Control of embryonic Xenopus morphogenesis by a Ral-GDS/Xral branch of the Ras signalling pathway.

Ras proteins mediate biological responses through various effectors and play a key role in relaying the Fibroblast Growth Factor (FGF) mesoderm induction signal during embryogenesis of the frog, Xenopus laevis. One Ras effector pathway involves the activation of the small G protein Ral. In the present study, we have investigated the role of key components in the Ral branch of FGF and Ras signalling during early Xenopus development. Treatment of animal caps with bFGF, which converts prospective ectoderm to mesoderm, activates Xral. The Ras mutant 12V37G, which can bind to Ral-GDS but not Raf, also activates Xral as well as causing developmental defects and cortical F-actin disassembly. A similar phenotype is induced by Ral-GDS itself. FGF-induced expression of several signature mesodermal genes, by contrast, is independent of Xral signalling. This and other data suggest that the RalB branch of Ras and FGF signalling regulates the actin cytoskeleton and morphogenesis in a transcriptionally independent manner. We also find Xral to be specifically activated in the marginal zone of Xenopus embryos, and find that disruption of the Ral pathway in this region prevents closure of the blastopore during gastrulation. We conclude that Ral signalling is autonomously required by mesodermal cells to effect essential morphogenetic changes during Xenopus gastrulation

Enhanced transmission of slit arrays in an extremely thin metallic film

Horizontal resonances of slit arrays are studied. They can lead to an enhanced transmission that cannot be explained using the single-mode approximation. A new type of cavity resonance is found when the slits are narrow for a wavelength very close to the period. It can be excited for very low thicknesses. Optimization shows these structures could constitute interesting monochromatic filters

RLIP mediates downstream signalling from RalB to the actin cytoskeleton during Xenopus early development.

The Ras protein activates at least three different pathways during early development. Two of them regulate mesodermal gene expression and the third is thought to participate in the control of actin cytoskeleton dynamics via the Ral protein. From a yeast two-hybrid screen of a Xenopus maternal cDNA library, we identified the Xenopus orthologue of the Ral interacting protein (RLIP, RIP1 or RalBP1), a putative effector of small G protein Ral. Previously we observed that a constitutively activated form of Ral GTPase (XralB G23V) induced bleaching of the animal hemisphere and disruption of the cortical actin cytoskeleton. To demonstrate that RLIP is the effector of RalB in early development, we show that the artificial targeting of RLIP to the membrane induces a similar phenotype to that of activated RalB. We show that overexpression of the Ral binding domain (RalBD) of XRLIP, which binds to the effector site of Ral, acts in competition with the endogenous effector of Ral and protects against the destructive effect of XralB G23V on the actin cytoskeleton. In contrast, the XRLIP has a synergistic effect on the activated form of XralB, which is dependent on the RalBD of RLIP. We provide evidence for the involvement of RLIP by way of its RalBD on the dynamics of the actin cytoskeleton and propose that signalling from Ral to RLIP is required for gastrulation

Poly(vinyl alcohol) hydrogel coatings with tunable surface exposure of hydroxyapatite.

International audienceInsufficient bone anchoring is a major limitation of artificial substitutes for connective osteoarticular tissues. The use of coatings containing osseoconductive ceramic particles is one of the actively explored strategies to improve osseointegration and strengthen the bone-implant interface for general tissue engineering. Our hypothesis is that hydroxyapatite (HA) particles can be coated robustly on specific assemblies of PVA hydrogel fibers for the potential anchoring of ligament replacements. A simple dip-coating method is described to produce composite coatings made of microscopic hydroxyapatite (HA) particles dispersed in a poly(vinyl alcohol) (PVA) matrix. The materials are compatible with the requirements for implant Good Manufacturing Practices. They are applied to coat bundles of PVA hydrogel fibers used for the development of ligament implants. By means of optical and electronic microscopy, we show that the coating thickness and surface state can be adjusted by varying the composition of the dipping solution. Quantitative analysis based on backscattered electron microscopy show that the exposure of HA at the coating surface can be tuned from 0 to over 55% by decreasing the weight ratio of PVA over HA from 0.4 to 0.1. Abrasion experiments simulating bone-implant contact illustrate how the coating cohesion and wear resistance increase by increasing the content of PVA relative to HA. Using pullout experiments, we find that these coatings adhere well to the fiber bundles and detach by propagation of a crack inside the coating. These results provide a guide to select coated implants for anchoring artificial ligaments

How modeling can reconcile apparently discrepant experimental results: the case of pacemaking in dopaminergic neurons.

Midbrain dopaminergic neurons are endowed with endogenous slow pacemaking properties. In recent years, many different groups have studied the basis for this phenomenon, often with conflicting conclusions. In particular, the role of a slowly-inactivating L-type calcium channel in the depolarizing phase between spikes is controversial, and the analysis of slow oscillatory potential (SOP) recordings during the blockade of sodium channels has led to conflicting conclusions. Based on a minimal model of a dopaminergic neuron, our analysis suggests that the same experimental protocol may lead to drastically different observations in almost identical neurons. For example, complete L-type calcium channel blockade eliminates spontaneous firing or has almost no effect in two neurons differing by less than 1% in their maximal sodium conductance. The same prediction can be reproduced in a state of the art detailed model of a dopaminergic neuron. Some of these predictions are confirmed experimentally using single-cell recordings in brain slices. Our minimal model exhibits SOPs when sodium channels are blocked, these SOPs being uncorrelated with the spiking activity, as has been shown experimentally. We also show that block of a specific conductance (in this case, the SK conductance) can have a different effect on these two oscillatory behaviors (pacemaking and SOPs), despite the fact that they have the same initiating mechanism. These results highlight the fact that computational approaches, besides their well known confirmatory and predictive interests in neurophysiology, may also be useful to resolve apparent discrepancies between experimental results

Recruitment of Cdc42 through the GAP domain of RLIP participates in remodeling of the actin cytoskeleton and is involved in Xenopus gastrulation.

