectively create a co-management network that can create a successful collective management of natural resources thereby sustaining these communities in the future.
- Full Text:
- Date Issued: 2012
Social networks in recently established human settlements in Grahamstown East/Rhini, South Africa
- Authors: Mukorombindo, Yeukai Chido
- Date: 2012
- Subjects: Social networks -- South Africa -- Grahamstown Human settlements -- South Africa -- Grahamstown Social capital (Sociology) Grahamstown (South Africa) -- Social life and customs Poor -- Social networks -- South Africa -- Grahamstown Grahamstown (South Africa) -- Social conditions Social change -- South Africa -- Grahamstown Informal sector (Economics) -- South Africa -- Grahamstown
- Language: English
- Type: Thesis , Masters , MSocSc
- Identifier: vital:3310 , http://hdl.handle.net/10962/d1003098
- Description: This thesis attempts to understand the concepts of social capital and social networks within the South African government’s current policy on “human settlements”. It considers the association between social networks, social capital and social cohesion, community development and improved general quality of life. The thesis also explores the possibility and challenges of using social capital and social networks amongst low income urban communities as a viable strategy against poverty and for the development of sustainable human settlements. The thesis will examine the nature and form in which informal social networks function in a low income urban community in South Africa and the benefits that arise from these. The thesis particularly looked at informal social security networks in the form of savings clubs/stokvels and burial societies as well as other informal social networks such as religious associations and neighbourhood social support groups. The study discovered that in light of the high unemployment rate, high poverty levels and increasing urban economic pressures, most low income households cannot access or rely on social networks as a means of survival but on grants and wages. Social security networks are only accessible to those who can afford monthly membership contributions thereby excluding the poorest of the poor. For those who can afford to be members of social security networks, the benefits are limited and they do not adequately address household needs. The study also showed how those who cannot afford to be members of social security networks still have access to some sort of communal social support. Neighbours stand out as valuable in this regard. However, the casual neighbourhood support networks are not ‘resource rich’ mainly due to, the inability of people to donate and reciprocate. Religious networks are mainly identified with emotional, psychological and spiritual well-being, providing friendship, comfort and advice but these benefits are only provided to members only in their time of need. The theoretical understanding of social networks producing social capital which is seen as being beneficial to the poorest of the poor is questioned, as the results show the inequalities and divisions that exist within informal social networks themselves. On the other hand, all the social networks considered in this thesis have managed to contribute towards strengthening neighbourly relations, trust, building community identity and promoting values of ubuntu- sharing and caring for one another which in the long-run benefits the community, both members and non-members alike.
- Full Text:
- Date Issued: 2012
- Authors: Mukorombindo, Yeukai Chido
- Date: 2012
- Subjects: Social networks -- South Africa -- Grahamstown Human settlements -- South Africa -- Grahamstown Social capital (Sociology) Grahamstown (South Africa) -- Social life and customs Poor -- Social networks -- South Africa -- Grahamstown Grahamstown (South Africa) -- Social conditions Social change -- South Africa -- Grahamstown Informal sector (Economics) -- South Africa -- Grahamstown
- Language: English
- Type: Thesis , Masters , MSocSc
- Identifier: vital:3310 , http://hdl.handle.net/10962/d1003098
- Description: This thesis attempts to understand the concepts of social capital and social networks within the South African government’s current policy on “human settlements”. It considers the association between social networks, social capital and social cohesion, community development and improved general quality of life. The thesis also explores the possibility and challenges of using social capital and social networks amongst low income urban communities as a viable strategy against poverty and for the development of sustainable human settlements. The thesis will examine the nature and form in which informal social networks function in a low income urban community in South Africa and the benefits that arise from these. The thesis particularly looked at informal social security networks in the form of savings clubs/stokvels and burial societies as well as other informal social networks such as religious associations and neighbourhood social support groups. The study discovered that in light of the high unemployment rate, high poverty levels and increasing urban economic pressures, most low income households cannot access or rely on social networks as a means of survival but on grants and wages. Social security networks are only accessible to those who can afford monthly membership contributions thereby excluding the poorest of the poor. For those who can afford to be members of social security networks, the benefits are limited and they do not adequately address household needs. The study also showed how those who cannot afford to be members of social security networks still have access to some sort of communal social support. Neighbours stand out as valuable in this regard. However, the casual neighbourhood support networks are not ‘resource rich’ mainly due to, the inability of people to donate and reciprocate. Religious networks are mainly identified with emotional, psychological and spiritual well-being, providing friendship, comfort and advice but these benefits are only provided to members only in their time of need. The theoretical understanding of social networks producing social capital which is seen as being beneficial to the poorest of the poor is questioned, as the results show the inequalities and divisions that exist within informal social networks themselves. On the other hand, all the social networks considered in this thesis have managed to contribute towards strengthening neighbourly relations, trust, building community identity and promoting values of ubuntu- sharing and caring for one another which in the long-run benefits the community, both members and non-members alike.
- Full Text:
- Date Issued: 2012
Structural analysis of effects of mutations on HIV-1 subtype C protease active site
- Mathu, Alexander Muchugia Nganga
- Authors: Mathu, Alexander Muchugia Nganga
- Date: 2012
- Subjects: HIV (Viruses) -- Research , HIV infections -- Treatment -- Research , Protease inhibitors -- Research , Viruses -- Effect of drugs on -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4013 , http://hdl.handle.net/10962/d1004073 , HIV (Viruses) -- Research , HIV infections -- Treatment -- Research , Protease inhibitors -- Research , Viruses -- Effect of drugs on -- Research
- Description: HIV/AIDS is a global pandemic that poses a great threat especially in Sub-Saharan Africa where the highest population of those infected with the virus is found. It has far reaching medical, socio-economic and scientific implications. The HIV-1 protease enzyme is a prime therapeutic target that has been exploited in an effort to reduce morbidity and mortality. However problems arise from drug toxicity and drug-resistant mutations of the protease which is a motivation for research for new, safer and effective therapies. Evidence exists to show that there are significant genomic differences in Subtype B and C that have a negative effect on the intrinsic binding of inhibitors. It is imperative to look at all perspectives from epidemiological, molecular to the pharmacological ones so as to achieve rational design of therapeutic agents. This study involved the use of in silico structural analysis of the effects of mutations in the active site. The data was provided by the National Institute of Communicable Diseases consisting of HIV-1 Subtype C protease sequences of 29 infants exhibiting drug-resistance to ritonavir and lopinavir. The major active site mutations causing drug resistance identified in this study were M46I, I54V and V82A using the Stanford HIV database tool. Homology modeling without extra restraints produced models with improved quality in comparison to those with restraints. MetaMQAPII results differed when models were visualized as dimers giving erroneous modeled regions in comparison to monomers. A broader study with a larger dataset of HIV-1 subtype C protease sequences is required to increase statistical confidence and in order to identify the pattern of drug resistant mutations. Homology modeling without extra restraints is preferred for calculating homology models for the HIV-1 subtype C. Further investigations needs to be done to ascertain the accuracy of validation results for dimers from MetaMQAPII as it is designed for evaluation of monomers.
- Full Text:
- Date Issued: 2012
- Authors: Mathu, Alexander Muchugia Nganga
- Date: 2012
- Subjects: HIV (Viruses) -- Research , HIV infections -- Treatment -- Research , Protease inhibitors -- Research , Viruses -- Effect of drugs on -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4013 , http://hdl.handle.net/10962/d1004073 , HIV (Viruses) -- Research , HIV infections -- Treatment -- Research , Protease inhibitors -- Research , Viruses -- Effect of drugs on -- Research
- Description: HIV/AIDS is a global pandemic that poses a great threat especially in Sub-Saharan Africa where the highest population of those infected with the virus is found. It has far reaching medical, socio-economic and scientific implications. The HIV-1 protease enzyme is a prime therapeutic target that has been exploited in an effort to reduce morbidity and mortality. However problems arise from drug toxicity and drug-resistant mutations of the protease which is a motivation for research for new, safer and effective therapies. Evidence exists to show that there are significant genomic differences in Subtype B and C that have a negative effect on the intrinsic binding of inhibitors. It is imperative to look at all perspectives from epidemiological, molecular to the pharmacological ones so as to achieve rational design of therapeutic agents. This study involved the use of in silico structural analysis of the effects of mutations in the active site. The data was provided by the National Institute of Communicable Diseases consisting of HIV-1 Subtype C protease sequences of 29 infants exhibiting drug-resistance to ritonavir and lopinavir. The major active site mutations causing drug resistance identified in this study were M46I, I54V and V82A using the Stanford HIV database tool. Homology modeling without extra restraints produced models with improved quality in comparison to those with restraints. MetaMQAPII results differed when models were visualized as dimers giving erroneous modeled regions in comparison to monomers. A broader study with a larger dataset of HIV-1 subtype C protease sequences is required to increase statistical confidence and in order to identify the pattern of drug resistant mutations. Homology modeling without extra restraints is preferred for calculating homology models for the HIV-1 subtype C. Further investigations needs to be done to ascertain the accuracy of validation results for dimers from MetaMQAPII as it is designed for evaluation of monomers.
- Full Text:
- Date Issued: 2012
Structural analysis of prodomain inhibition of cysteine proteases in plasmodium species
- Authors: Njuguna, Joyce Njoki
- Date: 2012
- Subjects: Plasmodium , Cysteine proteinases , Proteolytic enzymes , Malaria -- Chemotherapy , Antimalarials , Plasmodium falciparum
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4021 , http://hdl.handle.net/10962/d1004081 , Plasmodium , Cysteine proteinases , Proteolytic enzymes , Malaria -- Chemotherapy , Antimalarials , Plasmodium falciparum
- Description: Plasmodium is a genus of parasites causing malaria, a virulent protozoan infection in humans resulting in over a million deaths annually. Treatment of malaria is increasingly limited by parasite resistance to available drugs. Hence, there is a need to identify new drug targets and authenticate antimalarial compounds that act on these targets. A relatively new therapeutic approach targets proteolytic enzymes responsible for parasite‟s invasion, rupture and hemoglobin degradation at the erythrocytic stage of infection. Cysteine proteases (CPs) are essential for these crucial roles in the intraerythrocytic parasite. CPs are a diverse group of enzymes subdivided into clans and further subdivided into families. Our interest is in Clan CA, papain family C1 proteases, whose members play numerous roles in human and parasitic metabolism. These proteases are produced as zymogens having an N-terminal extension known as the prodomain which regulates the protease activity by selectively inhibiting its active site, preventing substrate access. A Clan CA protease Falcipain-2 (FP-2) of Plasmodium falciparum is a validated drug target but little is known of its orthologs in other malarial Plasmodium species. This study uses various structural bioinformatics approaches to characterise the prodomain‟s regulatory effect in FP-2 and its orthologs in Plasmodium species (P. vivax, P. berghei, P. knowlesi, P. ovale, P. chabaudi and P. yoelii). This was in an effort to discover short peptides with essential residues to mimic the prodomain‟s inhibition of these proteases, as potential peptidomimetic therapeutic agents. Residues in the prodomain region that spans over the active site are most likely to interact with the subsite residues inhibiting the protease. Sequence analysis revealed conservation of residues in this region of Plasmodium proteases that differed significantly in human proteases. Further prediction of the 3D structure of these proteases by homology modelling allowed visualisation of these interactions revealing differences between parasite and human proteases which will lead to significant contribution in structure based malarial inhibitor design.
- Full Text:
- Date Issued: 2012
- Authors: Njuguna, Joyce Njoki
- Date: 2012
- Subjects: Plasmodium , Cysteine proteinases , Proteolytic enzymes , Malaria -- Chemotherapy , Antimalarials , Plasmodium falciparum
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4021 , http://hdl.handle.net/10962/d1004081 , Plasmodium , Cysteine proteinases , Proteolytic enzymes , Malaria -- Chemotherapy , Antimalarials , Plasmodium falciparum
- Description: Plasmodium is a genus of parasites causing malaria, a virulent protozoan infection in humans resulting in over a million deaths annually. Treatment of malaria is increasingly limited by parasite resistance to available drugs. Hence, there is a need to identify new drug targets and authenticate antimalarial compounds that act on these targets. A relatively new therapeutic approach targets proteolytic enzymes responsible for parasite‟s invasion, rupture and hemoglobin degradation at the erythrocytic stage of infection. Cysteine proteases (CPs) are essential for these crucial roles in the intraerythrocytic parasite. CPs are a diverse group of enzymes subdivided into clans and further subdivided into families. Our interest is in Clan CA, papain family C1 proteases, whose members play numerous roles in human and parasitic metabolism. These proteases are produced as zymogens having an N-terminal extension known as the prodomain which regulates the protease activity by selectively inhibiting its active site, preventing substrate access. A Clan CA protease Falcipain-2 (FP-2) of Plasmodium falciparum is a validated drug target but little is known of its orthologs in other malarial Plasmodium species. This study uses various structural bioinformatics approaches to characterise the prodomain‟s regulatory effect in FP-2 and its orthologs in Plasmodium species (P. vivax, P. berghei, P. knowlesi, P. ovale, P. chabaudi and P. yoelii). This was in an effort to discover short peptides with essential residues to mimic the prodomain‟s inhibition of these proteases, as potential peptidomimetic therapeutic agents. Residues in the prodomain region that spans over the active site are most likely to interact with the subsite residues inhibiting the protease. Sequence analysis revealed conservation of residues in this region of Plasmodium proteases that differed significantly in human proteases. Further prediction of the 3D structure of these proteases by homology modelling allowed visualisation of these interactions revealing differences between parasite and human proteases which will lead to significant contribution in structure based malarial inhibitor design.
