Glycine-N-acyltransferase (GLYAT, EC 2.3.1.13) has been characterised in a number of species including: humans, chimpanzees, rhesus monkeys and bovines. The characterisation of GLYAT from various species contributes to a better understanding of the diversity of the enzyme which in turn might help improve the current understanding of detoxification in mammals. The GLYAT enzyme of both the chacma baboon and vervet monkey has not been characterised. In this project, tissue samples were obtained from a chacma baboon (Papio ursinus) and a vervet monkey (Chlorocebus pygerythrus) to determine the nucleic acid sequence that encodes GLYAT in these two species to broaden our current understanding on the diversity of GLYAT in primates. A liver of a chacma baboon was used to extract total RNA. Complementary DNA (cDNA) was synthesised using an oligo (dT) primer. An open reading frame (ORF) encoding GLYAT of the chacma baboon was amplified with a PCR (polymerase chain reaction) using primers designed from a human GLYAT transcript. The PCR product containing an ORF encoding GLYAT of the chacma baboon was cloned, sequenced and expressed. The recombinant GLYAT of the chacma baboon expressed well in bacteria, but was insoluble and did not have enzyme activity. A crude cytoplasmic extract was prepared from the liver of a chacma baboon. The objective was to compare enzyme activity between the native and recombinant GLYAT. The prepared liver extract from the chacma baboon was assayed for enzyme activity and compared to the activity in a liver extract from bovine, previously prepared by Ms M Snyders. Both the chacma baboon and bovine liver extracts had GLYAT enzyme activity. To obtain sequence information on vervet monkey GLYAT, leukocytes were isolated from blood obtained from a living vervet monkey. A human GLYAT gene sequence was used as a reference DNA sequence in the design of PCR primers that were used to amplify the exons of GLYAT of the vervet monkey. All six GLYAT exons were individually amplified and PCR products were sequenced. The sequences were combined to reconstruct an ORF encoding GLYAT of the vervet monkey. The ORFs coding the GLYAT of both chacma baboon and vervet monkey were found to be 888 bp long (excluding stop codon) and encoded a protein of 296 amino acids. A fragment of 1256 bp of the chacma baboon GLYAT transcript was sequenced. The two GLYAT ORF sequences were translated to amino acid sequences and aligned to that of GLYAT of primates obtained from the Ensembl sequence database. The GLYAT amino acid sequences of the chacma baboon, vervet monkey and rhesus monkey formed a related group, distinct from other primates. The chacma baboon and vervet monkey sequences were 99 % identical to the rhesus monkey sequence and 92.6 % identical to the human sequence. There were 4 new variations introduced by GLYAT amino acid sequences from the chacma baboon and the vervet monkey. The vervet monkey introduced an isoleucine in place of a valine at position 32 and an arginine in place of a histidine or glutamine at position 224. The chacma baboon introduced a tyrosine in place of isoleucine at position 201 and an arginine in place of histidine or glutamine at position 240. The knowledge generated in this project will broaden the understanding of GLYAT diversity relating to GLYAT in primates. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2011

Introduction: Targeted pharmaceuticals for labelling with radio-isotopes for very specific imaging (and possibly later for targeted therapy) play a major role in Theranostics which is currently an important topic in Nuclear Medicine as well as personalised medicine. There was a need for a very specific lung cancer radiopharmaceutical that would specifically be uptaken in integrin 3 expression cells to image patients using a Positron Emission Tomography- Computed Tomography (PET-CT) scanner. Background and problem statement: Cold kits of c (RGDyK)–SCN-Bz-NOTA were kindly donated by Seoul National University (SNU) to help meet Steve Biko Hospital’s need for this type of imaging. These cold kits showed great results internationally in labelling with a 0.1 M 68Ge/68Ga generator (t1/2 of 68Ge and 68Ga are 270.8 days and 67.6 min, respectively). However the same cold kits failed to show reproducible radiolabeling with the 0.6 M generator manufactured under cGMP conditions at iThemba LABS, Cape Town and distributed by IDB Holland, the Netherlands. Materials and methods: There was therefore a need for producing an in-house NOTA-RGD kit that would enable production of clinical 68Ga-NOTA-RGD in high yields from the IDB Holland/iThemba LABS generator. Quality control included ITLC