Versions of confinement: Melville's bodies and the psychology of conquest
- Authors: Goddard, Kevin Graham
- Date: 2003
- Subjects: Melville, Herman, 1819-1891 -- Criticism and interpretation Human body in literature
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:2216 , http://hdl.handle.net/10962/d1002259
- Description: This thesis explores aspects of Melville’s presentation of both the whale and the human bodies in Moby-Dick and human bodies in other important novels. It argues that Melville uses his presentation of bodies to explore some of the versions of confinement those bodies experience, and by doing so, analyses the psychology which subtends that confinement. Throughout Melville’s works bodies are confined, both within literal spatial limits and by the psychology which creates and/or accepts these spatial limits. The thesis argues that perhaps the most important version of bodily confinement Melville addresses is the impulse to conquer bodies, both that of the other and one’s own. It adopts a largely psychoanalytic approach to interpreting bodies and their impulse to conquer, so that the body is seen to figure both in its actions and its external appearance the operations of the inner psyche. The figure of the body is equally prevalent in Melville’s exploration of nationalist conquest, where, as with Manifest Destiny and antebellum expansionism, the psychological and physical lack experienced by characters can be read as motivating factors in the ideology of conquest. A final important strand of the thesis is its argument in favour of a gradual shift in Melville’s interpretation of the value and possibility of genuine communion between human beings and between humans and the whale. One may read Typee as an attempt by Melville to explore the possibility of a this-worldly utopia in which human beings can return to a version of primitive interconnectedness. This exploration may be seen to be extended in Moby-Dick, particularly in Ishmael’s attempts to find communion with others and in some moments of encounter with the whales. The thesis uses phenomenology as a theory to interpret what Melville is trying to suggest in these moments of encounter. However, it argues, finally, that such encounter, or ‘intersubjectivity’ is eventually jettisoned, especially in the works after Moby-Dick. By the end of Melville’s life and work, any hope of an intersubjective utopia he may have harboured as a younger man have been removed in favour of a refusal actually to assert any final ‘truth’ about social, political or even religious experience. Billy Budd, his last body, is hanged, and his final word is silence.
- Full Text:
- Date Issued: 2003
- Authors: Goddard, Kevin Graham
- Date: 2003
- Subjects: Melville, Herman, 1819-1891 -- Criticism and interpretation Human body in literature
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:2216 , http://hdl.handle.net/10962/d1002259
- Description: This thesis explores aspects of Melville’s presentation of both the whale and the human bodies in Moby-Dick and human bodies in other important novels. It argues that Melville uses his presentation of bodies to explore some of the versions of confinement those bodies experience, and by doing so, analyses the psychology which subtends that confinement. Throughout Melville’s works bodies are confined, both within literal spatial limits and by the psychology which creates and/or accepts these spatial limits. The thesis argues that perhaps the most important version of bodily confinement Melville addresses is the impulse to conquer bodies, both that of the other and one’s own. It adopts a largely psychoanalytic approach to interpreting bodies and their impulse to conquer, so that the body is seen to figure both in its actions and its external appearance the operations of the inner psyche. The figure of the body is equally prevalent in Melville’s exploration of nationalist conquest, where, as with Manifest Destiny and antebellum expansionism, the psychological and physical lack experienced by characters can be read as motivating factors in the ideology of conquest. A final important strand of the thesis is its argument in favour of a gradual shift in Melville’s interpretation of the value and possibility of genuine communion between human beings and between humans and the whale. One may read Typee as an attempt by Melville to explore the possibility of a this-worldly utopia in which human beings can return to a version of primitive interconnectedness. This exploration may be seen to be extended in Moby-Dick, particularly in Ishmael’s attempts to find communion with others and in some moments of encounter with the whales. The thesis uses phenomenology as a theory to interpret what Melville is trying to suggest in these moments of encounter. However, it argues, finally, that such encounter, or ‘intersubjectivity’ is eventually jettisoned, especially in the works after Moby-Dick. By the end of Melville’s life and work, any hope of an intersubjective utopia he may have harboured as a younger man have been removed in favour of a refusal actually to assert any final ‘truth’ about social, political or even religious experience. Billy Budd, his last body, is hanged, and his final word is silence.
- Full Text:
- Date Issued: 2003
Applications of the Baylis-Hillman reaction in the synthesis of coumarin derivatives
- Authors: Musa, Musiliyu Ayodele
- Date: 2003
- Subjects: Coumarins Heterocyclic compounds -- Derivatives
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4403 , http://hdl.handle.net/10962/d1006705
- Description: The reaction of specially prepared salicylaldehyde benzyl ethers with the activated alkenes, methyl acrylate or acrylonitrile, in the presence of the catalyst, DABCO, has afforded Baylis-Hillman products, which have been subjected to conjugate addition with either piperidine or benzylamine. Hydrogenolysis of these conjugate addition products in the presence of a palladium-on-carbon catalyst has been shown to afford the corresponding 3-substituted coumarins, while treatment of O-benzylated Baylis-Hillman adducts with HCl or HI afforded the corresponding 3-(halomethyl)coumarins directly, in up to 94%. The 3-(halomethyl)coumarins have also been obtained in excellent yields (up to 98%) and even more conveniently, by treating the unprotected Baylis-Hillman products with HCl in a mixture of AcOH and Ac₂O, obtained from tert-butyl acrylate and various salicylaldehydes. The generality of an established route to the synthesis of coumarins via an intramolecular Baylis-Hillman reaction, involving the use of salicylaldehyde acrylate esters in the presence of DABCO, has also been demonstrated. Reactions between the 3-(halomethyl)coumarins and various nitrogen and carbon nucleophiles have been shown to proceed with a high degree of regioselectivity at the exocyclic allylic centre to afford 3-substituted coumarin products. The electronimpact mass spectra of selected coumarin derivatives have been investigated using high-resolution and B/E linked scan data. Fragmentation pathways have been proposed and fragmentation modes associated with different coumarin-containing analogues have been compared. A series of coumarin-containing analogues of ritonavir (a clinically useful HIV-1 protease inhibitor) have been prepared and characterized. The synthetic approach has involved the coupling of coumarin derivatives with a hydroxyethylene dipeptide isostere to afford ritonavir analogues containing coumarin termini. An interactive docking procedure has been used to explore the docking of ritonavir and a coumarincontaining analogue into the enzyme active site.
- Full Text:
- Date Issued: 2003
- Authors: Musa, Musiliyu Ayodele
- Date: 2003
- Subjects: Coumarins Heterocyclic compounds -- Derivatives
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4403 , http://hdl.handle.net/10962/d1006705
- Description: The reaction of specially prepared salicylaldehyde benzyl ethers with the activated alkenes, methyl acrylate or acrylonitrile, in the presence of the catalyst, DABCO, has afforded Baylis-Hillman products, which have been subjected to conjugate addition with either piperidine or benzylamine. Hydrogenolysis of these conjugate addition products in the presence of a palladium-on-carbon catalyst has been shown to afford the corresponding 3-substituted coumarins, while treatment of O-benzylated Baylis-Hillman adducts with HCl or HI afforded the corresponding 3-(halomethyl)coumarins directly, in up to 94%. The 3-(halomethyl)coumarins have also been obtained in excellent yields (up to 98%) and even more conveniently, by treating the unprotected Baylis-Hillman products with HCl in a mixture of AcOH and Ac₂O, obtained from tert-butyl acrylate and various salicylaldehydes. The generality of an established route to the synthesis of coumarins via an intramolecular Baylis-Hillman reaction, involving the use of salicylaldehyde acrylate esters in the presence of DABCO, has also been demonstrated. Reactions between the 3-(halomethyl)coumarins and various nitrogen and carbon nucleophiles have been shown to proceed with a high degree of regioselectivity at the exocyclic allylic centre to afford 3-substituted coumarin products. The electronimpact mass spectra of selected coumarin derivatives have been investigated using high-resolution and B/E linked scan data. Fragmentation pathways have been proposed and fragmentation modes associated with different coumarin-containing analogues have been compared. A series of coumarin-containing analogues of ritonavir (a clinically useful HIV-1 protease inhibitor) have been prepared and characterized. The synthetic approach has involved the coupling of coumarin derivatives with a hydroxyethylene dipeptide isostere to afford ritonavir analogues containing coumarin termini. An interactive docking procedure has been used to explore the docking of ritonavir and a coumarincontaining analogue into the enzyme active site.
- Full Text:
- Date Issued: 2003
Structural and synthetic investigations of diterpenoid natural products from southern African marine invertebrates
- Authors: Gray, Christopher Anthony
- Date: 2003
- Subjects: Ethyl acetoacetate Diterpenes Limpets -- South Africa Natural products -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4349 , http://hdl.handle.net/10962/d1005014
- Description: This thesis is divided into two parts. The first part (Chapter Two) documents a bioassay guided investigation of the ethyl acetate extracts of four marine invertebrates from Mozambique (an Irciniid sponge, a Haliclona sp. sponge, an ascidian tentatively identified as Diplosoma sp., and the soft coral Cladiella kashmani). Eight known compounds [ilimaquinone (2.1), renierone (2.7), N-formyl-1,2-dihydrorenierone (2.8), 1,6-dimethyl-7-methoxy-5,8-dihydroisoquinoline-5,8-dione (2.9), mimosamycin (2.10) 7Z-allylidene-5-hydroxy-7,7a-dihydro-2H-cyclopenta[b]pyran-6-one (2.11), flaccidoxide (2.18) and 11S,12S-epoxycembra-1Z,3E,7E-trien-14S-ol (2.19)] and a new diterpene [13S,14R-diacetoxy-11S,12R-epoxycembra-1Z,3E,7E-triene (2.20)] were isolated and identified using standard spectroscopic techniques. Anomalies in the published spectral data of 2.1 and 2.8 were exposed and corrected, and the absolute stereochemistry of the cembrane diterpenes 2.18 and 2.20 established using the modified Mosher’s method. The comparative activities of the nine natural products against four cancer cell lines (A549, LOX, OVCAR3, SNB19) are reported. The second part of the thesis (Chapter Three – Chapter Six) is concerned with an ecological, structural and synthetic study of diterpenes from the endemic South African pulmonate limpet Trimusculus costatus. Two new labdane diterpenes [6b,7a-diacetoxylabda-8,13E-dien-15-ol (3.10) and 2a,6b,7a-triacetoxylabda-8,13E-dien-15-ol (3.11)] were isolated from T. costatus and evaluated for anti-feeding activity against the common predatory fish Pomadasys commersonnii. A strategy for the semi-synthesis of 3.10 from rhinocerotinoic acid (4.14), a diterpene reportedly present in the ubiquitous South African shrub Elytropappus rhinocerotis, was devised in order to allow further bioactivity tests to be performed and unequivocally assign the unknown absolute stereochemistry of the T. costatus metabolites. Attempts to isolate rhinocerotinoic acid from local specimens of Elytropappus rhinocerotis were unsuccessful, and as the repetition of a published synthesis of 4.14 from (-)-sclareol (4.15) gave rhinocerotinoic acid in unacceptably low yields with poor stereoselectivity, an improved synthesis of 4.14 is presented. Comprehensive studies using hispanone (5.1) as a model compound showed that 6,7-dioxygenated labda-8-enes could be prepared from compounds possessing a 7-oxo-labda-8-ene skeleton with some degree of stereocontrol. In the process, fourteen new hispanone analogues were prepared and most of these were tested for activity in a suite of ten agro-chemical assays. The novel compound 7b-hydroxy-9a-carbonitrile-15,16-epoxylabda-13(16),14-dien-6-one (5.34) exhibited significant activity against the crop fungus Phytophthora infestans and is currently being subjected to further agro-chemical tests. Unfortunately, the results from the oxygenation study performed on the model compound 5.1 could not be directly extrapolated to rhinocerotinoic acid. Attempts to prepare the naturally occurring 3.10 from 4.14 via an alternative route were unsuccessful but yielded an analogue of 3.10 in which the substituents at C-6 and C-7 are in a diequatorial rather than a diaxial configuration.
- Full Text:
- Date Issued: 2003
- Authors: Gray, Christopher Anthony
- Date: 2003
- Subjects: Ethyl acetoacetate Diterpenes Limpets -- South Africa Natural products -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4349 , http://hdl.handle.net/10962/d1005014
- Description: This thesis is divided into two parts. The first part (Chapter Two) documents a bioassay guided investigation of the ethyl acetate extracts of four marine invertebrates from Mozambique (an Irciniid sponge, a Haliclona sp. sponge, an ascidian tentatively identified as Diplosoma sp., and the soft coral Cladiella kashmani). Eight known compounds [ilimaquinone (2.1), renierone (2.7), N-formyl-1,2-dihydrorenierone (2.8), 1,6-dimethyl-7-methoxy-5,8-dihydroisoquinoline-5,8-dione (2.9), mimosamycin (2.10) 7Z-allylidene-5-hydroxy-7,7a-dihydro-2H-cyclopenta[b]pyran-6-one (2.11), flaccidoxide (2.18) and 11S,12S-epoxycembra-1Z,3E,7E-trien-14S-ol (2.19)] and a new diterpene [13S,14R-diacetoxy-11S,12R-epoxycembra-1Z,3E,7E-triene (2.20)] were isolated and identified using standard spectroscopic techniques. Anomalies in the published spectral data of 2.1 and 2.8 were exposed and corrected, and the absolute stereochemistry of the cembrane diterpenes 2.18 and 2.20 established using the modified Mosher’s method. The comparative activities of the nine natural products against four cancer cell lines (A549, LOX, OVCAR3, SNB19) are reported. The second part of the thesis (Chapter Three – Chapter Six) is concerned with an ecological, structural and synthetic study of diterpenes from the endemic South African pulmonate limpet Trimusculus costatus. Two new labdane diterpenes [6b,7a-diacetoxylabda-8,13E-dien-15-ol (3.10) and 2a,6b,7a-triacetoxylabda-8,13E-dien-15-ol (3.11)] were isolated from T. costatus and evaluated for anti-feeding activity against the common predatory fish Pomadasys commersonnii. A strategy for the semi-synthesis of 3.10 from rhinocerotinoic acid (4.14), a diterpene reportedly present in the ubiquitous South African shrub Elytropappus rhinocerotis, was devised in order to allow further bioactivity tests to be performed and unequivocally assign the unknown absolute stereochemistry of the T. costatus metabolites. Attempts to isolate rhinocerotinoic acid from local specimens of Elytropappus rhinocerotis were unsuccessful, and as the repetition of a published synthesis of 4.14 from (-)-sclareol (4.15) gave rhinocerotinoic acid in unacceptably low yields with poor stereoselectivity, an improved synthesis of 4.14 is presented. Comprehensive studies using hispanone (5.1) as a model compound showed that 6,7-dioxygenated labda-8-enes could be prepared from compounds possessing a 7-oxo-labda-8-ene skeleton with some degree of stereocontrol. In the process, fourteen new hispanone analogues were prepared and most of these were tested for activity in a suite of ten agro-chemical assays. The novel compound 7b-hydroxy-9a-carbonitrile-15,16-epoxylabda-13(16),14-dien-6-one (5.34) exhibited significant activity against the crop fungus Phytophthora infestans and is currently being subjected to further agro-chemical tests. Unfortunately, the results from the oxygenation study performed on the model compound 5.1 could not be directly extrapolated to rhinocerotinoic acid. Attempts to prepare the naturally occurring 3.10 from 4.14 via an alternative route were unsuccessful but yielded an analogue of 3.10 in which the substituents at C-6 and C-7 are in a diequatorial rather than a diaxial configuration.
