Ben Marais (1909-1999): The influences on and heritage of a South African Prophet during two periods of transformation

University of Pretoria / Dissertation / Department of Church History and Church Policy / Advised by Prof J W HofmeyrThis thesis in Church History presents a biographic study on the life of Ben Marais against the political and ecclesiastic background of South Africa of the 20th century. The significance of Ben Marais’ life is approached through his correspondence with the secretaries of the World Council of Churches during the 1960s and 1970s. The letters, pertaining to the World Council of Churches financial and moral support for the organisations fighting against Apartheid, reflect on Ben Marais’ involvement with the World Council and his particular concerns. Through a study on the life of Ben Marais insight can be gained into the thinking of the leadership of the NG Kerk. The study presents Ben Marais as a prophet who challenged the then popular tendencies in the NG Kerk theology on policy justification and on the relation between religion and nationalism. The central question in this study asks, what led an ordinary man, of humble background, to the insights he reflected, and guided him through times of transparent opposition to maintain his belief in what was right and just? What was the essence of his theology and understanding of the South African problem? To what extent could the church leaders of the present, and the future learn from his example and life, in terms of the tribulations faced, different schools of thought, and sentiments, both nationalistic and spiritual? The study then wishes to test the following hypothesis: Ben Marais can be considered as one of the steadfast and humble prophets of the church in Southern Africa during the 20th century, who serves as an example of Christian Brotherhood, regardless of the perplexities, for present and future generations on relations between the affairs of faith, state and society. The thesis presents a broader introduction on Church Historiography. Ben Marais’ own historiographical reflection is considered. The approaches to history are summarised as background to the periodisation model adopted by the study. The study wishes to work with a thematic model set against a chronological framework. Sensitivity to geographical concerns is also expressed. Afrikaner Nationalism is not seen in isolation, but in relation to African, English and Indian Nationalism

Transposable Elements, Inflammation, and Neurological Disease.

Transposable Elements (TE) are mobile DNA elements that can replicate and insert themselves into different locations within the host genome. Their propensity to self-propagate has a myriad of consequences and yet their biological significance is not well-understood. Indeed, retrotransposons have evaded evolutionary attempts at repression and may contribute to somatic mosaicism. Retrotransposons are emerging as potent regulatory elements within the human genome. In the diseased state, there is mounting evidence that endogenous retroelements play a role in etiopathogenesis of inflammatory diseases, with a disposition for both autoimmune and neurological disorders. We postulate that active mobile genetic elements contribute more to human disease pathogenesis than previously thought

Targeting endogenous retroviruses using a novel adenoviral vaccine technology

Human Endogenous Retroviruses (HERVs) are promising cancer vaccine targets as they are reactivated in cancers while being silent in healthy tissues. Around 8-9% of our genome is made up of HERVs and reactivation of HERVs, especially HERV-K, have been implicated in tumorigenesis via oncogenic signaling and immune evasion. As one of the means for cancer immune evasion, HERVs utilize an Immune Suppressive Domain (ISD) located in their envelope protein (Env). Here, our cancer vaccine strategy was to evaluate if adenoviral vaccines encoding a virus-like particle immunogen design including Gag for particle formation and an ISD mutated Env protein (ISDmut) as a surface target, could induce potent and efficacious immune responses. For this purpose, we used the adenoviral vectors hAd19a and hAd5. Please click Download on the upper right corner to see the full abstract

Functional characterization of two newly identified Human Endogenous Retrovirus coding envelope genes

A recent in silico search for coding sequences of retroviral origin present in the human genome has unraveled two new envelope genes that add to the 16 genes previously identified. A systematic search among the latter for a fusogenic activity had led to the identification of two bona fide genes, named syncytin-1 and syncytin-2, most probably co-opted by primate genomes for a placental function related to the formation of the syncytiotrophoblast by cell-cell fusion. Here, we show that one of the newly identified envelope gene, named envP(b), is fusogenic in an ex vivo assay, but that its expression – as quantified by real-time RT-PCR on a large panel of human tissues – is ubiquitous, albeit with a rather low value in most tissues. Conversely, the second envelope gene, named envV, discloses a placenta-specific expression, but is not fusogenic in any of the cells tested. Altogether, these results suggest that at least one of these env genes may play a role in placentation, but most probably through a process different from that of the two previously identified syncytins

Die Nederduitsch Hervormde Kerk van Afrika as volkskerk: Oorsig en herbesinning

The Nederduitsch Hervormde Kerk van Afrika as “volkskerk”: Overview and evaluationThe Church Order of the Nederduitsch Hervormde Kerk van Afrika (NHKA) states in Ordinance 4 that the NHKA is a “volkskerk”, meaning a Church that is ethnically based and focused on the ministry to Afrikaans speaking people. This article examines the history of the relationship between NHKA and Afrikaners that prevailed since the early 19th century. It argues that the establishment of separate and ethnically based churches in South Africa was, initially, the result of a specific understanding of Afrikaner nationalism and liberty. Only after the Second World War, due to criticism levelled at separate development and separate churches by the ecumenical movement, it was based on theological reflection. This article concludes that the term “volkskerk” has become theologically obsolete as well as practically unusable

Dogmatiek en Christelike Etiek binne die Fakulteit Teologie (Afd A) van die Universiteit van Pretoria

Dogmatics and Christian Ethics within the Faculty of Theology (Sec A) at the University of PretoriaThis article explores the history of the Department of Dogmatics and Christian Ethics within the Faculty of Theology. The focus is on two specific lines in this history,namely the period which ended in 1952 and the period from 1952 onwards. Attention is given to the thoughts of P J Muller, J H J A Greyvenstein, S P Engelbrecht, H P Wolmarans and B J Engelbrecht, and their influence on the study of Dogmatics and Ethics in the Department. The article concludes with a vision for the future of the Department at the University of Pretoria and it highlights the importance of theological research for the doctrine and life of the Church

