Structural analysis of effects of mutations on HIV-1 subtype C protease active site
- Mathu, Alexander Muchugia Nganga
- Authors: Mathu, Alexander Muchugia Nganga
- Date: 2012
- Subjects: HIV (Viruses) -- Research , HIV infections -- Treatment -- Research , Protease inhibitors -- Research , Viruses -- Effect of drugs on -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4013 , http://hdl.handle.net/10962/d1004073 , HIV (Viruses) -- Research , HIV infections -- Treatment -- Research , Protease inhibitors -- Research , Viruses -- Effect of drugs on -- Research
- Description: HIV/AIDS is a global pandemic that poses a great threat especially in Sub-Saharan Africa where the highest population of those infected with the virus is found. It has far reaching medical, socio-economic and scientific implications. The HIV-1 protease enzyme is a prime therapeutic target that has been exploited in an effort to reduce morbidity and mortality. However problems arise from drug toxicity and drug-resistant mutations of the protease which is a motivation for research for new, safer and effective therapies. Evidence exists to show that there are significant genomic differences in Subtype B and C that have a negative effect on the intrinsic binding of inhibitors. It is imperative to look at all perspectives from epidemiological, molecular to the pharmacological ones so as to achieve rational design of therapeutic agents. This study involved the use of in silico structural analysis of the effects of mutations in the active site. The data was provided by the National Institute of Communicable Diseases consisting of HIV-1 Subtype C protease sequences of 29 infants exhibiting drug-resistance to ritonavir and lopinavir. The major active site mutations causing drug resistance identified in this study were M46I, I54V and V82A using the Stanford HIV database tool. Homology modeling without extra restraints produced models with improved quality in comparison to those with restraints. MetaMQAPII results differed when models were visualized as dimers giving erroneous modeled regions in comparison to monomers. A broader study with a larger dataset of HIV-1 subtype C protease sequences is required to increase statistical confidence and in order to identify the pattern of drug resistant mutations. Homology modeling without extra restraints is preferred for calculating homology models for the HIV-1 subtype C. Further investigations needs to be done to ascertain the accuracy of validation results for dimers from MetaMQAPII as it is designed for evaluation of monomers.
- Full Text:
- Date Issued: 2012
- Authors: Mathu, Alexander Muchugia Nganga
- Date: 2012
- Subjects: HIV (Viruses) -- Research , HIV infections -- Treatment -- Research , Protease inhibitors -- Research , Viruses -- Effect of drugs on -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4013 , http://hdl.handle.net/10962/d1004073 , HIV (Viruses) -- Research , HIV infections -- Treatment -- Research , Protease inhibitors -- Research , Viruses -- Effect of drugs on -- Research
- Description: HIV/AIDS is a global pandemic that poses a great threat especially in Sub-Saharan Africa where the highest population of those infected with the virus is found. It has far reaching medical, socio-economic and scientific implications. The HIV-1 protease enzyme is a prime therapeutic target that has been exploited in an effort to reduce morbidity and mortality. However problems arise from drug toxicity and drug-resistant mutations of the protease which is a motivation for research for new, safer and effective therapies. Evidence exists to show that there are significant genomic differences in Subtype B and C that have a negative effect on the intrinsic binding of inhibitors. It is imperative to look at all perspectives from epidemiological, molecular to the pharmacological ones so as to achieve rational design of therapeutic agents. This study involved the use of in silico structural analysis of the effects of mutations in the active site. The data was provided by the National Institute of Communicable Diseases consisting of HIV-1 Subtype C protease sequences of 29 infants exhibiting drug-resistance to ritonavir and lopinavir. The major active site mutations causing drug resistance identified in this study were M46I, I54V and V82A using the Stanford HIV database tool. Homology modeling without extra restraints produced models with improved quality in comparison to those with restraints. MetaMQAPII results differed when models were visualized as dimers giving erroneous modeled regions in comparison to monomers. A broader study with a larger dataset of HIV-1 subtype C protease sequences is required to increase statistical confidence and in order to identify the pattern of drug resistant mutations. Homology modeling without extra restraints is preferred for calculating homology models for the HIV-1 subtype C. Further investigations needs to be done to ascertain the accuracy of validation results for dimers from MetaMQAPII as it is designed for evaluation of monomers.