- Full Text:
- Date Issued: 2003
Biological control initiatives against Lantana camara L. (Verbenaceae) in South Africa : an assessment of the present status of the programme, and an evaluation of Coelocephalapion camarae Kissinger (Coleoptera: Brentidae) and Falconia intermedia (Distant) (Heteroptera: Miridae), two new candidate natural enemies for release on the weed
- Authors: Baars, Jan-Robert
- Date: 2003
- Subjects: Lantana camara Lantana camera -- South Africa Biological pest control agents -- South Africa Beetles -- South Africa Hemiptera -- South Africa Weeds -- Biological control -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5647 , http://hdl.handle.net/10962/d1005329
- Description: Lantana camara (lantana), a thicket-forming shrub, a number of different varieties of which were introduced into South Africa as ornamental plants but which has become a serious invasive weed. Conventional control measures for lantana are expensive and ineffective and it has therefore been targeted for biological control since 1961. To date, eleven biological control agent species have become established on lantana in South Africa. However, most agents persist at low densities and only occasionally impact plant populations. Three species regularly cause significant damage, but only reach sufficiently high numbers by midsummer after populations crash during the winter. Overall, the impact of the biological control programme on the weed is negligible and this has been ascribed to the poor selection of agents for release, the accumulation of native parasitoids, differences in insect preference for different varieties of the weed and variable climatic conditions over the weed’s range. This study suggests that the importance of varietal preferences has been over-estimated. A predictive bioclimatic modelling technique showed that most of the agents established in South Africa have a wide climatic tolerance and that the redistribution and importation of new climatypes of these agents will not improve the level of control. Additional agents are required to improve the biocontrol in the temperate conditions, and also to increase damage in the sub-tropical areas where most of the agents are established and where the weed retains its leaves year round. New candidate agents that possess biological attributes that favour a high intrinsic rate of increase, a high impact per individual and that improve the synchrony between the weed and the agent in climatic conditions that promote the seasonal leaflessness of plants should receive prior consideration. A survey in Jamaica indicated that additional biological control agents are available in the region of origin but that care should be taken to prioritise the most effective agents. The various selection systems currently available in weed biocontrol produce contradictory results in the priority assigned to candidate agents and a new selection system is proposed. The biology and host range of two new candidate natural enemies, the leaf-galling weevil, Coelocephalapion camarae and the leaf-sucking mirid, Falconia intermedia were investigated for the biocontrol of lantana. The studies indicated that these have considerable biocontrol potential, in that the weevil has a wide climatic tolerance and has the potential to survive the host leaflessness typical of temperate conditions, while the mirid has a high intrinsic rate of increase, and the potential for several generations a year. Both agents caused a high level of damage to the leaves, with the weevil galling the vascular tissue in the leaf-petiole and the mirid causing chlorotic speckling of the leaves. During laboratory trials both agents accepted indigenous species in the genus Lippia. However, under multiple choice conditions these agents showed a significant and strong oviposition preference for lantana. A risk assessment and post release field trials indicated that F. intermedia is likely to attack some Lippia species in the presence of lantana, but the levels of damage are predicted to be relatively low. A possible low incidence of damage to indigenous species was considered a justifiable ‘trade-off’ for the potentially marked impact on L. camara. Preference and performance studies on the two candidate agents suggested that most of the South African lantana varieties are suitable host plants. The mirid preferred certain varieties in multiple choice experiments, but this is unlikely to affect its impact under field conditions. Permission for release was accordingly sought for both species. Finally, the challenges facing the biological control programme and the potential for improving the control of L. camara in South Africa are considered.
- Full Text:
- Date Issued: 2003
- Authors: Baars, Jan-Robert
- Date: 2003
- Subjects: Lantana camara Lantana camera -- South Africa Biological pest control agents -- South Africa Beetles -- South Africa Hemiptera -- South Africa Weeds -- Biological control -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5647 , http://hdl.handle.net/10962/d1005329
- Description: Lantana camara (lantana), a thicket-forming shrub, a number of different varieties of which were introduced into South Africa as ornamental plants but which has become a serious invasive weed. Conventional control measures for lantana are expensive and ineffective and it has therefore been targeted for biological control since 1961. To date, eleven biological control agent species have become established on lantana in South Africa. However, most agents persist at low densities and only occasionally impact plant populations. Three species regularly cause significant damage, but only reach sufficiently high numbers by midsummer after populations crash during the winter. Overall, the impact of the biological control programme on the weed is negligible and this has been ascribed to the poor selection of agents for release, the accumulation of native parasitoids, differences in insect preference for different varieties of the weed and variable climatic conditions over the weed’s range. This study suggests that the importance of varietal preferences has been over-estimated. A predictive bioclimatic modelling technique showed that most of the agents established in South Africa have a wide climatic tolerance and that the redistribution and importation of new climatypes of these agents will not improve the level of control. Additional agents are required to improve the biocontrol in the temperate conditions, and also to increase damage in the sub-tropical areas where most of the agents are established and where the weed retains its leaves year round. New candidate agents that possess biological attributes that favour a high intrinsic rate of increase, a high impact per individual and that improve the synchrony between the weed and the agent in climatic conditions that promote the seasonal leaflessness of plants should receive prior consideration. A survey in Jamaica indicated that additional biological control agents are available in the region of origin but that care should be taken to prioritise the most effective agents. The various selection systems currently available in weed biocontrol produce contradictory results in the priority assigned to candidate agents and a new selection system is proposed. The biology and host range of two new candidate natural enemies, the leaf-galling weevil, Coelocephalapion camarae and the leaf-sucking mirid, Falconia intermedia were investigated for the biocontrol of lantana. The studies indicated that these have considerable biocontrol potential, in that the weevil has a wide climatic tolerance and has the potential to survive the host leaflessness typical of temperate conditions, while the mirid has a high intrinsic rate of increase, and the potential for several generations a year. Both agents caused a high level of damage to the leaves, with the weevil galling the vascular tissue in the leaf-petiole and the mirid causing chlorotic speckling of the leaves. During laboratory trials both agents accepted indigenous species in the genus Lippia. However, under multiple choice conditions these agents showed a significant and strong oviposition preference for lantana. A risk assessment and post release field trials indicated that F. intermedia is likely to attack some Lippia species in the presence of lantana, but the levels of damage are predicted to be relatively low. A possible low incidence of damage to indigenous species was considered a justifiable ‘trade-off’ for the potentially marked impact on L. camara. Preference and performance studies on the two candidate agents suggested that most of the South African lantana varieties are suitable host plants. The mirid preferred certain varieties in multiple choice experiments, but this is unlikely to affect its impact under field conditions. Permission for release was accordingly sought for both species. Finally, the challenges facing the biological control programme and the potential for improving the control of L. camara in South Africa are considered.
- Full Text:
- Date Issued: 2003
The fundamental right to just administrative action: judicial review of administrative action in the democratic South Africa
- Authors: Plasket, Clive
- Date: 2003
- Subjects: Judicial review of administrative acts -- South Africa Administrative acts -- South Africa Administrative law -- South Africa Public administration -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3693 , http://hdl.handle.net/10962/d1003208
- Description: For most of its existence South African administrative law has been shaped by the doctrine of parliamentary sovereignty – the heart of the constitutional order from 1910 to 1994 – and a racist political system that favoured the white minority at the expense of the black majority. In these circumstances, the rules of administrative law were of limited use in protecting the individual from exercises of administrative power that infringed fundamental human rights, often on a grand scale. On 27 April 1994, however, a new political and constitutional order came into existence that swept away the very foundations of the old order: parliamentary sovereignty was replaced by constitutional supremacy and the racial exclusivity of the old order was replaced by a commitment to equality, freedom and dignity in a democratic state. A justiciable Bill of Rights was at centre stage in this new order. That Bill of Rights includes a fundamental right to just administrative action. It is both the new constitutional order and this rather unusual fundamental right that have changed the nature of South African administrative law. This thesis examines the effect of the fundamental right to just administrative action on the law and practice of the judicial review of administrative action. It does so principally by examining the legal position before and after 27 April 1994 with particular reference to: what is meant by administrative action; the exercise of administrative power by private bodies regulated by the rules of administrative law, on the one hand, and exercises of private power regulated by rules of private law, on the other; the rules of standing, the notion of justiciability and the constitutionality of rules that seek to limit the right of the individual to approach a court to review administrative action; the meaning and scope of the right to lawful, reasonable and procedurally fair administrative action, in terms of the common law, the Constitution and the Promotion of Administrative Justice Act 3 of 2000; the meaning, scope and efficacy of the rights to reasons for administrative actions and of access to information; the procedure of judicial review and remedies that may be granted for the infringement of a person’s right to just administrative action; and conclusions and recommendations with regard to progress made in the construction of South Africa’s new, democratically based, administrative law.
- Full Text:
- Date Issued: 2003
- Authors: Plasket, Clive
- Date: 2003
- Subjects: Judicial review of administrative acts -- South Africa Administrative acts -- South Africa Administrative law -- South Africa Public administration -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3693 , http://hdl.handle.net/10962/d1003208
- Description: For most of its existence South African administrative law has been shaped by the doctrine of parliamentary sovereignty – the heart of the constitutional order from 1910 to 1994 – and a racist political system that favoured the white minority at the expense of the black majority. In these circumstances, the rules of administrative law were of limited use in protecting the individual from exercises of administrative power that infringed fundamental human rights, often on a grand scale. On 27 April 1994, however, a new political and constitutional order came into existence that swept away the very foundations of the old order: parliamentary sovereignty was replaced by constitutional supremacy and the racial exclusivity of the old order was replaced by a commitment to equality, freedom and dignity in a democratic state. A justiciable Bill of Rights was at centre stage in this new order. That Bill of Rights includes a fundamental right to just administrative action. It is both the new constitutional order and this rather unusual fundamental right that have changed the nature of South African administrative law. This thesis examines the effect of the fundamental right to just administrative action on the law and practice of the judicial review of administrative action. It does so principally by examining the legal position before and after 27 April 1994 with particular reference to: what is meant by administrative action; the exercise of administrative power by private bodies regulated by the rules of administrative law, on the one hand, and exercises of private power regulated by rules of private law, on the other; the rules of standing, the notion of justiciability and the constitutionality of rules that seek to limit the right of the individual to approach a court to review administrative action; the meaning and scope of the right to lawful, reasonable and procedurally fair administrative action, in terms of the common law, the Constitution and the Promotion of Administrative Justice Act 3 of 2000; the meaning, scope and efficacy of the rights to reasons for administrative actions and of access to information; the procedure of judicial review and remedies that may be granted for the infringement of a person’s right to just administrative action; and conclusions and recommendations with regard to progress made in the construction of South Africa’s new, democratically based, administrative law.
- Full Text:
- Date Issued: 2003
The diamondback moth, Plutella xylostella (L.), (Lepidoptera: Plutellidae) and its biological control in the Eastern Cape Province, South Africa
- Authors: Smith, Tamara Jane
- Date: 2003
- Subjects: Plutellidae Plutellidae -- South Africa -- Eastern Cape Insect pests -- Biological control -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5626 , http://hdl.handle.net/10962/d1004742
- Description: The diamondback moth, Plutella xylostella (L.), is a pest on crucifer crops worldwide, damaging the leaves, florets and seed pods of many crucifers including cabbage, cauliflower, broccoli and canola. It has been controlled using broad-spectrum insecticides, but this has led to a rapid build-up of insecticide resistance. In the Grahamstown area of the Eastern Cape Province, South Africa, diamondback moth showed resistance to cypermethrin (a pyrethroid) on commercially grown cabbages. Therefore it is imperative that other methods of control be adopted, including both cultural control and biological control using parasitoids, and that these are incorporated into an Integrated Pest Management (IPM) programme. The diamondback moth and its parasitoids were monitored weekly from April 1997 to November 1999 at three sites near Grahamstown. One site was a commercial farm with an active insecticide spraying program; the others were unsprayed. Infestation levels were highest during spring (September to November) and autumn (March to May). Nine species of parasitoids were associated with the diamondback moth, with abundances being highest over spring and early summer (September to December). Cotesia plutellae (Kurdjumov) dominated the sprayed site, while the unsprayed sites yielded a complex of parasitoids, including C. plutellae, Diadegma mollipla (Holmgren), Diadromus collaris Gravenhorst and Oomyzus sokolowsldi (Kurdjumov). Parasitism levels ranged between 10 and 90%. There was a large amount of site-to-site and year-to-year variation. Parasitoids were an effective mortality factor against the diamondback moth. The effects of temperature on development and mortality, and of field size and non-crop plants on the distribution of diamondback moth and its parasitoids, were investigated. The results show that high temperatures can depress pest populations, and that the size and surroundings of fields can be manipulated to improve cultural control of the diamondback moth. Suggestions for effective rPM in the Eastern Cape Province include a reduction in insecticide applications, the use of bioinsecticides, for example Bacillus thuringiensis Berliner (Bt) and the encouragement of indigenous parasitoids by planting suitable nectar sources. Cultural control methods are also important and involve removal of cabbage refuse after harvest, management of wild crucifers around cabbage fields, scouting and monitoring the moth population and determining the optimal field size to assist with control by parasitoids.
- Full Text:
- Date Issued: 2003
- Authors: Smith, Tamara Jane
- Date: 2003
- Subjects: Plutellidae Plutellidae -- South Africa -- Eastern Cape Insect pests -- Biological control -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5626 , http://hdl.handle.net/10962/d1004742
- Description: The diamondback moth, Plutella xylostella (L.), is a pest on crucifer crops worldwide, damaging the leaves, florets and seed pods of many crucifers including cabbage, cauliflower, broccoli and canola. It has been controlled using broad-spectrum insecticides, but this has led to a rapid build-up of insecticide resistance. In the Grahamstown area of the Eastern Cape Province, South Africa, diamondback moth showed resistance to cypermethrin (a pyrethroid) on commercially grown cabbages. Therefore it is imperative that other methods of control be adopted, including both cultural control and biological control using parasitoids, and that these are incorporated into an Integrated Pest Management (IPM) programme. The diamondback moth and its parasitoids were monitored weekly from April 1997 to November 1999 at three sites near Grahamstown. One site was a commercial farm with an active insecticide spraying program; the others were unsprayed. Infestation levels were highest during spring (September to November) and autumn (March to May). Nine species of parasitoids were associated with the diamondback moth, with abundances being highest over spring and early summer (September to December). Cotesia plutellae (Kurdjumov) dominated the sprayed site, while the unsprayed sites yielded a complex of parasitoids, including C. plutellae, Diadegma mollipla (Holmgren), Diadromus collaris Gravenhorst and Oomyzus sokolowsldi (Kurdjumov). Parasitism levels ranged between 10 and 90%. There was a large amount of site-to-site and year-to-year variation. Parasitoids were an effective mortality factor against the diamondback moth. The effects of temperature on development and mortality, and of field size and non-crop plants on the distribution of diamondback moth and its parasitoids, were investigated. The results show that high temperatures can depress pest populations, and that the size and surroundings of fields can be manipulated to improve cultural control of the diamondback moth. Suggestions for effective rPM in the Eastern Cape Province include a reduction in insecticide applications, the use of bioinsecticides, for example Bacillus thuringiensis Berliner (Bt) and the encouragement of indigenous parasitoids by planting suitable nectar sources. Cultural control methods are also important and involve removal of cabbage refuse after harvest, management of wild crucifers around cabbage fields, scouting and monitoring the moth population and determining the optimal field size to assist with control by parasitoids.
- Full Text:
- Date Issued: 2003
An investigation of the isolation, characterisation and application of hydantoinases for the industrial production of amino acids
- Authors: Kirchmann, Shaun
- Date: 2003
- Subjects: Hydantoin Amino acids Hydrolysis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3969 , http://hdl.handle.net/10962/d1004028
- Description: This thesis describes a series of investigations into the hydantoin-hydrolysing activity of bacterial strains RU-KM1 and RU-OR, which were previously isolated for their ability to hydrolyse hydantoins to amino acids. The main aim of the study was to develop biotransformations with potential application in the production of enantiomerically pure amino acids using a bioreactor based system utilising the hydantoin hydrolysing enzymes of the two isolated microorganisms. Different substituted hydantoins may be used as substrates by these enzymes for the production of a variety of amino acids. These are not only important for amino acid production, but they may be used for production of other industrially important compounds, such as semisynthetic penicillin/ampicillin, L-aspartame (sweetener), Fluvalinate (insecticide), Enalapril (ACE inhibitor). Thus, the ability of the above-mentioned strains to hydrolyse these substrates was investigated, with the view to utilizing the maximum potential of these biocatalysts. Hydantoin conversion involves a two-step hydrolysis reaction which yields, initially, an N-carbamylamino acid intermediate, and subsequently, an amino acid. The hydantoin-hydrolysing enzymes of a Pseudomonas sp. RU-KM1, and an Agrobacterium sp. RU-OR were characterised as whole cells and in a crude extract preparation, and reaction conditions for its biocatalytic application were optimised. The optimum conditions for conversion of hydantoin to glycine were found to be 1 hour at 40 °C, with conversion yields greater than 30 % achieved. The enzymes of RU-KM1 demonstrated considerable stability, retaining 80 % of their activity after storage for 2 weeks at 4 °C. The activities of the enzymes were increased by the addition of a detergent to the extraction medium, suggesting that the enzymes might be membrane-bound. The results of the determination of the metal-dependence of the hydantoinase and N-carbamoylase of RU-KM1 suggested that these enzymes required metal ions for activity, with metal ions such as Cu[superscript (2+)], Fe[superscript (2+)], and Co[superscript (2+)] resulting in no significant change in enzyme activity, however there was an activation of the enzymes when Mn[superscript (2+)] was added to the enzymes. The stereoselectivity of the enzymes was investigated, and the results suggested that the hydantoinase was D-selective, whereas the N-carbamoylase was shown to be L-selective by other researchers. The hydantoin substrate selectivity of RU-KM1 and RU-OR was investigated, and the organisms were shown to be able to hydrolyse all of the seven substrates tested. However, there was a difference in activity levels between crude extract preparations and whole cells, with crude extracts generally showing slightly lower activity than whole cells in RU-KM1, and the whole cells or RU-OR showing the lower activity than its crude extract. Some difference was also observed in the order of preference of substrates between whole cells and crude extracts. The preferred substrate for RU-KM1 whole cells was isopropylhydantoin, whereas the crude extract preparation preferentially hydrolysed p-hydroxyphenylhydantoin, achieving 57 % and 52 % conversions respectively. RU-OR whole cells preferred methylhydantoin where as the crude extract preferred isopropylhydantoin, and showed 49 % and 51 % conversions respectively. The enzymes were characterised in terms of their temperature and pH optima, inducer requirements, and product inhibition studies. The hydantoinase of RU-KM1 was shown to be inducible with low levels of hydantoin, and thermostable upto 75 °C with its optima between 60 and 70 °C. The N-carbamoylase was shown to have its optima at 50 °C. The addition of ATP (0.5 mM), DTT (1 mM) and a protease inhibitor (2 mg.mL[superscript (-1)]) all increased the hydantoinase activity of RU-KM1 crude extract, however they had very little effect on the N-carbamoylase activity. The hydantoinase enzyme from extracts of RU-KM1 was partially purified by development of cell disruption methods using mechanical and lysing enzymes, followed by precipitation and chromatographic resolution. The results obtained showed a hydantoinase enzyme of between 48 and 66 kDa. RU-KM1 was grown under fermentation conditions using different minimal media. The activity and yields under these conditions were low. Previous attempt to grow the organism in a rich medium had resulted in an increase in biomass but no hydantoinase activity. A rich medium was developed by carbon and nitrogen optimisation and yielded biomass up to 30 g.L[superscript (-1)] dry cell weight. The hydantoinase activity was restored by nitrogen starvation in stationary phase. This resulted in high biomass with increased activity. This data is currently in press. Crude extract and whole cells were immobilised on flat sheet membranes, hollow fibre membranes and in alginate beads. Low hydantoinase activity was measured in bioreactors using membranes in different configurations. A significant increase in hydantoinase activity was measured when the crude extract was immobilised in sodium alginate, as a result of stabilisation of the N-carbamoylase. Temperature and pH optima were unaffected by the immobilisation procedure, however the durability of the enzymes increased 2-fold. Different configurations of the bioreactor were investigated, as well as a hydroxyphenylhydantoin as an alternative substrate in this study. The bioreactors showed a near 95 % conversion of the hydantoin to glycine, and a 99 % conversion using HPG. In conclusion, the hydantoin-hydrolysing enzymes of RU-KM1 have been shown to be possibly membrane associated, which is a novel finding. This study has shown that the hydantoinase of RU-KM1 is D-stereoselective, with high temperature stability. A growth medium was developed for the rapid production of active biomass. A bioreactor was developed using a single and a dual biocatalyst configuration, which was capable of hydrolysing hydantoin and monosubstituted hydantoins to produce amino acids. To our knowledge this system is the first such dual biocatalyst system reported for the production of amino acids.
