Les jeunes filles de Prosper Menière qui firent tourner beaucoup de têtes

Après la publication dans une revue anglo-saxonne d’un article consacré à la carrière de Prosper Menière, il nous a semblé utile, pour revenir sur quelques approximations, de demander à un biographe, auteur d’un livre consacré à l’éponyme des vertiges, une mise au point historiquement documentée qui, au-delà des spécialistes, oto-rhino-laryngologistes et neurologues, devrait intéresser l’ensemble des lecteurs de médecine/sciences

Cell cycle genes regulate vestigial and scalloped to ensure normal proliferation in the wing disc of Drosophila melanogaster.

In Drosophila, the Vestigial-Scalloped (VG-SD) dimeric transcription factor is required for wing cell identity and proliferation. Previous results have shown that VG-SD controls expression of the cell cycle positive regulator dE2F1 during wing development. Since wing disc growth is a homeostatic process, we investigated the possibility that genes involved in cell cycle progression regulate vg and sd expression in feedback loops. We focused our experiments on two major regulators of cell cycle progression: dE2F1 and the antagonist dacapo (dap). Our results reinforce the idea that VG/SD stoichiometry is critical for correct development and that an excess in SD over VG disrupts wing growth. We reveal that transcriptional activity of VG-SD and the VG/SD ratio are both modulated upon down-expression of cell cycle genes. We also detected a dap-induced sd upregulation that disrupts wing growth. Moreover, we observed a rescue of a vg hypomorphic mutant phenotype by dE2F1 that is concomitant with vg and sd induction. This regulation of the VG-SD activity by dE2F1 is dependent on the vg genetic background. Our results support the hypothesis that cell cycle genes fine-tune wing growth and cell proliferation, in part, through control of the VG/SD stoichiometry and activity. This points to a homeostatic feedback regulation between proliferation regulators and the VG-SD wing selector

Sensor potency of the moonlighting enzyme-decorated cytoskeleton

Background: There is extensive evidence for the interaction of metabolic enzymes with the eukaryotic cytoskeleton. The significance of these interactions is far from clear. Presentation of the hypothesis: In the cytoskeletal integrative sensor hypothesis presented here, the cytoskeleton senses and integrates the general metabolic activity of the cell. This activity depends on the binding to the cytoskeleton of enzymes and, depending on the nature of the enzyme, this binding may occur if the enzyme is either active or inactive but not both. This enzyme-binding is further proposed to stabilize microtubules and microfilaments and to alter rates of GTP and ATP hydrolysis and their levels. Testing the hypothesis: Evidence consistent with the cytoskeletal integrative sensor hypothesis is presented in the case of glycolysis. Several testable predictions are made. There should be a relationship between post-translational modifications of tubulin and of actin and their interaction with metabolic enzymes. Different conditions of cytoskeletal dynamics and enzyme-cytoskeleton binding should reveal significant differences in local and perhaps global levels and ratios of ATP and GTP. The different functions of moonlighting enzymes should depend on cytoskeletal binding. Implications of the hypothesis: The physical and chemical effects arising from metabolic sensing by the cytoskeleton would have major consequences on cell shape, dynamics and cell cycle progression. The hypothesis provides a framework that helps the significance of the enzyme-decorated cytoskeleton be determined

in vivo analysis of Drosophila deoxyribonucleoside kinase function in cell cycle, cell survival and anti-cancer drugs resistance.

in vitro studies have shown that Drosophila melanogaster has a highly efficient single deoxyribonucleoside kinase (dNK) multisubstrate enzyme. dNK is related to the mammalian Thymidine Kinase 2 (TK2) group involved in the nucleotide synthesis salvage pathway. To study the dNK function in vivo, we constructed transgenic Drosophila strains and impaired the nucleotide de novo synthesis pathway, using antifolates such as aminopterin. Our results show that dNK overexpression rescues both cell death and cell cycle arrest triggered by this anti-cancer drug, and confers global resistance on the fly. Moreover, we show that fly viability and growth depend on the exquisite ratio between dNK expression and its substrate thymidine (dT) in the medium, and that increased dT concentrations trigger apoptosis and a decrease in body mass when dNK is mis-expressed. Finally, dNK expression, unlike that of TK2, is cell cycle dependent and under the control of CyclinE and the dE2F1 transcription factor involved in the G1/S transition. dNK is therefore functionally more closely related to mammalian TK1 than to TK2. This strongly suggest that dNK plays a role in cell proliferation in physiological conditions

Uso de realidad virtual en la investigación e intervención en miedo y ansiedad: Una revisión sistemática breve

Los trastornos de miedo y ansiedad son uno de los diagnósticos más prevalentes en América Latina y el mundo. El tratamiento mediante exposición a Realidad Virtual (RV) se ha situado como una herramienta útil para crear contextos de extinción desde el enfoque cognitivo conductual, suscitando numerosos estudios sobre la eficacia de su uso en intervenciones sobre trastornos de ansiedad. Se levantó una revisión sistemática breve de alcance exploratorio y divulgativo. Se analizaron 128 investigaciones sobre trastornos de miedo o ansiedad con tecnología de RV y el grueso de los estudios se enfocan en el tratamiento de la ansiedad con ensayos clínicos basados en la exposición (67%), realizados con realidad virtual intensiva (RVi) (34%) o realidad virtual intensiva completa (RVic) (32%), diseño de ensayos clínicos randomizados (58%) o experimentales (27%) y realizados fuera de América Latina (97%). La investigación clínica en RV desde y hacia América Latina se torna cada vez más necesaria para levantar conocimiento, que considere desafíos de accesibilidad e implementación locales de esta tecnología.Versión original del auto

A stochastic automaton shows how enzyme assemblies may contribute to metabolic efficiency

<p>Abstract</p> <p>Background</p> <p>The advantages of grouping enzymes into metabolons and into higher order structures have long been debated. To quantify these advantages, we have developed a stochastic automaton that allows experiments to be performed in a virtual bacterium with both a membrane and a cytoplasm. We have investigated the general case of transport and metabolism as inspired by the phosphoenolpyruvate:sugar phosphotransferase system (PTS) for glucose importation and by glycolysis.</p> <p>Results</p> <p>We show that PTS and glycolytic metabolons can increase production of pyruvate eightfold at low concentrations of phosphoenolpyruvate. A fourfold increase in the numbers of enzyme EI led to a 40% increase in pyruvate production, similar to that observed <it>in vivo </it>in the presence of glucose. Although little improvement resulted from the assembly of metabolons into a hyperstructure, such assembly can generate gradients of metabolites and signaling molecules.</p> <p>Conclusion</p> <p><it>in silico </it>experiments may be performed successfully using stochastic automata such as HSIM (Hyperstructure Simulator) to help answer fundamental questions in metabolism about the properties of molecular assemblies and to devise strategies to modify such assemblies for biotechnological ends.</p