- Full Text:
- Date Issued: 2012
Testing the existence and direction of "spill-over" of mussel recruits beyond the boundaries of marine protected areas
- Authors: Ludford, Adam
- Date: 2011
- Subjects: Marine parks and reserves -- South Africa -- Transkei , Marine resources conservation -- South Africa -- Transkei , Mussels -- Ecology -- South Africa -- Transkei , Mexilhao mussel -- Reproduction -- South Africa -- Transkei , Mexilhao mussel -- Behavior -- South Africa -- Transkei
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5786 , http://hdl.handle.net/10962/d1005474 , Marine parks and reserves -- South Africa -- Transkei , Marine resources conservation -- South Africa -- Transkei , Mussels -- Ecology -- South Africa -- Transkei , Mexilhao mussel -- Reproduction -- South Africa -- Transkei , Mexilhao mussel -- Behavior -- South Africa -- Transkei
- Description: Landscape ecology helps in predicting the influence of habitat fragmentation on populations. Marine protected areas (MPAs) are expected to create areas of good quality patches and so improve connectivity among shores. MPAs are believed not only to protect adult populations, but also to enhance recruitment both within MPAs and on surrounding exploited shores, therefore improving their ability to recover from overexploitation. As such, MPAs are a preferred management tool for the conservation of natural populations. Although MPAs have been demonstrated to enhance adult abundances, little work has been done on their ability to provide so called "spill-over" of recruits nor has the generality of the influence of MPAs been investigated in a single region with multiple control sites. The Transkei region, on the east coast of South Africa, and the intertidal mussel, Perna perna, offer an ideal system to test the generality of the influence of MPAs on surrounding shores, due to the presence of multiple MPAs and exploited control sites. Patterns of adult abundance were surveyed at four MPAs and two comparably sized exploited control sites. Adult abundances were, in general, found to be higher within MPAs than at exploited control sites, with adult abundances decreasing towards the edge of MPAs and decreasing even more on the outside shores. To simplify the sorting procedure for samples of mussel recruits, a new method using fractionated elutriation was devised and tested. This new method was found to be more accurate, although not statistically significant but also substantially more time consuming. The increase in accuracy although not statistically significant could be biologically significant, especially when looking at low numbers. This new method could, therefore, be very useful especially when [...] is low. Recruitment was estimated over three months during the main reproductive season at two of the MPAs and at appropriate control sites. I predicted that recruitment patterns would mirror the patterns found in adult abundances and that there would be directionality in patterns of recruitment, with northern sites having greater recruitment due to the direction of near-shore ocean currents. Contrary to this, there were no correlations between adult abundance and recruitment for any of the months or sites, with no clear spatial pattern of recruitment in any of the three months. There was, however, a slight trend of greater recruitment at northern sites. To explain the lack of consistency in recruitment and adult abundances, wind data were used to examine the near-shore surface currents in this area, with theoretical surface currents showing similar patterns to those observed for recruitment. From a landscape perspective, the good patches created by MPAs supply recruits to the surrounding matrix but the low quality of habitat in the matrix prevents rehabilitation. The quality of the matrix must therefore be first improved by reseeding these shores. These results emphasise that while MPAs may function in protecting adult abundances, their influence on supplying recruits and hence recovery of near-by exploited shores may be overestimated. This lack of influence on near-by exploited shores highlights the need for reseeding of shores in conjunction with suitable management plans.