Nitrogen regulation of protein–protein interactions and transcript levels of GlnK PII regulator and AmtB ammonium transporter homologs in Archaea

Gene homologs of GlnK PII regulators and AmtB-type ammonium transporters are often paired on prokaryotic genomes, suggesting these proteins share an ancient functional relationship. Here, we demonstrate for the first time in Archaea that GlnK associates with AmtB in membrane fractions after ammonium shock, thus, providing a further insight into GlnK-AmtB as an ancient nitrogen sensor pair. For this work, Haloferax mediterranei was advanced for study through the generation of a pyrE2-based counterselection system that was used for targeted gene deletion and expression of Flag-tagged proteins from their native promoters. AmtB1-Flag was detected in membrane fractions of cells grown on nitrate and was found to coimmunoprecipitate with GlnK after ammonium shock. Thus, in analogy to bacteria, the archaeal GlnK PII may block the AmtB1 ammonium transporter under nitrogen-rich conditions. In addition to this regulated protein–protein interaction, the archaeal amtB-glnK gene pairs were found to be highly regulated by nitrogen availability with transcript levels high under conditions of nitrogen limitation and low during nitrogen excess. While transcript levels of glnK-amtB are similarly regulated by nitrogen availability in bacteria, transcriptional regulators of the bacterial glnK promoter including activation by the two-component signal transduction proteins NtrC (GlnG, NRI) and NtrB (GlnL, NRII) and sigma factor σN (σ54) are not conserved in archaea suggesting a novel mechanism of transcriptional control

Comprehensive search for intra- and inter-specific sequence polymorphisms among coding envelope genes of retroviral origin found in the human genome: genes and pseudogenes

BACKGROUND: The human genome carries a high load of proviral-like sequences, called Human Endogenous Retroviruses (HERVs), which are the genomic traces of ancient infections by active retroviruses. These elements are in most cases defective, but open reading frames can still be found for the retroviral envelope gene, with sixteen such genes identified so far. Several of them are conserved during primate evolution, having possibly been co-opted by their host for a physiological role. RESULTS: To characterize further their status, we presently sequenced 12 of these genes from a panel of 91 Caucasian individuals. Genomic analyses reveal strong sequence conservation (only two non synonymous Single Nucleotide Polymorphisms [SNPs]) for the two HERV-W and HERV-FRD envelope genes, i.e. for the two genes specifically expressed in the placenta and possibly involved in syncytiotrophoblast formation. We further show – using an ex vivo fusion assay for each allelic form – that none of these SNPs impairs the fusogenic function. The other envelope proteins disclose variable polymorphisms, with the occurrence of a stop codon and/or frameshift for most – but not all – of them. Moreover, the sequence conservation analysis of the orthologous genes that can be found in primates shows that three env genes have been maintained in a fully coding state throughout evolution including envW and envFRD. CONCLUSION: Altogether, the present study strongly suggests that some but not all envelope encoding sequences are bona fide genes. It also provides new tools to elucidate the possible role of endogenous envelope proteins as susceptibility factors in a number of pathologies where HERVs have been suspected to be involved

Restriction by APOBEC3 proteins of endogenous retroviruses with an extracellular life cycle: ex vivo effects and in vivo "traces" on the murine IAPE and human HERV-K elements

<p>Abstract</p> <p>Background</p> <p>APOBEC3 cytosine deaminases have been demonstrated to restrict infectivity of a series of retroviruses, with different efficiencies depending on the retrovirus. In addition, APOBEC3 proteins can severely restrict the intracellular transposition of a series of retroelements with a strictly intracellular life cycle, including the murine IAP and MusD LTR-retrotransposons.</p> <p>Results</p> <p>Here we show that the IAPE element, which is the infectious progenitor of the strictly intracellular IAP elements, and the infectious human endogenous retrovirus HERV-K are restricted by both murine and human APOBEC3 proteins in an <it>ex vivo </it>assay for infectivity, with evidence in most cases of strand-specific G-to-A editing of the proviruses, with the expected signatures. <it>In silico </it>analysis of the naturally occurring genomic copies of the corresponding endogenous elements performed on the mouse and human genomes discloses "traces" of APOBEC3-editing, with the specific signature of the murine APOBEC3 and human APOBEC3G enzymes, respectively, and to a variable extent depending on the family member.</p> <p>Conclusion</p> <p>These results indicate that the IAPE and HERV-K elements, which can only replicate via an extracellular infection cycle, have been restricted at the time of their entry, amplification and integration into their target host genomes by definite APOBEC3 proteins, most probably acting in evolution to limit the mutagenic effect of these endogenized extracellular parasites.</p

Ten-year plateau phase in human immunodeficiency virus induced motor neuron disease upon antiretroviral therapy: a first case from Eastern Africa.

We report an individual with rapidly progressive motor neuron disease (MND), phenotypically compatible with amyotrophic lateral sclerosis (ALS). The patient described in this case report proved positive for human immunodeficiency virus (HIV) and was initiated on antiretroviral therapy (ART). Following ART he clinically stabilised over 10 years and deteriorated again due to noncompliance or ART resistance. HIV infection can give rise to an MND mimic, HIV-ALS. The improvement in response to ART supports the notion that HIV-ALS is a treatable entity also in Africa. This is the first case report of a patient with HIV-ALS and long term follow up in Sub-Saharan Africa. The report raises the suggestion that an additional (retro)virus can play a role in the aetiology of ALS