Pharmacogenomic Research in South Africa: Lessons Learned and Future Opportunities in the Rainbow Nation

South Africa, like many other developing countries, stands to benefit from novel diagnostics and drugs developed by pharmacogenomics guidance due to high prevalence of disease burden in the region. This includes both communicable (e.g., HIV/AIDS and tuberculosis) and non-communicable (e.g., diabetes and cardiovascular) diseases. For example, although only 0.7% of the world’s population lives in South Africa, the country carries 17% of the global HIV/AIDS burden and 5% of the global tuberculosis burden. Nobel Peace Prize Laureate Archbishop Emeritus Desmond Tutu has coined the term Rainbow Nation, referring to a land of wealth in its many diverse peoples and cultures. It is now timely and necessary to reflect on how best to approach new genomics biotechnologies in a manner that carefully considers the public health needs and extant disease burden in the region. The aim of this paper is to document and review the advances in pharmacogenomics in South Africa and importantly, to evaluate the direction that future research should take. Previous research has shown that the populations in South Africa exhibit unique allele frequencies and novel genetic variation in pharmacogenetically relevant genes, often differing from other African and global populations. The high level of genetic diversity, low linkage disequilibrium and the presence of rare variants in these populations question the feasibility of the use of current commercially available genotyping platforms, and may partially account for genotype-phenotype discordance observed in past studies. However, the employment of high throughput technologies for genomic research, within the context of large clinical trials, combined with interdisciplinary studies and appropriate regulatory guidelines, should aid in acceleration of pharmacogenomic discoveries in high priority therapeutic areas in South Africa. Finally, we suggest that projects such as the H3Africa Initiative, the SAHGP and PGENI should play an integral role in the coordination of genomic research in South Africa, but also other African countries, by providing infrastructure and capital to local researchers, as well as providing aid in addressing the computational and statistical bottlenecks encountered at present

Effect of MIN-AD Ruminal Buffer and Roughage Level on Ruminal Metabolism and Extent of Digestion in Steers

Six ruminally and duodenally cannulated steers were used in a metabolism experiment to determine effects of adding a ruminal buffer to diets containing increasing levels of roughage. Steers were fed high-concentrate diets containing 4.5, 9.0, or 13.5% alfalfa hay with or without 1.0% MIN-AD ruminal buffer. There were no differences observed in feed intake, ruminal metabolism, or total tract digestibility due to MIN-AD inclusion in the diet. Average pH increased and time below pH 5.6 and pH 5.3 decreased with increasing alfalfa level. Total tract digestibility decreased with increasing alfalfa level. Addition of MIN-AD to high-concentrate diets did not produce a response similar to increasing the roughage level in the diet

Beef Fatty Acid Profiles from Steers Finished with De-oiled Dry Distillers Grains Plus Solubles vs. a Corn- Based Diet

A total of 128 steers were fed one of two finishing diets: 50% de-oiled dry distillers grains plus solubles (DDGS) or a corn- based control diet. Carcasses (n = 48) were selected to evaluate the effect of diet on the fatty acid profile of strip loin steaks. Th e C15:0, C16:1, C17:0, and C17:1 were greater for beef from steers finished on the corn- based control diet while the C18:1T, C18:2, C20:3ω6, total trans, ω6 and polyunsaturated fatty acids (PUFA) were greater in beef from cattle finished on 50% de-oiled DDGS. These findings confirm that feeding distillers grains plus solubles (be it wet or dry) increases the amount of PUFA’s in meat

Ocean redox structure across the Late Neoproterozoic Oxygenation Event: A nitrogen isotope perspective

International audienceThe end of the Neoproterozoic Era (1000 to 541 Ma) is widely believed to have seen the transition from a dominantly anoxic to an oxygenated deep ocean. This purported redox transition appears to be closely linked temporally with metazoan radiation and extraordinary perturbations to the global carbon cycle. However, the geochemical record of this transition is not straightforward, and individual data sets have been variably interpreted to indicate full oxygenation by the early Ediacaran Period (635 to 541 Ma) and deep ocean anoxia persevering as late as the early Cambrian. Because any change in marine redox structure would have profoundly impacted nitrogen nutrient cycling in the global ocean, the N isotope signature of sedimentary rocks (δ15Nsed) should reflect the Neoproterozoic deep-ocean redox transition. We present new N isotope data from Amazonia, northwest Canada, northeast Svalbard, and South China that span the Cryogenian glaciations (∼750 to 580 Ma). These and previously published data reveal a Nisotope distribution that closely resembles modern marine sediments, with a mode in δ15N close to +4 and range from −4 to +11. No apparent change is seen between the Cryogenian and Ediacarian. Data from earlier Proterozoic samples show a similar distribution, but shifted slightly towards more negative δ15N values and with a wider range. The most parsimonious explanation for the similarity of these Nisotopedistribution is that as in the modern ocean, nitrate (and hence O2) was stable in most of the middle–late Neoproterozoic ocean, and possibly much of Proterozoic Eon. However, nitrate would likely have been depleted in partially restricted basins and oxygen minimum zones (OMZs), which may have been more widespread than in the modern ocean