- Full Text:
- Date Issued: 2012
Studies on existing and new isolates of Cryptophlebia leucotreta granulovirus (CrleGV) on Thaumatotibia leucotreta populations from a range of geographic regions in South Africa
- Authors: Opoku-Debrah, John Kwadwo
- Date: 2012
- Subjects: Cryptophlebia leucotreta Cryptophlebia leucotreta -- South Africa Cryptophlebia leucotreta -- Biological control Cryptophlebia leucotreta -- Life cycles Baculoviruses Lepidoptera -- Biological control Tortricidae -- Biological control Microbial insecticides Pests -- Integrated control
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5778 , http://hdl.handle.net/10962/d1005466
- Description: Baculoviruses are arthropod-specific DNA viruses that are highly virulent to most lepidopteran insects. Their host specificity and compatibility with IPM programmes has enabled their usage as safe microbial insecticides (biopesticides). Two baculovirus-based biopesticides, Cryptogran and Cryptex, which have been formulated with Cryptophlebia leucotreta granulovirus (CrleGV) have been registered for the control of false codling moth (FCM), Thaumatotibia (=Cryptophlebia) leucotreta (Meyrick) (Lepidoptera: Tortricidae) in South Africa and have been successfully incorporated into IPM programmes. However, several studies have indicated that insects can develop resistance to baculovirus-based biopesticide as was shown with field populations of codling moth (CM), Cydia pomonella (L.), which developed resistance to the biopesticide Cydia pomonella granulovirus (CpGV-M) in Europe. Other studies have shown that, under laboratory conditions, FCM populations differ in their susceptibility to Cryptogran and Cryptex. In order to investigate difference in susceptibility as well as protect against any future resistance by FCM to Cryptogran and Cryptex, a search for novel CrleGV-SA isolates from diseased insects from different geographic regions in South Africa was performed. Six geographic populations (Addo, Citrusdal, Marble Hall, Nelspruit, Baths and Mixed colonies) of FCM were established and maintained in the laboratory. Studies on the comparative biological performance based on pupal mass, female fecundity, egg hatch, pupal survival, adult eclosion and duration of life cycle of the Addo, Citrusdal, Marble Hall, Nelspruit and Mixed colonies revealed a low biological performance for the Citrusdal colony. This was attributed to the fact that FCM populations found in the Citrusdal area are not indigenous and may have been introduced from a very limited gene pool from another region. When insects from five colonies, excluding the Baths colony, were subjected to stress by overcrowding , a latent baculovirus resident in the Addo, Nelspruit, Citrusdal, Marble Hall and Mixed colonies was brought into an overt lethal state. Transmission electron micrographs revealed the presence of GV occlusion bodies (OBs) in diseased insects. DNA profiles obtained by single restriction endonuclease analysis of viral genomic DNA using BamH 1, Sa/1, Xba1 , Pst1, Xh01 , Kpn1, Hindlll and EcoR1 revealed five CrleGV-SA isolates latent within the insect populations. The new isolates were named CrleGV-SA Ado, CrleGV-SA Cit, CrleGV-SA Mbl, CrleGVSA Nels and CrleGV-SA Mix isolates. The novelty of the five CrleGV-SA isolates was confirmed by the presence of unique submolar bands, indicating that each isolate was genetically different. PCR amplification and sequencing of the granulin and egt genes from the five isolates revealed several single nucleotide polymorph isms (SNPs) which, in some cases, resulted in amino acid substitutions. DNA profiles from RFLPs, as well as phylogenetic analysis based on granulin and egt sequencing showed the presence of two CrleGV-SA genome types for the CrleGV-SA isolate. Cryptex and CrleGV-SA Ado, CrleGV-SA Cit, CrleGV-SA Mbl and CrleGV-SA Mix were placed as members of Group one CrleGV-SA, and Cryptogran and CrleGV-SA Nels isolate were placed into Group two CrleGV-SA. In droplet feeding bioassays, the median survival time (STso) for neonate larvae inoculated with Group one and two CrleGV-SA were determined to range from 80 - 88 hours (3.33 - 3.67 days), for all five colonies. LDso values for Group one and two CrleGV-SA against neonates from the Addo, Citrusdal, Marble Hall, Nelspruit and Mixed colonies varied between some populations and ranged from 0.80 - 3.12 OBs per larva, indicating some level of variation in host susceptibility. This is the first study reporting the existence of genetically distinct CrleGV baculovirus isolates infecting FCM in different geographical areas of South Africa. The results of this study have broad-ranging implications for our understanding of baculovirus-host interactions and for the application of baculovirus basedbiopesticides.
- Full Text:
- Date Issued: 2012
- Authors: Opoku-Debrah, John Kwadwo
- Date: 2012
- Subjects: Cryptophlebia leucotreta Cryptophlebia leucotreta -- South Africa Cryptophlebia leucotreta -- Biological control Cryptophlebia leucotreta -- Life cycles Baculoviruses Lepidoptera -- Biological control Tortricidae -- Biological control Microbial insecticides Pests -- Integrated control
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5778 , http://hdl.handle.net/10962/d1005466
- Description: Baculoviruses are arthropod-specific DNA viruses that are highly virulent to most lepidopteran insects. Their host specificity and compatibility with IPM programmes has enabled their usage as safe microbial insecticides (biopesticides). Two baculovirus-based biopesticides, Cryptogran and Cryptex, which have been formulated with Cryptophlebia leucotreta granulovirus (CrleGV) have been registered for the control of false codling moth (FCM), Thaumatotibia (=Cryptophlebia) leucotreta (Meyrick) (Lepidoptera: Tortricidae) in South Africa and have been successfully incorporated into IPM programmes. However, several studies have indicated that insects can develop resistance to baculovirus-based biopesticide as was shown with field populations of codling moth (CM), Cydia pomonella (L.), which developed resistance to the biopesticide Cydia pomonella granulovirus (CpGV-M) in Europe. Other studies have shown that, under laboratory conditions, FCM populations differ in their susceptibility to Cryptogran and Cryptex. In order to investigate difference in susceptibility as well as protect against any future resistance by FCM to Cryptogran and Cryptex, a search for novel CrleGV-SA isolates from diseased insects from different geographic regions in South Africa was performed. Six geographic populations (Addo, Citrusdal, Marble Hall, Nelspruit, Baths and Mixed colonies) of FCM were established and maintained in the laboratory. Studies on the comparative biological performance based on pupal mass, female fecundity, egg hatch, pupal survival, adult eclosion and duration of life cycle of the Addo, Citrusdal, Marble Hall, Nelspruit and Mixed colonies revealed a low biological performance for the Citrusdal colony. This was attributed to the fact that FCM populations found in the Citrusdal area are not indigenous and may have been introduced from a very limited gene pool from another region. When insects from five colonies, excluding the Baths colony, were subjected to stress by overcrowding , a latent baculovirus resident in the Addo, Nelspruit, Citrusdal, Marble Hall and Mixed colonies was brought into an overt lethal state. Transmission electron micrographs revealed the presence of GV occlusion bodies (OBs) in diseased insects. DNA profiles obtained by single restriction endonuclease analysis of viral genomic DNA using BamH 1, Sa/1, Xba1 , Pst1, Xh01 , Kpn1, Hindlll and EcoR1 revealed five CrleGV-SA isolates latent within the insect populations. The new isolates were named CrleGV-SA Ado, CrleGV-SA Cit, CrleGV-SA Mbl, CrleGVSA Nels and CrleGV-SA Mix isolates. The novelty of the five CrleGV-SA isolates was confirmed by the presence of unique submolar bands, indicating that each isolate was genetically different. PCR amplification and sequencing of the granulin and egt genes from the five isolates revealed several single nucleotide polymorph isms (SNPs) which, in some cases, resulted in amino acid substitutions. DNA profiles from RFLPs, as well as phylogenetic analysis based on granulin and egt sequencing showed the presence of two CrleGV-SA genome types for the CrleGV-SA isolate. Cryptex and CrleGV-SA Ado, CrleGV-SA Cit, CrleGV-SA Mbl and CrleGV-SA Mix were placed as members of Group one CrleGV-SA, and Cryptogran and CrleGV-SA Nels isolate were placed into Group two CrleGV-SA. In droplet feeding bioassays, the median survival time (STso) for neonate larvae inoculated with Group one and two CrleGV-SA were determined to range from 80 - 88 hours (3.33 - 3.67 days), for all five colonies. LDso values for Group one and two CrleGV-SA against neonates from the Addo, Citrusdal, Marble Hall, Nelspruit and Mixed colonies varied between some populations and ranged from 0.80 - 3.12 OBs per larva, indicating some level of variation in host susceptibility. This is the first study reporting the existence of genetically distinct CrleGV baculovirus isolates infecting FCM in different geographical areas of South Africa. The results of this study have broad-ranging implications for our understanding of baculovirus-host interactions and for the application of baculovirus basedbiopesticides.
- Full Text:
- Date Issued: 2012
Synthesis, characterization and antimicrobial activity of copper (II) complexes of some hydroxybenzaldimines and their derivatives
- Authors: Sobola, Abdullahi Owolabi
- Date: 2012
- Subjects: Copper , Schiff bases , Ligands
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4534 , http://hdl.handle.net/10962/d1016258
- Description: This study focuses on the antimicrobial activity of Cu(II) complexes of some orthohydroxybenzaldimines and its derivatives. Four different categories of Schiff base ligands were prepared by condensing salicylaldehyde, o-vanillin, p-vanillin and vanillin with p- and osubstituted anilines; 1-aminonaphthalene; 2- and 3-aminopyridine; 2- and 3- aminomethylpyridine as well as 2-aminobenzimidazole. The last category was prepared from ophenylenediamine and o-vanillin. The Schiff base ligands have been characterized by a combination of elemental analysis and spectral (¹H- and ¹³C-NMR, UV/Visible, infrared and Raman) data. The existence of strong intramolecular hydrogen bonding in the orthohydoxybenzaldimines was evident from the chemical shift values of the hydroxyl proton in the ¹H-NMR spectra of the Schiff base ligands. The hydroxyl proton resonates at high frequency and thus absorbed far downfield at 13.46-11.83 ppm, reflecting the presence of hydrogen bonding between the hydroxyl proton and the imine nitrogen. In the p-substituted aniline analogues of the Schiff base, a plot of the chemical shift values of the hydroxyl proton against the Hammett's substituent parameters gave a linear correlation between the electronegativities of the substituents and the chemical shift values. The nitro group with the highest electronegativity caused the least deshielding of the hydroxyl proton and thus absorbed upfield compared to the less electronegative substituents such as the CH3 and OCH3 analogues. Likewise, in the solid state infrared spectra of the ligands, the hydroxyl stretching band of the ortho-hydroxyl Schiff base ligands was observed as a very broad band and at much lower frequency, 3100-2100 cm⁻¹, indicating the existence of strong intramolecular hydrogen bonding. In the same vein, ¹H- and ¹³C-NMR spectral data for the Schiff base ligands indicated that the prepared compounds exist in the enol form in aprotic solvent, chloroform. The methine proton appeared as singlet and there was no carbonyl signal in the ¹³C-NMR spectra of the Schiff base ligands. This was supported by the infrared data having no vibrational band attributable to the carbonyl stretching of the keto-form of the Schiff base ligands in solid state. However, the UV/Visible study of the Schiff base ligands in protic solvent, methanol, suggested the existence of some of the Schiff base ligands in keto-enol form. A band at greater than 400 nm was observed in the UV/Visible spectra of the ligands and this has been attributed to the presence of the keto form of orthohydroxyl Schiff base ligands in solution. A plot of the molar absorptivity (ε) of the band at greater than 400 nm against Hammett substituent parameters revealed that the intensity of the bands increased with the electronegativity of the substituents. The Cu(II) complexes of salicylaldehyde, o-vanillin and a few p-vanillin based Schiff base ligands are reported in this work. It was observed that introduction of Cu(II) ions into the ligand system resulted in the hydrolysis of the imine band in few cases. All the isolated complexes have been characterized by elemental analysis, conductivity measurement, infrared and UV/Visible spectral data. The structures of three of the Cu(II) complexes were further confirmed by X-ray single crystal diffraction. The Schiff base ligands either coordinated as neutral base through the imine nitrogen or via the imine nitrogen and the phenolic oxygen atoms. In addition, the benzimidazole-based and ovan-2-pico analogues equally coordinated through the imidazole N-3 nitrogen and the azine nitrogen respectively; thus acted as tridentate. In general, the synthesized Cu(II) complexes fell into seven categories viz: [Cu(LH)Cl(H₂O)]Cl; [Cu(LH)₂Cl₂].xH₂O; [CuL₂]; [Cu₂L₂]; [Cu(LH)Cl(H₂O)]Cl; and [MLCl]. The Cu(II) complexes of the form, M(LH)₂Cl₂.xH₂O were either 1:1 or non-electrolyte in methanol and DMF. The third category, CuL₂, was however, non-electrolyte existing as neutral four coordinate Cu(II) complexes. X-ray single crystal structure of Cu(II) complexes derived from the ammonia-based Schiff bases revealed a square planar geometry for the complexes and this agreed with the planar geometry that has been reported for Cu(II) complexes of N-arylsalicylaldimines of the type studied in this work. The complexes, [Cu₂L₂], resulted from the ortho-hydroxyaniline analogues and were polymeric with the Schiff base ligands coordinating to the Cu(II) ions as tridentate dibasic via the imine nitrogen, phenolic oxygen and the aminophenolic oxygen atoms. Cu(II) complexes prepared from ovan-2-ampy and ovan-2-pico Schiff bases were of the forms [Cu(LH)Cl(H₂O)]Cl and [CuLCl] respectively. The X-ray crystal structure of [Cu(ovan-2- pico)Cl] revealed a four-coordinate square planar geometry for the complex. In the same vein, the o-phenylenediamine complexes were of the form [Cu(L)(H₂O)], with the X-ray crystal structure of [Cu(bis-ovanphen)(H₂O)] revealing a square pyramidal geometry. The Schiff base ligands and the isolated Cu(II) complexes have been evaluated for their antimicrobial activity against three bacterial strains (Escherichia coli ATCC® 8739™*, Staphylococcus aureus subsp. aureus ATCC® 6538™* and Bacillus subtilis subsp. spizizeni ATCC® 6633™*) and one fungal strain, Candida albicans ATCC® 2091™*, using agar disc diffusion and broth dilution techniques. It was observed that the presence of the methoxyl group at the ortho-position of the aldehyde moiety of the Schiff base ligands enhanced the activity of the ligand tremendously and thus the o-vanillin analogues showed the highest potency against the tested organisms. In addition, the hydroxyaniline analogues were equally the most promising of all the substituted aniline based Schiff bases. The o-vanillin analogues of the aminopyridines and aminomethylpyridines also exhibited significant activity against the tested organisms. All the 2-aminobenzimidazole series were active against the tested organisms. It should be noted that E. coli was the least susceptible of all the microorganisms while the highest potency was exhibited against the fungus of choice, Candida albicans. Lastly, chelation of the Schiff base ligands with Cu(II) ions did not have significant influence on the activity of the free ligands.