- Full Text:
- Date Issued: 2011
- Authors: Ludford, Adam
- Date: 2011
- Subjects: Marine parks and reserves -- South Africa -- Transkei , Marine resources conservation -- South Africa -- Transkei , Mussels -- Ecology -- South Africa -- Transkei , Mexilhao mussel -- Reproduction -- South Africa -- Transkei , Mexilhao mussel -- Behavior -- South Africa -- Transkei
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5786 , http://hdl.handle.net/10962/d1005474 , Marine parks and reserves -- South Africa -- Transkei , Marine resources conservation -- South Africa -- Transkei , Mussels -- Ecology -- South Africa -- Transkei , Mexilhao mussel -- Reproduction -- South Africa -- Transkei , Mexilhao mussel -- Behavior -- South Africa -- Transkei
- Description: Landscape ecology helps in predicting the influence of habitat fragmentation on populations. Marine protected areas (MPAs) are expected to create areas of good quality patches and so improve connectivity among shores. MPAs are believed not only to protect adult populations, but also to enhance recruitment both within MPAs and on surrounding exploited shores, therefore improving their ability to recover from overexploitation. As such, MPAs are a preferred management tool for the conservation of natural populations. Although MPAs have been demonstrated to enhance adult abundances, little work has been done on their ability to provide so called "spill-over" of recruits nor has the generality of the influence of MPAs been investigated in a single region with multiple control sites. The Transkei region, on the east coast of South Africa, and the intertidal mussel, Perna perna, offer an ideal system to test the generality of the influence of MPAs on surrounding shores, due to the presence of multiple MPAs and exploited control sites. Patterns of adult abundance were surveyed at four MPAs and two comparably sized exploited control sites. Adult abundances were, in general, found to be higher within MPAs than at exploited control sites, with adult abundances decreasing towards the edge of MPAs and decreasing even more on the outside shores. To simplify the sorting procedure for samples of mussel recruits, a new method using fractionated elutriation was devised and tested. This new method was found to be more accurate, although not statistically significant but also substantially more time consuming. The increase in accuracy although not statistically significant could be biologically significant, especially when looking at low numbers. This new method could, therefore, be very useful especially when [...] is low. Recruitment was estimated over three months during the main reproductive season at two of the MPAs and at appropriate control sites. I predicted that recruitment patterns would mirror the patterns found in adult abundances and that there would be directionality in patterns of recruitment, with northern sites having greater recruitment due to the direction of near-shore ocean currents. Contrary to this, there were no correlations between adult abundance and recruitment for any of the months or sites, with no clear spatial pattern of recruitment in any of the three months. There was, however, a slight trend of greater recruitment at northern sites. To explain the lack of consistency in recruitment and adult abundances, wind data were used to examine the near-shore surface currents in this area, with theoretical surface currents showing similar patterns to those observed for recruitment. From a landscape perspective, the good patches created by MPAs supply recruits to the surrounding matrix but the low quality of habitat in the matrix prevents rehabilitation. The quality of the matrix must therefore be first improved by reseeding these shores. These results emphasise that while MPAs may function in protecting adult abundances, their influence on supplying recruits and hence recovery of near-by exploited shores may be overestimated. This lack of influence on near-by exploited shores highlights the need for reseeding of shores in conjunction with suitable management plans.
- Full Text:
- Date Issued: 2011
Population structure, physiology and feeding ecology of the mysid Mesopodopsis wooldridgei (Whittmann) in a large permanently open estuary
- Authors: Mesher, Colette Suzanne
- Date: 2005
- Subjects: Mysidacea -- Physiology , Mysidacea -- Ecology , Mysidacea -- Feeding and feeds , Zooplankton -- South Africa -- Great Fish Estuary
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5746 , http://hdl.handle.net/10962/d1005432 , Mysidacea -- Physiology , Mysidacea -- Ecology , Mysidacea -- Feeding and feeds , Zooplankton -- South Africa -- Great Fish Estuary
