Examination of Apoptosis Signaling in Pancreatic Cancer by Computational Signal Transduction Analysis

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer death. Changes in apoptosis signaling in pancreatic cancer result in chemotherapy resistance and aggressive growth and metastasizing. The aim of this study was to characterize the apoptosis pathway in pancreatic cancer computationally by evaluation of experimental data from high-throughput technologies and public data bases. Therefore, gene expression analysis of microdissected pancreatic tumor tissue was implemented in a model of the apoptosis pathway obtained by computational protein interaction prediction. METHODOLOGY/PRINCIPAL FINDINGS: Apoptosis pathway related genes were assembled from electronic databases. To assess expression of these genes we constructed a virtual subarray from a whole genome analysis from microdissected native tumor tissue. To obtain a model of the apoptosis pathway, interactions of members of the apoptosis pathway were analysed using public databases and computational prediction of protein interactions. Gene expression data were implemented in the apoptosis pathway model. 19 genes were found differentially expressed and 12 genes had an already known pathophysiological role in PDAC, such as Survivin/BIRC5, BNIP3 and TNF-R1. Furthermore we validated differential expression of IL1R2 and Livin/BIRC7 by RT-PCR and immunohistochemistry. Implementation of the gene expression data in the apoptosis pathway map suggested two higher level defects of the pathway at the level of cell death receptors and within the intrinsic signaling cascade consistent with references on apoptosis in PDAC. Protein interaction prediction further showed possible new interactions between the single pathway members, which demonstrate the complexity of the apoptosis pathway. CONCLUSIONS/SIGNIFICANCE: Our data shows that by computational evaluation of public accessible data an acceptable virtual image of the apoptosis pathway might be given. By this approach we could identify two higher level defects of the apoptosis pathway in PDAC. We could further for the first time identify IL1R2 as possible candidate gene in PDAC

L'historiographie marxiste et Martin Luther

Marxist historiography and Martin Luther. The author considers as capital in the evolution of Marxist historio¬ graphy the following problems : Luther's place in national history, the in¬ fluence of his work and of the Reformation as a revolutionary phenomenon on a world-wide scale. Other points deserve attention : the problem of Lu¬ ther the " progressive ", the revolutionary character of his work and the re¬ lation between theology and society.L'auteur considère comme des points capitaux dans l'évolution de l'historiographie marxiste les problèmes suivants : la place occupée par Luther dans l'histoire nationale, l'influence, à l'échelle mondiale, de son œuvre et de la Réforme en tant que phénomène révolutionnaire. Il est d'autres questions qui méritent attention : le problème du « progressisme » de Luther, le caractère révolutionnaire de son œuvre et les rapports entre théologie et société.Vogler Günter, Wolff Robert. L'historiographie marxiste et Martin Luther. In: Revue d'histoire et de philosophie religieuses, 63e année n°1-2, Janvier-juin 1983. Luther et l'Europe. pp. 155-166

Cultural meaning for women composers: Charlotte (“Minna”) Brandes and the Beautiful Dead in the German Enlightenment

This article explores the cultural meanings of female musical authorship in the late German Enlightenment through a case study of Charlotte ("Minna") Brandes, a composer, keyboardist, and opera singer. With Minna's death in 1788 at the age of twenty-three, her father, the playwright Johann Christian Brandes, and her close friend and teacher Johann Friedrich Hönicke prepared two memorials to her memory, a biography and a collection of her music, the latter titled Musikalische Nachlass von Minna Brandes (Hamburg, 1788). These memorials situated her authorship in the contexts of pedagogy and education, the composition of occasional works for the home, and the solace offered by music amidst bereavement and illness. The principal discourse was of death itself. Minna's memorialization shared with the novels of Goethe a topos of the beautiful female dead in which the female corpse (or its representation) was exhibited as a beautiful artifact. Death turned Minna from composer into a passive, aestheticized object of male authorship. These discursive contexts contained Minna's activities as a composer within a framework of bourgeois femininity. Both Minna's father and her teacher were at pains to stress that she sought neither fame nor fortune from her compositions. However, such representations of Minna were misleading. Her collected works suggest she was working toward a published collection of strophic German songs and toward the composition of operatic music for her own performance. The idealizing tropes of the memorials are also challenged by Johann Christian's later memoirs in which his daughter's turn to composition is situated in what he described as her multiple breaches of deferential daughterly conduct. Minna's reported profligacy during her final illness may have stimulated the posthumous publication of her music, which was possibly a form of fund raising for her multiply bereaved father, a corrective to his emotional and financial loss. The healthy list of 518 subscribers indicates that youthful female death was marketable as a topos occasioning the pleasures of melancholy