Literarisiertes Leben und gelebte Literatur - Interferenzen von Autobiographie, Briefkultur und galantem Roman um 1700

Der Beitrag untersucht Interferenzen von Literatur und Leben in höfischen Selbstzeugnissen um 1700. Am Beispiel einer autobiographischen Schlüsselerzählung von Aurora von Königsmarck wird zum einen gezeigt, wie die eigene Lebensgeschichte literarisch überformt in einer typischen galanten Erzählung dargeboten wird. An einem zweiten Beispiel, dem Briefwechsel zwischen Sophie Dorothea von Hannover und Graf Philipp von Königsmarck, lässt sich zum anderen erkennen, dass eben diese literarischen Muster aus dem Bereich der Galanterie wiederum Vorbilder für ganz reale Lebensentwürfe werden konnten. Der galante Diskurs um 1700 erweist sich als ein Diskurs, der der Verwischung der Grenzen zwischen Literatur und Leben Vorschub leistet. Dabei verstärken sich die selbstreflexiven Züge des frühneuzeitlichen Rollen-Ichs, was einerseits Handlungsspielräume neu eröffnet, andererseits von den Diskursteilnehmern eine komplexere Form von Fremd- und Selbstbeobachtung erfordert und sich deshalb als riskant erweist.

Stable expression of Escherichia coli beta-glucuronidase A (GusA) in Giardia lamblia: application to high-throughput drug susceptibility testing

OBJECTIVES: In order to create a suitable model for high-throughput drug screening, a Giardia lamblia WB C6 strain expressing Escherichia coli glucuronidase A (GusA) was created and tested with respect to susceptibility to the anti-giardial drugs nitazoxanide and metronidazole. METHODS: GusA, a well-established reporter gene in other systems, was cloned into the vector pPacVInteg allowing stable expression in G. lamblia under control of the promoter from the glutamate dehydrogenase (gdh) gene. The resulting transgenic strain was compared with the wild-type strain in a vitality assay, characterized with respect to susceptibility to nitazoxanide, metronidazole and -- as assessed in a 96-well plate format -- to a panel of 15 other compounds to be tested for anti-giardial activity. RESULTS: GusA was stably expressed in G. lamblia. Using a simple glucuronidase assay protocol, drug efficacy tests yielded results similar to those from cell counting. CONCLUSIONS: G. lamblia WB C6 GusA is a suitable tool for high-throughput anti-giardial drug screening.

Understanding the role of argininosuccinate lyase transcript variants in the clinical and biochemical variability of the urea cycle disorder argininosuccinic aciduria

Argininosuccinic aciduria (ASA) is an autosomal recessive urea cycle disorder caused by deficiency of argininosuccinate lyase (ASL) with a wide clinical spectrum from asymptomatic to severe hyperammonemic neonatal onset life-threatening courses. We investigated the role of ASL transcript variants in the clinical and biochemical variability of ASA. Recombinant proteins for ASL wild type, mutant p.E189G, and the frequently occurring transcript variants with exon 2 or 7 deletions were (co-)expressed in human embryonic kidney 293T cells. We found that exon 2-deleted ASL forms a stable truncated protein with no relevant activity but a dose-dependent dominant negative effect on enzymatic activity after co-expression with wild type or mutant ASL, whereas exon 7-deleted ASL is unstable but seems to have, nevertheless, a dominant negative effect on mutant ASL. These findings were supported by structural modeling predictions for ASL heterotetramer/homotetramer formation. Illustrating the physiological relevance, the predominant occurrence of exon 7-deleted ASL was found in two patients who were both heterozygous for the ASL mutant p.E189G. Our results suggest that ASL transcripts can contribute to the highly variable phenotype in ASA patients if expressed at high levels. Especially, the exon 2-deleted ASL variant may form a heterotetramer with wild type or mutant ASL, causing markedly reduced ASL activity.