- Full Text:
- Date Issued: 2012
- Authors: Sobola, Abdullahi Owolabi
- Date: 2012
- Subjects: Copper , Schiff bases , Ligands
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4534 , http://hdl.handle.net/10962/d1016258
- Description: This study focuses on the antimicrobial activity of Cu(II) complexes of some orthohydroxybenzaldimines and its derivatives. Four different categories of Schiff base ligands were prepared by condensing salicylaldehyde, o-vanillin, p-vanillin and vanillin with p- and osubstituted anilines; 1-aminonaphthalene; 2- and 3-aminopyridine; 2- and 3- aminomethylpyridine as well as 2-aminobenzimidazole. The last category was prepared from ophenylenediamine and o-vanillin. The Schiff base ligands have been characterized by a combination of elemental analysis and spectral (¹H- and ¹³C-NMR, UV/Visible, infrared and Raman) data. The existence of strong intramolecular hydrogen bonding in the orthohydoxybenzaldimines was evident from the chemical shift values of the hydroxyl proton in the ¹H-NMR spectra of the Schiff base ligands. The hydroxyl proton resonates at high frequency and thus absorbed far downfield at 13.46-11.83 ppm, reflecting the presence of hydrogen bonding between the hydroxyl proton and the imine nitrogen. In the p-substituted aniline analogues of the Schiff base, a plot of the chemical shift values of the hydroxyl proton against the Hammett's substituent parameters gave a linear correlation between the electronegativities of the substituents and the chemical shift values. The nitro group with the highest electronegativity caused the least deshielding of the hydroxyl proton and thus absorbed upfield compared to the less electronegative substituents such as the CH3 and OCH3 analogues. Likewise, in the solid state infrared spectra of the ligands, the hydroxyl stretching band of the ortho-hydroxyl Schiff base ligands was observed as a very broad band and at much lower frequency, 3100-2100 cm⁻¹, indicating the existence of strong intramolecular hydrogen bonding. In the same vein, ¹H- and ¹³C-NMR spectral data for the Schiff base ligands indicated that the prepared compounds exist in the enol form in aprotic solvent, chloroform. The methine proton appeared as singlet and there was no carbonyl signal in the ¹³C-NMR spectra of the Schiff base ligands. This was supported by the infrared data having no vibrational band attributable to the carbonyl stretching of the keto-form of the Schiff base ligands in solid state. However, the UV/Visible study of the Schiff base ligands in protic solvent, methanol, suggested the existence of some of the Schiff base ligands in keto-enol form. A band at greater than 400 nm was observed in the UV/Visible spectra of the ligands and this has been attributed to the presence of the keto form of orthohydroxyl Schiff base ligands in solution. A plot of the molar absorptivity (ε) of the band at greater than 400 nm against Hammett substituent parameters revealed that the intensity of the bands increased with the electronegativity of the substituents. The Cu(II) complexes of salicylaldehyde, o-vanillin and a few p-vanillin based Schiff base ligands are reported in this work. It was observed that introduction of Cu(II) ions into the ligand system resulted in the hydrolysis of the imine band in few cases. All the isolated complexes have been characterized by elemental analysis, conductivity measurement, infrared and UV/Visible spectral data. The structures of three of the Cu(II) complexes were further confirmed by X-ray single crystal diffraction. The Schiff base ligands either coordinated as neutral base through the imine nitrogen or via the imine nitrogen and the phenolic oxygen atoms. In addition, the benzimidazole-based and ovan-2-pico analogues equally coordinated through the imidazole N-3 nitrogen and the azine nitrogen respectively; thus acted as tridentate. In general, the synthesized Cu(II) complexes fell into seven categories viz: [Cu(LH)Cl(H₂O)]Cl; [Cu(LH)₂Cl₂].xH₂O; [CuL₂]; [Cu₂L₂]; [Cu(LH)Cl(H₂O)]Cl; and [MLCl]. The Cu(II) complexes of the form, M(LH)₂Cl₂.xH₂O were either 1:1 or non-electrolyte in methanol and DMF. The third category, CuL₂, was however, non-electrolyte existing as neutral four coordinate Cu(II) complexes. X-ray single crystal structure of Cu(II) complexes derived from the ammonia-based Schiff bases revealed a square planar geometry for the complexes and this agreed with the planar geometry that has been reported for Cu(II) complexes of N-arylsalicylaldimines of the type studied in this work. The complexes, [Cu₂L₂], resulted from the ortho-hydroxyaniline analogues and were polymeric with the Schiff base ligands coordinating to the Cu(II) ions as tridentate dibasic via the imine nitrogen, phenolic oxygen and the aminophenolic oxygen atoms. Cu(II) complexes prepared from ovan-2-ampy and ovan-2-pico Schiff bases were of the forms [Cu(LH)Cl(H₂O)]Cl and [CuLCl] respectively. The X-ray crystal structure of [Cu(ovan-2- pico)Cl] revealed a four-coordinate square planar geometry for the complex. In the same vein, the o-phenylenediamine complexes were of the form [Cu(L)(H₂O)], with the X-ray crystal structure of [Cu(bis-ovanphen)(H₂O)] revealing a square pyramidal geometry. The Schiff base ligands and the isolated Cu(II) complexes have been evaluated for their antimicrobial activity against three bacterial strains (Escherichia coli ATCC® 8739™*, Staphylococcus aureus subsp. aureus ATCC® 6538™* and Bacillus subtilis subsp. spizizeni ATCC® 6633™*) and one fungal strain, Candida albicans ATCC® 2091™*, using agar disc diffusion and broth dilution techniques. It was observed that the presence of the methoxyl group at the ortho-position of the aldehyde moiety of the Schiff base ligands enhanced the activity of the ligand tremendously and thus the o-vanillin analogues showed the highest potency against the tested organisms. In addition, the hydroxyaniline analogues were equally the most promising of all the substituted aniline based Schiff bases. The o-vanillin analogues of the aminopyridines and aminomethylpyridines also exhibited significant activity against the tested organisms. All the 2-aminobenzimidazole series were active against the tested organisms. It should be noted that E. coli was the least susceptible of all the microorganisms while the highest potency was exhibited against the fungus of choice, Candida albicans. Lastly, chelation of the Schiff base ligands with Cu(II) ions did not have significant influence on the activity of the free ligands.
- Full Text:
- Date Issued: 2012
Synthetic and bioactivity studies of antiplasmodial and antibacterial marine natural products
- Authors: Young, Ryan Mark
- Date: 2012
- Subjects: Antibacterial agents Marine natural products Marine pharmacology Plasmodium falciparum Staphylococcus aureus Isocyanides Imidazoles
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4378 , http://hdl.handle.net/10962/d1005043
- Description: This thesis is divided into two parts, assessing marine and synthetic compounds active firstly against Plasmodium falciparum (Chapter 3 and 4) and secondly active against methicillin resistant Staphylococcus aureus (MRSA, Chapter 5). In Chapter 3 the synthesis of nine new tricyclic podocarpanes (3.203-3.207 and 3.209-3.212) from the diterpene (+)-manool is described. Initial SAR study of synthetic podocarpanes concluded that the most active compound was a C-13 phenyl substituted podocarpane (3.204, IC₅₀ 6.6 μM). By preparing analogues with varying halogenated substituents on the phenyl ring (3.209-3.212) the antiplasmodial activity was improved (IC₅₀ 1.4 μM), while simultaneously decreasing the haemolysis previously reported for this class of compounds. Inspired by the antiplasmodial activity of Wright and Wattanapiromsakul’s tricycle marine isonitriles (2.16-2.21 and 2.24-2.27) an unsuccessfully attempt was made to convert tertiary alcohol moieties to isonitrile functionalities in compounds 3.188, 3.204-3.207 and 3.209-3.212. Over a decade ago Wright et al. proposed a putative antiplasmodial mechanism of action for marine isonitriles (2.4, 2.9, 2.15, 2.19 and 2.35) and isothiocyanate (2.34) which involved interference in haem detoxification by P. falciparum thus inhibiting the growth of the parasite. In Chapter 4 we describe how we successfully managed to scale down Egan’s β-haematin inhibition assay for the analyses of small quantities of marine natural products as potential β-haematin inhibitors. Our modified assay revealed that the most active antiplasmodial marine isonitrile 2.9 (IC₅₀ 13 nM) showed total β-haematin inhibition while 2.15 (IC₅₀ 81 nM) and 2.19 (IC₅₀ 31 nM) showed partial inhibition at three equivalents relative to haem. Using contempary molecular modelling techniques the charge on the isonitrile functionality was more accurately describe and the modified charge data sets was used to explore docking of marine isonitriles to haem using AutoDock. In Chapter 5 we describe how a lead South African marine bisindole MRSA pyruvate kinase inhibitor (5.8) was discovered in collaboration with colleagues at the University of British Columbia (UBC) and how this discovery inspired us to design a synthetic route to the dibrominated bisindole, isobromotopsentin (5.20) in an attempt to increase the bioactivity displayed by 5.8. We devised a fast and high yielding synthetic route using microwave assited organic synthesis. We first tested this synthesis using simple aryl glyoxals (5.27-5.32) as precursors to synthesize biphenylimidazoles (5.21-5.26), which later allowed us to synthesize the ascidian natural product 5.111. This method was sucessfully extended to the synthesis of deoxytopsentin (5.33) from an N-Boc protected indole methyl ketone (5.89). We subsequently were able to effectively remove the carbamate protection via thermal decomposition by heating the protected bisindole imidazole (5.90) in a microwave reactor for 5 min under argon. The synthesis of 5.20 resulted in an inseparable mixture of monoprotected and totally deprotected topsentin products, and due to time constraints we were not able to optimise this synthesis. Nonetheless our synthesis of the marine natural product 5.33 which was faster and higher yielding than previously reported routes could be extended to the synthesis of other topsentin bisindoles (5.138-5.140). Work towards this goal continues in our laboratory.
