Re-interpretation as transformation. Perspectives and challenges for Old Testament interpretation

This contribution explains that the re-interpretation of theological motifs or ideas leads to transforming theology and religion.  This phenomenon takes place within the corpus and boundaries of the Old Testament. Innerbiblical debate or “later” texts that re-interpret “earlier” texts underscore this process and confirm a transformed theology that is relevant and life-giving for the “new” or “later” context. Because these processes happened within the range of a long history of development of OldTestament literature, the article first discusses important hermeneutical realities or directives for Old Testament interpretation. It then mentions a few approaches to, and challenges of interpreting Old Testament literature. Finally, it briefly portrays how the book of Ruth re-interpreted certain pentateuchal texts as an act of transforming theology

The association among cytochrome P450 3A, progesterone receptor polymorphisms, plasma 17-alpha hydroxyprogesterone caproate concentrations, and spontaneous preterm birth

Background Infants born <37 weeks’ gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children <5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-alpha hydroxyprogesterone caproate reduces preterm birth by 33% in women with history of spontaneous preterm birth. We demonstrated previously that plasma concentrations of 17-alpha hydroxyprogesterone caproate vary widely among pregnant women and that women with 17-alpha hydroxyprogesterone caproate plasma concentrations in the lowest quartile had spontaneous preterm birth rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-alpha hydroxyprogesterone caproate plasma concentrations vary so much is unclear. Predominantly, 17-alpha hydroxyprogesterone caproate is metabolized by CYP3A4 and CYP3A5 enzymes. Objective We sought to: (1) determine the relation between 17-alpha hydroxyprogesterone caproate plasma concentrations and single nucleotide polymorphisms in CYP3A4 and CYP3A5; (2) test the association between progesterone receptor single nucleotide polymorphisms and spontaneous preterm birth; and (3) test whether the association between plasma concentrations of 17-alpha hydroxyprogesterone caproate and spontaneous preterm birth varied by progesterone receptor single nucleotide polymorphisms. Study Design In this secondary analysis, we evaluated genetic polymorphism in 268 pregnant women treated with 17-alpha hydroxyprogesterone caproate, who participated in a placebo-controlled trial to evaluate the benefit of omega-3 supplementation in women with history of spontaneous preterm birth. Trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were measured between 25-28 weeks of gestation after a minimum of 5 injections of 17-alpha hydroxyprogesterone caproate. We extracted DNA from maternal blood samples and genotyped the samples using TaqMan (Applied Biosystems, Foster City, CA) single nucleotide polymorphism genotyping assays for the following single nucleotide polymorphisms: CYP3A4*1B, CYP3A4*1G, CYP3A4*22, and CYP3A5*3; and rs578029, rs471767, rs666553, rs503362, and rs500760 for progesterone receptor. We adjusted for prepregnancy body mass index, race, and treatment group in a multivariable analysis. Differences in the plasma concentrations of 17-alpha hydroxyprogesterone caproate by genotype were evaluated for each CYP single nucleotide polymorphism using general linear models. The association between progesterone receptor single nucleotide polymorphisms and frequency of spontaneous preterm birth was tested using logistic regression. A logistic model also tested interaction between 17-alpha hydroxyprogesterone caproate concentrations with each progesterone receptor single nucleotide polymorphism for the outcome of spontaneous preterm birth. Results The association between CYP single nucleotide polymorphisms *22, *1G, *1B, and *3 and trough plasma concentrations of 17-alpha hydroxyprogesterone caproate was not statistically significant (P =.68,.44,.08, and.44, respectively). In an adjusted logistic regression model, progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 were not associated with the frequency of spontaneous preterm birth (P =.29,.10,.76,.09, and.43, respectively). Low trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were statistically associated with a higher frequency of spontaneous preterm birth (odds ratio, 0.78; 95% confidence ratio, 0.61–0.99; P =.04 for trend across quartiles), however no significant interaction with the progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 was observed (P =.13,.08,.10,.08, and.13, respectively). Conclusion The frequency of recurrent spontaneous preterm birth appears to be associated with trough 17-alpha hydroxyprogesterone caproate plasma concentrations. However, the wide variation in trough 17-alpha hydroxyprogesterone caproate plasma concentrations is not attributable to polymorphisms in CYP3A4 and CYP3A5 genes. Progesterone receptor polymorphisms do not predict efficacy of 17-alpha hydroxyprogesterone caproate. The limitations of this secondary analysis include that we had a relative small sample size (n = 268) and race was self-reported by the patients

Regulatory Architecture of the Neuronal Cacng2/Tarpγ2 Gene Promoter: Multiple Repressive Domains, a Polymorphic Regulatory Short Tandem Repeat, and Bidirectional Organization with Co-regulated lncRNAs