- Full Text:
- Date Issued: 2003
- Authors: Kirchmann, Shaun
- Date: 2003
- Subjects: Hydantoin Amino acids Hydrolysis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3969 , http://hdl.handle.net/10962/d1004028
- Description: This thesis describes a series of investigations into the hydantoin-hydrolysing activity of bacterial strains RU-KM1 and RU-OR, which were previously isolated for their ability to hydrolyse hydantoins to amino acids. The main aim of the study was to develop biotransformations with potential application in the production of enantiomerically pure amino acids using a bioreactor based system utilising the hydantoin hydrolysing enzymes of the two isolated microorganisms. Different substituted hydantoins may be used as substrates by these enzymes for the production of a variety of amino acids. These are not only important for amino acid production, but they may be used for production of other industrially important compounds, such as semisynthetic penicillin/ampicillin, L-aspartame (sweetener), Fluvalinate (insecticide), Enalapril (ACE inhibitor). Thus, the ability of the above-mentioned strains to hydrolyse these substrates was investigated, with the view to utilizing the maximum potential of these biocatalysts. Hydantoin conversion involves a two-step hydrolysis reaction which yields, initially, an N-carbamylamino acid intermediate, and subsequently, an amino acid. The hydantoin-hydrolysing enzymes of a Pseudomonas sp. RU-KM1, and an Agrobacterium sp. RU-OR were characterised as whole cells and in a crude extract preparation, and reaction conditions for its biocatalytic application were optimised. The optimum conditions for conversion of hydantoin to glycine were found to be 1 hour at 40 °C, with conversion yields greater than 30 % achieved. The enzymes of RU-KM1 demonstrated considerable stability, retaining 80 % of their activity after storage for 2 weeks at 4 °C. The activities of the enzymes were increased by the addition of a detergent to the extraction medium, suggesting that the enzymes might be membrane-bound. The results of the determination of the metal-dependence of the hydantoinase and N-carbamoylase of RU-KM1 suggested that these enzymes required metal ions for activity, with metal ions such as Cu[superscript (2+)], Fe[superscript (2+)], and Co[superscript (2+)] resulting in no significant change in enzyme activity, however there was an activation of the enzymes when Mn[superscript (2+)] was added to the enzymes. The stereoselectivity of the enzymes was investigated, and the results suggested that the hydantoinase was D-selective, whereas the N-carbamoylase was shown to be L-selective by other researchers. The hydantoin substrate selectivity of RU-KM1 and RU-OR was investigated, and the organisms were shown to be able to hydrolyse all of the seven substrates tested. However, there was a difference in activity levels between crude extract preparations and whole cells, with crude extracts generally showing slightly lower activity than whole cells in RU-KM1, and the whole cells or RU-OR showing the lower activity than its crude extract. Some difference was also observed in the order of preference of substrates between whole cells and crude extracts. The preferred substrate for RU-KM1 whole cells was isopropylhydantoin, whereas the crude extract preparation preferentially hydrolysed p-hydroxyphenylhydantoin, achieving 57 % and 52 % conversions respectively. RU-OR whole cells preferred methylhydantoin where as the crude extract preferred isopropylhydantoin, and showed 49 % and 51 % conversions respectively. The enzymes were characterised in terms of their temperature and pH optima, inducer requirements, and product inhibition studies. The hydantoinase of RU-KM1 was shown to be inducible with low levels of hydantoin, and thermostable upto 75 °C with its optima between 60 and 70 °C. The N-carbamoylase was shown to have its optima at 50 °C. The addition of ATP (0.5 mM), DTT (1 mM) and a protease inhibitor (2 mg.mL[superscript (-1)]) all increased the hydantoinase activity of RU-KM1 crude extract, however they had very little effect on the N-carbamoylase activity. The hydantoinase enzyme from extracts of RU-KM1 was partially purified by development of cell disruption methods using mechanical and lysing enzymes, followed by precipitation and chromatographic resolution. The results obtained showed a hydantoinase enzyme of between 48 and 66 kDa. RU-KM1 was grown under fermentation conditions using different minimal media. The activity and yields under these conditions were low. Previous attempt to grow the organism in a rich medium had resulted in an increase in biomass but no hydantoinase activity. A rich medium was developed by carbon and nitrogen optimisation and yielded biomass up to 30 g.L[superscript (-1)] dry cell weight. The hydantoinase activity was restored by nitrogen starvation in stationary phase. This resulted in high biomass with increased activity. This data is currently in press. Crude extract and whole cells were immobilised on flat sheet membranes, hollow fibre membranes and in alginate beads. Low hydantoinase activity was measured in bioreactors using membranes in different configurations. A significant increase in hydantoinase activity was measured when the crude extract was immobilised in sodium alginate, as a result of stabilisation of the N-carbamoylase. Temperature and pH optima were unaffected by the immobilisation procedure, however the durability of the enzymes increased 2-fold. Different configurations of the bioreactor were investigated, as well as a hydroxyphenylhydantoin as an alternative substrate in this study. The bioreactors showed a near 95 % conversion of the hydantoin to glycine, and a 99 % conversion using HPG. In conclusion, the hydantoin-hydrolysing enzymes of RU-KM1 have been shown to be possibly membrane associated, which is a novel finding. This study has shown that the hydantoinase of RU-KM1 is D-stereoselective, with high temperature stability. A growth medium was developed for the rapid production of active biomass. A bioreactor was developed using a single and a dual biocatalyst configuration, which was capable of hydrolysing hydantoin and monosubstituted hydantoins to produce amino acids. To our knowledge this system is the first such dual biocatalyst system reported for the production of amino acids.
- Full Text:
- Date Issued: 2003
A neural network based ionospheric model for the bottomside electron density profile over Grahamstown, South Africa
- Authors: McKinnell, L A
- Date: 2003
- Subjects: Neural networks (Computer science) Ionospheric electron density -- South Africa -- Grahamstown
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5477 , http://hdl.handle.net/10962/d1005262
- Description: This thesis describes the development and application of a neural network based ionospheric model for the bottomside electron density profile over Grahamstown, South Africa. All available ionospheric data from the archives of the Grahamstown (33.32ºS, 26.50ºE) ionospheric station were used for training neural networks (NNs) to predict the parameters required to produce the final profile. Inputs to the model, called the LAM model, are day number, hour, and measures of solar and magnetic activity. The output is a mathematical description of the bottomside electron density profile for that particular input set. The two main ionospheric layers, the E and F layers, are predicted separately and then combined at the final stage. For each layer, NNs have been trained to predict the individual ionospheric characteristics and coefficients that were required to describe the layer profile. NNs were also applied to the task of determining the hours between which an E layer is measurable by a groundbased ionosonde and the probability of the existence of an F1 layer. The F1 probability NN is innovative in that it provides information on the existence of the F1 layer as well as the probability of that layer being in a L-condition state - the state where an F1 layer is present on an ionogram but it is not possible to record any F1 parameters. In the event of an L-condition state being predicted as probable, an L algorithm has been designed to alter the shape of the profile to reflect this state. A smoothing algorithm has been implemented to remove discontinuities at the F1-F2 boundary and ensure that the profile represents realistic ionospheric behaviour in the F1 region. Tests show that the LAM model is more successful at predicting Grahamstown electron density profiles for a particular set of inputs than the International Reference Ionosphere (IRI). It is anticipated that the LAM model will be used as a tool in the pin-pointing of hostile HF transmitters, known as single-site location.
- Full Text:
- Date Issued: 2003
- Authors: McKinnell, L A
- Date: 2003
- Subjects: Neural networks (Computer science) Ionospheric electron density -- South Africa -- Grahamstown
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5477 , http://hdl.handle.net/10962/d1005262
- Description: This thesis describes the development and application of a neural network based ionospheric model for the bottomside electron density profile over Grahamstown, South Africa. All available ionospheric data from the archives of the Grahamstown (33.32ºS, 26.50ºE) ionospheric station were used for training neural networks (NNs) to predict the parameters required to produce the final profile. Inputs to the model, called the LAM model, are day number, hour, and measures of solar and magnetic activity. The output is a mathematical description of the bottomside electron density profile for that particular input set. The two main ionospheric layers, the E and F layers, are predicted separately and then combined at the final stage. For each layer, NNs have been trained to predict the individual ionospheric characteristics and coefficients that were required to describe the layer profile. NNs were also applied to the task of determining the hours between which an E layer is measurable by a groundbased ionosonde and the probability of the existence of an F1 layer. The F1 probability NN is innovative in that it provides information on the existence of the F1 layer as well as the probability of that layer being in a L-condition state - the state where an F1 layer is present on an ionogram but it is not possible to record any F1 parameters. In the event of an L-condition state being predicted as probable, an L algorithm has been designed to alter the shape of the profile to reflect this state. A smoothing algorithm has been implemented to remove discontinuities at the F1-F2 boundary and ensure that the profile represents realistic ionospheric behaviour in the F1 region. Tests show that the LAM model is more successful at predicting Grahamstown electron density profiles for a particular set of inputs than the International Reference Ionosphere (IRI). It is anticipated that the LAM model will be used as a tool in the pin-pointing of hostile HF transmitters, known as single-site location.
- Full Text:
- Date Issued: 2003
An investigation into the physico-chemical and neuroprotective properties of melatonin and 6-hydroxymelatonin
- Authors: Maharaj, Deepa Sukhdev
- Date: 2003
- Subjects: Melatonin Nervous system -- Degeneration -- Treatment
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3768 , http://hdl.handle.net/10962/d1003246
- Description: Until the beginning of this decade the antioxidant, melatonin, had been considered as little more than a tranquilizing hormone, responsible for regulating certain circadian and circannual rhythms. However, it is the discovery of melatonin as a free radical scavenger that has generated the most interest in recent years. The reduction of melatonin with age has been associated with neurodegenerative diseases such as Alzheimer’s disease (AD)and therefore, melatonin has been implicated to have an important clinical role in neuroprotection. Thus, for several years melatonin has attracted increasing attention from the general press with many advertisements touting this indoleamine to act as an aphrodisiac, rejuvenator, protector against diseases and a general wonder drug. However, melatonin formulations appear with no labelling for the correct storage conditions, dosage and side effects, as well as no control for purity and self-medicating with an unregulated product. In addition, there is much controversy surrounding the antioxidative properties of the indolemaine, 6-hydroxymelatonin (6-OHM). Therefore, the first part of this study aims to elucidate the physico-chemical and various stability characteristics of the pineal antioxidant, melatonin, while the second part is devoted to investigating the neuroprotective properties of the primary hepatic metabolite of melatonin, 6-OHM. The physical properties of melatonin were determined using various chemical techniques. This information served to both characterize and confirm the identity of melatonin raw material used in this study. In addition, this information serves to be essential as the physical properties of melatonin have not been reported in detail in literature, to date. Thereafter, using a validated high performance liquid chromatography (HPLC) method, the various physico-chemical and stability characteristics of melatonin were determined. Melatonin was shown to be extremely lipophilic, while the hygroscopic study indicates that melatonin raw material is extremely hygroscopic at temperatures above 40°C, whereas melatonin tablets are hygroscopic when left out of the original container. This study highlights the need for consumers to be aware of the proper storage of melatonin tablets to improve the stability and ensure long term integrity of the compound. Since, melatonin is most often administered orally, thus exposing it to a large variations in pH, within the gastrointestinal tract, it was decided to investigate the stability of melatonin over a range of pH’s and temperatures. The findings imply that melatonin is relatively stable at body temperature when ingested orally and that orally administered slow release preparations of melatonin should be relatively stable and therefore exhibit favourable bioavailability. However melatonin was shown to be unstable in solution. This provides important information and a challenge to the formulators of this drug substance in a liquid dosage form. An assessment of the photostability of melatonin dosage forms using International Committee on Harmonization (ICH) conditions revealed melatonin to be light sensitive and thus indicates a need for careful consideration of the packaging of these drug products. In addition a detailed assessment of the photochemistry and photoproducts formed during the UV photodegradation of melatonin is reported. Melatonin is shown to rapidly degrade in the presence of UV light, with the presence of oxygen accelerating the photodegradation. N1-acetyl-N2-formyl-5-methoxykynurenamine(AFMK) and 6-OHM were identified as the major photoproducts formed and these agents have been shown previously to retain antioxidant activity. One of the concerns of using melatonin in sunscreens is its photostability. However, it is reported in this study that the degraded solution of melatonin still possesses equipotent free radical scavenging ability as melatonin, despite the absence of melatonin in solution. In addition, melatonin is shown to reduce UV-induced oxidative stress in rat skin homogenate. Thus, these results make melatonin a likely candidate for inclusion in sunscreen preparations. Neuronal damage due to oxidative stress has been implicated in several neurodegenerative disorders. 6-OHM is not only formed as the major hepatic metabolite of melatonin, but also when melatonin reacts with toxic radicals as well as UV light. Thus the second part of the study aims to elucidate and further characterize the mechanism behind 6-OHM’s neuroprotection. The results show 6-OHM to be a more potent singlet oxygen and superoxide anion scavenger than melatonin. In addition, the results show 6-OHM to offer protection against, oxidative stress and lipid peroxidation induced by several neurotoxins in the rat brain and hippocampus. The hippocampus is an important region of the brain responsible for the formation of memory and any agent that induces stress in this area has detrimental effects and could lead to various types of dementia. Such agents include quinolinic acid (QA) and iron (II). Histological studies undertaken reveal that 6-OHM is able to protect hippocampal neurons against QA and iron (II) induced necrotic cell death. Immunohistochemical investigations showed that QA moderately induces apoptotic cell death in the hippocampus which is inhibited by both melatonin and 6-OHM. The study sought to elucidate possible mechanisms by which 6-OHM exerts its neuroprotective capabilities and the results show 6-OHM to inhibit the action of cyanide on the mitochondrial electron transport chain (ETC), one of the most common sources of free radicals. In addition, 6-OHM treatment alone, increased ETC activity above basal control levels and the results show 6-OHM to increase complex I activity in the mitochondrial ETC. Electrochemical, ultraviolet/visible spectroscopy (UV/Vis) and HPLC assessment show that an interaction exists between 6-OHM and iron (III) and 6-OHM is able to reduce iron (III) to a more biologically usable form viz. iron (II) which can be incorporated into important biomolecules such as heme. One dire consequence of this interaction is the ready provision of iron (II) to drive the Fenton reaction. However the biological and histological assessments show 6-OHM to prevent iron (II)-induced lipid peroxidation and necrotic cell death and thus, provide evidence of its antioxidant properties. The results also show 6-OHM to promote Hsp70 induction in the hippocampus. Heat shock proteins, especially Hsp 70 plays a role in cytoprotection by capturing denatured proteins and facilitating the refolding of these proteins once the stress has been relieved. 6-OHM treatment alone and together with QA was shown to increase the level of expression of Hsp70, both inducible and cognate forms of the protein. This suggests that 6-OHM helps to protect against cellular protein damage induced by any form of stress the cell may encounter. Melatonin treatment alone and in combination with QA was shown to prevent increases in the level of Hsp70 in the hippocampus, indicating that melatonin was able to reduce oxidative stress induced by QA such that Hsp70 expression was not required. The discovery of neuroprotective agents, such as melatonin and 6-OHM, is becoming important considering the rapid rise in the elderly population and the proportionate increase in neurological disorders. The findings of this study indicate the need for important information regarding the correct storage conditions and stability characteristics of melatonin dosage forms. In addition, the results indicate that 6-OHM has a definite role to play as an antioxidant. Thus further research may favour the use of these agents in the treatment of several neurodegenerative disorders.