- Description: This project had three main aims. The first aim was to investigate the metabolic physiology of the mysid Mesopodopsis wooldridgei. Secondly, the study examined the contribution of the mysid to the zooplankton community. Finally the study attempted to clarify the primary sources of carbon utilised by the mysid using stable carbon isotope analysis. The study was conducted in the freshwater dominated permanently open Great Fish Estuary (33°30’S; 27°08’E) located along the south-eastern coastline of southern Africa. Mass specific oxygen consumption rates of Mesopodopsis wooldridgei ranged between 0.11 and 8.38 ml O2 mg ww-1 h-1 and increased with an increase in water temperature. There were no significant differences in the respiration rates between the male and female mysids (P > 0.05). At a constant temperature (20°C), the oxygen consumption rate of M. wooldridgei decreased with an increase in salinity. Salinity tolerance of the mysid was strongly modified by temperature. At 5‰ and 30°C, mysids exhibited mass mortality. The Q10 value for M. wooldridgei at 15, 25 and 35‰ was estimated at 2.34, 1.44 and 2.14, respectively. Results of the study suggest that M. wooldridgei is well adapted to surviving in environments characterised by variations in temperature and salinity. Within the Great Fish Estuary, total chl. a concentration ranged between 2.68 μg L-1 and 31.12 μg L-1 and was always dominated by large phytoplankton cells (>5 μm). Average zooplankton abundance ranged between 62 and 28 917 ind. m-3 and biomass between 10 and 203 mg Dwt m-3. The zooplankton community was numerically dominated by the calanoid copepod Pseudodiaptomus hessei, which comprised up to 100% (range between 12 and 100%) of the total zooplankton counted. Total zooplankton biomass during the day was dominated by copepods and by mysids during the nighttime. Among the mysids, M. wooldridgei was the most numerically abundant mysid and comprised <10% of the total zooplankton abundance. Numerical analysis found no seasonal pattern in the total zooplankton abundance (including mysids). The lack of any seasonality could be attributed to the continuous freshwater inflow into the estuary due to the inter-basin transfer of water from the Gariep Dam to the Fish River system. A distinct spatial pattern in the zooplankton community structure was evident with the upper stations almost entirely dominated by the copepod P. hessei, while at stations occupied in the lower reaches of the estuary, the zooplankton community comprised a mixture of freshwater, estuarine and marine breeding zooplankton species. The mysids also demonstrated a distinct spatial pattern in their distribution. Mysids were generally absent from the upper reaches, while in the middle reaches Rhopalophthalmus terranatalis and M. wooldridgei were numerically dominant. Gastrosaccus brevifissura dominated in the lower regions of the estuary. Stable isotope analysis (δ13C) indicated that the dominant source of carbon utilised by the numerically dominant copepods and juvenile M. wooldridgei within the estuary was derived from the extensive phytoplankton stocks within the system. In contrast, sub-adult and adult mysids (R. terranatalis, M. wooldridgei and G. brevifissura) appeared to consume a combination of phytoplankton and copepods. The contribution of the various sources of carbon to the total carbon intake of the mysid remains unknown.
- Full Text:
- Date Issued: 2005
- Authors: Mesher, Colette Suzanne
- Date: 2005
- Subjects: Mysidacea -- Physiology , Mysidacea -- Ecology , Mysidacea -- Feeding and feeds , Zooplankton -- South Africa -- Great Fish Estuary
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5746 , http://hdl.handle.net/10962/d1005432 , Mysidacea -- Physiology , Mysidacea -- Ecology , Mysidacea -- Feeding and feeds , Zooplankton -- South Africa -- Great Fish Estuary
- Description: This project had three main aims. The first aim was to investigate the metabolic physiology of the mysid Mesopodopsis wooldridgei. Secondly, the study examined the contribution of the mysid to the zooplankton community. Finally the study attempted to clarify the primary sources of carbon utilised by the mysid using stable carbon isotope analysis. The study was conducted in the freshwater dominated permanently open Great Fish Estuary (33°30’S; 27°08’E) located along the south-eastern coastline of southern Africa. Mass specific oxygen consumption rates of Mesopodopsis wooldridgei ranged between 0.11 and 8.38 ml O2 mg ww-1 h-1 and increased with an increase in water temperature. There were no significant differences in the respiration rates between the male and female mysids (P > 0.05). At a constant temperature (20°C), the oxygen consumption rate of M. wooldridgei decreased with an increase in salinity. Salinity tolerance of the mysid