- Full Text:
- Date Issued: 2012
- Authors: Young, Ryan Mark
- Date: 2012
- Subjects: Antibacterial agents Marine natural products Marine pharmacology Plasmodium falciparum Staphylococcus aureus Isocyanides Imidazoles
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4378 , http://hdl.handle.net/10962/d1005043
- Description: This thesis is divided into two parts, assessing marine and synthetic compounds active firstly against Plasmodium falciparum (Chapter 3 and 4) and secondly active against methicillin resistant Staphylococcus aureus (MRSA, Chapter 5). In Chapter 3 the synthesis of nine new tricyclic podocarpanes (3.203-3.207 and 3.209-3.212) from the diterpene (+)-manool is described. Initial SAR study of synthetic podocarpanes concluded that the most active compound was a C-13 phenyl substituted podocarpane (3.204, IC₅₀ 6.6 μM). By preparing analogues with varying halogenated substituents on the phenyl ring (3.209-3.212) the antiplasmodial activity was improved (IC₅₀ 1.4 μM), while simultaneously decreasing the haemolysis previously reported for this class of compounds. Inspired by the antiplasmodial activity of Wright and Wattanapiromsakul’s tricycle marine isonitriles (2.16-2.21 and 2.24-2.27) an unsuccessfully attempt was made to convert tertiary alcohol moieties to isonitrile functionalities in compounds 3.188, 3.204-3.207 and 3.209-3.212. Over a decade ago Wright et al. proposed a putative antiplasmodial mechanism of action for marine isonitriles (2.4, 2.9, 2.15, 2.19 and 2.35) and isothiocyanate (2.34) which involved interference in haem detoxification by P. falciparum thus inhibiting the growth of the parasite. In Chapter 4 we describe how we successfully managed to scale down Egan’s β-haematin inhibition assay for the analyses of small quantities of marine natural products as potential β-haematin inhibitors. Our modified assay revealed that the most active antiplasmodial marine isonitrile 2.9 (IC₅₀ 13 nM) showed total β-haematin inhibition while 2.15 (IC₅₀ 81 nM) and 2.19 (IC₅₀ 31 nM) showed partial inhibition at three equivalents relative to haem. Using contempary molecular modelling techniques the charge on the isonitrile functionality was more accurately describe and the modified charge data sets was used to explore docking of marine isonitriles to haem using AutoDock. In Chapter 5 we describe how a lead South African marine bisindole MRSA pyruvate kinase inhibitor (5.8) was discovered in collaboration with colleagues at the University of British Columbia (UBC) and how this discovery inspired us to design a synthetic route to the dibrominated bisindole, isobromotopsentin (5.20) in an attempt to increase the bioactivity displayed by 5.8. We devised a fast and high yielding synthetic route using microwave assited organic synthesis. We first tested this synthesis using simple aryl glyoxals (5.27-5.32) as precursors to synthesize biphenylimidazoles (5.21-5.26), which later allowed us to synthesize the ascidian natural product 5.111. This method was sucessfully extended to the synthesis of deoxytopsentin (5.33) from an N-Boc protected indole methyl ketone (5.89). We subsequently were able to effectively remove the carbamate protection via thermal decomposition by heating the protected bisindole imidazole (5.90) in a microwave reactor for 5 min under argon. The synthesis of 5.20 resulted in an inseparable mixture of monoprotected and totally deprotected topsentin products, and due to time constraints we were not able to optimise this synthesis. Nonetheless our synthesis of the marine natural product 5.33 which was faster and higher yielding than previously reported routes could be extended to the synthesis of other topsentin bisindoles (5.138-5.140). Work towards this goal continues in our laboratory.
- Full Text:
- Date Issued: 2012
Systematic marine spatial planning and monitoring in a data poor environment: a case study of Algoa Bay, South Africa
- Authors: Chalmers, Russell
- Date: 2012
- Subjects: Spatial ecology -- South Africa -- Algoa Bay , Coastal zone management -- South Africa -- Algoa Bay
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5373 , http://hdl.handle.net/10962/d1015695
- Description: Globally the failure of traditional fisheries management approaches is evident through the increasing number of overexploited or depleted marine stocks. Past sectoral management has failed to address cumulative impacts of fisheries activities on ecosystem health. Ecosystem based approaches have been advocated as a viable alternative for sustainable management of marine ecosystems as they present a holistic and precautionary approach, which integrates management of multiple activities with that of maintaining ecological health. Although conceptually advanced, implementation has been poor due to the complexities of competing ecological and socio-economic management objectives. Marine spatial planning can facilitate the implementation of ecosystem based management as it is able to address the spatial heterogeneity of biological communities and anthropogenic activities. Ecosystem based management approaches aim to address the full range of anthropogenic drivers on the marine environment, including but not limited to fisheries, tourism, coastal development, and land and marine based pollution sources amongst others. Fisheries activities have a direct impact on the local marine environment and were therefore the focus of this study which forms a starting point for implementing ecosystem based management in Algoa Bay. It is envisaged that future research will build on this foundation and include additional anthropogenic drivers into the management and monitoring strategies developed in this study in order to achieve a truly holistic ecosystem approach to management in Algoa Bay. Algoa Bay is situated centrally within the warm-temperate Agulhas bioregion along the east coast of South Africa and is the largest and best formed logarithmic spiral bay along this section of coastline. A large city, two commercial ports and several coastal settlements are located within Algoa Bay and a wide range of marine based activities occur within the area. A large section of the coastline is proclaimed as a National Park yet only two small offshore marine areas are formally protected. The development of a large marine protected area (MPA) adjoining the terrestrial section was proposed in the mid-1990s but a lack of adequate spatial data with which to quantify the fishery costs and conservation benefits led to wide scale public opposition and halted the declaration process. The primary goal of this study was to obtain and analyse baseline data to understand spatial and temporal trends in the distribution and abundance of fish populations and fisheries activities in order to develop a spatial framework for marine conservation and management in a data limited situation using Algoa Bay, South Africa as a case study. Furthermore, it aims to contribute to the development of a monitoring framework to evaluate the success of implementation and the resultant changes in biological and socio-economic environments. This information will be used to re-initiate the stakeholder engagement process in the future.
- Full Text:
- Date Issued: 2012
- Authors: Chalmers, Russell
- Date: 2012
- Subjects: Spatial ecology -- South Africa -- Algoa Bay , Coastal zone management -- South Africa -- Algoa Bay
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5373 , http://hdl.handle.net/10962/d1015695
- Description: Globally the failure of traditional fisheries management approaches is evident through the increasing number of overexploited or depleted marine stocks. Past sectoral management has failed to address cumulative impacts of fisheries activities on ecosystem health. Ecosystem based approaches have been advocated as a viable alternative for sustainable management of marine ecosystems as they present a holistic and precautionary approach, which integrates management of multiple activities with that of maintaining ecological health. Although conceptually advanced, implementation has been poor due to the complexities of competing ecological and socio-economic management objectives. Marine spatial planning can facilitate the implementation of ecosystem based management as it is able to address the spatial heterogeneity of biological communities and anthropogenic activities. Ecosystem based management approaches aim to address the full range of anthropogenic drivers on the marine environment, including but not limited to fisheries, tourism, coastal development, and land and marine based pollution sources amongst others. Fisheries activities have a direct impact on the local marine environment and were therefore the focus of this study which forms a starting point for implementing ecosystem based management in Algoa Bay. It is envisaged that future research will build on this foundation and include additional anthropogenic drivers into the management and monitoring strategies developed in this study in order to achieve a truly holistic ecosystem approach to management in Algoa Bay. Algoa Bay is situated centrally within the warm-temperate Agulhas bioregion along the east coast of South Africa and is the largest and best formed logarithmic spiral bay along this section of coastline. A large city, two commercial ports and several coastal settlements are located within Algoa Bay and a wide range of marine based activities occur within the area. A large section of the coastline is proclaimed as a National Park yet only two small offshore marine areas are formally protected. The development of a large marine protected area (MPA) adjoining the terrestrial section was proposed in the mid-1990s but a lack of adequate spatial data with which to quantify the fishery costs and conservation benefits led to wide scale public opposition and halted the declaration process. The primary goal of this study was to obtain and analyse baseline data to understand spatial and temporal trends in the distribution and abundance of fish populations and fisheries activities in order to develop a spatial framework for marine conservation and management in a data limited situation using Algoa Bay, South Africa as a case study. Furthermore, it aims to contribute to the development of a monitoring framework to evaluate the success of implementation and the resultant changes in biological and socio-economic environments. This information will be used to re-initiate the stakeholder engagement process in the future.
- Full Text:
- Date Issued: 2012
Teachers' leadership roles at a public rural school in the Ohangwena Region, Namibia
- Nauyoma-Hamupembe, Ladipaleni Ndadiinina
- Authors: Nauyoma-Hamupembe, Ladipaleni Ndadiinina
- Date: 2012
- Subjects: Educational leadership -- Namibia -- Ohangwena Rural schools -- Namibia -- Ohangwena School management and organization -- Namibia -- Ohangwena Teachers -- Namibia -- Ohangwena Teacher-principal relationships -- Namibia -- Ohangwena
- Language: English
- Type: Thesis , Masters , MEd
- Identifier: vital:1794 , http://hdl.handle.net/10962/d1003679
- Description: The changing global and local circumstances and shift for democracy posed particular problems for school administration and leadership and made it difficult for principals to fulfil leadership responsibilities in schools alone. Hence principals require the assistance of all stakeholders in the school, and teachers in particular, to work together as a team and share the diverse leadership load for the improvement of schools. Thus, leadership in schools needs to be shared and distributed in a collaborative manner among teachers and principals working as a group to accomplish the primary objective of their schools, which is to improve learners’ achievement. For this idea to be embraced, I suggest it may require an urgent need for advanced knowledge and understanding of teacher leadership in schools, among teachers and principals, if schools are to thrive. This research studied the phenomenon of teacher leadership at a public rural school in the Ohangwena region of Namibia. It explored the teachers’ experiences of their leadership roles, and specifically the challenges inherent within the practice of teacher leadership in a school. A qualitative interpretive case study was conducted, employing document analysis, semi‐structured interviews and observations to produce data with regard to teachers’ experiences of their leadership roles, challenges inherent within its practice and possible strategies to promote teacher leadership. The analysis and the triangulation across the data sets suggested that teacher leadership existed in the case study school where it appeared in four different areas of leadership practice. These areas of leadership practices (Grant, 2008, p. 93) were, for example, in the classroom, outside the classroom in curricular and extra‐curricular activities, in school‐wide leadership development and between other neighbouring schools in the community. The school had a view of teacher leadership which was strongly located within the classroom and outside the classroom in curricular and extra‐curricular activities where teachers worked and interacted with their colleagues and learners. Teacher leadership was severely limited in the area of whole school development and almost non‐existent in the area outside the school between teachers across neighbouring schools, at circuit or district level and in the community. The study suggested that the nature of teacher leadership in the case study school was a restricted form of teacher leadership (Harris and Muijs, 2005) due to a range of factors which impeded its practice. The factors were, for example, a lack of involvement of all teachers in whole school leadership and school‐wide decision‐making. Other factors were limited time for teachers in the school, a lack of leadership development amongst the principal and teachers as well as resistance for teachers to leadership in the case study school.
- Full Text:
- Date Issued: 2012
- Authors: Nauyoma-Hamupembe, Ladipaleni Ndadiinina
- Date: 2012
- Subjects: Educational leadership -- Namibia -- Ohangwena Rural schools -- Namibia -- Ohangwena School management and organization -- Namibia -- Ohangwena Teachers -- Namibia -- Ohangwena Teacher-principal relationships -- Namibia -- Ohangwena
- Language: English
- Type: Thesis , Masters , MEd
- Identifier: vital:1794 , http://hdl.handle.net/10962/d1003679
- Description: The changing global and local circumstances and shift for democracy posed particular problems for school administration and leadership and made it difficult for principals to fulfil leadership responsibilities in schools alone. Hence principals require the assistance of all stakeholders in the school, and teachers in particular, to work together as a team and share the diverse leadership load for the improvement of schools. Thus, leadership in schools needs to be shared and distributed in a collaborative manner among teachers and principals working as a group to accomplish the primary objective of their schools, which is to improve learners’ achievement. For this idea to be embraced, I suggest it may require an urgent need for advanced knowledge and understanding of teacher leadership in schools, among teachers and principals, if schools are to thrive. This research studied the phenomenon of teacher leadership at a public rural school in the Ohangwena region of Namibia. It explored the teachers’ experiences of their leadership roles, and specifically the challenges inherent within the practice of teacher leadership in a school. A qualitative interpretive case study was conducted, employing document analysis, semi‐structured interviews and observations to produce data with regard to teachers’ experiences of their leadership roles, challenges inherent within its practice and possible strategies to promote teacher leadership. The analysis and the triangulation across the data sets suggested that teacher leadership existed in the case study school where it appeared in four different areas of leadership practice. These areas of leadership practices (Grant, 2008, p. 93) were, for example, in the classroom, outside the classroom in curricular and extra‐curricular activities, in school‐wide leadership development and between other neighbouring schools in the community. The school had a view of teacher leadership which was strongly located within the classroom and outside the classroom in curricular and extra‐curricular activities where teachers worked and interacted with their colleagues and learners. Teacher leadership was severely limited in the area of whole school development and almost non‐existent in the area outside the school between teachers across neighbouring schools, at circuit or district level and in the community. The study suggested that the nature of teacher leadership in the case study school was a restricted form of teacher leadership (Harris and Muijs, 2005) due to a range of factors which impeded its practice. The factors were, for example, a lack of involvement of all teachers in whole school leadership and school‐wide decision‐making. Other factors were limited time for teachers in the school, a lack of leadership development amongst the principal and teachers as well as resistance for teachers to leadership in the case study school.
