Zwei Wege zur 'Aufhellung der Finsternisse in der Welt'. Zum untergründigen Wechselverhältnis von Literatur & Malerei bei Thomas Bernhard & Francis Bacon:for subterranean exchange relationship between literature and painting in Thomas Bernhard & Francis Bacon

This chapter undertakes the first examination of the role the fine arts play in Thomas Bernhard’s prose works. Though not as prominent as the role of music, painting and the fine arts play a crucial role in Frost and Alte Meister; these two novels coincidentally also happen to be the first and last novels written by Bernhard. This chapter takes its cue from the positive role awarded to Francis Bacon in the novel Das Kalkwerk. Comparing and contrasting the relation and influence between the art of Bacon and the literature of Bernhard, I am able to demonstrate a number of surprising analogies. Following a brief biographical synopsis, I focus on four aesthetic operations that are crucial to both artists. Using the key terms of ‘middle way’, ‘variation’, ‘vibration’ and ‘mediation’, I am able to uncover surprising similarities between the novels and the paintings. These hidden connections are further confirmed by looking at the two artists’ shared major motifs, namely the slaughterhouse, the scream, the relation between animals and humans, and pain. This bleak outlook on the state of human civilisation that these two major artists of the end of the 20th century share, embodies both a warning and a prophesy for the 21st century.

The redoxomics of PTEN: walking a fine line between damage and signaling:mass spectrometry-based approaches to study the effect of oxidation on PTEN function, structure, and protein-protein interactions

The research described in this PhD thesis focuses on proteomics approaches to study the effect of oxidation on the modification status and protein-protein interactions of PTEN, a redox-sensitive phosphatase involved in a number of cellular processes including metabolism, apoptosis, cell proliferation, and survival. While direct evidence of a redox regulation of PTEN and its downstream signaling has been reported, the effect of cellular oxidative stress or direct PTEN oxidation on PTEN structure and interactome is still poorly defined. In a first study, GST-tagged PTEN was directly oxidized over a range of hypochlorous acid (HOCl) concentration, assayed for phosphatase activity, and oxidative post-translational modifications (oxPTMs) were quantified using LC-MS/MS-based label-free methods. In a second study, GSTtagged PTEN was prepared in a reduced and reversibly H2O2-oxidized form, immobilized on a resin support and incubated with HCT116 cell lysate to capture PTEN interacting proteins, which were analyzed by LC-MS/MS and comparatively quantified using label-free methods. In parallel experiments, HCT116 cells transfected with a GFP-tagged PTEN were treated with H2O2 and PTENinteracting proteins immunoprecipitated using standard methods. Several high abundance HOCl-induced oxPTMs were mapped, including those taking place at amino acids known to be important for PTEN phosphatase activity and protein-protein interactions, such as Met35, Tyr155, Tyr240 and Tyr315. A PTEN redox interactome was also characterized, which identified a number of PTEN-interacting proteins that vary with the reversible inactivation of PTEN caused by H2O2 oxidation. These included new PTEN interactors as well as the redox proteins peroxiredoxin-1 (Prdx1) and thioredoxin (Trx), which are known to be involved in the recycling of PTEN active site following H2O2-induced reversible inactivation. The results suggest that the oxidative modification of PTEN causes functional alterations in PTEN structure and interactome, with fundamental implications for the PTEN signaling role in many cellular processes, such as those involved in the pathophysiology of disease and ageing.