was strongly modified by temperature. At 5‰ and 30°C, mysids exhibited mass mortality. The Q10 value for M. wooldridgei at 15, 25 and 35‰ was estimated at 2.34, 1.44 and 2.14, respectively. Results of the study suggest that M. wooldridgei is well adapted to surviving in environments characterised by variations in temperature and salinity. Within the Great Fish Estuary, total chl. a concentration ranged between 2.68 μg L-1 and 31.12 μg L-1 and was always dominated by large phytoplankton cells (>5 μm). Average zooplankton abundance ranged between 62 and 28 917 ind. m-3 and biomass between 10 and 203 mg Dwt m-3. The zooplankton community was numerically dominated by the calanoid copepod Pseudodiaptomus hessei, which comprised up to 100% (range between 12 and 100%) of the total zooplankton counted. Total zooplankton biomass during the day was dominated by copepods and by mysids during the nighttime. Among the mysids, M. wooldridgei was the most numerically abundant mysid and comprised <10% of the total zooplankton abundance. Numerical analysis found no seasonal pattern in the total zooplankton abundance (including mysids). The lack of any seasonality could be attributed to the continuous freshwater inflow into the estuary due to the inter-basin transfer of water from the Gariep Dam to the Fish River system. A distinct spatial pattern in the zooplankton community structure was evident with the upper stations almost entirely dominated by the copepod P. hessei, while at stations occupied in the lower reaches of the estuary, the zooplankton community comprised a mixture of freshwater, estuarine and marine breeding zooplankton species. The mysids also demonstrated a distinct spatial pattern in their distribution. Mysids were generally absent from the upper reaches, while in the middle reaches Rhopalophthalmus terranatalis and M. wooldridgei were numerically dominant. Gastrosaccus brevifissura dominated in the lower regions of the estuary. Stable isotope analysis (δ13C) indicated that the dominant source of carbon utilised by the numerically dominant copepods and juvenile M. wooldridgei within the estuary was derived from the extensive phytoplankton stocks within the system. In contrast, sub-adult and adult mysids (R. terranatalis, M. wooldridgei and G. brevifissura) appeared to consume a combination of phytoplankton and copepods. The contribution of the various sources of carbon to the total carbon intake of the mysid remains unknown.
- Full Text:
- Date Issued: 2005
Age, growth and yield-per-recruit analysis of ndunduma Diplotaxodon limnothrissa (Teleostei: Cichlidae), in the southeastern arm of Lake Malawi
- Authors: Kanyerere, Geoffrey Zantute
- Date: 2004
- Subjects: Fishes -- Nyasa, Lake , Cichlids -- Nyasa, Lake , Fishes -- Growth -- Nyasa, Lake , Fishes -- Age -- Nyasa, Lake , Fishery resources -- Malawi , Fishery management -- Malawi
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5214 , http://hdl.handle.net/10962/d1005057 , Fishes -- Nyasa, Lake , Cichlids -- Nyasa, Lake , Fishes -- Growth -- Nyasa, Lake , Fishes -- Age -- Nyasa, Lake , Fishery resources -- Malawi , Fishery management -- Malawi
- Description: Diplotaxodon limnothrissa Turner (1995) is a widely distributed species occurring throughout Lake Malawi, extending from the surface to a depth of at least 220m. It is probably the most abundant cichlid in the lake with biomass estimates of around 87 000 tonnes in the pelagic zone alone. The species is exploited commercially in the southern part of the lake but since its inception the fishery has never been assessed. As such this study investigates some aspects of age and growth of the species besides applying a yield-per-recruit analysis to assess the status of the fishery. Analysis of sectioned sagittal otoliths revealed that D. limnothrissa is fast growing and relatively long-lived species, attaining ages in excess of 10 years. Growth in length was rapid in immature fish, with fish attaining almost half of their maximum size within their first year. Le ngth-at-age was described by the von Bertalanffy growth model with combined-sex growth described as Lt = 211.21(1-exp(- 0.24(t+1.36))) mm TL. Total, natural and fishing mortalities were estimated at 0.76 yr⁻¹, 0.31 yr⁻¹ and 0.45 yr⁻¹ respectively. Per-recruit analysis indicated that the D. limnothrissa stock in the southeast arm of the lake is fully exploited as indicated by the current spawner biomass-per-recruit ratios of 31-55% (SB/R)F=0. Modelling indicated that the current age-at-capture (2.67 years) is lower than the age at which yield is optimised (> 5 years) based on the F₀·₁ harvesting strategy. It is, therefore, recommended that the age-at-capture should be increased from 2.67 to 5 years to optimise yield.