- Full Text:
- Date Issued: 2012
The analysis of the strain level and the predicted human error probability for critical hospital tasks
- Authors: Burford, Eva-Maria
- Date: 2012
- Subjects: Nursing errors -- South Africa -- Prevention , Nursing -- South Africa -- Psychological aspects , Hospitals -- Employees -- Health and hygiene -- South Africa , Nursing -- Job stress -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5104 , http://hdl.handle.net/10962/d1005182 , Nursing errors -- South Africa -- Prevention , Nursing -- South Africa -- Psychological aspects , Hospitals -- Employees -- Health and hygiene -- South Africa , Nursing -- Job stress -- South Africa
- Description: South African hospitals, as a result of numerous factors, have the problem of an increasing workload for nursing staff, which in turn may affect patient treatment quality. This project aimed at addressing patient treatment quality specifically from the perspective of worker capabilities by investigating the strain level and predicted human error probability associated with specific patient-centered tasks in the South African health care sector. This was achieved through two independent yet interlinked studies which focused on seven patient-centred tasks. The tasks analysed were the tasks of setting up and changing intravenous medication, administering injection and pill medication, measuring blood glucose, temperature and heart rate and blood pressure. In the first study, work environment and task characteristics, task structure and execution were analysed. In addition to the task execution, the resulting strain levels, in the form of heart rate measures and subjective ratings of workload, were studied. The second study determined the error protocols and predictive error probability within the healthcare environment for the seven pre-defined tasks. The results for the first study established that different organizational and environment factors could affect task complexity and workload. The individual task components and information processing requirements for each task was also established. For the strain analysis, significant results for the tasks were determined for heart rate frequency and the heart rate variability measures, but some of these were contradictory. For the second study, specific error protocols and error reporting data were determined for the hospital where this research was conducted. Additionally the predictive error probability for the pre-defined tasks was determined. This combined approach and collective results indicate that strain and predictive error probability as a result of task workload can be determined in the field as well as being able to identify which factors have an effect on task strain and error probability. The value of this research lies in the foundation that the gathered information provides and the numerous potential applications of this data. These applications include providing recommendations aimed at improving nursing work environment with regards to workload, improving patient treatment as a result of a reduction in errors and the potential foundation these results provide for future research
- Full Text:
- Date Issued: 2012
- Authors: Burford, Eva-Maria
- Date: 2012
- Subjects: Nursing errors -- South Africa -- Prevention , Nursing -- South Africa -- Psychological aspects , Hospitals -- Employees -- Health and hygiene -- South Africa , Nursing -- Job stress -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5104 , http://hdl.handle.net/10962/d1005182 , Nursing errors -- South Africa -- Prevention , Nursing -- South Africa -- Psychological aspects , Hospitals -- Employees -- Health and hygiene -- South Africa , Nursing -- Job stress -- South Africa
- Description: South African hospitals, as a result of numerous factors, have the problem of an increasing workload for nursing staff, which in turn may affect patient treatment quality. This project aimed at addressing patient treatment quality specifically from the perspective of worker capabilities by investigating the strain level and predicted human error probability associated with specific patient-centered tasks in the South African health care sector. This was achieved through two independent yet interlinked studies which focused on seven patient-centred tasks. The tasks analysed were the tasks of setting up and changing intravenous medication, administering injection and pill medication, measuring blood glucose, temperature and heart rate and blood pressure. In the first study, work environment and task characteristics, task structure and execution were analysed. In addition to the task execution, the resulting strain levels, in the form of heart rate measures and subjective ratings of workload, were studied. The second study determined the error protocols and predictive error probability within the healthcare environment for the seven pre-defined tasks. The results for the first study established that different organizational and environment factors could affect task complexity and workload. The individual task components and information processing requirements for each task was also established. For the strain analysis, significant results for the tasks were determined for heart rate frequency and the heart rate variability measures, but some of these were contradictory. For the second study, specific error protocols and error reporting data were determined for the hospital where this research was conducted. Additionally the predictive error probability for the pre-defined tasks was determined. This combined approach and collective results indicate that strain and predictive error probability as a result of task workload can be determined in the field as well as being able to identify which factors have an effect on task strain and error probability. The value of this research lies in the foundation that the gathered information provides and the numerous potential applications of this data. These applications include providing recommendations aimed at improving nursing work environment with regards to workload, improving patient treatment as a result of a reduction in errors and the potential foundation these results provide for future research
- Full Text:
- Date Issued: 2012
The design, synthesis and antiplasmodial activity of a series of halogenated fosmidomycin analogues and hybrid drugs
- Authors: Afolayan, Anthonia Folake
- Date: 2012
- Subjects: Uncatalogued
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64370 , vital:28538
- Description: Malaria continues to be a devastating disease and a major cause of death in sub-Saharan Africa. With resistance against most of the available antimalarial drugs, there is a need for ongoing research and development of antimalarial agents. Fosmidomycin and its acetyl analogue FR900098 have been identified as potent inhibitors of Plasmodium falciparum, the causative agent of the most deadly form of malaria. Clinical trials of these agents have revealed poor absorption due to their high hydrophilicity. In the present studies the effect of halogenation of the acyl chain as well as the biological effect of extending the acyl sidechain was explored. This provided the basis on which fosmidomycin hybrids were designed to investigate the feasibility of hybrid extending into NADPH binding pocket. Synthesis of a series of halogenated FR900098 analogues was carried out in three stages. This included i) The introduction of the phosphonate group by reaction with 1,3dibromopropane in an Arbuzov reaction, ii) The introduction of a hydroxamate group by reaction of the propyl phosphonate by means of a nucleophilic substitution reaction with BocNHOBn and iii) The introduction of a halogenated acyl side chain on a protected fosmidomycin backbone. The synthesis of fosmidomycin-hybrids for which chloroquinefosmidomycin hybrids were used as the prototype, involved convergence of the two separately constructed moieties i.e. fosmidomycin and the quinoline moieties in a covalent linkage. The quinoline moiety was easily synthesized from the reaction of 4,7dichloroquinoline with 1,2-diamino ethane. The aminoquinoline so formed resulted in chloroquine-fosmidomycin hybrids 3.8 and 3.9 when reacted with halogenated FR900098 analogues. Antiplasmodial assays were conducted on the chloroquine-fosmidomycin hybrids and the halogenated fosmidomycin derivatives against the chloroquine resistant Gambian FCR-3 strain of P. falciparum. The most potent iodoacetyl fosmidomycin analogues 2.21 gave an IC50 value of 5.54 µM which is eight times more potent than the known antiplasmodial FR900098 which gave an IC50 value of 41.67 µM. All the halogenated FR900098 analogues showed better antiplasmodial activity than their non-halogenated derivatives. This indicated that the presence of halogens in the FR900098 analogues contributes to their biological Chapter 1 Literature review activity. The acetyl and propyl linked hybrids 3.8 and 3.9 showed potent antiplasmodial activity with IC50 values of 0.18 and 0.82 µM respectively. These were by far the most potent hybrids synthesized and provided leads for a new class of promising antimalarial agents. Preliminary E. coli DXR enzyme inhibition assays were carried out on the halogenated fosmidomycin analogues. The results showed good inhibition of the enzyme by the phosphonic acids of the chloroacetyl and chloropropyl analogues 2.1 and 2.2 respectively. Molecular modelling of the compounds on E. coli (PDB code: 2EGH) and P. falciparum (PDB code: 3AUA) DXR showed strong binding of the halogenated fosmidomycin analogues while the hybrids in the absence of docked NADPH showed minimum binding to the enzymes.
- Full Text:
- Date Issued: 2012
- Authors: Afolayan, Anthonia Folake
- Date: 2012
- Subjects: Uncatalogued
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64370 , vital:28538
- Description: Malaria continues to be a devastating disease and a major cause of death in sub-Saharan Africa. With resistance against most of the available antimalarial drugs, there is a need for ongoing research and development of antimalarial agents. Fosmidomycin and its acetyl analogue FR900098 have been identified as potent inhibitors of Plasmodium falciparum, the causative agent of the most deadly form of malaria. Clinical trials of these agents have revealed poor absorption due to their high hydrophilicity. In the present studies the effect of halogenation of the acyl chain as well as the biological effect of extending the acyl sidechain was explored. This provided the basis on which fosmidomycin hybrids were designed to investigate the feasibility of hybrid extending into NADPH binding pocket. Synthesis of a series of halogenated FR900098 analogues was carried out in three stages. This included i) The introduction of the phosphonate group by reaction with 1,3dibromopropane in an Arbuzov reaction, ii) The introduction of a hydroxamate group by reaction of the propyl phosphonate by means of a nucleophilic substitution reaction with BocNHOBn and iii) The introduction of a halogenated acyl side chain on a protected fosmidomycin backbone. The synthesis of fosmidomycin-hybrids for which chloroquinefosmidomycin hybrids were used as the prototype, involved convergence of the two separately constructed moieties i.e. fosmidomycin and the quinoline moieties in a covalent linkage. The quinoline moiety was easily synthesized from the reaction of 4,7dichloroquinoline with 1,2-diamino ethane. The aminoquinoline so formed resulted in chloroquine-fosmidomycin hybrids 3.8 and 3.9 when reacted with halogenated FR900098 analogues. Antiplasmodial assays were conducted on the chloroquine-fosmidomycin hybrids and the halogenated fosmidomycin derivatives against the chloroquine resistant Gambian FCR-3 strain of P. falciparum. The most potent iodoacetyl fosmidomycin analogues 2.21 gave an IC50 value of 5.54 µM which is eight times more potent than the known antiplasmodial FR900098 which gave an IC50 value of 41.67 µM. All the halogenated FR900098 analogues showed better antiplasmodial activity than their non-halogenated derivatives. This indicated that the presence of halogens in the FR900098 analogues contributes to their biological Chapter 1 Literature review activity. The acetyl and propyl linked hybrids 3.8 and 3.9 showed potent antiplasmodial activity with IC50 values of 0.18 and 0.82 µM respectively. These were by far the most potent hybrids synthesized and provided leads for a new class of promising antimalarial agents. Preliminary E. coli DXR enzyme inhibition assays were carried out on the halogenated fosmidomycin analogues. The results showed good inhibition of the enzyme by the phosphonic acids of the chloroacetyl and chloropropyl analogues 2.1 and 2.2 respectively. Molecular modelling of the compounds on E. coli (PDB code: 2EGH) and P. falciparum (PDB code: 3AUA) DXR showed strong binding of the halogenated fosmidomycin analogues while the hybrids in the absence of docked NADPH showed minimum binding to the enzymes.
- Full Text:
- Date Issued: 2012
The development of an orodispersible sildenafil citrate tablet intended for paediatric use
- Authors: Dagnolo, Bianca
- Date: 2012
- Subjects: Drug development -- Children -- Research -- South Africa , Pulmonary hypertension -- Children -- Research , Tablets (Medicine) -- Development , Pharmaceutical chemistry -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3751 , http://hdl.handle.net/10962/d1003229 , Drug development -- Children -- Research -- South Africa , Pulmonary hypertension -- Children -- Research , Tablets (Medicine) -- Development , Pharmaceutical chemistry -- Research
- Description: Sildenafil citrate (SC) is a phosphodiesterase-5 inhibitor that is used to treat pulmonary hypertension (PH) in paediatric patients. The purpose of these studies was to develop a formulation and manufacture an orodispersible tablet (ODT) that can be easily administered to neonates and children with PH. The advantages of ODT dosage forms include ease of administration, rapid dissolution of the API, SC. Furthermore the dosage form can be taken without water which is beneficial to patients without immediate access to potable fluids. A simple, rapid, accurate, precise and selective reversed-phase HPLC method was developed and validated in accordance with International Conference on Harmonization (ICH) guidelines and was successfully used for the analysis of SC as raw material and in SC containing pharmaceutical dosage forms. Preformulation studies were performed on SC, alone and in combination with potential excipients that could be used to make tablets. Investigations into potential interactions between SC and the excipients were performed using Differential Scanning Calorimetry (DSC) and Infrared Spectroscopy (IR). DSC results revealed that SC was compatible with all potential excipients except mannitol and magnesium stearate. However these interactions were not observed with IR and therefore it was concluded that the interactions were induced by the high temperatures that DSC operates at. Particle size and shape was also established by use of Scanning Electron Microscopy (SEM) and flow properties were monitored by calculating Carr’s Index (CI) and the Hausner Ratio (HR). Direct compression was used as the method of manufacture for SC tablets as this approach is simple and the most economic production approach. The powder blends were assessed for bulk and tapped density and the CI and HR were used to determine the flowability of the blends. The quality attributes of the resultant tablets that were monitored included uniformity of weight, friability, crushing strength, tensile strength, disintegration, wetting and in vitro dispersion times. Design of Experiments is an efficient statistical approach that has become a popular tool used in the pharmaceutical industry to optimize formulation compositions, as it allows for the investigation of several input factors at the same time whilst not using the tedious and traditional “ modification of one variable at a time” approach. A Central composite experimental design was chosen as the most appropriate means to optimize the formulation as it produces more accurate results as opposed to other experimental designs approaches as input factors are investigated at five different levels. Through the use of mathematical modelling, optimum concentrations of disintegrant(s) and an appropriate blending time were established. Analysis of the data from the experimental design and mathematical modelling studies reveal that no changes in disintegrant concentration or blending time altered the disintegration time of the formulation to any significant extent. This result is most likely due to the fact that the critical disintegrant concentration has been reached and increasing the disintegrant concentration further has no effect on disintegration time. It was also established that a change in the concentration of CMS and CRP altered the wetting time of the tablet significantly. Finally it was noted that there was a linear relationship between blending time and the uniformity of content of the tablets produced in these studies. The optimized product was a white tablet with a diameter of 7.31 mm with a thickness of 2.80mm.The dosage form had no visible cracks or evidence of picking or sticking. The tablet exhibits suitable friability and tensile strength while exhibiting a disintegration time of only 8s. Therefore an orodispersible tablet containing SC intended for paediatric use has been successfully developed, manufactured and optimized through the use of preformulation studies, appropriate quality control monitoring and mathematical modelling. These formulations require further optimization in respect of addition of flavours and or additional sweetening agents.