International audienceThe transduction pathways that branch out of fibroblast growth factor signaling are essential for the induction of the mesoderm and the specification of the vertebrate body plan. One of these pathways is thought to control remodeling of the actin cytoskeleton through the Ral binding protein (RLIP also known as RalBP1), an effector of the small G protein Ral. RLIP contains a region of homology with the GTPase-activating protein (GAP) domain involved in the regulation of GTPases of the Rho family. We demonstrate here that the GAP domain of RLIP is responsible for the stability of the actin cytoskeleton in Xenopus laevis embryos. We also demonstrate that the complete N-terminal domain of RLIP containing the mu2 binding domain (mu2BD) and the GAP domain induces disruption of the actin cytoskeleton when targeted to the plasma membrane. Neither domain, however, has any effect on the actin cytoskeleton when individually targeted to the plasma membrane. We also determined that Cdc42-GDP, but neither Rac-GDP nor Rho-GDP, rescues the effect of expression of the membrane-localized Xenopus RLIP on the actin cytoskeleton. We show that the GAP domain of RLIP interacts in vivo with Cdc42-GTP and Cdc42-GDP. Finally, a single mutation (K244A) in the GAP sequence prevented embryos from gastrulating. These results demonstrate that to participate in the control of the actin cytoskeleton, RLIP needs its complete N-terminal region coding for the mu2BD and the GAP domain. We suggest that RLIP, by coordinating two complementary mechanisms, the endocytosis of clathrin-coated pits and the remodeling of cortical actin, participates in the gastrulation process

Correlates of quality of life of pre-obese and obese patients: a pharmacy-based cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>The correlates of quality of life (QOL), as measured by the OSQOL questionnaire were investigated in a convenience sample of overweight patients recruited in pharmacies.</p> <p>Methods</p> <p>A convenience sample of patients with a Body Mass Index ≥ 28 kg/m²were recruited in community-based pharmacies. Baseline characteristics and QOL dimensions (1-Physical state, 2-Vitality-desire to do things, 3-Relations with others, 4-Psychological state) were reported in self-completed questionnaires from which the risk of obtaining a low QOL was assessed for each dimension.</p> <p>Results</p> <p>QOL was inadequate for all dimensions in the 494 patients included in the study (median age = 61, 48% women, 21% professional persons/top executives). Older pre-obese and obese patients were more likely to report impaired physical functioning (OR = 2.02, 95%CI = [1.10-3.70]), but were less severely affected socially (OR = 0.32, 95%CI = [0.15-0.69]). Pre-obese and obese professional persons and top executives showed better physical capabilities (OR = 0.35, 95%CI = [0.15-0.81]) and increased vitality (OR = 0.47, 95%CI = [0.23-0.95]). Overall, men's psychological state was better than females' (OR = 0.46, 95%CI = [0.25-0.82]). A body-mass index ≥ 35 kg/m²was significantly associated with poorer QOL scores on physical, relational and psychological dimensions.</p> <p>Conclusion</p> <p>Our data highlighted the influence of the severity of excess weight, gender, age and socioeconomic status on QOL. These factors should be taken into account when interpreting QOL in pre-obese and obese persons.</p

ADVICE, Allocation Dynamique des Voies de Circulation : Analyse système et choix technologique, livrable final de la Tache 2

Lutter efficacement contre la congestion routière, améliorer durablement la sécurité des automobilistes sont deux des objectifs majeurs des gestionnaires d'infrastructures routières. En milieu urbain, la congestion du trafic a un impact direct sur la qualité des transports collectifs (TC) de surface. Au-delà de leur extension, l'optimisation des infrastructures existantes et le déploiement de Systèmes de Transport Intelligent (STI), qui rendent possible la gestion dynamique du trafic, sont une solution. Le projet ADViCe, issu d'un travail collaboratif d'un Think Tank du LUTB « Systèmes de transport », propose d'évaluer la pertinence de la mise en place d'une stratégie d'allocation dynamique des voies de circulation. L'objectif étant d'améliorer l'efficacité des transports prioritaires (bus, pompiers, etc.) sans limiter sensiblement l'espace disponible pour les autres véhicules. Les objectifs du projet Advices sont : " Définir une méthodologie pour la mise en place d'une solution innovante de gestion du trafic " Développer les technologies adaptées et les mettre en oeuvre " Expérimenter les stratégies ADViCe " Evaluer et optimiser les scénarios de régulation Ce livrable représente le livrable final de la tache 2. Dans ce rapport nous identifierons les fonctions nécessaires à la gestion du trafic et nous décrirons les technologies permettant de les réaliser