Effect of Revalor-XR and Revalor-XH on Heifer Performance and Carcass Characteristics

A feedlot study evaluated the effects of 4 implant strategies (Revalor-XR on day 1, Revalor-XH on day 1, Revalor-200 on day 1, and Revalor-200 on day 70) on growth performance and carcass characteristics of feedlot heifers compared to non-implanted heifers fed 198 days. Intake was not impacted by treatments. Implanted cattle had greater carcass-adjusted ADG and lower F:G compared to cattle that received no implant. Implanted treatments had significantly greater HCW, dressing percentages, and lower marbling scores compared to non-implanted cattle. Heifers implanted with Revalor-XR, Revalor-XH, and Revalor-200 on day 70 had larger LM area resulting in lower calculated yield grades compared to Revalor-200 administered on day 1 and control cattle. The response in gain, feed efficiency, and yield grade suggest that Revalor-XR, Revalor-XH, and Revalor-200 implanted on day 70 respond similarly when heifers are fed to similar days

Relationship of Metabolizable Protein Balance, Purine Derivative Excretion, and 3-Methyl Histidine Excretion to Feed Efficiency in Individually Fed Finishing Heifers

Individually fed heifers were used to determine the relationship of 3-methyl histidine, purine derivatives, and metabolizableprotein balance to feed efficiency. Heifers were fed finishing dietsthat were either deficient or sufficient in metabolizable protein. Urine samples were collected and analyzed for early, late, and entire feeding period concentrations of 3-methyl histidine, purine derivatives, and creatinine. Results from this study indicated a negative relationship between feed efficiency and metabolizable protein balance, and no relationship between 3-methyl histidine excretion and feed efficiency, suggesting that protein turnover and microbial protein synthesis are not related to feed efficienc

Relationship of Metabolizable Protein Balance, Purine Derivative Excretion, and 3-Methyl Histidine Excretion to Feed Efficiency in Individually Fed Finishing Heifers

Individually fed heifers were used to determine the relationship of 3-methyl histidine, purine derivatives, and metabolizableprotein balance to feed efficiency. Heifers were fed finishing dietsthat were either deficient or sufficient in metabolizable protein. Urine samples were collected and analyzed for early, late, and entire feeding period concentrations of 3-methyl histidine, purine derivatives, and creatinine. Results from this study indicated a negative relationship between feed efficiency and metabolizable protein balance, and no relationship between 3-methyl histidine excretion and feed efficiency, suggesting that protein turnover and microbial protein synthesis are not related to feed efficienc

The potential use of service-oriented infrastructure framework to enable transparent vertical scalability of cloud computing infrastructure

Cloud computing technology has become familiar to most Internet users. Subsequently, there has been an increased growth in the use of cloud computing, including Infrastructure as a Service (IaaS). To ensure that IaaS can easily meet the growing demand, IaaS providers usually increase the capacity of their facilities in a vertical IaaS increase capability and the capacity for local IaaS amenities such as increasing the number of servers, storage and network bandwidth. However, at the same time, horizontal scalability is sometimes not enough and requires additional strategies to ensure that the large number of IaaS service requests can be met. Therefore, strategies requiring horizontal scalability are more complex than the vertical scalability strategies because they involve the interaction of more than one facility at different service centers. To reduce the complexity of the implementation of the horizontal scalability of the IaaS infrastructures, the use of a technology service oriented infrastructure is recommended to ensure that the interaction between two or more different service centers can be done more simply and easily even though it is likely to involve a wide range of communication technologies and different cloud computing management. This is because the service oriented infrastructure acts as a middle man that translates and processes interactions and protocols of different cloud computing infrastructures without the modification of the complex to ensure horizontal scalability can be run easily and smoothly. This paper presents the potential of using a service-oriented infrastructure framework to enable transparent vertical scalability of cloud computing infrastructures by adapting three projects in this research: SLA@SOI consortium, Open Cloud Computing Interface (OCCI), and OpenStack

Evaluation of Reimplant Window with Revalor-200 ® on Steer Performance and Carcass Characteristics

A feedlot study utilizing 800 crossbred steers (initial BW = 727 ± 55 lb) compared 5 different terminal implant (Revalor-200) times (160, 120, 100, 80, or 40 d prior to harvest) for steers fed 180 days on performance and carcass characteristics. All steers were implanted with Revalor-IS as an initial implant at trial initiation. Carcass-adjusted final BW, ADG, and F:G responded quadratically, with cattle implanted 80 to 120 d prior to harvest being the greatest. However, there was less than a 2% difference in performance between 120 and 80 days on terminal implant. Hot carcass weight responded quadratically, with no difference in fat thickness, rib eye area, marbling score, or calculated yield grade. When solved for the first derivative, all variables were maximized at 87 to 104 days on terminal implant when steers are fed for 180-d