- Full Text:
- Date Issued: 2003
- Authors: Maharaj, Deepa Sukhdev
- Date: 2003
- Subjects: Melatonin Nervous system -- Degeneration -- Treatment
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3768 , http://hdl.handle.net/10962/d1003246
- Description: Until the beginning of this decade the antioxidant, melatonin, had been considered as little more than a tranquilizing hormone, responsible for regulating certain circadian and circannual rhythms. However, it is the discovery of melatonin as a free radical scavenger that has generated the most interest in recent years. The reduction of melatonin with age has been associated with neurodegenerative diseases such as Alzheimer’s disease (AD)and therefore, melatonin has been implicated to have an important clinical role in neuroprotection. Thus, for several years melatonin has attracted increasing attention from the general press with many advertisements touting this indoleamine to act as an aphrodisiac, rejuvenator, protector against diseases and a general wonder drug. However, melatonin formulations appear with no labelling for the correct storage conditions, dosage and side effects, as well as no control for purity and self-medicating with an unregulated product. In addition, there is much controversy surrounding the antioxidative properties of the indolemaine, 6-hydroxymelatonin (6-OHM). Therefore, the first part of this study aims to elucidate the physico-chemical and various stability characteristics of the pineal antioxidant, melatonin, while the second part is devoted to investigating the neuroprotective properties of the primary hepatic metabolite of melatonin, 6-OHM. The physical properties of melatonin were determined using various chemical techniques. This information served to both characterize and confirm the identity of melatonin raw material used in this study. In addition, this information serves to be essential as the physical properties of melatonin have not been reported in detail in literature, to date. Thereafter, using a validated high performance liquid chromatography (HPLC) method, the various physico-chemical and stability characteristics of melatonin were determined. Melatonin was shown to be extremely lipophilic, while the hygroscopic study indicates that melatonin raw material is extremely hygroscopic at temperatures above 40°C, whereas melatonin tablets are hygroscopic when left out of the original container. This study highlights the need for consumers to be aware of the proper storage of melatonin tablets to improve the stability and ensure long term integrity of the compound. Since, melatonin is most often administered orally, thus exposing it to a large variations in pH, within the gastrointestinal tract, it was decided to investigate the stability of melatonin over a range of pH’s and temperatures. The findings imply that melatonin is relatively stable at body temperature when ingested orally and that orally administered slow release preparations of melatonin should be relatively stable and therefore exhibit favourable bioavailability. However melatonin was shown to be unstable in solution. This provides important information and a challenge to the formulators of this drug substance in a liquid dosage form. An assessment of the photostability of melatonin dosage forms using International Committee on Harmonization (ICH) conditions revealed melatonin to be light sensitive and thus indicates a need for careful consideration of the packaging of these drug products. In addition a detailed assessment of the photochemistry and photoproducts formed during the UV photodegradation of melatonin is reported. Melatonin is shown to rapidly degrade in the presence of UV light, with the presence of oxygen accelerating the photodegradation. N1-acetyl-N2-formyl-5-methoxykynurenamine(AFMK) and 6-OHM were identified as the major photoproducts formed and these agents have been shown previously to retain antioxidant activity. One of the concerns of using melatonin in sunscreens is its photostability. However, it is reported in this study that the degraded solution of melatonin still possesses equipotent free radical scavenging ability as melatonin, despite the absence of melatonin in solution. In addition, melatonin is shown to reduce UV-induced oxidative stress in rat skin homogenate. Thus, these results make melatonin a likely candidate for inclusion in sunscreen preparations. Neuronal damage due to oxidative stress has been implicated in several neurodegenerative disorders. 6-OHM is not only formed as the major hepatic metabolite of melatonin, but also when melatonin reacts with toxic radicals as well as UV light. Thus the second part of the study aims to elucidate and further characterize the mechanism behind 6-OHM’s neuroprotection. The results show 6-OHM to be a more potent singlet oxygen and superoxide anion scavenger than melatonin. In addition, the results show 6-OHM to offer protection against, oxidative stress and lipid peroxidation induced by several neurotoxins in the rat brain and hippocampus. The hippocampus is an important region of the brain responsible for the formation of memory and any agent that induces stress in this area has detrimental effects and could lead to various types of dementia. Such agents include quinolinic acid (QA) and iron (II). Histological studies undertaken reveal that 6-OHM is able to protect hippocampal neurons against QA and iron (II) induced necrotic cell death. Immunohistochemical investigations showed that QA moderately induces apoptotic cell death in the hippocampus which is inhibited by both melatonin and 6-OHM. The study sought to elucidate possible mechanisms by which 6-OHM exerts its neuroprotective capabilities and the results show 6-OHM to inhibit the action of cyanide on the mitochondrial electron transport chain (ETC), one of the most common sources of free radicals. In addition, 6-OHM treatment alone, increased ETC activity above basal control levels and the results show 6-OHM to increase complex I activity in the mitochondrial ETC. Electrochemical, ultraviolet/visible spectroscopy (UV/Vis) and HPLC assessment show that an interaction exists between 6-OHM and iron (III) and 6-OHM is able to reduce iron (III) to a more biologically usable form viz. iron (II) which can be incorporated into important biomolecules such as heme. One dire consequence of this interaction is the ready provision of iron (II) to drive the Fenton reaction. However the biological and histological assessments show 6-OHM to prevent iron (II)-induced lipid peroxidation and necrotic cell death and thus, provide evidence of its antioxidant properties. The results also show 6-OHM to promote Hsp70 induction in the hippocampus. Heat shock proteins, especially Hsp 70 plays a role in cytoprotection by capturing denatured proteins and facilitating the refolding of these proteins once the stress has been relieved. 6-OHM treatment alone and together with QA was shown to increase the level of expression of Hsp70, both inducible and cognate forms of the protein. This suggests that 6-OHM helps to protect against cellular protein damage induced by any form of stress the cell may encounter. Melatonin treatment alone and in combination with QA was shown to prevent increases in the level of Hsp70 in the hippocampus, indicating that melatonin was able to reduce oxidative stress induced by QA such that Hsp70 expression was not required. The discovery of neuroprotective agents, such as melatonin and 6-OHM, is becoming important considering the rapid rise in the elderly population and the proportionate increase in neurological disorders. The findings of this study indicate the need for important information regarding the correct storage conditions and stability characteristics of melatonin dosage forms. In addition, the results indicate that 6-OHM has a definite role to play as an antioxidant. Thus further research may favour the use of these agents in the treatment of several neurodegenerative disorders.
- Full Text:
- Date Issued: 2003
The phosphorylation and nuclear localization of the co-chaperone murine stress-inducible protein 1
- Authors: Longshaw, Victoria Mary
- Date: 2003
- Subjects: Phosphorylation Proteins Heat shock proteins
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3979 , http://hdl.handle.net/10962/d1004038
- Description: The co-chaperone murine stress-inducible protein 1 (mSTI1), a heat shock protein 70 (Hsp70)/ heat shock protein 90 (Hsp90) organizing protein (Hop) homologue, mediates the assembly of the Hsp70/Hsp90 chaperone heterocomplex. mSTI1 is phosphorylated in vitro by cell cycle kinases, proximal to a putative nuclear localization signal (NLS), substantiating a predicted CKII-cdc2-NLS (CcN) motif at position 189-239. Stable transfectants of NIH 3T3 fibroblasts that expressed mSTI1-EGFP, NLSmSTI1-EGFP and EGFP, were prepared. Fluorescence microscopy revealed mSTI1 was cytoplasmically localized, and that this localization was not affected by the fusion of mSTI1 with the EGFP moiety. NLSmSTI1-EGFP was targeted to the nucleus compared to EGFP, suggesting that the NLSmSTI1 was a functional NLS. The localization of mSTI1 was determined under normal and heat shock conditions, inhibition of nuclear export (leptomycin B), inhibition of CKII 5,6-dichlorobenzimidazole riboside, DRB), inhibition of cdc2 kinase (olomoucine), and G1/S phase arrest (hydroxyurea). mSTI1-EGFP and mSTI1 were excluded from the nucleus in the majority of resting cells, but accumulated in the nucleus following leptomycin B treatment, implying that mSTI1 possibly undergoes a functional import process, and export via the chromosomal region maintenance 1 (CRM-1)-mediated export pathway. Hydroxyurea and olomoucine (but not DRB or heat shock) treatment increased the proportion of cells in which mSTI1-EGFP exhibited cytoplasmic and nuclear localization. 2D gel electrophoresis detected three endogenous mSTI1 isoforms, which changed following hydroxyurea treatment. Furthermore, point inactivation and mimicking of phosphorylatable residues in mSTI1 altered the translocation of the protein and the isoform composition. Modification of mSTI1 at S189 and T198 decreased the number of isoforms of mSTI1-EGFP, suggesting that the protein is modified at these sites in vivo. The removal of the in vitro cdc2 kinase site at T198 promoted a nuclear localization during G1/S phase arrest. Therefore active cdc2 kinase, but not CKII, may be required for cytoplasmic localization of mSTI1. The CKII site appears to have no regulatory role under heat shock conditions or during the cell cycle. In vitro phosphorylation studies on untagged mSTI1 further supported the prediction that S189 is the only site recognised by CKII. The cdc2 kinase site at T198, however, although the major site, was not the only site phosphorylated in vitro. However, mSTI1 and cdc2 kinase did not interact in a detectable stable complex. Bioinformatic analysis of mSTI1 revealed NLS residues were conserved in STI1 proteins, and the NLS and TPR2A motifs were in close proximity. This may have mechanistic implications for the formation of the Hsp90-mSTI1 heterocomplex. The cytoplasmic or nuclear localization of mSTI1 is predicted to be the result of a dynamic equilibrium between nuclear import and nuclear export, the fulcrum of which may be shifted under different cell cycle conditions. These data provide the first evidence of regulated nuclear import/export of a major Hsp70/Hsp90 co-chaperone, and the regulation of this nuclear import by cell cycle status and cell cycle kinases.
- Full Text:
- Date Issued: 2003
- Authors: Longshaw, Victoria Mary
- Date: 2003
- Subjects: Phosphorylation Proteins Heat shock proteins
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3979 , http://hdl.handle.net/10962/d1004038
- Description: The co-chaperone murine stress-inducible protein 1 (mSTI1), a heat shock protein 70 (Hsp70)/ heat shock protein 90 (Hsp90) organizing protein (Hop) homologue, mediates the assembly of the Hsp70/Hsp90 chaperone heterocomplex. mSTI1 is phosphorylated in vitro by cell cycle kinases, proximal to a putative nuclear localization signal (NLS), substantiating a predicted CKII-cdc2-NLS (CcN) motif at position 189-239. Stable transfectants of NIH 3T3 fibroblasts that expressed mSTI1-EGFP, NLSmSTI1-EGFP and EGFP, were prepared. Fluorescence microscopy revealed mSTI1 was cytoplasmically localized, and that this localization was not affected by the fusion of mSTI1 with the EGFP moiety. NLSmSTI1-EGFP was targeted to the nucleus compared to EGFP, suggesting that the NLSmSTI1 was a functional NLS. The localization of mSTI1 was determined under normal and heat shock conditions, inhibition of nuclear export (leptomycin B), inhibition of CKII 5,6-dichlorobenzimidazole riboside, DRB), inhibition of cdc2 kinase (olomoucine), and G1/S phase arrest (hydroxyurea). mSTI1-EGFP and mSTI1 were excluded from the nucleus in the majority of resting cells, but accumulated in the nucleus following leptomycin B treatment, implying that mSTI1 possibly undergoes a functional import process, and export via the chromosomal region maintenance 1 (CRM-1)-mediated export pathway. Hydroxyurea and olomoucine (but not DRB or heat shock) treatment increased the proportion of cells in which mSTI1-EGFP exhibited cytoplasmic and nuclear localization. 2D gel electrophoresis detected three endogenous mSTI1 isoforms, which changed following hydroxyurea treatment. Furthermore, point inactivation and mimicking of phosphorylatable residues in mSTI1 altered the translocation of the protein and the isoform composition. Modification of mSTI1 at S189 and T198 decreased the number of isoforms of mSTI1-EGFP, suggesting that the protein is modified at these sites in vivo. The removal of the in vitro cdc2 kinase site at T198 promoted a nuclear localization during G1/S phase arrest. Therefore active cdc2 kinase, but not CKII, may be required for cytoplasmic localization of mSTI1. The CKII site appears to have no regulatory role under heat shock conditions or during the cell cycle. In vitro phosphorylation studies on untagged mSTI1 further supported the prediction that S189 is the only site recognised by CKII. The cdc2 kinase site at T198, however, although the major site, was not the only site phosphorylated in vitro. However, mSTI1 and cdc2 kinase did not interact in a detectable stable complex. Bioinformatic analysis of mSTI1 revealed NLS residues were conserved in STI1 proteins, and the NLS and TPR2A motifs were in close proximity. This may have mechanistic implications for the formation of the Hsp90-mSTI1 heterocomplex. The cytoplasmic or nuclear localization of mSTI1 is predicted to be the result of a dynamic equilibrium between nuclear import and nuclear export, the fulcrum of which may be shifted under different cell cycle conditions. These data provide the first evidence of regulated nuclear import/export of a major Hsp70/Hsp90 co-chaperone, and the regulation of this nuclear import by cell cycle status and cell cycle kinases.
- Full Text:
- Date Issued: 2003
A phenomenological study of how South African entrepreneurs experience and deal with ethical dilemmas
- Authors: Robinson, David Alan
- Date: 2003
- Subjects: Entrepreneurship -- South Africa Business ethics -- South Africa Decision making -- Moral and ethical aspects
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:1175 , http://hdl.handle.net/10962/d1002791
- Description: This research sets out to examine how entrepreneurs experience and deal with ethical dilemmas. An entrepreneur is defined as a person who creates something of value and assumes the risk of establishing and managing a business around it. An ethical dilemma comes about when the entrepreneur must choose between alternatives and where the morally correct choice is unclear. This may be due to conflicting personal values or loyalties, tensions arising out of the realization that the moral action is not in line with his self-interest, cross-cultural conflict, or moral ambiguity. Because of the nature of entrepreneurship, the entrepreneur typically lives with ever-present threats arising from limited resources, competition, and the risk of business failure. His actions must simultaneously ensure survival, maximize profit, limit risk, counter threats, optimize the use of resources, and reward him with a feeling of satisfaction. It is hardly surprising that conflicting priorities sometimes ensue. It is also widely believed that these entrepreneurial pursuits supersede the more general need to act in morally appropriate ways. This is a phenomenological study, based on interviews with seven entrepreneurs in established service-oriented ventures. They were asked to describe their business, any dilemmas they have experienced, how they were handled, and what challenges they experience as entrepreneurs in South Africa today. Using phenomenology as my vehicle for data collection and analysis, I sought to enter the lived-worlds of my participants to discover the essence of how ethical dilemmas are experienced in the entrepreneurial milieu. The study’s findings reflect that each entrepreneur has a distinctive world-view, which is represented by a complex mosaic of virtue ethics, deontology, utilitarianism and metaethical perspectives. The permutations are numerous, thus negating the possibility of typecasting entrepreneurs. Instead this research introduces the reader to aspects of entrepreneurial reality such as the complexity of cultural diversity, the freedom to limit the amount of personal energy given to business, and the existence of a more sensitive, searching inner soul beneath the apparent hard-nosed business-oriented public image. While examining entrepreneurial dilemmas in depth, this research introduces the dilemma drum as a tool to portray the argument form of any dilemma by making explicit the ethical component inherent in every business decision and facilitating its effective resolution in a non-prescriptive way. The findings identify certain individual characteristics of participant entrepreneurs that are unlike anything in the mainstream literature, dispelling notions of the entrepreneur as a societal misfit, an essential innovator with vision and flair, or a compulsive risk-taker, while confirming success as the key motivator rather than money per se, the importance of significant others, and the influence of culture and gender. They provide fresh insights into the psyche of the entrepreneur, which include: the existence of inner conviction - marrying the concept of goal-directedness with that of making a contribution to society; exercising the virtues in order to support a delicate balance between business and ethical imperatives; learning to respect energy flow; an alternative morality based on attracting and allowing benevolent or serendipitous events to happen naturally and redefining success as ‘being able to create what is needed as and when needed’; focusing one’s energy on the telos; developing a personal marketing formula suited to a culturallydiverse society; and the anxiety associated with being out-there on one’s own. The general statement, which is ultimately distilled from the seven situated descriptions, introduces a theory of entrepreneurial ethics that presents a new and different view of the lived-world of entrepreneurship, consisting of: Firstly, the key components of entrepreneurial success – having clear goals, energy, making a contribution to society, being connected, getting others on board, and work as an extension of self; secondly, what drives entrepreneurs – goal-orientation, sense of personal excitement, inner conviction, autonomy, and external recognition of success; thirdly, the entrepreneurial ethic – concern for credibility, commitment to service, contributing to quality of life; fourthly, the nature of entrepreneurial dilemmas - conflicting responsibilities, authenticity and credibility, risk and expansion, and awareness of diversity; fifthly, how entrepreneurs deal with ethical issues in their own distinctive ways – by holding fast to authentic virtues, bowing to community expectations, avoiding friction, adopting a ‘come-what-may’ or ‘what’s in it for me’ attitude, or pursuing a higher purpose where both parties benefit; sixthly, entrepreneurs’ world -views – beliefs, goals, ways of deriving satisfaction, virtuous behaviour; pen-ultimately, the challenges facing entrepreneurs in South Africa – overcoming the legacies of apartheid, containing crime, fostering an acceptable business ethic, and facilitating reconciliation between ethnic groups; and lastly, finding the power within – that illusive entrepreneurial spirit – self-reliance, looking beyond immediate obstacles, grasping opportunities, and understanding serendipity.