- Full Text:
- Date Issued: 2012
- Authors: Dagnolo, Bianca
- Date: 2012
- Subjects: Drug development -- Children -- Research -- South Africa , Pulmonary hypertension -- Children -- Research , Tablets (Medicine) -- Development , Pharmaceutical chemistry -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3751 , http://hdl.handle.net/10962/d1003229 , Drug development -- Children -- Research -- South Africa , Pulmonary hypertension -- Children -- Research , Tablets (Medicine) -- Development , Pharmaceutical chemistry -- Research
- Description: Sildenafil citrate (SC) is a phosphodiesterase-5 inhibitor that is used to treat pulmonary hypertension (PH) in paediatric patients. The purpose of these studies was to develop a formulation and manufacture an orodispersible tablet (ODT) that can be easily administered to neonates and children with PH. The advantages of ODT dosage forms include ease of administration, rapid dissolution of the API, SC. Furthermore the dosage form can be taken without water which is beneficial to patients without immediate access to potable fluids. A simple, rapid, accurate, precise and selective reversed-phase HPLC method was developed and validated in accordance with International Conference on Harmonization (ICH) guidelines and was successfully used for the analysis of SC as raw material and in SC containing pharmaceutical dosage forms. Preformulation studies were performed on SC, alone and in combination with potential excipients that could be used to make tablets. Investigations into potential interactions between SC and the excipients were performed using Differential Scanning Calorimetry (DSC) and Infrared Spectroscopy (IR). DSC results revealed that SC was compatible with all potential excipients except mannitol and magnesium stearate. However these interactions were not observed with IR and therefore it was concluded that the interactions were induced by the high temperatures that DSC operates at. Particle size and shape was also established by use of Scanning Electron Microscopy (SEM) and flow properties were monitored by calculating Carr’s Index (CI) and the Hausner Ratio (HR). Direct compression was used as the method of manufacture for SC tablets as this approach is simple and the most economic production approach. The powder blends were assessed for bulk and tapped density and the CI and HR were used to determine the flowability of the blends. The quality attributes of the resultant tablets that were monitored included uniformity of weight, friability, crushing strength, tensile strength, disintegration, wetting and in vitro dispersion times. Design of Experiments is an efficient statistical approach that has become a popular tool used in the pharmaceutical industry to optimize formulation compositions, as it allows for the investigation of several input factors at the same time whilst not using the tedious and traditional “ modification of one variable at a time” approach. A Central composite experimental design was chosen as the most appropriate means to optimize the formulation as it produces more accurate results as opposed to other experimental designs approaches as input factors are investigated at five different levels. Through the use of mathematical modelling, optimum concentrations of disintegrant(s) and an appropriate blending time were established. Analysis of the data from the experimental design and mathematical modelling studies reveal that no changes in disintegrant concentration or blending time altered the disintegration time of the formulation to any significant extent. This result is most likely due to the fact that the critical disintegrant concentration has been reached and increasing the disintegrant concentration further has no effect on disintegration time. It was also established that a change in the concentration of CMS and CRP altered the wetting time of the tablet significantly. Finally it was noted that there was a linear relationship between blending time and the uniformity of content of the tablets produced in these studies. The optimized product was a white tablet with a diameter of 7.31 mm with a thickness of 2.80mm.The dosage form had no visible cracks or evidence of picking or sticking. The tablet exhibits suitable friability and tensile strength while exhibiting a disintegration time of only 8s. Therefore an orodispersible tablet containing SC intended for paediatric use has been successfully developed, manufactured and optimized through the use of preformulation studies, appropriate quality control monitoring and mathematical modelling. These formulations require further optimization in respect of addition of flavours and or additional sweetening agents.
- Full Text:
- Date Issued: 2012
The diet and ecological role of black-backed jackals, Canis Mesomelas, in two conservation areas in the Eastern Cape Province, South Africa
- Authors: Brassine, Mathilde Chloé
- Date: 2012
- Subjects: Black-backed jackal -- South Africa -- Eastern Cape , Jackals -- South Africa -- Eastern Cape , Jackals -- Food , Wildlife conservation
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5660 , http://hdl.handle.net/10962/d1005344 , Black-backed jackal -- South Africa -- Eastern Cape , Jackals -- South Africa -- Eastern Cape , Jackals -- Food , Wildlife conservation
- Description: Mammalian predators are keystone species and can have disproportionately large impacts, relative to their abundance, on the communities and ecosystems they inhabit. In addition, predator-prey interactions (including bottom-up and top-down effects) are the fundamental linkage among species in food webs. Thus, understanding the food requirements of predators is imperative. There have been no comprehensive studies on the diet of black-backed jackals (Canis mesomelas) across a full seasonal cycle in the Albany Thicket Biome of the Eastern Cape Province. This biome is rich in plant diversity, is highly nutritious for herbivores and supports a large number of mammalian species, yet it is poorly conserved. The aim of the present study was to establish the diet of black-backed jackals on two conservation areas where thicket vegetation dominates (Great Fish River Reserve and Kwandwe Private Game Reserve). The diet was assessed using scats collected monthly from June 2009 to May 2010 and a sample of 25 stomachs over the same period. At both sites and across all seasons, mammalian hair was encountered most often (93% of all scats) and a total of 23 mammal species were consumed. Of the mammals recorded in the scats, hair from several ungulate species was encountered most frequently and these were mostly hider species (offspring hidden in tall vegetation just after birth). On a seasonal basis, the proportion of mammalian hair was lowest in autumn. However, the contribution of fruits (Carissa haematocarpa, Diospyros lycioides and Grewia robusta) to the diet was significantly higher during this season. This suggests that black-backed jackals may employ diet switching in the Eastern Cape as a mechanism to capitalise on seasonally abundant food sources. Based on the stomach content analysis, invertebrates were consumed as frequently as mammalian prey throughout the year but mammalian prey was recorded in greater quantity (i.e. volume and mass). Thus, scat analysis may have overestimated mammalian prey and fruits and underestimated the importance of invertebrates, particularly highly digestible species (e.g. termites). In spite of these differences, scat analysis demonstrated similar general and seasonal trends as the stomach content analysis. Thus, scat analysis can provide an efficient and relatively accurate source of information on the diet of blackbacked jackals in the Eastern Cape. Both stomach content and scat collection methods depicted the black-backed jackal as a generalist and opportunistic predator, mainly relying on mammals and invertebrates. Although the results of my study suggest that black-backed jackal may be important predators of certain ungulate species, further study on their prey preferences, actual biomass ingested and the effects on the population viability of prey species is required in order to develop a robust management plan for the species in the protected areas of the Eastern Cape.
- Full Text:
- Date Issued: 2012
- Authors: Brassine, Mathilde Chloé
- Date: 2012
- Subjects: Black-backed jackal -- South Africa -- Eastern Cape , Jackals -- South Africa -- Eastern Cape , Jackals -- Food , Wildlife conservation
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5660 , http://hdl.handle.net/10962/d1005344 , Black-backed jackal -- South Africa -- Eastern Cape , Jackals -- South Africa -- Eastern Cape , Jackals -- Food , Wildlife conservation
- Description: Mammalian predators are keystone species and can have disproportionately large impacts, relative to their abundance, on the communities and ecosystems they inhabit. In addition, predator-prey interactions (including bottom-up and top-down effects) are the fundamental linkage among species in food webs. Thus, understanding the food requirements of predators is imperative. There have been no comprehensive studies on the diet of black-backed jackals (Canis mesomelas) across a full seasonal cycle in the Albany Thicket Biome of the Eastern Cape Province. This biome is rich in plant diversity, is highly nutritious for herbivores and supports a large number of mammalian species, yet it is poorly conserved. The aim of the present study was to establish the diet of black-backed jackals on two conservation areas where thicket vegetation dominates (Great Fish River Reserve and Kwandwe Private Game Reserve). The diet was assessed using scats collected monthly from June 2009 to May 2010 and a sample of 25 stomachs over the same period. At both sites and across all seasons, mammalian hair was encountered most often (93% of all scats) and a total of 23 mammal species were consumed. Of the mammals recorded in the scats, hair from several ungulate species was encountered most frequently and these were mostly hider species (offspring hidden in tall vegetation just after birth). On a seasonal basis, the proportion of mammalian hair was lowest in autumn. However, the contribution of fruits (Carissa haematocarpa, Diospyros lycioides and Grewia robusta) to the diet was significantly higher during this season. This suggests that black-backed jackals may employ diet switching in the Eastern Cape as a mechanism to capitalise on seasonally abundant food sources. Based on the stomach content analysis, invertebrates were consumed as frequently as mammalian prey throughout the year but mammalian prey was recorded in greater quantity (i.e. volume and mass). Thus, scat analysis may have overestimated mammalian prey and fruits and underestimated the importance of invertebrates, particularly highly digestible species (e.g. termites). In spite of these differences, scat analysis demonstrated similar general and seasonal trends as the stomach content analysis. Thus, scat analysis can provide an efficient and relatively accurate source of information on the diet of blackbacked jackals in the Eastern Cape. Both stomach content and scat collection methods depicted the black-backed jackal as a generalist and opportunistic predator, mainly relying on mammals and invertebrates. Although the results of my study suggest that black-backed jackal may be important predators of certain ungulate species, further study on their prey preferences, actual biomass ingested and the effects on the population viability of prey species is required in order to develop a robust management plan for the species in the protected areas of the Eastern Cape.
- Full Text:
- Date Issued: 2012
The diet of black-backed jackal (Canis Mesomelas) on two contrasting land-use types in the Eastern Cape Province, South Africa and the validation of a new analytical method of mammalian hair identification
- Authors: Forbes, Ross William
- Date: 2012
- Subjects: Black-backed jackal -- South Africa -- Eastern Cape , Jackals -- South Africa -- Eastern Cape , Jackals -- Food , Mammals -- Identification
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5661 , http://hdl.handle.net/10962/d1005345 , Black-backed jackal -- South Africa -- Eastern Cape , Jackals -- South Africa -- Eastern Cape , Jackals -- Food , Mammals -- Identification
- Description: Diet assessments are critical for understanding the foraging behaviour, habitat use and trophic separation of mammalian predators and are vital for gaining insight into how predators influence prey populations. The aim of this research was to qualitatively describe the diet of black-backed jackals (Canis mesomelas, Schreber 1775) using scat analysis on two contrasting land-use types in the Eastern Cape Province, South Africa. Scats were collected on a monthly basis from November 2009 to October 2010 from two game reserves (Great Fish River Reserve and Shamwari Private Game Reserve) and two neighbouring livestock farms. The relative frequency of occurrence of mammal hair (33 – 47 %) and vegetation (32 – 45%)dominated jackal diet throughout the year across the four study sites. Other important prey items included invertebrates (8 – 21 %) and fruit and seeds (3 – 11 %). Birds and reptiles constituted ≤ 2 % of the diet and were only recorded on the game reserves. Significant seasonal dietary shifts were observed on the game reserves but not on the farms. Fruit and seeds were significantly more frequent in the diet during autumn at Great Fish River Reserve and invertebrates were significantly less common in the diet during winter on both reserves. In addition, vegetation was significantly more common in the diet during winter at Shamwari Private Game Reserve. The significant temporal variation of certain prey items is testament to black-backed jackals being opportunistic generalists, foraging on those food items which are most abundant, accessible and energetically beneficial. Land-use type also influenced the diet of black-backed jackals with significantly more invertebrates and, fruit and seeds being recorded on the game reserves than on the farms. By contrast, significantly more mammal hair and vegetation were present in the diet on the farms compared with the game reserves. The mammalian component of the diet was dominated by ruminants and rodents on the game reserves and by ruminants and livestock on the farms. The presence of livestock in the diet of black-backed jackals on the farms highlights their potential impact on the livestock industry in the region and may assist farmers in determining which predators are responsible for stock loss. Previous approaches for identifying mammalian hairs from predator scats have utilised dichotomous keys and reference collections but these are often time-consuming and require a trained individual to carry out the identification. Thus, I also tested the efficacy of an automated pattern recognition programme (HairSnap) for identifying mammalian hairs from black-backed jackal scats. The overall accuracy of the programme was 38 % with black-backed jackal, Greater kudu (Tragelaphus strepsiceros) and striped polecat (Ictonyx striatus) hairs being accurately identified more often (70 – 80 %) than any other species tested. It is likely that both the size and species composition of the sample resulted in the poor accuracy of the programme. However, with the implementation of several improvement measures (e.g. adjustment of the algorithm) the programme may offer a superior, bias-free method of mammalian hair identification. The dietary information gathered here furthers our knowledge of the biology of the blackbacked jackals, especially in the locally important thicket biome. Moreover, understanding their foraging habits allows for more effective management of the species on both game reserves and farmlands. I recommend that future research should focus on quantitatively assessing the diet of black-backed jackals in the Eastern Cape Province and elsewhere. This will compliment the dietary description provided in this study and may offer a biologically more meaningful indication of the relative importance of the prey items.