in citric acid to observe labelling efficiency as well as in sodium carbonate to evaluate colloid formation. HPLC was also performed at iThemba LABS as well as Necsa (South African Nuclear Energy Corporation). RGD was obtained from Futurechem, Korea. Kit mass integrity was determined by testing labelling efficiency of 10, 30 and 60 μg of RGD per cold kit. The RGD was buffered with sodium acetate trihydrate. The original kits were dried in a desiccator and in later studies only freeze dried. Manual labelling was also tested. The radiolabelled in-house kit’s ex vivo biodistribution in healthy versus tumour mice were examined by obtaining xenografts. The normal biodistribution was investigated in three vervet monkeys by doing PET-CT scans on a Siemens Biograph TP 40 slice scanner. Results: Cold kit formulation radiolabeling and purification methods were established successfully and SOPs (standard operating procedures) created. HPLC results showed highest radiochemical purity in 60 μg cold kit vials. 68Ga-NOTA-RGD showed increased uptake in tumours of tumour bearing mouse. The cold kit also showed normal distribution according to literature with fast blood clearance and excretion through kidneys into urine, therefore making it a suitable radiopharmaceutical for clinical studies. Conclusion: The in-house prepared cold kit with a 4 month shelf-life was successfully tested in mice and monkeys. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Introduction: Targeted pharmaceuticals for labelling with radio-isotopes for very specific imaging (and possibly later for targeted therapy) play a major role in Theranostics which is currently an important topic in Nuclear Medicine as well as personalised medicine. There was a need for a very specific lung cancer radiopharmaceutical that would specifically be uptaken in integrin 3 expression cells to image patients using a Positron Emission Tomography- Computed Tomography (PET-CT) scanner. Background and problem statement: Cold kits of c (RGDyK)–SCN-Bz-NOTA were kindly donated by Seoul National University (SNU) to help meet Steve Biko Hospital’s need for this type of imaging. These cold kits showed great results internationally in labelling with a 0.1 M 68Ge/68Ga generator (t1/2 of 68Ge and 68Ga are 270.8 days and 67.6 min, respectively). However the same cold kits failed to show reproducible radiolabeling with the 0.6 M generator manufactured under cGMP conditions at iThemba LABS, Cape Town and distributed by IDB Holland, the Netherlands. Materials and methods: There was therefore a need for producing an in-house NOTA-RGD kit that would enable production of clinical 68Ga-NOTA-RGD in high yields from the IDB Holland/iThemba LABS generator. Quality control included ITLC in citric acid to observe labelling efficiency as well as in sodium carbonate to evaluate colloid formation. HPLC was also performed at iThemba LABS as well as Necsa (South African Nuclear Energy Corporation). RGD was obtained from Futurechem, Korea. Kit mass integrity was determined by testing labelling efficiency of 10, 30 and 60 μg of RGD per cold kit. The RGD was buffered with sodium acetate trihydrate. The original kits were dried in a desiccator and in later studies only freeze dried. Manual labelling was also tested. The radiolabelled in-house kit’s ex vivo biodistribution in healthy versus tumour mice were examined by obtaining xenografts. The normal biodistribution was investigated in three vervet monkeys by doing PET-CT scans on a Siemens Biograph TP 40 slice scanner. Results: Cold kit formulation radiolabeling and purification methods were established successfully and SOPs (standard operating procedures) created. HPLC results showed highest radiochemical purity in 60 μg cold kit vials. 68Ga-NOTA-RGD showed increased uptake in tumours of tumour bearing mouse. The cold kit also showed normal distribution according to literature with fast blood clearance and excretion through kidneys into urine, therefore making it a suitable radiopharmaceutical for clinical studies. Conclusion: The in-house prepared cold kit with a 4 month shelf-life was successfully tested in mice and monkeys. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