- Full Text:
- Date Issued: 2003
- Authors: Robinson, David Alan
- Date: 2003
- Subjects: Entrepreneurship -- South Africa Business ethics -- South Africa Decision making -- Moral and ethical aspects
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:1175 , http://hdl.handle.net/10962/d1002791
- Description: This research sets out to examine how entrepreneurs experience and deal with ethical dilemmas. An entrepreneur is defined as a person who creates something of value and assumes the risk of establishing and managing a business around it. An ethical dilemma comes about when the entrepreneur must choose between alternatives and where the morally correct choice is unclear. This may be due to conflicting personal values or loyalties, tensions arising out of the realization that the moral action is not in line with his self-interest, cross-cultural conflict, or moral ambiguity. Because of the nature of entrepreneurship, the entrepreneur typically lives with ever-present threats arising from limited resources, competition, and the risk of business failure. His actions must simultaneously ensure survival, maximize profit, limit risk, counter threats, optimize the use of resources, and reward him with a feeling of satisfaction. It is hardly surprising that conflicting priorities sometimes ensue. It is also widely believed that these entrepreneurial pursuits supersede the more general need to act in morally appropriate ways. This is a phenomenological study, based on interviews with seven entrepreneurs in established service-oriented ventures. They were asked to describe their business, any dilemmas they have experienced, how they were handled, and what challenges they experience as entrepreneurs in South Africa today. Using phenomenology as my vehicle for data collection and analysis, I sought to enter the lived-worlds of my participants to discover the essence of how ethical dilemmas are experienced in the entrepreneurial milieu. The study’s findings reflect that each entrepreneur has a distinctive world-view, which is represented by a complex mosaic of virtue ethics, deontology, utilitarianism and metaethical perspectives. The permutations are numerous, thus negating the possibility of typecasting entrepreneurs. Instead this research introduces the reader to aspects of entrepreneurial reality such as the complexity of cultural diversity, the freedom to limit the amount of personal energy given to business, and the existence of a more sensitive, searching inner soul beneath the apparent hard-nosed business-oriented public image. While examining entrepreneurial dilemmas in depth, this research introduces the dilemma drum as a tool to portray the argument form of any dilemma by making explicit the ethical component inherent in every business decision and facilitating its effective resolution in a non-prescriptive way. The findings identify certain individual characteristics of participant entrepreneurs that are unlike anything in the mainstream literature, dispelling notions of the entrepreneur as a societal misfit, an essential innovator with vision and flair, or a compulsive risk-taker, while confirming success as the key motivator rather than money per se, the importance of significant others, and the influence of culture and gender. They provide fresh insights into the psyche of the entrepreneur, which include: the existence of inner conviction - marrying the concept of goal-directedness with that of making a contribution to society; exercising the virtues in order to support a delicate balance between business and ethical imperatives; learning to respect energy flow; an alternative morality based on attracting and allowing benevolent or serendipitous events to happen naturally and redefining success as ‘being able to create what is needed as and when needed’; focusing one’s energy on the telos; developing a personal marketing formula suited to a culturallydiverse society; and the anxiety associated with being out-there on one’s own. The general statement, which is ultimately distilled from the seven situated descriptions, introduces a theory of entrepreneurial ethics that presents a new and different view of the lived-world of entrepreneurship, consisting of: Firstly, the key components of entrepreneurial success – having clear goals, energy, making a contribution to society, being connected, getting others on board, and work as an extension of self; secondly, what drives entrepreneurs – goal-orientation, sense of personal excitement, inner conviction, autonomy, and external recognition of success; thirdly, the entrepreneurial ethic – concern for credibility, commitment to service, contributing to quality of life; fourthly, the nature of entrepreneurial dilemmas - conflicting responsibilities, authenticity and credibility, risk and expansion, and awareness of diversity; fifthly, how entrepreneurs deal with ethical issues in their own distinctive ways – by holding fast to authentic virtues, bowing to community expectations, avoiding friction, adopting a ‘come-what-may’ or ‘what’s in it for me’ attitude, or pursuing a higher purpose where both parties benefit; sixthly, entrepreneurs’ world -views – beliefs, goals, ways of deriving satisfaction, virtuous behaviour; pen-ultimately, the challenges facing entrepreneurs in South Africa – overcoming the legacies of apartheid, containing crime, fostering an acceptable business ethic, and facilitating reconciliation between ethnic groups; and lastly, finding the power within – that illusive entrepreneurial spirit – self-reliance, looking beyond immediate obstacles, grasping opportunities, and understanding serendipity.
- Full Text:
- Date Issued: 2003
Isolation of antigenic peptides of Cowdria ruminantium and their encoding genes using a genome-derived phage display library
- Authors: Fehrsen, Jeanni
- Date: 2003
- Subjects: Bacteriophages -- Genetics Ruminants -- Diseases Heartwater
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3920 , http://hdl.handle.net/10962/d1003979
- Description: The development of new and effective vaccines and immunodiagnostic reagents requires the characterisation of antigenically relevant proteins and their interactions with the products of the immune system. Phage display technology was investigated as a means of elucidating some of the antigenic properties of the rickettsial parasite, Cowdria ruminantium (Cowdria). Randomly fragmented gene-derived libraries have been useful in elucidating viral and other epitopes, but only limited work has been done with entire genomes. A phage display library expressing a repertoire of Cowdria peptides was constructed. It was sufficiently large to represent the organism's genome, but lacked phages displaying peptides coded for by genes containing a Pvu II restriction enzyme site, including the one coding for the major antigenic protein 1 (MAP1). This was considered advantageous since MAP1 is immunodominant and has already been well characterised. Affinity selection with antibodies against Cowdria proteins other than MAP1 allowed several antibody-reactive peptides to be isolated. These selected sequences were placed in the context of the genome by screening a lambda bacteriophage library and by comparison with Cowdria DNA sequences. Apart from showing that antigenic mimics were present in the phage display library, six open reading frames encoding putative Cowdria proteins were identified. All had similarities to, or motifs in common with, membrane proteins and are thus likely to be exposed to the host's humoral immune system. Some of the proteins identified were larger than the antigens used to elicit the antibodies used for selection, probably as a result of the presence of cross-reactive epitopes. Despite limitations experienced when extending a fragmented-gene approach for epitope location to genomes, it was possible to identify an antigenic region on MAP1 by comparison with selected mimics. In addition, binding peptide sequences were identified with two monoclonal antibodies that had been raised against non-Cowdria antigens. An epitope on the VP7 protein of bluetongue virus was identified and peptides were found that reacted with a monoclonal antibody directed against malignant catarrhal fever virus. Thus, apart from being able to identify several potentially important Cowdria epitopes and genes, the fragmented-genome library holds promise as a universal reagent for identifying useful mimics.
- Full Text:
- Date Issued: 2003
- Authors: Fehrsen, Jeanni
- Date: 2003
- Subjects: Bacteriophages -- Genetics Ruminants -- Diseases Heartwater
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3920 , http://hdl.handle.net/10962/d1003979
- Description: The development of new and effective vaccines and immunodiagnostic reagents requires the characterisation of antigenically relevant proteins and their interactions with the products of the immune system. Phage display technology was investigated as a means of elucidating some of the antigenic properties of the rickettsial parasite, Cowdria ruminantium (Cowdria). Randomly fragmented gene-derived libraries have been useful in elucidating viral and other epitopes, but only limited work has been done with entire genomes. A phage display library expressing a repertoire of Cowdria peptides was constructed. It was sufficiently large to represent the organism's genome, but lacked phages displaying peptides coded for by genes containing a Pvu II restriction enzyme site, including the one coding for the major antigenic protein 1 (MAP1). This was considered advantageous since MAP1 is immunodominant and has already been well characterised. Affinity selection with antibodies against Cowdria proteins other than MAP1 allowed several antibody-reactive peptides to be isolated. These selected sequences were placed in the context of the genome by screening a lambda bacteriophage library and by comparison with Cowdria DNA sequences. Apart from showing that antigenic mimics were present in the phage display library, six open reading frames encoding putative Cowdria proteins were identified. All had similarities to, or motifs in common with, membrane proteins and are thus likely to be exposed to the host's humoral immune system. Some of the proteins identified were larger than the antigens used to elicit the antibodies used for selection, probably as a result of the presence of cross-reactive epitopes. Despite limitations experienced when extending a fragmented-gene approach for epitope location to genomes, it was possible to identify an antigenic region on MAP1 by comparison with selected mimics. In addition, binding peptide sequences were identified with two monoclonal antibodies that had been raised against non-Cowdria antigens. An epitope on the VP7 protein of bluetongue virus was identified and peptides were found that reacted with a monoclonal antibody directed against malignant catarrhal fever virus. Thus, apart from being able to identify several potentially important Cowdria epitopes and genes, the fragmented-genome library holds promise as a universal reagent for identifying useful mimics.
- Full Text:
- Date Issued: 2003
Molecular characterization of the tetratricopeptide repeat-mediated interactions of murine stress-inducible protein 1 with major heat shock proteins
- Authors: Odunuga, Odutayo Odutola
- Date: 2003
- Subjects: Plants -- Effect of stress on Proteins -- Purification Electrophoresis Heat shock proteins
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4091 , http://hdl.handle.net/10962/d1007724
- Description: Murine stress-inducible protein 1 (mSTI1) is a co-chaperone that is homologous with the human heat shock protein 70 (Hsp70)/heat shock protein 90 (Hsp90)-organizing protein (Hop). The two proteins are homologues of the highly conserved stress-inducible protein 1 (STI1) family of co-chaperones. The STI1 proteins interact directly and simultaneously at some stage, with Hsp70 and Hsp90 in the formation of the hetero-multi-chaperone complexes that facilitate the folding of signal transducing kinases and functional maturation of steroid hormone receptors. The interactions of mSTI1 with both Hsp70 and Hsp90 is mediated by a versatile structural protein-protein interaction motif, the tetratricopeptide repeat (TPR). The TPR motif is a degenerate 34-amino acid sequence a-helical structural motif found in a significant number of functionally unrelated proteins. This study was aimed at characterizing the structural and functional determinants in the TPR domains of mSTI1 responsible for binding to and discriminating between Hsp70 and Hsp90. Guided by data from Hop's crystal structures and amino acid sequence alignment analyses, various biochemical techniques were used to both qualitatively and quantitatively characterize the contacts necessary for the N-terminal TPR domain (TPR1) of mSTI1 to bind to the C-terminal EEVD motif of heat shock cognate protein 70 (Hsc70) and to discriminate between Hsc70 and Hsp90. Substitutions in the first TPR motif of Lys⁸ or Asn¹² did not affect binding of mSTI1 to Hsc70, while double substitution of these residues abrogated binding. A substitution in the second TPR motif of Asn⁴³ lowered but did not abrogate binding. Similarly, a deletion in the second TPR motif coupled with a substitution of Lys⁸ or Asn¹² reduced but did not abrogate binding. Steady state fluorescence and circular dichroism spectroscopies revealed that the double substitution of Lys⁸ and Asn¹² resulted in perturbations of inter-domain interactions in mSTl1. Together these results suggest that mSTI1-Hsc70 interaction requires a network of electrostatic interactions not only between charged residues in the TPR1 domain of mSTI1 and the EEVD motif of Hsc70, but also outside the TPR1 domain. It is proposed that the electrostatic interactions in the first TPR motif collectively made by Lys⁸ and Asn¹² define part of the minimum interactions required for successful mSTI1-Hsc70 interaction. In the first central TPR domain (TPR1A), single substitution of Lys³°¹ was sufficient to abrogate the mSTI1-Hsp90 interaction. Using a truncated derivative of mSTI1 incapable of binding to Hsp90, residues predicted by crystallographic data to determine Hsp70 binding specificity were substituted in the TPR1 domain. The modified protein had reduced binding to Hsc70, but showed significant binding capacity for Hsp90. In contrast, topologically equivalent substitutions on a truncated derivative of mSTI1 incapable of binding to Hsc70 did not confer Hsc70 specificity on the TPR2A domain. These data suggest that binding of Hsc70 to the TPR1 domain is more specific than binding of Hsp90 to the TPR2A domain. In addition, residues C-terminal of helix A in the second TPR motif of mSTI1 were shown to be important in determining specific binding to Hsc70. Binding assays using surface plasmon resonance spectroscopy showed that the affinities of binding of mSTI1 to Hsc70 and Hsp90 were 2 μM and 1.5 μM respectively. Preliminary in vivo studies revealed differences in the dynamics of binding of endogenous and exogenous recombinant mSTI1 with Hsc70 and Hsp90. The outcome of this study poses serious implications for the mechanisms of mSTI1 interactions with Hsc70 and Hsp90 in the cell.
- Full Text:
- Date Issued: 2003
- Authors: Odunuga, Odutayo Odutola
- Date: 2003
- Subjects: Plants -- Effect of stress on Proteins -- Purification Electrophoresis Heat shock proteins
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4091 , http://hdl.handle.net/10962/d1007724
- Description: Murine stress-inducible protein 1 (mSTI1) is a co-chaperone that is homologous with the human heat shock protein 70 (Hsp70)/heat shock protein 90 (Hsp90)-organizing protein (Hop). The two proteins are homologues of the highly conserved stress-inducible protein 1 (STI1) family of co-chaperones. The STI1 proteins interact directly and simultaneously at some stage, with Hsp70 and Hsp90 in the formation of the hetero-multi-chaperone complexes that facilitate the folding of signal transducing kinases and functional maturation of steroid hormone receptors. The interactions of mSTI1 with both Hsp70 and Hsp90 is mediated by a versatile structural protein-protein interaction motif, the tetratricopeptide repeat (TPR). The TPR motif is a degenerate 34-amino acid sequence a-helical structural motif found in a significant number of functionally unrelated proteins. This study was aimed at characterizing the structural and functional determinants in the TPR domains of mSTI1 responsible for binding to and discriminating between Hsp70 and Hsp90. Guided by data from Hop's crystal structures and amino acid sequence alignment analyses, various biochemical techniques were used to both qualitatively and quantitatively characterize the contacts necessary for the N-terminal TPR domain (TPR1) of mSTI1 to bind to the C-terminal EEVD motif of heat shock cognate protein 70 (Hsc70) and to discriminate between Hsc70 and Hsp90. Substitutions in the first TPR motif of Lys⁸ or Asn¹² did not affect binding of mSTI1 to Hsc70, while double substitution of these residues abrogated binding. A substitution in the second TPR motif of Asn⁴³ lowered but did not abrogate binding. Similarly, a deletion in the second TPR motif coupled with a substitution of Lys⁸ or Asn¹² reduced but did not abrogate binding. Steady state fluorescence and circular dichroism spectroscopies revealed that the double substitution of Lys⁸ and Asn¹² resulted in perturbations of inter-domain interactions in mSTl1. Together these results suggest that mSTI1-Hsc70 interaction requires a network of electrostatic interactions not only between charged residues in the TPR1 domain of mSTI1 and the EEVD motif of Hsc70, but also outside the TPR1 domain. It is proposed that the electrostatic interactions in the first TPR motif collectively made by Lys⁸ and Asn¹² define part of the minimum interactions required for successful mSTI1-Hsc70 interaction. In the first central TPR domain (TPR1A), single substitution of Lys³°¹ was sufficient to abrogate the mSTI1-Hsp90 interaction. Using a truncated derivative of mSTI1 incapable of binding to Hsp90, residues predicted by crystallographic data to determine Hsp70 binding specificity were substituted in the TPR1 domain. The modified protein had reduced binding to Hsc70, but showed significant binding capacity for Hsp90. In contrast, topologically equivalent substitutions on a truncated derivative of mSTI1 incapable of binding to Hsc70 did not confer Hsc70 specificity on the TPR2A domain. These data suggest that binding of Hsc70 to the TPR1 domain is more specific than binding of Hsp90 to the TPR2A domain. In addition, residues C-terminal of helix A in the second TPR motif of mSTI1 were shown to be important in determining specific binding to Hsc70. Binding assays using surface plasmon resonance spectroscopy showed that the affinities of binding of mSTI1 to Hsc70 and Hsp90 were 2 μM and 1.5 μM respectively. Preliminary in vivo studies revealed differences in the dynamics of binding of endogenous and exogenous recombinant mSTI1 with Hsc70 and Hsp90. The outcome of this study poses serious implications for the mechanisms of mSTI1 interactions with Hsc70 and Hsp90 in the cell.