- Full Text:
- Date Issued: 2012
- Authors: Forbes, Ross William
- Date: 2012
- Subjects: Black-backed jackal -- South Africa -- Eastern Cape , Jackals -- South Africa -- Eastern Cape , Jackals -- Food , Mammals -- Identification
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5661 , http://hdl.handle.net/10962/d1005345 , Black-backed jackal -- South Africa -- Eastern Cape , Jackals -- South Africa -- Eastern Cape , Jackals -- Food , Mammals -- Identification
- Description: Diet assessments are critical for understanding the foraging behaviour, habitat use and trophic separation of mammalian predators and are vital for gaining insight into how predators influence prey populations. The aim of this research was to qualitatively describe the diet of black-backed jackals (Canis mesomelas, Schreber 1775) using scat analysis on two contrasting land-use types in the Eastern Cape Province, South Africa. Scats were collected on a monthly basis from November 2009 to October 2010 from two game reserves (Great Fish River Reserve and Shamwari Private Game Reserve) and two neighbouring livestock farms. The relative frequency of occurrence of mammal hair (33 – 47 %) and vegetation (32 – 45%)dominated jackal diet throughout the year across the four study sites. Other important prey items included invertebrates (8 – 21 %) and fruit and seeds (3 – 11 %). Birds and reptiles constituted ≤ 2 % of the diet and were only recorded on the game reserves. Significant seasonal dietary shifts were observed on the game reserves but not on the farms. Fruit and seeds were significantly more frequent in the diet during autumn at Great Fish River Reserve and invertebrates were significantly less common in the diet during winter on both reserves. In addition, vegetation was significantly more common in the diet during winter at Shamwari Private Game Reserve. The significant temporal variation of certain prey items is testament to black-backed jackals being opportunistic generalists, foraging on those food items which are most abundant, accessible and energetically beneficial. Land-use type also influenced the diet of black-backed jackals with significantly more invertebrates and, fruit and seeds being recorded on the game reserves than on the farms. By contrast, significantly more mammal hair and vegetation were present in the diet on the farms compared with the game reserves. The mammalian component of the diet was dominated by ruminants and rodents on the game reserves and by ruminants and livestock on the farms. The presence of livestock in the diet of black-backed jackals on the farms highlights their potential impact on the livestock industry in the region and may assist farmers in determining which predators are responsible for stock loss. Previous approaches for identifying mammalian hairs from predator scats have utilised dichotomous keys and reference collections but these are often time-consuming and require a trained individual to carry out the identification. Thus, I also tested the efficacy of an automated pattern recognition programme (HairSnap) for identifying mammalian hairs from black-backed jackal scats. The overall accuracy of the programme was 38 % with black-backed jackal, Greater kudu (Tragelaphus strepsiceros) and striped polecat (Ictonyx striatus) hairs being accurately identified more often (70 – 80 %) than any other species tested. It is likely that both the size and species composition of the sample resulted in the poor accuracy of the programme. However, with the implementation of several improvement measures (e.g. adjustment of the algorithm) the programme may offer a superior, bias-free method of mammalian hair identification. The dietary information gathered here furthers our knowledge of the biology of the blackbacked jackals, especially in the locally important thicket biome. Moreover, understanding their foraging habits allows for more effective management of the species on both game reserves and farmlands. I recommend that future research should focus on quantitatively assessing the diet of black-backed jackals in the Eastern Cape Province and elsewhere. This will compliment the dietary description provided in this study and may offer a biologically more meaningful indication of the relative importance of the prey items.
- Full Text:
- Date Issued: 2012
The dionysian in performance reclaiming the female transgressive performing body
- Authors: Solomon, Zanne
- Date: 2012
- Subjects: Dionysia , Feminism and theater , Human body in literature , Performance art , Performing arts , Body image in women , Self-perception in women , Human body -- Social aspects
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:2148 , http://hdl.handle.net/10962/d1002380
- Description: In this thesis I investigate the theoretical or philosophical notion/archetype of the Dionysian in relation to the transgressive female body in performance. I do so through 1) an investigation into the theories behind the Dionysian and the transgressive; 2) an examination of the performative practice of the transgressive female body; and 3) a personal exploration of the theatrical practice. 1) In the first chapter I introduce and thoroughly explore the archetypal concept of the Dionysian, and identify its significance because of its intrinsic association with the transgressive. I associate it with its oppositional force, the Apollonian, which is similarly significant because it is through the Dionysian disruption of the Apollonian from which the very notion of the transgressive springs. Through a review of Camille Paglia's seminal text on the subject of the Dionysian¹, this chapter provides a historical, mythological and theoretical context for the schism between the two archetypal aesthetics, starting from the description of the mythology of the ancient Greek gods, Dionysus and Apollo, and unpacks the transgressive nature of the Dionysian. Drawing on concurring theories of Friedrich Nietzsche and Julia Kristeva, as well as Hans Thies-Lehmann's writings on post-dramatic theatre², Chapter One attempts to firmly establish the inherent link between the Dionysian and theatre and performance, as well as the Dionysian and the transgressive, and provide a thorough theoretical framework for the rest of the thesis. 2) The second chapter investigates the work of two female performance artists³ who (re)present⁴ their bodies as transgressive in performance, namely Marina Abramovic and Karen Finley. It critically examines specific performance works of theirs, and through this examination it explores how they (re)present their bodies as transgressive in performance, and why they do so. This chapter furthermore establishes the connection between the transgressive female performing body, as (re)presented by Abramovic and Finley, and the Dionysian. In so doing it explores how they negotiate this ancient aesthetic or practice in a contemporary performance context. I believe that these performance artists are in fact striving to celebrate and reclaim the Dionysian within their work, and I attempt to establish this within this chapter. 3) The third chapter of this thesis analyses my own practical exploration of the transgressive female body in performance in a piece entitled Bleeding Mermaid (2008). It examines this exploration in the context of the theory of the Dionysian, as well as investigating how and why I (re)presented my body as transgressive in the performance. The analysis furthermore questions how I understand my work on the (re)presentation of the transgressive female body in relation to, and within the context of, Finley and Abramovic's work on the same subject. Through this investigation, I aim to establish a link between the Dionysian and the transgressive female performing body; and investigate the motivation(s) behind the (re)presentation of the transgressive female body in performance. I hope to open up a pathway to the reclamation of the Dionysian, both in performance practice and research. ¹Paglia, Camille. Sexual Personae: Art and Decadence from Nefertiti to Emily Dickinson. England: Penguin Books, 1990. ²Lehmann, Hans-Thies. Postdramatic Theatre. Trans. and Intro. Karen Jürs-Munby. London and New York: Routledge, 2006. ³Performance Art began around the 1960s in Europe and America. It is performance with a sense of immediacy – in that it is hard to replicate as it interacts with each unique audience – it is thus effectively a fresh/new experience each time. It breaks the boundaries of traditional theatre (form, structure, venue, time etc) and is often shocking or provocative in nature. It mixed the aesthetics of theatre and art, often taking place in installation settings. Performance Art has developed and morphed throughout the years, and is also referred to as Live Art in Britain. A performance artist is someone who produces performance art. It is possible that Performance Art no longer exists/is possible because it no longer shocks or affects the audience. ⁴My use of the brackets in (re)presented/(re)present throughout this thesis is because I would like to make simultaneous reference to the words/connotations of "presentation" and "representation", without being bound to the connotations of illusion/falseness/non-reality as is associated with the word "representation" (in opposition to the concept of the "real"), and thus be left only with the one-dimensional approach/meaning of "presentation".
- Full Text:
- Date Issued: 2012
- Authors: Solomon, Zanne
- Date: 2012
- Subjects: Dionysia , Feminism and theater , Human body in literature , Performance art , Performing arts , Body image in women , Self-perception in women , Human body -- Social aspects
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:2148 , http://hdl.handle.net/10962/d1002380
- Description: In this thesis I investigate the theoretical or philosophical notion/archetype of the Dionysian in relation to the transgressive female body in performance. I do so through 1) an investigation into the theories behind the Dionysian and the transgressive; 2) an examination of the performative practice of the transgressive female body; and 3) a personal exploration of the theatrical practice. 1) In the first chapter I introduce and thoroughly explore the archetypal concept of the Dionysian, and identify its significance because of its intrinsic association with the transgressive. I associate it with its oppositional force, the Apollonian, which is similarly significant because it is through the Dionysian disruption of the Apollonian from which the very notion of the transgressive springs. Through a review of Camille Paglia's seminal text on the subject of the Dionysian¹, this chapter provides a historical, mythological and theoretical context for the schism between the two archetypal aesthetics, starting from the description of the mythology of the ancient Greek gods, Dionysus and Apollo, and unpacks the transgressive nature of the Dionysian. Drawing on concurring theories of Friedrich Nietzsche and Julia Kristeva, as well as Hans Thies-Lehmann's writings on post-dramatic theatre², Chapter One attempts to firmly establish the inherent link between the Dionysian and theatre and performance, as well as the Dionysian and the transgressive, and provide a thorough theoretical framework for the rest of the thesis. 2) The second chapter investigates the work of two female performance artists³ who (re)present⁴ their bodies as transgressive in performance, namely Marina Abramovic and Karen Finley. It critically examines specific performance works of theirs, and through this examination it explores how they (re)present their bodies as transgressive in performance, and why they do so. This chapter furthermore establishes the connection between the transgressive female performing body, as (re)presented by Abramovic and Finley, and the Dionysian. In so doing it explores how they negotiate this ancient aesthetic or practice in a contemporary performance context. I believe that these performance artists are in fact striving to celebrate and reclaim the Dionysian within their work, and I attempt to establish this within this chapter. 3) The third chapter of this thesis analyses my own practical exploration of the transgressive female body in performance in a piece entitled Bleeding Mermaid (2008). It examines this exploration in the context of the theory of the Dionysian, as well as investigating how and why I (re)presented my body as transgressive in the performance. The analysis furthermore questions how I understand my work on the (re)presentation of the transgressive female body in relation to, and within the context of, Finley and Abramovic's work on the same subject. Through this investigation, I aim to establish a link between the Dionysian and the transgressive female performing body; and investigate the motivation(s) behind the (re)presentation of the transgressive female body in performance. I hope to open up a pathway to the reclamation of the Dionysian, both in performance practice and research. ¹Paglia, Camille. Sexual Personae: Art and Decadence from Nefertiti to Emily Dickinson. England: Penguin Books, 1990. ²Lehmann, Hans-Thies. Postdramatic Theatre. Trans. and Intro. Karen Jürs-Munby. London and New York: Routledge, 2006. ³Performance Art began around the 1960s in Europe and America. It is performance with a sense of immediacy – in that it is hard to replicate as it interacts with each unique audience – it is thus effectively a fresh/new experience each time. It breaks the boundaries of traditional theatre (form, structure, venue, time etc) and is often shocking or provocative in nature. It mixed the aesthetics of theatre and art, often taking place in installation settings. Performance Art has developed and morphed throughout the years, and is also referred to as Live Art in Britain. A performance artist is someone who produces performance art. It is possible that Performance Art no longer exists/is possible because it no longer shocks or affects the audience. ⁴My use of the brackets in (re)presented/(re)present throughout this thesis is because I would like to make simultaneous reference to the words/connotations of "presentation" and "representation", without being bound to the connotations of illusion/falseness/non-reality as is associated with the word "representation" (in opposition to the concept of the "real"), and thus be left only with the one-dimensional approach/meaning of "presentation".
- Full Text:
- Date Issued: 2012
The dispersal of African wild dogs (Lycaon Pictus) from protected areas in the Northern KwaZulu‐Natal Province, South Africa.