<p>The vervet monkey, Chlorocebus aethiops, an Old World monkey, has been often used in biomedical research programs (toxicological studies and fertility) because of the inaccessibility of relevant human tissues. Data from nonhuman primates have been a vital component of advances in areas such as infertility, contraception, and other reproductive processes because of the phylogenetic closeness of the primates to humans. The aims and objectives of the study were 1) to describe the gross morphology, histology and ultrastructure of the male reproductive system, 2) to describe and compare the processes of spermatogenesis and spermiogenesis of the vervet monkey to humans and other nonhuman primates, and 3) to evaluate the vervet monkey as a possible experimental model for future human reproductive studies.</p> <p>Twenty-nine adult male vervet monkeys, aged between 5 and 11 years, were used. Gross morphological features of different organs of the reproductive tract were recorded. Light and electron microscopic techniques, and methacrylate sections were used on selected tissues of the reproductive tract. The results showed that the vervet monkey has a male&nbsp / reproductive system similar to many non-human primates studied and man. The epididymis was distinctively subdivided into the caput, corpus, and the caudal regions. No significant differences were observed on the epithelial height of these three regions. Four cell types, apical, principal, and basal cells, and the intraepithelial lymphocytes were observed. The basal cell distribution showed significant differences among three regions of the epididymis (P &le / 0.01). There were numerous phagocytic vesicles found in three regions of the epididymis. The Sertoli cells showed perforated sleeve-like processes which encased elongated and mature spermatids ready for spermiation. The nuclei of the Sertoli cells were found to be multilobed (4 to 5) compared to the less lobular nuclei of the human Sertoli cells (2 to 3). The Leydig cells showed typical features of steroidogenic cells with abundant smooth endoplasmic reticulum, numerous large mitochondria, and few rough endoplasmic reticulum.</p> <p>It was concluded that the gross morphology and structure of the reproductive tract of the vervet monkey has many similarities to humans and other mammals. Secondly, the organization of spermatogenesis is similar to that found in humans, and is commonly known as a helical arrangement. The results further suggest that the vervet monkey could be regarded as suitable model for human male reproductive studies.</p> <p>&nbsp / </p>

<p>The vervet monkey, Chlorocebus aethiops, an Old World monkey, has been often used in biomedical research programs (toxicological studies and fertility) because of the inaccessibility of relevant human tissues. Data from nonhuman primates have been a vital component of advances in areas such as infertility, contraception, and other reproductive processes because of the phylogenetic closeness of the primates to humans. The aims and objectives of the study were 1) to describe the gross morphology, histology and ultrastructure of the male reproductive system, 2) to describe and compare the processes of spermatogenesis and spermiogenesis of the vervet monkey to humans and other nonhuman primates, and 3) to evaluate the vervet monkey as a possible experimental model for future human reproductive studies.</p> <p>Twenty-nine adult male vervet monkeys, aged between 5 and 11 years, were used. Gross morphological features of different organs of the reproductive tract were recorded. Light and electron microscopic techniques, and methacrylate sections were used on selected tissues of the reproductive tract. The results showed that the vervet monkey has a male&nbsp / reproductive system similar to many non-human primates studied and man. The epididymis was distinctively subdivided into the caput, corpus, and the caudal regions. No significant differences were observed on the epithelial height of these three regions. Four cell types, apical, principal, and basal cells, and the intraepithelial lymphocytes were observed. The basal cell distribution showed significant differences among three regions of the epididymis (P &le / 0.01). There were numerous phagocytic vesicles found in three regions of the epididymis. The Sertoli cells showed perforated sleeve-like processes which encased elongated and mature spermatids ready for spermiation. The nuclei of the Sertoli cells were found to be multilobed (4 to 5) compared to the less lobular nuclei of the human Sertoli cells (2 to 3). The Leydig cells showed typical features of steroidogenic cells with abundant smooth endoplasmic reticulum, numerous large mitochondria, and few rough endoplasmic reticulum.</p> <p>It was concluded that the gross morphology and structure of the reproductive tract of the vervet monkey has many similarities to humans and other mammals. Secondly, the organization of spermatogenesis is similar to that found in humans, and is commonly known as a helical arrangement. The results further suggest that the vervet monkey could be regarded as suitable model for human male reproductive studies.</p> <p>&nbsp / </p>