- Full Text:
- Date Issued: 2003
Metallophthalocyanines as photocatalysts for transformation of chlorophenols and self-assembled monolayers for electrochemical detection of thiols and cyanides
- Authors: Ozoemena, Kenneth Ikechukwu
- Date: 2003
- Subjects: Electrochemistry Cyanides Thiols Chlorophenols Photocatalysis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4089 , http://hdl.handle.net/10962/d1007709
- Description: Photochemical properties of sulphonated phthalocyanine complexes of aluminium, zinc, tin and silicon, and octa-carboxyphthalocyanine complexes of aluminium and zinc have been investigated. These water-soluble metallophthalocyanine (MPc) complexes, especially the sulphonated aluminium and zinc phthalocyanines, were found to be good photosensitisers for the transformation of the toxic mono-, tri- and penta-chlorophenols in aqueous solutions. The efficiency of MPc sensitiser towards photo-transformation of chlorophenols depends on its effectiveness to generate singlet oxygen as well as its photostability. Octa-substituted thiol-derivatised phthalocyanine complexes of cobalt, iron and zinc were synthesized and their spectral and electrochemical properties investigated. The photochemical properties ofthe zinc phthalocyanine complexes in non-aqueous solutions were comparable to those in literature. Ultrathin films of the octasubstituted thiol-derivatised phthalocyanine complexes of cobalt, iron and zinc were, for the first time, immobilized onto gold electrodes using the self-assembling technique. Surface electrochemistry indicates that the ultrathin films are surface-confined self-assembled monolayer (SAM) species. Gold electrodes modified with the redox-active SAMs of cobalt and iron phthalocyanine complexes proved to be potential electrochemical sensors for the detection of thiols (L-cysteine, homocysteine and penicillamine) and thiocyanate in aqueous solutions (pH 4). The limits of detection for the thiols and thiocyanate were in the range of ∼ 10⁻⁷ and 10⁻⁶ mol dm⁻³, respectively. The modification process was reproducible and the modified electrodes showed good stability and, if stored in pH 4 buffer solutions, could be used for the analysis of thiols and thiocyanate for about a month without the need for recalibration. Etching of gold marred electrochemical detection of cyanide with the MPc-SAM-modified gold electrodes. Interestingly, however, kinetic and equilibria studies revealed strong interaction of octabutylthiophthalocyaninatoiron (II), FeOBTPc, with cyanide in both DMF and DMSO solutions.
- Full Text:
- Date Issued: 2003
- Authors: Ozoemena, Kenneth Ikechukwu
- Date: 2003
- Subjects: Electrochemistry Cyanides Thiols Chlorophenols Photocatalysis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4089 , http://hdl.handle.net/10962/d1007709
- Description: Photochemical properties of sulphonated phthalocyanine complexes of aluminium, zinc, tin and silicon, and octa-carboxyphthalocyanine complexes of aluminium and zinc have been investigated. These water-soluble metallophthalocyanine (MPc) complexes, especially the sulphonated aluminium and zinc phthalocyanines, were found to be good photosensitisers for the transformation of the toxic mono-, tri- and penta-chlorophenols in aqueous solutions. The efficiency of MPc sensitiser towards photo-transformation of chlorophenols depends on its effectiveness to generate singlet oxygen as well as its photostability. Octa-substituted thiol-derivatised phthalocyanine complexes of cobalt, iron and zinc were synthesized and their spectral and electrochemical properties investigated. The photochemical properties ofthe zinc phthalocyanine complexes in non-aqueous solutions were comparable to those in literature. Ultrathin films of the octasubstituted thiol-derivatised phthalocyanine complexes of cobalt, iron and zinc were, for the first time, immobilized onto gold electrodes using the self-assembling technique. Surface electrochemistry indicates that the ultrathin films are surface-confined self-assembled monolayer (SAM) species. Gold electrodes modified with the redox-active SAMs of cobalt and iron phthalocyanine complexes proved to be potential electrochemical sensors for the detection of thiols (L-cysteine, homocysteine and penicillamine) and thiocyanate in aqueous solutions (pH 4). The limits of detection for the thiols and thiocyanate were in the range of ∼ 10⁻⁷ and 10⁻⁶ mol dm⁻³, respectively. The modification process was reproducible and the modified electrodes showed good stability and, if stored in pH 4 buffer solutions, could be used for the analysis of thiols and thiocyanate for about a month without the need for recalibration. Etching of gold marred electrochemical detection of cyanide with the MPc-SAM-modified gold electrodes. Interestingly, however, kinetic and equilibria studies revealed strong interaction of octabutylthiophthalocyaninatoiron (II), FeOBTPc, with cyanide in both DMF and DMSO solutions.
- Full Text:
- Date Issued: 2003
Pyrroloiminoquinone metabolites from South African Latrunculid sponges
- Authors: Antunes, Edith Martins
- Date: 2003
- Subjects: Sponges -- South Africa PQQ (Biochemistry) Marine metabolites -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4340 , http://hdl.handle.net/10962/d1005001
- Description: An in depth chemical investigation of the major and minor pyrroloiminoquinone metabolites produced by four species of endemic South African Latrunculid sponges, collected from Algoa Bay and the Tsitsikamma Marine Reserve off the south eastern coast of South Africa, yielded eleven new and twelve known pyrroloiminoquinone metabolites. The structures of the new metabolites were determined using standard spectroscopic techniques. Tsitsikamma pedunculata was shown to contain 7,8-dehydro-3-dihydro-discorhabdin C (2.1), 14-bromo-7,8-dehydro-3-dihydro-discorhabdin C (2.2), discorhabdin S (2.3), 14-bromo-1-hydroxy-discorhabdin S (2.4), 1-bromo-2-hydroxy-4-debromo-discorhabdin S (2.5), and 2,4-debromo-3-dihydro-discorhabdin C (2.6), together with the known compounds 14-bromo-discorhabdin C (1.51), 14-bromo-3-dihydro-discorhabdin C (1.52) and 3-dihydro-discorhabdin C. The metabolites from T. pedunculata were characterised by the presence of a reduced C-3 carbonyl and bromination at C-14. Compounds isolated from a second Latrunculid sponge, Latrunculia lorii, ranged from a substituted bicyclic pyrrolecarboxylic acid, makaluvic acid A (1.47), to the simple tricyclic known pyrroloiminoquinones makaluvamine C (1.33) and damirone B (1.20) and the more complex discorhabdin D type metabolites, discorhabdin M (3.2), 1-amino discorhabdin D (3.3), 1-methoxy discorhabdin D (3.4) and 1-alanyl discorhabdin D (3.5). Discorhabdin G* (3.1) was also isolated and characterised. This is the first reported occurrence of the known compounds 1.20, 1.33 and 1.47 in a Latrunculia sponge. Discorhabdin and bis-pyrroloiminoquinone type compounds predominated in Tsitsikamma favus. Three known, tsitsikammamines A (1.71) and B (1.72), 1.52, and five new pyrroloiminoquinones, tsitsikammamine N-oxime (4.1), tsitsikammamine B N-oxime (4.2), 2.1, 2.4 and 2.6, were isolated from this sponge. A fourth Latrunculid sponge (Strongylodesma sp.) yielded three known compounds, discorhabdins A (1.57), D (1.61) and 1.53, and one new pyrroloiminoquinone 3.3. The dual role of these metabolites as cytotoxic agents and pigments resulted in an attempt to relate the photochemical properties of these metabolites to their cytotoxicity. The pyrroloiminoquinone metabolites studied exhibited moderate singlet oxygen quantum yields, while three compounds (1.57, 4.1 and 4.2) were shown to be capable of producing radicals at a wavelength of 532 nm. The possibility of a correlation between the electrochemical properties and anti-cancer (HCT-116) activity of selected pyrroloiminoquinones was explored. A study of the oesophageal and ovarian cytotoxicities of two pyrroloiminoquinones (1.57 and 1.72), together with an investigation into the intercalation and topoisomerase I inhibitory activity of the bis-pyrroloiminoquinones (1.71, 1.72, 4.1 and 4.2), are presented.
- Full Text:
- Date Issued: 2003
- Authors: Antunes, Edith Martins
- Date: 2003
- Subjects: Sponges -- South Africa PQQ (Biochemistry) Marine metabolites -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4340 , http://hdl.handle.net/10962/d1005001
- Description: An in depth chemical investigation of the major and minor pyrroloiminoquinone metabolites produced by four species of endemic South African Latrunculid sponges, collected from Algoa Bay and the Tsitsikamma Marine Reserve off the south eastern coast of South Africa, yielded eleven new and twelve known pyrroloiminoquinone metabolites. The structures of the new metabolites were determined using standard spectroscopic techniques. Tsitsikamma pedunculata was shown to contain 7,8-dehydro-3-dihydro-discorhabdin C (2.1), 14-bromo-7,8-dehydro-3-dihydro-discorhabdin C (2.2), discorhabdin S (2.3), 14-bromo-1-hydroxy-discorhabdin S (2.4), 1-bromo-2-hydroxy-4-debromo-discorhabdin S (2.5), and 2,4-debromo-3-dihydro-discorhabdin C (2.6), together with the known compounds 14-bromo-discorhabdin C (1.51), 14-bromo-3-dihydro-discorhabdin C (1.52) and 3-dihydro-discorhabdin C. The metabolites from T. pedunculata were characterised by the presence of a reduced C-3 carbonyl and bromination at C-14. Compounds isolated from a second Latrunculid sponge, Latrunculia lorii, ranged from a substituted bicyclic pyrrolecarboxylic acid, makaluvic acid A (1.47), to the simple tricyclic known pyrroloiminoquinones makaluvamine C (1.33) and damirone B (1.20) and the more complex discorhabdin D type metabolites, discorhabdin M (3.2), 1-amino discorhabdin D (3.3), 1-methoxy discorhabdin D (3.4) and 1-alanyl discorhabdin D (3.5). Discorhabdin G* (3.1) was also isolated and characterised. This is the first reported occurrence of the known compounds 1.20, 1.33 and 1.47 in a Latrunculia sponge. Discorhabdin and bis-pyrroloiminoquinone type compounds predominated in Tsitsikamma favus. Three known, tsitsikammamines A (1.71) and B (1.72), 1.52, and five new pyrroloiminoquinones, tsitsikammamine N-oxime (4.1), tsitsikammamine B N-oxime (4.2), 2.1, 2.4 and 2.6, were isolated from this sponge. A fourth Latrunculid sponge (Strongylodesma sp.) yielded three known compounds, discorhabdins A (1.57), D (1.61) and 1.53, and one new pyrroloiminoquinone 3.3. The dual role of these metabolites as cytotoxic agents and pigments resulted in an attempt to relate the photochemical properties of these metabolites to their cytotoxicity. The pyrroloiminoquinone metabolites studied exhibited moderate singlet oxygen quantum yields, while three compounds (1.57, 4.1 and 4.2) were shown to be capable of producing radicals at a wavelength of 532 nm. The possibility of a correlation between the electrochemical properties and anti-cancer (HCT-116) activity of selected pyrroloiminoquinones was explored. A study of the oesophageal and ovarian cytotoxicities of two pyrroloiminoquinones (1.57 and 1.72), together with an investigation into the intercalation and topoisomerase I inhibitory activity of the bis-pyrroloiminoquinones (1.71, 1.72, 4.1 and 4.2), are presented.
- Full Text:
- Date Issued: 2003
Change and continuity : perceptions about childhood diseases among the Tumbuka of Northern Malawi
- Munthali, Alister Chaundumuka
- Authors: Munthali, Alister Chaundumuka
- Date: 2003
- Subjects: Tumbuka (African people) Ethnology -- Malawi Diseases -- Causes and theories of causation Health behavior -- Malawi Health attitudes -- Malawi Children -- Diseases -- Malawi
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:2114 , http://hdl.handle.net/10962/d1007718
- Description: The objectives of this study were to determine what the Tumbuka people of northern Malawi consider to be the most dangerous childhood diseases, to explore their perceptions about the aetiology, prevention and treatment of these diseases, and to determine how such perceptions have changed over the years. The study was done in Chisinde and surrounding villages in western Rumphi District, northern Malawi. Although a household questionnaire was used to collect some quantitative data, the major data collection methods comprised participant observation, in-depth interviews with mothers with children under five and old men and women, and key informant interviews with traditional healers, traditional birth attendants, village headmen, health surveillance assistants and clinical officers. Informants in this study mentioned chikhoso chamoto, diarrhoea, malaria, measles, and conjunctivitis as the most dangerous childhood diseases in the area. Old men and women added that in the past smallpox was also a dangerous disease that affected both children and adults. Apart from measles and smallpox, community-based health workers and those at the local health centre also mentioned the same list of diseases as the most dangerous diseases prevalent among under-five children. Though health workers and informants mentioned the same diseases, the informants' perspectives about the aetiology and prevention of these diseases and the way they sought treatment during childhood illness episodes, in some cases, differed significantly from those of biomedicine. For example, while health workers said that the signs and symptoms presented by a child suffering from "chikhoso chamoto" were those of either kwashiorkor or marasmus, both young and elderly informants said that a child could contract this illness through contact with a person who had been involved in sexual intercourse. Biomedically, diarrhoea is caused by the ingestion of pathogenic agents, which are transmitted through, among other factors, drinking contaminated water and eating contaminated foods. While young men and women subscribed to this biomedical view, at the same time, just like old men and women, they also believed that if a breastfeeding mother has sexual intercourse, sperms will contaminate her breast milk and, once a child feeds on this milk, he or she will develop diarrhoea. They, in addition, associated diarrhoea with the process of teething and other infections, such as malaria and measles. In malaria-endemic areas such as Malawi, the occurrence of convulsions, splenomegaly and anaemia in children under five may be biomedically attributed to malaria. However, most informants in this study perceived these conditions as separate disease entities caused by, among other factors, witchcraft and the infringement of Tumbuka taboos relating to food, sexual intercourse and funerals. Splenomegaly and convulsions were also perceived as hereditary diseases. Such Tumbuka perceptions about the aetiology of childhood diseases also influenced their ideas about prevention and the seeking of therapy during illness episodes. Apart from measles, other childhood vaccine-preventable diseases (i.e. tetanus, diphtheria, tuberculosis, pertussis and poliomyelitis) were not mentioned, presumably because they are no longer occurring on a significant scale, which is an indication of the success of vaccination programmes. This study reveals that there is no outright rejection of vaccination services in the study area. Some mothers, though, felt pressured to go for vaccination services as they believed that non-vaccinated children were refused biomedical treatment at the local health centres when they fell ill. While young women with children under five mentioned vaccination as a preventative measure against diseases such as measles, they also mentioned other indigenous forms of 'vaccination', which included the adherence to societal taboos, the wearing of amulets, the rubbing of protective medicines into incisions, isolation of children under five (e.g. a newly born child is kept in the house, amongst other things, to protect him or her against people who are ritually considered hot because of sexual intercourse) who are susceptible to disease or those posing a threat to cause disease in children under five. For example, since diarrhoea is perceived to be caused by, among other things, a child feeding on breast milk contaminated with sperms, informants said that there is a strong need for couples to observe postpartum sexual intercourse. A couple with newly delivered twins is isolated from the village because of the belief that children will swell if they came into contact with them. Local methods of disease prevention seem therefore to depend on what is perceived to be the cause of the illness and the decision to adopt specific preventive measures depends on, among other factors, the diagnosis of the cause and of who is vulnerable. The therapy-seeking process is a hierarchical movement within and between aetiologies; at the same time, it is not a random process, but an ordered process of choices in response to negative feedback, and subject to a number of factors, such as the aetiology of the disease, distance, social costs, cost of the therapeutic intervention, availability of medicines, etc. The movement between systems (i.e. from traditional medicine to biomedicine and vice-versa) during illness episodes depends on a number of factors, including previous experiences of significant others (i.e. those close to the patient), perceptions about the chances of getting healed, the decisions of the therapy management group, etc. For example, febrile illness in children under five may be treated using herbs or antipyretics bought from the local grocery shops. When the situation worsens (e.g. accompanied by convulsions), a herbalist will be consulted or the child may be taken to the local health centre. The local health centre refers such cases to the district hospital for treatment. Because of the rapidity with which the condition worsens, informants said that sometimes such children are believed to be bewitched, hence while biomedical treatment is sought, at the same time diviners are also consulted. The therapeutic strategies people resort to during illness episodes are appropriate rational decisions, based on prevailing circumstances, knowledge, resources and outcomes. Boundaries between the different therapeutic options are not rigid, as people move from one form of therapy to another and from one mode of classification to another. Lastly, perceptions about childhood diseases have changed over the years. Old men and women mostly attribute childhood illnesses to the infringement of taboos (e.g. on . sexual intercourse), witchcraft and other supernatural forces. While young men and women also subscribe to these perceptions, they have at the same time also appropriated the biomedical disease explanatory models. These biomedical models were learnt at school, acquired during health education sessions conducted by health workers in the communities as well as during under-five clinics, and health education programmes conducted on the national radio station. Younger people, more frequently than older people, thus move within and between aetiological models in the manner described above.