CACNG2 (TARPγ2, Stargazin) is a multi-functional regulator of excitatory neurotransmission and has been implicated in the pathological processes of several brain diseases. Cacng2 function is dependent upon expression level, but currently, little is known about the molecular mechanisms that control expression of this gene. To address this deficit and investigate disease-related gene variants, we have cloned and characterized the rat Cacng2 promoter and have defined three major features: (i) multiple repressive domains that include an array of RE-1 silencing transcription factor (REST) elements, and a calcium regulatory element-binding factor (CaRF) element, (ii) a (poly-GA) short tandem repeat (STR), and (iii) bidirectional organization with expressed lncRNAs. Functional activity of the promoter was demonstrated in transfected neuronal cell lines (HT22 and PC12), but although selective removal of REST and CaRF domains was shown to enhance promoter-driven transcription, the enhanced Cacng2 promoter constructs were still about fivefold weaker than a comparable rat Synapsin-1 promoter sequence. Direct evidence of REST activity at the Cacng2 promoter was obtained through co-transfection with an established dominant-negative REST (DNR) construct. Investigation of the GA-repeat STR revealed polymorphism across both animal strains and species, and size variation was also observed in absence epilepsy disease model cohorts (Genetic Absence Epilepsy Rats, Strasbourg [GAERS] and non-epileptic control [NEC] rats). These data provide evidence of a genotype (STR)-phenotype correlation that may be unique with respect to proximal gene regulatory sequence in the demonstrated absence of other promoter, or 3′ UTR variants in GAERS rats. However, although transcriptional regulatory activity of the STR was demonstrated in further transfection studies, we did not find a GAERS vs. NEC difference, indicating that this specific STR length variation may only be relevant in the context of other (Cacna1h and Kcnk9) gene variants in this disease model. Additional studies revealed further (bidirectional) complexity at the Cacng2 promoter, and we identified novel, co-regulated, antisense rat lncRNAs that are paired with Cacng2 mRNA. These studies have provided novel insights into the organization of a synaptic protein gene promoter, describing multiple repressive and modulatory domains that can mediate diverse regulatory inputs

Die <i>liter&#234;r-historiese</i> lees van 'n teks

The discussion on methodology in the South African exegetical and hermeneutical debate has not been completed yet. Several contributions during the past six years have kept this debate alive. Nevertheless, the duration of the discussion has brought growth and more understanding for different viewpoints and approaches. The aim of this article is to argue that both literary and historical aspects in the reading of any Old Testament text are important. Although it is not the only text approach, it proposes the literary-historical reading of texts is a comprehensive way to expose and understand Biblical texts

Psalms en hulle Sitz(e) im Leben. 'n Analise aan die hand van Psalm 55 en 74

It is hermeneutically unthinkable to expose any Old Testament text, without taking its historic and/or cultic Sitz im Leben into consideration. This especially applies for the texts of the psalms. But, vague formulations and generalised language, though, make this effort in the psalms extremely difficult. In view of the eclectic chosen examples of Psalms 55 and 74, this article shows how several Sitz(e) im Leben are identified by exegetes for the understanding of a psalm. More than one historical situation could have instigated the origin and content of a psalm. To determine the socalled "original" Sitz of psalms, is therefore almost impossible. But, this state of affairs should not cause the exegete or preacher to be sinical about exegetical method or diachronic research of psalm texts. Various identified Sitz(e) behind the text should create a common dealer - an athmosphere or interpretation-direction - which create afreedom in the exegete or reader's mind to identifY suitable situations for the reinterpretation or actualisation of a psalm. In this regard, a literary or textimmanent reading is not complete without diachronic exegesis. Despite uncertainty about the so-called "original" Sitz im Leben behind most psalms, exegetes should be more than enthusiastic to struggle with the search for a historic or cultic Sitz(e) behind the text. This will add value to the understanding of every psalm

Gebed: 'n Proses wat verandering bemiddel

Prayer is an integral part of the believer's communion with God. It reflects different dimensions and functions in the faith-relationship between God and man. Worship, praise, thanksgiving, intercession, petition, confession and trust are only a few to be mentioned. A neglected aspected of the prayer experience is the lament. Prayer is, in this sense, an exposure of the self and the circumstances of the petitioner before God. The purpose of this article is to illuminate the theological meaning of the lament as prayer for the individual and the faith community. Prayer is also understood within the broader scope of different expressive human deeds. It is a process which mediates perspective and essential change in the life of the believer and faith community. In a final application it is argued that the lament-prayer can contribute to change and renewal in a transitional and disturbed South African church and society