Researchers in the field of social learning have suggested that certain biases may exist in whom animals learn from, creating a non-random flow of social information. A number of potential biases have been proposed based upon theoretical models, including biases to copy more dominant individuals or individuals who receive the best payoff from their behaviour, but empirical evidence for these biases is lacking. This thesis presents the first examination of dominance-based bias in a wild population of primates and of a payoff-based bias in captive capuchins. In two field experiments, dominant and low-ranking females from each of three wild groups of vervet monkeys (Chlorocebus aethiops pygerythrus) in KwaZulu-Natal, South Africa were trained to demonstrate contrasting behaviours to their group before observers were provided with a choice between the two modelled preferences. No evidence was found for a consistent bias to copy the behaviour of the dominant female in either experiment. Instead, in both experiments, a preference for one behaviour emerged, regardless of model rank. In the latter experiment, higher-ranking females were significantly more likely to match the dominant model's action than were low-ranking females. The low-ranking models were more likely than their high-ranking counterparts to switch behaviours, despite their trained behaviour continuing to be productive. An analyses of the observations revealed that observers were biased towards attending to kin, and observer age appeared to influence access to the dominant models, but no overall preference to attend to the dominant female was found. Together these findings indicate that kinship, sex, age and preferences for specific behaviours are more important factors than model rank in vervet monkey social learning. Finally, I examined whether captive tufted capuchins (Sapajus apella) utilized a payoff-based social learning bias in their foraging decisions. Subjects did not utilize public information when choosing between demonstrated resource-rich and resource-poor sites, suggesting that the social learning abilities of capuchins may not extend to determining the profitability of feeding sites, although limitations of the study are discussed.

Philosophiae Doctor - PhD / The vervet monkey, Chlorocebus aethiops, an Old World monkey, has been often used in biomedical research programs (toxicological studies and fertility) because of the inaccessibility of relevant human tissues. Data from nonhuman primates have been a vital component of advances in areas such as infertility, contraception, and other reproductive processes because of the phylogenetic closeness of the primates to humans. The aims and objectives of the study were 1) to describe the gross morphology, histology and ultrastructure of the male reproductive system, 2) to describe and compare the processes of spermatogenesis and spermiogenesis of the vervet monkey to humans and other nonhuman primates, and 3) to evaluate the vervet monkey as a possible experimental model for future human reproductive studies. Twenty-nine adult male vervet monkeys, aged between 5 and 11 years, were used. Gross morphological features of different organs of the reproductive tract were recorded. Light and electron microscopic techniques, and methacrylate sections were used on selected tissues of the reproductive tract. The results showed that the vervet monkey has a male reproductive system similar to many non-human primates studied and man. The epididymis was distinctively subdivided into the caput, corpus, and the caudal regions. No significant differences were observed on the epithelial height of these three regions. Four cell types, apical, principal, and basal cells, and the intraepithelial lymphocytes were observed. The basal cell distribution showed significant differences among three regions of the epididymis (P ≤ 0.01). There were numerous phagocytic vesicles found in three regions of the epididymis. The Sertoli cells showed perforated sleeve-like processes which encased elongated and mature spermatids ready for spermiation. The nuclei of the Sertoli cells were found to be multilobed (4 to 5) compared to the less lobular nuclei of the human Sertoli cells (2 to 3). The Leydig cells showed typical features of steroidogenic cells with abundant smooth endoplasmic reticulum, numerous large mitochondria, and few rough endoplasmic reticulum. It was concluded that the gross morphology and structure of the reproductive tract of the vervet monkey has many similarities to humans and other mammals. Secondly, the organization of spermatogenesis is similar to that found in humans, and is commonly known as a helical arrangement. The results further suggest that the vervet monkey could be regarded as suitable model for human male reproductive studies

