Sobre a Europa e sua lida com os outros

O artigo empreende a tentativa de refletir criticamente sobre a possibilidade de um contato não danoso com o outro, indicada sob o mote da interculturalidade, à luz do pensamento radical de Lévinas e Derrida sobre a alteridade. Essa reflexão se encontra sob a suspeita de que as filosofias ou fenomenologias da interculturalidade não dão conta da negatividade do encontro intercultural de fato com o outro irredutível, como a história do imperialismo e colonialismo europeus produziram. Para comprovar isso, eu refletirei sobre as funções, as quais o conceito de cultura assumiu nos discursos sobre a Europa. No centro da questão se encontra a comprovação de que a identificação da superioridade europeia sob o signo da cultura implica na constituição do outro como um outro ameaçador, a qual promove a brutalidade desta lida, ou seja, a história da violência – tanto interna quanto externa – da Europa. Sobre este plano de fundo eu concluo com o rascunho de alguns contornos de uma política da não-indiferença cultural, cujas raízes vejo remeterem ao pensamento de uma descolonização do imaginário da Europa

The interplay between genotype, metabolic state and cofactor treatment governs phenylalanine hydroxylase function and drug response

The discovery of a pharmacological treatment for phenylketonuria (PKU) raised new questions about function and dysfunction of phenylalanine hydroxylase (PAH), the enzyme deficient in this disease. To investigate the interdependence of the genotype, the metabolic state (phenylalanine substrate) and treatment (BH4 cofactor) in the context of enzyme function in vitro and in vivo, we (i) used a fluorescence-based method for fast enzyme kinetic analyses at an expanded range of phenylalanine and BH4 concentrations, (ii) depicted PAH function as activity landscapes, (iii) retraced the analyses in eukaryotic cells, and (iv) translated this into the human system by analyzing the outcome of oral BH4 loading tests. PAH activity landscapes uncovered the optimal working range of recombinant wild-type PAH and provided new insights into PAH kinetics. They demonstrated how mutations might alter enzyme function in the space of varying substrate and cofactor concentrations. Experiments in eukaryotic cells revealed that the availability of the active PAH enzyme depends on the phenylalanine-to-BH4 ratio. Finally, evaluation of data from BH4 loading tests indicated that the patient's genotype influences the impact of the metabolic state on drug response. The results allowed for visualization and a better understanding of PAH function in the physiological and pathological state as well as in the therapeutic context of cofactor treatment. Moreover, our data underscore the need for more personalized procedures to safely identify and treat patients with BH4-responsive PAH deficienc

Pahenu1 is a mouse model for tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency and promotes analysis of the pharmacological chaperone mechanism in vivo

The recent approval of sapropterin dihydrochloride, the synthetic form of 6[R]-l-erythro-5,6,7,8-tetrahydrobiopterin (BH4), for the treatment of phenylketonuria (PKU) as the first pharmacological chaperone drug initiated a paradigm change in the treatment of monogenetic diseases. Symptomatic treatment is now replaced by a causal pharmacological therapy correcting misfolding of the defective phenylalanine hydroxylase (PAH) in numerous patients. Here, we disclose BH4 responsiveness in Pahenu1, a mouse model for PAH deficiency. Loss of function resulted from loss of PAH, a consequence of misfolding, aggregation, and accelerated degradation of the enzyme. BH4 attenuated this triad by conformational stabilization augmenting the effective PAH concentration. This led to the rescue of the biochemical phenotype and enzyme function in vivo. Combined in vitro and in vivo analyses revealed a selective pharmaceutical action of BH4 confined to the pathological metabolic state. Our data provide new molecular-level insights into the mechanisms underlying protein misfolding with loss of function and support a general model of pharmacological chaperone-induced stabilization of protein conformation to correct this intracellular phenotype. Pahenu1 will be essential for pharmaceutical drug optimization and to design individually tailored therapie

Anterior Thalamic High Frequency Band Activity Is Coupled with Theta Oscillations at Rest