- Full Text:
- Date Issued: 2004
- Authors: Kanyerere, Geoffrey Zantute
- Date: 2004
- Subjects: Fishes -- Nyasa, Lake , Cichlids -- Nyasa, Lake , Fishes -- Growth -- Nyasa, Lake , Fishes -- Age -- Nyasa, Lake , Fishery resources -- Malawi , Fishery management -- Malawi
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5214 , http://hdl.handle.net/10962/d1005057 , Fishes -- Nyasa, Lake , Cichlids -- Nyasa, Lake , Fishes -- Growth -- Nyasa, Lake , Fishes -- Age -- Nyasa, Lake , Fishery resources -- Malawi , Fishery management -- Malawi
- Description: Diplotaxodon limnothrissa Turner (1995) is a widely distributed species occurring throughout Lake Malawi, extending from the surface to a depth of at least 220m. It is probably the most abundant cichlid in the lake with biomass estimates of around 87 000 tonnes in the pelagic zone alone. The species is exploited commercially in the southern part of the lake but since its inception the fishery has never been assessed. As such this study investigates some aspects of age and growth of the species besides applying a yield-per-recruit analysis to assess the status of the fishery. Analysis of sectioned sagittal otoliths revealed that D. limnothrissa is fast growing and relatively long-lived species, attaining ages in excess of 10 years. Growth in length was rapid in immature fish, with fish attaining almost half of their maximum size within their first year. Le ngth-at-age was described by the von Bertalanffy growth model with combined-sex growth described as Lt = 211.21(1-exp(- 0.24(t+1.36))) mm TL. Total, natural and fishing mortalities were estimated at 0.76 yr⁻¹, 0.31 yr⁻¹ and 0.45 yr⁻¹ respectively. Per-recruit analysis indicated that the D. limnothrissa stock in the southeast arm of the lake is fully exploited as indicated by the current spawner biomass-per-recruit ratios of 31-55% (SB/R)F=0. Modelling indicated that the current age-at-capture (2.67 years) is lower than the age at which yield is optimised (> 5 years) based on the F₀·₁ harvesting strategy. It is, therefore, recommended that the age-at-capture should be increased from 2.67 to 5 years to optimise yield.
- Full Text:
- Date Issued: 2004
The synthesis and properties of some polymer hydrogels
- Authors: Hird, Bryn
- Date: 1984 , 2013-04-05
- Subjects: Colloids
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4428 , http://hdl.handle.net/10962/d1006975 , Colloids
- Description: The interactions between water molecules and polyelectrolyte species in aqueous solutions are reviewed and are used to infer interactions occuring in swollen crosslinked polyelectrolyte hydrogels. Linear poly(acrylic acid ) and derivatives neutralised to varying degrees with alkali-metal hydroxides are prepared and characterised. Samples of these compounds are crosslinked by 'Y - irradiation to form hydrogels. Hydration studies on linear polymers, crosslinked material and a commercial polyacrylate hydrogel indicate a possible hydration structure and provide some insight into the nature of water-polymer interactions within a sHollen polyacrylate gel. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1984
- Authors: Hird, Bryn
- Date: 1984 , 2013-04-05
- Subjects: Colloids
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4428 , http://hdl.handle.net/10962/d1006975 , Colloids
- Description: The interactions between water molecules and polyelectrolyte species in aqueous solutions are reviewed and are used to infer interactions occuring in swollen crosslinked polyelectrolyte hydrogels. Linear poly(acrylic acid ) and derivatives neutralised to varying degrees with alkali-metal hydroxides are prepared and characterised. Samples of these compounds are crosslinked by 'Y - irradiation to form hydrogels. Hydration studies on linear polymers, crosslinked material and a commercial polyacrylate hydrogel indicate a possible hydration structure and provide some insight into the nature of water-polymer interactions within a sHollen polyacrylate gel. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1984
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