Philosophiae Doctor - PhD / Introduction: Plant extracts and herbal preparations are often marketed as natural and safe alternatives to conventional medicines for the prevention and treatment of a variety of ailments, without proof of efficacy and safety. Cardiovascular, hematopoetic, hepatic and renal impairment resulting from the use of conventional drugs is widely acknowledged. However, there is less awareness of the potential toxicity of herbal preparations and other botanicals, many of which are widely perceived by the public as being effective and harmless, and are commonly used for self medication without supervision. In addition, potential interactions between herbal medicines and conventional drugs may compromise with patient management. In the safety evaluation of most substances, non human primates are preferred to rodent species for preclinical animal safety studies, because of their biological similarity to humans. They are regarded to be the best metabolic models for humans in a broad range of investigations. Additionally, a disadvantage of using small animal species in toxicological testing is that they require higher doses of drugs and more frequent administrations than in larger species. In light of these considerations, vervet monkeys are used here to investigate toxicity of a plant-derived triterpene, oleanolic acid. The focus is to determine effects of different concentrations of this triterpene on the cardiovascular, hematopoetic, hepatic and renal systems. Materials and methods: 12 male vervet monkeys used in this study were equally divided into four groups, i.e. three treatment groups (4, 10 and 25 mg/kg bodyweight), and one control group. Each individual in a treatment group received a specified concentration of oleanolic acid in food for 16 weeks. Monkeys in the control group received the vehicle (food) alone. Bodyweight, body temperature, respiratory rate, heart rate, systolic pressure, diastolic pressure, and mean arterial pressure were recorded from ketamine-anaethetized monkeys at baseline and every second week until week 16. In addition, blood samples were collected at baseline and every fourth week for clinical biochemistry indicators (serum electrolytes, enzymes, proteins, lipids, nitrogenous compounds, bilirubins and glucose) and hematological tests (red cell count and its indices, hemoglobin, haematocrit, white blood cell and differential count and platelet count). Results: No animal showed deviation from their normal behavioral patterns, food and water intake, was in poor health or died during and after completion of the study. The average bodyweights were not statistically significantly different between controls and the treated groups. The biphasic changes in the average body temperature of treated monkeys were similar to those seen in the control group during the first eight weeks of the study. No statistically significant differences were found in body temperature determinations between controls and the treated groups. Fluctuations observed in the respiratory rates of the treated monkeys were not statistically significantly different from that of the control group. Although not statistically significantly different from the controls, the systolic, diastolic and mean arterial pressures in the group treated with 25 mg/kg oleanolic acid were lower at week 16 compared to baseline, while those of the groups treated with 4 and 10 mg/kg oleanolic acid were relatively unchanged. Except for a reduction in systolic pressure of the control group, other blood pressure parameters were stable. Heart rates in the treated groups were not statistically significantly different from those in the controls. In all groups, except the control, high density lipoprotein concentrations were higher at week 16 compared to baseline. Fluctuations in low-density lipoprotein and total cholesterol concentrations were similar between controls and the treated groups. The triglycerides were lower at week 16 compared to baseline for all four groups. Upward trends from baseline to the end of the study were observed in creatine kinase concentrations of the controls and the groups that received 4 and 25 mg/kg. Concentrations of this enzyme were unchanged in the group that received 10 mg/kg oleanolic acid between baseline and the end of the study. No statistically significant differences were found with cholesterol, triglyceride and creatine kinase concentrations between treated groups and the controls. Serum