Cross-frequency coupling (CFC) between slow and fast brain rhythms, in the form of phase–amplitude coupling (PAC), is proposed to enable the coordination of neural oscillatory activity required for cognitive processing. PAC has been identified in the neocortex and mesial temporal regions, varying according to the cognitive task being performed and also at rest. PAC has also been observed in the anterior thalamic nucleus (ATN) during memory processing. The thalamus is active during the resting state and has been proposed to be involved in switching between task-free cognitive states such as rest, in which attention is internally-focused, and externally-focused cognitive states, in which an individual engages with environmental stimuli. It is unknown whether PAC is an ongoing phenomenon during the resting state in the ATN, which is modulated during different cognitive states, or whether it only arises during the performance of specific tasks. We analyzed electrophysiological recordings of ATN activity during rest from seven patients who received thalamic electrodes implanted for treatment of pharmacoresistant focal epilepsy. PAC was identified between theta (4–6 Hz) phase and high frequency band (80–150 Hz) amplitude during rest in all seven patients, which diminished during engagement in tasks involving an external focus of attention. The findings are consistent with the proposal that theta–gamma coupling in the ATN is an ongoing phenomenon, which is modulated by task performance

L’Europe et ses violences. Contribution à une généalogie phénoménologique des violences extrêmes

In the framework of a critical analysis of Europe, which appears to be tom between its indifference towards its others and its historic responsibility for them, this article proposes a phenomenological interpretation of extreme collective violence. After first elucidating the very possibility of a phenomenology of violence, the author focuses on the intertwining of our lived and our objective body. As he sees it, this generic «bodily difference» haunts the subject’s self-constitution at various levels. It can thus be exploited by various «body politics», which conjure up the phantasma of an integral, pure, and masterful «political body». As the author argues, these «body politics» do not operate on a cognitive level alone, but affect our embodiments pre-reflectively, generating indifference on the intercorporeal level and constituting a precondition for the actual use of extreme violence against others. As conclusion to this phenomenological genealogy, the author inquires finally into the implications of these insights into the passive incorporation of indifference for our understanding of Europe and its responsibility for the violence inflicted on its others.Dans le contexte d’une analyse critique de l’Europe, qui semble déchirée entre l’indifférence envers ses autres et la responsabilité à leur égard, cet article propose une interprétation des formes extrêmes de violence collective. L’auteur commence par éclaircir la possibilité même d’une analyse phénoménologique de la violence pour ensuite se concentrer sur l’entrelacs du corps objectif et du corps vécu, «différence chamelle» qui, d’après lui, hante l’autoconstitution du sujet dans plus d’une dimension. La non-coïncidence du sujet avec lui-même peut alors être exploitée par diverses «politiques du corps», nourrissant le fantasme d’intégrité d’un «corps politique» pur et souverain. Ces politiques n’opèrent pas uniquement dans le registre cognitif et réflexif, mais affectent notre incorporation de façon pré-réflexive. En engendrant de l’indifférence sur le plan de notre intercorporéité, elles mettent en place les conditions pour l’exercice concret de violences extrêmes envers autrui. En conclusion, l’auteur s’interroge sur les implications de cette mise en évidence de l’incorporation passive de l’indifférence pour la réflexion sur l’Europe et sa responsabilité à l’égard de ses autres.Staudigl Michael. L’Europe et ses violences. Contribution à une généalogie phénoménologique des violences extrêmes. In: Revue Philosophique de Louvain. Troisième série, tome 109, n°1, 2011. pp. 107-136

Recovering the Vertical: Confronting Religious Violence in a Phenomenological Key

This paper examines the relationship between religion and violence from a phenomenological point of view. In the context of the so-called "return of the religious" and the crisis of contemporary social imaginaries, it deals with the supposedly disruptive and liberating potentials of religion in general, and religious violence in particular. The discussion revolves around the concept of "verticality" as developed by A. Steinbock and offers a generative interpretation of verticality's liberating and transformative potentials. The paper proceeds to demonstrate how religion and violence are interrelated on a variety of levels. In conclusion the author argues that we need to understand the relationship between religion and violence in terms of its contingent actualization and display but must avoid pitting it down as an essential feqture of religious systems of knowledge and practice