- Whittington‐Jones, Brendan Mark
- Authors: Whittington‐Jones, Brendan Mark
- Date: 2012
- Subjects: African wild dog , African wild dog -- Conservation -- South Africa -- KwazuluNatal , African wild dog -- Dispersal -- South Africa -- KwaZulu-Natal , African wild dog -- Effect of human beings on -- South Africa -- KwaZulu Natal
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5893 , http://hdl.handle.net/10962/d1013414
- Description: The number of African wild dogs Lycaon pictus in Northern KwaZulu‐Natal, South Africa has increased substantially over the last six years. This is largely due to a managed metapopulation approach of introductions onto protected areas and private game reserves since 1998. Because of the increasing wild dog population, the likelihood of rural communities surrounding protected areas encountering dispersing wild dogs in northern KwaZulu‐Natal has also increased. Resident wild dog populations currently occur in Hluhluwe‐iMfolozi Park (HiP), Mkhuze Game Reserve (MGR) of Isimangaliso Wetland Park and Thanda Private Game Reserve (TPGR) all of which are bordered by a matrix of natural habitats and human settlements. Thus, land outside these protected areas could be utilized to expand wild dog distribution and provide connectivity between existing resident populations of wild dogs within KwaZulu‐Natal. To investigate the viability of such an approach, Maximum Entropy Modelling (Maxent) was used to characterize habitat niche selection of dispersing wild dogs, and to identify potential dispersal linkages between current wild dog metapopulation reserves. The model was calibrated using 132 location points collected from 2006 until 2009. From 2008 to 2009 I also conducted a survey of 247 community members in tribal authorities bordering HiP and MGR, to understand factors influencing attitudes towards wild dogs. A habitat suitability model with seven predictor variables had an AUC of 0.96 (SD = 0.02) and indicated four variables which best predicted probability of presence for dispersing wild dogs: elevation, road density, land cover and human density. The results suggest that elevation and land cover may be of greater influence for dispersing wild dogs than human density or activity. Elevation was the single most effective variable indicating a higher probability of presence for dispersing wild dogs in lower lying locations; peaking at approximately 200 – 300m a.s.l. Wild dogs also showed a preference for Woodland and Bushland habitats which in KwaZulu‐Natal tend to be found on lower lying topography. A preference for areas of lower human density and a highest probability of presence at road densities of approximately 0.7km/km2 or less would suggest that while wild dogs may show a tendency to avoid areas of high human activity, they can coexist in close proximity to humans. Respondent’s attitudes, knowledge of wild dogs and livestock husbandry were interpreted by the development of a set of indices. Attitudes were positively related to formal education levels and wild dog‐specific education, but were not influenced by demographic factors such as gender, age and employment status. Eighty three percent of respondents believed efforts to protect wild dogs should continue. Respondents with higher numbers of livestock tended to have more positive attitudes towards wild dogs despite generally incurring higher losses to carnivore depredation than those with less livestock. This appears to be because the financial burden of livestock losses to those with fewer livestock is perceived to be a loss of a greater proportion of total financial wealth. The study highlighted the substantial scope for improvement in livestock management. Theft (34 percent), drought (30 percent) and disease (14 percent) were ranked as the greatest problems facing livestock owners while predators were ranked as the greatest problem by only 4 percent of respondents. My findings suggest that wild dogs are generally viewed positively or with ambivalence. Concerns over the potentially increasing threat to livestock, as natural prey numbers outside protected areas decline and wild dogs disperse from natal packs, are likely to be manageable. However, wild dog population expansion within KwaZulu‐Natal will continue to rely on managed core populations on perimeter‐fenced metapopulation reserves with tolerant communities and landowners contributing to the connectivity of isolated reserves. Generation of tolerance can be instilled through continued advocacy and education, supported by conflict mitigation initiatives and rapid response to conflict reports. The implementation of incentive schemes for adjoining private landowners to co‐manage wild dog populations will need to be addressed in conjunction with managed metapopulation practices and law enforcement, to promote range expansion, and reduce potentially lethal edge effects and wild dog‐human conflict.
- Full Text:
- Date Issued: 2012
- Authors: Whittington‐Jones, Brendan Mark
- Date: 2012
- Subjects: African wild dog , African wild dog -- Conservation -- South Africa -- KwazuluNatal , African wild dog -- Dispersal -- South Africa -- KwaZulu-Natal , African wild dog -- Effect of human beings on -- South Africa -- KwaZulu Natal
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5893 , http://hdl.handle.net/10962/d1013414
- Description: The number of African wild dogs Lycaon pictus in Northern KwaZulu‐Natal, South Africa has increased substantially over the last six years. This is largely due to a managed metapopulation approach of introductions onto protected areas and private game reserves since 1998. Because of the increasing wild dog population, the likelihood of rural communities surrounding protected areas encountering dispersing wild dogs in northern KwaZulu‐Natal has also increased. Resident wild dog populations currently occur in Hluhluwe‐iMfolozi Park (HiP), Mkhuze Game Reserve (MGR) of Isimangaliso Wetland Park and Thanda Private Game Reserve (TPGR) all of which are bordered by a matrix of natural habitats and human settlements. Thus, land outside these protected areas could be utilized to expand wild dog distribution and provide connectivity between existing resident populations of wild dogs within KwaZulu‐Natal. To investigate the viability of such an approach, Maximum Entropy Modelling (Maxent) was used to characterize habitat niche selection of dispersing wild dogs, and to identify potential dispersal linkages between current wild dog metapopulation reserves. The model was calibrated using 132 location points collected from 2006 until 2009. From 2008 to 2009 I also conducted a survey of 247 community members in tribal authorities bordering HiP and MGR, to understand factors influencing attitudes towards wild dogs. A habitat suitability model with seven predictor variables had an AUC of 0.96 (SD = 0.02) and indicated four variables which best predicted probability of presence for dispersing wild dogs: elevation, road density, land cover and human density. The results suggest that elevation and land cover may be of greater influence for dispersing wild dogs than human density or activity. Elevation was the single most effective variable indicating a higher probability of presence for dispersing wild dogs in lower lying locations; peaking at approximately 200 – 300m a.s.l. Wild dogs also showed a preference for Woodland and Bushland habitats which in KwaZulu‐Natal tend to be found on lower lying topography. A preference for areas of lower human density and a highest probability of presence at road densities of approximately 0.7km/km2 or less would suggest that while wild dogs may show a tendency to avoid areas of high human activity, they can coexist in close proximity to humans. Respondent’s attitudes, knowledge of wild dogs and livestock husbandry were interpreted by the development of a set of indices. Attitudes were positively related to formal education levels and wild dog‐specific education, but were not influenced by demographic factors such as gender, age and employment status. Eighty three percent of respondents believed efforts to protect wild dogs should continue. Respondents with higher numbers of livestock tended to have more positive attitudes towards wild dogs despite generally incurring higher losses to carnivore depredation than those with less livestock. This appears to be because the financial burden of livestock losses to those with fewer livestock is perceived to be a loss of a greater proportion of total financial wealth. The study highlighted the substantial scope for improvement in livestock management. Theft (34 percent), drought (30 percent) and disease (14 percent) were ranked as the greatest problems facing livestock owners while predators were ranked as the greatest problem by only 4 percent of respondents. My findings suggest that wild dogs are generally viewed positively or with ambivalence. Concerns over the potentially increasing threat to livestock, as natural prey numbers outside protected areas decline and wild dogs disperse from natal packs, are likely to be manageable. However, wild dog population expansion within KwaZulu‐Natal will continue to rely on managed core populations on perimeter‐fenced metapopulation reserves with tolerant communities and landowners contributing to the connectivity of isolated reserves. Generation of tolerance can be instilled through continued advocacy and education, supported by conflict mitigation initiatives and rapid response to conflict reports. The implementation of incentive schemes for adjoining private landowners to co‐manage wild dog populations will need to be addressed in conjunction with managed metapopulation practices and law enforcement, to promote range expansion, and reduce potentially lethal edge effects and wild dog‐human conflict.
- Full Text:
- Date Issued: 2012
The economics of converting a sheep farm into a springbuck (Antidorcas marsupialis) ranch in Graaff-Reinet: a simulation analysis
- Authors: Dlamini, Thula Sizwe
- Date: 2012
- Subjects: Livestock projects -- South Africa -- Eastern Cape Livestock productivity -- South Africa -- Eastern Cape Livestock -- Economic aspects -- South Africa -- Eastern Cape Sheep -- Breeding -- South Africa -- Eastern Cape Springbok -- Breeding -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:1003 , http://hdl.handle.net/10962/d1002738
- Description: In Graaff-Reinet, domestic livestock farming and springbuck ranching are similar in that they both rely on the rangeland for their sustainability. However, as a consequence of repeated monotonous domestic livestock farming, resulting in compromised biological productivity and diversity, the rangelands have disintegrated. This, unfortunately, has placed the future sustainability of these rangelands and the livelihoods of the local people in an indeterminate state. In recent years, there has been an increasing interest in springbuck ranching for meat production as an alternative to domestic livestock farming in the area following (a) fears of worsening environmental challenges; (b) declining profitability in commercial domestic livestock farming and; (c) growing calls for the sustainable use of these rangelands for the benefit of future generations. The springbuck has emerged as a credible alternative to utilising the rangelands - as opposed to sheep - because of its promise to addressing the above challenges. This is in an attempt to tap into the multitude of benefits that the springbuck possesses (by virtue of being part of the natural capital of the area) that have a potential towards restoring ecological integrity by extenuating some of the detrimental effects of sheep farming on the rangelands and presenting opportunities for diversifying incomes. Yet, despite the general increase in interest, a resistance towards the uptake of springbuck ranching for meat production exists. The main contention is that springbuck meat production cannot out-perform the economic returns of wool sheep farming. This study attempts to address these concerns by investigating the profitability and economic sustainability of converting a sheep farm into a springbuck ranch in Graaff-Reinet. The study uses stochastic simulation to estimate the probability distribution of some key output variables, namely: net cash income, ending cash balance, real net worth and the net present value (NPV) in evaluating the profitability of converting a 5 000ha sheep-dominated farm into a springbuck-dominated ranch under three alternative scenarios. The use of stochastic simulation allows for the incorporation of downside risk associated with the production and marketing of wool, mutton and springbuck meat. The study uses stochastic prices and yields to calculate net returns variability. Incorporating scenario analysis helped to evaluate how alternative wool sheep-dominated and springbuck-dominated combinations would perform based on the probable outcomes of different assumptions in the various scenarios. By applying stochastic efficiency with respect to a function (SERF) criterion to the simulated NPVs, this study compares the profitability of alternative scenarios based on various risk aversion coefficients. The study finds that converting a 5 000ha wool sheep dominated farm into a springbuck dominated ranch could potentially be a more profitable investment than wool sheep farming over a 15 year planning horizon, in Graaff-Reinet. The SERF results indicate that for all scenarios tested, the best strategy of converting a wool sheep dominated farm into a springbuck ranch would be one which comprise a combination of 70% springbuck, 20% mutton and 10% wool production as the likely profitable enterprise mix. Using economic sustainability analysis, the study reveals that because of low costs in springbuck ranching, springbuck meat production enterprises are most likely to be more financially sustainable than wool sheep-dominated enterprises. This suggests that rangeland owners may be better off converting their wool sheep-dominated farms into springbuck-dominated ranches. Thus, as the call for more environmentally benign rangeland utilising economic-ecological systems intensifies, rangeland owners in the Eastern Cape Karoo have a practicable option. At the very least, there exists an option to broaden their incomes whilst promoting ecological restoration with springbuck meat production.
- Full Text:
- Date Issued: 2012
- Authors: Dlamini, Thula Sizwe
- Date: 2012
- Subjects: Livestock projects -- South Africa -- Eastern Cape Livestock productivity -- South Africa -- Eastern Cape Livestock -- Economic aspects -- South Africa -- Eastern Cape Sheep -- Breeding -- South Africa -- Eastern Cape Springbok -- Breeding -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:1003 , http://hdl.handle.net/10962/d1002738
- Description: In Graaff-Reinet, domestic livestock farming and springbuck ranching are similar in that they both rely on the rangeland for their sustainability. However, as a consequence of repeated monotonous domestic livestock farming, resulting in compromised biological productivity and diversity, the rangelands have disintegrated. This, unfortunately, has placed the future sustainability of these rangelands and the livelihoods of the local people in an indeterminate state. In recent years, there has been an increasing interest in springbuck ranching for meat production as an alternative to domestic livestock farming in the area following (a) fears of worsening environmental challenges; (b) declining profitability in commercial domestic livestock farming and; (c) growing calls for the sustainable use of these rangelands for the benefit of future generations. The springbuck has emerged as a credible alternative to utilising the rangelands - as opposed to sheep - because of its promise to addressing the above challenges. This is in an attempt to tap into the multitude of benefits that the springbuck possesses (by virtue of being part of the natural capital of the area) that have a potential towards restoring ecological integrity by extenuating some of the detrimental effects of sheep farming on the rangelands and presenting opportunities for diversifying incomes. Yet, despite the general increase in interest, a resistance towards the uptake of springbuck ranching for meat production exists. The main contention is that springbuck meat production cannot out-perform the economic returns of wool sheep farming. This study attempts to address these concerns by investigating the profitability and economic sustainability of converting a sheep farm into a springbuck ranch in Graaff-Reinet. The study uses stochastic simulation to estimate the probability distribution of some key output variables, namely: net cash income, ending cash balance, real net worth and the net present value (NPV) in evaluating the profitability of converting a 5 000ha sheep-dominated farm into a springbuck-dominated ranch under three alternative scenarios. The use of stochastic simulation allows for the incorporation of downside risk associated with the production and marketing of wool, mutton and springbuck meat. The study uses stochastic prices and yields to calculate net returns variability. Incorporating scenario analysis helped to evaluate how alternative wool sheep-dominated and springbuck-dominated combinations would perform based on the probable outcomes of different assumptions in the various scenarios. By applying stochastic efficiency with respect to a function (SERF) criterion to the simulated NPVs, this study compares the profitability of alternative scenarios based on various risk aversion coefficients. The study finds that converting a 5 000ha wool sheep dominated farm into a springbuck dominated ranch could potentially be a more profitable investment than wool sheep farming over a 15 year planning horizon, in Graaff-Reinet. The SERF results indicate that for all scenarios tested, the best strategy of converting a wool sheep dominated farm into a springbuck ranch would be one which comprise a combination of 70% springbuck, 20% mutton and 10% wool production as the likely profitable enterprise mix. Using economic sustainability analysis, the study reveals that because of low costs in springbuck ranching, springbuck meat production enterprises are most likely to be more financially sustainable than wool sheep-dominated enterprises. This suggests that rangeland owners may be better off converting their wool sheep-dominated farms into springbuck-dominated ranches. Thus, as the call for more environmentally benign rangeland utilising economic-ecological systems intensifies, rangeland owners in the Eastern Cape Karoo have a practicable option. At the very least, there exists an option to broaden their incomes whilst promoting ecological restoration with springbuck meat production.
- Full Text:
- Date Issued: 2012