concentrations of aspartate aminotransferase were unchanged in the controls and the groups treated with 4 and 10 mg/kg oleanolic acid, but changes in this parameter over time were statistically significantly different (P = 0.0452) from the controls in the group that received 25 mg/kg oleanolic acid. Despite wide fluctuations in the alanine aminotransferase concentrations in the groups that received 4 and 25 mg/kg oleanolic acid, no statistically significant differences were found with any of the treated groups compared to the controls. No statistically significantly different changes were seen in alkaline phosphatase activities between controls and the treated groups. Reductions in gamma-glutamyl transferase activities in the groups that received 4 and 25 mg/kg oleanolic acid were not statistically significantly different from concentrations of this enzyme in the controls. In addition, no statistically significant differences were evident between controls and the group that received 10 mg/kg oleanolic acid. There were no statistically significantly different changes in the total and conjugated bilirubin and glucose concentrations between controls and the treated groups. Fluctuations over time in the serum albumin and globulin concentrations were similar between treated groups and the controls, whereas total protein concentrations were relatively constant. Consequently, no statistically significant differences were found between controls and the treated groups. Wide fluctuations were observed in the creatinine concentrations of the groups that received 4 mg/kg oleanolic acid, while no such changes were encountered in the controls and the group that received 10 and 25 mg/kg oleanolic acid. Serum urea concentrations increased in all groups over time, except for the group that received 10 mg/kg oleanolic acid. Both urea and creatinine concentrations in the treated groups were not statistically significantly different from concentrations in the controls. Serum concentrations of sodium, chloride, potassium, calcium and magnesium and phosphate in the treated groups were not statistically significantly different from these electrolyte concentrations in the controls. Decline in red cell and hemoglobin concentrations of the controls and the group that received 25 mg/kg oleanolic acid were not statistically significantly different between these groups. In addition, no statistical significant differences were found in red cell and hemoglobin concentrations between controls and the groups that received 4 and 10 mg/kg oleanolic acid. Controls and the treated groups showed upward trends in haematocrit concentrations. Mean corpuscular volumes were statistically significantly increased; P = 0.0027 (4 mg/kg), P = 0.0010 (10 mg/kg), and P = 0.0022 (25 mg/kg), while mean corpuscular hemoglobin concentrations were statistically significantly reduced; P = 0.0017 (4 mg/kg), P = 0.0004 (10 mg/kg), P = 0.0002 (25 mg/kg) in the treated groups as compared to the controls. No statistically significant differences were evident in the concentrations of mean corpuscular hemoglobin between controls and the treated groups. White blood cell counts of the treated groups were not statistically significantly different from those of the controls throughout the study period. No statistically significant differences were found in the differential white cells and platelet counts between treated groups and the controls. Discussions: The results of this study showed that administration of oleanolic acid had no effects on the general wellbeing, bodyweights, body temperature, respiratory and heart rates, and blood pressure of vervet monkeys. A statistically significant increase in the aspartate aminotransferase activity of the group treated with 25 mg/kg oleanolic acid, together with the increase in the alanine aminotransferase levels during the same time period, might indicate oleanolic acid-induced hypersensitivity, and accordingly hepatocellular alteration. However, since serum concentrations of these enzymes returned to baseline levels, as well as the absence of variations over time in other parameters of the hepatic function, particularly alkaline phosphatase activity, it is likely that there was no underlying subacute liver disease. Serum renal function parameters also appeared to be within normal physiological limits. No pronounced changes were observed in the hematological parameters of monkeys that received oleanolic acid. Conclusion: This study's results, suggest that oleanolic acid does not produce cumulative liver enzyme alterations, and has no detrimental effects on the renal, hematopoetic and cardiovascular systems of vervet monkeys.

