C009 Perte du gradient transmural de la fonction mitochondriale et altération du couplage excitation-contraction dans l’insuffisance cardiaque ischémique

L’insuffisance cardiaque (IC) est caractérisée par des altérations du métabolisme énergétique associées à une augmentation de la production de radicaux libres (RL). Les RL altèrent le couplage excitation-contraction (CEC) des myocytes en interagissant avec la signalisation calcique et les protéines contractiles. Chez des rats ayant subit une ligature de l’artère coronaire gauche (PMI), nous avons déterminé si, au stade d’insuffisance cardiaque, la perte du gradient transmural de contractilité et l’altération de la signalisation Ca2+ étaient associées à une dysfonction mitochondriale régionalisée au sein de la paroi du ventricule gauche (VG).Les propriétés métaboliques ont été évaluées en mesurant l’autofluorescence du NADH (microscopie multiphotonique), et les activités de la citrate synthase (CS) et de la cytochrome-c oxydase (COX) de cardiomyocytes isolés du sous-endocarde (ENDO) et du sousépicarde (EPI) du VG de rats PMI ou contrôles (sham). Parallèlement, nous avons mesuré les activités de la superoxyde dismutase (SOD) et de la catalase ainsi que la production mitochondriale de RL (MitoSOX) en microscopie confocale. Le raccourcissement cellulaire, la sensibilité au Ca2+ des myofilaments, le transitoire Ca2+, ainsi que les sparks Ca2+ ont été mesurés en absence ou en présence d’un antioxydant (N-acetyl cysteine NAC: 20mM).Chez les shams, l’utilisation du NADH au cours d’une stimulation électrique est plus importante dans l’ENDO que dans l’EPI et s’accompagne d’activités CS et COX plus élevées. Ce gradient transmural de capacité oxydative disparait au cours de l’IC en raison d’altérations localisées uniquement dans l’ENDO. Ces perturbations métaboliques sont associées à une diminution des défenses antioxydantes et à une élévation de la production de RL dans l’ENDO. Le NAC améliore les propriétés contractiles, la fuite diastolique de Ca2+ du réticulum sarcoplasmique (baisse de la fréquence des sparks spontanés) et réduit le nombre de transitoires Ca2+ ectopiques pro-arythmogéniques dans l’ENDO.En conclusion, la perte du gradient transmural de contractilité au cours de l’IC est partiellement due à une altération régionalisée de la fonction mitochondriale. De plus, la production exacerbée de RL associée aux troubles métaboliques participe à la genèse d’événements arythmiques dans la région sous-endocardique

Some Empirical Criteria for Attributing Creativity to a Computer Program

Peer reviewedPostprin

Cell Microbiol.

Helicobacter pylori is one of the most common bacterial pathogens, infecting about 50% of the world population. The presence of a pathogenicity island (PAl) in H. pylori has been associated with gastric disease. We present evidence that the H. pylori protein encoded by the cytotoxin- associated gene A (cagA) is translocated and phosphorylated in infected epithelial cells. Two-dimensional gel electrophoresis (2-DE) of proteins isolated from infected AGS cells revealed H. pylori strain-specific and time- dependent tyrosine phosphorylation and dephosphorylation of several 125-135 kDa and 75-80 kDa proteins. Immunoblotting studies, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), cell fractionation and confocal microscopy demonstrated that one of the 125-135 kDa proteins represents the H. pylori CagA protein, which is translocated into the host cell membrane and the cytoplasm. Translocation of CagA was dependent on functional cagA gene and virulence (vir) genes of a type IV secretion apparatus composed of virB4, virB7, virB10, virB11 and virD4 encoded in the cag PAl of H. pylori. Our findings support the view that H. pylori actively translocates virulence determinants, including CagA, which could be involved in the development of a variety of gastric disease.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Origin of symbol-using systems: speech, but not sign, without the semantic urge

Natural language—spoken and signed—is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish the origin of a system capable of evolution from the subsequent evolution that system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initially side-stepping not only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint

Using resource graphs to represent conceptual change

We introduce resource graphs, a representation of linked ideas used when reasoning about specific contexts in physics. Our model is consistent with previous descriptions of resources and coordination classes. It can represent mesoscopic scales that are neither knowledge-in-pieces or large-scale concepts. We use resource graphs to describe several forms of conceptual change: incremental, cascade, wholesale, and dual construction. For each, we give evidence from the physics education research literature to show examples of each form of conceptual change. Where possible, we compare our representation to models used by other researchers. Building on our representation, we introduce a new form of conceptual change, differentiation, and suggest several experimental studies that would help understand the differences between reform-based curricula.Comment: 27 pages, 14 figures, no tables. Submitted for publication to the Physical Review Special Topics Physics Education Research on March 8, 200

The study of metaphor as part of Critical Discourse Analysis

This article discusses how the study of metaphoric and more generally, figurative language use contributes to critical discourse analysis (CDA). It shows how cognitive linguists’ recognition of metaphor as a fundamental means of concept- and argument-building can add to CDA's account of meaning constitution in the social context. It then discusses discrepancies between the early model of conceptual metaphor theory and empirical data and argues that discursive-pragmatic factors as well as sociolinguistic variation have to be taken into account in order to make cognitive analyses more empirically and socially relevant. In conclusion, we sketch a modified cognitive approach informed by Relevance Theory within CDA

Using conceptual metaphor and functional grammar to explore how language used in physics affects student learning

This paper introduces a theory about the role of language in learning physics. The theory is developed in the context of physics students' and physicists' talking and writing about the subject of quantum mechanics. We found that physicists' language encodes different varieties of analogical models through the use of grammar and conceptual metaphor. We hypothesize that students categorize concepts into ontological categories based on the grammatical structure of physicists' language. We also hypothesize that students over-extend and misapply conceptual metaphors in physicists' speech and writing. Using our theory, we will show how, in some cases, we can explain student difficulties in quantum mechanics as difficulties with language.Comment: Accepted for publication in Phys. Rev. ST:PE

From Teamchef Arminius to Hermann Junior: glocalised discourse about a national foundation myth

If for much of the nineteenth and twentieth centuries, the ‘Battle of the Teutoburg Forest’, fought in 9 CE between Roman armies and Germanic tribes, was predominantly a reference point for nationalist and chauvinist discourses in Germany, the first decade of the twenty-first century has seen attempts to link public remembrance with local/regional identities on the one hand and international/intercultural contact on the other. In the run up to and during the ‘anniversary year’ of 2009, German media, sports institutions and various other official institutions articulating tourist, economic and political interests attempted to create a new ‘glocalised’ version of the public memory of the Teutoburg battle. Combining methods of Cognitive Linguistics and Critical Discourse Analysis, the paper analyses the narrative and argumentative topoi employed in this re-orientation of public memory, with a special emphasis on hybrid, post-national identity-construction. Das zweitausendjährige Gedenkjahr der „Schlacht im Teutoburger Wald“ im Jahr 2009 bot eine günstige Gelegenheit, die bis in die zweite Hälfte des 20. Jahrhunderts dominante Tradition nationalistisch–chauvinistischer Deutungen des Sieges von germanischen Stämmen über drei römische Legionen zu korrigieren und zu überwinden. Der Aufsatz analysiert mit Hilfe diskurslinguistischer Methoden die Anstrengungen regionaler Institutionen und Medien, die nationale Vereinnahmung des historischen Gedenkens kritisch zu thematisieren sowie neue, zum eine lokal situierte, zum andern international orientierte Identifikationsangebote anzubieten. Die Analyse zeigt, dass solche „de-nationalisierten“ Identifikationsangebote zwar teilweise auch früher verwendet wurden, aber heutzutage rekontextualisiert und auf innovative Weise in den Vordergrund gestellt werden

Theory blending: extended algorithmic aspects and examples

In Cognitive Science, conceptual blending has been proposed as an important cognitive mechanism that facilitates the creation of new concepts and ideas by constrained combination of available knowledge. It thereby provides a possible theoretical foundation for modeling high-level cognitive faculties such as the ability to understand, learn, and create new concepts and theories. Quite often the development of new mathematical theories and results is based on the combination of previously independent concepts, potentially even originating from distinct subareas of mathematics. Conceptual blending promises to offer a framework for modeling and re-creating this form of mathematical concept invention with computational means. This paper describes a logic-based framework which allows a formal treatment of theory blending (a subform of the general notion of conceptual blending with high relevance for applications in mathematics), discusses an interactive algorithm for blending within the framework, and provides several illustrating worked examples from mathematics