- Full Text:
- Date Issued: 2003
- Authors: Munthali, Alister Chaundumuka
- Date: 2003
- Subjects: Tumbuka (African people) Ethnology -- Malawi Diseases -- Causes and theories of causation Health behavior -- Malawi Health attitudes -- Malawi Children -- Diseases -- Malawi
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:2114 , http://hdl.handle.net/10962/d1007718
- Description: The objectives of this study were to determine what the Tumbuka people of northern Malawi consider to be the most dangerous childhood diseases, to explore their perceptions about the aetiology, prevention and treatment of these diseases, and to determine how such perceptions have changed over the years. The study was done in Chisinde and surrounding villages in western Rumphi District, northern Malawi. Although a household questionnaire was used to collect some quantitative data, the major data collection methods comprised participant observation, in-depth interviews with mothers with children under five and old men and women, and key informant interviews with traditional healers, traditional birth attendants, village headmen, health surveillance assistants and clinical officers. Informants in this study mentioned chikhoso chamoto, diarrhoea, malaria, measles, and conjunctivitis as the most dangerous childhood diseases in the area. Old men and women added that in the past smallpox was also a dangerous disease that affected both children and adults. Apart from measles and smallpox, community-based health workers and those at the local health centre also mentioned the same list of diseases as the most dangerous diseases prevalent among under-five children. Though health workers and informants mentioned the same diseases, the informants' perspectives about the aetiology and prevention of these diseases and the way they sought treatment during childhood illness episodes, in some cases, differed significantly from those of biomedicine. For example, while health workers said that the signs and symptoms presented by a child suffering from "chikhoso chamoto" were those of either kwashiorkor or marasmus, both young and elderly informants said that a child could contract this illness through contact with a person who had been involved in sexual intercourse. Biomedically, diarrhoea is caused by the ingestion of pathogenic agents, which are transmitted through, among other factors, drinking contaminated water and eating contaminated foods. While young men and women subscribed to this biomedical view, at the same time, just like old men and women, they also believed that if a breastfeeding mother has sexual intercourse, sperms will contaminate her breast milk and, once a child feeds on this milk, he or she will develop diarrhoea. They, in addition, associated diarrhoea with the process of teething and other infections, such as malaria and measles. In malaria-endemic areas such as Malawi, the occurrence of convulsions, splenomegaly and anaemia in children under five may be biomedically attributed to malaria. However, most informants in this study perceived these conditions as separate disease entities caused by, among other factors, witchcraft and the infringement of Tumbuka taboos relating to food, sexual intercourse and funerals. Splenomegaly and convulsions were also perceived as hereditary diseases. Such Tumbuka perceptions about the aetiology of childhood diseases also influenced their ideas about prevention and the seeking of therapy during illness episodes. Apart from measles, other childhood vaccine-preventable diseases (i.e. tetanus, diphtheria, tuberculosis, pertussis and poliomyelitis) were not mentioned, presumably because they are no longer occurring on a significant scale, which is an indication of the success of vaccination programmes. This study reveals that there is no outright rejection of vaccination services in the study area. Some mothers, though, felt pressured to go for vaccination services as they believed that non-vaccinated children were refused biomedical treatment at the local health centres when they fell ill. While young women with children under five mentioned vaccination as a preventative measure against diseases such as measles, they also mentioned other indigenous forms of 'vaccination', which included the adherence to societal taboos, the wearing of amulets, the rubbing of protective medicines into incisions, isolation of children under five (e.g. a newly born child is kept in the house, amongst other things, to protect him or her against people who are ritually considered hot because of sexual intercourse) who are susceptible to disease or those posing a threat to cause disease in children under five. For example, since diarrhoea is perceived to be caused by, among other things, a child feeding on breast milk contaminated with sperms, informants said that there is a strong need for couples to observe postpartum sexual intercourse. A couple with newly delivered twins is isolated from the village because of the belief that children will swell if they came into contact with them. Local methods of disease prevention seem therefore to depend on what is perceived to be the cause of the illness and the decision to adopt specific preventive measures depends on, among other factors, the diagnosis of the cause and of who is vulnerable. The therapy-seeking process is a hierarchical movement within and between aetiologies; at the same time, it is not a random process, but an ordered process of choices in response to negative feedback, and subject to a number of factors, such as the aetiology of the disease, distance, social costs, cost of the therapeutic intervention, availability of medicines, etc. The movement between systems (i.e. from traditional medicine to biomedicine and vice-versa) during illness episodes depends on a number of factors, including previous experiences of significant others (i.e. those close to the patient), perceptions about the chances of getting healed, the decisions of the therapy management group, etc. For example, febrile illness in children under five may be treated using herbs or antipyretics bought from the local grocery shops. When the situation worsens (e.g. accompanied by convulsions), a herbalist will be consulted or the child may be taken to the local health centre. The local health centre refers such cases to the district hospital for treatment. Because of the rapidity with which the condition worsens, informants said that sometimes such children are believed to be bewitched, hence while biomedical treatment is sought, at the same time diviners are also consulted. The therapeutic strategies people resort to during illness episodes are appropriate rational decisions, based on prevailing circumstances, knowledge, resources and outcomes. Boundaries between the different therapeutic options are not rigid, as people move from one form of therapy to another and from one mode of classification to another. Lastly, perceptions about childhood diseases have changed over the years. Old men and women mostly attribute childhood illnesses to the infringement of taboos (e.g. on . sexual intercourse), witchcraft and other supernatural forces. While young men and women also subscribe to these perceptions, they have at the same time also appropriated the biomedical disease explanatory models. These biomedical models were learnt at school, acquired during health education sessions conducted by health workers in the communities as well as during under-five clinics, and health education programmes conducted on the national radio station. Younger people, more frequently than older people, thus move within and between aetiological models in the manner described above.
- Full Text:
- Date Issued: 2003
Development of integrated algal ponding systems in the treatment of wine distillery wastewaters
- Authors: Dekker, Leendert Gideon
- Date: 2003
- Subjects: Sewage -- Purification -- Anaerobic treatment Wine and wine making -- Waste disposal -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4062 , http://hdl.handle.net/10962/d1004530
- Description: In South Africa, wastewater disposal in the wine and distilling industry is undergoing a profound transformation as a result of fundamental changes in regulations and license requirements. To deal with this problem conventional Waste Stabilisation Ponding systems have been used by the industry together with irrigation and evaporation disposal practises. Although effective in the evaporation and containment disposal functions, these pond systems are generally not properly designed and/or managed, resulting in overloading and, at times, the generation of seriously offensive odour problems. Preliminary studies on the feasibility of utilising the Advanced Integrated Wastewater Ponding System as a core treatment technology in winery wastewater treatment were conducted. Results indicated that specific problems had to be addressed before successful ponding treatment could be achieved. This research programme undertook an investigation of the performance of a demonstration ponding system treating household sewage, which formed the basis of the research due to limited experience reported on ponds treating wine industry wastewaters. Malfunctions identified were in correlation with the preliminary winery waste ponding survey, which included unstable fermentation pit functions and inadequate nutrient removal. Retrofitting the fermentation pit with a nylon net across the rising water column resulted in improved retention of active anaerobic sludge, especially during periods of system start-up and/or organic overloading. An investigation into nutrient removal utilising algal biomass provided a valuable contribution towards development of an independent nutrient removal system. Harvested algal biomass was passively manipulated to release polysaccharides under anoxic conditions, with subsequent use as a carbon source by denitrifying organisms. Following denitrification, the still viable algal cells were introduced into a High Rate Algal Pond raceway for photosynthetically produced alkalinity. This high pH environment resulted in induced calcium phosphate mineral formation and subsequent precipitation, as well as effective ammonia stripping from the water. Based on the novel positive research outcomes a decision was made to proceed to the construction of a pilot-scale integrated ponding system treating wastewater from a wine lees factory. The system linked the Anaerobic Baffle Reactor, for pre-treatment, with the improved Advanced Integrated Wastewater Ponding System. The potential of this system has shown that a Waste Stabilisation Ponding system can be engineered to treat wine industry wastewaters and thereby effectively reduce the organic and nutrient loads, by using low-cost retrofitted upgrading unit operations. Valuable algal biomass may also be recovered as a by-product of the treatment process.
- Full Text:
- Date Issued: 2003
- Authors: Dekker, Leendert Gideon
- Date: 2003
- Subjects: Sewage -- Purification -- Anaerobic treatment Wine and wine making -- Waste disposal -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4062 , http://hdl.handle.net/10962/d1004530
- Description: In South Africa, wastewater disposal in the wine and distilling industry is undergoing a profound transformation as a result of fundamental changes in regulations and license requirements. To deal with this problem conventional Waste Stabilisation Ponding systems have been used by the industry together with irrigation and evaporation disposal practises. Although effective in the evaporation and containment disposal functions, these pond systems are generally not properly designed and/or managed, resulting in overloading and, at times, the generation of seriously offensive odour problems. Preliminary studies on the feasibility of utilising the Advanced Integrated Wastewater Ponding System as a core treatment technology in winery wastewater treatment were conducted. Results indicated that specific problems had to be addressed before successful ponding treatment could be achieved. This research programme undertook an investigation of the performance of a demonstration ponding system treating household sewage, which formed the basis of the research due to limited experience reported on ponds treating wine industry wastewaters. Malfunctions identified were in correlation with the preliminary winery waste ponding survey, which included unstable fermentation pit functions and inadequate nutrient removal. Retrofitting the fermentation pit with a nylon net across the rising water column resulted in improved retention of active anaerobic sludge, especially during periods of system start-up and/or organic overloading. An investigation into nutrient removal utilising algal biomass provided a valuable contribution towards development of an independent nutrient removal system. Harvested algal biomass was passively manipulated to release polysaccharides under anoxic conditions, with subsequent use as a carbon source by denitrifying organisms. Following denitrification, the still viable algal cells were introduced into a High Rate Algal Pond raceway for photosynthetically produced alkalinity. This high pH environment resulted in induced calcium phosphate mineral formation and subsequent precipitation, as well as effective ammonia stripping from the water. Based on the novel positive research outcomes a decision was made to proceed to the construction of a pilot-scale integrated ponding system treating wastewater from a wine lees factory. The system linked the Anaerobic Baffle Reactor, for pre-treatment, with the improved Advanced Integrated Wastewater Ponding System. The potential of this system has shown that a Waste Stabilisation Ponding system can be engineered to treat wine industry wastewaters and thereby effectively reduce the organic and nutrient loads, by using low-cost retrofitted upgrading unit operations. Valuable algal biomass may also be recovered as a by-product of the treatment process.
- Full Text:
- Date Issued: 2003
Biogeography and community structure of fishes in South African estuaries
- Authors: Harrison, Trevor D
- Date: 2003
- Subjects: Estuarine ecology -- South Africa Estuarine fishes -- South Africa Fish communities -- South Africa Biogeography -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5235 , http://hdl.handle.net/10962/d1005078
- Description: The biogeography and community structure of the fishes of South African estuaries was investigated. In all, 109 systems were examined representing two broad types: temporarily closed and permanently open estuaries. Multivariate analyses of the fish communities identified three biogeographic regions. A cool-temperate region extended along the west and southwest coasts; a warmtemperate zone stretched along the south, southeast and east coasts and a subtropical region occurred along the east coast. The boundaries of these biogeographic regions were also delineated. The general physico-chemical characteristics of the estuaries within the three biogeographic regions also reflected regional differences in climate, rainfall and ocean conditions. Estuarine temperatures followed the trend for marine coastal waters, decreasing from subtropical estuaries toward cool-temperate systems. The low rainfall and runoff in the warm-temperate region together with high evaporation rates and strong seawater input resulted in higher salinities in these estuaries. These factors also accounted for the predominantly clearer waters in warm-temperate estuaries. The estuaries in the three biogeographic regions were also shown to contain somewhat distinctive fish assemblages. Temperature and salinity appeared to be the two main factors affecting the distribution and abundance of fishes in South African estuaries. Subtropical systems were characterised by fishes mostly of tropical origin as well as certain south coast endemic species. Warm-temperate estuaries were dominated by endemic taxa with some tropical species also present. The fish fauna of cooltemperate estuaries mostly comprised south coast endemic species with cosmopolitan and temperate taxa also present. Certain functional components of the ichthyofauna also exhibited slight differences between regions. Freshwater fishes were a major component of closed subtropical estuaries while estuarine resident species were more abundant in warm-temperate estuaries. Overall, estuarine-dependent marine species dominated the fish fauna of the estuaries in all biogeographic regions, signifying that South African estuaries perform a vital nursery function for this group of fishes. Slight differences were also apparent in the trophic structure of the fishes; these were related to environmental differences between regions. Zooplanktivores and fishes that feed on aquatic macrophytes/invertebrates assumed a relatively higher importance in warm-temperate systems. Overall, detritivores dominated the estuarine fish fauna in all regions, indicating that detritus forms the main energy source in South African estuaries.
- Full Text:
- Date Issued: 2003
- Authors: Harrison, Trevor D
- Date: 2003
- Subjects: Estuarine ecology -- South Africa Estuarine fishes -- South Africa Fish communities -- South Africa Biogeography -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5235 , http://hdl.handle.net/10962/d1005078
- Description: The biogeography and community structure of the fishes of South African estuaries was investigated. In all, 109 systems were examined representing two broad types: temporarily closed and permanently open estuaries. Multivariate analyses of the fish communities identified three biogeographic regions. A cool-temperate region extended along the west and southwest coasts; a warmtemperate zone stretched along the south, southeast and east coasts and a subtropical region occurred along the east coast. The boundaries of these biogeographic regions were also delineated. The general physico-chemical characteristics of the estuaries within the three biogeographic regions also reflected regional differences in climate, rainfall and ocean conditions. Estuarine temperatures followed the trend for marine coastal waters, decreasing from subtropical estuaries toward cool-temperate systems. The low rainfall and runoff in the warm-temperate region together with high evaporation rates and strong seawater input resulted in higher salinities in these estuaries. These factors also accounted for the predominantly clearer waters in warm-temperate estuaries. The estuaries in the three biogeographic regions were also shown to contain somewhat distinctive fish assemblages. Temperature and salinity appeared to be the two main factors affecting the distribution and abundance of fishes in South African estuaries. Subtropical systems were characterised by fishes mostly of tropical origin as well as certain south coast endemic species. Warm-temperate estuaries were dominated by endemic taxa with some tropical species also present. The fish fauna of cooltemperate estuaries mostly comprised south coast endemic species with cosmopolitan and temperate taxa also present. Certain functional components of the ichthyofauna also exhibited slight differences between regions. Freshwater fishes were a major component of closed subtropical estuaries while estuarine resident species were more abundant in warm-temperate estuaries. Overall, estuarine-dependent marine species dominated the fish fauna of the estuaries in all biogeographic regions, signifying that South African estuaries perform a vital nursery function for this group of fishes. Slight differences were also apparent in the trophic structure of the fishes; these were related to environmental differences between regions. Zooplanktivores and fishes that feed on aquatic macrophytes/invertebrates assumed a relatively higher importance in warm-temperate systems. Overall, detritivores dominated the estuarine fish fauna in all regions, indicating that detritus forms the main energy source in South African estuaries.