Magister Pharmaceuticae - MPharm / Cardiovascular diseases (CVDs) such as ischaemic heart diseases, heart failure and stroke remain a major cause of death globally. Various deep-rooted factors influence CVD development; these include but are not limited to elevated blood lipids, high blood pressure, obesity and diabetes. A considerable number of proteins are involved directly and indirectly in the transport, maintenance and elimination of plasma lipids, including high and low-density lipoprotein cholesterol (HDL-C and LDL-C). There are several mechanisms involved in the removal of LDL particles from systemic circulation. One such mechanism is associated with the gene that encodes proprotein convertase subtilisin/kexin type 9 (PCSK9), which has become an exciting therapeutic target for the reduction of residual risk of CVDs. Currently, statins are the mainstay treatment to reduce LDL-C, and a need exists to further develop more effective LDL-C-lowering drugs that might supplement statins. This study was aimed at contributing to the generation of knowledge regarding the effect of niacin in reducing LDL levels through PCSK9 interaction. The aims/objectives of this study were achieved by utilizing two approaches, which included animal intervention with niacin followed by genetic screening of five prioritized genes involved in cholesterol synthesis and regulation. For animal intervention, 16 vervet monkeys were divided into two groups of eight animals consisting of a control and an experimental (niacin) group. The control group was given a normal standard diet of pre-cooked maize meal throughout the study, while the experimental group received the same diet supplemented with 100 mg/kg of niacin (SR) for 12 weeks. During the niacin intervention, blood was collected at baseline, every four weeks during the treatment period and the end of the washout period. The collected blood was used for biochemical analysis (total cholesterol, triglycerides, LDL-C, and HDL-C) and downstream genetic applications. The second phase included the screening of PCSK9, LDLR, SREBP-2, CETP and APOB-100 using genotyping and gene expression. Niacin administration produced statistically significant increases in plasma HDL-C at fourtime points (T1, T2, T3 and T4), which resulted in an overall increase in plasma HDL-C. Additionally, niacin administration resulted in a slight reduction in LDL-C and total cholesterol levels. Furthermore, the genotyping analysis revealed 13 sequence variants identified in PCSK9, LDLR, SREBP-2, CETP and APOB-100 genes. Five of these variants were predicted to be disease-causing and correlated with gene expression patterns. Three identified PCSK9 variants (H177N, R148S, G635G) were categorized as LOF mutations, and this was supported by a decline in gene expression in animals harbouring these variants. The LDLR also had LOF variants that were the reason for its decreased mRNA expression. Additionally, SREBP-2 proved to be a key mediator of cholesterol pathways. Therefore, the findings of the study conclusively suggest that niacin does increase HDL-C and decrease LDL-C and total cholesterol. Moreover, an interaction between niacin administration and PCSK9 was observed which resulted in decreased gene expression.

The movements of two vervet monkey troops were studied to determine whether they optimize their rate of food intake in relation to seasonal energy availability. The effect of variation in habitat structure on the troops’ foraging strategies while utilizing temporally and spatially distributed resources was determined. Troop home range boundaries were delineated, the various plant communities and species utilised by the troops identified and classified, and variations in home range and vegetation structure were reported. The diets of the troops were determined and compared. Effects of coexistence on competition were assessed. Vervet food trees were randomly selected, marked and seasonal phenological data collected. Samples of food items constituting the two troops diets were collected for energy analysis. Using geostatistical interpolation techniques, monthly energy values were extrapolated onto home range grids for the two vervet monkey troops. Grids were stored as database files that were interrogated through GIS simulation models. Using the stochastic processes inherent in Markov chain theory, a series of non-returning random walks were simulated for comparison to original routes taken by the two troops. Results from comparisons of home range energy, day range lengths and areas, shortest route energy to actual route energy, time spent in high energy areas, and energy utilisation from actual and randomly generated routes indicated that the two troops optimize resource energy available to them by adopting flexible foraging strategies. In environments where temporal and spatial variations in habitat structure affect the distribution of resources, it is essential that animals develop optimal foraging strategies to survive. For the two troops investigated, foraging strategies fluctuate between being time minimizers in more heterogeneous environments where resources are abundant, and energy maximisers in homogeneous environments where resources are constrained by low diversity and seasonality. / Environmental Sciences (Department) / D.Litt et Phil (Environmental Management)