A physiologically based pharmacokinetic model to characterise the association between CYP2B6 polymorphisms and efavirenz pharmacokinetics in pregnancy

A research report submitted to the faculty of health science, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of MSC MED pharmaceutical affairsMT201

Comparing Different European Income Tax Policies Making Work Pay

Raising the participation at the lower end of the labour market abstract is hindered by the high burden of taxation. Therefore, recently, in some European countries serious efforts have been made to make work pay. In this paper an overview of these current efforts is given. With the exception of Germany there seems to be a consistent policy of making work pay through the introduction of a substantial in-work tax credit and a decrease of the basic rate. In some countries due to distributing aspects the in-work tax credit is targeted to families with children. Moreover, two countries have a back to work allowance or premium for benefit claimants. Given the limited resources for future tax reforms, increase of in-work credits seem appropriate for further progress in making work pay

Trace element analysis in precious metals using time resolved emission spectroscopy

Please read the abstract in the section 00front of this documentDissertation (MSc (Applied Sciences:Chemistry))--University of Pretoria, 2005.Chemistryunrestricte

Efficient production of the Nylon 12 monomer ω-aminododecanoic acid methyl ester from renewable dodecanoic acid methyl ester with engineered Escherichia coli

The expansion of microbial substrate and product scopes will be an important brick promoting future bioeconomy. In this study, an orthogonal pathway running in parallel to native metabolism and converting renewable dodecanoic acid methyl ester (DAME) via terminal alcohol and aldehyde to 12-aminododecanoic acid methyl ester (ADAME), a building block for the high-performance polymer Nylon 12, was engineered in Escherichia coli and optimized regarding substrate uptake, substrate requirements, host strain choice, flux, and product yield. Efficient DAME uptake was achieved by means of the hydrophobic outer membrane porin AlkL increasing maximum oxygenation and transamination activities 8.3 and 7.6-fold, respectively. An optimized coupling to the pyruvate node via a heterologous alanine dehydrogenase enabled efficient intracellular L-alanine supply, a prerequisite for self-sufficient whole-cell transaminase catalysis. Finally, the introduction of a respiratory chain-linked alcohol dehydrogenase enabled an increase in pathway flux, the minimization of undesired overoxidation to the respective carboxylic acid, and thus the efficient formation of ADAME as main product. The completely synthetic orthogonal pathway presented in this study sets the stage for Nylon 12 production from renewables. Its effective operation achieved via fine tuning the connectivity to native cell functionalities emphasizes the potential of this concept to expand microbial substrate and product scopes

Isolation of isoprene degrading bacteria from soils, development of isoA gene probes and identification of the active isoprene degrading soil community using DNA-stable isotope probing

Emissions of biogenic volatile organic compounds (bVOCs), are an important element in the global carbon cycle, accounting for a significant proportion of fixed carbon. They contribute directly and indirectly to global warming and climate change and have a major effect on atmospheric chemistry. Plants emit isoprene to the atmosphere in similar quantities to emissions of methane from all sources and each account for approximately one third of total VOCs. Although methanotrophs, capable of growth on methane, have been intensively studied, we know little of isoprene biodegradation. Here we report the isolation of two isoprene-degrading strains from the terrestrial environment and describe the design and testing of PCR primers targeting isoA, the gene encoding the active-site component of the conserved isoprene monooxygenase, which are capable of retrieving isoA sequences from isoprene-enriched environmental samples. Stable isotope probing experiments, using biosynthesized 13C-labelled isoprene, identified the active isoprene-degrading bacteria in soil. This study identifies novel isoprene-degrading strains using both culture-dependent and, for the first time, culture-independent methods and provides the tools and foundations for continued investigation of the biogeography and molecular ecology of isoprene-degrading bacteria. This article is protected by copyright. All rights reserved

The role of serological testing in the SARS-CoV-2 outbreak

Antibody tests for the novel coronavirus, SARS-CoV2, have been developed both as rapid diagnostic assays and for high-throughput formal serology platforms. Although these tests may be a useful adjunct to a diagnostic strategy, they have a number of limitations. Because of the antibody and viral dynamics of the coronavirus, their sensitivity can be variable, especially at early time points after symptom onset. Additional data are required on the performance of the tests in the South African population, especially with regard to development and persistence of antibody responses and whether antibodies are protective against reinfection. These tests may, however, be useful in guiding the public health response, providing data for research (including seroprevalence surveys and vaccine initiatives) and development of therapeutic strategies

Mutagenesis and expression of methane monooxygenase to alter regioselectivity with aromatic substrates

Soluble methane monooxygenase (sMMO) from methane-oxidising bacteria can oxygenate more than 100 hydrocarbons and is one of the most catalytically versatile biological oxidation catalysts. Expression of recombinant sMMO has to date not been achieved in Escherichia coli and so an alternative expression system must be used to manipulate it genetically. Here we report substantial improvements to the previously described system for mutagenesis of sMMO and expression of recombinant enzymes in a methanotroph (Methylosinus trichosporium OB3b) expression system. This system has been utilised to make a number of new mutants and to engineer sMMO to increase its catalytic precision with a specific substrate whilst increasing activity by up to 6-fold. These results are the first 'proof-of-principle' experiments illustrating the feasibility of developing sMMO-derived catalysts for diverse applications. [Abstract copyright: © FEMS 2017.

Trimethylation of H3K27 during human cerebellar development in relation to medulloblastoma

Medulloblastoma (MB), the most common malignant childhood brain tumor, encompasses a collection of four clinically and molecularly distinct tumor subgroups, i.e. WNT, SHH, Group 3 and Group 4. These tumors are believed to originate from precursor cells during cerebellar development. Although the exact etiology of these brain tumors is not yet known, histone modifications are increasingly recognized as key events during cerebellum development and MB tumorigenesis. Recent studies show that key components involved in post-translational modifications of histone H3 lysine 27 (H3K27) are commonly deregulated in MB. In this descriptive study, we have investigated the trimethylation status of H3K27, as well as the expression of the H3K27 methylase EZH2 and demethylases KDM6A and KDM6B, during human cerebellum development in relation to MB. H3K27 Trimethylation status differed between the MB subgroups. Moreover, trimethylation of H3K27 and expression of its modifiers EZH2, KDM6A and KDM6B were detected in a spatio-temporal manner during development of the human cerebellum, with consistent high occurrence in the four proliferative zones, which are believed to harbor the precursor cells of the different MB subgroups. Our results suggest that H3K27 trimethylation in MB is deregulated by EZH2, KDM6A and KDM6B. Moreover, we provide evidence that during development of the human cerebellum H3K27me3 and its regulators are expressed in a spatio-temporal manner