- Full Text:
- Date Issued: 2003
Predictive modelling of species' potential geographical distributions
- Authors: Robertson, Mark Peter
- Date: 2003
- Subjects: Alien plants -- South Africa -- Geographical distribution Species -- Geographical distribution -- Mathematical models Cicadas -- South Africa -- Geographical distribution Scaevola plumieri -- South Africa -- Geographical distribution
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5816 , http://hdl.handle.net/10962/d1007189
- Description: Models that are used for predicting species' potential distributions are important tools that have found applications in a number of areas of applied ecology. The majority of these models can be classified as correlative, as they rely on strong, often indirect, links between species distribution records and environmental predictor variables to make predictions. Correlative models are an alternative to more complex mechanistic models that attempt to simulate the mechanisms considered to underlie the observed correlations with environmental attributes. This study explores the influence of the type and quality of the data used to calibrate correlative models. In terms of data type, the most popular techniques in use are group discrimination techniques, those that use both presence and absence locality data to make predictions. However, for many organisms absence data are either not available or are considered to be unreliable. As the available range of profile techniques (those using presence only data) appeared to be limited, new profile techniques were investigated and evaluated. A new profile modelling technique based on fuzzy classification (the Fuzzy Envelope Model) was developed and implemented. A second profile technique based on Principal Components Analysis was implemented and evaluated. Based on quantitative model evaluation tests, both of these techniques performed well and show considerable promise. In terms of data quality, the effects on model performance of false absence records, the number of locality records (sample size) and the proportion of localities representing species presence (prevalence) in samples were investigated for logistic regression distribution models. Sample size and prevalence both had a significant effect on model performance. False absence records had a significant influence on model performance, which was affected by sample size. A quantitative comparison of the performance of selected profile models and group discrimination modelling techniques suggests that different techniques may be more successful for predicting distributions for particular species or types of organism than others. The results also suggest that several different model design! sample size combinations are capable of making predictions that will on average not differ significantly in performance for a particular species. A further quantitative comparison among modelling techniques suggests that correlative techniques can perform as well as simple mechanistic techniques for predicting potential distributions.
- Full Text:
- Date Issued: 2003
- Authors: Robertson, Mark Peter
- Date: 2003
- Subjects: Alien plants -- South Africa -- Geographical distribution Species -- Geographical distribution -- Mathematical models Cicadas -- South Africa -- Geographical distribution Scaevola plumieri -- South Africa -- Geographical distribution
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5816 , http://hdl.handle.net/10962/d1007189
- Description: Models that are used for predicting species' potential distributions are important tools that have found applications in a number of areas of applied ecology. The majority of these models can be classified as correlative, as they rely on strong, often indirect, links between species distribution records and environmental predictor variables to make predictions. Correlative models are an alternative to more complex mechanistic models that attempt to simulate the mechanisms considered to underlie the observed correlations with environmental attributes. This study explores the influence of the type and quality of the data used to calibrate correlative models. In terms of data type, the most popular techniques in use are group discrimination techniques, those that use both presence and absence locality data to make predictions. However, for many organisms absence data are either not available or are considered to be unreliable. As the available range of profile techniques (those using presence only data) appeared to be limited, new profile techniques were investigated and evaluated. A new profile modelling technique based on fuzzy classification (the Fuzzy Envelope Model) was developed and implemented. A second profile technique based on Principal Components Analysis was implemented and evaluated. Based on quantitative model evaluation tests, both of these techniques performed well and show considerable promise. In terms of data quality, the effects on model performance of false absence records, the number of locality records (sample size) and the proportion of localities representing species presence (prevalence) in samples were investigated for logistic regression distribution models. Sample size and prevalence both had a significant effect on model performance. False absence records had a significant influence on model performance, which was affected by sample size. A quantitative comparison of the performance of selected profile models and group discrimination modelling techniques suggests that different techniques may be more successful for predicting distributions for particular species or types of organism than others. The results also suggest that several different model design! sample size combinations are capable of making predictions that will on average not differ significantly in performance for a particular species. A further quantitative comparison among modelling techniques suggests that correlative techniques can perform as well as simple mechanistic techniques for predicting potential distributions.
- Full Text:
- Date Issued: 2003
On the use of metabolic rate measurements to assess the stress response in juvenile spotted grunter, Pomadasys commersonnii (Haemulidae, Pisces)
- Authors: Radull, John
- Date: 2003
- Subjects: Fishes -- Metabolism Fishes -- Physiology Pomadasys -- Physiology Grunts (Fishes) -- Physiology Stress (Psychology) Stress (Physiology)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5350 , http://hdl.handle.net/10962/d1007564
- Description: Quantitication of stress requires the use of a stress indicator that is easy to measure, and which can be readily interpreted in terms of the potential long-term effects to an organism. This study evaluates the suitability of metabolic rate as an indicator of the stress response in fish. By comparing the metabolic with the cortisol stress response, the most commonly used indicator of stress in fish, it was possible to assess the suitability of metabolic rate as a stress indicator. Changes in metabolic rate were used to predict the long-term effects of transport-related stressors. This study also detennined the baseline metabolic rates of the tish. The standard and the active metabolic rates of juvenile P. cummersonnii were 0.16 ± 0.02 (mean ± S.D, n = 6) mg O₂g⁻¹h⁻¹, and 0.56 ± 0.04 mg O₂g⁻¹h⁻¹, respectively, whereas the routine metabolic rate for the fish was 0.25 ± 0.03 mg O₂g⁻¹h¹. The relationship between metabolic rate and body weight was described by the equation ϺO₂ = 0.64 W⁻°·³⁸. 24-h oxygen consumption measurements showed that juvenile P. commersonnii exhibited diel rhythmicity in oxygen consumption rate, the higher rates occurring at night and the lower rates during the daytime. The higher nocturnal metabolic activity may have been due to increased activity induced by an endogenous rhythm related to feeding. Diel rhythmicity has direct implications for the measurement of baseline metabolic rates since it could result in overestimation or underestimation of these rates. 24-h continuous oxygen consumption measurements enabled the detection of the rhythmicity in oxygen consumption rate, and thereby ensured a greater degree of accuracy in the estimation of these parameters. The metabolic stress response in juvenile P. commersonnii was best described by the equation, y = -0.0013 x² + 0.0364 x ÷ 0.3052, where x = time after application of stressor, and y = oxygen consumption rate. Using the derivative of this equation, the metabolic stress response was estimated to peak approximately 14 min after application of a simulated capture and handling stressor. Oxygen consumption increased by about 300 % as a result of the stress. Approximately 15 min after application of a similar stressor, plasma cortisol levels in stressed fish was 200 % higher than baseline levels. However, cortisol levels in fish sampled 30 min after the disturbance was similar to the baseline cortisol levels, indicating that full recovery had occurred. Although the patterns in the metabolic and cortisol stress responses were similar, metabolic rate could be measured continuously, thereby ensuring accurate interpretation of the data. Furthermore, increases in metabolic rate during the stress response are a culmination of physiological events from the primary to the tertiary levels of biological organization and are, therefore, easier to interpret in terms of long-term effects on the fish. Different transportation procedures elicited variable degrees of stress in juvenile P. commersonnii. The cost of metabolism attributed to the effects of capture and handling was twice as much as that attributed to acute temperature elevation. Acute temperature decrease resulted in a signiticant reduction in the oxygen consumption rate (ANOVA, P < 0.05). Oxygen consumption by the fish was not affected by fish density (ANOVA: F = 2.002, P = 0.5), or by oxygen depletion at dissolved oxygen concentrations above the critical level. Below this level, however, oxygen consumption decreased linearly with further decrease in dissolved oxygen concentration. These results showed that the highest energetic cost to juvenile P. commersonnii was incurred as a result of capture and handling. The results also showed that by subjecting fish to different stressors, it was possible to categorize them according to their relative metabolic costs to the fish. At 25º C, the effective concentration of 2-phenoxyethanol to fully anaesthetize (Stage IV, McFarland 1960) juvenile P. commersonnii was 0.4 ml l⁻¹ and the most appropriate concentration for deep sedation (Stage II, McFarland 1960) of the fish for at least 24 h was 0.2 ml l⁻¹. A maximum of 3 minutes was required by the fish to recover from the effects of the anaesthetic. There was no correlation between fish weight and the rate of induction of anaesthesia (r² = 0.001, p = 0.3). At the peak of the metabolic stress response, oxygen consumption was twice as high in the un-anaesthetized fish compared to the fish anaesthetized after the application of the simulated capture and handling stressor, suggesting that anaesthetization with 2-phenoxyethanol may have reduced the effect of the disturbance on the fish. Similar oxygen consumption rates for the fish anaesthetized prior to capture and the non-stressed fish suggested that the increases in metabolic rate could be linked to the struggling associated with attempts by fish to escape from the perceived stressor. Anaesthetization of juvenile P. commersonnii with 0.3 ml l⁻¹ 2-phenoxyethanol resulted in a more than 200 % increase in plasma cortisol concentration. The elevated levels of plasma cortisol in the anaesthetized fish suggested a manifestation of 2-phenoxyethanol as a stressor. At the time of capture, cortisol levels in fish that were anaesthetized prior to capture were the same as those measured in the disturbed fish at the peak of the stress response (ANOVA, p = 0.95), suggesting that the anaesthetized fish were already experiencing considerable stress at the time they were captured. Undisturbed juvenile P. commersonnii that were anaesthetized for 1 h also had cortisol levels that were five times higher than those measured in undisturbed-unanaesthetized fish, indicating that the duration of exposure to the anaesthetic had a significant effect on plasma cortisol levels. The results presented in this study demonstrate the usefulness of metabolic rate as an indicator of acute stress in fish. This was achieved by comparing the metabolic and the cortisol stress responses. The ease and accuracy with which oxygen consumption of fish could be measured made it possible to measure the stress response more accurately than by plasma cortisol concentration. It was also possible to monitor metabolic rate continuously over a long duration using polarographic oxygen sensors, thus enabling a better evaluation of the stress response. These results, thus, suggest that metabolic rate measurements could be a more practical way to quantify the effects of acute stressors on juvenile fishes. By detailing the profile of the metabolic stress response in P. commersonnii, this study makes a contribution towards understanding the physiological effects of stress in fishes. The study also contributes towards the quantification of baseline metabolic rates of this species under captivity. This study also contributes towards understanding the effects of 2-phenoxyethanol on the stress physiology of fish. By anaesthetizing fish under different conditions of stress, it was possible to evaluate the effect of 2-phenoxyethanol on the metabolic stress response. The ability of 2-phenoxyethanol to reduce physical activity of the fish, and thereby reduce the impact of acute stress on the metabolic stress response, makes it a good agent for the mitigation of stress during the capture and handling of fish. However, the increase in plasma cortisol concentration during prolonged anaesthetization using this drug suggests that the anaesthetic might be a stressor to fish and may, therefore, not be suitable for long-term sedation.
- Full Text:
- Date Issued: 2003
- Authors: Radull, John
- Date: 2003
- Subjects: Fishes -- Metabolism Fishes -- Physiology Pomadasys -- Physiology Grunts (Fishes) -- Physiology Stress (Psychology) Stress (Physiology)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5350 , http://hdl.handle.net/10962/d1007564
- Description: Quantitication of stress requires the use of a stress indicator that is easy to measure, and which can be readily interpreted in terms of the potential long-term effects to an organism. This study evaluates the suitability of metabolic rate as an indicator of the stress response in fish. By comparing the metabolic with the cortisol stress response, the most commonly used indicator of stress in fish, it was possible to assess the suitability of metabolic rate as a stress indicator. Changes in metabolic rate were used to predict the long-term effects of transport-related stressors. This study also detennined the baseline metabolic rates of the tish. The standard and the active metabolic rates of juvenile P. cummersonnii were 0.16 ± 0.02 (mean ± S.D, n = 6) mg O₂g⁻¹h⁻¹, and 0.56 ± 0.04 mg O₂g⁻¹h⁻¹, respectively, whereas the routine metabolic rate for the fish was 0.25 ± 0.03 mg O₂g⁻¹h¹. The relationship between metabolic rate and body weight was described by the equation ϺO₂ = 0.64 W⁻°·³⁸. 24-h oxygen consumption measurements showed that juvenile P. commersonnii exhibited diel rhythmicity in oxygen consumption rate, the higher rates occurring at night and the lower rates during the daytime. The higher nocturnal metabolic activity may have been due to increased activity induced by an endogenous rhythm related to feeding. Diel rhythmicity has direct implications for the measurement of baseline metabolic rates since it could result in overestimation or underestimation of these rates. 24-h continuous oxygen consumption measurements enabled the detection of the rhythmicity in oxygen consumption rate, and thereby ensured a greater degree of accuracy in the estimation of these parameters. The metabolic stress response in juvenile P. commersonnii was best described by the equation, y = -0.0013 x² + 0.0364 x ÷ 0.3052, where x = time after application of stressor, and y = oxygen consumption rate. Using the derivative of this equation, the metabolic stress response was estimated to peak approximately 14 min after application of a simulated capture and handling stressor. Oxygen consumption increased by about 300 % as a result of the stress. Approximately 15 min after application of a similar stressor, plasma cortisol levels in stressed fish was 200 % higher than baseline levels. However, cortisol levels in fish sampled 30 min after the disturbance was similar to the baseline cortisol levels, indicating that full recovery had occurred. Although the patterns in the metabolic and cortisol stress responses were similar, metabolic rate could be measured continuously, thereby ensuring accurate interpretation of the data. Furthermore, increases in metabolic rate during the stress response are a culmination of physiological events from the primary to the tertiary levels of biological organization and are, therefore, easier to interpret in terms of long-term effects on the fish. Different transportation procedures elicited variable degrees of stress in juvenile P. commersonnii. The cost of metabolism attributed to the effects of capture and handling was twice as much as that attributed to acute temperature elevation. Acute temperature decrease resulted in a signiticant reduction in the oxygen consumption rate (ANOVA, P < 0.05). Oxygen consumption by the fish was not affected by fish density (ANOVA: F = 2.002, P = 0.5), or by oxygen depletion at dissolved oxygen concentrations above the critical level. Below this level, however, oxygen consumption decreased linearly with further decrease in dissolved oxygen concentration. These results showed that the highest energetic cost to juvenile P. commersonnii was incurred as a result of capture and handling. The results also showed that by subjecting fish to different stressors, it was possible to categorize them according to their relative metabolic costs to the fish. At 25º C, the effective concentration of 2-phenoxyethanol to fully anaesthetize (Stage IV, McFarland 1960) juvenile P. commersonnii was 0.4 ml l⁻¹ and the most appropriate concentration for deep sedation (Stage II, McFarland 1960) of the fish for at least 24 h was 0.2 ml l⁻¹. A maximum of 3 minutes was required by the fish to recover from the effects of the anaesthetic. There was no correlation between fish weight and the rate of induction of anaesthesia (r² = 0.001, p = 0.3). At the peak of the metabolic stress response, oxygen consumption was twice as high in the un-anaesthetized fish compared to the fish anaesthetized after the application of the simulated capture and handling stressor, suggesting that anaesthetization with 2-phenoxyethanol may have reduced the effect of the disturbance on the fish. Similar oxygen consumption rates for the fish anaesthetized prior to capture and the non-stressed fish suggested that the increases in metabolic rate could be linked to the struggling associated with attempts by fish to escape from the perceived stressor. Anaesthetization of juvenile P. commersonnii with 0.3 ml l⁻¹ 2-phenoxyethanol resulted in a more than 200 % increase in plasma cortisol concentration. The elevated levels of plasma cortisol in the anaesthetized fish suggested a manifestation of 2-phenoxyethanol as a stressor. At the time of capture, cortisol levels in fish that were anaesthetized prior to capture were the same as those measured in the disturbed fish at the peak of the stress response (ANOVA, p = 0.95), suggesting that the anaesthetized fish were already experiencing considerable stress at the time they were captured. Undisturbed juvenile P. commersonnii that were anaesthetized for 1 h also had cortisol levels that were five times higher than those measured in undisturbed-unanaesthetized fish, indicating that the duration of exposure to the anaesthetic had a significant effect on plasma cortisol levels. The results presented in this study demonstrate the usefulness of metabolic rate as an indicator of acute stress in fish. This was achieved by comparing the metabolic and the cortisol stress responses. The ease and accuracy with which oxygen consumption of fish could be measured made it possible to measure the stress response more accurately than by plasma cortisol concentration. It was also possible to monitor metabolic rate continuously over a long duration using polarographic oxygen sensors, thus enabling a better evaluation of the stress response. These results, thus, suggest that metabolic rate measurements could be a more practical way to quantify the effects of acute stressors on juvenile fishes. By detailing the profile of the metabolic stress response in P. commersonnii, this study makes a contribution towards understanding the physiological effects of stress in fishes. The study also contributes towards the quantification of baseline metabolic rates of this species under captivity. This study also contributes towards understanding the effects of 2-phenoxyethanol on the stress physiology of fish. By anaesthetizing fish under different conditions of stress, it was possible to evaluate the effect of 2-phenoxyethanol on the metabolic stress response. The ability of 2-phenoxyethanol to reduce physical activity of the fish, and thereby reduce the impact of acute stress on the metabolic stress response, makes it a good agent for the mitigation of stress during the capture and handling of fish. However, the increase in plasma cortisol concentration during prolonged anaesthetization using this drug suggests that the anaesthetic might be a stressor to fish and may, therefore, not be suitable for long-term sedation.
- Full Text:
- Date Issued: 2003