How Thioredoxin Dissociates Its Mixed Disulfide

The dissociation mechanism of the thioredoxin (Trx) mixed disulfide complexes is unknown and has been debated for more than twenty years. Specifically, opposing arguments for the activation of the nucleophilic cysteine as a thiolate during the dissociation of the complex have been put forward. As a key model, the complex between Trx and its endogenous substrate, arsenate reductase (ArsC), was used. In this structure, a Cys29Trx-Cys89ArsC intermediate disulfide is formed by the nucleophilic attack of Cys29Trx on the exposed Cys82ArsC-Cys89ArsC in oxidized ArsC. With theoretical reactivity analysis, molecular dynamics simulations, and biochemical complex formation experiments with Cys-mutants, Trx mixed disulfide dissociation was studied. We observed that the conformational changes around the intermediate disulfide bring Cys32Trx in contact with Cys29Trx. Cys32Trx is activated for its nucleophilic attack by hydrogen bonds, and Cys32Trx is found to be more reactive than Cys82ArsC. Additionally, Cys32Trx directs its nucleophilic attack on the more susceptible Cys29Trx and not on Cys89ArsC. This multidisciplinary approach provides fresh insights into a universal thiol/disulfide exchange reaction mechanism that results in reduced substrate and oxidized Trx

Modélisation des systèmes complexes. Effets de solvant sur les modes de vibration d'un soluté au sein d'une solution

Le modèle du milieu continu polarisable, dans le formalisme du champ de réaction self consistant, est étendu pour permettre le calcul des vibrations moléculaires au sein d'un liquide au moyen des méthodes de la chimie quantique. Appliqué aux vibrations νC=O d'une série de composés carbonylés en solution dans le cyclohexane et dans l'acétonitrile, le modèle se révèle tout-à-fait apte à permettre le calcul des fréquences de vibrations d'un soluté. L'origine moléculaire de l'effet de solvant est discutée

What is Called Thinking? When Deleuze Walks Along Heideggerian Paths

When on the last page of What Is Philosophy?, Deleuze and Guattari (1995: 218) claim that philosophy needs a non-philosophy, this statement is the result of a long engagement with the problem of thinking in society. It is this engagement that we intend to reconstruct in this article. By developing an original definition of thinking after Heidegger, Deleuze is able to claim that philosophy is not the only ‘thinking’ discipline. Our point of departure is Deleuze's constant reference to a phrase from Heidegger's lecture course What Is Called Thinking?: ‘We are not yet thinking’ (Deleuze 1988: 116, 1989: 167, 1994: 144, 2002: 108; Deleuze and Guattari 1995: 56). This phrase points to the demand for a new distribution of the relation between philosophy and its outside. The purpose of this article is to trace Heidegger's influence on Deleuze's definition of thinking and to raise two points. First, Deleuze borrows some elements of Heidegger's definition of thinking to further his own understanding of politics as an involuntary practice. For both, the question of thinking is political. Second, by departing from Heidegger, Deleuze can democratise the definition of thinking, beyond its confinement to philosophy, by turning to cinema. Deleuze calls cinema the art of the masses because it brings the masses in contact with external signs. Finally, in the last part of this article, we will discuss how Deleuze raises stupidity (and not error) as a transcendental problem that should be constantly fought. In this way, we hope to shed light on how Deleuze moves from Heidegger's question ‘what is called thinking?’ to the problem of stupidity and shame